Design and Optimization of Catalysts Based on Mechanistic Insights

Review pubs.acs.org/CR

Cite This: Chem. Rev. XXXX, XXX, XXX−XXX

Design and Optimization of Catalysts Based on Mechanistic Insights Derived from Quantum Chemical Reaction Modeling Seihwan Ahn,†,‡,∥ Mannkyu Hong,†,‡,∥ Mahesh Sundararajan,†,‡ Daniel H. Ess,*,§ and Mu-Hyun Baik*,†,‡ †

Department of Chemistry, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, Republic of Korea Center for Catalytic Hydrocarbon Functionalizations, Institute for Basic Science (IBS), Daejeon, 34141, Republic of Korea § Department of Chemistry and Biochemistry, Brigham Young University, Provo, Utah 84602, United States Downloaded via UNIV OF LOUISIANA AT LAFAYETTE on May 8, 2019 at 23:08:43 (UTC). See https://pubs.acs.org/sharingguidelines for options on how to legitimately share published articles.

‡

ABSTRACT: Until recently, computational tools were mainly used to explain chemical reactions after experimental results were obtained. With the rapid development of software and hardware technologies to make computational modeling tools more reliable, they can now provide valuable insights and even become predictive. In this review, we highlighted several studies involving computational predictions of unexpected reactivities or providing mechanistic insights for organic and organometallic reactions that led to improved experimental results. Key to these successful applications is an integration between theory and experiment that allows for incorporation of empirical knowledge with precise computed values. Computer modeling of chemical reactions is already a standard tool that is being embraced by an ever increasing group of researchers, and it is clear that its utility in predictive reaction design will increase further in the near future.

CONTENTS 1. Introduction 1.1. Overview 1.2. Strategies of Catalyst Design 1.3. Scope of This Review 2. Organocatalysts 2.1. Hydrogen-Bond Donor Catalysts 2.1.1. Urea 2.1.2. Phenol 2.1.3. Proline 2.2. Lewis Acidic Organocatalysts 2.2.1. Phosphorus 2.3. Lewis Basic Organocatalysts 2.3.1. Ionic Liquid 2.3.2. N-Heterocyclic Carbene 2.3.3. NX−OY 2.3.4. Cysteine 2.4. Theoretical Enzyme Design 3. Organometallic Catalysts 3.1. Small Molecule Activation 3.1.1. N2 Fixation 3.1.2. O2 Activation 3.1.3. CO2 Activation 3.2. Small Molecule Insertion 3.2.1. Hydrogenation 3.2.2. Ethylene Oligomerization 3.2.3. H2O Oxidation 3.3. Cross-coupling Reactions 3.3.1. C−C/Si Coupling © XXXX American Chemical Society

3.3.2. C−B Coupling 3.3.3. C−N Coupling 3.3.4. C−O/S Coupling 4. Challenges of in-Silico Catalyst Design 5. Conclusions and Future Outcome Author Information Corresponding Authors ORCID Author Contributions Notes Biographies Acknowledgments References

A A B B C C C D E E E F F G G H I J J J K M P P Q R T T

AD AG AJ AK AL AL AL AL AL AL AL AM AM

1. INTRODUCTION 1.1. Overview

As high performance computing hardware has become cheap and easy to access, and efficient and user-friendly quantum chemical modeling software has been commercialized, quantum chemical reaction modeling techniques have been embraced widely in chemical research. One area of research that has been particularly receptive to these modern tools of Special Issue: Computational Design of Catalysts from Molecules to Materials Received: January 30, 2019

A

DOI: 10.1021/acs.chemrev.9b00073 Chem. Rev. XXXX, XXX, XXX−XXX

Chemical Reviews

Review

inquiry is the organic and organometallic catalysis field. Initially, computer models were employed to rationalize and better understand experimental observations, often using minimalistic models where dramatic structural and mechanistic simplifications were necessary to keep the computational cost tractable. In particular, the emergence of density functional theory (DFT) as a de facto standard in reaction modeling opened the door to obtaining useful and realistic models of complicated chemical reactions.1−3 Molecules of realistic size and complexity can now be calculated and complete reaction cycles can now be modeled with little to no structural simplifications. The next logical step is employing these models to optimize, if not predict, new reactions beyond what purely experimental approaches allow. There are several obvious potential advantages of virtually optimizing novel or practical catalysts and developing new reactions in the computer before experiment.4 Once a mechanism is established with a computational model, making changes to the catalyst and substrate compositions to assess the impact of such changes is relatively easy and can require little time and effort, compared to experiment. Virtual screening efforts with the aim of discovering molecules and material with desirable properties are rapidly gaining popularity. Due to the complexity of reaction mechanisms, these reactions often require special attention. While automated optimization techniques have seen remarkable advances, most successful studies still rely on classical chemical logic and conventional strategies of reaction design. In addition to delivering energies and structures of intermediates that may not be accessible experimentally, DFT calculations offer the unique advantage of allowing for a qualitative examination of the electronic structure that is responsible for the numerical result in question.5 In principle, general concepts that not only explain one specific reaction but are valid for a whole class of reactions can be obtained from a detailed analysis of the computed results. In this review, we highlight prominent examples of such rational design strategies, where computational studies enhanced or completely led to the discovery of new chemistry. These studies show that computational methods can be used to predict new chemical reactions, in addition to fulfilling their traditional role of explaining what is experimentally observed. It is clear that calculations have begun delivering on the promise of being a powerful predictive design tool, but computer-aided de novo design of unprecedented chemical reactions continues to pose unique challenges and it cannot be carried out routinely or automatically at the moment.

variables while keeping the substrate class constant and analyzing reaction mixtures in search of the hypothesized products. One way to enhance these screening efforts is incorporating the experimental trends and combining them with the computations to formulate a quantitative structure− activity relationship (QSAR) or a quantitative structureselectivity relationship (QSSR), which can be employed for a structure guided optimization. These methods, popularized by Hansch, have seen much utility in the last 50 years and many examples of successfully employing QSARs to understand and optimize reactions exist.6 One notable example was reported by Kozlowski, where QSSR was employed to accurately predict the enantioselectivity of asymmetric amino-alcohol catalysts in the ethylation of aldehydes with diethylzinc.7,8 Denmark and co-workers have recently reported the use of QSAR and QSSR in a quest for discovering efficient, asymmetric, ammonium-ion phase transfer catalysts.9−12 A recent report by Doyle and Dreher describes the use of similar ideas and descriptor-based machine learning techniques to confirm that experimentally observed effects of additives in C−N cross-coupling reactions can be modeled13 appropriately within such a data-driven approach, but the use of machine learning for catalyst design is in its infancy. More recently, Kulik exploited graphical processing units to accelerate quantum mechanical calculations,14 and machine learning techniques were used to rationalize the HOMO−LUMO gaps of 15,000 open-shell transition metal complexes and 5,600 spin crossover complexes.15,16 An entirely different strategy compared to QSAR/QSSR is to adopt mechanism-based reasoning to computationally screen a variety of substrates and catalysts with a single series of mechanistic steps in focus until promising candidates are identified. This approach attempts to bypass the inefficiencies of traditional experimental screening where the overwhelming majority of the experiments are unsuccessful by design. By reducing the search space based on a proposed mechanism, the efficiency of experimental screening efforts should in principle be increased. Recent reports employing such a strategy include electrospray ionization mass spectrometry (ESI-MS) screening by Pfaltz,17 UV−vis discovery of new photocatalysts by Glorius,18 IR analysis by Sigman,19 and molecular graph and reaction work analysis by Kim.20 1.3. Scope of This Review

As with any other research tool, quantum chemical calculations deliver results that must be interpreted in an appropriate context, which requires a reasonably deep understanding of both the computational methodology and the chemistry that is being modeled. Due to the relatively short history of realistic, large-scale computer models being available, there is a significant imbalance in the required domain expertise: researchers capable of constructing technically sophisticated computer models of chemical reactions are largely unfamiliar with the vast and often complicated, sometimes unprecise empirical knowledge that derives from years of experimental research. As a result, there are many studies where computer models were incorrectly interpreted or unrealistic predictions were made. Also, due to the ease of using some computer software and hardware, many experimentalists have recently started heavily relying on calculations to complement experimental results, but the computational assumptions, inaccuracies, and over interpretations are common pitfalls that are not readily obvious. Automation, massive screening,

1.2. Strategies of Catalyst Design

A mechanistic hypothesis is often indispensable for the development of new chemical transformations. Computational reaction modeling can provide a deep understanding of a chemical mechanism that can be specifically probed and evaluated. The computational search for new chemical reactions takes inspiration from experimental reaction screening efforts undertaken in the past. Conventionally, a reaction screening consists of enumerating through possible reactant, catalyst, and additive combinations. While many methods of reaction screening have been tried, they can be categorized into two groups: (i) reaction-based screening and (ii) mechanism-based screening. The reaction-based screening is a commonly employed method and consists of testing different reaction condition B

DOI: 10.1021/acs.chemrev.9b00073 Chem. Rev. XXXX, XXX, XXX−XXX

Chemical Reviews

Review

these energies can be calculated to a level of internal consistency that allows for useful qualitative conclusions to be drawn. Computer models of organocatalysts that incorporate these hydrogen-bonds have been particularly successful, and striking examples are presented below. 2.1.1. Urea. Etter and co-workers31 observed that N,Ndiaryl ureas cocrystallize with Lewis base donors, suggesting that the hydrogen-bond donor ability of the urea can be used to form well-defined, stable adducts. This insight inspired the development of numerous urea and thiourea-based organocatalysts.31−34 With this basis, many groups have taken advantage of these catalysts with different Lewis bases harnessing the power of hydrogen-bonding interactions.35−37 Schreiner and Wittkopp reported that a 3,3′,5,5′-tetratrifluoromethyl thiocarbanilide catalyst is an effective organocatalyst for Diels−Alder reactions,38,39 and it was utilized for various applications, such as the Baylis−Hillman,40 Friedel−Craftstype,41 and acetalization42 reactions. Nevertheless, investigations into more acidic thiourea catalysts were not reported until 2008.43 Rozas and Connon reported an in-silico DFT study that resulted in the discovery of a new class of urea and thiourea catalysts capable of effectively catalyzing several organic transformations (Figure 1a).43 These calculations

machine learning, and artificial intelligence are promising attempts to overcome some of these difficulties, and there is little doubt that these technologies will have a profound impact on the way computer simulations of chemical reactions will be used in the future, but their current use is limited.21,22 From an optimistic perspective, these new tools enable the detachment of the chemical discovery process from personal bias and allow for a more objective exploration of possible reaction mechanisms. Critically, it could be argued that an algorithmic search that ignores chemical precedence and intuitive trends from past experiences and employs a combinatorial approach does not take advantage of the high-quality domain knowledge that has been built over decades, if not centuries. The problem is of course that the chemical knowledge that is often denoted “chemical intuition” is difficult to represent in a machine learnable form. It is also unlikely that complete and totally unbiased exploration of chemical reaction mechanism space is ever going to be realistic. In part due to these limitations, the most successful applications of computational methods for improving chemical reactions still rely on ad hoc analyses of prototype reactions, from which key mechanistic insights are derived. With automation and machine learning still at an early stage of development, manual analysis and human intelligence continue to dominate the rational design of chemical reactions. Using chemically reasonable, often intuition and experience based logic, potential improvement strategies are derived and tested with highly focused and purposefully designed systems. This approach is intensive in manual labor, and the outcome is highly dependent on the chemical knowledge and the ability of the operator to interpret the numerical results and conceptualize them into a unifying model. In this review, we focus on recent examples of theory-guided homogeneous catalyst designs based on such rational design principles.

2. ORGANOCATALYSTS In organocatalysis, a chemical reaction is governed by catalysts containing predominantly main group atoms such as carbon, hydrogen, oxygen, nitrogen, and sulfur within the scope of organic molecules.23 An organocatalyst has many experimental advantages and avoids the general toxicity associated with many heavy metals, and as far as computational modeling is concerned, these purely organic systems avoid the intrinsic computational challenges associated with the electronic structure of the metal center. Several recent reviews have focused on organocatalysts,23−27 and we will provide an overview of some predictive computational work and describe the experimental tests of these mechanistic predictions.

Figure 1. (a) Urea-type catalysts capable of effectively catalyzing epoxide addition. (b) Increased interaction energy by the tosyl group.

2.1. Hydrogen-Bond Donor Catalysts

A dominating chemical feature in organocatalysts is the activation of substrates employing noncovalent interactions, most notably hydrogen-bonds.28 As is commonly seen in enzymatic and supramolecular host−guest interactions, hydrogen-bond donor type catalysts can act as contact points for hydrogen-bond accepting substrates that are held in a structurally well-defined manner at the reactive site leading to stereoselective reactions. While these interactions are generally relatively weak, they are strong enough to introduce chemically meaningful selectivities. From a computational molecular modeling perspective,29,30 it is difficult to precisely predict absolute hydrogen-bond energies, since they are only a few kcal/mol in value. Fortunately, there is good evidence that

showed that the activity of Schreiner’s catalyst could be significantly enhanced by replacing the phenyl group with a tosyl group, resulting in a stronger hydrogen-bonding interaction between the catalyst and the substrate (Figure 1b). Guided by this theoretical finding, a series of experiments was carried out and the scope of the reaction was extended to various reactions, such as Friedel−Crafts-type reactions or formation of β-amino alcohol products derived from aniline. As anticipated, the computationally optimized organocatalyst showed outstanding performance compared to the previous catalysts. A similar strategy of optimizing the hydrogen-bond donor capability using a computer model was adopted by Hajra and co-workers, who reported a catalyst-free, solvent C

DOI: 10.1021/acs.chemrev.9b00073 Chem. Rev. XXXX, XXX, XXX−XXX

Chemical Reviews

Review

model, can accurately model a reaction where pKa changes are only one of the major factors that impact the overall reaction mechanism, or differentiate between multiple mechanisms. All these legitimate concerns notwithstanding, DFT calculations can deliver insights with enough confidence on which to base reaction design. To do this, error-cancellation must play a significant role in delivering reasonable energies. Based on the initial results Houk and Li investigated a variety of chiral squaramides in the asymmetric Friedel−Crafts reaction of indoles with acyl phosphonates and identified catalysts that may display improved catalytic activity. The catalyst was then tested experimentally with different substrates to give very good enantioselectivity up to 96% ee and yield up to 93%. To better understand the mechanism of stereoinduction, the authors calculated four plausible transition-state geometries, which represented two different substrate binding modes. The authors found that the lowest energy transition state is characterized by the sulfinyl oxygen being hydrogenbonded to the indole N−H bond to afford the experimentally observed product.48 Subsequently, the modified catalysts with N-tert-butyl sulfinyl squaramide were utilized for unanticipated purposes, namely as agents for anion recognition54 and chiral sensing.55,56 2.1.2. Phenol. Organocatalysts acting as hydrogen-bond donors can be used for activating carbon dioxide (CO2) for incorporation into epoxides, in particular to form various types of cyclic carbonates.57,58 Recently, a new family of CO2 converting scorpionate organocatalysts was designed through extensive DFT calculations (Figure 3a).59 The mechanism of the cyclic carbonate synthesis is well-established,60−63 and formed the foundation for a design strategy that aimed at a one-component bifunctional organocatalyst starting from a simple molecular fragment synthesized previously.64,65 Two

(water) assisted regio- and sterospecific ring opening of spiroazirdine oxindole.44 Rawal and co-workers pioneered the development of chiral squaramide derivatives to render enantioselective conjugate addition of 1,3-dicarbonyl compounds to β-nitrostyrenes.45 Unfortunately, the application of chiral squaramide organocatalysts is limited due to self-aggregation, low solubility, and low activity. Building on Rawal’s work, and incorporating insights from prior work on hydrogen-bonding organocatalysts,38,46,47 Houk and Li identified the acidity of these asymmetric squaramide systems as a viable target for modification, since acidity is usually associated with protondonating ability and, hence, hydrogen-bond strength.48 Based on organocatalyst systems developed by Ellman and coworkers, replacing N-aryl groups on urea and thiourea with Nsulfinyl groups,49−52 a new chiral squaramide organocatalyst was designed and optimized in the computer (Figure 2a).48 A

Figure 2. (a) Asymmetric Friedel−Crafts reaction of indoles with acyl phosphonates. (b) Functions of each structure of the organocatalyst (left). New transition state proposed with the squareamide catalyst (right).

systematic comparison of the N-tert-butylsulfinyl substituted (thio)urea and 3,5-bis(trifluoromethyl)phenyl substituted (thio)urea showed that the incorporation of N-tert-butylsulfinyl gave stronger electronic effects, resulting in a significant decrease in pKa. In addition, the presence of the tert-butyl group was known to increase the solubility of these systems. Moreover, a new transition-state structure was located during the computational investigation (Figure 2b).48 This study highlights the aforementioned point about balancing the accuracy of the quantum chemical model against its practical utility for deriving chemically plausible insights. The accurate prediction of pKa values is exceedingly difficult, and without any context accuracies, within 1−2 pKa units are necessary for pKa predictions to be chemically meaningful. pKa calculations are generally difficult because loss of a proton leads to a change of the molecular charge and is often accompanied by unbound electron densities, and the change of the solvation energy for such a molecular fission process is difficult to model properly. Additionally, the simple classical treatment of the translational entropy change for such a process is also questionable.53 Given these concerns, it should not be expected that a standard DFT calculation, combined with a simple and computationally cheap continuum solvation

Figure 3. (a) Epoxide−CO2 coupling with original (blue) and computationally predicted (red) organocatalyst and their experimental yield. (b) Functions of each moiety of the scorpionate organocatalyst with the overall barrier depending on the functional groups on the para-position. (unit: kcal/mol). D

DOI: 10.1021/acs.chemrev.9b00073 Chem. Rev. XXXX, XXX, XXX−XXX

Chemical Reviews

Review

strategies based on theoretical insights were considered, (i) reducing the translational entropy cost by covalently attaching an ammonium iodide moiety to the catalyst and (ii) designing an additional hydrogen-bonding interaction by incorporating two phenolic hydroxyl groups. Calculations revealed that the last ring cyclization of the substrate assisted by two hydrogen bonds to the substrate carbonate had the highest overall barrier of 24.1 kcal/mol. The catalyst was optimized by eliminating the ortho- position methyl group to avoid steric hindrance and varying the functional groups containing electron-donating or withdrawing groups at the para-position of the phenols. Among the different substituents, the lowest barrier was predicted with an electron-donating −NMe2 group (21.0 kcal/ mol), since the formation of the final product required a weaker hydrogen-bond (length up to ∼1.9 Å) which can be induced by electron-donating functional groups (Figure 3b). Experiments were guided by these computational predictions and resulted in the discovery of one of the most active singlecomponent CO2 converting organocatalyst reported thus far and gave ∼98% yield within 7 h at room temperature and only 10 bar pressure of CO2. This study is a prominent example of a synergistic and iterative optimization of a catalyst employing a precise mechanistic insight from a combined computational and experimental study. 2.1.3. Proline. Based on a reaction mechanism, transitionstate calculations can directly test catalyst selectivity control.29 For example, Houk, Tanaka, and Barbas used transition-state calculations to examine several factors controlling diastereoselectivity for the (S)-proline Mannich reaction of aldehydes with N-p-methoxyphenyl protected imines, which generates syn-amino aldehydes.66,67 Using a closed transition-state structure with hydrogen-bonding, the (S)-proline catalyst was redesigned to (3R,5R)-5-methyl-3-pyrrolidinecarboxylic, which provided diastereoselectivity to the previously unavailable anti stereoisomer. Before experiments, HF/6-31G* calculations predicted that this new organocatalyst would provide 95:5 anti:syn diastereoselectivity and ∼98% ee for the reaction of propionaldehyde and N-PMP-protected α-imino methyl glyoxylate. Consistent with the design criteria, experiments using the new organocatalyst gave quantitative agreement the ab initio predictions (Figure 4a).66,67 Interestingly, the transition-state calculations showed that the positional change of the carboxylic acid in the organocatalyst was responsible for the majority of the selectivity with the anti:syn ratio decreasing to 82:18 without the methyl group (Figure 4b).66,67 However, in this case the calculations were less quantitative with an experimental anti:syn ratio of 95:5.

Figure 4. (a) Mannich reaction of aldehydes with N-p-methoxyphenyl protected imines with improved selectivity with computationally designed catalyst. (b) syn- and anti-Mannich product forming transition states.

substitution of sp3 electrophiles are less known while the enantioselective ring opening of oxetanes is thoroughly studied and experimentally explored in detail for example by the Sun group.73−75 Houk and co-workers investigated one of the Sun catalysts that uses a SPINOL-derived PA catalyst (SPINOL = 1,1′-spirobiindane-7,7′-diol) and HCl as a nucleophile (Figure 5a).76 This catalyst is capable of asymmetric desymmetrization of oxetanes to selectively form the R isomer in ∼94% ee, showing much higher selective and reactivity than the BINOL based PA (BINOL = 1,1′-bi-2-naphthol) catalysts. Computational analysis of the transition state responsible for the enantioselectivity showed that deprotonation of HCl coupled to the protonation of the oxetane oxygen is a key feature at the transition state. The transition state leading to the formation of the (R)-isomer is marginally preferred over that giving the (S)-isomer by 1.8 kcal/mol. The quadrant projections indicate that the energy difference originates from the orientation of the catalyst walls (6,6′-aryls) and the spirobiindane relative to the two substrates. Major steric repulsion between the phenyl substituent of the oxetane and the cyclohexyl chain occurs in the (S)-TS form and the complex distorts itself to avoid such sterically demanding interaction. A distortion/interaction analysis suggested that this distortion of the (S)-TS conformation is energetically unfavorable resulting in a slightly higher energy barrier than the (R)-TS. Compared to BINOL-derived catalysts, the less flexible spirobiindane backbone led to the higher enantioselectivity by enhancing steric interactions. A general, “back-ofthe envelope” model (Figure 5b) was proposed to elucidate the basic principles of the asymmetric oxetane opening reactions catalyzed by various catalysts.74,75,77 The SPINOL-based catalysts were examined for the glycosylations of complex polyols and afforded the desired product in higher yield (82%) and selectivity (73:27 r.r.).78

2.2. Lewis Acidic Organocatalysts

The presence of a Lewis acid or a Lewis base functional group, or both, in an organocatalyst can efficiently activate electrophilic or nucleophilic substrates. Ideally, if self-aggregation and self-neutralization can be avoided, the presence of both Lewis acidic and basic sites can enhance the reactivity and be used to increase chemo- and stereoselectivities of chemical reactions.68,69 In the following sections (2.2 and 2.3), some prominent examples of these ambivalent catalysts that were computationally identified, optimized, and experimentally confirmed will be highlighted. 2.2.1. Phosphorus. Phosphoric acid (PA) catalysts are known to be bifunctional because they possess both acid and base components that can activate electrophiles and nucleophiles.70−72 Utilizing these versatile catalysts for the E

DOI: 10.1021/acs.chemrev.9b00073 Chem. Rev. XXXX, XXX, XXX−XXX

Chemical Reviews

Review

Figure 6. (a) Chiral phosphoric acid catalyzed spiroketalization reaction and the suggested concerted cyclization transition state. (b) Concerted asynchronous transition state of forming (R)-spiroketal.

Figure 5. (a) Asymmetric desymmetrization of oxetanes by chiral phosphoric acids. (b) Proposed “back-of-the-envelope” model.

Chiral PA was more energetically plausible than the (R)-Chiral PA due to the high steric interactions between the phenyl groups in the enol ether and the aryl substituents of the organocatalyst, which was consistent with the experiments (Figure 6b). In the same year, Varga and Pápai reported the tetrahydropyranylation of alcohols using a thiourea.83 Interestingly, the thiourea behaved as a Brønsted acid to form an oxacarbenium ion which was similar to the PA catalyst observed by Zimmerman and Nagorny.79

Another interesting example of using PA catalysts is for asymmetric spiroketalization. Zimmerman and Nagorny used a chiral PA to asymmetrically functionalize spiroketal scaffolds that can be applied to the synthesis of various natural products (Figure 6a).79 The computational studies provided a rational mechanistic concept for the origin of the stereoselectivity in these reactions. Three potential mechanistic scenarios were considered: (i) reaction proceeds via an oxocarbenium intermediate, (ii) an anomeric phosphate intermediate is involved, and (iii) the cyclization proceeds in a concerted fashion without any intermediate. For relatively large systems with many degrees of structural freedom, it is often difficult to propose a precise mechanism and capture the intermediates and transition states. This is not simply a matter of computational cost due to the size of the molecule, but locating mechanistically significant intermediate and transition state structures becomes difficult due to the potential energy surface often becoming less defined due to spurious and often meaningless degrees of molecular motion. In this study, the growing string method (GSM) was utilized, which allows for locating transition states in a flat and ill-defined energy surface.80−82 GSM improves the search for the transition states in asynchronous and concerted transformations notably. Three potential mechanisms involving the phosphate catalyst were proposed based on preliminary studies. It was found that mechanisms involving the formation of oxocarbenium intermediates were not likely due to the nature of the polar transition state and a relatively high energy barrier (∼21.1 kcal/mol). Instead, a single-step asynchronous mechanism was proposed. With a plausible mechanism in hand, through stereochemical system modeling, the transition state of (S)spiroketalization of the enol ether substrate involving (S)-

2.3. Lewis Basic Organocatalysts

2.3.1. Ionic Liquid. CO2 capture and conversion into synthetically useful compounds have recently gained prominence in small molecule activation. CO2 is inert and difficult to activate due to its very high bond dissociation energy (128.4 kcal/mol).84 In this regard, ionic liquids (ILs) showed remarkable performance85−87 by acting as absorbents and activators.88,89 The Wang group recently reported a new route for the synthesis of 3(2H)-furanone which is a fundamental building block of various pharmaceuticals90,91 by utilizing CO2 (Figure 7a).92 Their reaction design takes advantage of a series of Lewis base-functionalized ILs in the presence of CO2 to facilitate the hydration of diynes into furanone. The anionic and cationic partners should be matched appropriately for the design of an active IL catalyst to initiate the reaction. This work led to the conceptual prediction of a suitable range of basicity (pKa) for the anions through electronic structure calculations. As mentioned above, pKa predictions are challenging.93 Since the pKa of the reactant diyne alcohol (2methyl-6-phenylhexa-3,5-diyn-2-ol) along with the CO2 has a pKa of about 11.2, the benzimidazolide (BenIm) and the triazolide (Triz) which had similar calculated pKa values were predicted to be efficient anions (Figure 7b).92 This prediction F

DOI: 10.1021/acs.chemrev.9b00073 Chem. Rev. XXXX, XXX, XXX−XXX

Chemical Reviews

Review

In these reactions, the NHC was generally accepted to activate either the Si−H bond or the CO2 itself (Figure 8a).95,99−102 Through DFT calculations, Zhou and Li reported

Figure 7. (a) Effective synthesis of 3(2H)-Furnanones with CO2 and ionic liquids. (b) Quantum chemically predicted pKa values of the substrate and IL base catalysts. (c) Transition state of the highest barrier and the calculated NBO charges.

was confirmed when the ILs with [BenIm] as the anion were tested experimentally and gave the most active catalyst among other anions tested, such as imidazolide, benzotriazolide, tetrazolide, etc. Another aspect is that the role of the cation was revealed by DFT calculations and NMR analysis (Figure 7c).92 With the experimentally most active species [HDBU][BenIm] in hand (84% yield), the calculated reaction mechanism with only the [BenIm] shows that the intramolecular cyclization step has the energetically highest barrier, namely, 23.3 kcal/mol without the cation, 24.6 kcal/mol with the cation [HDBU], and 25.6 kcal/mol with cation [N1111]. By examining the natural bond orbital (NBO) charges in that state, the charges on the C and O involved in the cyclization with only [BenIm] were 0.126 and −0.799, respectively. The NBO charge difference of C and O in [HDBU][BenIm], an example of a protic ionic liquid, was calculated to be as large as 0.861. Conversely, the NBO charge difference was found to be 0.855 in the aprotic ionic liquid [N1111][BenIm]. This small but meaningful difference was interpreted as an indication that the protic ionic liquid [HDBU][BenIm] will more effectively facilitate this reaction. This analysis was in line with the experimental results where the [N4444][BenIm] showed a slightly decreased yield of 72%, compared to the results of [HDBU][BenIm]. 2.3.2. N-Heterocyclic Carbene. Like hydrogen-bonded systems and ILs, N-heterocyclic carbenes (NHC) are one of the most promising organocatalysts known to activate CO2. Some time ago, Cantat94 and Ying95 reported a NHC catalyzed reductive functionalization of CO2 into formamides and methanol. Recently, Cantat reported the formation of various N-heterocycles such as benzimidazole or quinazolinone96 or even methyl amine derivatives97,98 from CO2 using the NHC organocatalyst. Polymethylhydrosiloxane and phenylsilanes are particularly effective as reductants in combination with amines as functionalizing reagents.

Figure 8. (a) NHC organocatalysts used for reductive functionalization of CO2 with Si−H bond. (b) Previously proposed activation modes and newly discovered activation mode discovered by DFT.

a novel mode by which NHCs can activate and functionalize CO2 that acts as a precatalyst (Figure 8b).103 The active species is proposed to be the tightly bound ion pair [(NHC)H]+[Carbamate]−, an ionic liquid that is formed in situ. The ion-pair adducts are formed under room temperature and ambient pressures whose barriers are computed to be less than 13.5 kcal/mol. This indicates that it is a fast equilibrium process that should be considered as zero energy reference. The anionic oxygen of the carbamate moiety becomes the new active site that is free to perform nucleophilic attack on the Sisubstrate. The new activation modes, especially the ion pair [IPrH]+[Carbamate]− activating the Si−H bond via a concerted linear backside SN2 attack, involving the amine substrate gave a relative free energy of only 19.3 kcal/mol, which was more favorable than the classical activation modes proposed previously. Similarly, Wang performed DFT calculations to understand the mechanism of transforming CO2 to CH4 using a NHC organocatalyst via the formation of an ammonium hydroborate ion pair.104 In the following year, the Dyson group reported the N-formylation of amines mediated by fluoride and hydroxide anions.105 They studied the influence of various hydrosilanes on the reaction rate. For Ph2SiH2, the reaction rate decreased, in good agreement with the steric congestion caused by the hydrosilanes as they proceed via the SN2-type mechanism as proposed by Li.103 2.3.3. NX−OY. Stereoselective allylation and propargylation of aldehydes represent an important class of transformations that gives quick access to stereodefined homoallylic and G

DOI: 10.1021/acs.chemrev.9b00073 Chem. Rev. XXXX, XXX, XXX−XXX

Chemical Reviews

Review

homopropargylic alcohols.106 One of the widely used methods to achieve these products is through Lewis-base catalysis of alkyltrichlorosilanes, which was pioneered by Denmark.107 While a plethora of examples taking advantage of N-oxide catalysis for allylation exist,106 success in attaining stereoselective catalysis in propargylation reactions is relatively rare.108 One such example was recently reported by Takenaka and co-workers where a homopropargyl was generated in high yields and high enantioselectivity by taking advantage of a helical chiral N-oxide catalyst (Figure 9a).109 The selectivity

dioxide catalysts and experimentally cross-checked the calculated ee.111 The computational results were found to be in good agreement with experimental results, and two of the allylation catalysts were found to be effective for propargylation reactions.111 More recently, Wheeler and co-workers expanded on these findings by taking advantage of AARON to computationally screen 59 potential catalysts for propargylation reactions and made a series of experimentally testable computational predictions. Interestingly, 12 catalysts were identified and calculated to achieve >95% ee.112 This work is a prominent example of a focused, large-scale survey of chemical catalyst reactivity aided by computational modeling of a specific mechanistic proposal. More recently, Wheeler and coworkers have generalized the AARON program for calculating predicting transition-state selectivity for both organocatalysts and transition-metal catalysts with highly complex ligand architectures.113 The current implementation requires users to input a transition-state template library and ligand information, and then AARON automates DFT conformational transition state searching (for rotatable substituents) using a hierarchical decision scheme. Proof-of-principle use was demonstrated for complex Pd-catalyzed Heck allenylation and Rh-catalyzed hydrogenation of enamides. A similar type of automated searching tool with a transition-state template, but using transition-state force fields, was recently reported by Wiest and Norrby.114 2.3.4. Cysteine. In section 2.1.3, we discussed the theorydriven experimental studies that employ proline. Being a Lewis base, cysteine is also widely found in active sites of several metalloproteins and it can also act as a catalyst in organic reactions using its thiol side chain.115 In 2007, Miller developed a new method for the enantioselective Rauhut− Currier cyclization with a protected cysteine catalyst and tBuOK.116 Experiments showed that the type of the N-terminal protecting group and the number of added water equivalents are crucial in determining the enantioselectivity. Later, the role of the K+ counterion and the water additive was quantified through detailed electronic structure calculations by Houk and co-workers.117 In this paper, water molecules and counterions are actively involved in the catalysis which are modeled explicitly at the DFT level and compared against those without these fragments. First, the mechanism was modeled using methanethiolate as a truncated model system for cysteine. The computational reaction modeling proceeded as follows (i) Addition of the thiolate across the double bond of the bis(enone) substrate in either syn- or anti- form. Here, K+ is coordinated to the carbonyl oxygen of the substrate. (ii) Intramolecular Michael addition follows, where the stereoselectivity is determined. (iii) The preformed enolate intermediate is protonated by water followed by an E1cB elimination mechanism which is the rate-determining step. (iv) Finally, the thiolate model is replaced by the cysteine amino acid as a nucleophile and the rate determining E1cB pathway was probed with eight different isomers. These calculations suggest that the water is a key component in this reaction due to its stabilizing ability of the oxyanion intermediate and the potassium cation supports the preorganization of the hydroxide which is close to the deprotonation site. Thus, the computational study provided valuable insights on the potential energy surface of enantioselective Rauhut−Currier cyclization reaction observed experimentally.

Figure 9. (a) Helical chiral 2,2′-bipyridine N-monoxide organocatalyst and its derivative used in the propargylation. (b) Si face and Re face interactions by the N-oxide organocatalyst with the substrates.

increases by an extending the conjugated group. A follow-up DFT study on this reaction mechanism concluded that the origin of enantioselectivity lies in electrostatic interactions between the silyl chlorines and the aldehydic carbonyl which was distinctively different from the previously proposed reasons (Figure 9b).110 These systems are nontrivial as the chiral N-oxide catalysts are efficient for stereoselective allylation, whereas they failed to produce high enantioselectivity in propargylation reactions. This was in contrast to chiral phosphoric acids, which can be used effectively for both reactions. To gain a deeper understanding of these reactivity patterns, Wheeler and coworkers employed DFT to study the N-oxide catalyzed allylation and propargylation reactions of alkyltrichlorosilanes with benzaldehyde.108 This study unveiled the origin of enantioselectivity in these reactions to be in line with Takenaka’s proposal, namely, that favorable electrostatic interactions between the chlorine atoms on silicon (δ−) and the vinylic hydrogen atoms (δ+) promote the stereoselectivity. Based on their findings in the aforementioned studies, Wheeler developed a toolkit called AARON (Automated Alkylation Reaction Optimizer for N-oxides) that was used to computationally examine 820 transition states for 18 N,N′H

DOI: 10.1021/acs.chemrev.9b00073 Chem. Rev. XXXX, XXX, XXX−XXX

Chemical Reviews

Review

2.4. Theoretical Enzyme Design

Theozymes are hypothetical enzymes computationally designed to mimic enzyme pockets using computer models. Often these constructs are structural and/or functional models of the natural enzymes. This area has received much attention recently due to the importance of its applications in biocatalysis.118,119 Using bioinspired manifolds, a chemical reaction can be accelerated through the careful design and deployment of these theozymes to lower the reaction barriers. They also hold significant value as a conceptual model that simplifies and visualizes the mode of action of the reactive site of the enzyme. In any enzymatic reaction, the barrier for a given transformation can be lowered by various interactions of the substrate with different amino acid residues (Figure 10).120 Figure 11. (a) Transesterification reaction of computationally designed spiroligozyme. (b) Conceptual description of the QMtheozyme from the “inside-out” approach. (c) Transition state of alcohol activation of the triad and the dyad.

of the acylation of spiroligomer derivatives complemented the computational investigation. The spiroligomer with the 4pyridyl group gave the best activity, and it was found to be optimally positioned toward the benzyl alcohol anchored by a hydrogen-bond. This rapid formation of the acyl-enzyme intermediate inspired the authors to perform transesterification reactions of vinyl trifluoroacetate with methanol. Interestingly, the lack of “oxyanion hole” to stabilize the transition state limited the reactivity of the corresponding spiroligomer. When a 3-substituted urea benzoyl was added, a great acceleration of methanolysis was observed offering further support for the conceptual model derived from the theozyme construct. The calculated energy barrier was in excellent agreement with the design. Recently, Tantillo and Siegel investigated why the enoylacyl-carrier protein reductase (FabI) has an unusual substrate promiscuity toward α,β-unsaturated aldehydes.129 Five FabI enzymes and 13 substrates with varying oxidation states and with varying chain lengths were chosen and examined by combining docking and DFT calculations (Figure 12).129 The inherent catalytic reactivity of the substrate is dictated by the hydrogen-bonding interactions with the tyrosine residue of FabI, as elucidated by quantum chemical calculations. Of the chosen substrate molecules, s-trans substrates did not develop the hydrogen-bonds, whereas the corresponding s-cis substrates formed these hydrogen-bonds and were the catalytically relevant substrates. This study is remarkable because it demonstrates the power of combining two methods with different scales of resolution to solve a challenging problem. DFT calculations are ineffective to predict proper docking of a substrate into an active enzyme pocket. Employing standard docking protocols based on classical mechanics calculations, the authors were able to identify the most relevant structure of how the substrates bind. To discover the energetic and structural impacts of the specific substrate with the enzyme, quantum chemical calculations are employed. This workflow affords a high-resolution model that was capable of reproducing the experimentally observed reactivity trends and at the same time provides an atomistically detailed mechanism of action and selectivity. Another prominent example of using a computer model of an enzyme to design an enzymatic reactivity from firstprinciples is the Kemp elimination catalysis (Figure 13a).130

Figure 10. Hypothetical energy diagram proposed by Mak and Siegel.

Notably, pioneering work by Shaik,121 Siegbahn,122 Harvey,123 and Ryde124 has contributed significantly to the theoretical investigation of metalloenzyme mechanisms which are beyond the scope of this review. Using the theozyme model, the nature and the type of amino acid residues that should be modified can be predicted and rational design strategies can be developed.125 These in-silico predictions can be and have been verified with experiments. Modeling chemical reactions through the theozyme technique allows for a priori predictions that can increase the efficiency of experimental work notably by reducing the number of experiments and accelerating the discovery process. The concept of theozymes is only two decades old, and experimental work on enzymatic systems is particularly laborious; hence, the number of studies is relatively small. Several reactions that have been studied and optimized using the theozyme construct have recently been highlighted by Nanda and Koder.126 Recently, a spiroligomer catalyst was designed capable of methanolysis of vinyl trifluoroacetate (Figure 11a).127 Houk and Schafmeister introduced an “inside-out’ approach in theozymes to stabilize the transition state by adding a hydrophobic effect of aldol reactions.128 This “inside-out” approach was applied to the transesterification theozyme construction (Figure 11b).127 First, the alcohol activity change was studied using DFT calculations and implementing a nucleophilic pyridine group and a spiroligomer dyad instead of a Ser-His-Glu triad found in the natural enzyme. The transition state of the alcohol activation of the dyad was ∼6 kcal/mol higher than that of the triad in a concerted activation/addition mechanism where the activated oxygen of the −OH attacks the ester (Figure 11c).127 Since the calculated barrier for the transition state was calculated to be reasonable at 14.7 kcal/ mol for the pyridine, the study was expanded to analyze the nucleophilicity change of the alcohol depending on the location of the pyridyl groups. Experimental kinetic studies I

DOI: 10.1021/acs.chemrev.9b00073 Chem. Rev. XXXX, XXX, XXX−XXX

Chemical Reviews

Review

Figure 12. Decision tree for predicting potential new substrates for FabI.

