Synthesis of Planar Chiral Ferrocenes via Transition-Metal-Catalyzed

Article pubs.acs.org/accounts

Synthesis of Planar Chiral Ferrocenes via Transition-Metal-Catalyzed Direct C−H Bond Functionalization De-Wei Gao, Qing Gu, Chao Zheng, and Shu-Li You* State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Lingling Lu, Shanghai 200032, China CONSPECTUS: Ferrocenes are of great interest in the fields of materials science, organic synthesis, and biomedical research. Of particular significance is the fact that ferrocenes bearing planar chirality have been demonstrated to be highly efficient ligands or catalysts in asymmetric catalysis, some of which have been employed in the industrial synthesis of pharmaceuticals and agrochemicals. So far, the main methods for the synthesis of planar chiral ferrocenes involve diastereoselective directed ortho-metalation (DoM), enantioselective DoM, and chiral resolution. Despite the fact that these approaches are well developed and widely applied, the use of chiral auxiliaries or external stoichiometric chiral bases is required in most cases. Additionally, the practicality of these processes is hampered by the requirement of sensitive organometallic reagents, the poor compatibility with functional groups, and the low atom economy in some cases. Therefore, the development of highly efficient strategies to introduce planar chirality on the backbone of ferrocene that do not possess these limitations is highly desirable. Meanwhile, transition-metal-catalyzed asymmetric C−H bond functionalization reactions have attracted much attention over the past few years owing to their emerging potential for providing a straightforward approach for the preparation of chiral molecules. In addition to the majority of the work focusing on the installation of central chirality, methods for the catalytic asymmetric synthesis of planar chiral compounds via C−H bond functionalization have also been explored. In this Account, we summarize our recent efforts aimed at the development of novel methods to synthesize planar chiral compounds via asymmetric C−H bond functionalization and also highlight related achievements by other groups. First, we briefly introduce the precedent examples of diastereoselective and enantioselective synthesis of planar chiral ferrocenes. Subsequently, asymmetric syntheses of structurally diverse planar chiral ferrocenes via Pd [Pd(II), Pd(0)]-, Ir-, Rh-, Au-, and Ptcatalyzed C−H bond functionalization are described. These methods have impressive advantages over traditional approaches for the synthesis of functionalized planar chiral ferrocenes in terms of both step- and atom-economies. Notably, the products of these processes are easily transformed into a variety of new catalysts or ligands, which have been demonstrated to promote efficient asymmetric reactions. Moreover, DFT calculations have been conducted to explore the origin of the excellent enantioselectivity of Pd-catalyzed enantioselective C−H bond functionalization reactions. Progress made in the area of asymmetric C−H bond functionalization provides an effective platform for the design and synthesis of planar chiral ferrocenes.

1. INTRODUCTION Since its serendipitous discovery and proof of its sandwich-type structure was disclosed in the early 1950s, ferrocene has gained much attention because of its wide applications in organic synthesis, material science, and medicinal chemisty.1 Sandwich type compounds like ferrocene have been extensively investigated as chiral ligands or catalysts.2 In particular, some of these ligands have been applied in the industrial scale production of fine chemicals. For example, an asymmetric hydrogenation reaction of an imine catalyzed by Ir/(R,Sp)Xyliphos, used for the production of (S)-metolachlor, is the largest scale asymmetric process known. The turnover number (TON) and turnover frequency (TOF) of this process are remarkably high, matching the catalytic efficiencies of enzymes (Scheme 1).3 Owing to the wide use of planar chiral ferrocenes in both academic and industrial chemistry, intense attention has © 2017 American Chemical Society

been paid to the efficient introduction of planar chirality on the ferrocene backbone.4 Ferrocene-based planar chirality is created when two or more different substituents are introduced on one of the cyclopentadienyl (Cp) rings to remove the plane of symmetry in the parent substance. The asymmetric synthesis of planar chiral ferrocenes has been intensively investigated in the past decades. The most commonly used strategies involve diastereoselective directed ortho-metalation (DoM), enantioselective DoM, and chiral resolution.5 However, these methods often rely on the utilization of stoichmetric amounts of preinstalled chiral auxiliaries or chiral bases. Additionally, the practical use of these processes is hampered by the required utilization of Received: November 13, 2016 Published: January 25, 2017 351

