Mechanistic Insights into the Ruthenium-Catalyzed [4 + 1] Annulation

Article Cite This: Organometallics XXXX, XXX, XXX−XXX

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Mechanistic Insights into the Ruthenium-Catalyzed [4 + 1] Annulation of Benzamides and Propargyl Alcohols by DFT Studies Baoping Ling,* Yuxia Liu, Yuan-Ye Jiang, Peng Liu, and Siwei Bi* School of Chemistry and Chemical Engineering, Qufu Normal University, Qufu 273165, People’s Republic of China

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S Supporting Information *

ABSTRACT: The mechanism of ruthenium-catalyzed [4 + 1] annulation of benzamide and propargyl alcohol has been investigated by density functional theory calculations. The reaction undergoes N−H and C−H deprotonations by a concerted metalation-deprotonation mechanism to afford a 5membered ruthenacyclic species, which then undergoes ring expansion by alkyne insertion to deliver a 7-membered ring intermediate. Our study focused on how the successive hydrogen migrations take place that remains unclear. The 1,2proton migration and 1,3-proton transfer from O to C are successively finished by using acetate anion as a shuttle (a stepwise process). In contrast to the experimental proposal that the reaction experiences a Ru(II)−Ru(0)−Ru(II) transformation, our study unveiled a Ru(II)−Ru(IV)−Ru(II) transformation in the reaction. In addition, our calculations suggested that the EtO−N bond cleavage rather than the C−H activation is likely to be the rate-determining step for the entire reaction, which is not in contradiction with the experimentally reported kinetic isotope effect values.

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INTRODUCTION Selective construction of C−C and C−X (X = heteroatoms) bonds is one of the main challenges in synthetic chemistry.1 Transition-metal-catalyzed cross-coupling reactions have emerged as a powerful tool to build molecular complexity.2 The coupling of nucleophilic and electrophilic centers of these reactions features an electroneutral process. However, this method needs prefunctionalization of the substrate and the resulting byproducts containing elements such as boron, silicon, tin, or zinc are not easy to separate. Oxidative cross coupling with an oxidant involved is a cleaner alternative to the traditional cross-coupling reactions, which does not require prefunctionalization and does not lead to waste. Transition-metal-catalyzed cycloaddition via oxidative cross coupling is a powerful approach to access bioactive heterocyclic compounds.3 One class of typical transition-metal-catalyzed intermolecular annulations have emerged widely with internal alkynes and aromatic compounds as coupling partners. The internal alkynes generally serve as two-carbon reaction partners4 but seldom as one-carbon reaction partners.5 Very recently, Zhou, Liu, and co-workers developed Ru-catalyzed redoxneutral [4 + 1] annulation of benzamides and propargyl alcohols, in which propargyl alcohol act as one-carbon units, as shown in Scheme 1.6 This is the first example involving the combination of arene C−H activation with cheap ruthenium as the catalyst and intermolecular [4 + 1] annulation with internal alkynes. The isoindolinone derivatives formed in the reaction represent some of the most prevalent scaffolds in pharmaceuticals and bioactive natural products.7 These reactions feature © XXXX American Chemical Society

Scheme 1. Title Reaction

inexpensive ruthenium catalyst, mild reaction conditions, gramscale synthesis, and N-substituted quaternary isoindolinones. On the basis of the experimental observations, a plausible mechanism has been proposed by the authors, as shown in Scheme 2.6 First, the deprotonations of benzamide take place catalyzed by the Ru(II) catalyst; then, alkyne insertion gives a 7membered ring complex II. Subsequently, the intermediate II undergoes hydrogen migration and reductive elimination to afford the intermediate IV, which is followed by oxidative addition and protonation to yield the product and regenerate the catalyst. From II, the alternative pathway is that the direct reductive elimination, N−O(Et) bond cleavage, and protonation sequentially proceed to generate byproduct 4a and release the catalyst. However, the detailed mechanism and the role of base are elusive. Theoretical and computational investigation on the newly developed Ru-catalyzed redoxneutral [4 + 1] annulation of benzamides and propargyl alcohols is necessary and valuable because further theoretical insights could provide a deeper understanding for these reactions and Received: October 24, 2018

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DOI: 10.1021/acs.organomet.8b00769 Organometallics XXXX, XXX, XXX−XXX

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Organometallics

The different computational methods, such as B3LYP12/ SMD,13 M06/PCM,14 and M06/SMD were used to calculate the energy profiles for N−H deprotonation, isomerization, and C−H activation at the same level of theory. Full optimization in dichloroethane (DCE) with M06/SMD was also tested. The calculated data shows that the single-point calculation in DCE with M06/SMD was suitable for the system (Supporting Information Figure S1). Vibrational frequencies were calculated at the same level of theory to verify all stationary points as minima (no imaginary frequency) or first-order saddle points (only one imaginary frequency) and also obtain the thermodynamic corrections at 298.15 K. Intrinsic reaction coordinate calculations were also conducted to confirm that each transition state connects two relevant minima.15 The solution single-point energies were obtained by using a self-consistent reaction field (SCRF) with the SMD model based on the optimized structures. Dichloroethane (ε = 10.125) was employed as the solvent, corresponding to the original experimental conditions. All SCRF calculations were carried out at the M06 level using a larger basis set of SDD16 with f polarization function for Ru and the 6-311++G(d,p) basis set for other atoms. Unless stated otherwise, the solution-phase Gibbs free energies (ΔGsol) in the following discussion are calculated by adding the thermodynamic corrections in the gas phase to the solution-phase singlepoint energies.

Scheme 2. Plausible Mechanism Proposed by Liu et al.

valuable information for designing new related transition-metalcatalyzed annulation reactions. The density functional theory (DFT) study in the current study revealed that some elementary steps were involved in the reaction mechanism, such as the Hbonding-stabilized N−H deprotonation and regioselectivity of alkyne insertion and AcOH-assisted N−OR bond cleavage. These insights are expected to be considered or utilized in developing new catalytic reactions given that the aforementioned elementary steps are involved.