Table 1. Selected Bond Dissociation Energies84,137,138 (unit: kcal/mol) Molecule

ΔE

Molecule

ΔE

H2 N2 O2 CO

104.2 228.6 120.3 258.9

CO2 H2O NO CH4

128.4 118.8 152.8 103.5

converted to commodity chemicals such as methanol (from CO2)132 or ammonia (from N2).133 Additionally, due to the serious problems arising from the emissions associated with burning fossil fuels, these reactions represent an avenue of pollution reduction. Many of these reactions are successfully carried out in nature by metalloenzymes sometimes involving multimetallic active sites as found in photosystem II (H2O oxidation),134 nitrogenase (N2 fixation),135 and hydrogenases (H2 splitting),136 to name a few prominent examples. In almost all cases, these activations are redox reactions and the necessary protons and electrons are often provided by amino acids or other small molecules, such as water. Inspired by these enzymatic systems, both experimental and computational studies have been carried out to understand the mode of action and possibly to engineer artificial systems that can carry out the same reactions. Small molecule activation in general is a large research area with a long tradition. The latest advances are regularly reviewed, and several recent reviews139 and special issues140−142 are available. Thus, only a few computational studies will be highlighted to demonstrate the latest trends and showcase the challenges ahead in this vast and highly active research area. 3.1.1. N2 Fixation. Nitrogen activation continues to be a difficult challenge, as the N−N triple bond has a bond dissociation energy of nearly 228.6 kcal/mol (Table 1), has no dipole moment, and is not soluble to any practical degree in common solvents. In nature, nitrogenases possessing a Mo−Fe (or Mo−V) multinuclear center convert N2 to ammonia.135 From an industrial viewpoint, the renowned Haber−Bosch process produces tons of ammonia from N2 employing harsh reaction conditions, such as high temperature and pressure, using an Fe-based catalyst that remains still poorly defined and not well understood. A handful of attempts were made previously to design processes that operate at milder conditions.143−148 Stephan and co-workers recently proposed a frustrated Lewis acid/base pair that may activate N2, where the mechanism was supported by X-ray diffraction studies and DFT calculations.149 Although the Piers borane is Lewis acidic enough to firmly bind N2, no value added chemical such as ammonia was reported thus far.

Figure 13. (a) Kemp elimination reaction mechanism and the target transition state. (b) Computationally tested amino acids for the insilico designed enzyme.

Using ROSETTA, a computational tool developed by Baker for the de novo design and prediction of protein structures,131 eight enzymes were designed to use two different catalytic motifs during the Kemp elimination. In this reaction, a proton is abstracted from the C3-position of the 5-nitrobenzoisoxazole, which is usually difficult to achieve. The quantum chemical and classical methods combined in the theozyme model suggested that amino acids containing a carboxylate and an imidazole in their side-chain may increase the enzymatic activity. The negative charge accumulated in the transition state was stabilized by hydrogen-bonds to the amino acid residues or to solvent water or through hydrophobic interactions (Figure 13b).130 These are molecular features that can be captured in a consistent and meaningful manner in these calculations. To test the validity of these boding models, experiments including site-directed mutagenesis and highresolution single crystal diffraction were carried out, confirming that all key features of the enzymatic structure−activity relationship have been properly captured. The catalyst optimized in this in-silico process displayed reaction rates that are up to 100,000-times faster.

3. ORGANOMETALLIC CATALYSTS 3.1. Small Molecule Activation

Small molecules are often inert due to their very large bond dissociation energies that range from ∼100 to ∼260 kcal/mol (Table 1).84 When these molecules are activated, they can be J

DOI: 10.1021/acs.chemrev.9b00073 Chem. Rev. XXXX, XXX, XXX−XXX

Chemical Reviews

Review

from the proton source, or even from the choice of the density functional. The imido species, [Mo(V)]NH, is a potential intermediate in the Schrock catalytic cycle,159 and it can be generated through a proton-coupled electron transfer (PCET) from the nitride intermediate, [Mo(VI)N], which has been crystallographically characterized. Recently, a joint experimental (EPR/ENDOR) and computational study was carried out to elucidate the electronic structure of this key intermediate.159 Due to the strong static correlation that renders standard DFT methods unreliable, the multireference wave function method CASSCF was chosen to model the electronic structure including spin−orbit coupling and Jahn−Teller vibronic coupling. These studies have now established a firm foundation for this extraordinary catalyst, and a highly plausible and detailed mechanism for the generation of ammonia from molecular dinitrogen employing a well-defined and wellcharacterized homogeneous catalyst is available. Whereas groundbreaking in the sense that this Mo-catalyst was the first molecular catalyst that can produce ammonia from N2, the catalytic performance is far from being anywhere close to technical exploitation. Thus, one of the major motivations for studying this system is to find a way of improving the catalytic performance. Without doubt, any such rational optimization effort requires a firm understanding of the mechanism and conceptual clarity on which are the key intermediates in the catalytic cycle. 3.1.2. O2 Activation. In the last six decades, dioxygen activation has been one of the most intensively studied small molecule reactions.166,167 Being an ubiquitous molecule with a variety of biological and technical functions, dioxygen is of utmost importance. O2 activation is critical, for example in respiration and alkane oxidation. The fundamental oxidation reactions typically follow the equations shown below.

Organometallic complexes containing mononuclear and dinuclear metal centers of iron and molybdenum are promising catalyst candidates for N2 activation and were investigated extensively in a series of pioneering studies by Cummins,150,151 Schrock,152 Peters,153 and Nishibayashi.154 Over the years, several new catalysts containing other transition metals such as vanadium,155 cobalt,156 ruthenium/osmium,157 and rhodium158 were also reported. A recent study by Leitner and coworkers leveraged the known molybdenum catalyst by elucidating the mechanism through DFT, leading to the discovery of new metal complexes consisting of [M(H)2(H2)(PXP)] pincer complexes.152 Specifically, ruthenium, iron, and osmium metals with PNP, PSP, and POP ligands were examined computationally. The catalytic reaction mechanism employing the Schrock catalyst (Figure 14) was investigated in detail by a series of DFT calculations, as will be discussed in detail below.159

O2 + 4H+ + 4e− → 2H 2O

(i)

R−H + O2 + 2H+ + 2e− → R−OH + H 2O

(ii)

The first reaction can be catalyzed by cytochrome oxidases containing copper and iron, and the second reaction is often catalyzed by cytochrome P450. In addition, hemoglobins (oxygen transport) and myoglobins (oxygen storage) perform important biochemical processes.168 The dioxygen bound to metal species can generate three types of intermediates, peroxo, superoxo, or hydro-peroxo, which have distinct electronic structures and reactivities (Table 2).169 Several of

Figure 14. Proposed catalytic cycle for the Schrock catalyst.

Due to the large system size of the original Schrock catalyst, the HIPT (hexaisopropylterphenyl, 3,5(2,4,6-iPr3C6H2)2C6H3) side chain was truncated to simple protons160,161 or phenyl moieties162,163 in order to keep the computational cost tractable. Several density functionals were recently benchmarked against the CCSD(T) data by Reiher.164 DFT calculations with the full-catalytic system that contained 280 atoms and incorporating solvent and scalar-relativistic effects were reported by Neese and Thimm.165 The catalytic N2-activation cycle of Schrock’s catalyst consists of a series of proton and electron transfers in which the oxidation state of the molybdenum varies from III to VI. Most of the reaction steps were exergonic except the first N2 protonation step [Mo−N2] → [Mo−N2H]1+ and the last reduction step [Mo− NH3]1+ → [Mo−NH3]0, which were endergonic processes. The computed N2 reduction reaction profile was in excellent agreement with the experimental estimates; albeit, the protonation enthalpies had substantial errors (∼12 kcal/mol) which could arise from several factors such as from solvation,

Table 2. Spin State, Bond Length (Å), Bond Order, and Stretching Frequency (cm−1) of Dioxygen184

Dioxygen Superoxo Peroxo

Spin State S=1 S = 1/2 S=0

O−O

O−O Bond Length

O−O Bond Order

O−O Stretching

[OO] [O−O]•− [O−O]2−

1.21 1.33 1.49

2.0 1.5 1.0

1580 1098 877

these dioxygen intermediates are often unstable, and they are characterized by spectroscopic methods.170−176 Resonance Raman techniques are very powerful methods to characterize the nature of dioxygen adducts.177−179 In conjunction with experimental data, calculations were carried out to characterize the electronic structure and reactivity of dioxygen adducts.180−183 K

DOI: 10.1021/acs.chemrev.9b00073 Chem. Rev. XXXX, XXX, XXX−XXX

Chemical Reviews

Review

electron counts where no such radicaloid oxo groups were expected. From fundamental perspectives, single-determinant methods, such as DFT, are not capable of capturing open-shell configurations properly, as they require multireference methods, such as CASSCF. But because these complexes are typically large in molecular size and metals are notoriously difficult to model properly in high-level ab initio calculations, most calculations that inspired the development of the nonclassical concept of the metal-oxo complexes were based on DFT. The widely accepted rationale for employing a method that is in principle incapable of treating the complex problem at hand has been an important insight contributed by Noodleman.203 This so-called broken-symmetry DFT calculation, where the orbitals are transformed to be maximally localized and do not observe the symmetry constraints of the molecule, can produce an approximation for the intrinsically multistate wave function that constitutes a state-averaged representation and can afford a working model for these complex electronic structures. Whereas countless studies204,205 applying this principle have proven the usefulness of this approximate method for capturing antiferromagnetic coupling and metal−ligand redox noninnocence, a lingering and unanswered question was how appropriate these approximations really are. Specifically, Mulliken spin projections are typically employed to divide the calculated electron density to each of the atoms in the molecule, which is then used as evidence for the nonclassical radicaloid character of the oxygen atom in the molecular assembly. To assess whether or not the widely utilized spin analysis based on broken-symmetry DFT is appropriate, the electronic structure of a realistic Mn(V)O species was studied using different computational methods and systematically compared.206 As illustrated in Figure 16, three spin states denoted as singlet (S = 0), triplet (S = 1), and quintet (S = 2) can be imagined for this system.206 In general, the MnO bond can be polar or covalent, where the former is often found in early transition metal-oxos whereas the latter is formed by equal

Dioxygen adducts with transition metal complexes can be prepared with several macrocycles (Figure 15), thanks to the pioneering work by Que,185 Nam,186,187 Tolman,188 and others.189−191

Figure 15. Metal−oxygen intermediates of superoxo,192 hydroperoxo,193 oxo,194 and peroxo186 species. Hydrogen atoms on the ligand centers are removed for clarity.

Among the intermediates encountered during a transition metal assisted activation of dioxygen are metal-oxo species that have attracted much attention historically. In 1962, Gray and Ballhausen proposed the electronic structure of a vanadyl ion [VO]2+ using ligand field theory, which led to what is widely known as the oxo-wall proposal.195,196 For a given tetragonal symmetry, the formation of a high valent metal-oxo species is not possible beyond Group 8 elements, because the M−O π* orbitals become overpopulated in these electron-rich systems. And because these frontier orbitals are metal−oxygen antibonding in character, their occupation leads to a weakening of the M−O bond. Another effect that is often underappreciated is that the Brønsted basicity of terminal oxygen increases significantly when the M−O π* orbitals are occupied and the terminal oxo moiety readily undergoes protonation. In good agreement with the proposal of the oxo-wall, manganese and iron are commonly found to form terminal oxo species, for example in many metalloenzymes, where various oxidation states up to Mn(IV) and Fe(IV) with d3 and d4 valence configurations, respectively, can be seen. Curiously, cobalt does not easily form analogous species and terminal cobalt-oxo species were not known until recently.197−199 Recently, nonclassical metal-oxo species where open-shell configurations can be adopted have been recognized as a viable alternative to the classical metal-oxo complexes. Electronic structure calculations have played a key role in clarifying that high-valent metal centers are sometimes capable of formally oxidizing the oxo-moiety to generate a metal−oxygen fragment in which the oxygen is better characterized as a radicaloid oxyl species, where the oxygen fragment has a formal oxidation state of −I.200,201 This concept can be extended to two electrons to formally give M−O fragments where more than one unpaired electron is assigned to the oxygen, thus giving what is best characterized as a metal-oxene, where the oxygen displays biradicaloid character and adopts a formal oxidation state of zero.202 Recently, a high spin (S = 3/2) Co-oxo was reported by Nam and co-workers supported by a series of spectroscopic and quantum chemical calculations.197 As several of these high valent species are spectroscopically characterized, their geometric and electronic structure and reactivity are routinely studied with DFT or ab initio methods. The assignment of the formal oxidation states and the development of the concept of these open-shell alternatives have often relied on the observation that unrestricted spin DFT calculations revealed radical-character on the terminal oxo groups even for systems with even-numbered total

Figure 16. Simplified MO diagram of Mn−O with three different spin states. L

DOI: 10.1021/acs.chemrev.9b00073 Chem. Rev. XXXX, XXX, XXX−XXX

Chemical Reviews

Review

complex, a theoretically proposed intermediate in the HAT reaction mechanism.210 3.1.3. CO2 Activation. Iron porphyrins are one of the most outstanding catalysts for CO2 reduction whose electronic structures have been extensively studied.211−215 Very recently, the electronic structures of the one electron and two electron reduced species were revisited by computing the advanced spectroscopic parameters and compared against the higherresolution experimental data (Table 3).216,217 The resting state

contribution from both manganese 3dxz/3dyz orbitals and the oxygen 2px/2py orbitals. Upon double excitation, metal-based or ligand-based charge transfer was calculated. On the other hand, in the covalent MO case, the bonding and antibonding orbitals had a similar amount of ligand and metal character. These variations were interpreted as the physical basis for assigning different oxidation states, in this case Mn(IV) to the metal in polar MO. If the covalent character dominates the MO bonding, the classical assignment of Mn(V)O was found to be more appropriate. These are quantified by the degree of covalency and the effective electron count between the manganese and the terminal oxygen. Furthermore, a common reaction that the Mn-oxo moiety performs, namely an O−O bond forming reaction with an external water molecule, was examined, again employ both broken-symmetry DFT and high-level multireference calculations. The O−O bond can be formed either through radical recombination or nucleophilic attack. It was found that the effect of radical character was relatively small for nucleophilic attack and likely not a required feature for this mechanism; however, the oxyl radical effect was more sizable for radical coupling pathways. Most interestingly, this extensive comparative study for both the electronic structure and the chemical reaction modeling of metal-oxo species concluded that while broken-symmetry DFT is incapable of capturing all the details of the innately complicated electronic structure, it can reproduce the most important components of the metal− oxygen interaction. The reactivities of several known transition-metal-oxo species broadly fall into one of two categories: single-state or multistate reactivity (Figure 17).207,208 Whereas C−H

Table 3. Experimental and Computed Pre-edge in eV and Isomer Shift δ, in mm/s of Fe-Porphyrins216

Fe(↑↑)−P Fe(↑↑)−P(↓) Fe(↑↑)−P(↓↓)

Spin

Exp Preedge

DFT Preedge

Exp δ

DFT δ

S=1 S = 1/2 S=0

7110.5 7110.5 7110.1

7111.3 7111.6 7111.6

0.57 (0.50) 0.65 (0.52) 0.49 (0.45)

0.55 0.48 0.59

of the Fe(II)-porphyrins is the intermediate spin S = 1 triplet state. Due to the noninnocent nature of porphyrin ligand, the first and the second reduction can be either Fe-centered or ligand-centered. The electron acceptor molecular orbital of the complex is ligand based Gouterman orbitals, and thus the reduction is expected to be ligand-centered. The computed XAS pre-edge energies and the Müssbauer parameters of the ligand-centered reduced species match closely with the experimental data. Thus, the spin state can be best described as open-shell singlet (S = 0) for the doubly reduced species. A comprehensive review of this extensively large body of work on CO2 reduction is not possible and not meaningful for this review.139 Instead, we offer a few distinctive examples that highlight the current trend and showcase some of the challenges. CO2 is an exceedingly poor Lewis acid and requires a powerful electro- or photocatalyst to undergo any reaction. The reduction potential of the catalyst plays a critical role in the CO2 reduction mechanism that is often influenced by ionpair formation, particularly, when the catalyst is highly charged. Recently, the connection between experimentally observed redox potentials and the degree of contact ion pairing has been quantitatively examined using several Co(I/II) and Co(II/III) complexes (Table 4).218 The computed redox potential for Table 4. Experimental and Computed Redox Potentialsa

Figure 17. Schematic representation of single state (left) and twostate reactivity (right) found in synthetic Fe(IV)O biomimetic systems.

Co(II) + e− → Co(I)

Co(L1)3 Co(L2)3 Co(L3)3

activation by naturally occurring Fe(IV)O cytochrome P450 enzyme follows a quintet state reactivity, nearly all synthetic models follow a two-state reaction profile. In synthetic mimics, the ground state of FeO is a S = 1 triplet state with the S = 2 state being higher in energy. However, the transition state involving hydrogen atom transfer (HAT) was found to follow an S = 2 quintet pathway.209 Recently, Meyer and co-workers proposed a nonclassical triplet reactivity of an Fe(IV)O species ligated with macrocyclic tetracarbene ligand.182 The metal-oxo species are highly reactive and are capable of activating several C−H bonds through HAT and rebound (RB) mechanisms. The crucial hydroxo species was a missing intermediate between the HAT and RB mechanism. Recently, Goldberg isolated a reactive Mn(IV)−hydroxide

a

Co(III) + e− → Co(II)

Co(III) + Cl− + e− ⇆ Co(II)·Cl−

E1/2 (Exp)

E0 (Calc)

E1/2 (Exp)

E0 (Calc)

E0 (Calc)

−1.36 −1.24 −1.28

−1.40 −1.21 −1.15

−0.05 +0.16 +0.65

+0.77 +1.02 +1.36

−0.03 +0.17 +0.61

All potentials are referenced against the Fc/Fc+ (unit: V)218.

Co(I/II)-polypyridyl species was found to be within ∼50 mV of the experimental values, but for the corresponding Co(II/ III) couple, a discrepancy as large as 800 mV was found between computed and experimental redox potentials. Upon incorporating a simple ion-pair model using a chloride anion, the computed redox potentials were found to be 40 mV of the experimental values. These calculations suggested that the contact ion pairing is not critically important for the energies of the Co(I/II) couple, but the higher cationic charge of the M

DOI: 10.1021/acs.chemrev.9b00073 Chem. Rev. XXXX, XXX, XXX−XXX

Chemical Reviews

Review

although the CH4 production is low yielding with a reported yield of 22%, this work is clearly a major step forward in this field. Interestingly, without the photocatalyst, methane formation was not observed. A full-scale computational modeling treatment of this system has not been reported yet, but several metal decorated nitrogen-doped carbon (M−N− C) materials are also known to perform CO2 reduction230,231 efficiently. These systems may be related, and DFT calculations have been carried out to elucidate the key intermediates of these reduction reactions.230,232,233 Beyond the mononuclear species, the Maverick group considered dinuclear and the Bouwman group considered tetranuclear systems suggesting that two CO2 molecules can be reduced to oxalate.234,235 Lan and co-workers carried out DFT calculations on the CO2 → C2O42− conversion of the Bouwman’s copper catalyst.236 Although the computational work found a plausible mechanism for the experimentally observed formation of the oxalate, these quantum chemical calculations do not support the mechanistic proposal suggested by Bouwman that the key step where C−C coupling occurs follows a diradical coupling pathway. Instead, a mixed valence radical anion Cu2I/II(CO2•−) intermediate is proposed by the DFT calculations. The calculations further suggest that the two CO2 molecules are not reduced simultaneously but are reduced sequentially to form the dinuclear Cu(II)-oxalate product. Directly accessing a C−C coupled product from CO2 reduction constitutes an important breakthrough, and it is therefore surprising that only little progress has been made in nearly a decade since the initial report by Bouwman. In 2016, Yang reported the hydrogenation of CO2 to methanol catalyzed by a [FeFe]-hydrogenase.237 Previously, the Bullock group reported an iron complex carrying a Cp and diphosphine ligands with pendant amines capable of carrying out a similar reaction.238 Yang reported that this iron complex showed a relatively high barrier of 27.6 kcal/mol. To move further, the Cp ligand was replaced with two carbonyls and various functional groups were also tested. The calculated catalytic cycle revealed that H2 cleavage was likely rate-limiting. The impact of different functional groups was evaluated computationally, and it was concluded that the electrondonating groups may increase the reactivity, whereas the electron-withdrawing groups may slow down the reaction. Computational catalyst design strategies were extended for the hydrogenation of carbon dioxide to formic acid with various metals by the Yang group.239 Motivated by the iron cyclopentadienone catalyst, which was shown to be competent for the hydrogenation of ketones,240−242 bicarbonates, and CO2,243,244 a series of modified cobalt and manganese catalysts with improved catalytic abilities were identified (Figure 19a).239 The mechanism was modeled replacing iron with cobalt and manganese along with substituting the carbonyl group of the original iron complex with CN and NO. The mechanism starts with the approach of the CO2 forming a formate group attached to the metal, the hydroxyl proton in the cyclopentadienone transfers to one of the oxygen atoms of the formate, yielding a formic acid. Next, the formic acid is replaced by H2 molecule, generating a dihydrogen complex, and the splitting of H2 by methanol or water simultaneously regenerates the catalyst. Various metal-based complexes were computationally evaluated for the H2 splitting transition state, and the cobalt complex associated with the methanol assisted H2 splitting showed the lowest barrier (Figure 19b).239

Co(II/III) couple cannot be modeled properly without considering the formation of such a contact ion pair. Experimental analysis of the cyclic voltammograms supports this assignment, as the ion pair formation reaction process has a profound impact on the electrochemical behavior of these species. Whereas it is plausible that the redox behavior of a molecule is highly dependent on the presence or absence of a counterion in the vicinity of the redox-site, counterion effects are often ignored in quantum chemical simulations of reaction mechanisms. Song and co-workers have studied the mechanism of CO2 reduction with a popular [Ni(cyclam)]2+ complex,219,220 which shows 90% Faradaic efficiency with negligible H2 evolution. The resting state of the catalyst contains a Ni(II)-center, which undergoes a one electron reduction at −1.21 V in order to bind CO2. Upon reduction, the redox-active Ni(I)-3dz2 orbital strongly overlaps with the vacant CO2 π* orbital, ultimately injecting two electrons into the CO2 fragment. The electronic structure of this intermediate is best described as Ni(III)CO2−. Thus, the CO2 binding to the electron-rich catalyst is formally an oxidative coupling, where a Ni(I) becomes a Ni(III)-center. A rapid protonating of the carboxylate follows to generate formate, and addition of a second proton leads to the formation of CO and water. This mechanistic study highlights the utility of computational methods to shed light on an otherwise vague and ill-defined mechanism, where the computational models serve as equal partners to experimental mechanistic investigations, such as detecting, if not isolating, intermediates, carrying out isotope labeling studies, and determining reaction rates. The mechanism of reducing CO2 to CO has been investigated by an overwhelmingly large number of research groups with various metal ions,221−223 hydrogen-bonding donor stabilizing the CO2 binding,224−226 and the influence of weak Brønsted acids.227 CO desorption occurs frequently; thus, further reducing CO to formaldehyde (2H+/2e−), methanol (4H+/4e−) or methane (6H+/6e−) remains a largely unmet challenge. Recently, Robert and co-workers228,229 reported a remarkable breakthrough in this area. Using a functionalized Fe-porphyrin and an Ir-photocatalyst, these researchers were able to carry out the electrocatalytic conversion CO2 → CH4 (Figure 18).228,229 Side products such as formaldehyde or methanol were not detected and

Figure 18. Proposed photocatalytic CO2 reduction to CH4 with a Feporphyrin and Ir-photocatalyst. N

DOI: 10.1021/acs.chemrev.9b00073 Chem. Rev. XXXX, XXX, XXX−XXX

Chemical Reviews

Review

center. Finally, the CO2 coordinates in an η2 fashion followed by C−C bond formation and regenerates the catalyst. Other possible mechanistic pathways were investigated and rejected based on unreasonable energies. With the full mechanistic proposal in hand, the reaction was optimized by first comparing the functional groups that are directly bound to the phosphorus atoms in the PNP-pincer ligand, where functional groups such as tert-butyl, phenyl, and 1-pyrrolidinyl were tested. The estimated TOF was highest with the 1-pyrrolidinyl group. Another variation considered was with the modification of the PNP skeleton, and the PONOP pincer motif with oxygen atoms inserted into the pincer-ligand structure was identified as a promising target. Interestingly, electron-donating groups at the 4-position further improved the performance. Moreover, the effect of the anionic ligand was modeled where Br− had the highest efficiency compared to other halogens. Finally, the substituent on the arene substrate and the effect of the solvent type were tested. Two different catalysts were eventually designed and showed excellent calculated TOFs (Figure 20).248

Figure 19. (a) Predicted catalytic cycle for the hydrogenation of CO2 with a series of different Cp-based metal complexes. (b) Transition state of H2 splitting step without assistance (black), methanol assisted (red), and water assisted (blue) pathways (unit: kcal/mol).

In another eye-catching example of computational work to improve the hydrogenation of carbon dioxide into formic acids, Yang designed base metal PNP pincer catalysts.245 Inspired by Nozaki’s PNP Ir(III)-trihydride complex that shows excellent TON in the formation of HCOOK from CO2 and H2 in aqueous KOH,246 Yang designed PNP-pincer systems that consist of iridium, iron, and cobalt in the presence of OH−. Incidentally, a very similar (PNP)Fe-catalyst was prepared by Milstein for the hydrogenation of ketones very recently.247 Yang proposed various mechanistic scenarios and through intensive calculations discovered that the most favorable pathway starts with the CO2 attack toward one of the trans hydrides. The resulting HCOO− moiety dissociates and H2 binds to the vacant coordination site and, finally, the H2 is cleaved by the external base OH− to give water. Then the catalyst is regenerated. Within the mechanism, the formation of the H2O step is the highest barrier with 22.6 kcal/mol in the cobalt complex. Holscher and Leitner designed a ruthenium catalyst for direct carboxylation of arylic C−H bonds with CO2 through intensive DFT calculations.248 The reaction was performed by Au(NHC) complexes,249 CuCl(NHC) complexes,250 or rhodium catalysts with phosphine ligands.251 In this study, Ru(II) pincer complexes were used, and to compare the catalytic activities of the other designed derivatives, the energetic span model was employed which attempts to predict the efficiency of catalysis in terms of turnover frequency (TOF).252,253 With the parent Ru−pincer complex that was reported previously to activate arylic C−H bonds,254 the mechanism was investigated in detail. The prototypical carboxylation mechanism starts with the benzene replacing the coordination of one benzoate oxygen. σ-bond metathesis leads to the key C−H activation between the uncoordinated oxygen and one of the C−H moieties of the benzene to give a benzoic acid. Next, the benzoic acid is removed from the metal

Figure 20. Computationally designed ruthenium catalysts for the CO2 coupling and their calculated TOFs.

Calculations on protodecarboxylation of aromatic carboxylic acids with copper and silver complexes have been conducted by Gooßen.255 Decarboxylation of benzoic acids is useful because after the extrusion of CO2, it forms a carbon nucleophile and can perform C−C coupling reactions with various electrophiles.256−258 However, these types of reactions currently require harsh reaction conditions. Various copper and silver catalysts were screened computationally based on the proposed mechanism, and experiments were conducted subsequently on the most promising candidates. First, the mechanism of the previously reported Cu(I)-1,10-phenanthroline complexes was modeled.259−261 Calculations showed that the extrusion of the CO2 from the copper benzoates to give an aryl-copper bond is associated with the highest barrier of the whole catalytic cycle. The unsubstituted phenanthroline required a reaction temperature of 170 °C having an activation barrier of 31.4 kcal/mol. Electron-donating groups yielded lower barriers, with the strongest electron-donating group NMe2giving a barrier of 30.6 kcal/mol. Moreover, silver catalysts were modeled, because experimental data were available from previous experimental studies.255 The Ag(I)− phenanthroline complex showed an activation energy of 29.5 O

DOI: 10.1021/acs.chemrev.9b00073 Chem. Rev. XXXX, XXX, XXX−XXX

Chemical Reviews

Review

kcal/mol which was nearly ∼2 kcal/mol lower than what was found with the copper catalyst. However, since phenanthroline is not a common ligand for silver complexes, NMP (N-methyl2-pyrrolidone) ligands were used which showed similar barriers (29.2 kcal/mol) in the CO2 extrusion step. While the unsubstituted benzoic acid substrate worked well for the Cu(I) phenanthroline catalyst, the electron rich benzoic acids substituted on the ortho-position were predicted to be preferable for the Ag(NMP) complex. The experimental results for both metals were in excellent agreement with the predicted barriers mentioned above. The silver complex promoted the decarboxylation in a temperature range of 80− 120 °C which is 50 °C lower than that for the best copper complex. This work is a good demonstration of how precisely experimental outcomes under different scenarios can be predicted. Given the variety in catalyst, substrates, and reaction conditions, the precision of the computational predictions is remarkable and surprisingclearly, the systematic cancellation of errors in the underlying theoretical models plays a pivotal role, since the DFT methods employed in this and most of the studies mentioned in this review are incapable of delivering absolute energies for these complex chemical reactions at this demonstrated level of accuracy. The mechanism of forming acrylates from ethylene and CO2 was studied by Xu and Sautet in 2014.262 Several nickel catalysts were designed for this purpose previously, and recently, Kühn263 demonstrated that the choice of ligands can affect the production of methyl acrylate. The mechanism is well-known264,265 and the catalytic cycle starts with the oxidative addition of CO2 which results in a nickelalactone intermediate which interacts with the electrophile methyl iodide and opens the ring. The third step involves a β-hydride elimination that produces a methyl acrylate which subsequently undergoes a final reductive elimination of HI, and the ethylene is recoordinated to the complex. The authors modeled two different types of ligands for nickelalactones with various N-donor ligands (tmeda (N,N,N′,N’-tetramethylethylenediamine) and pyridine) and P-donor ligands (dppe (bis(diphenylphosphino)ethane), dppp (bis(diphenylphosphino)propane), and dppb (bis(diphenylphosphino)butane)). But the well-known pathway stated above did not offer a clear explanation for the efficiency difference as a function of the ligands. Therefore, other pathways were suggested that can yield side products through ligand uncoordination, rearrangement on the nickelalactone, and iodide dissociation forming an ion pair. The electrophile reacts with the nickelalactone to generate a square-pyramidal complex, which can generate two side products via iodide dissociation and uncoordination of the bidentate ligand with barrier of only 16.5 kcal/mol assisted by the favorable Ni−I covalent bond. Another side reaction involves the hydrogenation of the α-carbon in the substrate and involves a square-planar intermediate that affords a low barrier of only ∼2 kcal/mol. Subsequently, the carbonyl oxygen can coordinate to the Ni-center, pushing the iodide to an axial position which leads to dissociation. Comparing the precise energy profiles of these two well-known pathways that lead to side products when employing the N-donor ligand (tmeda) and P-donor ligand (dmpe) was meaningful. Studying these reactions using experimental techniques alone is challenging, and computations offered a viable and attractive alternative. It was revealed that the intermediates with equatorial iodides were less destabilized by dmpe than tmeda

because the N-donor imposes a much stronger trans influence than the P-donor ligands. Furthermore, calculations suggested that the monodentate ligands were not appropriate since the side product pathway prefers an uncoordination of one ligand. With a bidentate ligand the decoordination can be rendered reversible. To summarize, this study offers an example where the optimization strategy did not target the productive pathway, namely the formation of methyl acrylate, but focused on slowing down the unproductive pathways where the substrates can leak into undesired products. 3.2. Small Molecule Insertion

The saturation of hydrocarbons accomplished through the addition of activated small molecules such as dihydrogen is a widely used reaction in food and petrochemical industries.266−268 In this section, we will highlight some of the studies where computer-aided design led to innovative concepts in hydrogenation and water oxidation catalysis. 3.2.1. Hydrogenation. In 1966, Wilkinson reported the serendipitous discovery of (PPh3)3RhCl, known today as Wilkinson’s catalyst, prepared by refluxing RhCl3-hydrate in ethanol in the presence of excess amount of triphenylphosphine.269 Wilkinson and co-workers demonstrated in subsequent publications the utility of this highly versatile catalyst in hydrogenation protocols. In addition, Wilkinson later reported the synthesis of neutral Ru(II) complex, RuHCl(PPh3)3, capable of catalytic hydrogenation.270 Optimization of this catalyst by other groups yielded a superb general catalyst platform.271 In addition to the original Wilkinson’s catalyst, a variety of late metal−phosphine compounds were identified in this class of catalyst and are commonly used.272,273 In a recent report by Rowley and Woo, DFT calculations were used to elucidate the mechanism for the hydrogenation of ethylene with RuHCl(PiPr3)2(CO) and this model was used to design and propose a new hemilabile ligand (Figure 21).274

Figure 21. Ru-based catalysts for hydrogenation of ethylene and the relative Gibbs free energy for two intermediates.

The catalytic reaction was proposed to start with the dissociation of a phosphine ligand to form the monophosphine Ru(II) complex, followed by ethylene and H2 binding. The alkene inserts into the Ru−H bond that allows ruthenium to oxidatively add into the H−H bond to form a Ru(III) dihydride. Reductive elimination of ethane regenerates the P

DOI: 10.1021/acs.chemrev.9b00073 Chem. Rev. XXXX, XXX, XXX−XXX

Chemical Reviews

Review

catalyst. Three potential ligands were evaluated: (i) diphenylphosphanodihydrooxazole, (ii) benzamide-derived aryl phosphine, and (iii) hemilabile NHC ligand with a tethered pyridine. The authors found that the large bite-angle of the oxazole ligand along with its highly basic lone pair were advantageous features that were crucial for the reactivity and stabilization of the ruthenium complex in the absence of hydrogen. Moreover, the energy difference of the ethylene adduct was crucial for the performance of the catalyst. Based on these results, a full catalytic mechanism was calculated for this system, showing that it is potentially viable in the hydrogenation of olefins.274 Achieving enantioselectivity in hydrogenation is often very important, especially in the pharmaceutical industry. Identifying chiral catalysts that induce significant enantioselectivity is usually challenging and the majority of enantioselective catalyst are developed by laborious trial and error methods in the laboratory. Therefore, computational design is particularly attractive. Recently, Wiest and co-workers showed that an enantioselective hydrogenation catalyst can be predicted in the computer first.275 A series of ligands were modeled with rhodium as the active metal, and the impact of these ligands on the catalytic cycle was evaluated computationally and correlated with subsequent experimental results. The ee was in excellent agreement, and the assessment of a total of 29 molecular species that included ligands and derivatives resulted in an R2 of 0.92.275 This study outlines a powerful workflow for designing enantioselective catalysts. In a different study, Eisenstein and Crabtree disclosed the first quinoline hydrogenation catalyst with an NHC ancillary ligand.276 Neutral Ir(NHC) species were prepared either through the base-assisted NHC metalation from an imidazolium salt and Ir(cod)Cl2 or by transmetalation of a silver carbene. With this precatalyst in hand, the authors found that the hydrogenation of quinoline systems proceeds at room temperature under only 1 atm of H2 in the presence of triphenylphosphine.276 These conditions are among the mildest reported for the hydrogenation of quinolines. After observing the iridium hydride species by NMR, the authors proposed one of two mechanisms to be operative: an inner sphere or an outer-sphere pathway (Figure 22a).276 Using DFT, the inner-sphere mechanism was ruled out as it was associated with very high barriers relative to the stepwise outersphere mechanism (Figure 22b).276 Based on these results clearly showing that H2 binding is preferred over substrate binding, the authors propose the possibility of designing asymmetric catalysts based on these novel and relatively mild conditions.276 3.2.2. Ethylene Oligomerization. Industrial ethylene oligomerization generates 1-alkenes at ∼3,000,000 tons/year worldwide, which are used for the synthesis of polymers and detergents, among many compounds.277 While chromium catalysts are known for the selective generation of 1hexene,278−280 new molecular chromium catalysts are desirable for the selective generation of 1-octene. Ess and a team from Chevron Phillips Chemical Company recently reported the development of a predictive DFT transition-state selectivity model that was used to successfully design a new family of phosphine monocyclic imine chromium catalysts.281 This predictive model was predicated upon the reaction mechanism (Figure 23a). This low-valent high-spin quartet cationic chromacycle mechanism was outlined by Britovsek and McGuinness for related chromium catalysts.282,283 With this

Figure 22. (a) Inner- and outer-sphere mechanisms for the hydrogenation of quinoline by (NHC)Ir catalysts. (b) Calculated energy values for the highest transition state of each mechanism.