DOI: 10.1021/acs.accounts.6b00573 Acc. Chem. Res. 2017, 50, 351−365

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Accounts of Chemical Research Scheme 1. Enantioselective Hydrogenation of Imine by Ir/(R,Sp)-Xyliphos

Scheme 2. Diastereoselective Cross-Coupling Reaction by Using Chiral Oxazoline as Directing Group

sensitive organometallic reagents, the poor compatibility of these reactions with functional groups, and the low atom economy accompanying some reactions. In comparison, catalytic asymmetric synthesis should be a straighforward and efficient approach to access planar chiral compounds. Several groups have made important contributions to this area. For instance, Kündig et al. developed an elegant desymmetrization of dihalogenated metallocenes by Pd-catalyzed cross coupling.6 In addition, the group of Ogasawara and Takahashi has ingeniously designed a protocol using asymmetric ring-closing metathesis to introduce planar chirality.7 In view of their atom and step economies, transition-metalcatalyzed asymmetric direct C−H bond functionalization reactions should be the most convenient and powerful method for the construction of planar chiral ferrocenes. The main challenge restricting the development of this approach is the ability to discriminate between the inert enantiotopic C−H bonds under harsh reaction conditions. Fortunately, elegant examples of methods to introduce central-chirality by employing enantioselective C−H bond activation have been described by the groups of Yu, Cramer, Kündig, and others.8 However, the use of enantioselective C−H bond functionalization for introducing planar chirality has been relatively underexplored. To date, some important advances have been made in this area, especially those relying on the transition-metal-catalyzed asymmetric C−H bond functionalization strategy.9 In this Account, we summarize progress made in studies of this topic beginning with diastereoselective C−H bond activation of ferrocenes by using chiral auxiliary followed by the development of chiral catalysts to realize chiral recognition of two enantiotopic C−H bonds of ferrocene.

Scheme 3. Rh(III)-Catalyzed Diastereoselective C−H Bond Amidation of Chiral Oxazolyl Ferrocene with Isocyanates

Scheme 4. Cu-Catalyzed Enantioselective Insertion of Carbenoid into C−H Bond of Ferrocene

activation event. In 2007, our group reported a method for diastereoselective synthesis of planar chiral ferrocene (S,Rp)-2 that uses reaction of the enantiopure ferrocenyl oxazoline (S)-1 with simple benzene.10 Notably, the single diastereoisomer (S,Rp)-2 is generated in this process when the in situ generated palladium dimer I is employed. To obtain the diastereoisomer of (S,Rp)-2, the TMS-derivative (S,Sp)-3 was reacted with benzene under the same conditions utilized for reaction of (S)1. This process generates the corresponding coupling product (S,Sp)-4 (54%), which is subsequently converted to (S,Sp)-2 by TMS group removal through treatment with TBAF (Scheme 2). In 2012, Shibata and co-workers described a Rh-catalyzed diastereoselective C−H bond amidation with isocyanates employing the same chiral oxazoline containing ferrocene. The process generates the desired amidation products as single diastereoisomers in moderate yields (Scheme 3).11

2. DIASTEREOSELECTIVE AND SEMINAL ENANTIOSELECTIVE SYNTHESIS OF PLANAR CHIRAL FERROCENES The efficacy of diastereoselective C−H functionalization depends on the choice of an appropriate chiral auxiliary, which is responsible for high stereocontrol during the C−H 352


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Accounts of Chemical Research Scheme 5. Pd-Catalyzed Asymmetric C−H Bond Arylation of Ferrocenes with Arylboronic Acids

The results of a seminal study of catalytic enantioselective synthesis of planar chiral ferrocenes via C−H bond functionalization were reported by Siegel and Schmalz in 1997.12 A remarkable observation made in this effort is that the cyclization products 7 are efficiently produced with a significant level of enantioselectivity through asymmetric carbene insertion into the ortho C−H bond of ferrocene catalyzed by CuOTf/bisoxazoline (L1) (Scheme 4). The two substrates examined in this study gave the desired products with moderate levels of ee.

3. ENANTIOSELECTIVE SYNTHESIS OF PLANAR CHIRAL FERROCENES VIA Pd(II)-CATALYZED DIRECT C−H BOND FUNCTIONALIZATION An attractive alternative to using metalation of a ferrocene possessing a chiral auxiliary is an approach that employs a chiral reagent to generate a planar chiral metallacycle. Early work by Figure 1. Plausible catalytic cycle of Pd-catalyzed asymmetric C−H bond arylation.