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RESULTS AND DISCUSSION Relative Stabilities of Various [RuCl2(p-cymene)]2 Adducts. In this reaction system, five species are included: the catalyst [RuCl2(p-cymene)]2, the benzamide substrate, propargyl alchohol, the base additive CsOAc, and the solvent dichloroethene. Both substrates and the base additive can coordinate with the catalyst. Thus, the relative stabilities of various [RuCl2(p-cymene)]2 adducts should be considered. All of the possible [RuCl2(p-cymene)]2 adducts formed with the species mentioned above were calculated (Figure S2 in the Supporting Information). The calculation results display that (pcymene)Ru(OAc)2 (Cat 1 in Figure 1) is found to be the most stable and used as the active catalyst in our calculations. The

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COMPUTATIONAL DETAILS All DFT calculations were performed using Gaussian 09 program.8 Geometry optimizations were conducted with the M06 hybrid functional9 in gas phase. The LANL2DZ basis set10 was used for Ru atom and the 6-31G(d,p) basis set for the other atoms. Polarization functions were added for Ru (ζf = 1.235).11

Figure 1. Gibbs free-energy profile of N−H deprotonation, isomerization, C−H activation, and alkyne insertion into Ru−C bond involved in the reactions from the catalyst to the intermediate II in Scheme 1. The relative Gibbs energies and relative enthalpic energies (in parentheses) are given in kcal/mol. L6 refers to p-cymene ligand donating 6 electrons. B


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Organometallics

Figure 2. Structure (A) and lowest unoccupied molecular orbital + 2 (B) of the alkyne 2a with spatial plots and atomic contributions (isovalue = 0.02).

process (Figure 1). As shown in the deprotonation transition structure of TS3, there is a H···OEt hydrogen bond (1.84 Å). For comparison, complex 2′ derived from 2 is designed, where the ethoxyl in 2 is replaced by a methyl group. Then, we performed a N···H distance scan of 2′ and found that the potential energy rises constantly (Figure S3B). In other words, no transition state is present, indirectly supporting the role of ethoxyl in TS3. Additionally, the acidity of complex 2 is stronger than that of 2′ because the electron density in the N atom of N− OEt is clearly lower than that in the N atom of N−Me due to higher electronegativity of O atom compared with methyl carbon atom. This further indicates that the ethoxyl plays a crucial role in N−H deprotonation. The regioselectivity for alkyne insertion was also considered and examined. Theoretical explanations for regioselective alkyne insertion into TM−C bond have been reported previously, which are closely related to the different electron densities at the two acetylenic carbon atoms of the substrate alkyne.18 As shown in Figure 1, insertion of the asymmetric alkyne into the Ru−C bond of 8 involves two possibilities. Step 9 → 11 finishes the insertion with the methyl-substituted olefinic carbon coupling with phenyl carbon, whereas step 9′ → 11′ features the methylsubstituted olefinic carbon coupling with the Ru center. The former insertion with a barrier of 13.4 kcal/mol, which leads to the formation of the desired product, is slightly not favored over the latter insertion with a barrier of 12.7 kcal/mol. However, TS10 is lower than TS10′ by 1.9 kcal/mol in Gibbs free energy and 3.5 kcal/mol in enthalpy, which coincides with the experimental observations. We attribute the relative stability of the two transition states to the hydrogen-bonding formation in the insertion step 9 → 11. The computed EtO···HO distances are 1.80, 1.86, and 1.93 Å, respectively. The presence of the hydrogen bonding in the step 9 → 11 lowers the insertion energy profile and thereby leads to the regioselective generation of the experimental product. The regioselectivity of alkyne insertion into the Ru−C bond can be further understood in terms of molecular orbital interactions. The insertion can be viewed as the nucleophilic attack of the carbon from Ru−C at the alkynyl carbon atom of the alkyne. Thus, the larger orbital coefficient of the π* anti-bonding orbital of the alkyne favors the insertion. As calculated, the coefficients of the alkynyl C17 and

Scheme 3. Possible Reactions Proposed Starting with Insertion Product 11

geometry of the catalyst shows that one of the acetates is bidentate whereas the other is monodentate, indicating that there are three coordination sites on the Ru center except for the η̧6-coordination of p-cymene. Formation Mechanism of the 7-Membered Ruthenacycle Intermediate 11. The sequential N−H deprotonation (Cat 1 → 5), C(sp2)-H activation, via a concerted metalationdeprotonation (CMD) process (5 → 8), and alkyne insertion (8 → 11) have been investigated experimentally and theoretically.17 The reversed sequence, i.e., C−H activation followed by N−H deprotonation, was also considered. However, this possibility was excluded owing to higher energy barriers of C− H activation (Figure S3A). It is noteworthy that the ethoxyl bound to nitrogen helps complete the N−H deprotonation C


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Figure 3. Gibbs free-energy profile associated with the hydrogen migrations in the presence of acetate. The relative Gibbs energies and relative enthalpic energies (in parentheses) are given in kcal/mol.

2, the abstraction of the allylic proton by the ruthenium complex and 1,2-hydride migration were observed in experiments, which has been examined with the aid of computations (Supporting Information Figures S4 and S5A,C). The calculated results indicated that two pathways were infeasible due to the high energy barriers. Additionally, we have designed other processes: 1,3-hydrogen migration (Figure S5B) and acetate acid-assisted 1,2-hydrogen migration (Figure S5D,E) can also be excluded due to considerable high barriers involved. Starting with 11 (i.e., II in Scheme 2), diversified reactions were also proposed and examined. Scheme 3 shows the possible reactions together with calculated overall activation barriers. In case (a), a direct EtO−N oxidative addition to Ru(II) is proposed, giving the Ru(IV) complex a-14. PivO−N oxidative additions similar to those in Rh(III) were reported previously and found to be feasible,20 but RO−N (R = alkyl) oxidative additions similar to those in Rh(III) or Ru(II) are rare. Clearly, case (a) is difficult to occur with an activation barrier computed as high as 31.1 kcal/mol and the energy profiles are given in Figure S6. For comparison, the energy barrier is calculated to only be 6.9 kcal/mol if the ethyl is substituted by pivaloyl (Figure S7), which agrees well with the previous reports.20 In case (b) of Scheme 3, electrophilic attack by HOAc toward the ethoxyl oxygen is assumed to break the EtO−N bond. This proposal is unavailable because the overall activation barrier to the EtO−N bond breaking is computed to be as high as 35.3 kcal/mol. In case (c), direct N−C(sp2) reductive elimination from Ru(II) is suggested to generate a 6-membered heterocyclic Ru(0) complex c-14. The activation barrier calculated is

Scheme 4. Possible Reactions Proposed Starting with 20

16 are 29.5 and 20.2%,17d,19 respectively. Clearly, the insertion with C17 attacking at the carbon of Ru−C is favored over with C16, which is supportive of the above calculated regioselectivity (Figure 2). Protonation Mechanism of the Ru-Bonded sp 2 Carbon. For the hydrogen migration step II → III in Scheme D


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Figure 4. Gibbs free-energy profile associated with N−O bond cleavage, subsequent product formation, and catalyst regeneration. The relative Gibbs energies and relative enthalpic energies (in parentheses) are given in kcal/mol.