Figure 23. (a) Mechanism for Cr-catalyzed ethylene oligomerization to 1-hexene and 1-octene. (b) Example of DFT predicted 1-hexene:1octene selectivity ratios, and experimental verification.

mechanism, Ess and co-workers proposed that selectivity occurred by the catalytic pathway splitting at the chromacycloheptane intermediate D. A β-hydrogen transfer pathway Q

DOI: 10.1021/acs.chemrev.9b00073 Chem. Rev. XXXX, XXX, XXX−XXX

Chemical Reviews

Review

peroxo/aqua complex. The highly oxidizing Ru(V)-center can remove another electron from the peroxo moiety to yield a Ru(IV)/Ru(III)-superoxo/aqua complex, which releases O2 and forms the Ru(III)/Ru(III) resting state.201 The overall energetics of this pathway was in line with experimental observations.291 The radicaloid character of the oxo group in this dinuclear ruthenium complex was later experimentally confirmed by Meyer.292 And this mechanism, first proposed based on computations only and initially received with much scepticism, is now accepted widely as the consensus mechanism. In a recent report, a series of dinuclear ruthenium complexes with the formulas [Ru2(II)(bpp)(trpy)2(μ-L)]2+ (bpp = bis(2pyridyl)-3,5-pyrazolate, trpy = 2,2′:6′,2′′-terpyridine; L = Cl, AcO) and [Ru2(II)(bpp)(trpy)2(H2O)2]3+ was isolated by Llobet and co-workers.293 Generating the bisaqua complex [(tpy)Ru(II)−OH2]2L3+ (tpy = terpyridine; L = bipyridylpyrazolylic anion) resulted in a catalytically active complex capable of oxidizing water to generate O2 at 3 times the rate of the Meyer catalyst.293 In another example of DFT illuminating the details of the oxidation mechanism, Baik performed a computational study of this catalyst (Figure 25).294 Based on the insights gained from previous work on Meyer’s blue dimer system, the authors hypothesized that one of two pathways for O−O bond formation was operative: (i) The formation of a dinuclear peroxo complex via the coupling of the two oxo groups or (ii) the formation of a hydroxo/ hydroperoxo complex similar to the aforementioned case of the blue dimer.294 Starting with the [(tpy)Ru(IV)O]2L3+ complex, Baik showed that the complex undergoes a spin crossover followed by a protonation, which leads to a [Ru(IV)/Ru(IV)-hydroxy/oxo]4+ complex at 11.8 kcal/mol. A resonance form of this complex, [Ru(III)/Ru(V)-hydroxy/ oxo]4+, reacts with water to yield a [Ru(III)/Ru(III)-aqua/ hydroperoxy]4+ system. This is followed by the formation of [Ru(II)/Ru(II)-aqua/peroxy] which exchanges O2 for H2O to start the cycle over. Based on this result, in the same paradigm as the Meyer catalyst, it was shown that only one Ru-center was responsible for the production of O2, while the other center was acting as a base that helps the deprotonation of water. This prediction gave a solid conceptual foundation to a widely accepted notion that mononuclear metallic systems should, in theory, be tunable toward effective water oxidation. This new mechanistic understanding outlined above led to the development of highly effective multinuclear complexes295−299 as well as mononuclear catalysts.300−306 Recently, Sun and co-workers reported Ru-bda (bda = 2,2′bipyridine-6,6′-dicarboxylate) water oxidation catalysts (Figure 26a).307 These catalysts were highly active and showed oxygen production rates over 300 s−1, while most of the previously reported catalysts showed about 5 s−1. Based on previous studies, Ahlquist and Sun ventured to make a more robust catalyst with the assistance of DFT modeling.308 The working hypothesis was that a major pathway for catalyst decomposition is instigated with losing an axial ligand. To design away from this limitation, a series of DFT calculations were performed to assess the strength of the metal−ligand bonds of various N-heterocycles. Starting by assessing the relative energies of ligand exchange with water, the authors uncovered a correlation between the HOMO energies of these ligands and the stability of their corresponding ruthenium complexes (Figure 26b).307 Following these calculations, three complexes that were predicted to be stable, those with pyridazine,

leads directly to 1-hexene while ethylene coordination and migratory insertion leads to the chromacyclononane intermediate F and then 1-octene. Based on this selectivity mechanism, an experimentally benchmarked DFT linear regression model was developed that propelled the discovery of the monocyclic imine ligands where deletion of a pyrrole methyl group led to a significant shift in the selectivity from 1-hexene to a mixture of 1-hexene and 1octene (Figure 23b). It is rare for molecular catalyst predictions to be verified experimentally.284 In this case, subsequent experimental ligand and catalyst synthesis and reaction testing quantitatively confirmed the predictions. 3.2.3. H2O Oxidation. For more than 200 years, fossil fuels were the backbone of the industrial revolution.285 Diminishing reserves of easily accessible fossil fuels and the negative environmental effects associated with the rapid increase of greenhouse gases demand a new, sustainable energy source, including geothermal, tidal, wind, and solar energy.286 Among them, solar energy is most attractive due to the abundance of sunlight, and nature provides an elegant blueprint of how this energy can be turned into chemical energy via photosynthesis. In the context of artificial photosynthesis, water is the best candidate for providing both protons and electrons that are needed to reduce carbon dioxide to ultimately form hydrocarbons. The oxidation of water results in the release of oxygen gas, protons, and electrons.287 A seminal piece of work was reported in 1985 by Meyer and co-workers, in which the first molecular catalyst, [(bpy)2(OH2)RuORu(OH2)(bpy)2]4+ capable of water oxidation was disclosed (Figure 24).288 This remarkable catalyst,

Figure 24. X-ray structure for Meyer’s ruthenium catalyst. H-atoms and counterions removed for clarity.

which has been named the “blue dimer”, served as a central inspiration to the scientific community, and it was thoroughly studied to gain an understanding of how this complex system oxidizes water at room temperature and ambient conditions. For nearly two decades, the mechanism was not agreed upon and various possibilities were discussed.289,290 A major breakthrough toward establishing a consensus mechanism came from computational modeling in 2006. An exhaustive DFT study considering all plausible spin states, oxidation states, and ferro-/antiferromagnetic coupling properties of this dinuclear ruthenium complex proposed for the first time a complete catalytic cycle and identified a number of chemical and electronic features of how water oxidation is accomplished.201 The Ru(V)−oxo complex, which is the active form of the catalyst, is most appropriately described as a Ru(IV)− oxyl radical, and it can engage a water molecule. This Ru(IV) species causes the scission of an O−H bond of water to form the hydroperoxo intermediate, (HOO)RuIVORuIVOH. Intramolecular disproportionation following a proton transfer results in the formation of the unsymmetric Ru(V)/Ru(III)R

DOI: 10.1021/acs.chemrev.9b00073 Chem. Rev. XXXX, XXX, XXX−XXX

Chemical Reviews

Review

Figure 25. Proposed Ru-catalyzed water oxidation steps and their electronic configuration (unit: kcal/mol).

thorough study, the authors concluded that despite both pathways having similar energetics thermodynamically, the oxo-oxo pathway was kinetically favorable and had a lower overpotential.315 Tanaka and co-workers reported the synthesis of a new type of dinuclear ruthenium manifold that separates the two nuclei by a bis(terpyridine)-substituted anthracene linker which is capable of O2 evolution from H2O (Figure 28a).318,319 Interestingly, this catalyst has quinone type ligands which are known to be potentially redox noninnocent. To properly identify the O−O bond forming step, Baik and co-workers employed DFT calculations to delineate the key intermediates and transition-states responsible for this reactivity (Figure 28b).320,321 Based on UV−vis studies reported by Tanaka, the catalyst was speculated to undergo a double deprotonation with tert-butoxide to form an intermediate containing the key O−O bond.318,319 Furthermore, it was found that the free energy associated with these deprotonations is ∼21 kcal/mol, which was too high to justify spontaneous deprotonation at pH = 4.320 Surprisingly, the authors found that the O−O bond forming step occurs through an intramolecular coupling of the two oxyl groups, rather than an intermolecular reaction with water. Unlike the previously studied dinuclear ruthenium complexes, this manifold holds the Ru-centers in a rigid fashion that makes the solvent (water) inaccessible for the reactive sites which are pointed inside the framework. In addition, the Ru(III)-oxo moieties are significantly less reactive toward water O−H cleavage compared with the aforementioned Ru(IV)-oxo scaffolds. Lastly, the intramolecular formation of

pyrimidine, and phthalazine, were prepared. Within these complexes, the pyridazine and phthalazine offered an improvement over the previous catalysts, as they were experimentally shown to be much more robust having an uphill H2O exchange free energy level. As predicted, the phthalazine ligated ruthenium system not only was the most robust but also performed exceptionally well in Ce(IV)-promoted water oxidation, affording an oxygen production rate of 286 s−1 and a TON of 55,400.308 Inspired by a report on the isolation of a mononuclear Ru(II) complex in 2008 by Thummel and co-workers,309 Thummel, Muckerman, and Kowalczyk310 evaluated this catalyst in water oxidation using experiments guided by DFT calculations. Cobalt has been one of a handful of transition metals to show activity as a water oxidation catalyst. Co(III) cubane systems have been among the most important advances in this area,311−314 and the first Co(II) cubane system was reported by Patzke and co-workers in 2013.315 Contributing to the uniqueness of this catalyst are the Co(II)-based core, which adds robustness, and the lability of the ligands, which affords flexibility. In a recent series of studies reported by Hodel and Luber,316,317 DFT calculations were employed to gain deeper insights in this system. The authors investigated two reasonable pathways for H2O oxidation: (i) A single-site mechanism where the formation of the O−O bond occurs via nucleophilic attack at the oxygen of one Co(IV)-oxo unit or (ii) an oxo-oxo coupling from two adjacent Co(IV)−oxo intermediates being the operative pathway for the formation of the O−O bond and release of O2 (Figure 27).316 After a S

DOI: 10.1021/acs.chemrev.9b00073 Chem. Rev. XXXX, XXX, XXX−XXX

Chemical Reviews

Review

Figure 28. (a) Tanaka’s bis(ruthenium-hydroxo) complex capable of water oxidation. (b) Electronic ground state of the dihydrodo complex and the two electron, two proton oxidation event.

3.3. Cross-coupling Reactions

Cross-coupling reactions are one of the long-standing research topics in chemistry.322−325 For several decades, chemists have developed methods for activating many hydrocarbons and simple molecules to be converted into valuable chemicals. Cross-coupling reactions constitute a massive and intensely active research area with several dedicated reviews322,324,325 and special issues326−329 available already. Thus, we will highlight only a few selected examples where the interplay between computations and experiments were particularly fruitful and interesting. 3.3.1. C−C/Si Coupling. 3.3.1.1. Iron. In 2009, Norrby330 reported an iron-catalyzed C−C cross-coupling of aryl electrophiles with alkyl Grignard reagents through titration monitoring, Hammett study, and computational modeling. Adding electron-withdrawing functional groups to the paraposition of the aryl triflate indicated high ρ values (up to ρ = +3.8), suggesting that inducing a positive charge polarization on the aromatic ring accelerated the oxidative addition. Furthermore, the combination of σ and σ• showed a similar trend (R2 = 0.956), suggesting that electron transfer from the aromatic ring to the Fe-center is rapid during the oxidative addition step. Computational studies suggested a suitable mechanism revealing various intermediates with the Fe-center adopting different oxidation states. In general, these iron complexes were found to prefer high spin-states, whereas the aryl-substituted Fe(III) complexes favor an intermediate spin (S = 3/2). Moreover, the Fe(I)/Fe(III) cycle was favored in good agreement with the proposed mechanism where oxidative addition occurred in advance, and this step was the ratelimiting step. Three years later, the same reaction at low temperature was studied by Norrby.331 As expected, strongly electron-withdrawing functional groups enabled the reaction at low temperatures confirming the computed barriers. Under strongly reducing conditions, the reactivity decreased, however, and the previously proposed Fe(I)/Fe(III) pathway did not fully explain this tendency. Therefore, another catalytic cycle with Fe(0)/Fe(II) was examined, and the calculated barriers of oxidative addition and reductive elimination were 20.8 and 49.6 kcal/mol, respectively. The computed values showed that (i) the relatively high barrier of oxidative addition should slow down the reaction considerably and (ii) the barrier

Figure 26. (a) Two previously reported Ru-bda water oxidation catalysts (red) and three complexes that were predicted (blue). (b) Correlation between the HOMO energies of the ligands and the stability of their corresponding ruthenium complexes.

Figure 27. Proposed oxo−oxo coupling pathway for Co−cubane water oxidation.

an O−O bond is entropically much less taxing than the intermolecular formation of an O−O bond.321 Smith and co-workers recently reported a series of new, mononuclear, and high-spin manganese complexes.301 One of these complexes was shown to be a viable water oxidation catalyst. To better understand the mode of action of this novel system, a detailed computational study was carried out on the potential pathways involved in this catalyst’s unique O−O bond forming step. The mechanism starts off with Mn(II) binding two water molecules to form the bisaqua complex, calculated at −12.3 kcal/mol. After two deprotonations and a loss of an electron, the resulting bishydroxy Mn(III) complex undergoes a double deprotonation and loss of an electron to form an oxyl/oxo Mn(IV) complex, that subsequently forms a Mn(III) peroxy intermediate. This complex is further oxidized to release O2 and regenerate the catalyst. T

DOI: 10.1021/acs.chemrev.9b00073 Chem. Rev. XXXX, XXX, XXX−XXX

Chemical Reviews

Review

between the hydride and the silyl group and ring strain (Figure 29b).333 The computed results proposed a new pathway via a concerted oxidative addition/hydride insertion and ruthenacyclopropene. Three years after this work was reported, Tuttle and Thiel reported a Ru-catalyzed olefin hydrosilylation to give diethoxymethylsilane and dimethoxymethylvinylsilane.336 DFT calculations showed that the overall enthalpy was 21.8 kcal/ mol via σ-bond metathesis, which is in qualitative agreement with the observed result stated above. Another mechanistic study of hydrosilylation was reported by Yang and Wei utilizing a high valent Ru(VI)-nitrido complex.337 For [RuN(saldach)(CH3OH)]+ (saldach = the dianion of racemic N,N′-cyclohexanediylbis(salicylideneimine)) with a Ru(VI)-d2 center, two possible mechanisms were examined: [2 + 2] addition and the ionic outer-sphere mechanism by an active site of the Si−H bond. First, the [2 + 2] addition pathway was ruled out due to a high activation barrier of 37.8 kcal/mol. In the pathway involving the addition of the Si−H bond to the nitrido ligand, the addition of the silane was found to be exergonic and, thus, viable. But the formation of the silylcarbenium ion and the silyl ether had a relatively high barrier of 29.2 and 37.8 kcal/mol, respectively, rendering the reaction pathway thermodynamically favorable but kinetically hindered. In contrast, an ionic outer-sphere pathway allows for the direct engagement between the Si−H bond and the Ru-center being favored with the computed barrier of 22.9 kcal/mol at the silylcarbenium formation step. As is often found, the spin state of the low-valent [RuN(saldach)]+ with a Ru(III)-d5 center was found to be of importance in the reaction. Combining NMR and DFT analysis, the Michael addition of both dimethyl malonate and β-keto ester to cyclic enones with chiral amido ruthenium complexes was investigated in 2010 by Ikariya (Figure 30a).338 Two features were found by the calculations: (i) The NH moiety on the ruthenium catalyst plays a crucial role in the catalytic cycle, and (ii) based on the measured results, the reaction follows either the O-bound enolate complexes or the double hydrogen-bonded complexes. The NMR and DFT results indicated that the C- and O-bound complexes were generated via the C−H activation of 1,3-

of reductive elimination is high, suppressing the reactivity. Thus, the DFT calculations indicated that the Fe(0)/Fe(II) manifold is not viable and the Fe(I)/Fe(III)/Fe(II) cycle is the most plausible mechanism. As mentioned above, the catalytic activity was determined by the oxidation state of the Fe-center. Following the proposed cycle, an intensive mechanistic study was performed to clearly identify the relevant oxidation states of the Fe-center.332 These studies confirmed that the transmetalation step is promoted by a high spin Fe-center. The strong ligand field of the aryl afforded an intermediate spin (S = 3/2) on the aryl Fe(III) complexes, and finally, the second transmetalation and the following reductive elimination were completed maintaining the same spin state. 3.3.1.2. Ruthenium. In 2003, Wu and Trost reported cationic ruthenium catalysts that hydrosilylate alkynes.333 Two stepwise pathways were investigated by Chalk and Harrod previously.334,335 Whereas the Chalk−Harrod (CH) mechanism generates the syn-addition product only, the modified Chalk−Harrod (mCH) method yields both anti- and synaddition products via isomerization. For inter- and intramolecular reactions, the hydride-insertion step was preferred over silyl-insertion. For example, the Ru(Cp)(HCN)+ complex was computed to show the lowest barrier of 12.6 kcal/mol at the hydride insertion step. With regard to regiochemistry, for silyl insertion, the anti-Markovnikov transition state was located with a relative barrier that was 7.6 kcal/mol lower than the Markovnikov transition structure (Figure 29a).333 In addition, the counterclockwise rotation of the Cα−Cβ bond of alkynes in the hydride insertion afforded the trans addition product. Finally, for an intramolecular reaction, H-endo is more stable than H-exo, because of the stabilizing interaction

Figure 29. (a) Intermolecular silylation mediated by ruthenium catalysts and their Markovnikov, anti-Markovnikov transition state energy barriers depending on whether it is a hydride-insertion (H-TS) or a silyl-insertion (Si-TS). (b) Intramolecular silylation and the transition state energy barriers (unit: kcal/mol).

Figure 30. (a) Michael addition of dimethyl malonate to cyclic enones with chiral amido ruthenium complexes. (b) Transition state for the β-keto ester asymmetric addition to cyclic enone. U

DOI: 10.1021/acs.chemrev.9b00073 Chem. Rev. XXXX, XXX, XXX−XXX

Chemical Reviews

Review

DFT calculations were carried out for the Rh-catalyzed [2+2+2],343 [3+2+2],344 [5+2],345 and [6+2]346 cyclizations. In 2008, while studying the mechanism of a diastereoselective Rh-catalyzed Pauson−Khand (PK) reaction, an unusual discovery was made in the computer model (Figure 32a).347 It

dicarbonyls on the NH moiety. The O-bound enolate complexes had relatively high barriers of nearly 25 kcal/mol, whereas the double hydrogen-bond complex was 8.2 kcal/mol, which was thermodynamically and kinetically stable (Figure 30b).338 Moreover, based on the proposed mechanism, DFT calculations elucidated the preference of (S)-products and predicted that the increased bulkiness of the coordinated arene enhances enantiomeric excess. Although visible-light photoredox catalysis gained attention as a new synthetic method in the last few decades,339 the redox potentials of heavy-atom based photocatalysts were poorly appreciated. In 2015, Hansen reported the DFT-computed redox potentials of photoredox catalysts, suggesting a way to promote catalysis with these systems.340 To find a suitable photocatalyst, the studies of ground- and excited-state redox potentials were carried out. With SC-ZORA relativistic corrections, the experimentally measured and the computed values had excellent correlations of R2 = 0.996 and 0.980 for ground- and excited-state redox potentials, respectively. The DFT prediction provided a potential catalyst that goes through C−H functionalization of 1-methylindole with diethylbromomalonate. Ir(ppy)3, Ir(ppy)3−, and Ru(bpy)3+ were able to cleave the C−Br bond, and the resulting malonyl radical afforded a new C−C bond product with a low barrier. Recently, Fürstner and collaborators developed a regioselective intermolecular Alder-ene-type C−C cross-coupling reaction (Figure 31).341 The (Cp*)Ru(Cl) analogue was

Figure 32. (a) Diastereoselective Pauson−Khand (PK) reaction catalyzed by a rhodium catalyst. (b) Charges (red) in transition states of the four-coordinate and the five-coordinate Rh-analogue. (c) Electronic effect of the C4′ position with the computed barrier.

was found that the diastereoselectivity is intimately connected to the coordination number of the Rh-center in the catalyst. Surprisingly, the catalyst fragments RhICl(CO) and RhICl(CO)2 that are thought to coexist in equilibrium under the reaction conditions were predicted to give two completely different diastereochemical outcomes. In the case of RhICl(CO), which gives a four-coordinate intermediate once the eneyne substrate is bound, the calculations showed that the energy difference of the transition states leading to the two possible diastereomers was only 1.2 kcal/mol. This small energy difference predicts a diastereomeric ratio (d.r.) of ∼10:1 at best. This finding was not consistent with the experimental observation that suggested a d.r. of ∼100:1. Interestingly, RhICl(CO)2, which gives a five-coordinate Rhcenter due to the additional carbonyl bound to the rhodium, showed a much more decisive difference of 6.7 kcal/mol between the two transition states leading to the two diastereomers. Because the binding of the additional carbonyl was calculated to be slightly uphill in energy, these calculations led to the testable prediction that lowering the CO pressure and with that the CO concentration in solution should show a deterioration of the experimentally observed diastereoselectivity. Employing a pure CO gas and mixtures of CO/Ar gases, this computational prediction was confirmed. This intriguing observation was explained employing the molecular orbitals involved in the oxidative cyclametalation step. The fivecoordinate Rh-center enables a closed-shell carbocyclization where the π-electrons of the eneyne substrate become localized to generate a partially positive C3 center, which can be

Figure 31. Regioselectivity of the coupling reaction between 2-butyn1-ol and crotyl alcohol with key intermediates.

appropriate for two hydrogen-bonds to link on the Cl site simultaneously. The peripheral hydrogen-bonding influences the selectivity, which was confirmed experimentally. To gain more insight, DFT calculations were performed, and in the reaction between 2-butyn-1-ol and crotyl alcohol, the head-tohead complex was located with a lower free energy by 4.9 kcal/ mol than the head-to-tail alignment. Similarly, in the transition states, the loss of hydrogen-bonds gave rise to the same trend obtained due to the enthalpic penalty. In addition, the computed results for diastereoselectivity showed that the steric repulsion between the propargylic methyl group and the Cp* ring favored the 1,4-anti isomer more than the 1,4-syn isomer. 3.3.1.3. Rhodium. Transition-metal catalyzed high-order [m +n+o] carbocyclization is a useful tool to synthesize polycyclic products which can be used in various fields.342 To elucidate the precise mechanism and delineate the experimental observations of this versatile and useful synthetic method, V

DOI: 10.1021/acs.chemrev.9b00073 Chem. Rev. XXXX, XXX, XXX−XXX

Chemical Reviews

Review

Figure 33. (a) Experimental exploration of asymmetric ynamide [5+2] cycloisomerization. (b) Computation guided ligand design with its energy barriers and experimental outcome.

reaction temperature was an attractive target for rational design, because the required temperature for the reaction was >120 °C, which limits this method notably in its synthetic utility. By installing halogen groups at the terminal alkyne position, the barrier was predicted to be as low as 24.5 kcal/ mol, which meant this reaction may take place at room temperature. These predictions were found to be correct in experiments. This computer-aided prediction was special, as the suggested functionalization is neither obvious nor within what experimentalist would have considered a standard optimization strategy. Recently, Liu and Brummond reported the Rh(I)-catalyzed allenic PK reaction (APKR).350 An active allene-yne species with transition metals and monodentate phosphoramidite ligand (S)-MonoPhos were examined. Although the enantioselectivity was determined as the oxidative cyclization step, as seen previously, a small difference between the two transition

stabilized by the inductive effect of the methyl group at the C2 position via hyperconjugation only in the transition state that forms the syn-product that is observed (Figure 32b).348,349 When the four-coordinate rhodium is used for this reaction, the metal does not have the correct frontier orbitals to promote such a cyclization and the metallacyclization proceeds via a radical pathway, where the stereodirecting electronic effect of the methyl group does not apply. The concept of the charge polarization at the transition state was exploited in a different subsequent study to rationally design another diastereoselective Rh-catalyzed PK reaction.349 By adding electron-withdrawing halogen functionalities at the alkynyl C4′ position, the charge distribution in the reactant was changed to more closely resemble what is found in the transition states. This was conceptually predicted to lower the transition state and confirmed computationally (Figure 32c).349 Lower transition state energy and with that lower W

DOI: 10.1021/acs.chemrev.9b00073 Chem. Rev. XXXX, XXX, XXX−XXX

Chemical Reviews

Review

states associated with the two enantiomers indicated the poor enantioselectivity in reasonable agreement with the experimental observations. To improve the enantioselectivity, various phosphoramidite ligands were explored and the role of the denticity of the ligands was analyzed in greater detail. It was found that the monodentate ligands are generally more reactive, but their conformational flexibility is a source for poor enantioselectivity. Bidentate ligands, on the other hand, display less flexibility but low reactivity and were not productive. This finding led to the design of the hemilabile bidentate class of ligands based on the (S)-MonoPhos-alkene skeleton that may combine the benefits of both systems, avoiding the drawbacks. Experiments suggested that the reaction was an example for a dynamic kinetic asymmetric transformation (DyKAT), and the computational investigation showed that the APKR (R)product can be formed when the alkene arm is unbound, to give the desired major enantiomer. The distortion−interaction analysis elucidated that this preference originated from the steric repulsions between the ligand and the substrate. Synthesis of eight-membered rings has been studied using several transition-metal catalyzed cycloadditions. In 2007, Yu and Wender showed the synthesis of ring fused cyclooctenes by computational design and subsequent experimental verification.351 [5+2+1] cycloaddition of ene-vinylcyclopropanes (ene-VCPs) and CO catalyzed by rhodium catalysts was chosen for this study. The calculated barriers of the reductive elimination steps were 25−30 kcal/mol. The combined experimental and computational studies identified an intriguing role of the CO functionality. In the absence of CO, a [5+2] cycloaddition at elevated temperatures was identified to be the main reaction pathway. In the presence of CO, lower yields were observed in general regardless of which ene-vinylcyclopropane substrate was used. Rh(I)-catalyzed intramolecular [3+2] cycloaddition of 1ene- and 1-yne-vinylcyclopropanes was studied by Yu and coworkers.352 The mechanism consists of four parts; adduct formation, cyclopropane ring-opening, alkene/alkyne insertion, and reductive elimination. For both substrates, the rate- and stereoselectivity-determining step is the alkene/alkyne insertion with a barrier of 22.1 and 18.8 kcal/mol, respectively, which explained the higher reactivity of 1-yne-vinylcyclopropanes, consistent with the experimental observation. A detailed analysis of the transition states showed that the 1,3-diaxial interactions and tether/substituent repulsions determined the diastereoselectivity. The bulkiness of the supporting ligand, such as bidentate phosphine, prohibited the byproduct formation via β-hydride elimination. Four years later, the analogous [4+2] cycloaddition was reported where the ynediene and ene-diene reacted in an analogous fashion.353 In 2016, Peng, Paton, and Anderson carried out the computational study in the [5+2] cycloisomerization of ynamidevinylcyclopropanes to [5.3.0]-azabicycles.345 Experimentally, aryl-substituted ynamides with electron-withdrawing groups show high efficiency and phosphoramidite ligands play a crucial role in determining enantioselectivity. These experimental findings were incorporated into the computational ligand design. The mechanism study revealed that the oxidative coupling of enynamide is rate-limiting. The ligand L1 was chosen and the electronic properties were controlled at the para-position of the benzylic group (Figure 33a).345 The L3 ligand showed the largest barrier difference compared to other ligands, and the experiments confirmed this prediction for most cases (Figure 33b).345

Morehead and Sargent carried out a QM/MM study on the Rh-catalyzed intramolecular hydroacylation of 4-pentenals.354 The position of the acyl group affected the reaction efficiency at the oxidative addition step, and the pathway including isomerization and carbonyl deinsertion led to the reaction with the cyclopentanone. In addition, the solvent on the substrate was found to impact the reductive elimination step and the side-reaction of decarbonylation deactivated the catalyst. Later, Woo and Dong reported an intramolecular ketone hydroacylation mediated by rhodium catalysts.355 Experiments suggested two catalysts, [Rh(dppp)]2(BF4)2 and [Rh((R)DTBM-SEGPHOS)]BF4 which showed good diastereoselectivity and high enantioselectivity, respectively. As mentioned above, the decarbonylation was competitive with oxidative addition and formed a Rh(CO) complex. The calculated ratelimiting step was ketone insertion which was consistent with the experimental observations. The intermolecular hydroacylation of alkenes was studied by Bo and Castillón.356 Neutral and cationic systems such as RhCl(PPh3)3 or [Rh(NBD)(PPh3)2]BF4 were modeled by DFT calculations. The neutral system afforded the oxidative addition product, whereas the cationic system needed the assistance of chloride anion. Notably, the transition states for oxidative addition showed similar barriers and nearly identical structures. However, in the case of the cationic system, the oxidative addition products were less stable than the neutral system, and this result supported the role of chloride as a stabilizer. The synthesis of linear aldehydes from alkenes has been a challenge because of the fast isomerization. In 2009, Carvajal and Shaik carried out computational studies on the selective hydroformylation of butene and octene with four catalysts.357 Although the computed energy profiles of butene and octene showed similar trends, the TOF of octene for isomerization was always lower than for butene and the hydride transfer step was revealed as a rate-limiting step. In addition, the complex with bulkier ligands formed η2-adducts of 2-octene leading to the linear aldehyde. Recently, a similar study for n-decene with the (H)Rh(CO)(BiPhePhos) catalyst was conducted by Stein.358 Due to the steric demand of the ligand bound to the metal center, van der Waals interactions must be considered for understanding the reactions and designing catalyst optimization strategies. In 2014, Kumar and Jackson reported ligand effects on the regioselectivity of olefins with the Rh(PPh3)(CO)(H) catalyst.359 The regioselectivity was determined not only by electronic effects imposed by ligands but also by the ligand−ligand and ligand−substrate nonbonding interactions. Similarly, the hydroformylation of 1,3butadiene with bisphosphite ligands was studied in 2014 by Hofmann.360 In contrast to a previous study,361 although the catalytic step depended on two transition states, reductive elimination or H2 addition, the temperature and pressure also might change the rate-determining step. The electronic property of phosphine ligands was found to be an important factor affecting the catalytic efficiency. In 2016, Vanka studied the activity differences between HRh(CO2)L and HRh(CO2)L2 as a function of the nature of the L ligand, where special attention was given to PPh3, PPhPy2, and PPy3.362 The computed results were analyzed by systematically comparing the structural parameters, the NBO-derived properties, and the frontier orbitals. These results were combined to propose a conceptual understanding of the generally higher chemical reactivity of the monodentate ligands, and it was proposed that X

DOI: 10.1021/acs.chemrev.9b00073 Chem. Rev. XXXX, XXX, XXX−XXX

Chemical Reviews

Review

the stability of alkene π-complexes is a key factor to determine the activity of these catalysts. For synthetic purposes, metal-carbenoids from diazo compounds are considered to be useful and versatile intermediates. In 2009, Autschbach and Davies reported the intermolecular cyclopropanation of para-substituted styrenes.363 For cyclopropanation, the donor/acceptor pair and the acceptor carbenoid showed different geometrical features, namely the staggered and eclipsed conformations, respectively. In particular, the stability of the donor/acceptor carbenoid intermediate gave rise to a cyclization transition state with a very low barrier of only 4.5 kcal/mol. In the case of C−H functionalization reactions, the acceptor carbenoid showed higher reactivity than the donor/acceptor carbenoid. These theoretical findings were exploited to develop a predictive model for C−H insertion stereoselectivity. This model suggested that the moderate size difference between L and M substituents should show high stereoselectivity, and experiments confirmed this prediction precisely. The Rh-catalyzed enantioselective synthesis of allenes using propargylic alcohols was studied in 2012 by Davies.364 The reaction of donor/acceptor carbenoids proceeded through a tandem oxonium ylide formation and [2,3]-sigmatropic rearrangement, instead of the O−H insertion. To elucidate the factors determining this departure from the standard mechanism, DFT calculations were carried out for both the primary propargylic alcohol and the highly substituted propargylic alcohol. The computed results showed that a highly substituted propargylic alcohol favored the formation of the 2,3-sigmatropic rearrangement products, which was influenced by a biradical character that was detected unexpectedly. In addition, two methyl groups affected the O−H insertion step, but not the 2,3-sigmatropic rearrangement. Two years later, Musaev and Davies reported the rhodium-catalyzed enantioselective cyclopropanation of electron-deficient alkenes.365 The electrophilic nature of metalbound carbenes has limited investigations of this versatile intermediate for electron-rich and electron-neutral alkenes, but the dirhodium catalyst Rh2(S-TCPTAD)4 (S-TCPTAD = Ntetrachloro-phthaloyl-(S)-(1-adamantyl)glycinate) does not only perform C−H amination but is an excellent catalyst for cyclopropanations. DFT studies were conducted for the reaction of vinyldiazoacetate with methyl acrylate, N,Ndimethylacrylamide, and methyl vinyl ketone. Calculations suggest that in the process of the cyclopropanation, instead of a conventional synchronous pathway (Figure 34a), a novel asynchronous pathway is operative (Figure 34b).364 For methyl acrylate and N,N-dimethylacrylamide, cyclopropanation was favored, whereas the methyl vinyl ketone preferentially gave the ylide because the epoxide formation was rapid. DFT calculations elucidated the role of the proposed catalyst with various types of substrates and delineated the deluge of experimental observations into a precise mechanistic concept. Hydrocarboxylation of alkenes using CO2 is useful for generating alkyl carboxylic acids. Very recently, Hopmann reported the Rh-catalyzed hydrocarboxylation and proposed an unusual transition state for the C−C bond formation step.366 Conventionally, CO2 insertion into a M−CRm fragment is expected to traverse a transition state (Figure 35a).366 In this system, however, the Rh-center was found to interact with CO2 and the organolithium substrate. First, the Rh−cyclooctadiene complex engages the arylic fragment of the organolithium substrate in an unexpected η6 coordination and it is this

Figure 34. (a) Conventional cyclopropanation pathway. (b) Asynchronous cyclopropanation and the transition state.

Figure 35. (a) Generalized mechanism for hydrocarboxylation of alkenes with CO2 and proposed conformation of C−CO2 bond formation transition state. (b) Transition state for CO2 insertion displaying an η6 coordination of the substrate with additional CH···O interactions suggested by computational modeling.

reactant complex that can react with CO2, where the organolithium portion of the molecule can nucleophilically attack CO2. The CO2 insertion was found to be the likely ratelimiting step, and the pathway involving a more traditional rhodacycle intermediate was rejected due to high energies. Nonetheless, the reactivity was not high due to the innate difficulty of engaging the CO2 reflected in a relatively high barrier for CO2 insertion. Furthermore, DFT calculations emphasized the importance of a nonclassical hydrogen bond between the olefinic C−H bond of the cyclooctadiene moiety and the carbonyl of the organolithium portion of the substrate (Figure 35b).366 Obviously, one of the perhaps most valuable contributions that computational studies of mechanisms have delivered over the last two decades is the precise structure of Y

DOI: 10.1021/acs.chemrev.9b00073 Chem. Rev. XXXX, XXX, XXX−XXX

Chemical Reviews

Review

transition states and the ability to precisely dissect the role of molecular interactions in determining the barrier heights. And this study offers an excellent example of how information that is typically difficult if not impossible to obtain from standard experimental techniques can be derived with ease from computational studies. Very recently, Korenaga reported the computational study of the Rh-catalyzed asymmetric 1,4-addition of an arylboronic acid to a coumarin substrate.367 Experimentally it was found that despite employing electron-deficient chiral diphosphine ligands that are expected to be highly active, these catalysts were found to perform poorly for the desired the 1,4-addition reaction and the hydrolysis of arylboronic acids. To design a more effective ligand, DFT calculations were carried out for several chiral diphosphine ligands, and it was found that the CH−π interaction with an electron-poor ligand indeed gives the anticipated stabilization of the transition state. Encouraged and guided by these precisely calculated transition states, the effect of installing strongly electron-withdrawing functional groups on the diphosphine ligand was tested computationally and a 3-fluoro-4-trifluoromethylphenyl modified diphosphine ligand was ultimately identified as most promising. Gratifyingly, the subsequent experimental test showed that this new catalyst was highly active and allowed reducing the catalyst loading by 2 orders of magnitude compared to the previous catalyst. Reasonable to excellent yields in the range of 71−95% and ee’s of >99% were generally observed. The power of this novel computer-designed catalyst was showcased to prepare the commercial antimuscarinic drug Detrusitol in gram-scale. 3.3.1.4. Iridium. In 2016, Wu and Sun investigated the Ircatalyzed hydrosilylation of internal thioalkynes.368 Despite various studies of catalytic silylation, the regio- and stereoselective hydrosilylation of unsymmetrical internal alkynes was reported only once and the mechanism remained poorly understood.369 Using the ubiquitous [(COD)IrCl]2 catalyst, reasonable results were obtained under mild conditions, regardless of type of thioalkynes and silanes employed. In DFT calculations, syn-hydrosilylation following the Chalk− Harrod mechanism335 (oxidative addition → hydrometalation → reductive elimination) showed high barriers above 31.2 kcal/mol with a Ir(III)-d6 center. The Ir(I) hydride complex was applied as an active catalyst, and the mechanism was found to be described above (hydrometalation → oxidative addition → reductive elimination) which showed a relatively low barrier of 27.1 kcal/mol (Figure 36).368 In addition, the alkyne insertion step was found to determine the regioselectivity. The computational study of the Ir-catalyzed hydroarylation of alkenes was reported in 2016 by Huang and Liu.370 The regioselective hydroarylation of olefins is a long-standing challenge, and much progress has been made over the last few decades. But, a fully satisfying solution is still not available and significant research continues to be dedicated to this broadly relevant reaction. In this computational contribution, a new mechanism was elucidated and the authors examined which factors determine the selectivity in catalysis. In contrast to the Chalk−Harrod type mechanism, these computational investigations showed that the reaction proceeds through the following sequence: C−H oxidative addition, migratory insertion into Ir−C, and C−H reductive elimination. The selectivity was determined at the migratory insertion step, and the reaction was under kinetic and not thermodynamic control. Based on this mechanistic finding, the ligand effect on the selectivity was explored. The DFT calculations showed that

Figure 36. Proposed Ir(I) hydride mechanism of hydrosilylation of internal thioalkynes and transition state for the formation of active Ir(I) species.

when the size of the ligand is increased, the ratio of branched to linear product enhanced for vinylarenes and aliphatic alkenes, and this trend was found to be a reflection of the bite angle that the ligands display (Figure 37).370

Figure 37. Ir-catalyzed selective hydroarylation of alkenes depending on the bite angle between ligands.

Recently, Sunoj reported the computational study of the asymmetric dual chiral catalysis (ADCC) using iridium phosphoramidites and diarylprolinol silyl ethers (Figure 38a).371 Combining a transition metal catalyst and an organocatalyst in one pot reaction conditions has attracted some attention as a new way of controlling complex chemical reactions and possibly designing new stereoselective reactions. To understand the diastereoselectivity, transition state analysis was performed by dividing the structure into four moieties and formally dissecting the overall interaction into three noncovalent interactions (Figure 38b).371 It was found that the number of interactions in the catalyst−catalyst assembly is a critical factor for enhancing diastereoselectivity, as detailed by atoms-in-molecules and noncovalent interaction plot analysis. In good agreement with experimental results, it was found that the most active catalysts have maximal numbers of catalyst− catalyst contacts. Cross-coupling reactions are tremendously important in organic chemistry. Typically, an arylhalide, which serves as a source for an electrophilic aryl fragment, and a substrate that Z

DOI: 10.1021/acs.chemrev.9b00073 Chem. Rev. XXXX, XXX, XXX−XXX

Chemical Reviews

Review

oxidative addition to ultimately produce an Ar−M−R fragment. Of course, whether the oxidative addition happens before or after CMD is a detail that must be worked out for each particular reaction. The final step in this conceptual mechanism is the reductive elimination that affords the Ar−R coupled product. A general observation is that the final reductive elimination in C−H arylation reactions is most difficult and often ratelimiting.376−379 Recently, Baik and Chang studied an Ircatalyzed arylation reaction and found the mechanism described above to be operative precisely.380 Using a wellestablished Ir(I)(Cp*) platform, an arylic C−H bond of a substrate carrying a directing group was successfully activated and oxidative addition to bind the nucleophilic coupling partner from arylhalides was also carried out. But, as observed by others previously, the final reductive elimination from the Ir(III)-complex carrying both coupling partners proved impossible, despite significant experimental efforts. A full computational investigation of this general mechanistic approach was carried out and a key conclusion was drawn: While the oxidative addition to process the arylhalide is considered routine, it is still a challenging transformation from a fundamental perspective and requires that the metal center is relatively electron-rich. This is realized in the ubiquitous Ir(I)Cp* platform by the highly electron-donating Cp* ligand. As a consequence, the Ir(III)-system that is formed as a result of the oxidative addition is reluctant to perform a reductive elimination to complete the cross-coupling. In other words, the catalysts considered for these new cross-coupling reactions are optimized to be effective at oxidative additions and they will therefore be ineffective for the reductive elimination required in the final step. Whereas this conclusion is perhaps logical and intuitively plausible, it also implies that conventional optimization strategies will fail: The logical way of enabling the reductive elimination is to functionalize the ligands on the catalyst to reduce the electron-density on the metal. Doing so, the reductive elimination will without doubt become easier, but the oxidative addition preceding the final step will also be compromised. Thus, this is a classical case of the requirements of the first and second step of the catalysis opposing each other. Further computational studies confirmed that no simple functionalization exists that will allow for lowering the reductive elimination barrier without compromising the oxidative addition step. A breakthrough was achieved by recognizing that the Ir(III) resting state that carried both coupling partners can be oxidized either chemically or electrochemically to the corresponding Ir(IV) or Ir(V) species. The increased oxidation state will of course lead to a much more favorable reductive elimination. DFT calculations offered a quantitative model with the reductive elimination barriers being 34.4, 15.7, and 4.8 kcal/mol for the Ir(III), Ir(IV), and Ir(V) complexes, respectively (Figure 39).380 Experiments confirmed that this new paradigm of oxidatively induced reductive elimination is a viable way of enhancing the reductive elimination step without jeopardizing the previous oxidative addition. Both chemical and electrochemical oxidations were found to be effective, and EPR studies supported the formation of an Ir(IV) intermediate before product formation. Whereas the concept of oxidatively accelerating a reductive elimination is intuitively easy to understand, this prototype study is arguably the most comprehensive and clear study to date that points out the logic behind the optimization process.