Table 1. Effect of Kinetic Resolution

entry

time (h)

9a/9a′

ee (%)

1 2 3 4 5

2 4 6 8 10

33:1 28:1 17:1 9:1 7:1

94 95 98 99 99

Sokolov demonstrated the success of this approach. 13 Specifically, enantioselective palladation of dimethylaminomethylferrocene promoted by a stoichiometric amount of a chiral amino acid was found to produce an optically active planar chiral ferrocenylpalladium chloride dimer in high yield. High asymmetric induction accompanies this process when optimized reaction conditions are employed. However, the practicality of the method is diminished by the requirement that the optically active palladium(II) complex must be prepared in advance and a stoichiometric amount of the ligand is required. A major breakthrough in palladium-catalyzed asymmetric C− H bond activation was made by the Yu group. The process employed a monoprotected amino acid (MPAA) as the chiral ligand and led to a new approach to catalytic asymmetric C−H functionalization reactions.14 Inspired by these pioneering studies, in 2013 we designed a method for catalytic asymmetric arylation of planar chiral ferrocenes that utilizes Pd-catalyzed 353


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Accounts of Chemical Research

Scheme 6. Enantioselective Synthesis of Planar Chiral Ferrocenes via Pd(II)-Catalyzed Oxidative Heck and Annulation Reactions

(Rp)-9a and Boc-L-Val-OH for the formation of bis-arylative product 9a′ (Table 1). Thus, nearly enantiopure (Sp)-9a could be easily obtained by prolonging the reaction time. The plausible catalytic cycle, proposed for this process, is initiated by selective cleavage of the C−H bond in ferrocene 8a via concerted metalation−deprotonation (CMD). In this enantioselectivity-determining step, the internal base MPAA assists in generating cyclic Pd(II) intermediate A.16 Subsequently, A is transformed to the intermediate B by transmetalation with phenyl boronic acid, and finally reductive elimination of B forms (Sa)-9a. The release of a Pd(0) species and its subsequent oxidation by air to form a Pd(II) species completes the catalytic cycle (Figure 1). At almost the same time, an asymmetric oxidative Heck method, employing a similar strategy to control enantioselectivity, was developed for the efficient synthesis of planar chiral ferrocenes by Cui, Wu, and their co-workers.17 Olefins, such as acrylates, substituted styrenes, vinylcyclohexanes, and

cross-coupling reactions of dialkylaminomethylferrocene with arylboronic acids.15 The method, which utilizes commercially available and inexpensive Boc-L-Val-OH as the chiral ligand and air as the green oxidant, is highly practical. The reaction proceeds smoothly to afford the arylation products in good yields and with excellent levels of enantioselectivity (Scheme 5). Notably, a substrate bearing a bromo-substituent is compatible with the reaction conditions, and the presence of the C−Br bond in the product enables a range of subsequent transformations. Furthermore, the compatibility of the process with diverse functional groups suggests that the reaction can be used to prepare a vast array of enantiopure ferrocenes as novel ligands or catalysts. It should be noted that a bis-arylative product 9a′ can be formed and a moderate kinetic resolution of secondary arylation is observed. Both the ee of planar chiral ferrocene (Sp)-9a and ratio of 9a′ were slightly improved during the process of reaction, indicating the matched chirality between 354


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Accounts of Chemical Research Scheme 7. Enantioselective Oxidative C−H/C−H Cross-Coupling Reaction