N−O Bond Cleavage Mechanism. For the N−O bond cleavage in the transition-metal-catalyzed reactions similar to the studied reaction, the substituent attached at the nitrogen atom is normally carboxylate, such as acetate and pivalate.20,21 To the best of our knowledge, the N−OR (R = alkyl) bond cleavage in such kind of reactions is rare.20,22 Lin and co-workers reported the Rh(III)-catalyzed intramolecular C−H activation of Osubstituted N-hydroxybenzamides and cyclohexadienone-containing 1,6-enynes. When OR is OPiv, the N−OPiv bond cleaves easily, whereas when OR is OMe, the N−OMe bond remains intact.23 Xia and co-workers have studied the N−OMe cleavage involved in the Rh(III)-catalyzed C−H activation of benzamide derivatives, and they also found that acetate acid plays a crucial role in breaking the N−O bond.20d In the current study, the RO−N (R = ethyl) cleavage is to be investigated. Starting with 20, three possible reaction pathways were proposed and the corresponding energy barrier were also calculated, as shown in Scheme 4. In case (a), the N−C bond formation via a direct reductive elimination to generate Ru(0) complex a-22 is ruled out because the overall energy barrier is extremely high, 75.2 kcal/mol. In case (b), a direct EtO−N oxidative addition to Ru(II) to yield the Ru(IV) complex b-23 was also explored with and without AcOH and this step requires an overall energy barrier of 54.4 and 49.5 kcal/mol, respectively. Thus, this pathway is also excluded. The detailed energy profiles of cases (a) and (b) were displayed in the Supporting Information Figure S10. In case (c), electrophilic attack by acetate acid on the ethoxyl oxygen takes place to promote the cleavage of EtO−N bond; the overall energy barrier is calculated to be 24.3 kcal/mol, and the detailed energy profile is given in

moderate (23.7 kcal/mol), but the subsequent reactions have higher activation energies (41.2 or 41.5 kcal/mol). The complete energy profiles of cases (b) and (c) were presented in the Supporting Information Figures S8 and S9. In case (d), acetate that was added in the experiment is used to abstract a proton from the HO-bonded carbon. The overall activation barrier is calculated to be 17.2 kcal/mol, and the detailed calculation results are given in Figure 3. Therefore, we concluded that case (d) is the most suitable pathway starting with 11. As shown in Figure 3, the intermediate 11 abstracts a proton from the HO-bonded carbon with the assistance with AcO− from 11 → 14 via TS13. However, the formation of intermediate 17′ is more facile than the formation of 14 (Figure S4). Subsequently, the transformation from 17′ to 19′ is less favored kinetically than that from 11 to 14. Therefore, we suggest that there is equilibrium between 11 and 17′ and eventually the reaction tends to undergo the path toward 14 rather than 19′. After the C−H deprotonation by acetate in 14, an enol-keto transformation via TS15 readily takes place with acetate acid acting as a shuttle, giving intermediate 16. Then, with the assistance of acetate acid again, protonation of carbonyl-bonded carbon is followed to afford intermediate 18. Then, the resultant acetate anion is dissociated to yield a more stable species 20, which is stabilized by an agostic interaction between Ru and C−H bond with the Ru−C and Ru−H distances being 2.370 and 1.899 Å. The highest energy barrier along the pathway is found to be 17.2 kcal/mol, corresponding to the difference between TS13 and 11 (C−H deprotonation by AcO−). It is clear that the introduction of acetate is of great importance in lowering the energy barrier of the reaction. E


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Organometallics Scheme 5. Modified Mechanism of Ruthenium-Catalyzed Annulation of Benzamide and Propargyl Alcohola

a

The blue pathway is presented by Liu et al., and the red pathway is proposed on the basis of our calculations.

exchanging acetate acid with acetate via TS27′ to achieve the intermediate 28′, then 28′ undergoes isomerization and the N− C reductive elimination via TS30′ to yield the product P. This pathway is disfavored because the overall energy barrier was computed to be 33.9 kcal/mol, which is defined by the energy gap between TS30′ and 24′ and increased by 26.0 kcal/mol as compared to that of 23 → 27 (Figure 4). Primary Kinetic Isotope Effect (KIE) and the RateDetermining Step. To further explore the C−H activation process, Liu and group performed two types of kinetic isotope effect (KIE) experiments. One is the two parallel reactions with a measured KIE value of 1.7, and the other is the intermolecular competitive reaction with a measured KIE value of 4.0.6a The small KIE value of 1.7 measured from the parallel experiments agrees well with our calculation results that the C−H bond activation is not rate-determining. The relatively high KIE value of 4.0 is also understandable because the C−H activation step is irreversible. Specifically, when the C−H bond cleavage is irreversible, the kinetic differences between C−H and C−D bond cleavage still differentiate the generation rate of undeuterated and deuterated products even if the C−H bond cleavage is not the rate-determining step, leading to a primary KIE effect.24 As shown in Figure 1, the relative free energies of the transition states (TS3 and TS6) for the N−H deprotonation and the C−H activation are 17.0 and 11.4 kcal/mol, clearly indicating that the C−H activation is not the rate-determining step. Additionally, we have calculated the KIE of the EtO−N

Figure 4. Accordingly, we speculated that the most favorable pathway of EtO−N cleavage is case (c). As shown in Figure 4, the coordination of acetate acid to Ru(II) complex 20 leads to a C−H bond cleavage by agostic interaction. Then, the Ru(II) complex 21 is oxidized to Ru(IV) complex 23 by acetate acid via a 7-membered ring transition state TS22. This step requires an energy barrier of 24.3 kcal/ mol, which is easier than those along the two pathways mentioned in Scheme 4. The triplet state of 23 has also been calculated and is found to have energy similar to that in the singlet state. Thus, both electronic states might be co-present (see the calculated data in Table S1 of the Supporting Information). From 23, prior to the reductive elimination, a conformational change is required to make the N atom adjacent to the Ru-bonded C atom (23 via TS24 to 25). Then, the reductive elimination is followed (25 via TS26 to 27), resulting in formation of the significantly stable intermediate 27. This process overcomes the Gibbs energy of activation of 7.9 kcal/ mol. Subsequently, the amino protonation occurs by the exchange of acetate acid with alcohol to generate the product P and the catalyst 1 (Cat 1) concurrently. This process is much easier to occur with a barrier of only 2.4 kcal/mol (step 27 → P). The entire catalytic cycle is favorable thermodynamically to be exergonic by 90.5 kcal/mol than the initial state. Starting from 23, we have also considered the possible pathway with a reversed sequence, i.e., the amino protonation prior to the N−C reductive elimination, and the complete energy profile is given in Figure S11. We attempted to first protonate the amino by F


Organometallics

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bond cleavage (20 → TS22 in Figure 4) on the basis of the Eyring equation25

ASSOCIATED CONTENT

* Supporting Information S

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.organomet.8b00769. Results calculated by different computational methods, relative stabilities of various Ru(OAc)2 adducts, relaxed surface scan, energy profile for N−O oxidative addition with the substituent of pivaloyl, calculated energy profiles of unfavored pathways (PDF) Cartesian coordinates and calculated energies (in hartrees) of all structures presented herein (XYZ)

≠ κk T k = B e−(ΔG / RT ) h

where kB is Boltzmann’s constant, h is Planck’s constant, ΔG≠ is the Gibbs energy of activation, and κ is the transmission coefficient that is often assumed to be equal to one. The freeenergy barriers from 20 → TS22 are calculated to be 24.3 kcal/ mol without deuterium and 24.6 kcal/mol with deuterium, respectively. Thus, the KIE is calculated to be 1.6, suggesting that the C−H activation is not rate-determining. For the entire catalytic cycle, the EtO−N bond cleavage needs to overcome an overall energy barrier of 24.3 kcal/mol (from 20 → 23 via TS22 in Figure 4), which is the rate-determining step. In summary, the [4 + 1] annulation of benzamide and propargyl alcohol catalyzed by ruthenium catalyst has been given in Scheme 5. First, benzamide coordinates to the active catalyst 1 to give the intermediate 8 through N−H deprotonation and C−H activation by CMD. Alkyne insertion of 2a into the Ru−C bond of 8 generates the 7-membered Ru(II) complex 11. Then, acetate-assisted C−H deprotonation, enol-keto conversion, and protonation with the help of acetate acid occur sequentially to generate the intermediate 19. After ligand exchange, EtO−N bond cleavage takes place to yield the Ru(IV) complex 23 through the ethoxyl protonation by acetate acid and this process is likely to be the rate-determining step. The Ru(IV) complex 23 undergoes the N−C reductive elimination to produce the Ru(II) complex 27. Finally, the 5membered ring intermediate 27 is protonated again by acetate acid to release the product P and regenerate the catalyst.