Figure 38. (a) Asymmetric dual chiral catalysis (ADCC) using iridium phosphoramidites and diarylprolinol silyl ethers. (b) Classification of intramolecular interactions in the stereocontrolling transition state.

contains a nucleophilic aryl, such as an organoboron moiety, Ar−BR2, are brought together with an appropriate catalyst such as various palladium complexes to form an Ar−Ar crosscoupled product, which is known as the Suzuki reaction322 and was recognized with a Nobel prize in 2010.372 Other variants of the cross-coupling reactions follow similar strategies but differ in which functionality they use to mask the nucleophilic coupling partner. In the powerful Negishi373,374 variant, an organozinc compound is used, while in Stille coupling an organotin substrate is cross-coupled.375 While extremely powerful, all these methods require a prefunctionalization step to obtain the nucleophilic coupling partner, and much effort has been dedicated to develop the next generation of C− C coupling method which can employ much more abundant motifs, such as a simple C−H bond. It is envisioned to first carry out a selective C−H bond activation, which will produce the nucleophilic aryl moiety, for example, and then carry out a cross-coupling with an arylhalide. This strategy is viable, because C−H activation catalysis has been used with a tremendous number of groups and one paradigm that has emerged is that C−H bonds can be cleaved by employing an electrophilic transition metal center in combination with a Brønsted base such as acetate, which will carry out a concerted metalation deprotonation (CMD) reaction to afford the M−R and acetic acid. To be used within a cross-coupling reaction, this metal center must next engage the arylhalide via an AA

DOI: 10.1021/acs.chemrev.9b00073 Chem. Rev. XXXX, XXX, XXX−XXX

Chemical Reviews

Review

Figure 39. Calculated energy profiles for reductive elimination from the Ir(III)-, Ir(IV)-, and Ir(V)-aryl intermediates.

The conceptual advance of using oxidations and reductions as a means of controlling portions of a catalytic cycle is of course generally applicable, and the convenience of using electrochemical methods to do so is highly attractive. Finally, the synergy between computational and experimental methods that meet on equal grounds and cross-fertilize ideas leading to what may be called a computer-inspired experiment or experiment-inspired computational modeling is more clearly visible in this work than in many other examples. 3.3.1.5. Palladium. Palladium is an extremely important and highly versatile metal for organometallic reaction chemistry. Consequently, much research effort in computational chemistry has focused on palladium complexes, and numerous reviews have recently appeared.381−384 Thus, we do not comment further on this active and vast area of research but only mention the following studies that are particularly relevant. The reductive elimination of ArCF3 from related Pd(II) species has been a challenging feat and has been pursued by several research groups both experimentally and computationally.385−390 The reason for the limited success in this area was that the reaction shows a particularly strong dependence on the ligand attached to the metal. In 2006, Grushin and coworkers reported the facile decomposition of the Xantphos Pd(II) species that formed PhCF3 when subjected to temperatures as low as 50 °C.391 Interestingly, there was also a report that replacing Xantphos with dppe rendered the corresponding Pd(II) species unreactive, even at temperatures as high as 140 °C.392,393 In addition, Buchwald and co-workers reported the trifluoromethylation of aryl chlorides in high yields using Ruphos and Brettphos as their ligand.394,395 These three examples, coupled with the fact that small ligands have proven ineffective in these processes, led to the understanding that this reactivity favors large bite-angle ligands. Schoenebeck and co-workers tested this hypothesis and built a computational model, designed a new ligand, and showed that bite-angle is not the overall determining factor in these reactions.390 The key to this success was the use of bidentate ligands with large bite angles to facilitate reductive elimination, which was known to be the turnover limiting step in this process. Interestingly, the Xantphos and dppe ligands with a phenyl group had a barrier of 25.7 and 34.0 kcal/mol, respectively (Figure 40a).390 In contrast, when the phenyl group was substituted by a proton, their barriers were almost the same. This result suggested that a bite angle cannot be the only factor controlling the reactivity. Instead, electronic factors

Figure 40. (a) C−C bond formation using Xantphos and dppe ligands with a phenyl group, and the computed barrier for elimination of PhCF3. (b) Computationally designed [(dfmpe)Pd(II)(Ph)(CF3)] complex and the computed properties.

in the catalyst fragment must be considered (Figure 40b).390 Based on the calculated results, the CF3 groups were added to afford the computed barrier 24.8 kcal/mol. Subsequent experiments confirmed that the reaction can be carried out using the proposed complex at 80 °C in 100 min. Kinetics experiments revealed an experimental activation free enthalpy of nearly 28 kcal/mol, which is in reasonable agreement with the computed values. This series of studies are interesting, because a very precise and plausible conceptual hypothesis had emerged previously using experimental clues alone. The biteangle of bidentate ligands has frequently been implicated to be important for controlling the chemical reactivity of metal complexes. And the change in frontier orbital energies as the angles of the ligands coordinate to a metal are varied is a textbook example in ligand field theory. Thus, the previously proposed relationship between the bite-angle and the reactivity toward ArCF3 generation was plausible and well within the tradition of ligand field theory. A more detailed computational analysis gave a more precise concept and showed that a much more effective control mechanism exists in employing electronwithdrawing functional groups. This example also highlights the power of natively combining both theory and experiment in an integrated research group. 3.3.1.6. Copper. In 2005, Nakamura showed based on calculations why organocuprate (R2Cu−) was a suitable carbon electrophile to form a C−C bond (Figure 41a).396 This theoretical insight was based on a molecular orbital analysis of the catalyst and substrates, where copper was systematically compared to silver and gold (Figure 41b).396 First, the HOMO (dz2) level of the copper complex was located at −0.02 eV, which was higher than in the silver (−0.49 eV) and gold (−0.79 eV) analogues. For the conjugate addition to occur easily, the HOMO−1 orbital that contains a significant amount of lone pair orbital character of the methyl anion must mix with HOMO−2, which is found to be mostly a metal-dxz AB

DOI: 10.1021/acs.chemrev.9b00073 Chem. Rev. XXXX, XXX, XXX−XXX

Chemical Reviews

Review

copper alkoxide generates the silyl ether product via a σ-bond metathesis with a hydrosilylating agent. Experimentally, the rate-limiting step was found to be sensitive to the amount of both ketone and silane used. In line with these experimental results, DFT calculations revealed two controlling factors: (i) At the first stage, the bulkier group of the ketone resulted in increased total strain energy and decreased interaction energy, simultaneously. (ii) On the other hand, at the second phase, the hydride character on the Si−H bond is more strongly related to controlling of the barriers. The additional experiments supported the calculation, and the computationally optimized copper hydride complex was reasonable. The study also revealed that a Lewis base was the rate-limiting reagent. 3.3.1.7. Gold. The Au(I)-catalyzed [4 + 1] cycloaddition of methylenecyclopropane with 7-naphthyl-1,3,5-cycloheptatriene was reported by Echavarren.401−403 Because no intermediate could be experimentally isolated, the mechanism remained speculative and without much support. Song and Xie carried out DFT calculations on this system to construct a suitable mechanism.404 The proposed reaction pathway consisted of three steps: (i) the formation of η2-cyclobutene−Au(I) complex via ring expansion; (ii) the formation of the Au(I) carbene complex through the retro-Buchner reaction; (iii) the Au(I) carbene complex generates cyclopentene via hydrogen atom transfer. For the Au(I) catalyst, the rate-limiting step was the formation of the carbene complex by breaking two C−C bonds at the second step with a barrier of 27.1 kcal/mol, and the total reaction was exergonic by 40.9 kcal/mol. In contrast, the alternative metal system considered, namely, [Ag(CH3CN)]+ and [Cu(CH3CN)]+, showed much higher barriers for the hydrogen atom transfer step of 44.9 and 41.2 kcal/mol, respectively. Moreover, the steric repulsions between phosphine and naphthalyl moiety decreased the catalytic activity, yielding a higher barrier. In 2016, Li and Wang reported DFT studies on the [4 + 3] intramolecular cycloaddition of trienyne.405 Three possible pathways are envisioned when the Au(I) catalyst approaches the C−C triple bond: (i) cyclization toward the expected seven-membered ring by passing through a five-membered cyclic carbene intermediate, (ii) noncyclic C−C coupling, and (iii) formation of the unfavored five-membered ring. Among the three pathways, the first pathway had the lowest barrier of 24.1 kcal/mol associated with a Cope rearrangement, and the calculated TOF of 5.90 × 10−6 s−1 based on the barrier was well matched by the experimentally observed value. To gain further insight, the controlling factors for the catalytic activity and selectivity were explored. The bulkier XPhos ligand gave a lower barrier (23.9 kcal/mol) and a higher TOF (7.86 × 10−6 s−1) than the Ph3P ligand. Moreover, the replacement of the methyl group on the C7 position with (CH2)4OBn decreased the TOF; however, this substitution improved the selectivity. As mentioned in the introduction, if the intrinsic uncertainties of the computational methods are considered, the levels of accuracy in these predictions are puzzling and serve as demonstrations of the power of error cancellation when chemically similar systems are compared to each other. The reactivity of gold carbenes inspired the development of C−H functionalization reactions of phenols with diazo compounds by Xia and Zhang.406 First, a precise mechanism was needed, and two possibilities were considered. Both C−H insertion and O−H insertion are plausible, and it was anticipated that the ligands present in the catalyst should determine which pathway is taken. The authors found that

Figure 41. (a) General reaction of organocuprate and an electrophile. (b) High-lying Kohn−Sham frontier orbitals of (CH3)2M(I)− (M = Cu, Ag, Au).

orbital. In this context, the energy differences of these two orbitals were found to be smallest when copper was used. Furthermore, the MO analysis showed that (CH3)3Cu(I)− was the strong nucleophile. With this qualitative MO-description in hand, the energetics of the reductive elimination step was investigated. For (CH3)3M(III)P(CH3)3, the copper system was stable thermodynamically and the structure remained intact throughout the reaction step. Interestingly, the copper complex adopts a T-shaped structure at the transition state, whereas the silver and gold complexes cannot maintain the M−P(CH3)3 bond and are predicted to decompose. Fragment energy analysis elucidated the difference between the copper, silver, and gold complexes. Jiménez-Osés and Fraile contributed an interesting study on the stereoselective Cu-bis(oxazoline)-catalyzed C−H insertion reaction.397 Based on previous experimental observations,398 a ring-opening/cyclization cascade reaction was proposed with the epimerization of Cα in the presence of a base. To determine the absolute configuration of the reactants, computational VCD spectroscopy at the B3LYP/6-31G(d) level of theory was conducted. The computed results were verified experimentally by a strikingly well matched VCD spectra. Next, mechanistic studies were performed and 16 transition states were located where all transition states had a quasi-linear hydride transfer from THF C2 to the copper− carbene complex Cα via an asynchronous way. The (2R,αS) enantiomer was predicted to be preferred, which was again in good agreement with the experimental results. Interestingly, it was found that dispersion interactions that were specifically modeled using Grimme’s D3 corrections399 were important to properly match the experimentally observed stereoselectivity in these systems. Hydrosilylation is widely considered a useful tool for carbonyl bond reduction because of the mild reaction conditions and atom-efficiency, as it only requires a single step for the reduction and the protection steps. In 2014, Leyssens reported an (NHC)Cu(I)-catalyzed hydrosilylation of ketones.400 The catalytic cycle consists of two steps where (i) the active species (NHC)CuH and the ketone react to give a copper alkoxide via a four-center transition state and (ii) the AC

DOI: 10.1021/acs.chemrev.9b00073 Chem. Rev. XXXX, XXX, XXX−XXX

Chemical Reviews

Review

(PhO)3PAuSbF6 preferred the C−H insertion, while the Ph3PAuSbF6 was found to display a higher reactivity toward O−H insertion (Figure 42a).406 Such a diversity was neither

Figure 42. (a) Coupling of phenols and diazo compounds with (PhO)3PAuSbF6, and Ph3PAuSbF6. (b) Reaction temperature on the chemoselectivity and the competitive pathways for the formation of two key intermediates.

Figure 43. Calculated free energy profiles and the corresponding structures of intermediates and transition states of (a) anisole/ phenol/toluene/benzene for the para-site C−H insertions catalyzed by (PhO)3PAuSbF6. (b) H3C−H, (CH3)H2C−H, and (CH3)2HC−H electrophilic addition catalyzed by (PhO)3PAuSbF6.

precedented nor intuitively predictable. The control experiments showed that these predictions were correct, and further analysis indicated that the C−H insertion pathway at the paraposition of the substrates is under thermodynamic control, whereas the O−H insertion product is kinetically preferred (Figure 42b).406 In the example above, the reactivities of toluene and benzene were poor, although the gold catalyst was able to activate the aromatic C(sp2)−H bonds of phenols and anisole. To investigate this somewhat puzzling trend, a DFT study of a series of arenes was conducted by Xia.407 The addition of gold carbene at the para-position of the anisole was preferred with a calculated overall barrier of 20.3 kcal/mol at the intramolecular hydrogen transfer step. Interestingly, the calculations proposed a water-assisted mechanism to be most preferable. To verify this unanticipated prediction, control experiments were carried out for confirmation, and the computer models were found to be accurate. Calculations further showed that benzene and toluene require higher barriers compared to phenol and anisole (Figure 43a).407 The electronic structure analysis elucidated that the electron-donating ability in aromatic rings was responsible for this trend. Moreover, the barriers of the insertion of gold carbenes into C−H bonds were related to the dissociation energy of the C−H bond of alkanes (Figure 43b).407 3.3.2. C−B Coupling. Transition-metal-catalyzed borylation of hydrocarbons408−411 has seen remarkable progress, and some pioneering contributions by Hartwig,412−418 Marder,419−422 and Smith423−428 have built a strong mechanistic foundation for this interesting and highly versatile reaction

platform in organic chemistry. In this section, we will highlight some work on Rh- and Ir-based catalysts, where computational studies offered some unexpected and surprising insights. At the onset of developing a new synthetic methodology, it is useful to evaluate the strengths of bonds that are being formed versus those being broken to estimate whether or not the proposed reaction is viable. A precise knowledge of these energies can help to anticipate the need for additives that may undergo a transformation for the sole purpose of delivering energy that will help to drive the reaction of interest or facilitate the regeneration of the catalyst. Two decades ago, experimental bond energies of only a handful of boron compounds including boranes were available, and it was recognized that these bond energies should be calculated using state of the art quantum chemical methods. To do so, Hartwig429 carried out high-level ab initio calculations using the G-2 and CBS-4 methods, and these values have served as the de facto standard for estimating whether a proposed borylation mechanism was reasonable before performing the experiments. 3.3.2.1. Rhodium. As early as 2005, Hartwig and Hall reported a computational study on the terminal functionalization of alkanes and arenes catalyzed by rhodium catalysts.430 The study uses (Cp*)Rh(Bpin)2R (R = Bpin, H) as the borylating catalyst, and B2pin2 was employed to be the boron source and also to deliver the chemical energy for driving the reaction to completion. Mechanistically, a sequence of AD

DOI: 10.1021/acs.chemrev.9b00073 Chem. Rev. XXXX, XXX, XXX−XXX

Chemical Reviews

Review

oxidative addition and reductive elimination or σ-bond metathesis was considered. This modeling study established a number of interesting insights: (i) In the C−H activation transition state partial B−H bonding between the C−H and one of the boryl ligands on the metal develops, and that gives rise to an important lowering of the barrier. Interestingly, it was found that this structural motif persists in both mechanisms considered. (ii) The C−H bond cleavage step is likely the rate-determining step during the catalysis. (iii) The π-donating ability of the atoms adjacent to the boron atom plays a crucial role in generating the transition state for the σbond metathesis. In another computational work, the Rh(I)-catalyzed borylation via C−F bond activation was studied by Macgregor and Braun.431 In contrast to the Ir(III)/Ir(V) catalysis,413,424 the Rh(I)/Rh(III) catalytic cycle was proposed for the Rh(Bpin)(PEt3)3 system (Figure 44a).431 It was shown that

oxidative addition of the diboron reagent, while the C−CN bond activation was calculated to be easy to accomplish. In addition, a specific Ir−B complex was proposed and the DFT calculations showed similar results for the Rh−B complex, where the overall barrier was higher only by 1.1 kcal/mol. Two years after this theoretical discovery was reported, an experiment was performed by Esteruelas.436 As predicted, the oxidative addition of the diboron reagent required a relatively higher reaction temperature of 90 °C and NMR and X-ray diffraction studies confirmed the previously proposed mechanism precisely. In 2014, Takacs and Zeng reported a mechanistic study of a carbonyl-directed Rh(I)-catalyzed hydroboration of cyclic γ,δunsaturated amides.437 In contrast to the previous computational work, a two-point binding mechanism was suggested, in which the carbonyl group of the amide and the CC π-bond alkene were bound to an Rh(I)-center in a cis fashion. Based on this theoretical finding, experiments were performed for oxime-derived catalytic asymmetric hydroboration (CAHB)438 and combination with Suzuki−Miyaura cross-coupling.439,440 3.3.2.2. Iridium. In 2003, Sakaki reported the mechanism of the catalytic borylation of benzene using a computer model.441 Previously, Hartwig413 designed an Ir(III) tris(boryl) complex capable of catalytically borylating arenes with an Ir(III)-d6 center, and the C−H bond activation was thought to proceed via oxidative addition. For the first time, a complete catalytic cycle was proposed based on a model system invoking an Ir(V) complex (Figure 45a).441 The computed results suggested that Ir(Beg)(diim) (eg = ethyleneglycolato, diim = diimine) with an Ir(I)-d8 center can undergo oxidative addition to form the Ir(III) intermediate with a reasonable barrier, and the formation of the Ir(III)(Beg)3(diim) was calculated to be exergonic. Various pathways were considered and the final mechanism proposed a seven-coordinate oxidative addition intermediate Ir(Beg)3(bpy)(C6H5)(H) with an Ir(V)-d4 center, the formation of which had the highest barrier of 24.2 kcal/mol (Figure 45b).441 This step was proposed to be ratedetermining. In addition, the calculations revealed the role of B2eg2 and the reason why this substrate is suitable for catalysis compared to the pathway involving HBeg at the catalyst regeneration step. This theoretical work further suggested that the role of the bpy ligand and the pinacolato-boryl group was to stabilize the Ir(V)-d4 intermediate. With this theoretical concept of the mechanism, new catalyst design guidelines were established for late transition metal complexes.409 The computational research advances were met by notable progress in experimental investigations of the iridium catalysts, such as Ir(III)(dtbpy)(Bpin)3 (dtbpy = 4,4′-di-tert-butyl-2,2′bipyridine),409 and a number of mechanistic details were disclosed through additional computational studies.441 However, the theoretical understanding of the regioselectivity remained elusive. Previously, Marder422 presented an interesting correlation between pKa of the C−H bond and the regioselectivity of the Ir-catalyzed borylation. To elucidate the controlling factors of regioselectivity, Merlic and Houk carried out DFT calculations using the distortion/interaction model (Figure 46).442,443 The distortion/interaction model compares the energies of distortion that a molecule has to go through from the ground state to reach the transition state, where chemically meaningful fragments are defined and the distortion energies are evaluated separately. With these distortion energies in hand, the interaction energies between the

Figure 44. (a) Rh-catalyzed borylation of pentafluoropyridine. (b) Transition states for the oxidative addition and boryl-assisted pathway on the 2-, 4-position of the pentafluoropyridine.

both the Lewis acidity of boron and the electron-donating ability of the nitrogen atom lone pair can stabilize the transition state in the C−F cleavage step. For pentafluoropyridine, DFT calculations predicted that the boryl-assisted pathway has the electronically lowest barrier of 4.1 kcal/mol (Figure 44b).431 This computational prediction was experimentally confirmed with a 2-boryl product of 45% yield in the presence of the catalyst. Transition-metal catalyzed C−CN bond functionalization has gained attention due to some remarkable advantages, such as broad substrate scope, ease of removal of byproducts, and high selectivity.432 Chatani developed a Rh(I)-catalyzed borylation of nitriles via C−CN bond activation.433 In a related study in 2013, Fu conducted a mechanistic study of Rhcatalyzed borylation of nitriles and proposed a new type of iridium complex that can be effectively used in borylation.434 The DFT calculations suggested that a deinsertion pathway is suitable via 2,1-insertion of the CN bond into the Rh−B bond. Combining with the energy span model,435 DFT studies indicated that the potential rate-determining step was the AE

DOI: 10.1021/acs.chemrev.9b00073 Chem. Rev. XXXX, XXX, XXX−XXX

Chemical Reviews

Review

calculations revealed that the interaction energy between the iridium catalyst and arene dominantly determined the regioselectivity rather than the fragment distortion energy. As reported by Sakaki441 and Hartwig444 previously, the C−H bond cleavage step determined the overall rate of the reaction and regioselectivity. Transition state analysis was performed at the C−H activation step for various arenes; i.e. benzene, mono- and 1,2-disubstituted benzenes, and 5-membered heterocycles. For toluene, the barrier of ortho-C−H bond activation, TS-o, was higher by 2.5 kcal/mol than other transition states due to the steric effect. In addition, the C−H bond of toluene was longer than that of other substituted arenes, which is an evidence for a structurally late transition state. For monosubstituted benzenes, the electronic effect did not control the regioselectivity, whereas 1,2-disubstituted benzenes showed opposite trends. The same approach was carried out for various arene derivatives. The calculations showed a strong correlation between the activation energy and the Ir−aryl bond strength of the Ir−aryl interaction energy. The concept and use of an organometallic transition-state bond energy were introduced by Ess and co-workers for the regioselectivity of Pd−acetate arene C−H activation reactions.445 This theoretical understanding provided a practical guide for designing and optimizing the catalysis to control the selectivities of borylation reactions in substituted arenes and 5membered heterocycles. Recently, Nakao446 and Itami and Musaev447 reported the regioselective C−H borylation of arenes. A sustainable way of utilizing methane as a feedstock for more complex chemicals is a holy grail technology that remains elusive due to methane’s inertness. Inspired by Hartwig’s work, the catalytic borylation of methane was studied in 2016 by Sanford448 and by Baik and Mindiola.449 Sanford reported methane borylation mediated by a Ru catalyst, and at the same time, Baik and Mindiola showed an Ir-catalyzed methane borylation where experiments and calculations were uniquely combined (Figure 47).449,450 DFT calculations were employed to ask why the versatile and powerful iridium catalyst championed by Hartwig for a variety of C−H bonds is

Figure 45. (a) Borylation of benzene with B2pin2 and the truncated model structures for calculations. (b) Computationally proposed catalytic cycle of the borylation of benzene.

Figure 46. Oxidative addition transition state for the reaction of toluene and the computational, experimental results depending on the position of the oxidative addition stage.

fragments are evaluated. This procedure affords a chemically intuitive energy decomposition of the transition state energy, which allows for rationally changing the chemical composition to adjust the transition state energy. At the C−H oxidative addition step, the transition state structure was divided into two parts: the iridium catalyst and the arene scaffold. The

Figure 47. Catalytic borylation of methane and the transition state barriers of oxidative addition with phenanthroline and dmpe ligands. AF

DOI: 10.1021/acs.chemrev.9b00073 Chem. Rev. XXXX, XXX, XXX−XXX

Chemical Reviews

Review

application as organocatalysts.461−463 While many examples of both intra- and intermolecular diamination of alkenes exist,461 asymmetric diamination of alkenes that yields highly enantioenriched, vicinal, diamines remains rare.464 In 2007, Shi and co-workers reported the first transition-metal catalyzed asymmetric diamination of conjugated dienes and trienes with di-tert-butyldiaziridinone.465 These Pd-catalyzed reactions worked best with tetramethylpiperidine-derived BINOL phosphorus imidite ligands. 465 The discovery of this remarkable reaction enabled by BINOL ligands prompted a detailed DFT study by Jindal and Sunoj, which elucidated the mechanism and identified the role of the chiral ligands in controlling the enantioselectivity. In addition, transition-state analysis revealed that the first C−N bond formation step is what controls the stereoselectivity in this catalysis, as it dictates the geometry of the π-allyl palladium prior to reductive elimination.466 Using this model, the authors showed that the calculated ee with different chiral phosphoramidite ligands is in good agreement with experimental observations (Figure 48).464 Sunoj and co-workers took advantage of these results

incapable of processing methane. Detailed calculations on the putative reaction of the iridium catalyst with methane showed that the barrier for activating the first C−H bond of methane using the (1,10-phenanthroline)Ir(Bpin)3 catalyst is nearly 35.4 kcal/mol following the proposed mechanism. Such a high barrier indicates that the C−H bond cleavage was possible only under harsh conditions, such as high temperatures in the range of 100−250 °C and high pressures of methane. Experimental studies showed that these qualitative interpretations are correct, and trace amounts of borylated methane products were detected at ∼150 °C and up to ∼8000 kPa pressure of methane gas. Based on this encouraging study showing that the reaction with methane is at least possible, an optimization strategy was developed by analyzing the computed transition state structure and energy. One useful conclusion was that a significant energetic effort is expected at the transition state to polarize electron density away from the metal, which is plausible and intuitively understandable for an oxidative addition. This electron density distortion energy was relatively high, because the Ir(III)-center constitutes a relatively hard Lewis base. To lower this energy component, the Ir(III)-center must be made softer, and computations indicated that replacing the hard N-donor ligands with much softer Pdonor ligands, such as phosphines, may be a viable strategy. Interestingly, a simple bidentate phosphine ligand, 1,2bis(dimethylphosphino)ethane (dmpe), was calculated to lower the barrier by 3.1 kcal/mol compared to the phenanthroline, which would translate to a ∼1000-fold increase in reaction rate. Experimental studies on (dmpe)Ir(Bpin)3 produced the monoborylated methane in 52% yield with a TON of 104. Subsequently, a thorough mechanistic study of methane monoborylation was reported.450 In addition, this energy difference was elucidated by electronic energy difference analysis. 3.3.3. C−N Coupling. Ubiquitous nitrogen-containing molecules in natural products and pharmaceutical agents have prompted the development of a synthetic method to form C−N bonds.451 C−N cross-coupling reactions have received considerable attention during the past hundred years, with the earliest seminal work, which have been reported by Ullmann452−455 and Goldberg.456,457 Recently, transitionmetal-catalyzed C−H amination made tremendous progress and several methods have been established.451 Since the pioneering work by Breslow,458,459 various aminating reagents have been reported. It is not an exaggeration to state that C−N bond formations are one of the cornerstones of synthetic organic chemistry. In addition to various amination reactions, hydroamination is among the most atom-economical ways to combine two widely available functional groups to afford synthetically and biologically useful N-containing products. Both inter- and intramolecular hydroamination have garnered a great deal of attention, resulting in a wide breadth of literature reports of hydrominations for alkenes and alkynes.460 As stated for other reactions mentioned above, the field of C− N coupling reactions is vast, and over the past decade numerous computational studies have accompanied an even greater number of excellent experimental studies. Here, we can only mention a handful of studies that we feel are particularly interesting, keeping the focus of this review in mind. 3.3.3.1. Palladium. The diamination of alkenes is a chemical transformation of great importance due to the presence of 1,2diamines in various natural products that possess important biological properties, are drug candidates, and have potential

Figure 48. Pd-catalyzed diamination of conjugated dienes by di-tertbutyldiaziridinone with selected chiral phosphoramidites with the computationally predicted and experimental ee’s.

as the foundation for the rational design of novel organometallic catalysts. The transition states of the phosphoramidites with bis(isopropyl)- and dimethyl-amine revealed that M06 and M06-2X geometries tend to slightly overestimate the ee due to the overestimation of the C−H···π interaction energy in the transition state. To address this issue, M06 energy calculations were performed on B3LYP geometries to achieve the best agreement with experiments. Using these methods in transition state modeling, the authors screened 23 types of catalysts and identified 8 rationally designed catalysts that have greater than 99% calculated ee.464 Next, the effect of the binol 3,3′ substituent and the amido group on the stereoselectivity was investigated. Modeling with bulkier groups on the binol substituent predicted a better ee up to 99%. On the other hand, the α- and β-substituted amido groups did not increase the ee’s. These transition state modeling steps for asymmetric diamination led to a promising catalyst which has a bulky group at the binol, and this type of catalysts showed the ee’s up to >99%. 3.3.3.2. Rhodium. The first in-depth in-silico study of catalytic hydroamination of ethylene with ammonia was reported by Hölscher and Leitner in 2010 (Figure 49a).467 Special attention was given to how the composition of the ligands impacts the properties of the metal center and how this AG

DOI: 10.1021/acs.chemrev.9b00073 Chem. Rev. XXXX, XXX, XXX−XXX

Chemical Reviews

Review

rhodium catalyst interacted with CO and amines, the computed results showed that the five-coordinated product was preferred kinetically and thermodynamically, which is well matched with spectroscopic results. In addition, DFT calculations predicted that the reaction with H2 is dependent on the type of solvent, and this insight was confirmed by NMR ̈ Maron, and Kalck and deuterium labeling studies. Urrutigoity, reported the HAM of styrene mediated by rhodium complexes.472 Experimentally, chiral phosphine ligands containing rhodium catalysts lost enantioselectivity during one-pot reaction. The speculation was that the relatively high temperature interrupts the enantioselective hydrogenation of styrene. DFT calculations revealed that for each enantiomer the computed energies were almost identical and the difference of the overall barrier is in the range of ±3.5 kcal/mol. The result was in reasonable agreement with the experimental observations. The theoretical insights predicted that the bite angle of phosphine ligands might play a crucial role in determining the enantioselectivity. Experiments were carried out using large phosphine groups, and as expected, the enantioselectivity was increased.473,474 Aziridines were used as a building block in bioactive natural products. Despite the synthetical importance, most of the synthetic methods require strong external oxidants. Moreover, an electron-withdrawing N-protecting group was frequently used to prevent the formation of undesired products, but it gave rise to low stereoselectivity due to the high reactivity.475 In contrast to the previous methods, Ess, Kurti, and Flack reported the direct stereospecific conversion of various olefins to N−H aziridines using DPH (DPH = o-(2,4-dinitrophenyl)hydroxylamine) in the absence of external oxidants.475 TFE (CF3CH2OH), which has a highly polar, hydroxylic, and nonnucleophilic property was a suitable solvent. Additionally, elevating temperature and increasing catalyst loading increased the reaction efficiency. With these experimental results in hand, DFT calculations were conducted to delineate the mechanism considering several possible pathways involving Rh-nitrene, Rh-amine, and other Rh−N adducts. Among these pathways, the calculated overall barrier of spin-state interconversion in the Rh-nitrene pathway showed the lowest barrier of 17.6 kcal/ mol, which was well matched with the experimental results. DFT calculations of Rh-catalyzed C−H amination of 2phenylpyridine using phenyl azide were carried out in 2016 by Ajitha and Jung.476 The assumption was that 2-phenylpyridine behaves as both substrate and base. The deprotonation and molecular nitrogen formation step had a barrier of 24.8 and 27.7 kcal/mol, respectively. At the first stage. the Rh(III)amido intermediate was generated in a highly exergonic step (−55.6 kcal/mol). One of the roles of 2-phenylpyridine is to regenerate the catalyst. At the deprotonation and protonation step, the barrier without the assistance of a base was computed to be 34.5 kcal/mol, whereas the base additive reduced the barrier to 25.2 kcal/mol, which translates to a dramatic increase in reactivity. Based on this DFT result, a precise strategy for enhancing the reactivity using a proper base was developed. In 2015, Chang reported a new amidating source, 1,4,2dioxazol-5-one, as a substitute of organic azides.477 In the case of the Cp*Rh(III)-catalyzed amination reactions, kinetic and coordination studies confirmed that the binding affinity of nitrogen sources to the metal center is important to the reaction efficiency.478 DFT calculations also elucidated the kinetic and thermodynamic preference of 1,4,2-dioxazol-5-one

Figure 49. (a) Catalytic hydroamination of ethylene with ammonia. (b) Computational screening to find a new rhodium catalyst with PE(CH2CH2X)P ligands (E = B, C, N; X = O, NH, CH2, PH, SiH2).

modulation changes the structure and energetics of the intermediates and transition states of the key steps of the catalytic cycle. The authors hypothesized that three steps might affect the reaction efficiency. They are (i) N−H bond metathesis, (ii) C−N bond formation between the amide group and ethylene, and (iii) N−H bond metathesis by liberating ethylamine. After calculations were completed using various ligands, the Ru−NCN complex (NCN = 2,5bis(dimethylaminomethyl)benzene) was chosen as a catalyst, as this complex showed the lowest barriers for all three steps. The computed results also indicated that the Rh(III)-amido complexes, Rh(NCN)(H)(NH2) and Rh(NCN)(C2H5)(NH2), were suitable precatalysts. The computed barrier of Rh(NCN)(C2H5)(NH2) was 15.2 kcal/mol for ethylamine formation that was low enough to proceed with the reaction. The DFT results also showed that the precatalyst did not only successfully catalyze this reaction but also required no activation. In addition, the oligomerization/polymerization pathway was found to be potentially sensitive to unproductive side reactions. Three years after this in-silico proposal, a new rhodium catalyst with PE(CH2CH2X)P ligands (E = B, C, N; X = O, NH, CH2, PH, SiH2) for hydroamination of C2H4 with NH3 was reported by Hölscher and Leitner (Figure 49b).468 In contrast with the previous PEP ligands, the authors introduced an ethyl side arm onto the E site to block the binding site and control the electronic properties. First, the Rh−PC(CH2CH2X)P system was investigated to identify a suitable X group. The energy span model predicted that the NH group is promising with a computed barrier of 32.2 kcal/mol. The DFT calculations revealed that CH2CH2NH was the relevant ligand. Using the same approach, some factors that can influence the catalysis were investigated: the type of metal, the charge of the complex, the solvent, and peripheral ligand substitutions. Based on this computational study, it was found that the optimal catalyst, RhiPrPC(CH2CH2NH)iPrP, in CH2Cl2 has an activation energy of 26.8 kcal/mol. Moreover, side reactions and outer sphere mechanisms were negligible. Although hydroaminomethylation (HAM) of alkenes had advanced regioselectivity and chemoselectivity, the precise mechanism was poorly explored.469,470 In 2012, Maron, Claver, and Kalck studied the Rh-catalyzed hydroaminomethylation for cationic and neutral species.471 As the four-coordinated AH

DOI: 10.1021/acs.chemrev.9b00073 Chem. Rev. XXXX, XXX, XXX−XXX

Chemical Reviews

Review

energy was evidence of a metastable intermediate. This calculated result corresponded to the H/D KIE results and elucidated why this intermediate was hard to localize using spectroscopic methods. As aforementioned, the discovery of 1,4,2-dioxazolone derivatives as a general amidation reagent represents an important advance in this area, because they give access to amidation products under mild conditions relative to their organic azide counterparts. Despite this notable advantage and the generally understood paradigm of C−H amidation reactions, the C−N bond forming process in these reactions remained unclear. To uncover the details of this process, Baik and Chang carried out detailed theoretical and experimental studies on systematically comparing the Rh(III)- and Ir(III)catalyzed amidations (Figure 50a).487 The DFT calculations for each rhodium and iridium catalyst revealed that the turnover-limiting step was the metal-imido species formation and dissociation of the nitrile ligand with a computed barrier of 22.8 and 15.5 kcal/mol, respectively (Figure 50b).487 The computed and experimental geometric parameters are consistent with a stronger relativistic contraction of the Ir-

relative to the analogous acyl azides. As expected, compared to the case of acyl azide, the calculated overall barrier was lower by 12.7 kcal/mol and the product was located at a low free energy of 4.3 kcal/mol, which gave insight to designing mild condition catalysis. Mechanistic understanding of intermolecular amination was rarely studied since the degree of freedom increases at the C− H insertion step,478−481 adding additional challenges to the modeling effort. Wang investigated site-selective C−H amination methods using a Rh2II,II(esp)2 catalyst (esp = α,α,α′,α′-tetramethyl-1,3-benzenedipropanoate).482 The catalytic cycle consists of two parts: (i) the metal−nitrene formation and (ii) the C−H bond activation and C−N bond formation. The Rh−nitrene complex preferred the triplet spinstate, and both σ-type and π-type 3c/4e bonds in Rh−Rh−N led to a strong electrophilic reactivity. The site-selectivity was determined at the second stage. In particular, para-substitution of substrates with a strong electron-donating group enhanced the benzylic product formation. 3.3.3.3. Iridium. Although alkylation of amines is useful, previous methods had some drawbacks, such as the waste generated during the preparation of alkyl halides483 and low selectivity of polyalkylation.484 In 2008, Eisenstein carried out a DFT study for Ir-catalyzed alkylation of amines with alcohols.485 Three possible model catalysts which follow the same pathway had three parts in the catalytic cycle: (i) oxidation of alcohol through dehydrogenation, (ii) formation of imine via condensation of the aldehyde, and (iii) generation of amine by hydrogenation of the imine. For Ir(Cp)(CO3), the β-H elimination was suspected as the rate-determining step with a computed barrier of 17.6 kcal/mol; however, the catalyst regeneration via amine dissociation was located at 22.1 kcal/mol uphill. The DFT results predicted that the reaction may proceed under harsh conditions, and a less basic amine was suggested to promote the reaction. As predicted, the yield increased up to 53% with TsNH2 (Ts = p-CH3C6H4SO2) at a faster rate than PhCh2NH2. For other catalysts, the β-H elimination was revealed to be most difficult with a barrier of 33.2 and 27.2 kcal/mol for Ir(Cp)(Cl)2 and Ir(Cp(NH2Me)(Cl))+, respectively. To better understand the ligand effect at the β-H elimination, NBO analysis was conducted. At this transition state, the Ir−O π-bond that was present in the intermediate disappeared. Their mechanistic finding suggested that a harder base −OMe which has less π-bond character and the Ir(Cp)(CO2H)(OMe) gave a low barrier around 10.5 kcal/mol with an Ir(III)-d6 center while the Ir(Cp)(CO2H)(NMe2) which has more π-bond character afforded higher barriers. Similarly, the DFT results of other catalysts were in reasonable agreement with the hypothesis. Although the related cyclohydroamination methods have been well developed and a variety of products can be prepared, late transition-metal catalyzed intramolecular hydroamination of unactivated alkenes with amines was poorly understood until recently. Tobisch and Stradiotto reported an Ir-catalyzed alkene hydroamination study that combined experimental and theoretical methods.486 The mechanistic study was carried out for two pathways which consist of CC bond and N−H bond activation. The DFT calculations proposed that the reaction take place via electrophilic CC bond activation, and the calculated overall barrier is 24.6 kcal/mol at the reductive elimination step, in good agreement with experimental Eyring data. Moreover, the putative Ir(III)-hydrido complex was located with a free energy of 19.9 kcal/mol. This relatively high