Because of its high atom economy, an asymmetric oxidative cross-coupling reaction of two arenes via a double C−H activation pathway would undoubtedly be the most expedient and straightforward method to synthesize chiral biaryls. However, most of the previously reported examples of asymmetric C−H bond arylation require the utilization of at least one aryl (pseudo)halide or a organometallic reagent as a cross-coupling partners.20 The strategy of a 2-fold C−H bond activation was only described in the context of a racemic reaction previously. Recently, we developed an asymmetric oxidative cross-coupling reaction that uses Pd(OAc)2 and Boc21 L -Ile-OH as the catalytic system. The reactions of dimethylaminomethylferrocenes and electron-rich heteroarenes generate planar chiral ferrocenes in high yields, with high regioselectivity and near perfect enantioselectivity (Scheme 7). The process takes place via a 2-fold C−H bond activation pathway without the need for prefunctionalizing of either coupling partner. It is worth noting that this atom-economical reaction utilizes oxygen in the air as a green oxidant and it does not require the use of significant excesses of either coupling partner. However, both electron-deficient and electron-neutral arenes are not suitable substrates for the coupling reaction conducted under the developed conditions. A plausible catalytic cycle for this 2-fold C−H bond activation reaction is similar to that for cross-coupling reaction of ferrocene with aryl boronic acids (Figure 1). The only difference is that the arylation of intermediate A proceeds by electrophilic substitution with benzofuran rather than transmetalation with an aryl boronic acid (Figure 2). The new method is applicable to the efficient preparation of an array of bidentate N,X-ligands (Scheme 8A). Planar chiral ferrocenes bearing similar privileged scaffolds are generally synthesized by using stoichiometric chiral reagents. Additionally, the diphenylcarbinol derivative 16a was demonstrated to be an efficient ligand for the asymmetric diethylzinc addition to benzaldehyde and 1-naphthaldehyde (90% yield and 86% ee, and 86% yield and 87% ee, respectively, Scheme 8B).

Figure 2. Plausible catalytic cycle of Pd-catalyzed asymmetric twofold C−H bond reaction.

acrylamides, are suitable substrates for the process, which produces alkenylation products in good yields and with excellent levels of ee (Scheme 6A). Soon afterward, we described a highly efficient approach to the synthesis of planar chiral ferrocenes that involves Pd(II)-catalyzed asymmetric annulation of N,N-disubstituted aminomethylferrocenes with diarylethynes (Scheme 6B).19 The development of this reaction was stimulated by an earlier report by Cui and Wu describing a racemic version of the process.18 The P,N-bidentate ligand (Sp)-L2 can be readily synthesized starting from (Sp)-11a, generated using this process, via DoM followed by quenching with Ph2PCl. A preliminary examination of the use of (Sp)-L2 in Pd(0)-catalyzed asymmetric allylic alkylations showed that the reactions generate alkylation product in promising levels of enantioselectivity (Scheme 6C). 355


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Accounts of Chemical Research Scheme 8. Transformations of 15a and Asymmetric Diethylzinc Addition Reaction

Scheme 9. Catalytic Enantioselective C−H Acylation of Ferrocene Derivatives

Apart from the development of arylation, oxidative Heck, and annulation reactions, other reactions of this type have been less well explored. In 2014, Cui, Wu, and co-workers reported a novel catalytic enantioselective C−H acylation reaction that uses Pd(OAc)2 and Ac-L-Phe-OH as the catalytic system.22 Diaryldiketones bearing either electron-withdrawing or electron-donating groups are well suited for the new acylation reaction. These substrates react to form various planar chiral ferrocenes in satisfactory yields and levels of enantioselectivity (Scheme 9). Interestingly, the reactions proceed smoothly in moderate yields and levels of chiral induction when dialkyldiketones are used as the carbonyl substrates. During the investigation of the reaction mechanism, they found that the radical scavenger TEMPO inhibits the process. Thus, a radical mechanistic pathway was proposed, in which a cyclopalladated intermediate C is formed via selective C−H bond activation. Then, Pd(III) or Pd(IV) intermediate D is generated by the reaction of the benzoyl radical with C, which is released by the reaction of diphenyldiketone with tert-butyl

Figure 3. Proposed reaction mechanism of catalytic enantioselective C−H acylation.

hydroperoxide. Finally, reductive elimination of the highly reactive species D produces the desired product with regeneration of the Pd(II) species (Figure 3).

4. ENANTIOSELECTIVE SYNTHESIS OF PLANAR CHIRAL FERROCENES VIA Pd(0)-CATALYZED DIRECT C−H BOND FUNCTIONALIZATION As described above, Pd(II)-catalyzed asymmetric C−H bond activation has become an important tool for the synthesis of planar chiral ferrocene derivatives. However, the need for high catalyst loadings and external oxidants restricts the practical applications of these processes. Recently, Pd(0)-catalyzed intramolecular asymmetric C−H arylation reactions of readily available starting materials that occur under mild reaction 356