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AUTHOR INFORMATION

Corresponding Authors

*E-mail: [email protected] (B.L.). *E-mail: [email protected] (S.B.). ORCID

Baoping Ling: 0000-0001-5033-3514 Yuxia Liu: 0000-0003-1139-8563 Yuan-Ye Jiang: 0000-0002-4763-9173 Siwei Bi: 0000-0003-3969-7012 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS This work was supported by the National Natural Science Foundation of China (Nos 21603116, 21873055, 21702119, and 21473100) and Natural Science Foundation of Shandong Province (No. ZR2017QB001).

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REFERENCES

(1) (a) Busch, M.; Wodrich, M. D.; Corminboeuf, C. C. A generalized picture of C−C cross-coupling. ACS Catal. 2017, 7, 5643−5653. (b) Neumann, C. N.; Ritter, T. Facile C-F bond formation through a concerted nucleophilic aromatic substitution mediated by the phenofluor reagent. Acc. Chem. Res. 2017, 50, 2822−2833. (c) Race, N. J.; Hazelden, I. R.; Faulkner, A.; Bower, J. F. Recent development in the use of aza-Heck cyclization for the synthesis of chiral Nheterocycles. Chem. Sci. 2017, 8, 5248−5260. (d) Walia, P. K.; Kumar, M.; Bhalla, V. Tailoring of hetero-oligophenylene stabilized nanohybrid materials: potential tandem photo-promoted systems for C−C and C−X bond formation reactions via C−H activation. ChemistrySelect 2017, 2, 3758−3768. (e) Azam, M.; Dwivedi, S.; AlResayes, S. I.; Adil, S. F.; Islam, M. S.; Trzesowska-Kruszynska, A.; Kruszynski, R.; Lee, D. Cu(II) salen complex with propylene linkage: an efficient catalyst in the formation of CX bonds (X = N, O, S) and biological investigations. J. Mol. Struct. 2017, 1130, 122−127. (f) Weaver, J. D.; Recio, A.; Grenning, A. J.; Tunge, J. A. Transition metal-catalyzed decarboxylative allylation and benzylation reactions. Chem. Rev. 2011, 111, 1846. (g) Zhu, R.-Y.; Farmer, M. E.; Chen, Y.-Q.; Yu, J.-Q. A simple and versatile amide directing group for C−H functionalizations. Angew. Chem., Int. Ed. 2016, 55, 10578−10599. (h) Gulías, M.; Mascareñas, J. L. Metal-catalyzed annulations through activation and cleavage of C−H bonds. Angew. Chem., Int. Ed. 2016, 55, 11000−11019. (i) Wang, H.; Grohmann, C.; Nimphius, C.; Glorius, F. Mild Rh(III)-catalyzed C−H activation and annulation with alkyne MIDA boronates: short, efficient synthesis of heterocyclic boronic acid derivatives. J. Am. Chem. Soc. 2012, 134, 19592−19595. (j) Trost, B. M. On inventing reactions for atom economy. Acc. Chem. Res. 2002, 35, 695−705. (k) Nakamura, I.; Yamamoto, Y. Transition-metal-catalyzed reactions in heterocyclic synthesis. Chem. Rev. 2004, 104, 2127−2198. (l) D’Souza, D. M.; Müller, T. J. Multi-component syntheses of heterocycles by transition-metal catalysis. Chem. Soc. Rev. 2007, 36,

CONCLUSIONS

The mechanisms and regioselectivities of Ru(II)-catalyzed [4 + 1] annulation of benzamide and propargyl alcohol were elucidated with the aid of DFT calculations, and the improved catalytic cycle is presented. The reaction undergoes N−H and C−H deprotonations by CMD mechanism to afford a 5membered ruthenacyclic species, which then undergoes ring expansion by alkyne insertion to deliver a 7-membered ring intermediate. Our study focused on how the successive hydrogen migrations take place. The 1,2-proton migration and 1,3-proton transfer from O to C are successively finished by using acetate anion as a shuttle (a stepwise process). During this process, ethoxyl plays an essential role in controlling the N−H deprotonation and regioselectivity of alkyne insertion through a H···OEt hydrogen bond and the involvement of OAc− into the system lowers the energy barrier of C−H deprotonation. In contrast to the experimental proposal that the reaction experiences a Ru(II)−Ru(0)−Ru(II) transformation, our study unveiled a Ru(II)−Ru(IV)−Ru(II) transformation in the reaction. Our calculations revealed that the 6-membered Ru(II) complex undergoes first the EtO−N bond cleavage assisted by HOAc to yield a Ru(IV) intermediate and then reductive elimination takes place to lead to a Ru(II) complex, which is protonated again by HOAc to afford the product and release the Ru(II) catalyst. The EtO−N bond cleavage with an overall energy barrier of 24.3 kcal/mol is the rate-determining step for the whole reaction. G