Figure 50. (a) Ir-catalyzed amidation using 1,4,2-dioxazolone derivatives. (b) DFT-calculated barriers for CO2 elimination step. (c) Qualitative MO-diagram of the metal−imido complex. AI

DOI: 10.1021/acs.chemrev.9b00073 Chem. Rev. XXXX, XXX, XXX−XXX

Chemical Reviews

Review

molecular kinetic isotope experiment (KIE) studies advocated the concerted insertion pathway suggested by the DFT calculation. The combination with the theoretical and experimental study reached the synthesis of γ-lactam from biorelevant molecules, such as L-leucine and citronellic acid. 3.3.4. C−O/S Coupling. The importance of ArSCF3 compounds has increased notably in the pharmaceutical and agrochemical field.490−492 In 2015, Schoenebeck reported an air-stable dinuclear Pd(I)-catalyzed trifluoromethylthiolation of aryl iodides and bromides, instead of using Pd(0) catalysts.493 In this catalysis, the whole reaction was exergonic, and the Pd(I)−Pd(I) catalyst with ArI showed that the overall barrier for the ArI → ArSCF3 exchange process was 28.0 ± 3.9 and 27.1 kcal/mol, experimentally and computationally, respectively. The reaction using this catalyst indicated excellent yields for most cases of aryl iodides and bromides (92−99%). For the Pd(I)−Pd(I) catalyst with ArBr, the calculated overall barrier was higher by 3 kcal/mol than iodides, and the reaction was viable at the same conditions and the yields were slightly lower than the cases of ArI. Namely, the DFT calculations predicted the reactivity and the experiments confirmed the actual role of the dimeric catalyst. This work is an excellent example of how the seamless integration of computational and experimental methods can be leveraged to iteratively enhance the understanding of a catalytic process and derive rational design strategies for improved catalytic performance. In the same year, Schoenebeck reported a similar work employing nickel catalysts for trifluoromethylthiolation of aryl chlorides.494 In contrast to the Pd-catalyzed reaction stated above, the experiments suggested that the nickel catalysts proceed via the Ni(0)/Ni(II) pathway. DFT calculations showed that the ligand dppf (dppf = 1,1′-bis(diphenylphosphino)ferrocene) offering a wide bite-angle had a promisingly low barrier of 24.4 kcal/mol compared to other ligands that have a smaller bite-angle, and it was revealed that a weakly binding propensity of the auxiliary ligand (e.g., COD) plays a crucial role for enhancing the catalytic efficiency (Figure 51a).494 This insight gave rise to experiments where various aryl and heterocyclic chlorides gave moderate yields (40−96%). In addition, the understanding of the role of auxiliary ligand led to the use of MeCN additive instead of COD. As expected, the strategy derived from calculations showed better results, and based on the energetic span analysis, this enhancement originated from energetically raising the Ni(0) intermediate. A year later, another study was reported that aimed to find a suitable leaving group with a lower barrier than ArSCF3, and DFT calculations were conducted on phenol derivatives (Ph− OR) (Figure 51b).495 Based on this theoretical finding, the initial test with phenyl triflate gave the desired product in excellent conversion of 83%. Next, to expand this approach, calculations were performed on various functional groups, such as ketones, and most cases showed higher barriers than that for the PhOTf substrate. The scope for the functional groups indicated moderate yields from 70−96%. This method was applied to vinyl triflates and nonaflates, and the experimental results were again well-matched with computed results. Although the proposed catalyst (dppf)Ni(0)(COD) showed a reasonable reactivity for aryl chlorides, the trend for aryl halides was inconsistent with bond strength. To evaluate the inconsistency of the catalysis and in order to find an appropriate catalyst, Schoenebeck carried out computations and experiments, and it was found that the trend of the

center, rendering the metal center a harder Lewis acid. The experimental results were in good agreement with the computer-aided predictions. The qualitative FMO analysis in combination with the relativistic effect-corrected hardness of the metal centers explained precisely the reactivity differences observed between the two metal centers (Figure 50c).487 As expected, the Ir−N σ-bonding orbital was located at a lower energy than the corresponding orbital of the Rh−N σ-bond by 0.3 eV. In addition, the M−N π-bonding orbital showed a similar trend. A year after this discovery, a new amidation protocol of stoichiometric C−H amidation was reported by Chang.488 In this report, the generation of the Ir-imido complex using 1,4,2dioxazolone derivatives was facile and far superior to attempts utilizing acyl azides. DFT calculations guided the mechanistic study and discovered that prior to the formation of the Irimido species, ligand exchange of the precatalyst with 1,4,2dioxazolones was more favorable (10.8 kcal/mol) than that with acylazides (16.8 kcal/mol). In addition, the decarboxylation to afford the imido complex was calculated with an accessible barrier of 20.3 kcal/mol, and the loss of nitrogen was found to have a prohibitive barrier of 34.9 kcal/mol. This computational model provided a crucial mechanistic key and was used to provide a new tool for stoichiometric, late-stage, C(sp2)−H amidation. Building on this progress, Chang and Baik recently reported a major breakthrough in the synthesis of γ-lactams using this novel platform of C−H amidation mediated by iridium catalysts and dioxazolones.489 In this work, the authors reported good yield and selectivity for activated benzylic substrates. Attempts at amidation of unactivated alkyl substrates were riddled with failure due to a common and easy pathway leading to decomposition of the iridium complex into the isonitrile. While this Curtius-type rearrangement is a well-known limitation for metal-imido species, the authors used computational modeling to understand and overcome this intrinsic problem. The three potential pathways that were observed to consume the Ir-imido species were the following: (i) C(sp2)−H activation of the ligand and subsequent C−N coupling, (ii) Curtius-type decomposition of the catalyst complex to form the isonitrile, and (iii) C(sp3)−H activation followed by C−N coupling to form the γ-lactam, which is the target reaction. DFT calculations revealed that the two side reactions (i) and (ii) have activation barriers of 9.1 and 9.6 kcal/mol, respectively. The target reaction pathway (iii) was calculated to have a barrier of 12.0 kcal/mol. These energy barriers were consistent with what was observed in experiment and were not surprising. Interestingly, NBO charge analysis of the metal center showed that there is a significant change of partial charge at the Ir metal for the two side pathways (i) and (ii) whereas the charge changed from 0.40 before the reaction to 0.32 and 0.27, respectively. Fortunately, the charge at the iridium did not show such a significant change for the target pathway (iii) where the calculated charge changed very slightly, from 0.40 to 0.39. Taking advantage of these computational discoveries, the authors hypothesized that electron-rich ligands on iridium would result in significant changes on the partial charge of the iridium which will avoid the side reactions and force the reaction to proceed toward the target reaction. Based on this hypothesis, adopting electron-donating groups in the ligand quickly moved this reaction into a high yielding, highly selective transformation for benzylic, tertiary, secondary, and primary C(sp3) and C(sp2)−H bonds. Interestingly, intraAJ

DOI: 10.1021/acs.chemrev.9b00073 Chem. Rev. XXXX, XXX, XXX−XXX

Chemical Reviews

Review

Figure 52. (a) Reaction pathway for the OMBV transformation. (b) Plot of calculated M−CH3 BDFE against OMBV activation barriers.

The computed results showed that the activation barriers decreased from right to left in the same series and from bottom to top in the same groups. Moreover, there is a correlation between the activation barrier and other factors such as M− CH3 bond dissociation energy, Gibbs free energy of reaction, and nucleophilicity on the carbon of the methyl group in the ground and transition states. For example, weaker M−CH3 bonds gave lower activation barriers (Figure 52b).497 In this context, lowering the activation barrier of late transition metal complexes was a challenging issue. In the same year, Gunnoe, Cundari, and Groves carried out a combined experimental and computational study for the insertion of an oxygen atom into the Re−CH3 bond of MTO (MTO = methylrhenium trioxide).500 Methanol is formed via a BV transition state, and the disadvantage of late transition metal complexes was overcome by introducing an organo-cocatalyst, flavin, which increased the rate up to 600 times.

Figure 51. (a) Nickel catalysts containing bisphosphine ligands with different bite angles for trifluoromethylthiolation of aryl chlorides. (b) Phenol derivatives used for trifluoromethylthiolation.

catalysis depends on the generation of the β-fluoride elimination product, (dppf)Ni(0)(SCF2).496 However, in the case of the intermediate [(dppf)Ni(II)(SCF3)(Ph)], the computed results indicated that the formation of PhSCF3 was favorable compared to the β-fluoride elimination product. For this reason, the reactivities were related to the initial oxidative addition step. Despite the enhanced reactivities, [(dppf)Ni(I)−X] (X = Cl, Br, I) had suffered from the competition of β-fluoride elimination product. To overcome these disadvantages, the N-derived ligand, dmbpy (dmbpy = 4,4′-dimethoxybipyridine) was introduced. In contrast to the Ni(0)/Ni(II) pathway via the intermediate [(dmbpy)Ni(II)(SCF3)(Ph)], the Ni(I)/Ni(III) cycle proceeded through the (dmbpy)Ni(I)(SCF3) which showed a low barrier for the desired product process.496 In 2012, Cundari and Gunnoe reported on the C−O bond forming reaction via an organometallic Baeyer−Villiger (OMBV) reaction.497 Previously, C−O bonds were commonly formed via oxygen-atom insertion into an M−R bond and this process played a key step in Shilov-type catalysis.498 For instance, the electron-rich late transition metal complexes, such as the bipyridyl−Pt(II) complex, prohibit the transformation from M−R to M−O−R due to the high activation barriers.499 To establish the trend, DFT calculations were performed for the metallo-Criegee intermediate [(bpy)xM(Me)(OOH)]n including a series of Group 7−10 (x = 1 for four-coordinate with d8-square planar complexes; x = 2 for six-coordinate with d6-octahedral complexes; n is a total charge) (Figure 52a).497

4. CHALLENGES OF IN-SILICO CATALYST DESIGN In this review, we have presented several studies involving computationally driven experimental studies. Over the course of the last 20 years, computational molecular modeling has matured from being a specialist’s tool with very limited impact to an equal partner to many experimental methods of investigation. The success in constructing realistic models for often highly complicated mechanisms and catalytic cycles has accelerated, and the field has matured significantly. As many of the successful examples we mention in this review emphasize, computational tools can be used in a predictive sense and are now indispensable for the rational design and optimization of new generations of powerful catalysts. The following are some of the challenges that must be considered for every practitioner. (i) Choice of Computational Method: A dominating number of computational studies reported here use the immensely successful B3LYP density functional. Although it has been considered the standard in the last 25 years and it has proven to be extremely useful, it is far from being ideal.501 Nevertheless, the B3LYP still provides a good compromise AK

DOI: 10.1021/acs.chemrev.9b00073 Chem. Rev. XXXX, XXX, XXX−XXX

Chemical Reviews

Review

between accuracy in predictions and computational cost.502 Grimme showed that the B3LYP density functional can be systematically improved through geometrical counterpoise correction.503 Much effort has been spent to develop new functionals, and recently, several highly optimized density functionals have been developed and many have been conceived specifically with transition metals in mind.504−506 Nonetheless, transition metals continue to challenge quantum chemical methods. For example, the performance of the new generation density functionals developed by Head-Gordon507 should be assessed in future studies, as they show very promising behavior and impressively small errors for a variety of properties such as thermochemistry, vibrational frequencies, and barrier heights. (ii) Potential Energy Surface: For reliable barrier height predictions in the potential energy surface, the thermodynamic parameters should be computed accurately. As witnessed in N2 fixation studies, the N2 reduction is accompanied by a series of proton-coupled electron transfers. The computed thermodynamic corrections in vacuum will be much higher than those in solution phase. The loss of translational and rotational entropy due to solvation is included in the free energy of solvation G(solv), and not adding gas-phase entropy corrections when calculating the gas-phase free energy may lead to inconsistencies and noncanceling errors.53 Several organometallic catalysts are highly charged species that are typically associated with counterions. The resting state of the catalyst becomes active upon redox events through ion pair formation. These uncommon redox events should be incorporated in the computer models for the accurate prediction of redox potentials. Many organometallic catalysts such as Schrock’s catalyst in N2 activation have bulky and flexible ligands which are essential and should not be truncated. The orientations of these ligand centers should be modeled properly through careful conformational search, which is nontrivial.508−510 This is particularly important in theozyme based reaction modeling. (iii) Linking Experiments and Theory: With a powerful theoretical method and a reliable computer model, it is essential to gauge the in-silico predictions with the experimental data. Both experimental and computational researchers should appreciate and learn from the limitations of others. Indeed, several experimentalists are not shy about carrying out computations to interpret their results. Similarly, computational researchers should more actively consider difficulties encountered in experiments and learn empirical chemical concepts. These artifacts can be ironed out through successful, healthy, and long-term collaborative projects.

packages can be used more efficiently to solve difficult electronic structures of reactive intermediates often found in experiments. The GUI-interface enabled electronic structure packages are tempting to the experimental community such that routine DFT calculations can be used as a black-box even by a nonexpert, and finally (iii) the willingness of computational chemists to collaborate with the suitable experimental group and vice versa can tackle any “Holy Grail” problem.

AUTHOR INFORMATION Corresponding Authors

*Daniel H. Ess E-mail: [email protected]. *Mu-Hyun Baik E-mail: [email protected]. ORCID

Mannkyu Hong: 0000-0002-7770-1230 Daniel H. Ess: 0000-0001-5689-9762 Mu-Hyun Baik: 0000-0002-8832-8187 Author Contributions ∥

S.A. and M.H. contributed equally to this work.

Notes

The authors declare no competing financial interest. Biographies Seihwan Ahn received his B.S. degree in chemistry from Kyungpook National University (Daegu, Korea) in 2012. He obtained his Ph.D. from KAIST working on the development of new organometallic reactions using computational approaches (in 2019, with Prof. MuHyun Baik). He is currently a staff engineer at Samsung Display Corporation. Mannkyu Hong received his B.S. degree in chemical and biomolecular engineering from KAIST in 2015. After finishing his M.S. course in pharmaceutical chemistry at Seoul National University under the guidance of Prof. Jeewoo Lee, he is currently pursuing his Ph.D. under the tutelage of Prof. Mu-Hyun Baik at KAIST. His scientific interest lies in elucidating the mechanistic details of biocatalysis and theoretical/computational modeling of biochemical conversion. Mahesh Sundararajan obtained his Ph.D. from University of Manchester, UK (in 2005, with Prof. Ian Hillier). He completed his postdoctoral training at Manchester (until 2007) and worked with Prof. Frank Neese at University of Bonn (until 2010) through an Alexander von Humboldt fellowship. In 2010, he joined as scientific officer in Theoretical Chemistry Section at Bhabha Atomic Research Centre, India. Since 2017, he has been working with Prof. Mu-Hyun Baik as a senior postdoctoral fellow at Institute for Basic Science, IBS, Korea. His research interests are focused on applying electronic structure methods to understand the structure functional relationship of metalloproteins, host−guest chemistry, small molecular activation, and nuclear waste management processes.

5. CONCLUSIONS AND FUTURE OUTCOME Prior to this millennium, dominant computational studies of organic or organometallic reactions were stand-alone. Since then, the reputation of quantum chemical calculations has grown tremendously. In this review, we have shown the predictive power of modern electronic structure methods in the design of organic and organometallic catalysts. The future of computational prediction is brighter than ever due to the following reasons: (i) The ever-improving software and the cost of the hardware are becoming more easily accessible, enabling us to tackle challenging problems and extremely complex catalytic reactions, and (ii) the development of robust electronic structure programs in modern quantum chemical

Daniel H. Ess received a B.S. degree in biochemistry at Brigham Young University (BYU) in 2000. Following two years of volunteer service for the Church of Jesus Christ of Latter-day Saints, he completed his Ph.D. at University of California, Los Angeles (2003− 2007) in computational organic chemistry. From 2007−2009 he was appointed as a postdoc at both The Scripps Research Institute Florida and Caltech. Following another postdoc appointment at the University of North Carolina at Chapel Hill, he began his independent career at BYU as an assistant professor in the Department of Chemistry and Biochemistry. In 2016 he was promoted to associate professor. He currently works with petrochemical companies to computationally design catalysts. He is AL

DOI: 10.1021/acs.chemrev.9b00073 Chem. Rev. XXXX, XXX, XXX−XXX

Chemical Reviews

Review

(12) Denmark, S. E.; Henle, J. J. Redefining Q: Quaternary Ammonium Cross Sectional Area (XSA) as a General Descriptor for Transport-Limiting PTC Rate Approximations. Chem. Sci. 2015, 6, 2211−2218. (13) Ahneman, D. T.; Estrada, J. G.; Lin, S.; Dreher, S. D.; Doyle, A. G. Predicting Reaction Performance in C−N Cross-Coupling Using Machine Learning. Science 2018, 360, 186−190. (14) Liu, F.; Sanchez, D. M.; Kulik, H. J.; Martínez, T. J. Exploiting Graphical Processing Units to Enable Quantum Chemistry Calculation of Large Solvated Molecules with Conductor-like Polarizable Continuum Models. Int. J. Quantum Chem. 2019, 119, No. e25760. (15) Janet, J. P.; Chan, L.; Kulik, H. J. Accelerating Chemical Discovery with Machine Learning: Simulated Evolution of Spin Crossover Complexes with an Artificial Neural Network. J. Phys. Chem. Lett. 2018, 9, 1064−1071. (16) Nandy, A.; Duan, C.; Janet, J. P.; Gugler, S.; Kulik, H. J. Strategies and Software for Machine Learning Accelerated Discovery in Transition Metal Chemistry. Ind. Eng. Chem. Res. 2018, 57, 13973− 13986. (17) Markert, C.; Pfaltz, A. Screening of Chiral Catalysts and Catalyst Mixtures by Mass Spectrometric Monitoring of Catalytic Intermediates. Angew. Chem., Int. Ed. 2004, 43, 2498−2500. (18) Hopkinson, M. N.; Gómez-Suárez, A.; Teders, M.; Sahoo, B.; Glorius, F. Accelerated Discovery in Photocatalysis Using a Mechanism-Based Screening Method. Angew. Chem., Int. Ed. 2016, 55, 4361−4366. (19) Bess, E. N.; Guptill, D. M.; Davies, H. M. L.; Sigman, M. S. Using IR Vibrations to Quantitatively Describe and Predict SiteSelectivity in Multivariate Rh-Catalyzed C−H Functionalization. Chem. Sci. 2015, 6, 3057−3062. (20) Kim, Y.; Kim, J. W.; Kim, Z.; Kim, W. Y. Efficient Prediction of Reaction Paths through Molecular Graph and Reaction Network Analysis. Chem. Sci. 2018, 9, 825−835. (21) Mosquera, M. A.; Fu, B.; Kohlstedt, K. L.; Schatz, G. C.; Ratner, M. A. Wave Functions, Density Functionals, and Artificial Intelligence for Materials and Energy Research: Future Prospects and Challenges. ACS Energy Lett. 2018, 3, 155−162. (22) Paruzzo, F. M.; Hofstetter, A.; Musil, F.; De, S.; Ceriotti, M.; Emsley, L. Chemical Shifts in Molecular Solids by Machine Learning. Nat. Commun. 2018, 9, 4501. (23) List, B. Introduction: Organocatalysis. Chem. Rev. 2007, 107, 5413−5415. (24) de Villegas, M. D. D.; Gálvez, J. A.; Etayo, P.; Badorrey, R.; López-Ram-de-Víu, P. Recent Advances in Enantioselective Organocatalyzed Anhydride Desymmetrization and Its Application to the Synthesis of Valuable Enantiopure Compounds. Chem. Soc. Rev. 2011, 40, 5564−5587. (25) Seo, H.; Katcher, M. H.; Jamison, T. F. Photoredox Activation of Carbon Dioxide for Amino Acid Synthesis in Continuous Flow. Nat. Chem. 2017, 9, 453−456. (26) Guo, H.; Fan, Y. C.; Sun, Z.; Wu, Y.; Kwon, O. Phosphine Organocatalysis. Chem. Rev. 2018, 118, 10049−10293. (27) Ravelli, D.; Fagnoni, M.; Albini, A. Photoorganocatalysis. What For? Chem. Soc. Rev. 2013, 42, 97−113. (28) Knowles, R. R.; Jacobsen, E. N. Attractive Noncovalent Interactions in Asymmetric Catalysis: Links between Enzymes and Small Molecule Catalysts. Proc. Natl. Acad. Sci. U. S. A. 2010, 107, 20678−20685. (29) Wheeler, S. E.; Seguin, T. J.; Guan, Y.; Doney, A. C. Noncovalent Interactions in Organocatalysis and the Prospect of Computational Catalyst Design. Acc. Chem. Res. 2016, 49, 1061− 1069. (30) Walden, D. M.; Ogba, O. M.; Johnston, R. C.; Cheong, P. H.-Y. Computational Insights into the Central Role of Nonbonding Interactions in Modern Covalent Organocatalysis. Acc. Chem. Res. 2016, 49, 1279−1291. (31) Etter, M. C.; Panunto, T. W. 1,3-Bis(m-Nitrophenyl)urea: An Exceptionally Good Complexing Agent for Proton Acceptors. J. Am. Chem. Soc. 1988, 110, 5896−5897.

also the director of a National Science Foundation funded Research Experiences for Undergraduate (REU) site at BYU (reu.chem.byu.edu) as well as the creator and director of chemistry and biochemistry camps for children ages 9−14 (chemcamp.byu.edu). Mu-Hyun Baik received his Vordiplom (=Bachelor degree) from the Heinrich-Heine-Universität Düsseldorf (Germany) in 1994 and his Ph.D. from the University of North Carolina in Chapel Hill in 2000. After completing his postdoctoral training at Columbia University in New York, he was appointed an assistant professor of chemistry at Indiana University Bloomington in 2003. In 2008, he was promoted to associate professor of chemistry with tenure at Indiana University. In 2015, he moved to Korea to become an associate director of the Center for Catalytic Hydrocarbon Functionalizations within the Institute for Basic Science (IBS) and was appointed a professor of chemistry at the Korea Advanced Institute of Science and Technology (KAIST) in Daejeon, Korea.

ACKNOWLEDGMENTS We thank the Research Corporation (Scialog Award to M.H.B.) and the Institute for Basic Science (IBS-R010-A1) in Korea for financial support. D.H.E. thanks Chevron Phillips Chemical Company and the U.S. Department of Energy, Office of Science, Basic Energy Sciences, Catalysis Science Program, under Award DE-SC0018329. M.S. thanks B.A.R.C. for sanctioning Extraordinary Leave (EOL). REFERENCES (1) Ziegler, T. Approximate Density Functional Theory as a Practical Tool in Molecular Energetics and Dynamics. Chem. Rev. 1991, 91, 651−667. (2) Geerlings, P.; De Proft, F.; Langenaeker, W. Conceptual Density Functional Theory. Chem. Rev. 2003, 103, 1793−1873. (3) Cohen, A. J.; Mori-Sánchez, P.; Yang, W. Challenges for Density Functional Theory. Chem. Rev. 2012, 112, 289−320. (4) Streitwieser, A. Perspectives on Computational Organic Chemistry. J. Org. Chem. 2009, 74, 4433−4446. (5) Fernández-Alvarez, V. M.; Ho, S. K. Y.; Britovsek, G. J. P.; Maseras, F. A DFT-Based Mechanistic Proposal for the Light-Driven Insertion of Dioxygen into Pt(II)−C Bonds. Chem. Sci. 2018, 9, 5039−5046. (6) Cherkasov, A.; Muratov, E. N.; Fourches, D.; Varnek, A.; Baskin, I. I.; Cronin, M.; Dearden, J.; Gramatica, P.; Martin, Y. C.; Todeschini, R.; Consonni, V.; Kuz’min, V. E.; Cramer, R.; Benigni, R.; Yang, C.; Rathman, J.; Terfloth, L.; Gasteiger, J.; Richard, A.; Tropsha, A. QSAR Modeling: Where Have You Been? Where Are You Going To? J. Med. Chem. 2014, 57, 4977−5010. (7) Ianni, J. C.; Annamalai, V.; Phuan, P.-W.; Panda, M.; Kozlowski, M. C. A Priori Theoretical Prediction of Selectivity in Asymmetric Catalysis: Design of Chiral Catalysts by Using Quantum Molecular Interaction Fields. Angew. Chem., Int. Ed. 2006, 45, 5502−5505. (8) Kozlowski, M. C.; Dixon, S. L.; Panda, M.; Lauri, G. Quantum Mechanical Models Correlating Structure with Selectivity: Predicting the Enantioselectivity of β-Amino Alcohol Catalysts in Aldehyde Alkylation. J. Am. Chem. Soc. 2003, 125, 6614−6615. (9) Denmark, S. E.; Gould, N. D.; Wolf, L. M. A Systematic Investigation of Quaternary Ammonium Ions as Asymmetric PhaseTransfer Catalysts. Synthesis of Catalyst Libraries and Evaluation of Catalyst Activity. J. Org. Chem. 2011, 76, 4260−4336. (10) Denmark, S. E.; Gould, N. D.; Wolf, L. M. A Systematic Investigation of Quaternary Ammonium Ions as Asymmetric PhaseTransfer Catalysts. Application of Quantitative Structure Activity/ selectivity Relationships. J. Org. Chem. 2011, 76, 4337−4357. (11) Denmark, S. E.; Cullen, L. R. Development of a Phase-TransferCatalyzed, [2,3]-Wittig Rearrangement. J. Org. Chem. 2015, 80, 11818−11848. AM

DOI: 10.1021/acs.chemrev.9b00073 Chem. Rev. XXXX, XXX, XXX−XXX

Chemical Reviews

Review

through Assisted tert-Butyl C−H Hydrogen Bonding. J. Org. Chem. 2017, 82, 8662−8667. (55) Li, Y.; Yang, G.-H.; He, C. Q.; Li, X.; Houk, K. N.; Cheng, J.-P. Chirality Sensing of α-Hydroxyphosphonates by N-Tert-Butyl Sulfinyl Squaramide. Org. Lett. 2017, 19, 4191−4194. (56) Yang, G.-H.; Li, Y.; Li, X. Chirality Sensing of Molecules with Diverse Functional Groups by Using N-Tert-Butyl Sulfinyl Squaramide. Asian J. Org. Chem. 2018, 7, 770−775. (57) North, M.; Pasquale, R.; Young, C. Synthesis of Cyclic Carbonates from Epoxides and CO2. Green Chem. 2010, 12, 1514− 1539. (58) Martín, C.; Fiorani, G.; Kleij, A. W. Recent Advances in the Catalytic Preparation of Cyclic Organic Carbonates. ACS Catal. 2015, 5, 1353−1370. (59) Hong, M.; Kim, Y.; Kim, H.; Cho, H. J.; Baik, M.-H.; Kim, Y. Scorpionate Catalysts for Coupling CO2 and Epoxides to Cyclic Carbonates: A Rational Design Approach for Organocatalysts. J. Org. Chem. 2018, 83, 9370−9380. (60) Riduan, S. N.; Zhang, Y. Recent Developments in Carbon Dioxide Utilization under Mild Conditions. Dalton Trans 2010, 39, 3347−3357. (61) Sopeña, S.; Fiorani, G.; Martín, C.; Kleij, A. W. Highly Efficient Organocatalyzed Conversion of Oxiranes and CO2 into Organic Carbonates. ChemSusChem 2015, 8, 3248−3254. (62) Büttner, H.; Steinbauer, J.; Werner, T. Synthesis of Cyclic Carbonates from Epoxides and Carbon Dioxide by Using Bifunctional One-Component Phosphorus-Based Organocatalysts. ChemSusChem 2015, 8, 2655−2669. (63) Whiteoak, C. J.; Nova, A.; Maseras, F.; Kleij, A. W. Merging Sustainability with Organocatalysis in the Formation of Organic Carbonates by Using CO2 as a Feedstock. ChemSusChem 2012, 5, 2032−2038. (64) Kim, S. H.; Ahn, D.; Go, M. J.; Park, M. H.; Kim, M.; Lee, J.; Kim, Y. Dinuclear Aluminum Complexes as Catalysts for Cycloaddition of CO2 to Epoxides. Organometallics 2014, 33, 2770−2775. (65) Tshuva, E. Y.; Goldberg, I.; Kol, M.; Goldschmidt, Z. Zirconium Complexes of Amine−Bis(phenolate) Ligands as Catalysts for 1-Hexene Polymerization: Peripheral Structural Parameters Strongly Affect Reactivity. Organometallics 2001, 20, 3017−3028. (66) Cheong, P. H.-Y.; Zhang, H.; Thayumanavan, R.; Tanaka, F.; Houk, K. N.; Barbas, C. F., III. Pipecolic Acid-Catalyzed Direct Asymmetric Mannich Reactions. Org. Lett. 2006, 8, 811−814. (67) Zhang, H.; Mitsumori, S.; Utsumi, N.; Imai, M.; GarciaDelgado, N.; Mifsud, M.; Albertshofer, K.; Cheong, P. H.-Y.; Houk, K. N.; Tanaka, F.; Barbas, C. F., III Catalysis of 3-Pyrrolidinecarboxylic Acid and Related Pyrrolidine Derivatives in Enantioselective AntiMannich-Type Reactions: Importance of the 3-Acid Group on Pyrrolidine for Stereocontrol. J. Am. Chem. Soc. 2008, 130, 875−886. (68) Kanai, M.; Kato, N.; Ichikawa, E.; Shibasaki, M. Power of Cooperativity: Lewis Acid-Lewis Base Bifunctional Asymmetric Catalysis. Synlett 2005, 10, 1491−1508. (69) Paull, D. H.; Abraham, C. J.; Scerba, M. T.; Alden-Danforth, E.; Lectka, T. Bifunctional Asymmetric Catalysis: Cooperative Lewis Acid/base Systems. Acc. Chem. Res. 2008, 41, 655−663. (70) Akiyama, T. Stronger Brønsted Acids. Chem. Rev. 2007, 107, 5744−5758. (71) Parmar, D.; Sugiono, E.; Raja, S.; Rueping, M. Complete Field Guide to Asymmetric BINOL-Phosphate Derived Brønsted Acid and Metal Catalysis: History and Classification by Mode of Activation; Brønsted Acidity, Hydrogen Bonding, Ion Pairing, and Metal Phosphates. Chem. Rev. 2014, 114, 9047−9153. (72) Reid, J. P.; Simón, L.; Goodman, J. M. A Practical Guide for Predicting the Stereochemistry of Bifunctional Phosphoric Acid Catalyzed Reactions of Imines. Acc. Chem. Res. 2016, 49, 1029−1041. (73) Yang, W.; Sun, J. Organocatalytic Enantioselective Synthesis of 1,4-Dioxanes and Other Oxa-Heterocycles by Oxetane Desymmetrization. Angew. Chem. 2016, 128, 1900−1903. (74) Chen, Z.; Wang, Z.; Sun, J. Catalytic Enantioselective Synthesis of Tetrahydroisoquinolines and Their Analogues Bearing a C4

(32) Etter, M. C.; Urbanczyk-Lipkowska, Z.; Zia-Ebrahimi, M.; Panunto, T. W. Hydrogen Bond-Directed Cocrystallization and Molecular Recognition Properties of Diarylureas. J. Am. Chem. Soc. 1990, 112, 8415−8426. (33) Etter, M. C. Encoding and Decoding Hydrogen-Bond Patterns of Organic Compounds. Acc. Chem. Res. 1990, 23, 120−126. (34) Etter, M. C. Hydrogen Bonds as Design Elements in Organic Chemistry. J. Phys. Chem. 1991, 95, 4601−4610. (35) Schreiner, P. R. Metal-Free Organocatalysis through Explicit Hydrogen Bonding Interactions. Chem. Soc. Rev. 2003, 32, 289−296. (36) Takemoto, Y. Recognition and Activation by Ureas and Thioureas: Stereoselective Reactions Using Ureas and Thioureas as Hydrogen-Bonding Donors. Org. Biomol. Chem. 2005, 3, 4299−4306. (37) Connon, S. J. Organocatalysis Mediated by (Thio)urea Derivatives. Chem. - Eur. J. 2006, 12, 5418−5427. (38) Schreiner, P. R.; Wittkopp, A. H-Bonding Additives Act like Lewis Acid Catalysts. Org. Lett. 2002, 4, 217−220. (39) Wittkopp, A.; Schreiner, P. R. Metal-Free, Noncovalent Catalysis of Diels-Alder Reactions by Neutral Hydrogen Bond Donors in Organic Solvents and in Water. Chem. - Eur. J. 2003, 9, 407−414. (40) Maher, D. J.; Connon, S. J. Acceleration of the DABCOPromoted Baylis−Hillman Reaction Using a Recoverable H-Bonding Organocatalyst. Tetrahedron Lett. 2004, 45, 1301−1305. (41) Dessole, G.; Herrera, R. P.; Ricci, A. H-Bonding Organocatalysed Friedel-Crafts Alkylation of Aromatic and Heteroaromatic Systems with Nitroolefins. Synlett 2004, 2004, 2374−2378. (42) Kotke, M.; Schreiner, P. R. Acid-Free, Organocatalytic Acetalization. Tetrahedron 2006, 62, 434−439. (43) Fleming, E. M.; Quigley, C.; Rozas, I.; Connon, S. J. Computational Study-Led Organocatalyst Design: A Novel, Highly Active Urea-Based Catalyst for Addition Reactions to Epoxides. J. Org. Chem. 2008, 73, 948−956. (44) Hajra, S.; Roy, S. S.; Aziz, S. M.; Das, D. Catalyst-Free “OnWater” Regio- and Stereospecific Ring-Opening of Spiroaziridine Oxindole: Enantiopure Synthesis of Unsymmetrical 3,3′-Bisindoles. Org. Lett. 2017, 19, 4082−4085. (45) Malerich, J. P.; Hagihara, K.; Rawal, V. H. Chiral Squaramide Derivatives Are Excellent Hydrogen Bond Donor Catalysts. J. Am. Chem. Soc. 2008, 130, 14416−14417. (46) Sigman, M. S.; Jacobsen, E. N. Schiff Base Catalysts for the Asymmetric Strecker Reaction Identified and Optimized from Parallel Synthetic Libraries. J. Am. Chem. Soc. 1998, 120, 4901−4902. (47) Okino, T.; Hoashi, Y.; Takemoto, Y. Enantioselective Michael Reaction of Malonates to Nitroolefins Catalyzed by Bifunctional Organocatalysts. J. Am. Chem. Soc. 2003, 125, 12672−12673. (48) Li, Y.; He, C. Q.; Gao, F.-X.; Li, Z.; Xue, X.-S.; Li, X.; Houk, K. N.; Cheng, J.-P. Design and Applications of N-tert-Butyl Sulfinyl Squaramide Catalysts. Org. Lett. 2017, 19, 1926−1929. (49) Robak, M. T.; Trincado, M.; Ellman, J. A. Enantioselective AzaHenry Reaction with an N-Sulfinyl Urea Organocatalyst. J. Am. Chem. Soc. 2007, 129, 15110−15111. (50) Kimmel, K. L.; Robak, M. T.; Ellman, J. A. Enantioselective Addition of Thioacetic Acid to Nitroalkenes via N-Sulfinyl Urea Organocatalysis. J. Am. Chem. Soc. 2009, 131, 8754−8755. (51) Kimmel, K. L.; Weaver, J. D.; Ellman, J. A. Enantio- and Diastereoselective Addition of Cyclohexyl Meldrum’s Acid to β- and α,β-Disubstituted Nitroalkenesvia N-Sulfinyl Urea Catalysis. Chem. Sci. 2012, 3, 121−125. (52) Kimmel, K. L.; Weaver, J. D.; Lee, M.; Ellman, J. A. Catalytic Enantioselective Protonation of Nitronates Utilizing an Organocatalyst Chiral Only at Sulfur. J. Am. Chem. Soc. 2012, 134, 9058− 9061. (53) Ryu, H.; Park, J.; Kim, H. K.; Park, J. Y.; Kim, S.-T.; Baik, M.-H. Pitfalls in Computational Modeling of Chemical Reactions and How To Avoid Them. Organometallics 2018, 37, 3228−3239. (54) Li, Y.; Yang, G.-H.; Shen, Y.-Y.; Xue, X.-S.; Li, X.; Cheng, J.-P. N-tert-Butyl Sulfinyl Squaramide Receptors for Anion Recognition AN

DOI: 10.1021/acs.chemrev.9b00073 Chem. Rev. XXXX, XXX, XXX−XXX

Chemical Reviews

Review

Effect of Thermodynamic Cycle, Model Chemistry, and Explicit Solvent Molecules. J. Phys. Chem. B 2012, 116, 11999−12006. (94) Jacquet, O.; Das Neves Gomes, C.; Ephritikhine, M.; Cantat, T. Recycling of Carbon and Silicon Wastes: Room Temperature Formylation of N−H Bonds Using Carbon Dioxide and Polymethylhydrosiloxane. J. Am. Chem. Soc. 2012, 134, 2934−2937. (95) Riduan, S. N.; Zhang, Y.; Ying, J. Y. Conversion of Carbon Dioxide into Methanol with Silanes over N-Heterocyclic Carbene Catalysts. Angew. Chem., Int. Ed. 2009, 48, 3322−3325. (96) Jacquet, O.; Das Neves Gomes, C.; Ephritikhine, M.; Cantat, T. Complete Catalytic Deoxygenation of CO2 into Formamidine Derivatives. ChemCatChem 2013, 5, 117−120. (97) Jacquet, O.; Frogneux, X.; Gomes, C. D. N.; Cantat, T. CO2 as a C1-Building Block for the Catalytic Methylation of Amines. Chem. Sci. 2013, 4, 2127−2131. (98) Blondiaux, E.; Pouessel, J.; Cantat, T. Carbon Dioxide Reduction to Methylamines under Metal-Free Conditions. Angew. Chem., Int. Ed. 2014, 53, 12186−12190. (99) Huang, F.; Lu, G.; Zhao, L.; Li, H.; Wang, Z.-X. The Catalytic Role of N-Heterocyclic Carbene in a Metal-Free Conversion of Carbon Dioxide into Methanol: A Computational Mechanism Study. J. Am. Chem. Soc. 2010, 132, 12388−12396. (100) Wang, B.; Cao, Z. Sequential Covalent Bonding Activation and General Base Catalysis: Insight into N-Heterocyclic Carbene Catalyzed Formylation of N−H Bonds Using Carbon Dioxide and Silane. RSC Adv. 2013, 3, 14007−14015. (101) Riduan, S. N.; Ying, J. Y.; Zhang, Y. Mechanistic Insights into the Reduction of Carbon Dioxide with Silanes over N-Heterocyclic Carbene Catalysts. ChemCatChem 2013, 5, 1490−1496. (102) Das Neves Gomes, C.; Jacquet, O.; Villiers, C.; Thuéry, P.; Ephritikhine, M.; Cantat, T. A Diagonal Approach to Chemical Recycling of Carbon Dioxide: Organocatalytic Transformation for the Reductive Functionalization of CO2. Angew. Chem., Int. Ed. 2012, 51, 187−190. (103) Zhou, Q.; Li, Y. The Real Role of N-Heterocyclic Carbene in Reductive Functionalization of CO2: An Alternative Understanding from Density Functional Theory Study. J. Am. Chem. Soc. 2015, 137, 10182−10189. (104) Wen, M.; Huang, F.; Lu, G.; Wang, Z.-X. Density Functional Theory Mechanistic Study of the Reduction of CO2 to CH4 Catalyzed by an Ammonium Hydridoborate Ion Pair: CO2 Activation via Formation of a Formic Acid Entity. Inorg. Chem. 2013, 52, 12098− 12107. (105) Hulla, M.; Bobbink, F. D.; Das, S.; Dyson, P. J. Carbon Dioxide Based N-Formylation of Amines Catalyzed by Fluoride and Hydroxide Anions. ChemCatChem 2016, 8, 3338−3342. (106) Ding, C.-H.; Hou, X.-L. Catalytic Asymmetric Propargylation. Chem. Rev. 2011, 111, 1914−1937. (107) Denmark, S. E.; Beutner, G. L. Lewis Base Catalysis in Organic Synthesis. Angew. Chem., Int. Ed. 2008, 47, 1560−1638. (108) Lu, T.; Porterfield, M. A.; Wheeler, S. E. Explaining the Disparate Stereoselectivities of N-Oxide Catalyzed Allylations and Propargylations of Aldehydes. Org. Lett. 2012, 14, 5310−5313. (109) Chen, J.; Captain, B.; Takenaka, N. Helical Chiral 2,2’Bipyridine N-Monoxides as Catalysts in the Enantioselective Propargylation of Aldehydes with Allenyltrichlorosilane. Org. Lett. 2011, 13, 1654−1657. (110) Lu, T.; Zhu, R.; An, Y.; Wheeler, S. E. Origin of Enantioselectivity in the Propargylation of Aromatic Aldehydes Catalyzed by Helical N-Oxides. J. Am. Chem. Soc. 2012, 134, 3095− 3102. (111) Rooks, B. J.; Haas, M. R.; Sepúlveda, D.; Lu, T.; Wheeler, S. E. Prospects for the Computational Design of Bipyridine N,N′-Dioxide Catalysts for Asymmetric Propargylation Reactions. ACS Catal. 2015, 5, 272−280. (112) Doney, A. C.; Rooks, B. J.; Lu, T.; Wheeler, S. E. Design of Organocatalysts for Asymmetric Propargylations through Computational Screening. ACS Catal. 2016, 6, 7948−7955.

Stereocenter: Formal Synthesis of (+)-(8S, 13R)-Cyclocelabenzine. Chem. - Eur. J. 2013, 19, 8426−8430. (75) Wang, Z.; Chen, Z.; Sun, J. Catalytic Enantioselective Intermolecular Desymmetrization of 3-Substituted Oxetanes. Angew. Chem. 2013, 125, 6817−6820. (76) Champagne, P. A.; Houk, K. N. Origins of Selectivity and General Model for Chiral Phosphoric Acid-Catalyzed Oxetane Desymmetrizations. J. Am. Chem. Soc. 2016, 138, 12356−12359. (77) Chen, Z.; Wang, B.; Wang, Z.; Zhu, G.; Sun, J. Complex Bioactive Alkaloid-Type Polycycles through Efficient Catalytic Asymmetric Multicomponent Aza-Diels-Alder Reaction of Indoles with Oxetane as Directing Group. Angew. Chem., Int. Ed. 2013, 52, 2027−2031. (78) Tay, J.-H.; Argüelles, A. J.; DeMars, M. D.; Zimmerman, P. M.; Sherman, D. H.; Nagorny, P. Regiodivergent Glycosylations of 6Deoxy-Erythronolide B and Oleandomycin-Derived Macrolactones Enabled by Chiral Acid Catalysis. J. Am. Chem. Soc. 2017, 139, 8570− 8578. (79) Khomutnyk, Y. Y.; Argüelles, A. J.; Winschel, G. A.; Sun, Z.; Zimmerman, P. M.; Nagorny, P. Studies of the Mechanism and Origins of Enantioselectivity for the Chiral Phosphoric AcidCatalyzed Stereoselective Spiroketalization Reactions. J. Am. Chem. Soc. 2016, 138, 444−456. (80) Zimmerman, P. M. Automated Discovery of Chemically Reasonable Elementary Reaction Steps. J. Comput. Chem. 2013, 34, 1385−1392. (81) Zimmerman, P. Reliable Transition State Searches Integrated with the Growing String Method. J. Chem. Theory Comput. 2013, 9, 3043−3050. (82) Zimmerman, P. M. Single-Ended Transition State Finding with the Growing String Method. J. Comput. Chem. 2015, 36, 601−611. (83) Madarász, Á .; Dósa, Z.; Varga, S.; Soós, T.; Csámpai, A.; Pápai, I. Thiourea Derivatives as Brønsted Acid Organocatalysts. ACS Catal. 2016, 6, 4379−4387. (84) Mayer, S. E. Estimation of Activation Energies for Nitrous Oxide, Carbon Dioxide, Nitrogen Dioxide, Nitric Oxide, Oxygen, and Nitrogen Reactions by a Bond-Energy Method. J. Phys. Chem. 1969, 73, 3941−3946. (85) Bates, E. D.; Mayton, R. D.; Ntai, I.; Davis, J. H., Jr. CO2 Capture by a Task-Specific Ionic Liquid. J. Am. Chem. Soc. 2002, 124, 926−927. (86) Cadena, C.; Anthony, J. L.; Shah, J. K.; Morrow, T. I.; Brennecke, J. F.; Maginn, E. J. Why Is CO2 so Soluble in Imidazolium-Based Ionic Liquids? J. Am. Chem. Soc. 2004, 126, 5300−5308. (87) Gurkan, B. E.; de la Fuente, J. C.; Mindrup, E. M.; Ficke, L. E.; Goodrich, B. F.; Price, E. A.; Schneider, W. F.; Brennecke, J. F. Equimolar CO2 Absorption by Anion-Functionalized Ionic Liquids. J. Am. Chem. Soc. 2010, 132, 2116−2117. (88) Zhao, Y.; Yu, B.; Yang, Z.; Zhang, H.; Hao, L.; Gao, X.; Liu, Z. A Protic Ionic Liquid Catalyzes CO2 Conversion at Atmospheric Pressure and Room Temperature: Synthesis of Quinazoline-2,4(1H,3H)-Diones. Angew. Chem., Int. Ed. 2014, 53, 5922−5925. (89) Zhao, Y.; Yang, Z.; Yu, B.; Zhang, H.; Xu, H.; Hao, L.; Han, B.; Liu, Z. Task-Specific Ionic Liquid and CO2-Cocatalysed Efficient Hydration of Propargylic Alcohols to α-Hydroxy Ketones. Chem. Sci. 2015, 6, 2297−2301. (90) Stierle, A. A.; Stierle, D. B.; Patacini, B. The Berkeleyamides, Amides from the Acid Lake Fungus Penicillum rubrum. J. Nat. Prod. 2008, 71, 856−860. (91) Jerris, P. J.; Smith, A. B., III Synthesis and Configurational Assignment of Geiparvarin: A Novel Antitumor Agent. J. Org. Chem. 1981, 46, 577−585. (92) Chen, K.; Shi, G.; Zhang, W.; Li, H.; Wang, C. ComputerAssisted Design of Ionic Liquids for Efficient Synthesis of 3(2H)Furanones: A Domino Reaction Triggered by CO2. J. Am. Chem. Soc. 2016, 138, 14198−14201. (93) Sutton, C. C. R.; Franks, G. V.; da Silva, G. First Principles pKa Calculations on Carboxylic Acids Using the SMD Solvation Model: AO

DOI: 10.1021/acs.chemrev.9b00073 Chem. Rev. XXXX, XXX, XXX−XXX

Chemical Reviews

Review

(133) Foster, S. L.; Bakovic, S. I. P.; Duda, R. D.; Maheshwari, S.; Milton, R. D.; Minteer, S. D.; Janik, M. J.; Renner, J. N.; Greenlee, L. F. Catalysts for Nitrogen Reduction to Ammonia. Nat. Catal. 2018, 1, 490−500. (134) Rutherford, A. W.; Faller, P. Photosystem II: Evolutionary Perspectives. Philos. Trans. R. Soc. London B: Biol. Sci. 2003, 358, 245−253. (135) Chatt, J.; Dilworth, J. R.; Richards, R. L. Recent Advances in the Chemistry of Nitrogen Fixation. Chem. Rev. 1978, 78, 589−625. (136) Lubitz, W.; Ogata, H.; Rüdiger, O.; Reijerse, E. Hydrogenases. Chem. Rev. 2014, 114, 4081−4148. (137) Ruscic, B. Active Thermochemical Tables: Sequential Bond Dissociation Enthalpies of Methane, Ethane, and Methanol and the Related Thermochemistry. J. Phys. Chem. A 2015, 119, 7810−7837. (138) Blanksby, S. J.; Ellison, G. B. Bond Dissociation Energies of Organic Molecules. Acc. Chem. Res. 2003, 36, 255−263. (139) Francke, R.; Schille, B.; Roemelt, M. Homogeneously Catalyzed Electroreduction of Carbon DioxideMethods, Mechanisms, and Catalysts. Chem. Rev. 2018, 118, 4631−4701. (140) Meyer, F.; Tolman, W. B. Forums on Small-Molecule Activation: From Biological Principles to Energy Applications. Inorg. Chem. 2015, 54, 5039. (141) Kelley, P.; Day, M. W.; Agapie, T. Hydrogen Evolution Catalyzed by Aluminum-Bridged Cobalt Diglyoximate Complexes. Eur. J. Inorg. Chem. 2013, 2013, 3840−3845. (142) Milani, B.; Licini, G.; Clot, E.; Albrecht, M. Small Molecule Activation. Dalton Trans 2016, 45, 14419−14420. (143) Flöser, B. M.; Tuczek, F. Synthetic Nitrogen Fixation with Mononuclear Molybdenum Complexes: Electronic-Structural and Mechanistic Insights from DFT. Coord. Chem. Rev. 2017, 345, 263− 280. (144) Wickramasinghe, L. A.; Ogawa, T.; Schrock, R. R.; Müller, P. Reduction of Dinitrogen to Ammonia Catalyzed by Molybdenum Diamido Complexes. J. Am. Chem. Soc. 2017, 139, 9132−9135. (145) Tanaka, H.; Nishibayashi, Y.; Yoshizawa, K. Interplay between Theory and Experiment for Ammonia Synthesis Catalyzed by Transition Metal Complexes. Acc. Chem. Res. 2016, 49, 987−995. (146) MacKay, B. A.; Fryzuk, M. D. Dinitrogen Coordination Chemistry: On the Biomimetic Borderlands. Chem. Rev. 2004, 104, 385−401. (147) Geri, J. B.; Shanahan, J. P.; Szymczak, N. K. Testing the Push−Pull Hypothesis: Lewis Acid Augmented N2 Activation at Iron. J. Am. Chem. Soc. 2017, 139, 5952−5956. (148) McWilliams, S. F.; Bill, E.; Lukat-Rodgers, G.; Rodgers, K. R.; Mercado, B. Q.; Holland, P. L. Effects of N2 Binding Mode on IronBased Functionalization of Dinitrogen to Form an Iron(III) Hydrazido Complex. J. Am. Chem. Soc. 2018, 140, 8586−8598. (149) Tang, C.; Liang, Q.; Jupp, A. R.; Johnstone, T. C.; Neu, R. C.; Song, D.; Grimme, S.; Stephan, D. W. 1,1-Hydroboration and a Borane Adduct of Diphenyldiazomethane: A Potential Prelude to FLP-N2 Chemistry. Angew. Chem. 2017, 129, 16815−16819. (150) Laplaza, C. E.; Johnson, M. J. A.; Peters, J. C.; Odom, A. L.; Kim, E.; Cummins, C. C.; George, G. N.; Pickering, I. J. Dinitrogen Cleavage by Three-Coordinate Molybdenum(III) Complexes: Mechanistic and Structural Data1. J. Am. Chem. Soc. 1996, 118, 8623−8638. (151) Laplaza, C. E.; Cummins, C. C. Dinitrogen Cleavage by a Three-Coordinate Molybdenum(III) Complex. Science 1995, 268, 861−863. (152) Yandulov, D. V.; Schrock, R. R. Catalytic Reduction of Dinitrogen to Ammonia at a Single Molybdenum Center. Science 2003, 301, 76−78. (153) Anderson, J. S.; Rittle, J.; Peters, J. C. Catalytic Conversion of Nitrogen to Ammonia by an Iron Model Complex. Nature 2013, 501, 84−87. (154) Arashiba, K.; Miyake, Y.; Nishibayashi, Y. A Molybdenum Complex Bearing PNP-Type Pincer Ligands Leads to the Catalytic Reduction of Dinitrogen into Ammonia. Nat. Chem. 2011, 3, 120− 125.

(113) Guan, Y.; Ingman, V. M.; Rooks, B. J.; Wheeler, S. E. AARON: An Automated Reaction Optimizer for New Catalysts. J. Chem. Theory Comput. 2018, 14, 5249−5261. (114) Rosales, A. R.; Wahlers, J.; Limé, E.; Meadows, R. E.; Leslie, K. W.; Savin, R.; Bell, F.; Hansen, E.; Helquist, P.; Munday, R. H.; Wiest, O.; Norrby, P.-O. Rapid Virtual Screening of Enantioselective Catalysts Using CatVS. Nat. Catal. 2019, 2, 41−45. (115) McMurry, J.; Begley, T. P.; Begley, T. The Organic Chemistry of Biological Pathways; Roberts and Company Publishers, 2005. (116) Aroyan, C. E.; Miller, S. J. Enantioselective Rauhut-Currier Reactions Promoted by Protected Cysteine. J. Am. Chem. Soc. 2007, 129, 256−257. (117) Osuna, S.; Dermenci, A.; Miller, S. J.; Houk, K. N. The Roles of Counterion and Water in a Stereoselective Cysteine-Catalyzed Rauhut-Currier Reaction: A Challenge for Computational Chemistry. Chem. - Eur. J. 2013, 19, 14245−14253. (118) Tantillo, D. J.; Houk, K. N. Theozymes and Catalyst Design. In Stimulating Concepts in Chemistry; Vögtle, F., Stoddart, J. F., Shibasaki, M., Eds.; Wiley-VCH Verlag GmbH & Co. KGaA: Weinheim, FRG, 2000; pp 79−88. (119) Tantillo, D. J.; Chen, J.; Houk, K. N. Theozymes and Compuzymes: Theoretical Models for Biological Catalysis. Curr. Opin. Chem. Biol. 1998, 2, 743−750. (120) Mak, W. S.; Siegel, J. B. Computational Enzyme Design: Transitioning from Catalytic Proteins to Enzymes. Curr. Opin. Struct. Biol. 2014, 27, 87−94. (121) Shaik, S.; Kumar, D.; de Visser, S. P.; Altun, A.; Thiel, W. Theoretical Perspective on the Structure and Mechanism of Cytochrome P450 Enzymes. Chem. Rev. 2005, 105, 2279−2328. (122) Siegbahn, P. E. M.; Blomberg, M. R. A. Quantum Chemical Studies of Proton-Coupled Electron Transfer in Metalloenzymes. Chem. Rev. 2010, 110, 7040−7061. (123) Lonsdale, R.; Houghton, K. T.; Ż urek, J.; Bathelt, C. M.; Foloppe, N.; de Groot, M. J.; Harvey, J. N.; Mulholland, A. J. Quantum Mechanics/molecular Mechanics Modeling of Regioselectivity of Drug Metabolism in Cytochrome P450 2C9. J. Am. Chem. Soc. 2013, 135, 8001−8015. (124) Ryde, U.; Söderhjelm, P. Ligand-Binding Affinity Estimates Supported by Quantum-Mechanical Methods. Chem. Rev. 2016, 116, 5520−5566. (125) Fianchini, M. Synthesis Meets Theory: Past, Present and Future of Rational Chemistry. Phys. Sci. Rev. 2017, 2, 20170134. (126) Nanda, V.; Koder, R. L. Designing Artificial Enzymes by Intuition and Computation. Nat. Chem. 2010, 2, 15−24. (127) Kheirabadi, M.; Ç elebi-Ö lçüm, N.; Parker, M. F. L.; Zhao, Q.; Kiss, G.; Houk, K. N.; Schafmeister, C. E. Spiroligozymes for Transesterifications: Design and Relationship of Structure to Activity. J. Am. Chem. Soc. 2012, 134, 18345−18353. (128) Zhao, Q.; Lam, Y.-H.; Kheirabadi, M.; Xu, C.; Houk, K. N.; Schafmeister, C. E. Hydrophobic Substituent Effects on Proline Catalysis of Aldol Reactions in Water. J. Org. Chem. 2012, 77, 4784− 4792. (129) Freund, G. S.; O’Brien, T. E.; Vinson, L.; Carlin, D. A.; Yao, A.; Mak, W. S.; Tagkopoulos, I.; Facciotti, M. T.; Tantillo, D. J.; Siegel, J. B. Elucidating Substrate Promiscuity within the FabI Enzyme Family. ACS Chem. Biol. 2017, 12, 2465−2473. (130) Röthlisberger, D.; Khersonsky, O.; Wollacott, A. M.; Jiang, L.; DeChancie, J.; Betker, J.; Gallaher, J. L.; Althoff, E. A.; Zanghellini, A.; Dym, O.; Albeck, S.; Houk, K. N.; Tawfik, D. S.; Baker, D. Kemp Elimination Catalysts by Computational Enzyme Design. Nature 2008, 453, 190−195. (131) Zanghellini, A.; Jiang, L.; Wollacott, A. M.; Cheng, G.; Meiler, J.; Althoff, E. A.; Röthlisberger, D.; Baker, D. New Algorithms and an in Silico Benchmark for Computational Enzyme Design. Protein Sci. 2006, 15, 2785−2794. (132) Jadhav, S. G.; Vaidya, P. D.; Bhanage, B. M.; Joshi, J. B. Catalytic Carbon Dioxide Hydrogenation to Methanol: A Review of Recent Studies. Chem. Eng. Res. Des. 2014, 92, 2557−2567. AP

DOI: 10.1021/acs.chemrev.9b00073 Chem. Rev. XXXX, XXX, XXX−XXX

Chemical Reviews

Review

(155) Ishida, Y.; Kawaguchi, H. Reactivity of Group 5 Element Dinitrogen Complexes and N2-Derived Nitrides. In Nitrogen Fixation; Nishibayashi, Y., Ed.; Springer International Publishing: Cham, 2017; pp 45−69. (156) Suzuki, T.; Fujimoto, K.; Takemoto, Y.; Wasada-Tsutsui, Y.; Ozawa, T.; Inomata, T.; Fryzuk, M. D.; Masuda, H. Efficient Catalytic Conversion of Dinitrogen to N(SiMe3)3 Using a Homogeneous Mononuclear Cobalt Complex. ACS Catal. 2018, 8, 3011−3015. (157) Fajardo, J., Jr; Peters, J. C. Catalytic Nitrogen-to-Ammonia Conversion by Osmium and Ruthenium Complexes. J. Am. Chem. Soc. 2017, 139, 16105−16108. (158) Lindley, B. M.; van Alten, R. S.; Finger, M.; Schendzielorz, F.; Würtele, C.; Miller, A. J. M.; Siewert, I.; Schneider, S. Mechanism of Chemical and Electrochemical N2 Splitting by a Rhenium Pincer Complex. J. Am. Chem. Soc. 2018, 140, 7922−7935. (159) Sharma, A.; Roemelt, M.; Reithofer, M.; Schrock, R. R.; Hoffman, B. M.; Neese, F. EPR/ENDOR and Theoretical Study of the Jahn−Teller-Active [HIPTN3N]MoVL Complexes (L = N−, NH). Inorg. Chem. 2017, 56, 6906−6919. (160) Neese, F. The Yandulov/Schrock Cycle and the Nitrogenase Reaction: Pathways of Nitrogen Fixation Studied by Density Functional Theory. Angew. Chem., Int. Ed. 2006, 45, 196−199. (161) Schrock, R. R. Catalytic Reduction of Dinitrogen to Ammonia by Molybdenum: Theory versus Experiment. Angew. Chem., Int. Ed. 2008, 47, 5512−5522. (162) Cao, Z.; Zhou, Z.; Wan, H.; Zhang, Q. Enzymatic and Catalytic Reduction of Dinitrogen to Ammonia: Density Functional Theory Characterization of Alternative Molybdenum Active Sites. Int. J. Quantum Chem. 2005, 103, 344−353. (163) Magistrato, A.; Robertazzi, A.; Carloni, P. Nitrogen Fixation by a Molybdenum Catalyst Mimicking the Function of the Nitrogenase Enzyme: A Critical Evaluation of DFT and Solvent Effects. J. Chem. Theory Comput. 2007, 3, 1708−1720. (164) Simm, G. N.; Reiher, M. Systematic Error Estimation for Chemical Reaction Energies. J. Chem. Theory Comput. 2016, 12, 2762−2773. (165) Thimm, W.; Gradert, C.; Broda, H.; Wennmohs, F.; Neese, F.; Tuczek, F. Free Reaction Enthalpy Profile of the Schrock Cycle Derived from Density Functional Theory Calculations on the Full [MoHIPTN3N] Catalyst. Inorg. Chem. 2015, 54, 9248−9255. (166) Mason, H. S.; Fowlks, W. L.; Peterson, E. Oxygen Transfer and Electron Transport by The Phenolase Complex1. J. Am. Chem. Soc. 1955, 77, 2914−2915. (167) Hayaishi, O.; Katagiri, M.; Rothberg, S. Mechanisms of The Pyrocatechase Reaction. J. Am. Chem. Soc. 1955, 77, 5450−5451. (168) Collman, J. P.; Fu, L. Synthetic Models for Hemoglobin and Myoglobin. Acc. Chem. Res. 1999, 32, 455−463. (169) Mingos, D. M. P. Geometries of Dioxygen (O2), Superoxo (O2−) and Peroxo (O22−) Complexes. Nature, Phys. Sci. 1971, 230, 154−156. (170) Cramer, C. J.; Tolman, W. B. Mononuclear Cu−O2 Complexes: Geometries, Spectroscopic Properties, Electronic Structures, and Reactivity. Acc. Chem. Res. 2007, 40, 601−608. (171) Elwell, C. E.; Gagnon, N. L.; Neisen, B. D.; Dhar, D.; Spaeth, A. D.; Yee, G. M.; Tolman, W. B. Copper-Oxygen Complexes Revisited: Structures, Spectroscopy, and Reactivity. Chem. Rev. 2017, 117, 2059−2107. (172) Adam, S. M.; Garcia-Bosch, I.; Schaefer, A. W.; Sharma, S. K.; Siegler, M. A.; Solomon, E. I.; Karlin, K. D. Critical Aspects of Heme−Peroxo−Cu Complex Structure and Nature of Proton Source Dictate Metal−Operoxo Breakage versus Reductive O−O Cleavage Chemistry. J. Am. Chem. Soc. 2017, 139, 472−481. (173) Citek, C.; Herres-Pawlis, S.; Stack, T. D. P. Low Temperature Syntheses and Reactivity of Cu2O2 Active-Site Models. Acc. Chem. Res. 2015, 48, 2424−2433. (174) Gagnon, N.; Tolman, W. B. [CuO]+ and [CuOH]2+ Complexes: Intermediates in Oxidation Catalysis? Acc. Chem. Res. 2015, 48, 2126−2131.

(175) Zhang, X.; Furutachi, H.; Fujinami, S.; Nagatomo, S.; Maeda, Y.; Watanabe, Y.; Kitagawa, T.; Suzuki, M. Structural and Spectroscopic Characterization of (μ-Hydroxo or μ-Oxo)(μ-peroxo)diiron(III) Complexes: Models for Peroxo Intermediates of NonHeme Diiron Proteins. J. Am. Chem. Soc. 2005, 127, 826−827. (176) Duan, P.-C.; Manz, D.-H.; Dechert, S.; Demeshko, S.; Meyer, F. Reductive O2 Binding at a Dihydride Complex Leading to Redox Interconvertible μ-1,2-Peroxo and μ-1,2-Superoxo Dinickel (II) Intermediates. J. Am. Chem. Soc. 2018, 140, 4929−4939. (177) Das, T. K.; Couture, M.; Ouellet, Y.; Guertin, M.; Rousseau, D. L. Simultaneous Observation of the OO and FeO2 Stretching Modes in Oxyhemoglobins. Proc. Natl. Acad. Sci. U. S. A. 2001, 98, 479−484. (178) Holland, P. L.; Cramer, C. J.; Wilkinson, E. C.; Mahapatra, S.; Rodgers, K. R.; Itoh, S.; Taki, M.; Fukuzumi, S.; Que, L., Jr.; Tolman, W. B. Resonance Raman Spectroscopy as a Probe of the Bis(μOxo)dicopper Core. J. Am. Chem. Soc. 2000, 122, 792−802. (179) Cho, J.; Kang, H. Y.; Liu, L. V.; Sarangi, R.; Solomon, E. I.; Nam, W. Mononuclear Nickel(II)-Superoxo and Nickel(III)-Peroxo Complexes Bearing a Common Macrocyclic TMC Ligand. Chem. Sci. 2013, 4, 1502−1508. (180) Chen, Y.; Sakaki, S. Theoretical Study of Mononuclear Nickel(I), Nickel(0), Copper(I), and Cobalt(I) Dioxygen Complexes: New Insight into Differences and Similarities in Geometry and Bonding Nature. Inorg. Chem. 2013, 52, 13146−13159. (181) Fan, R.; Serrano-Plana, J.; Oloo, W. N.; Draksharapu, A.; Delgado-Pinar, E.; Company, A.; Martin-Diaconescu, V.; Borrell, M.; Lloret-Fillol, J.; García-España, E.; Guo, Y.; Bominaar, E. L.; Que, L., Jr.; Costas, M.; Münck, E. Spectroscopic and DFT Characterization of a Highly Reactive Nonheme FeV−Oxo Intermediate. J. Am. Chem. Soc. 2018, 140, 3916−3928. (182) Kupper, C.; Mondal, B.; Serrano-Plana, J.; Klawitter, I.; Neese, F.; Costas, M.; Ye, S.; Meyer, F. Nonclassical Single-State Reactivity of an Oxo-Iron(IV) Complex Confined to Triplet Pathways. J. Am. Chem. Soc. 2017, 139, 8939−8949. (183) Shaik, S.; Hirao, H.; Kumar, D. Reactivity of High-Valent Iron−Oxo Species in Enzymes and Synthetic Reagents: A Tale of Many States. Acc. Chem. Res. 2007, 40, 532−542. (184) Holland, P. L. Metal−dioxygen and Metal−dinitrogen Complexes: Where Are the Electrons? Dalton Trans 2010, 39, 5415−5425. (185) Que, L., Jr.; Watanabe, Y. Oxygenase Pathways: Oxo, Peroxo, and Superoxo. Science 2001, 292, 651−653. (186) Cho, J.; Jeon, S.; Wilson, S. A.; Liu, L. V.; Kang, E. A.; Braymer, J. J.; Lim, M. H.; Hedman, B.; Hodgson, K. O.; Valentine, J. S.; Solomon, E. I.; Nam, W. Structure and Reactivity of a Mononuclear Non-Haem Iron(III)-Peroxo Complex. Nature 2011, 478, 502−505. (187) Nam, W. Synthetic Mononuclear Nonheme Iron−Oxygen Intermediates. Acc. Chem. Res. 2015, 48, 2415−2423. (188) Lewis, E. A.; Tolman, W. B. Reactivity of Dioxygen-Copper Systems. Chem. Rev. 2004, 104, 1047−1076. (189) Tyeklar, Z.; Karlin, K. D. Copper-Dioxygen Chemistry: A Bioinorganic Challenge. Acc. Chem. Res. 1989, 22, 241−248. (190) Tang, L. L.; Gunderson, W. A.; Weitz, A. C.; Hendrich, M. P.; Ryabov, A. D.; Collins, T. J. Activation of Dioxygen by a TAML Activator in Reverse Micelles: Characterization of an FeIIIFeIV Dimer and Associated Catalytic Chemistry. J. Am. Chem. Soc. 2015, 137, 9704−9715. (191) Collins, T. J.; Ryabov, A. D. Targeting of High-Valent IronTAML Activators at Hydrocarbons and Beyond. Chem. Rev. 2017, 117, 9140−9162. (192) Cho, J.; Woo, J.; Nam, W. An “End-on” Chromium(III)Superoxo Complex: Crystallographic and Spectroscopic Characterization and Reactivity in C−H Bond Activation of Hydrocarbons. J. Am. Chem. Soc. 2010, 132, 5958−5959. (193) Guzei, I. A.; Bakac, A. Macrocyclic Hydroperoxocobalt(III) Complex: Photochemistry, Spectroscopy, and Crystal Structure. Inorg. Chem. 2001, 40, 2390−2393. AQ

DOI: 10.1021/acs.chemrev.9b00073 Chem. Rev. XXXX, XXX, XXX−XXX

Chemical Reviews

Review

(194) Rohde, J.-U.; In, J.-H.; Lim, M. H.; Brennessel, W. W.; Bukowski, M. R.; Stubna, A.; Münck, E.; Nam, W.; Que, L., Jr. Crystallographic and Spectroscopic Characterization of a Nonheme Fe(IV)=O Complex. Science 2003, 299, 1037−1039. (195) Ballhausen, C. J.; Gray, H. B. The Electronic Structure of the Vanadyl Ion. Inorg. Chem. 1962, 1, 111−122. (196) Winkler, J. R.; Gray, H. B. Electronic Structures of Oxo-Metal Ions. In Molecular Electronic Structures of Transition Metal Complexes I; Mingos, D. M. P., Day, P., Dahl, J. P., Eds.; Springer Berlin Heidelberg: Berlin, Heidelberg, 2012; pp 17−28. (197) Wang, B.; Lee, Y.-M.; Tcho, W.-Y.; Tussupbayev, S.; Kim, S.T.; Kim, Y.; Seo, M. S.; Cho, K.-B.; Dede, Y.; Keegan, B. C.; Ogura, T.; Kim, S. H.; Ohta, T.; Baik, M.-H.; Ray, K.; Shearer, J.; Nam, W. Synthesis and Reactivity of a Mononuclear Non-Haem Cobalt(IV)Oxo Complex. Nat. Commun. 2017, 8, 14839. (198) Goetz, M. K.; Hill, E. A.; Filatov, A. S.; Anderson, J. S. Isolation of a Terminal Co(III)-Oxo Complex. J. Am. Chem. Soc. 2018, 140, 13176−13180. (199) Hong, S.; Pfaff, F. F.; Kwon, E.; Wang, Y.; Seo, M.-S.; Bill, E.; Ray, K.; Nam, W. Spectroscopic Capture and Reactivity of a Low-Spin Cobalt(IV)-Oxo Complex Stabilized by Binding Redox-Inactive Metal Ions. Angew. Chem., Int. Ed. 2014, 53, 10403−10407. (200) Baik, M.-H.; Gherman, B. F.; Friesner, R. A.; Lippard, S. J. Hydroxylation of Methane by Non-Heme Diiron Enzymes: Molecular Orbital Analysis of C−H Bond Activation by Reactive Intermediate Q. J. Am. Chem. Soc. 2002, 124, 14608−14615. (201) Yang, X.; Baik, M.-H. cis,cis-[(bpy)2RuVO]2O4+ Catalyzes Water Oxidation Formally via in Situ Generation of Radicaloid RuIV−O·. J. Am. Chem. Soc. 2006, 128, 7476−7485. (202) Crandell, D. W.; Ghosh, S.; Berlinguette, C. P.; Baik, M.-H. How a [Co(IV) a Bond and a Half O]2+ Fragment Oxidizes Water: Involvement of a Biradicaloid [Co(II)−(·O·)]2+ Species in Forming the O−O Bond. ChemSusChem 2015, 8, 844−852. (203) Noodleman, L. Valence Bond Description of Antiferromagnetic Coupling in Transition Metal Dimers. J. Chem. Phys. 1981, 74, 5737−5743. (204) Mouesca, J.-M. Density Functional Theory−Broken Symmetry (DFT−BS) Methodology Applied to Electronic and Magnetic Properties of Bioinorganic Prosthetic Groups. In Metalloproteins: Methods and Protocols; Fontecilla-Camps, J. C., Nicolet, Y., Eds.; Humana Press: Totowa, NJ, 2014; pp 269−296. (205) Blachly, P. G.; Sandala, G. M.; Giammona, D. A.; Liu, T.; Bashford, D.; McCammon, J. A.; Noodleman, L. Use of BrokenSymmetry Density Functional Theory To Characterize the IspH Oxidized State: Implications for IspH Mechanism and Inhibition. J. Chem. Theory Comput. 2014, 10, 3871−3884. (206) Ashley, D. C.; Baik, M.-H. The Electronic Structure of [Mn(V)O]: What Is the Connection between Oxyl Radical Character, Physical Oxidation State, and Reactivity? ACS Catal. 2016, 6, 7202−7216. (207) England, J.; Martinho, M.; Farquhar, E. R.; Frisch, J. R.; Bominaar, E. L.; Münck, E.; Que, L., Jr. A Synthetic High-Spin Oxoiron(IV) Complex: Generation, Spectroscopic Characterization, and Reactivity. Angew. Chem., Int. Ed. 2009, 48, 3622−3626. (208) Nam, W.; Lee, Y.-M.; Fukuzumi, S. Tuning Reactivity and Mechanism in Oxidation Reactions by Mononuclear Nonheme Iron(IV)-Oxo Complexes. Acc. Chem. Res. 2014, 47, 1146−1154. (209) Hirao, H.; Kumar, D.; Que, L., Jr; Shaik, S. Two-State Reactivity in Alkane Hydroxylation by Non-Heme Iron-Oxo Complexes. J. Am. Chem. Soc. 2006, 128, 8590−8606. (210) Zaragoza, J. P. T.; Siegler, M. A.; Goldberg, D. P. A Reactive Manganese(IV)-Hydroxide Complex: A Missing Intermediate in Hydrogen Atom Transfer by High-Valent Metal-Oxo Porphyrinoid Compounds. J. Am. Chem. Soc. 2018, 140, 4380−4390. (211) Scheidt, W. R.; Reed, C. A. Spin-State/stereochemical Relationships in Iron Porphyrins: Implications for the Hemoproteins. Chem. Rev. 1981, 81, 543−555.