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Organometallics 1095−1108. (m) Guimond, N.; Gouliaras, C.; Fagnou, K. Rhodium(III)-catalyzed isoquinolone synthesis: the N−O bond as a handle for C-N bond formation and catalyst turnover. J. Am. Chem. Soc. 2010, 132, 6908−6909. (2) (a) Qian, L.; Sun, M.; Dong, J.; Xu, Q.; Zhou, Y.; Yin, S. Palladiumcatalyzed desulfitative cross-coupling of arylsulfonyl hydrazides with terminal alkynes: a general approach toward functionalized internal alkynes. J. Org. Chem. 2017, 82, 6764−6769. (b) Tan, G.; Zhu, L.; Liao, X.; Lan, Y.; You, J. Rhodium/copper co-catalyzed highly trans-selective 1,2-diheteroarylation of alkynes with Azoles via C−H addition/ oxidation cross-coupling: a combined experimental and theoretical study. J. Am. Chem. Soc. 2017, 139, 15724−15737. (c) Liu, C.; Szostak, M. Decarbonylative phosphorylation of amides by palladium and nickel catalysis: the Hiraocross-coupling of amide derivatives. Angew. Chem., Int. Ed. 2017, 56, 12718−12722. (d) Henry, M. C.; Mostafa, M. A. B.; Sutherland, A. Recent advanced in transition-metal-catalyzed, directed aryl C−H/N−H cross-coupling reactions. Synthesis 2017, 49, 4586− 4598. (e) Vijayan, A.; Jumaila, C. U.; Baiju, T. V.; Radhakrishnan, K. V. Palladium-catalyzed cross-coupling of aryl iodides with heterobicyclic olefins: access to hydroarylated and heteroannulated motifs. ChemistrySelect 2017, 2, 5913−5916. (f) Kaga, A.; Chiba, S. Engaging radicals in transition metal-catalyzed cross-coupling with alkyl electrophiles: recent advances. ACS Catal. 2017, 7, 4697−4706. (g) He, S.; Tan, G.; Luo, A.; You, J. Rhodium-catalyzed oxidative C−H/C−H crosscoupling of aniline with heteroarene: N-nitroso group enabled mild conditions. Chem. Commun. 2018, 54, 7794−7797. (h) Zeng, L.; Li, H.; Tang, S.; Guo, X.; Deng, Y.; Zhang, G.; Pao, C.; Chen, J.; Lee, J.; Lei, A. Cobalt-catalyzed electrochemical oxidative C−H/N−H carbonylation with hydrogen evolution. ACS Catal. 2018, 8, 5448−5453. (3) (a) Nandakumar, A.; Midya, S. P.; Landge, V. G.; Balaraman, E. Transition-metal-catalyzed hydrogen-transfer annulations: access to heterocyclic scaffolds. Angew. Chem., Int. Ed. 2015, 54, 11022−11034. (b) Feng, J.; Zhang, J. An atom-economic synthesis of bicyclo[3.1.0]hexanes by rhodium N-heterocyclic carbene-catalyzed diastereoselective tandem hetero-[5 + 2] cycloaddition/claisen rearrangement reaction of vinylic oxiranes with alkynes. J. Am. Chem. Soc. 2011, 133, 7304−7307. (c) Zhang, D.; Zhang, Z.; Shi, M. Transition metalcatalyzed carbocyclization of nitrogen and oxygen-tethered 1,n-enynes and diynes: synthesis of five or 6-membered heterocyclic compounds. Chem. Commun. 2012, 48, 10271−10279. (d) Li, B.; Feng, H.; Xu, S.; Wang, B. Ruthenium-catalyzed isoquinolone synthesis through C−H activation using an oxidizing directing group. Chem. - Eur. J. 2011, 17, 12573−12577. (e) Wang, Q.; Qi, X.; Lu, L.-Q.; Li, T.-R.; Yuan, Z.-G.; Zhang, K.; Li, B.-J.; Lan, Y.; Xiao, W.-J. Iron-catalyzed decarboxylative (4 + 1) cycloadditions: exploiting the reactivity of ambident ironstabilized intermediates. Angew. Chem., Int. Ed. 2016, 55, 2840−2844. (4) For selected examples of transition-metal-catalyzed annulations with internal alkynes acting as two-carbon reaction partners, see: (a) Nishigaki, S.; Shibata, Y.; Tanaka, K. Rhodium-catalyzed chemoand regioselective intermolecular cross-cyclotrimerization of nonactivated terminal and internal alkynes. J. Org. Chem. 2017, 82, 11117−11125. (b) Kawaguchi, Y.; Yasuda, S.; Mukai, C. Mechanistic investigation of Rh(I)-catalyzed cycloisomerization of benzylalleneinternal alkynes via C−H activation. J. Org. Chem. 2017, 82, 7666− 7674. (c) Liao, G.; Song, H.; Yin, X.; Shi, B. Expeditious synthesis of pyrano[2,3,4-DE]quinolines via Rh(III)-catalyzed cascade C−H activation/annulation/lactonization of quinolin-4-ol with alkynes. Chem. Commun. 2017, 53, 7284−7287. (d) Gandeepan, P.; Rajamalli, P.; Cheng, C. H. Diastereoselective [3 + 2] annulation of aromatic/ vinylic amides with bicyclic alkenes through cobalt-catalyzed C−H activation and intramolecular nucleophilic addition. Angew. Chem., Int. Ed. 2016, 55, 4308−4311. (e) Xie, Y.; Wu, X.; Li, C.; Wang, J.; Li, J.; Liu, H. Ruthenium(II)-catalyzed redox-neutral [3 + 2] annulation of indoles with internal alkynes via C−H bond activation: accessing a pyrroloindolone scaffold. J. Org. Chem. 2017, 82, 5263−5273. (f) Tulichala, R. N. P.; Shankar, M.; Swamy, K. Ruthenium-catalyzed oxidative annulation and hydroarylation of chromene-3-carboxamides with alkynes via double C−H functionalization. J. Org. Chem. 2017, 82, 5068−5079. (g) Warratz, S.; Kornhaaß, C.; Cajaraville, A.; Niepötter,

B.; Stalke, D.; Ackermann, L. Ruthenium(II)-catalyzed C−H activation/alkyne annulation by weak coordination with O2 as the sole oxidant. Angew. Chem., Int. Ed. 2015, 54, 5513−5517. (h) Sun, B.; Yoshino, T.; Kanai, M.; Matsunaga, S. Cp*CoIII catalyzed site-delective C−H activation of unsymmetrical O-acyl oximes: synthesis of multisubstituted isoquinolines from terminal and internal alkynes. Angew. Chem., Int. Ed. 2015, 54, 12968−12972. (i) Yu, D.-G.; de Azambuja, F.; Gensch, T.; Daniliuc, C. G.; Glorius, F. The C−H activatio/1,3-diyne strategy: highly selective direct synthesis of diverse bisheterocycles by RhIII catalysis. Angew. Chem., Int. Ed. 2014, 53, 9650−9654. (j) Zhang, X.; Qi, Z.; Li, X. Rhodium(III)-catalyzed C−C and C-O coupling of quinoline N-oxides with alkynes: combination of C−H activation with O-atom transfer. Angew. Chem., Int. Ed. 2014, 53, 10794−10798. (k) Grigorjeva, L.; Daugulis, O. Cobalt-catalyzed, amino quinoline-directed C(sp2)-H bond alkenylation by alkynes. Angew. Chem., Int. Ed. 2014, 53, 10209−10212. (l) Huckins, J. R.; Bercot, E. A.; Thiel, O. R.; Hwang, T. L.; Bio, M. M. Rh(III)-catalyzed C−H activation and double directing group strategy for the regioselective synthesis of naphthyridinones. J. Am. Chem. Soc. 2013, 135, 14492−14495. (m) Mei, R.; Sauermann, N.; Oliveira, J. C. A.; Ackermann, L. Electroremovable traceless hydrazides for cobaltcatalyzed electro-oxidative C−H/N−H activation with internal alkynes. J. Am. Chem. Soc. 2018, 140, 7913−7921. (n) Zhao, Q.; Fu, W.; Kwong, F. Palladium-catalyzed regioselective aromatic extension of internal alkynes through a norbornene-controlled reaction sequence. Angew. Chem., Int. Ed. 2018, 57, 3381−3385. (5) For selected examples of transition-metal-catalyzed annulations with internal alkynes acting as one-carbon reaction partners, see: (a) Sonehara, T.; Murakami, S.; Yamazaki, S.; Kawatsura, M. Ironcatalyzed intermolecular hydrothiolation of internal alkynes with thiosalicylic acids, and sequential intramolecular cyclization reaction. Org. Lett. 2017, 19, 4299−4302. (b) Liu, H.; Song, S.; Wang, C.; Feng, C.; Loh, T. Redox-neutral rhodium-catalyzed [4 + 1] annulation through formal dehydrogenative vinylidene insertion. ChemSusChem. 2017, 10, 58−61. (c) Miura, H.; Terajima, S.; Tsutsui, K.; Shishido, T. Ruthenium-catalyzed addition of aromatic amides to internal alkynes and subsequent intramolecular cyclization for the atom-economical synthesis of isoindolinones. J. Org. Chem. 2017, 82, 1231−1239. (d) Wang, C.; Ye, L.; Feng, C.; Loh, T. C-F bond cleavage enabled redox-neutral [4 + 1] annulation via C−H bond activation. J. Am. Chem. Soc. 2017, 139, 1762−1765. (e) Dateer, R. B.; Chang, S. Selective cyclization of arylnitrones to indolines under external oxidant-free conditions: dual role of Rh(III) catalyst in the C−H activation and oxygen atom transfer. J. Am. Chem. Soc. 2015, 137, 4908−4911. For a recent review of [4 + 1] transformations, see: (f) Chen, J.-R.; Hu, X.-Q.; Lu, L.-Q.; Xiao, W.-J. Formal [4 + 1] annulation reactions in the synthesis of carbocyclic and heterocyclic systems. Chem. Rev. 2015, 115, 5301−5365. (g) Hong, S. Y.; Jeong, J.; Chang, S. [4 + 2] or [4 + 1] annulation: changing the reaction pathway of a rhodium-catalyzed process by tuning the Cp ligand. Angew. Chem., Int. Ed. 2017, 56, 2408− 2412. (h) Kardile, R. D.; Kale, B. S.; Sharma, P.; Liu, R.-S. Goldcatalyzed [4 + 1]-annulation reactions between 1,4-diyn-3-ols and isoxazoles to construct a pyrrole core. Org. Lett. 2018, 20, 3806−3809. (i) Wu, H.; Li, X.; Tang, X.; Feng, T.; Huang, G. Mechanisms of rhodium(III)-catalyzed C−H functionalizations of benzamides with α,α-difluoromethylene alkynes. J. Org. Chem. 2018, 83, 9220−9230. (j) Ma, X.-X.; Liu, J.-B.; Huang, F.; Sun, C.-Z.; Chen, D.-Z. Osubstituted groups-controlled selectivity in Rh(III)-catalyzed coupling of benzamides with α,α-difluoromethylene alkynes: A computational mechanistic study. Cat. Sci. Technol. 2018, 8, 3590−3598. (k) Wu, X.; Ji, H. Rhodium-catalyzed [4 + 1] cyclization via C−H activation for the synthesis of divergent heterocycles bearing a quaternary carbon. J. Org. Chem. 2018, 83, 4650−4656. (l) Zhu, C.; Wang, C.-Q.; Feng, C. Recent advance in transition-metal-catalyzed oxidant-free 4 + 1 annulation through C−H bond activation. Tetrahedron Lett. 2018, 59, 430−437. (m) Teng, L.; Zhou, C.; Yan, X.; Wang, J. Solvent-dependent asymmetric synthesis of alkynyl and monofluoroalkenyl isoindolinones by CpRhIII-catalyzed C−H activation. Angew. Chem., Int. Ed. 2018, 57, 4048−4052. H


Article

Organometallics

of electronic structure methods. J. Chem. Theory Comput. 2009, 5, 324− 333. (10) (a) Wadt, W. R.; Hay, P. J. Ab initio effective core potentials for molecular calculations. Potential for main group elements sodium to bismuth. J. Chem. Phys. 1985, 82, 284−298. (b) Hay, P. J.; Wadt, W. R. Ab initio effective core potentials for molecular calculations. Potentials for the transition metal atoms scandium to mercury. J. Chem. Phys. 1985, 82, 299−310. (11) Ehlers, A. W.; Böhme, M.; Dapprich, S.; Gobbi, A.; Höllwarth, A.; Jonas, V.; Köhler, K. F.; Stegmann, R.; Frenking, G.; et al. A set of fpolarization functions for pseudo-potential basis sets of the transition metals Sc Cu Y Ag and La Au. Chem. Phys. Lett. 1993, 208, 111−114. (12) (a) Becke, A. D. Density-functional thermochemistry. III. The role of exact exchange. J. Chem. Phys. 1993, 98, 5648−5652. (b) Lee, C.; Yang, W.; Parr, R. G. Development of the colle-salvetti correlationenergy formula into a functional of the electron density. Phys. Rev. B: Condens. Matter Mater. Phys. 1988, 37, 785−789. (13) (a) Marenich, A. V.; Cramer, C. J.; Truhlar, D. G. J. Universal solvation model based on solute electron density and on a continuum model of the solvent defined by the bulk dielectric constant and atomic surface tensions. J. Phys. Chem. B 2009, 113, 6378−6396. (b) 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. (c) Yue, X.; Qi, X.; Bai, R.; Lei, A.; Lan, Y. Mononuclear or dinuclear? Mechanistic study of the zinc-catalyzed oxidative coupling of aldehydes and acetylenens. Chem. - Eur. J. 2017, 23, 6419−6425. (d) Qi, X.; Li, Y.; Zhang, G.; Li, Y.; Lei, A.; Liu, C.; Lan, Y. Dinuclear versus mononuclear pathways in zinc mediated nucleophilic addition: a combined experimental and DFT study. Dalton Trans. 2015, 44, 11165−11171. (e) Qi, X.; Bai, R.; Zhu, L.; Jin, R.; Lei, A.; Lan, Y. Mechanism of synergistic Cu(II)/Cu(I)-mediated alkyne coupling: dinuclear 1,2reductive elimination after minimum energy crossing point. J. Org. Chem. 2016, 81, 1654−1660. (14) (a) Barone, V.; Cossi, M. Quantum calculation of molecular energies and energy gradients in solution by a conductor solvent model. J. Phys. Chem. A 1998, 102, 1995−2001. (b) Cossi, M.; Rega, N.; Scalmani, G.; Barone, V. Energies, structures, and electronic properties of molecules in solution with the C-PCM solvation model. J. Comput. Chem. 2003, 24, 669−681. (c) Tomasi, J.; Mennucci, B.; Cammi, R. Quantum mechanical continuum solvatioin models. Chem. Rev. 2005, 105, 2999−3094. (15) (a) Fukui, K. Formulation of the reaction coordinate. J. Phys. Chem. 1970, 74, 4161−4163. (b) Fukui, K. The path of chemical reactions-the IRC approach. Acc. Chem. Res. 1981, 14, 363−368. (16) (a) Dolg, M.; Wedig, U.; Stoll, H.; Preuss, H. Energy-adjusted ab initio pseudopotentials for the first row transition elements. J. Chem. Phys. 1987, 86, 866−872. (b) Andrae, D.; Haussermann, U.; Dolg, M.; Stoll, H.; Preuss, H. Energy-adjusted abinitio pseudopotentials for the 2nd and 3rd row transition-elements. Theor. Chem. Acc. 1990, 77, 123− 141. (17) (a) Jiang, Y.-Y.; Man, X.; Bi, S. Advances in theoretical study on transition-metal-catalyzed C−H activation. Sci. China: Chem. 2016, 59, 1448−1466. (b) Wu, W.; Liu, Y.; Bi, S. Mechanistic insight into conjugated N-N bond cleavage by Rh(III)-catalyzed redox-neutral C− H activation of pyrazolones. Org. Biomol. Chem. 2015, 13, 8251−8260. (c) Walsh, A. P.; Jones, W. D. Mechanistic insights of a concerted metalation-deprotonation reaction with [Cp*RhCl2]2. Organometallics 2015, 34, 3400−3407. (d) Yu, J.-L.; Zhang, S.-Q.; Hong, X. Mechanisms and origins of chemo- and regioselectivities of Ru(II)catalyzed decarboxylative C−H alkenylation of aryl carboxylic acids with alkynes: a computational study. J. Am. Chem. Soc. 2017, 139, 7224−7243. (e) Deng, C.; Lam, W. H.; Lin, Z. Computational studies on Rhodium(III) catalyzed C−H functionalization versus deoxygenation of quinoline N−Oxides with diazo compounds. Organometallics 2017, 36, 650−656. (f) Wang, K.; Ping, Y.; Chang, T.; Wang, J. Palladium-catalyzed [3 + 3] annulation of vinyl chromium(0) carbene