(212) Lang, G.; Spartalian, K.; Reed, C. A.; Collman, J. P. Mössbauer Effect Study of the Magnetic Properties of S = 1 Ferrous Tetraphenylporphyrin. J. Chem. Phys. 1978, 69, 5424−5427. (213) Collman, J. P.; Hoard, J. L.; Kim, N.; Lang, G.; Reed, C. A. Synthesis, Stereochemistry, and Structure-Related Properties of α,β,γ,δ-tetraphenylporphinatoiron(II). J. Am. Chem. Soc. 1975, 97, 2676−2681. (214) Meunier, B.; de Visser, S. P.; Shaik, S. Mechanism of Oxidation Reactions Catalyzed by Cytochrome p450 Enzymes. Chem. Rev. 2004, 104, 3947−3980. (215) Rovira, C.; Kunc, K.; Hutter, J.; Ballone, P.; Parrinello, M. Equilibrium Geometries and Electronic Structure of Iron−Porphyrin Complexes: A Density Functional Study. J. Phys. Chem. A 1997, 101, 8914−8925. (216) Römelt, C.; Song, J.; Tarrago, M.; Rees, J. A.; van Gastel, M.; Weyhermüller, T.; DeBeer, S.; Bill, E.; Neese, F.; Ye, S. Electronic Structure of a Formal Iron(0) Porphyrin Complex Relevant to CO2 Reduction. Inorg. Chem. 2017, 56, 4745−4750. (217) Römelt, C.; Ye, S.; Bill, E.; Weyhermüller, T.; van Gastel, M.; Neese, F. Electronic Structure and Spin Multiplicity of Iron Tetraphenylporphyrins in Their Reduced States as Determined by a Combination of Resonance Raman Spectroscopy and Quantum Chemistry. Inorg. Chem. 2018, 57, 2141−2148. (218) Yang, C.; Nikiforidis, G.; Park, J. Y.; Choi, J.; Luo, Y.; Zhang, L.; Wang, S.-C.; Chan, Y.-T.; Lim, J.; Hou, Z.; Baik, M.-H.; Lee, Y.; Byon, H. R. Designing Redox-Stable Cobalt-Polypyridyl Complexes for Redox Flow Batteries: Spin-Crossover Delocalizes Excess Charge. Adv. Energy Mater. 2018, 8, 1702897. (219) Song, J.; Klein, E. L.; Neese, F.; Ye, S. The Mechanism of Homogeneous CO2 Reduction by Ni(cyclam): Product Selectivity, Concerted Proton-Electron Transfer and C−O Bond Cleavage. Inorg. Chem. 2014, 53, 7500−7507. (220) Froehlich, J. D.; Kubiak, C. P. Homogeneous CO2 Reduction by Ni(cyclam) at a Glassy Carbon Electrode. Inorg. Chem. 2012, 51, 3932−3934. (221) Sahoo, D.; Yoo, C.; Lee, Y. Direct CO2 Addition to a Ni(0)− CO Species Allows the Selective Generation of a Nickel(II) Carboxylate with Expulsion of CO. J. Am. Chem. Soc. 2018, 140, 2179−2185. (222) Riplinger, C.; Sampson, M. D.; Ritzmann, A. M.; Kubiak, C. P.; Carter, E. A. Mechanistic Contrasts between Manganese and Rhenium Bipyridine Electrocatalysts for the Reduction of Carbon Dioxide. J. Am. Chem. Soc. 2014, 136, 16285−16298. (223) Keith, J. A.; Grice, K. A.; Kubiak, C. P.; Carter, E. A. Elucidation of the Selectivity of Proton-Dependent Electrocatalytic CO2 Reduction by fac-Re(bpy)(CO)3Cl. J. Am. Chem. Soc. 2013, 135, 15823−15829. (224) Nichols, E. M.; Derrick, J. S.; Nistanaki, S. K.; Smith, P. T.; Chang, C. J. Positional Effects of Second-Sphere Amide Pendants on Electrochemical CO2 Reduction Catalyzed by Iron Porphyrins. Chem. Sci. 2018, 9, 2952−2960. (225) Costentin, C.; Robert, M.; Savéant, J.-M. Current Issues in Molecular Catalysis Illustrated by Iron Porphyrins as Catalysts of the CO2-to-CO Electrochemical Conversion. Acc. Chem. Res. 2015, 48, 2996−3006. (226) Dey, S.; Ahmed, M. E.; Dey, A. Activation of Co(I) State in a Cobalt-Dithiolato Catalyst for Selective and Efficient CO2 Reduction to CO. Inorg. Chem. 2018, 57, 5939−5947. (227) Riplinger, C.; Carter, E. A. Influence of Weak Brønsted Acids on Electrocatalytic CO2 Reduction by Manganese and Rhenium Bipyridine Catalysts. ACS Catal. 2015, 5, 900−908. (228) Rao, H.; Schmidt, L. C.; Bonin, J.; Robert, M. Visible-LightDriven Methane Formation from CO2 with a Molecular Iron Catalyst. Nature 2017, 548, 74−77. (229) Rao, H.; Lim, C.-H.; Bonin, J.; Miyake, G. M.; Robert, M. Visible-Light-Driven Conversion of CO2 to CH4 with an Organic Sensitizer and an Iron Porphyrin Catalyst. J. Am. Chem. Soc. 2018, 140, 17830−17834. AR

DOI: 10.1021/acs.chemrev.9b00073 Chem. Rev. XXXX, XXX, XXX−XXX

Chemical Reviews

Review

(230) Ju, W.; Bagger, A.; Hao, G.-P.; Varela, A. S.; Sinev, I.; Bon, V.; Roldan Cuenya, B.; Kaskel, S.; Rossmeisl, J.; Strasser, P. Understanding Activity and Selectivity of Metal-Nitrogen-Doped Carbon Catalysts for Electrochemical Reduction of CO2. Nat. Commun. 2017, 8, 944. (231) Shi, J.-J.; Hu, X.-M.; Madsen, M. R.; Lamagni, P.; Bjerglund, E. T.; Pedersen, S. U.; Skrydstrup, T.; Daasbjerg, K. Facile Synthesis of Iron- and Nitrogen-Doped Porous Carbon for Selective CO2 Electroreduction. ACS Appl. Nano Mater. 2018, 1, 3608−3615. (232) Hu, X.-M.; Hval, H. H.; Bjerglund, E. T.; Dalgaard, K. J.; Madsen, M. R.; Pohl, M.-M.; Welter, E.; Lamagni, P.; Buhl, K. B.; Bremholm, M.; Beller, M.; Pedersen, S. U.; Skrydstrup, T.; Daasbjerg, K. Selective CO2 Reduction to CO in Water Using Earth-Abundant Metal and Nitrogen-Doped Carbon Electrocatalysts. ACS Catal. 2018, 8, 6255−6264. (233) Li, X.; Bi, W.; Chen, M.; Sun, Y.; Ju, H.; Yan, W.; Zhu, J.; Wu, X.; Chu, W.; Wu, C.; Xie, Y. Exclusive Ni−N4 Sites Realize NearUnity CO Selectivity for Electrochemical CO2 Reduction. J. Am. Chem. Soc. 2017, 139, 14889−14892. (234) Pokharel, U. R.; Fronczek, F. R.; Maverick, A. W. Reduction of Carbon Dioxide to Oxalate by a Binuclear Copper Complex. Nat. Commun. 2014, 5, 5883. (235) Angamuthu, R.; Byers, P.; Lutz, M.; Spek, A. L.; Bouwman, E. Electrocatalytic CO2 Conversion to Oxalate by a Copper Complex. Science 2010, 327, 313−315. (236) Lan, J.; Liao, T.; Zhang, T.; Chung, L. W. Reaction Mechanism of Cu(I)-Mediated Reductive CO2 Coupling for the Selective Formation of Oxalate: Cooperative CO2 Reduction To Give Mixed-Valence Cu2(CO2•−) and Nucleophilic-Like Attack. Inorg. Chem. 2017, 56, 6809−6819. (237) Chen, X.; Yang, X. Bioinspired Design and Computational Prediction of Iron Complexes with Pendant Amines for the Production of Methanol from CO2 and H2. J. Phys. Chem. Lett. 2016, 7, 1035−1041. (238) Liu, T.; Dubois, D. L.; Bullock, R. M. An Iron Complex with Pendent Amines as a Molecular Electrocatalyst for Oxidation of Hydrogen. Nat. Chem. 2013, 5, 228−233. (239) Ge, H.; Chen, X.; Yang, X. A Mechanistic Study and Computational Prediction of Iron, Cobalt and Manganese Cyclopentadienone Complexes for Hydrogenation of Carbon Dioxide. Chem. Commun. 2016, 52, 12422−12425. (240) Casey, C. P.; Guan, H. An Efficient and Chemoselective Iron Catalyst for the Hydrogenation of Ketones. J. Am. Chem. Soc. 2007, 129, 5816−5817. (241) Thorson, M. K.; Klinkel, K. L.; Wang, J.; Williams, T. J. Mechanism of Hydride Abstraction by Cyclopentadienone-Ligated Carbonylmetal Complexes (M = Ru, Fe). Eur. J. Inorg. Chem. 2009, 2009, 295−302. (242) Hodgkinson, R.; Del Grosso, A.; Clarkson, G.; Wills, M. Iron Cyclopentadienone Complexes Derived from C2-Symmetric BisPropargylic Alcohols; Preparation and Applications to Catalysis. Dalton Trans 2016, 45, 3992−4005. (243) Zhu, F.; Zhu-Ge, L.; Yang, G.; Zhou, S. Iron-Catalyzed Hydrogenation of Bicarbonates and Carbon Dioxide to Formates. ChemSusChem 2015, 8, 609−612. (244) Thai, T.-T.; Mérel, D. S.; Poater, A.; Gaillard, S.; Renaud, J.-L. Highly Active Phosphine-Free Bifunctional Iron Complex for Hydrogenation of Bicarbonate and Reductive Amination. Chem. Eur. J. 2015, 21, 7066−7070. (245) Yang, X. Hydrogenation of Carbon Dioxide Catalyzed by PNP Pincer Iridium, Iron, and Cobalt Complexes: A Computational Design of Base Metal Catalysts. ACS Catal. 2011, 1, 849−854. (246) Tanaka, R.; Yamashita, M.; Nozaki, K. Catalytic Hydrogenation of Carbon Dioxide Using Ir(III)-Pincer Complexes. J. Am. Chem. Soc. 2009, 131, 14168−14169. (247) Langer, R.; Leitus, G.; Ben-David, Y.; Milstein, D. Efficient Hydrogenation of Ketones Catalyzed by an Iron Pincer Complex. Angew. Chem., Int. Ed. 2011, 50, 2120−2124.

(248) Uhe, A.; Hölscher, M.; Leitner, W. Carboxylation of Arene C−H Bonds with CO2: A DFT-Based Approach to Catalyst Design. Chem. - Eur. J. 2012, 18, 170−177. (249) Boogaerts, I. I. F.; Nolan, S. P. Carboxylation of C−H Bonds Using N-Heterocyclic Carbene Gold(I) Complexes. J. Am. Chem. Soc. 2010, 132, 8858−8859. (250) Zhang, L.; Cheng, J.; Ohishi, T.; Hou, Z. Copper-Catalyzed Direct Carboxylation of C−H Bonds with Carbon Dioxide. Angew. Chem., Int. Ed. 2010, 49, 8670−8673. (251) Mizuno, H.; Takaya, J.; Iwasawa, N. Rhodium(I)-Catalyzed Direct Carboxylation of Arenes with CO2 via Chelation-Assisted C− H Bond Activation. J. Am. Chem. Soc. 2011, 133, 1251−1253. (252) Kozuch, S.; Shaik, S. A Combined Kinetic-Quantum Mechanical Model for Assessment of Catalytic Cycles: Application to Cross-Coupling and Heck Reactions. J. Am. Chem. Soc. 2006, 128, 3355−3365. (253) Uhe, A.; Kozuch, S.; Shaik, S. Automatic Analysis of Computed Catalytic Cycles. J. Comput. Chem. 2011, 32, 978−985. (254) Prechtl, M. H. G.; Hölscher, M.; Ben-David, Y.; Theyssen, N.; Loschen, R.; Milstein, D.; Leitner, W. H/D Exchange at Aromatic and Heteroaromatic Hydrocarbons Using D2O as the Deuterium Source and Ruthenium Dihydrogen Complexes as the Catalyst. Angew. Chem., Int. Ed. 2007, 46, 2269−2272. (255) Gooßen, L. J.; Rodríguez, N.; Linder, C.; Lange, P. P.; Fromm, A. Comparative Study of Copper- and Silver-Catalyzed Protodecarboxylations of Carboxylic Acids. ChemCatChem 2010, 2, 430− 442. (256) Shang, R.; Fu, Y.; Wang, Y.; Xu, Q.; Yu, H.-Z.; Liu, L. CopperCatalyzed Decarboxylative Cross-Coupling of Potassium Polyfluorobenzoates with Aryl Iodides and Bromides. Angew. Chem., Int. Ed. 2009, 48, 9350−9354. (257) Shang, R.; Fu, Y.; Li, J.-B.; Zhang, S.-L.; Guo, Q.-X.; Liu, L. Synthesis of Aromatic Esters via Pd-Catalyzed Decarboxylative Coupling of Potassium Oxalate Monoesters with Aryl Bromides and Chlorides. J. Am. Chem. Soc. 2009, 131, 5738−5739. (258) Gooßen, L. J.; Deng, G.; Levy, L. M. Synthesis of Biaryls via Catalytic Decarboxylative Coupling. Science 2006, 313, 662−664. (259) Goossen, L. J.; Rodríguez, N.; Melzer, B.; Linder, C.; Deng, G.; Levy, L. M. Biaryl Synthesis via Pd-Catalyzed Decarboxylative Coupling of Aromatic Carboxylates with Aryl Halides. J. Am. Chem. Soc. 2007, 129, 4824−4833. (260) Gooßen, L. J.; Rudolphi, F.; Oppel, C.; Rodríguez, N. Synthesis of Ketones from Alpha-Oxocarboxylates and Aryl Bromides by Cu/Pd-Catalyzed Decarboxylative Cross-Coupling. Angew. Chem., Int. Ed. 2008, 47, 3043−3045. (261) Goossen, L. J.; Rodríguez, N.; Linder, C. Decarboxylative Biaryl Synthesis from Aromatic Carboxylates and Aryl Triflates. J. Am. Chem. Soc. 2008, 130, 15248−15249. (262) Guo, W.; Michel, C.; Schwiedernoch, R.; Wischert, R.; Xu, X.; Sautet, P. Formation of Acrylates from Ethylene and CO2 on Ni Complexes: A Mechanistic Viewpoint from a Hybrid DFT Approach. Organometallics 2014, 33, 6369−6380. (263) Lee, S. Y. T.; Cokoja, M.; Drees, M.; Li, Y.; Mink, J.; Herrmann, W. A.; Kühn, F. E. Transformation of Nickelalactones to Methyl Acrylate: On the Way to a Catalytic Conversion of Carbon Dioxide. ChemSusChem 2011, 4, 1275−1279. (264) Braunstein, P.; Matt, D.; Nobel, D. Reactions of Carbon Dioxide with Carbon-Carbon Bond Formation Catalyzed by Transition-Metal Complexes. Chem. Rev. 1988, 88, 747−764. (265) Bruckmeier, C.; Lehenmeier, M. W.; Reichardt, R.; Vagin, S.; Rieger, B. Formation of Methyl Acrylate from CO2 and Ethylene via Methylation of Nickelalactones. Organometallics 2010, 29, 2199− 2202. (266) Genet, J.-P. Asymmetric Catalytic Hydrogenation. Design of New Ru Catalysts and Chiral Ligands: From Laboratory to Industrial Applications. Acc. Chem. Res. 2003, 36, 908−918. (267) Blaser, H.-U.; Malan, C.; Pugin, B.; Spindler, F.; Steiner, H.; Studer, M. Selective Hydrogenation for Fine Chemicals: Recent AS

DOI: 10.1021/acs.chemrev.9b00073 Chem. Rev. XXXX, XXX, XXX−XXX

Chemical Reviews

Review

Trends and New Developments. Adv. Synth. Catal. 2003, 345, 103− 151. (268) Clapham, S. E.; Hadzovic, A.; Morris, R. H. Mechanisms of the H2-Hydrogenation and Transfer Hydrogenation of Polar Bonds Catalyzed by Ruthenium Hydride Complexes. Coord. Chem. Rev. 2004, 248, 2201−2237. (269) Osborn, J. A.; Jardine, F. H.; Young, J. F.; Wilkinson, G. The Preparation and Properties of tris(triphenylphosphine)halogenorhodium(I) and Some Reactions Thereof Including Catalytic Homogeneous Hydrogenation of Olefins and Acetylenes and Their Derivatives. J. Chem. Soc. A 1966, 0, 1711−1732. (270) Tanielyan, S. K.; Augustine, R. L.; Marin, N.; Alvez, G. Anchored Wilkinson Catalyst. ACS Catal. 2011, 1, 159−169. (271) Nelson, D. J.; Li, R.; Brammer, C. Using Correlations to Compare Additions to Alkenes: Homogeneous Hydrogenation by Using Wilkinson’s Catalyst. J. Org. Chem. 2005, 70, 761−767. (272) Richter, B.; Spek, A. L.; van Koten, G.; Deelman, B.-J. Fluorous Versions of Wilkinson’s Catalyst. Activity in Fluorous Hydrogenation of 1-Alkenes and Recycling by Fluorous Biphasic Separation. J. Am. Chem. Soc. 2000, 122, 3945−3951. (273) Perea-Buceta, J. E.; Fernández, I.; Heikkinen, S.; Axenov, K.; King, A. W. T.; Niemi, T.; Nieger, M.; Leskelä, M.; Repo, T. Diverting Hydrogenations with Wilkinson’s Catalyst towards Highly Reactive Rhodium(I) Species. Angew. Chem., Int. Ed. 2015, 54, 14321−14325. (274) Rowley, C. N.; Woo, T. K. Computational Design of Ruthenium Hydride Olefin-Hydrogenation Catalysts Containing Hemilabile Ligands. Can. J. Chem. 2009, 87, 1030−1038. (275) Donoghue, P. J.; Helquist, P.; Norrby, P.-O.; Wiest, O. Prediction of Enantioselectivity in Rhodium Catalyzed Hydrogenations. J. Am. Chem. Soc. 2009, 131, 410−411. (276) Dobereiner, G. E.; Nova, A.; Schley, N. D.; Hazari, N.; Miller, S. J.; Eisenstein, O.; Crabtree, R. H. Iridium-Catalyzed Hydrogenation of N-Heterocyclic Compounds under Mild Conditions by an OuterSphere Pathway. J. Am. Chem. Soc. 2011, 133, 7547−7562. (277) Arpe, H.-J. Industrial Organic Chemistry; Wiley, 2010. (278) Carter, A.; Cohen, S. A.; Cooley, N. A.; Murphy, A.; Scutt, J.; Wass, D. F. High Activity Ethylene Trimerisation Catalysts Based on Diphosphine Ligands. Chem. Commun. 2002, 8, 858−859. (279) Agapie, T. Selective Ethylene Oligomerization: Recent Advances in Chromium Catalysis and Mechanistic Investigations. Coord. Chem. Rev. 2011, 255, 861−880. (280) McGuinness, D. S. Olefin Oligomerization via Metallacycles: Dimerization, Trimerization, Tetramerization, and beyond. Chem. Rev. 2011, 111, 2321−2341. (281) Kwon, D.-H.; Fuller, J. T.; Kilgore, U. J.; Sydora, O. L.; Bischof, S. M.; Ess, D. H. Computational Transition-State Design Provides Experimentally Verified Cr(P,N) Catalysts for Control of Ethylene Trimerization and Tetramerization. ACS Catal. 2018, 8, 1138−1142. (282) Britovsek, G. J. P.; McGuinness, D. S. A DFT Mechanistic Study on Ethylene Tri- and Tetramerization with Cr/PNP Catalysts: Single versus Double Insertion Pathways. Chem. - Eur. J. 2016, 22, 16891−16896. (283) Britovsek, G. J. P.; McGuinness, D. S.; Tomov, A. K. Mechanistic Study of Ethylene Tri- and Tetramerisation with Cr/ PNP Catalysts: Effects of Additional Donors. Catal. Sci. Technol. 2016, 6, 8234−8241. (284) Ess, D. H. Rapid Enantioselective Catalyst Optimization. Nat. Catal 2019, 2, 8−9. (285) Zou, C.; Zhao, Q.; Zhang, G.; Xiong, B. Energy Revolution: From a Fossil Energy Era to a New Energy Era. Nat. Gas Ind. B 2016, 3, 1−11. (286) Owusu, P. A.; Asumadu-Sarkodie, S. A Review of Renewable Energy Sources, Sustainability Issues and Climate Change Mitigation. Cogent Eng. 2016, 3, 891. (287) Blakemore, J. D.; Crabtree, R. H.; Brudvig, G. W. Molecular Catalysts for Water Oxidation. Chem. Rev. 2015, 115, 12974−13005. (288) Gilbert, J. A.; Eggleston, D. S.; Murphy, W. R.; Geselowitz, D. A.; Gersten, S. W.; Hodgson, D. J.; Meyer, T. J. Structure and Redox

Properties of the Water-Oxidation Catalyst [(bpy)2(OH2)RuORu(OH2)(bpy)2]4+. J. Am. Chem. Soc. 1985, 107, 3855−3864. (289) Hurst, J. K. Water Oxidation Catalyzed by Dimeric μ-Oxo Bridged Ruthenium Diimine Complexes. Coord. Chem. Rev. 2005, 249, 313−328. (290) Rüttinger, W.; Dismukes, G. C. Synthetic Water-Oxidation Catalysts for Artificial Photosynthetic Water Oxidation. Chem. Rev. 1997, 97, 1−24. (291) Liu, F.; Concepcion, J. J.; Jurss, J. W.; Cardolaccia, T.; Templeton, J. L.; Meyer, T. J. Mechanisms of Water Oxidation from the Blue Dimer to Photosystem II. Inorg. Chem. 2008, 47, 1727− 1752. (292) Moonshiram, D.; Alperovich, I.; Concepcion, J. J.; Meyer, T. J.; Pushkar, Y. Experimental Demonstration of Radicaloid Character in a Ru(V)O Intermediate in Catalytic Water Oxidation. Proc. Natl. Acad. Sci. U. S. A. 2013, 110, 3765−3770. (293) Sens, C.; Romero, I.; Rodríguez, M.; Llobet, A.; Parella, T.; Benet-Buchholz, J. A New Ru Complex Capable of Catalytically Oxidizing Water to Molecular Dioxygen. J. Am. Chem. Soc. 2004, 126, 7798−7799. (294) Yang, X.; Baik, M.-H. The Mechanism of Water Oxidation Catalysis Promoted by [tpyRu(IV)O]2L3+: A Computational Study. J. Am. Chem. Soc. 2008, 130, 16231−16240. (295) Neudeck, S.; Maji, S.; López, I.; Meyer, S.; Meyer, F.; Llobet, A. New Powerful and Oxidatively Rugged Dinuclear Ru Water Oxidation Catalyst: Control of Mechanistic Pathways by Tailored Ligand Design. J. Am. Chem. Soc. 2014, 136, 24−27. (296) Concepcion, J. J.; Jurss, J. W.; Brennaman, M. K.; Hoertz, P. G.; Patrocinio, A. O. T.; Murakami Iha, N. Y.; Templeton, J. L.; Meyer, T. J. Making Oxygen with Ruthenium Complexes. Acc. Chem. Res. 2009, 42, 1954−1965. (297) Concepcion, J. J.; Jurss, J. W.; Templeton, J. L.; Meyer, T. J. Mediator-Assisted Water Oxidation by the Ruthenium “Blue Dimer” Cis,cis-[(bpy)2(H2O)RuORu(OH2)(bpy)2]4+. Proc. Natl. Acad. Sci. U. S. A. 2008, 105, 17632−17635. (298) Geletii, Y. V.; Botar, B.; Kögerler, P.; Hillesheim, D. A.; Musaev, D. G.; Hill, C. L. An All-Inorganic, Stable, and Highly Active Tetraruthenium Homogeneous Catalyst for Water Oxidation. Angew. Chem., Int. Ed. 2008, 47, 3896−3899. (299) Piccinin, S.; Sartorel, A.; Aquilanti, G.; Goldoni, A.; Bonchio, M.; Fabris, S. Water Oxidation Surface Mechanisms Replicated by a Totally Inorganic Tetraruthenium-Oxo Molecular Complex. Proc. Natl. Acad. Sci. U. S. A. 2013, 110, 4917−4922. (300) Yoshida, M.; Masaoka, S.; Abe, J.; Sakai, K. Catalysis of Mononuclear Aquaruthenium Complexes in Oxygen Evolution from Water: A New Radical Coupling Path Using Hydroxocerium(IV) Species. Chem. Asian J. 2010, 5, 2369−2378. (301) Crandell, D. W.; Xu, S.; Smith, J. M.; Baik, M.-H. Intramolecular Oxyl Radical Coupling Promotes O−O Bond Formation in a Homogeneous Mononuclear Mn-Based Water Oxidation Catalyst: A Computational Mechanistic Investigation. Inorg. Chem. 2017, 56, 4435−4445. (302) Hirahara, M.; Ertem, M. Z.; Komi, M.; Yamazaki, H.; Cramer, C. J.; Yagi, M. Mechanisms of Photoisomerization and WaterOxidation Catalysis of Mononuclear Ruthenium(II) Monoaquo Complexes. Inorg. Chem. 2013, 52, 6354−6364. (303) Ozkanlar, A.; Cape, J. L.; Hurst, J. K.; Clark, A. E. Covalent Hydration” Reactions in Model Monomeric Ru 2,2’-Bipyridine Complexes: Thermodynamic Favorability as a Function of Metal Oxidation and Overall Spin States. Inorg. Chem. 2011, 50, 8177− 8187. (304) Tong, L.; Thummel, R. P. Mononuclear Ruthenium Polypyridine Complexes That Catalyze Water Oxidation. Chem. Sci. 2016, 7, 6591−6603. (305) Yoshida, M.; Masaoka, S. Cerium(IV)-Driven Oxidation of Water Catalyzed by Mononuclear Ruthenium Complexes. Res. Chem. Intermed. 2014, 40, 3169−3182. AT

DOI: 10.1021/acs.chemrev.9b00073 Chem. Rev. XXXX, XXX, XXX−XXX

Chemical Reviews

Review

(326) Buchwald, S. L. Cross Coupling. Acc. Chem. Res. 2008, 41, 1439. (327) Crabtree, R. H. Introduction to Selective Functionalization of C−H Bonds. Chem. Rev. 2010, 110, 575. (328) Gladysz, J. A. Introduction to Frontiers in Transition Metal Catalyzed Reactions (and a Brief Adieu). Chem. Rev. 2011, 111, 1167−1169. (329) Beller, M. Preface for the Themed Issue of Chemical Society Reviews. Chem. Soc. Rev. 2011, 40, 4891−4892. (330) Kleimark, J.; Hedström, A.; Larsson, P.-F.; Johansson, C.; Norrby, P.-O. Mechanistic Investigation of Iron-Catalyzed Coupling Reactions. ChemCatChem 2009, 1, 152−161. (331) Kleimark, J.; Larsson, P.-F.; Emamy, P.; Hedström, A.; Norrby, P.-O. Low Temperature Studies of Iron-Catalyzed CrossCoupling of Alkyl Grignard Reagents with Aryl Electrophiles. Adv. Synth. Catal. 2012, 354, 448−456. (332) Hedström, A.; Lindstedt, E.; Norrby, P.-O. On the Oxidation State of Iron in Iron-Mediated C−C Couplings. J. Organomet. Chem. 2013, 748, 51−55. (333) Chung, L. W.; Wu, Y.-D.; Trost, B. M.; Ball, Z. T. A Theoretical Study on the Mechanism, Regiochemistry, and Stereochemistry of Hydrosilylation Catalyzed by Cationic Ruthenium Complexes. J. Am. Chem. Soc. 2003, 125, 11578−11582. (334) Harrod, J. F.; Chalk, A. J. Dicobalt Octacarbonyl as a Catalyst for Hydrosilation of Olefins. J. Am. Chem. Soc. 1965, 87, 1133−1133. (335) Chalk, A. J.; Harrod, J. F. Homogeneous Catalysis. II. The Mechanism of the Hydrosilation of Olefins Catalyzed by Group VIII Metal Complexes1. J. Am. Chem. Soc. 1965, 87, 16−21. (336) Tuttle, T.; Wang, D.; Thiel, W.; Köhler, J.; Hofmann, M.; Weis, J. Mechanism of Olefin Hydrosilylation Catalyzed by RuCl2(CO)2(PPh3)2: A DFT Study. Organometallics 2006, 25, 4504−4513. (337) Wang, J.; Huang, L.; Yang, X.; Wei, H. Mechanistic Investigation Into Catalytic Hydrosilylation with a High-Valent Ruthenium(VI)−Nitrido Complex: A DFT Study. Organometallics 2015, 34, 212−220. (338) Gridnev, I. D.; Watanabe, M.; Wang, H.; Ikariya, T. Mechanism of Enantioselective C−C Bond Formation with Bifunctional Chiral Ru Catalysts: NMR and DFT Study. J. Am. Chem. Soc. 2010, 132, 16637−16650. (339) Prier, C. K.; Rankic, D. A.; MacMillan, D. W. C. Visible Light Photoredox Catalysis with Transition Metal Complexes: Applications in Organic Synthesis. Chem. Rev. 2013, 113, 5322−5363. (340) Demissie, T. B.; Ruud, K.; Hansen, J. H. DFT as a Powerful Predictive Tool in Photoredox Catalysis: Redox Potentials and Mechanistic Analysis. Organometallics 2015, 34, 4218−4228. (341) Rummelt, S. M.; Cheng, G.-J.; Gupta, P.; Thiel, W.; Fürstner, A. Hydroxy-Directed Ruthenium-Catalyzed Alkene/Alkyne Coupling: Increased Scope, Stereochemical Implications, and Mechanistic Rationale. Angew. Chem., Int. Ed. 2017, 56, 3599−3604. (342) Inglesby, P. A.; Evans, P. A. Stereoselective Transition MetalCatalysed Higher-Order Carbocyclisation Reactions. Chem. Soc. Rev. 2010, 39, 2791−2805. (343) Haraburda, E.; Torres, Ó .; Parella, T.; Solà, M.; Pla-Quintana, A. Stereoselective Rhodium-Catalysed [2 + 2+2] Cycloaddition of Linear Allene-Ene/yne-Allene Substrates: Reactivity and Theoretical Mechanistic Studies. Chem. - Eur. J. 2014, 20, 5034−5045. (344) Yu, H.; Lu, Q.; Dang, Z.; Fu, Y. Mechanistic Study of the Rhodium-Catalyzed [3 + 2+2] Carbocyclization of Alkenylidenecyclopropanes with Alkynes. Chem. - Asian J. 2013, 8, 2262−2273. (345) Straker, R. N.; Peng, Q.; Mekareeya, A.; Paton, R. S.; Anderson, E. A. Computational Ligand Design in Enantio- and Diastereoselective Ynamide [5 + 2] Cycloisomerization. Nat. Commun. 2016, 7, 10109. (346) Zhang, X.; Wang, J.; Zhao, H.; Zhao, H.; Wang, J. RhodiumCatalyzed [6 + 2] Cycloaddition of Internal Alkynes with Cycloheptatriene: Catalytic Study and DFT Calculations of the Reaction Mechanism. Organometallics 2013, 32, 3529−3536.

(306) Mulyana, Y.; Keene, F. R.; Spiccia, L. Cooperative Effects in Homogenous Water Oxidation Catalysis by Mononuclear Ruthenium Complexes. Dalton Trans 2014, 43, 6819−6827. (307) Staehle, R.; Tong, L.; Wang, L.; Duan, L.; Fischer, A.; Ahlquist, M. S. G.; Sun, L.; Rau, S. Water Oxidation Catalyzed by Mononuclear Ruthenium Complexes with a 2,2’-Bipyridine-6,6’Dicarboxylate (bda) Ligand: How Ligand Environment Influences the Catalytic Behavior. Inorg. Chem. 2014, 53, 1307−1319. (308) Duan, L.; Araujo, C. M.; Ahlquist, M. S. G.; Sun, L. Highly Efficient and Robust Molecular Ruthenium Catalysts for Water Oxidation. Proc. Natl. Acad. Sci. U. S. A. 2012, 109, 15584−15588. (309) Tseng, H.-W.; Zong, R.; Muckerman, J. T.; Thummel, R. Mononuclear Ruthenium(II) Complexes That Catalyze Water Oxidation. Inorg. Chem. 2008, 47, 11763−11773. (310) Muckerman, J. T.; Kowalczyk, M.; Badiei, Y. M.; Polyansky, D. E.; Concepcion, J. J.; Zong, R.; Thummel, R. P.; Fujita, E. New Water Oxidation Chemistry of a Seven-Coordinate Ruthenium Complex with a Tetradentate Polypyridyl Ligand. Inorg. Chem. 2014, 53, 6904−6913. (311) McCool, N. S.; Robinson, D. M.; Sheats, J. E.; Dismukes, G. C. A Co4O4 “Cubane” Water Oxidation Catalyst Inspired by Photosynthesis. J. Am. Chem. Soc. 2011, 133, 11446−11449. (312) Berardi, S.; La Ganga, G.; Natali, M.; Bazzan, I.; Puntoriero, F.; Sartorel, A.; Scandola, F.; Campagna, S.; Bonchio, M. Photocatalytic Water Oxidation: Tuning Light-Induced Electron Transfer by Molecular Co4O4 Cores. J. Am. Chem. Soc. 2012, 134, 11104− 11107. (313) La Ganga, G.; Puntoriero, F.; Campagna, S.; Bazzan, I.; Berardi, S.; Bonchio, M.; Sartorel, A.; Natali, M.; Scandola, F. LightDriven Water Oxidation with a Molecular Tetra-cobalt(III) Cubane Cluster. Faraday Discuss. 2012, 155, 177−190. (314) Symes, M. D.; Surendranath, Y.; Lutterman, D. A.; Nocera, D. G. Bidirectional and Unidirectional PCET in a Molecular Model of a Cobalt-Based Oxygen-Evolving Catalyst. J. Am. Chem. Soc. 2011, 133, 5174−5177. (315) Evangelisti, F.; Güttinger, R.; Moré, R.; Luber, S.; Patzke, G. R. Closer to Photosystem II: A Co4O4 Cubane Catalyst with Flexible Ligand Architecture. J. Am. Chem. Soc. 2013, 135, 18734−18737. (316) Hodel, F. H.; Luber, S. What Influences the Water Oxidation Activity of a Bioinspired Molecular CoII4O4 Cubane? An In-Depth Exploration of Catalytic Pathways. ACS Catal. 2016, 6, 1505−1517. (317) Hodel, F. H.; Luber, S. Redox-Inert Cations Enhancing Water Oxidation Activity: The Crucial Role of Flexibility. ACS Catal. 2016, 6, 6750−6761. (318) Wada, T.; Tsuge, K.; Tanaka, K. Electrochemical Oxidation of Water to Dioxygen Catalyzed by the Oxidized Form of the Bis(ruthenium − Hydroxo) Complex in H2O. Angew. Chem. Int. Ed 1991, 91, 1441−1457. (319) Wada, T.; Tsuge, K.; Tanaka, K. Syntheses and Redox Properties of Bis(hydroxoruthenium) Complexes with Quinone and Bipyridine Ligands. Water-Oxidation Catalysis. Inorg. Chem. 2001, 40, 329−337. (320) Ghosh, S.; Baik, M.-H. Redox Properties of Tanaka’s Water Oxidation Catalyst: Redox Noninnocent Ligands Dominate the Electronic Structure and Reactivity. Inorg. Chem. 2011, 50, 5946− 5957. (321) Ghosh, S.; Baik, M.-H. The Mechanism of O−O Bond Formation in Tanaka’s Water Oxidation Catalyst. Angew. Chem., Int. Ed. 2012, 51, 1221−1224. (322) Miyaura, N.; Suzuki, A. Palladium-Catalyzed Cross-Coupling Reactions of Organoboron Compounds. Chem. Rev. 1995, 95, 2457− 2483. (323) Miyaura, N. Cross-Coupling Reactions: A Practical Guide; Springer, 2002. (324) Sun, C.-L.; Shi, Z.-J. Transition-Metal-Free Coupling Reactions. Chem. Rev. 2014, 114, 9219−9280. (325) Biffis, A.; Centomo, P.; Del Zotto, A.; Zecca, M. Pd Metal Catalysts for Cross-Couplings and Related Reactions in the 21st Century: A Critical Review. Chem. Rev. 2018, 118, 2249−2295. AU

DOI: 10.1021/acs.chemrev.9b00073 Chem. Rev. XXXX, XXX, XXX−XXX

Chemical Reviews

Review

(347) Wang, H.; Sawyer, J. R.; Evans, P. A.; Baik, M.-H. Mechanistic Insight into the Diastereoselective Rhodium-Catalyzed Pauson− Khand Reaction: Role of Coordination Number in Stereocontrol. Angew. Chem. 2008, 120, 348−351. (348) Park, Y.; Ahn, S.; Kang, D.; Baik, M.-H. Mechanism of RhCatalyzed Oxidative Cyclizations: Closed versus Open Shell Pathways. Acc. Chem. Res. 2016, 49, 1263−1270. (349) Baik, M.-H.; Mazumder, S.; Ricci, P.; Sawyer, J. R.; Song, Y.G.; Wang, H.; Evans, P. A. Computationally Designed and Experimentally Confirmed Diastereoselective Rhodium-Catalyzed Pauson-Khand Reaction at Room Temperature. J. Am. Chem. Soc. 2011, 133, 7621−7623. (350) Burrows, L. C.; Jesikiewicz, L. T.; Lu, G.; Geib, S. J.; Liu, P.; Brummond, K. M. Computationally Guided Catalyst Design in the Type I Dynamic Kinetic Asymmetric Pauson-Khand Reaction of Allenyl Acetates. J. Am. Chem. Soc. 2017, 139, 15022−15032. (351) Wang, Y.; Wang, J.; Su, J.; Huang, F.; Jiao, L.; Liang, Y.; Yang, D.; Zhang, S.; Wender, P. A.; Yu, Z.-X. A Computationally Designed Rh(I)-Catalyzed Two-Component [5 + 2+1] Cycloaddition of EneVinylcyclopropanes and CO for the Synthesis of Cyclooctenones. J. Am. Chem. Soc. 2007, 129, 10060−10061. (352) Jiao, L.; Lin, M.; Yu, Z.-X. Density Functional Theory Study of the Mechanisms and Stereochemistry of the Rh(I)-Catalyzed Intramolecular [3 + 2] Cycloadditions of 1-Ene- and 1-YneVinylcyclopropanes. J. Am. Chem. Soc. 2011, 133, 447−461. (353) Liao, W.; Yu, Z.-X. DFT Study of the Mechanism and Stereochemistry of the Rh(I)-Catalyzed Diels-Alder Reactions between Electronically Neutral Dienes and Dienophiles. J. Org. Chem. 2014, 79, 11949−11960. (354) Hyatt, I. F. D.; Anderson, H. K.; Morehead, A. T.; Sargent, A. L. Mechanism of Rhodium-Catalyzed Intramolecular Hydroacylation: A Computational Study. Organometallics 2008, 27, 135−147. (355) Shen, Z.; Dornan, P. K.; Khan, H. A.; Woo, T. K.; Dong, V. M. Mechanistic Insights into the Rhodium-Catalyzed Intramolecular Ketone Hydroacylation. J. Am. Chem. Soc. 2009, 131, 1077−1091. (356) Marcé, P.; Godard, C.; Feliz, M.; Yáñez, X.; Bo, C.; Castillón, S. Rhodium-Catalyzed Intermolecular Hydroiminoacylation of Alkenes: Comparison of Neutral and Cationic Catalytic Systems. Organometallics 2009, 28, 2976−2985. (357) Carvajal, M. À .; Kozuch, S.; Shaik, S. Factors Controlling the Selective Hydroformylation of Internal Alkenes to Linear Aldehydes. 1. The Isomerization Step. Organometallics 2009, 28, 3656−3665. (358) Kohls, E.; Stein, M. The Thermochemistry of Long Chain Olefin Isomers during Hydroformylation. New J. Chem. 2017, 41, 7347−7355. (359) Kumar, M.; Chaudhari, R. V.; Subramaniam, B.; Jackson, T. A. Ligand Effects on the Regioselectivity of Rhodium-Catalyzed Hydroformylation: Density Functional Calculations Illuminate the Role of Long-Range Noncovalent Interactions. Organometallics 2014, 33, 4183−4191. (360) Schmidt, S.; Deglmann, P.; Hofmann, P. Density Functional Investigations of the Rh-Catalyzed Hydroformylation of 1,3Butadiene with Bisphosphite Ligands. ACS Catal. 2014, 4, 3593− 3604. (361) Huo, C.-F.; Li, Y.-W.; Beller, M.; Jiao, H. Regioselective Hydroformylation of Butadiene: Density Functional Studies. Organometallics 2005, 24, 3634−3643. (362) Dangat, Y.; Rizvi, M. A.; Pandey, P.; Vanka, K. Exploring Activity Differences between the Hydroformylation Catalysts: Insights from Theory. J. Organomet. Chem. 2016, 801, 30−41. (363) Hansen, J.; Autschbach, J.; Davies, H. M. L. Computational Study on the Selectivity of Donor/acceptor-Substituted Rhodium Carbenoids. J. Org. Chem. 2009, 74, 6555−6563. (364) Li, Z.; Boyarskikh, V.; Hansen, J. H.; Autschbach, J.; Musaev, D. G.; Davies, H. M. L. Scope and Mechanistic Analysis of the Enantioselective Synthesis of Allenes by Rhodium-Catalyzed Tandem Ylide formation/[2,3]-Sigmatropic Rearrangement between Donor/ acceptor Carbenoids and Propargylic Alcohols. J. Am. Chem. Soc. 2012, 134, 15497−15504.

(365) Wang, H.; Guptill, D. M.; Alvarez, A. V.; Musaev, D. G.; Davies, H. M. L. Rhodium-Catalyzed Enantioselective Cyclopropanation of Electron Deficient Alkenes. Chem. Sci. 2013, 4, 2844−2850. (366) Pavlovic, L.; Vaitla, J.; Bayer, A.; Hopmann, K. H. RhodiumCatalyzed Hydrocarboxylation: Mechanistic Analysis Reveals Unusual Transition State for Carbon−Carbon Bond Formation. Organometallics 2018, 37, 941−948. (367) Korenaga, T.; Sasaki, R.; Takemoto, T.; Yasuda, T.; Watanabe, M. Computationally-Led Ligand Modification Using Interplay between Theory and Experiments: Highly Active Chiral Rhodium Catalyst Controlled by Electronic Effects and CH-π Interactions. Adv. Synth. Catal. 2018, 360, 322−333. (368) Song, L.-J.; Ding, S.; Wang, Y.; Zhang, X.; Wu, Y.-D.; Sun, J. Ir-Catalyzed Regio- and Stereoselective Hydrosilylation of Internal Thioalkynes: A Combined Experimental and Computational Study. J. Org. Chem. 2016, 81, 6157−6164. (369) Field, L. D.; Ward, A. J. Catalytic Hydrosilylation of Acetylenes Mediated by Phosphine Complexes of Cobalt(I), Rhodium(I), and Iridium(I). J. Organomet. Chem. 2003, 681, 91−97. (370) Huang, G.; Liu, P. Mechanism and Origins of LigandControlled Linear Versus Branched Selectivity of Iridium-Catalyzed Hydroarylation of Alkenes. ACS Catal. 2016, 6, 809−820. (371) Bhaskararao, B.; Sunoj, R. B. Asymmetric Dual Chiral Catalysis Using Iridium Phosphoramidites and Diarylprolinol Silyl Ethers: Insights into Stereodivergence. ACS Catal. 2017, 7, 6675− 6685. (372) Suzuki, A. Cross-Coupling Reactions Of Organoboranes: An Easy Way To Construct C−C Bonds (Nobel Lecture). Angew. Chem., Int. Ed. 2011, 50, 6722−6737. (373) Negishi, E.-I. Magical Power of Transition Metals: Past, Present, and Future (Nobel Lecture). Angew. Chem., Int. Ed. 2011, 50, 6738−6764. (374) Haas, D.; Hammann, J. M.; Greiner, R.; Knochel, P. Recent Developments in Negishi Cross-Coupling Reactions. ACS Catal. 2016, 6, 1540−1552. (375) Stille, J. K. The Palladium-Catalyzed Cross-Coupling Reactions of Organotin Reagents with Organic Electrophiles[New Synthetic Methods(58)]. Angew. Chem., Int. Ed. Engl. 1986, 25, 508− 524. (376) Chu, J.-H.; Lin, P.-S.; Wu, M.-J. Palladium(II)-Catalyzed Ortho Arylation of 2-Phenoxypyridines with Potassium Aryltrifluoroborates via C−H Functionalization. Organometallics 2010, 29, 4058−4065. (377) Li, W.; Yin, Z.; Jiang, X.; Sun, P. Palladium-Catalyzed Direct Ortho C−H Arylation of 2-Arylpyridine Derivatives with Aryltrimethoxysilane. J. Org. Chem. 2011, 76, 8543−8548. (378) Romero-Revilla, J. A.; García-Rubia, A.; Goméz Arrayás, R.; Fernández-Ibáñez, M. Á .; Carretero, J. C. Palladium-Catalyzed Coupling of Arene C−H Bonds with Methyl- and Arylboron Reagents Assisted by the Removable 2-Pyridylsulfinyl Group. J. Org. Chem. 2011, 76, 9525−9530. (379) Spangler, J. E.; Kobayashi, Y.; Verma, P.; Wang, D.-H.; Yu, J.Q. α-Arylation of Saturated Azacycles and N-Methylamines via Palladium(II)-Catalyzed C(sp3)−H Coupling. J. Am. Chem. Soc. 2015, 137, 11876−11879. (380) Shin, K.; Park, Y.; Baik, M.-H.; Chang, S. Iridium-Catalysed Arylation of C−H Bonds Enabled by Oxidatively Induced Reductive Elimination. Nat. Chem. 2018, 10, 218−224. (381) Sperger, T.; Sanhueza, I. A.; Kalvet, I.; Schoenebeck, F. Computational Studies of Synthetically Relevant Homogeneous Organometallic Catalysis Involving Ni, Pd, Ir, and Rh: An Overview of Commonly Employed DFT Methods and Mechanistic Insights. Chem. Rev. 2015, 115, 9532−9586. (382) Sperger, T.; Sanhueza, I. A.; Schoenebeck, F. Computation and Experiment: A Powerful Combination to Understand and Predict Reactivities. Acc. Chem. Res. 2016, 49, 1311−1319. (383) Poree, C.; Schoenebeck, F. A Holy Grail in Chemistry: Computational Catalyst Design: Feasible or Fiction? Acc. Chem. Res. 2017, 50, 605−608. AV

DOI: 10.1021/acs.chemrev.9b00073 Chem. Rev. XXXX, XXX, XXX−XXX

Chemical Reviews

Review

(384) Hickman, A. J.; Sanford, M. S. High-Valent Organometallic Copper and Palladium in Catalysis. Nature 2012, 484, 177−185. (385) Ball, N. D.; Kampf, J. W.; Sanford, M. S. Aryl-CF3 BondForming Reductive Elimination from Palladium(IV). J. Am. Chem. Soc. 2010, 132, 2878−2879. (386) Lundgren, R. J.; Stradiotto, M. Transition-Metal-Catalyzed Trifluoromethylation of Aryl Halides. Angew. Chem., Int. Ed. 2010, 49, 9322−9324. (387) Anstaett, P.; Schoenebeck, F. Reductive Elimination of ArCF3 from Bidentate PdII Complexes: A Computational Study. Chem. - Eur. J. 2011, 17, 12340−12346. (388) Cui, L.; Saeys, M. Aryl Fluoride Reductive Elimination from Pd II Complexes: A Descriptor to Guide Ligand Selection. ChemCatChem 2011, 3, 1060−1064. (389) Bakhmutov, V. I.; Bozoglian, F.; Gómez, K.; González, G.; Grushin, V. V.; Macgregor, S. A.; Martin, E.; Miloserdov, F. M.; Novikov, M. A.; Panetier, J. A.; Romashov, L. V. CF3−Ph Reductive Elimination from [(Xantphos)Pd(CF3)(Ph)]. Organometallics 2012, 31, 1315−1328. (390) Nielsen, M. C.; Bonney, K. J.; Schoenebeck, F. Computational Ligand Design for the Reductive Elimination of ArCF3 from a Small Bite Angle Pd(II) Complex: Remarkable Effect of a Perfluoroalkyl Phosphine. Angew. Chem., Int. Ed. 2014, 53, 5903−5906. (391) Grushin, V. V.; Marshall, W. J. Facile Ar−CF3 Bond Formation at Pd. Strikingly Different Outcomes of Reductive Elimination from [(Ph3P)2Pd(CF3)Ph] and [(Xantphos)Pd(CF3)Ph]. J. Am. Chem. Soc. 2006, 128, 12644−12645. (392) van Haaren, R. J.; Goubitz, K.; Fraanje, J.; van Strijdonck, G. P. F.; Oevering, H.; Coussens, B.; Reek, J. N. H.; Kamer, P. C. J.; van Leeuwen, P. W. N. M. An X-Ray Study of the Effect of the Bite Angle of Chelating Ligands on the Geometry of Palladium(allyl) Complexes: Implications for the Regioselectivity in the Allylic Alkylation. Inorg. Chem. 2001, 40, 3363−3372. (393) van Leeuwen, P. W. N. M.; Kamer, P. C. J.; Reek, J. N. H.; Dierkes, P. Ligand Bite Angle Effects in Metal-Catalyzed C−C Bond Formation. Chem. Rev. 2000, 100, 2741−2770. (394) Maiti, D.; Fors, B. P.; Henderson, J. L.; Nakamura, Y.; Buchwald, S. L. Palladium-Catalyzed Coupling of Functionalized Primary and Secondary Amines with Aryl and Heteroaryl Halides: Two Ligands Suffice in Most Cases. Chem. Sci. 2011, 2, 57−68. (395) Cho, E. J.; Senecal, T. D.; Kinzel, T.; Zhang, Y.; Watson, D. A.; Buchwald, S. L. The Palladium-Catalyzed Trifluoromethylation of Aryl Chlorides. Science 2010, 328, 1679−1681. (396) Nakanishi, W.; Yamanaka, M.; Nakamura, E. Reactivity and Stability of Organocopper(I), Silver(I), and Gold(I) Ate Compounds and Their Trivalent Derivatives. J. Am. Chem. Soc. 2005, 127, 1446− 1453. (397) Jiménez-Osés, G.; Vispe, E.; Roldán, M.; RodríguezRodríguez, S.; López-Ram-de-Viu, P.; Salvatella, L.; Mayoral, J. A.; Fraile, J. M. Stereochemical Outcome of Copper-Catalyzed C-H Insertion Reactions. An Experimental and Theoretical Study. J. Org. Chem. 2013, 78, 5851−5857. (398) Davies, H. M. L.; Hansen, T.; Churchill, M. R. Catalytic Asymmetric C−H Activation of Alkanes and Tetrahydrofuran. J. Am. Chem. Soc. 2000, 122, 3063−3070. (399) Grimme, S.; Antony, J.; Ehrlich, S.; Krieg, H. A Consistent and Accurate Ab Initio Parametrization of Density Functional Dispersion Correction (DFT-D) for the 94 Elements H−Pu. J. Chem. Phys. 2010, 132, 154104. (400) Vergote, T.; Nahra, F.; Merschaert, A.; Riant, O.; Peeters, D.; Leyssens, T. Mechanistic Insight into the (NHC)copper(I)-Catalyzed Hydrosilylation of Ketones. Organometallics 2014, 33, 1953−1963. (401) Solorio-Alvarado, C. R.; Wang, Y.; Echavarren, A. M. Cyclopropanation with Gold(I) Carbenes by Retro-Buchner Reaction from Cycloheptatrienes. J. Am. Chem. Soc. 2011, 133, 11952−11955. (402) Wang, Y.; McGonigal, P. R.; Herlé, B.; Besora, M.; Echavarren, A. M. Gold(I) Carbenes by Retro-Buchner Reaction: Generation and Fate. J. Am. Chem. Soc. 2014, 136, 801−809.

(403) Wang, Y.; Muratore, M. E.; Rong, Z.; Echavarren, A. M. Formal (4 + 1) Cycloaddition of Methylenecyclopropanes with 7Aryl-1,3,5-Cycloheptatrienes by Triple gold(I) Catalysis. Angew. Chem., Int. Ed. 2014, 53, 14022−14026. (404) Song, Z.; Liu, C.; Chen, X.; Yan, W.; Cao, Y.; Xie, H.; Lei, Q.; Fang, W. The Mechanisms for Triple Gold(I)-Catalyzed (4 + 1) Cycloaddition of Methylenecyclopropane with 7-Naphthyl-1,3,5Cycloheptatriene: Insight into from Density Functional Calculations. Comput. Theor. Chem. 2016, 1084, 25−35. (405) Li, M.-R.; Wang, G.-C. Computational Study on GoldCatalyzed (4 + 3) Intramolecular Cycloaddition of Trienyne: Mechanism, Reactivity and Selectivity. RSC Adv. 2016, 6, 73454− 73468. (406) Liu, Y.; Yu, Z.; Zhang, J. Z.; Liu, L.; Xia, F.; Zhang, J. Origins of Unique Gold-Catalysed Chemo- and Site-Selective C−H Functionalization of Phenols with Diazo Compounds. Chem. Sci. 2016, 7, 1988−1995. (407) Liu, Y.; Yu, Z.; Luo, Z.; Zhang, J. Z.; Liu, L.; Xia, F. Mechanistic Investigation of Aromatic C(sp2)-H and Alkyl C(sp3)-H Bond Insertion by Gold Carbenes. J. Phys. Chem. A 2016, 120, 1925− 1932. (408) Mkhalid, I. A. I.; Barnard, J. H.; Marder, T. B.; Murphy, J. M.; Hartwig, J. F. C−H. Activation for the Construction of C−B Bonds. Chem. Rev. 2010, 110, 890−931. (409) Hartwig, J. F. Borylation and Silylation of C−H Bonds: A Platform for Diverse C−H Bond Functionalizations. Acc. Chem. Res. 2012, 45, 864−873. (410) Neeve, E. C.; Geier, S. J.; Mkhalid, I. A. I.; Westcott, S. A.; Marder, T. B. Diboron(4) Compounds: From Structural Curiosity to Synthetic Workhorse. Chem. Rev. 2016, 116, 9091−9161. (411) Tagata, T.; Nishida, M. Aromatic C−H Borylation Catalyzed by Iridium/2,6-Diisopropyl-N-(2-Pyridylmethylene)aniline Complex. Adv. Synth. Catal. 2004, 346, 1655−1660. (412) Chen, H.; Schlecht, S.; Semple, T. C.; Hartwig, J. F. Thermal, Catalytic, Regiospecific Functionalization of Alkanes. Science 2000, 287, 1995−1997. (413) Ishiyama, T.; Takagi, J.; Ishida, K.; Miyaura, N.; Anastasi, N. R.; Hartwig, J. F. Mild Iridium-Catalyzed Borylation of Arenes. High Turnover Numbers, Room Temperature Reactions, and Isolation of a Potential Intermediate. J. Am. Chem. Soc. 2002, 124, 390−391. (414) Murphy, J. M.; Liao, X.; Hartwig, J. F. Meta Halogenation of 1,3-Disubstituted Arenes via Iridium-Catalyzed Arene Borylation. J. Am. Chem. Soc. 2007, 129, 15434−15435. (415) Hartwig, J. F. Regioselectivity of the Borylation of Alkanes and Arenes. Chem. Soc. Rev. 2011, 40, 1992−2002. (416) Liskey, C. W.; Hartwig, J. F. Iridium-Catalyzed Borylation of Secondary C−H Bonds in Cyclic Ethers. J. Am. Chem. Soc. 2012, 134, 12422−12425. (417) Li, Q.; Liskey, C. W.; Hartwig, J. F. Regioselective Borylation of the C−H Bonds in Alkylamines and Alkyl Ethers. Observation and Origin of High Reactivity of Primary C−H Bonds Beta to Nitrogen and Oxygen. J. Am. Chem. Soc. 2014, 136, 8755−8765. (418) Larsen, M. A.; Hartwig, J. F. Iridium-Catalyzed C−H Borylation of Heteroarenes: Scope, Regioselectivity, Application to Late-Stage Functionalization, and Mechanism. J. Am. Chem. Soc. 2014, 136, 4287−4299. (419) Nguyen, P.; Blom, H. P.; Westcott, S. A.; Taylor, N. J.; Marder, T. B. Synthesis and Structures of the First Transition-Metal Tris(boryl) Complexes: Iridium Complexes (η6-arene)Ir(BO2C6H4)3. J. Am. Chem. Soc. 1993, 115, 9329−9330. (420) Shimada, S.; Batsanov, A. S.; Howard, J. A. K.; Marder, T. B. Formation of Aryl- and Benzylboronate Esters by Rhodium-Catalyzed C−H Bond Functionalization with Pinacolborane. Angew. Chem., Int. Ed. 2001, 40, 2168−2171. (421) Kleeberg, C.; Dang, L.; Lin, Z.; Marder, T. B. A Facile Route to Aryl Boronates: Room-Temperature, Copper-Catalyzed Borylation of Aryl Halides with Alkoxy Diboron Reagents. Angew. Chem., Int. Ed. 2009, 48, 5350−5354. AW

DOI: 10.1021/acs.chemrev.9b00073 Chem. Rev. XXXX, XXX, XXX−XXX

Chemical Reviews

Review

(440) Hoang, G. L.; Takacs, J. M. Enantioselective γ-Borylation of Unsaturated Amides and Stereoretentive Suzuki-Miyaura CrossCoupling. Chem. Sci. 2017, 8, 4511−4516. (441) Tamura, H.; Yamazaki, H.; Sato, H.; Sakaki, S. IridiumCatalyzed Borylation of Benzene with Diboron. Theoretical Elucidation of Catalytic Cycle Including Unusual Iridium(V) Intermediate. J. Am. Chem. Soc. 2003, 125, 16114−16126. (442) Bickelhaupt, F. M.; Houk, K. N. Analyzing Reaction Rates with the Distortion/Interaction-Activation Strain Model. Angew. Chem., Int. Ed. 2017, 56, 10070−10086. (443) Green, A. G.; Liu, P.; Merlic, C. A.; Houk, K. N. Distortion/ Interaction Analysis Reveals the Origins of Selectivities in IridiumCatalyzed C−H Borylation of Substituted Arenes and 5-Membered Heterocycles. J. Am. Chem. Soc. 2014, 136, 4575−4583. (444) Boller, T. M.; Murphy, J. M.; Hapke, M.; Ishiyama, T.; Miyaura, N.; Hartwig, J. F. Mechanism of the Mild Functionalization of Arenes by Diboron Reagents Catalyzed by Iridium Complexes. Intermediacy and Chemistry of Bipyridine-Ligated Iridium Trisboryl Complexes. J. Am. Chem. Soc. 2005, 127, 14263−14278. (445) Petit, A.; Flygare, J.; Miller, A. T.; Winkel, G.; Ess, D. H. Transition-State Metal Aryl Bond Stability Determines Regioselectivity in Palladium Acetate Mediated C-H Bond Activation of Heteroarenes. Org. Lett. 2012, 14, 3680−3683. (446) Yang, L.; Semba, K.; Nakao, Y. para-Selective C−H Borylation of (Hetero)Arenes by Cooperative Iridium/Aluminum Catalysis. Angew. Chem. 2017, 129, 4931−4935. (447) Haines, B. E.; Saito, Y.; Segawa, Y.; Itami, K.; Musaev, D. G. Flexible Reaction Pocket on Bulky Diphosphine−Ir Complex Controls Regioselectivity in para-Selective C−H Borylation of Arenes. ACS Catal. 2016, 6, 7536−7546. (448) Cook, A. K.; Schimler, S. D.; Matzger, A. J.; Sanford, M. S. Catalyst-Controlled Selectivity in the C-H Borylation of Methane and Ethane. Science 2016, 351, 1421−1424. (449) Smith, K. T.; Berritt, S.; González-Moreiras, M.; Ahn, S.; Smith, M. R., III; Baik, M.-H.; Mindiola, D. J. Catalytic Borylation of Methane. Science 2016, 351, 1424−1427. (450) Ahn, S.; Sorsche, D.; Berritt, S.; Gau, M. R.; Mindiola, D. J.; Baik, M.-H. Rational Design of a Catalyst for the Selective Monoborylation of Methane. ACS Catal. 2018, 8, 10021−10031. (451) Park, Y.; Kim, Y.; Chang, S. Transition Metal-Catalyzed C−H Amination: Scope, Mechanism, and Applications. Chem. Rev. 2017, 117, 9247−9301. (452) Ullmann, F. Ueber Eine Neue Bildungsweise von Diphenylaminderivaten. Ber. Dtsch. Chem. Ges. 1903, 36, 2382−2384. (453) Ullmann, F. Ueber Eine Neue Darstellungsweise von Phenyläthersalicylsäure. Ber. Dtsch. Chem. Ges. 1904, 37, 853−854. (454) Ullmann, F.; Sponagel, P. Ueber Die Phenylirung von Phenolen. Ber. Dtsch. Chem. Ges. 1905, 38, 2211−2212. (455) Ullmann, F.; Illgen, E. Ü ber Carbazole Der AnthrachinonReihe. Ber. Dtsch. Chem. Ges. 1914, 47, 380−383. (456) Goldberg, I. Ueber Phenylirungen Bei Gegenwart von Kupfer Als Katalysator. Ber. Dtsch. Chem. Ges. 1906, 39, 1691−1692. (457) Goldberg, I. Ü ber Phenylierung von Primären Aromatischen Aminen. Ber. Dtsch. Chem. Ges. 1907, 40, 4541−4546. (458) Breslow, R.; Gellman, S. H. Intramolecular Nitrene CarbonHydrogen Insertions Mediated by Transition-Metal Complexes as Nitrogen Analogs of Cytochrome P-450 Reactions. J. Am. Chem. Soc. 1983, 105, 6728−6729. (459) Svastits, E. W.; Dawson, J. H.; Breslow, R.; Gellman, S. H. Functionalized Nitrogen Atom Transfer Catalyzed by Cytochrome P450. J. Am. Chem. Soc. 1985, 107, 6427−6428. (460) Müller, T. E.; Hultzsch, K. C.; Yus, M.; Foubelo, F.; Tada, M. Hydroamination: Direct Addition of Amines to Alkenes and Alkynes. Chem. Rev. 2008, 108, 3795−3892. (461) Cardona, F.; Goti, A. Metal-Catalysed 1,2-Diamination Reactions. Nat. Chem. 2009, 1, 269−275. (462) Lucet, D.; Le Gall, T.; Mioskowski, C. The Chemistry of Vicinal Diamines. Angew. Chem., Int. Ed. 1998, 37, 2580−2627.

(422) Tajuddin, H.; Harrisson, P.; Bitterlich, B.; Collings, J. C.; Sim, N.; Batsanov, A. S.; Cheung, M. S.; Kawamorita, S.; Maxwell, A. C.; Shukla, L.; Morris, J.; Lin, Z.; Marder, T. B.; Steel, P. G. IridiumCatalyzed C−H Borylation of Quinolines and Unsymmetrical 1,2Disubstituted Benzenes: Insights into Steric and Electronic Effects on Selectivity. Chem. Sci. 2012, 3, 3505−3515. (423) Cho, J.-Y.; Iverson, C. N.; Smith, M. R., III. Steric and Chelate Directing Effects in Aromatic Borylation. J. Am. Chem. Soc. 2000, 122, 12868−12869. (424) Cho, J.-Y.; Tse, M. K.; Holmes, D.; Maleczka, R. E., Jr; Smith, M. R., III. Remarkably Selective Iridium Catalysts for the Elaboration of Aromatic C-H Bonds. Science 2002, 295, 305−308. (425) Preshlock, S. M.; Ghaffari, B.; Maligres, P. E.; Krska, S. W.; Maleczka, R. E., Jr; Smith, M. R., III. High-Throughput Optimization of Ir-Catalyzed C−H Borylation: A Tutorial for Practical Applications. J. Am. Chem. Soc. 2013, 135, 7572−7582. (426) Preshlock, S. M.; Plattner, D. L.; Maligres, P. E.; Krska, S. W.; Maleczka, R. E., Jr.; Smith, M. R., III. A Traceless Directing Group for C−H Borylation. Angew. Chem., Int. Ed. 2013, 52, 12915−12919. (427) Ghaffari, B.; Preshlock, S. M.; Plattner, D. L.; Staples, R. J.; Maligres, P. E.; Krska, S. W.; Maleczka, R. E., Jr; Smith, M. R., III. Silyl Phosphorus and Nitrogen Donor Chelates for Homogeneous Ortho Borylation Catalysis. J. Am. Chem. Soc. 2014, 136, 14345− 14348. (428) Chattopadhyay, B.; Dannatt, J. E.; Andujar-De Sanctis, I. L.; Gore, K. A.; Maleczka, R. E., Jr; Singleton, D. A.; Smith, M. R., III. IrCatalyzed Ortho-Borylation of Phenols Directed by Substrate-Ligand Electrostatic Interactions: A Combined Experimental/in Silico Strategy for Optimizing Weak Interactions. J. Am. Chem. Soc. 2017, 139, 7864−7871. (429) Rablen, P. R.; Hartwig, J. F. Accurate Borane Sequential Bond Dissociation Energies by High-Level Ab Initio Computational Methods. J. Am. Chem. Soc. 1996, 118, 4648−4653. (430) Hartwig, J. F.; Cook, K. S.; Hapke, M.; Incarvito, C. D.; Fan, Y.; Webster, C. E.; Hall, M. B. Rhodium Boryl Complexes in the Catalytic, Terminal Functionalization of Alkanes. J. Am. Chem. Soc. 2005, 127, 2538−2552. (431) Teltewskoi, M.; Panetier, J. A.; Macgregor, S. A.; Braun, T. A Highly Reactive Rhodium(I)-Boryl Complex as a Useful Tool for C− H Bond Activation and Catalytic C-F Bond Borylation. Angew. Chem., Int. Ed. 2010, 49, 3947−3951. (432) Tobisu, M.; Chatani, N. Catalytic Reactions Involving the Cleavage of Carbon-Cyano and Carbon-Carbon Triple Bonds. Chem. Soc. Rev. 2008, 37, 300−307. (433) Tobisu, M.; Kinuta, H.; Kita, Y.; Rémond, E.; Chatani, N. Rhodium(I)-Catalyzed Borylation of Nitriles through the Cleavage of Carbon-Cyano Bonds. J. Am. Chem. Soc. 2012, 134, 115−118. (434) Jiang, Y.-Y.; Yu, H.-Z.; Fu, Y. Mechanistic Study of Borylation of Nitriles Catalyzed by Rh−B and Ir−B Complexes via C−CN Bond Activation. Organometallics 2013, 32, 926−936. (435) Kozuch, S.; Shaik, S. How to Conceptualize Catalytic Cycles? The Energetic Span Model. Acc. Chem. Res. 2011, 44, 101−110. (436) Esteruelas, M. A.; Oliván, M.; Vélez, A. Conclusive Evidence on the Mechanism of the Rhodium-Mediated Decyanative Borylation. J. Am. Chem. Soc. 2015, 137, 12321−12329. (437) Yang, Z.-D.; Pal, R.; Hoang, G. L.; Zeng, X. C.; Takacs, J. M. Mechanistic Insights into Carbonyl-Directed Rhodium-Catalyzed Hydroboration: Ab Initio Study of a Cyclic γ,δ-Unsaturated Amide. ACS Catal. 2014, 4, 763−773. (438) Shoba, V. M.; Thacker, N. C.; Bochat, A. J.; Takacs, J. M. Synthesis of Chiral Tertiary Boronic Esters by Oxime-Directed Catalytic Asymmetric Hydroboration. Angew. Chem., Int. Ed. 2016, 55, 1465−1469. (439) Hoang, G. L.; Yang, Z.-D.; Smith, S. M.; Pal, R.; Miska, J. L.; Pérez, D. E.; Pelter, L. S. W.; Zeng, X. C.; Takacs, J. M. Enantioselective Desymmetrization via Carbonyl-Directed Catalytic Asymmetric Hydroboration and Suzuki-Miyaura Cross-Coupling. Org. Lett. 2015, 17, 940−943. AX

DOI: 10.1021/acs.chemrev.9b00073 Chem. Rev. XXXX, XXX, XXX−XXX

Chemical Reviews

Review

(463) Saibabu Kotti, S. R. S.; Timmons, C.; Li, G. Vicinal Diamino Functionalities as Privileged Structural Elements in Biologically Active Compounds and Exploitation of Their Synthetic Chemistry. Chem. Biol. Drug Des. 2006, 67, 101−114. (464) Jindal, G.; Sunoj, R. B. Rational Design of Catalysts for Asymmetric Diamination Reaction Using Transition State Modeling. Org. Biomol. Chem. 2014, 12, 2745−2753. (465) Du, H.; Yuan, W.; Zhao, B.; Shi, Y. Catalytic Asymmetric Diamination of Conjugated Dienes and Triene. J. Am. Chem. Soc. 2007, 129, 11688−11689. (466) Jindal, G.; Sunoj, R. B. Mechanistic Insights into the Role of Chiral Ligands in Asymmetric Diamination Reactions. Chem. - Eur. J. 2012, 18, 7045−7049. (467) Uhe, A.; Hölscher, M.; Leitner, W. A Computational Study of Rhodium Pincer Complexes with Classical and Nonclassical Hydride Centres as Catalysts for the Hydroamination of Ethylene with Ammonia. Chem. - Eur. J. 2010, 16, 9203−9214. (468) Hölscher, M.; Uhe, A.; Leitner, W. Rhodium Catalyzed Hydroamination of C2H4 with NH3 with Pincer Derived PE(CH2CH2X)P Ligands − Fighting the Energy Span. J. Organomet. Chem. 2013, 748, 13−20. (469) Eilbracht, P.; Schmidt, A. M. Synthetic Applications of Tandem Reaction Sequences Involving Hydroformylation. In Catalytic Carbonylation Reactions; Beller, M., Ed.; Springer Berlin Heidelberg: Berlin, Heidelberg, 2006; pp 65−95. (470) Crozet, D.; Urrutigoïty, M.; Kalck, P. Recent Advances in Amine Synthesis by Catalytic Hydroaminomethylation of Alkenes. ChemCatChem 2011, 3, 1102−1118. (471) Crozet, D.; Gual, A.; McKay, D.; Dinoi, C.; Godard, C.; Urrutigoïty, M.; Daran, J.-C.; Maron, L.; Claver, C.; Kalck, P. Interplay between Cationic and Neutral Species in the RhodiumCatalyzed Hydroaminomethylation Reaction. Chem. - Eur. J. 2012, 18, 7128−7140. (472) Crozet, D.; Kefalidis, C. E.; Urrutigoïty, M.; Maron, L.; Kalck, P. Hydroaminomethylation of Styrene Catalyzed by Rhodium Complexes Containing Chiral Diphosphine Ligands and Mechanistic Studies: Why Is There a Lack of Asymmetric Induction? ACS Catal. 2014, 4, 435−447. (473) Villa-Marcos, B.; Xiao, J. Metal and Organo-Catalysed Asymmetric Hydroaminomethylation of Styrenes. Chin. J. Catal. 2015, 36, 106−112. (474) Chen, C.; Jin, S.; Zhang, Z.; Wei, B.; Wang, H.; Zhang, K.; Lv, H.; Dong, X.-Q.; Zhang, X. Rhodium/Yanphos-Catalyzed Asymmetric Interrupted Intramolecular Hydroaminomethylation of Trans1,2-Disubstituted Alkenes. J. Am. Chem. Soc. 2016, 138, 9017−9020. (475) Jat, J. L.; Paudyal, M. P.; Gao, H.; Xu, Q.-L.; Yousufuddin, M.; Devarajan, D.; Ess, D. H.; Kürti, L.; Falck, J. R. Direct Stereospecific Synthesis of Unprotected N−H and N−Me Aziridines from Olefins. Science 2014, 343, 61−65. (476) Ajitha, M. J.; Huang, K.-W.; Kwak, J.; Kim, H. J.; Chang, S.; Jung, Y. A Potential Role of a Substrate as a Base for the Deprotonation Pathway in Rh-Catalysed C−H Amination of Heteroarenes: DFT Insights. Dalton Trans 2016, 45, 7980−7985. (477) Park, Y.; Park, K. T.; Kim, J. G.; Chang, S. Mechanistic Studies on the Rh(III)-Mediated Amido Transfer Process Leading to Robust C−H Amination with a New Type of Amidating Reagent. J. Am. Chem. Soc. 2015, 137, 4534−4542. (478) Park, S. H.; Kwak, J.; Shin, K.; Ryu, J.; Park, Y.; Chang, S. Mechanistic Studies of the Rhodium-Catalyzed Direct C−H Amination Reaction Using Azides as the Nitrogen Source. J. Am. Chem. Soc. 2014, 136, 2492−2502. (479) Hennessy, E. T.; Liu, R. Y.; Iovan, D. A.; Duncan, R. A.; Betley, T. A. Iron-Mediated Intermolecular N-Group Transfer Chemistry with Olefinic Substrates. Chem. Sci. 2014, 5, 1526−1532. (480) Manca, G.; Gallo, E.; Intrieri, D.; Mealli, C. DFT Mechanistic Proposal of the Ruthenium Porphyrin-Catalyzed Allylic Amination by Organic Azides. ACS Catal. 2014, 4, 823−832.

(481) Du Bois, J. Rhodium-Catalyzed C−H Amination - An Enabling Method for Chemical Synthesis. Org. Process Res. Dev. 2011, 15, 758−762. (482) Wang, J.; Zhao, C.; Weng, Y.; Xu, H. Insight into the Mechanism and Site-Selectivity of Rh2II,II(esp)2-Catalyzed Intermolecular C−H Amination. Catal. Sci. Technol. 2016, 6, 5292−5303. (483) Hartwig, J. F. Discovery and Understanding of TransitionMetal-Catalyzed Aromatic Substitution Reactions. Synlett 2006, 2006, 1283−1294. (484) Salvatore, R. N.; Nagle, A. S.; Jung, K. W. Cesium Effect: High Chemoselectivity in Direct N-Alkylation of Amines. J. Org. Chem. 2002, 67, 674−683. (485) Balcells, D.; Nova, A.; Clot, E.; Gnanamgari, D.; Crabtree, R. H.; Eisenstein, O. Mechanism of Homogeneous Iridium-Catalyzed Alkylation of Amines with Alcohols from a DFT Study. Organometallics 2008, 27, 2529−2535. (486) Hesp, K. D.; Tobisch, S.; Stradiotto, M. [Ir(COD)Cl]2 as a Catalyst Precursor for the Intramolecular Hydroamination of Unactivated Alkenes with Primary Amines and Secondary Alkyl- or Arylamines: A Combined Catalytic, Mechanistic, and Computational Investigation. J. Am. Chem. Soc. 2010, 132, 413−426. (487) Park, Y.; Heo, J.; Baik, M.-H.; Chang, S. Why Is the Ir(III)Mediated Amido Transfer Much Faster Than the Rh(III)-Mediated Reaction? - A Combined Experimental and Computational Study. J. Am. Chem. Soc. 2016, 138, 14020−14029. (488) Hwang, Y.; Park, Y.; Chang, S. Mechanism-Driven Approach To Develop a Mild and Versatile C−H Amidation through IrIII Catalysis. Chem. - Eur. J. 2017, 23, 11147−11152. (489) Hong, S. Y.; Park, Y.; Hwang, Y.; Kim, Y. B.; Baik, M.-H.; Chang, S. Selective Formation of γ-Lactams via C-H Amidation Enabled by Tailored Iridium Catalysts. Science 2018, 359, 1016− 1021. (490) Toulgoat, F.; Alazet, S.; Billard, T. Direct Trifluoromethylthiolation Reactions: The “Renaissance” of an Old Concept. Eur. J. Org. Chem. 2014, 2014, 2415−2428. (491) Liang, T.; Neumann, C. N.; Ritter, T. Introduction of Fluorine and Fluorine-Containing Functional Groups. Angew. Chem., Int. Ed. 2013, 52, 8214−8264. (492) Landelle, G.; Panossian, A.; Pazenok, S.; Vors, J.-P.; Leroux, F. R. Recent Advances in Transition Metal-Catalyzed Csp2-Monofluoro-, Difluoro-, Perfluoromethylation and Trifluoromethylthiolation. Beilstein J. Org. Chem. 2013, 9, 2476−2536. (493) Yin, G.; Kalvet, I.; Schoenebeck, F. Trifluoromethylthiolation of Aryl Iodides and Bromides Enabled by a Bench-Stable and Easy-toRecover Dinuclear Palladium(I) Catalyst. Angew. Chem., Int. Ed. 2015, 54, 6809−6813. (494) Yin, G.; Kalvet, I.; Englert, U.; Schoenebeck, F. Fundamental Studies and Development of Nickel-Catalyzed Trifluoromethylthiolation of Aryl Chlorides: Active Catalytic Species and Key Roles of Ligand and Traceless MeCN Additive Revealed. J. Am. Chem. Soc. 2015, 137, 4164−4172. (495) Dürr, A. B.; Yin, G.; Kalvet, I.; Napoly, F.; Schoenebeck, F. Nickel-Catalyzed Trifluoromethylthiolation of Csp2-O Bonds. Chem. Sci. 2016, 7, 1076−1081. (496) Kalvet, I.; Guo, Q.; Tizzard, G. J.; Schoenebeck, F. When Weaker Can Be Tougher: The Role of Oxidation State (I) in P- vs NLigand-Derived Ni-Catalyzed Trifluoromethylthiolation of Aryl Halides. ACS Catal. 2017, 7, 2126−2132. (497) Figg, T. M.; Webb, J. R.; Cundari, T. R.; Gunnoe, T. B. Carbon-Oxygen Bond Formation via Organometallic Baeyer-Villiger Transformations: A Computational Study on the Impact of Metal Identity. J. Am. Chem. Soc. 2012, 134, 2332−2339. (498) Webb, J. R.; Bolaño, T.; Gunnoe, T. B. Catalytic OxyFunctionalization of Methane and Other Hydrocarbons: Fundamental Advancements and New Strategies. ChemSusChem 2011, 4, 37−49. (499) Figg, T. M.; Cundari, T. R.; Gunnoe, T. B. Non-Redox OxyInsertion via Organometallic Baeyer−Villiger Transformations: A Computational Hammett Study of Platinum(II) Complexes. Organometallics 2011, 30, 3779−3785. AY

DOI: 10.1021/acs.chemrev.9b00073 Chem. Rev. XXXX, XXX, XXX−XXX

Chemical Reviews

Review

(500) Pouy, M. J.; Milczek, E. M.; Figg, T. M.; Otten, B. M.; Prince, B. M.; Gunnoe, T. B.; Cundari, T. R.; Groves, J. T. Flavin-Catalyzed Insertion of Oxygen into Rhenium-Methyl Bonds. J. Am. Chem. Soc. 2012, 134, 12920−12923. (501) Paier, J.; Marsman, M.; Kresse, G. Why Does the B3LYP Hybrid Functional Fail for Metals? J. Chem. Phys. 2007, 127, 024103. (502) Sousa, S. F.; Fernandes, P. A.; Ramos, M. J. General Performance of Density Functionals. J. Phys. Chem. A 2007, 111, 10439−10452. (503) Kruse, H.; Goerigk, L.; Grimme, S. Why the Standard B3LYP/ 6-31G* Model Chemistry Should Not Be Used in DFT Calculations of Molecular Thermochemistry: Understanding and Correcting the Problem. J. Org. Chem. 2012, 77, 10824−10834. (504) Khungar, B.; Roy, A.; Kumar, A.; Sadhu, B.; Sundararajan, M. Predicting the Redox Properties of Uranyl Complexes Using Electronic Structure Calculations. Int. J. Quantum Chem. 2017, 117, e25370. (505) Sundararajan, M.; Neese, F. Detailed QM/MM Study of the Electron Paramagnetic Resonance Parameters of Nitrosyl Myoglobin. J. Chem. Theory Comput. 2012, 8, 563−574. (506) Sundararajan, M. Quantum Chemical Challenges for the Binding of Simple Alkanes to Supramolecular Hosts. J. Phys. Chem. B 2013, 117, 13409−13417. (507) Mardirossian, N.; Head-Gordon, M. Survival of the Most Transferable at the Top of Jacob’s Ladder: Defining and Testing the ωB97M(2) Double Hybrid Density Functional. J. Chem. Phys. 2018, 148, 241736. (508) Peng, Q.; Duarte, F.; Paton, R. S. Computing Organic Stereoselectivity - from Concepts to Quantitative Calculations and Predictions. Chem. Soc. Rev. 2016, 45, 6093−6107. (509) Luccarelli, J.; Paton, R. S. Hydrogen-Bond Dependent Conformational Switching: A Computational Challenge from Experimental Thermochemistry. J. Org. Chem. 2019, 84, 613−621. (510) Brueckner, A. C.; Ogba, O. M.; Snyder, K. M.; Richardson, H. C.; Cheong, P. H.-Y. Conformational Searching for Complex, Flexible Molecules. In Applied Theoretical Organic Chemistry; World Scientific (Europe), 2017; pp 147−164.

AZ

DOI: 10.1021/acs.chemrev.9b00073 Chem. Rev. XXXX, XXX, XXX−XXX