(6) (a) Wu, X.; Wang, B.; Zhou, S.; Zhou, Y.; Liu, H. Rutheniumcatalyzed redox-neutral [4 + 1] annulation of benzamides and propargyl alcohols via C−H bond activation. ACS Catal. 2017, 7, 2494−2499. (b) Wu, X.; Wang, B.; Zhou, Y.; Liu, H. Propargyl alcohols as onecarbon synthons: redox-neutral rhodium-catalyzed C−H bond activation for the synthesis of isoindolinones bearing a quaternary. Org. Lett. 2017, 19, 1294−1297. (7) (a) Patil, P. C.; Luzzio, F. A.; Ronnebaum, J. M. Selective alkylation/oxidation of N-substituted isoindolinone derivatives: synthesis of N-phthaloylated natural and unnatural α-amino acid analogues. Tetrahedron Lett. 2017, 58, 3730−3733. (b) Yin, Y.; Fu, Q.; Wu, W.; Cai, M.; Zhou, X.; Zhang, Y. Producing novel fibrinolytic isoindolinone derivatives in marine fungus stachybotrys longispora FG216 by the rational supply of amino compounds according to its synthesis pathway. Mar. Drugs 2017, 15, No. 214. (c) Bhattarai, D.; Jung, J. H.; Han, S.; Lee, H.; Oh, S. J.; Ko, H. W.; Lee, K. Design, synthesis, and biological evaluation of structurally modified isoindolinone and quinazolinone derivatives as hedgehog pathway inhibitors. Eur. J. Med. Chem. 2017, 125, 1036−1050. (d) Cao, Z.; Zhu, H.; Meng, X.; Guan, J.; Zhang, Q.; Tian, L.; Sun, X.; Chen, G.; You, J. Metal-free reaction of ortho-carbonylated alkynyl-substituted aryladehydes with common amines: selective access to functionalized isoindolinone and indenamine derivatives. Chem. - Eur. J. 2016, 22, 16979−16985. (e) Jiménez, J.; Kim, B.; Walsh, P. J. Tandem C(sp3)-H arylation/ oxidation and arylation/allylic substitution of isoindolinones. Adv. Synth. Catal. 2016, 358, 2829−2837. (f) Yamamoto, C.; Takamatsu, K.; Hirano, K.; Miura, M. Copper-catalyzed intramolecular benzylic C−H amination for the synthesis of isoindolinones. J. Org. Chem. 2016, 81, 7675−7684. (g) Li, H.-J.; Zhang, Y.-Q.; Tang, L.-F. A simple and efficient synthesis of isoindolinone derivatives based on reaction of ortho-lithiated aromatic imines with CO. Tetrahedron 2015, 71, 7681− 7686. (h) Choomuenwai, V.; Beattie, K. D.; Healy, P. C.; Andrews, K. T.; Fechner, N.; Davis, R. A. Entonalactams A-C: isoindolinone derivatives from an australian rainforest fungus belonging to the genus entonaema. Phytochemistry 2015, 117, 10−16. (i) Liu, L.; Bai, S.-H.; Li, Y.; Ding, X.-D.; Liu, Q.; Li, J. A three-component cascade cyclization to construct 3-(2-oxopropyl)-2-arylisoindolinone derivatives via coppercatalyzed annulation. Adv. Synth. Catal. 2018, 360, 1617−1621. (j) Kawęcki, R.; Stanczyk, W.; Jaglinska, A. Stereoselective synthesis of isoindolinones and tert-butyl sulfoxides. Tetrahedron 2018, 74, 578− 584. (8) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Scalmani, G.; Barone, V.; Mennucci, B.; Petersson, G. A.; Nakatsuji, H.; Caricato, M.; Li, X.; Hratchian, H. P.; Izmaylov, A. F.; Bloino, J.; Zheng, G.; Sonnenberg, J. L.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Vreven, T.; Montgomery, J. A., Jr.; Peralta, J. E.; Ogliaro, F.; Bearpark, M.; Heyd, J. J.; Brothers, E.; Kudin, K. N.; Staroverov, V. N.; Kobayashi, R.; Normand, J.; Raghavachari, K.; Rendell, A.; Burant, J. C.; Iyengar, S. S.; Tomasi, J.; Cossi, M.; Rega, N.; Millam, J. M.; Klene, M.; Knox, J. E.; Cross, J. B.; Bakken, V.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Martin, R. L.; Morokuma, K.; Zakrzewski, V. G.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Dapprich, S.; Daniels, A. D.; Farkas, O.; Foresman, J. B.; Ortiz, J. V.; Cioslowski, J.; Fox, D. J. Gaussian 09; Gaussian, Inc.: Wallingford, CT, 2009. (9) (a) Zhao, Y.; Truhlar, D. G. Density functionals with broad applicability in chemistry. Acc. Chem. Res. 2008, 41, 157−167. (b) Zhao, Y.; Truhlar, D. G. The M06 suite of density functionals for main group thermochemistry, thermochemical kinetics, noncovalent interactions, excited states, and transition elements: two new functionals and systematic testing of four M06-class functionals and 12 other functionals. Theor. Chem. Acc. 2008, 120, 215−241. (c) Truhlar, D. G. Molecular modeling of complex chemical systems. J. Am. Chem. Soc. 2008, 130, 16824−16827. (d) Zhao, Y.; Truhlar, D. G. Benchmark energetic data in a model system for grubbs II metathesis catalysis and their use for the development, assessment, and validation I


Article

Organometallics complexes through carbene migration insertion/Tsuji-Trost reaction. Angew. Chem., Int. Ed. 2017, 56, 13140−13144. (18) (a) Mbaezue, I. I.; Ylijoki, K. E. O. [5 + 1 + 2 + 1] vs [5 + 1 + 1 + 2] rhodium-catalyzed cycloaddition reactions of vinyl cyclopropanes with terminal alkynes and carbon monoxide: density functional theory investigations of convergent mechanistic pathways and reaction regioselectivity. Organometallics 2017, 36, 2832−2842. (b) Chen, P.; Sun, Y.; Wu, Y.; Liu, L.; Zhu, J.; Zhao, Y. A theoretical study on the mechanism of ruthenium(II)-catalyzed phosphoryl-directed orthoselective C−H bond activations: the phosphoryl hydroxy group triggered Ru(II)/Ru(0) catalytic cycle. Org. Chem. Front. 2017, 4, 1482−1492. (c) Mei, R.; Wang, H.; Warrata, S.; Macgregor, S. A.; Ackermann, L. Cobalt-catalyzed oxidase C−H/N−H alkyne annulation: mechanistic insights and access to anticancer agents. Chem. - Eur. J. 2016, 22, 6759−6763. (d) Tang, Y.; Bi, S.; Liu, Y.; Liu, C.; Liang, H.; Ling, B. Theoretical study on Pd-catalyzed reaction of aryl iodide with unsymmetrical alkyne. J. Organomet. Chem. 2016, 803, 134−141. (e) Mu, W.-H.; Xia, S.-Y.; Li, J.-X.; Fang, D.-C.; Wei, G.; Chass, G. A. Competing mechanisms, substituent effects, and regioselectivities of nickel-catalyzed [2 + 2 + 2] cycloaddition between carboryne and alkynes: a DFT study. J. Org. Chem. 2015, 80, 9108−9117. (19) (a) Deng, X.; Dang, Y.; Wang, Z.-X.; Wang, X. How does an earth-abundant copper-based catalyst achieve anti-markovnikov hydrobromination of alkynes? A DFT mechanistic study. Organometallics 2016, 35, 1923−1930. (b) Lu, T.; Chen, F. Multiwfn: a multifunctional wavefunction analyzer. J. Comput. Chem. 2012, 33, 580−592. (20) (a) Xing, Z.; Huang, F.; Sun, C.; Zhao, X.; Liu, J.; Chen, D. Density functional theory study of Rh(III)-catalyzed C−H activations and intermolecular annulations between benzamide derivatives and allenes. Inorg. Chem. 2015, 54, 3958−3969. (b) Guo, W.; Zhou, T.; Xia, Y. Mechanistic understanding of the aryl-dependent ring formations in Rh(III)-catalyzed C−H activation/cycloaddition of benzamides and methylenecyclopropanes by DFT calculations. Organometallics 2015, 34, 3012−3020. (c) Guo, W.; Xia, Y. Mechanics understanding of the divergent reactivity of cyclopropenes in Rh(III)-catalyzed C−H activation/cycloaddition reactions of N-phenoxyacetamide and Npivaloxybenzamide. J. Org. Chem. 2015, 80, 8113−8121. (d) Xu, L.; Zhu, Q.; Huang, G.; Cheng, B.; Xia, Y. Computational elucidation of the internal oxidant-controlled reaction pathways in Rh(III)-catalyzed aromatic C−H functionalization. J. Org. Chem. 2012, 77, 3017−3024. (21) (a) Chen, W.-J.; Lin, Z. Rhodium(III)-catalyzed hydrazinedirected C−H activation for indole synthesis: mechanism and role of internal oxidant probed by DFT studies. Organometallics 2015, 34, 309−318. (b) Li, X. G.; Liu, K.; Zou, G.; Liu, P. N. Rhodium(III)catalyzed, C−H activated annulation to form isocoumarins and alphapyrones using O-N bond as an internal oxidant. Adv. Synth. Catal. 2014, 356, 1496−1500. (c) Yang, Y.-F.; Houk, K. N.; Wu, Y.-D. Computational exploration of RhIII/RhV and RhIII/RhI catalysis in rhodium(III)-catalyzed C−H activation reactions of N-phenoxyacetamides with alkynes. J. Am. Chem. Soc. 2016, 138, 6861−6868. (d) Lu, N.; Wang, H. Theoretical mechanism studies on the competitive CO-induced N-N bond cleavage of N2O with N−O bond cleavage mediated by (η̧5C5Me5)Mo[N(iPr)C(Me)-N(iPr)](CO)2. Dalton Trans. 2013, 42, 13931−13939. (e) Robinson, R., Jr.; Shaw, M. F.; Stranger, R.; Yates, B. F. Theoretical study of the mechanism for the sequential N−O and N-N bond cleavage within N2O adducts of N-heterocyclic carbenes by a vanadium(III) complex. Dalton Trans. 2016, 45, 1047−1054. (f) Guimond, N.; Gorelsky, S. I.; Fagnou, K. Rhodium(III)-catalyzed heterocycle synthesis using an internal oxidant: improved reactivity and mechanistic studies. J. Am. Chem. Soc. 2011, 133, 6449−6457. (g) Piou, T.; Romanov-Michailidis, F.; Romanova-Michaelides, M.; Jackson, K. E.; Semakul, N.; Newell, B. S.; Rithner, C. D.; Rovis, T.; et al. Correlating reactivity and selectivity to cyclopentadienyl ligand properties in Rh(III)-catalyzed C−H activation reactions: an experimental and computational study. J. Am. Chem. Soc. 2017, 139, 1296−1310. (22) Wang, Z.; Xie, P.; Xia, Y. Recent progress in Ru(II)-catalyzed C− H activations with oxidizing directing groups. Chin. Chem. Lett. 2018, 29, 47−53.

(23) Fukui, Y.; Liu, P.; Liu, Q.; He, Z.-T.; Wu, N.-Y.; Tian, P.; Lin, G.Q. Tunable arylative cyclization of 1,6-enynes triggered by rhodium(III)-catalyzed C−H activation. J. Am. Chem. Soc. 2014, 136, 15607− 15614. (24) Simmon, E. M.; Hartwig, J. F. On the interpretation of deuterium kinetic isotope effects in C−H bond functionalizations by transitionmetal complexes. Angew. Chem., Int. Ed. 2012, 51, 2−9. (25) (a) Eyring, H. The Activated Complex in Chemical Reactions. J. Chem. Phys. 1935, 3, 107−115. (b) Eyring, H.; Polanyi, M. Ü ber Einfache Gasreaktionen. Z. Phys. Chem. B. 1931, 12, 279−311. (c) Laidler, K. J.; King, M. C. The development of Transition-State Theory. J. Phys. Chem. 1983, 87, 2657−2664. (d) Polanyi, J. C. Some concepts in reaction dynamics. Science 1987, 236, 680−690.

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