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Accounts of Chemical Research Scheme 10. Pd(0)-Catalyzed Enantioselective Intramolecular C−H Arylation

occurs smoothly to form the planar chiral ferrocene product in quantitative yield and an excellent level of ee (Scheme 10B). This newly developed method has been applied to the straightforward synthesis of a planar chiral P,N-ligand, in which planar chirality was previously introduced by using a DoM strategy.24 By using the method we developed, 5 g of the C−H arylation product 19a is generated without any erosion of yield and enantioselectivity. Subsequently, 19a was subjected to oxime formation, reduction (dr = 1:1), and reductive amination to form the tertiary amine (S,Rp)-22 in 36% yield (three steps). Finally, the desired P,N-ligand (S,Rp)-23, whose use in Pdcatalyzed asymmetric allylic alkylation and amination reactions has led to excellent levels of chiral induction, was produced from 22 by amine-directed lithiation and subsequent trapping with Ph2PCl in 68% yield (Scheme 11A). Interestingly, starting from 19a, Guiry and co-workers prepared a novel family of planar-chiral ferrocenyl diols, which were demonstrated to serve as efficient catalysts in asymmetric hetero-Diels−Alder reactions that generate cycloadducts in moderate yields with up to 92% ee (Scheme 11B).25 About the same time, Gu, Kang, and co-workers reported using a similar strategy to design a process for the efficient synthesis of planar chiral ferrocenes from aryl iodides.26 Besides ferrocenes, ruthenocene derivatives also serve as suitable substrates. The process, which has good functional group

conditions have been developed for the highly efficient synthesis of planar chiral ferrocenes.23 Compared with previous oxidative C−H arylation reactions, this overall redox-neutral process (Pd0/PdII catalysis) does not require the use of external stoichiometric oxidants, which means that potential oxidation of the substrates, products, or ligands can be avoided. Therefore, chiral phosphines can be used as ligands in this process. Commercially available axial bisphosphines including (R)-BINAP were found to be suitable chiral ligands for the reaction. Thus, under optimized conditions (2.5 mol % of Pd(OAc)2, 5.0 mol % of (R)-BINAP), ferrocenes bearing sterically and electronically different substituents can be utilized. Even substrate 18h containing a pentamethyl substituted Cp (Cp*) ring reacts to yield the nearly enantiopure corresponding product 19h in excellent yield. Of particular note is the fact that the reactivity and enantioselectivity of the alternative process using the Pd(OAc)2/MPPA catalytic system are significantly reduced when a Cp*-derived ferrocene substrate is employed. C2-Symmetric planar chiral ferrocenes, the products of double arylation, are formed efficiently when aryl bromides are introduced on each Cp ring (97% yield and >99% ee, Scheme 10A). Furthermore, a gram scale reaction to form 19a takes place in 99% yield and 97% ee, demonstrating the practical utility of the process. Even when the catalytic loading is lowered to 0.5 mol %, the reaction 357


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Scheme 11. Efficient Synthesis of Planar Chrial P,N-Ligand (S,Rp)-23 and Diol 24 and Application in Asymmetric HeteroDiels−Alder Reaction

tolerance, generates planar chiral ruthenocenes with high levels of enantioselectivity. In addition, chiral BINOL-derived phosphoric acid was recently shown by Duan, Ye, and coworkers to induce asymmetry in the Pd(0)-catalyzed C−H arylation reactions of ferrocenes, albeit in some cases with only moderate enantioselectivity.27 By utilizing an amide linker in the substrate and (R,Sa)-OPINAP as the chiral ligand, the Gu group recently devised a method for enantioselective synthesis of planar chiral quinilinoferrocenes albeit with moderate levels of enantioselectivity.28 Soon afterward, a Pd(0)-catalyzed process for asymmetric synthesis of these scaffolds was reported by Liu, Zhao, and co-workers. The reaction (Scheme 12), using a TADDOL-derived phosphoramidite ligand, generates products in high yields and levels of enantioselectivity.29 These methods can be employed in a concise route for the preparation of ferrocenes bearing a lactam skeleton. Chiral ferrocenes containing a pyridine core are useful as nucleophilic or Lewis base catalysts for an array of asymmetric reactions. However, to date, the preparation of these substances has mainly relied on resolution or chiral HPLC separation. Recently, we developed a highly efficient synthesis of planar chiral ferrocenylpyridine derivatives via Pd-catalyzed intramolecular C−H arylations.30 When carried out using 2.5 mol % of Pd(OAc)2 and 5.0 mol % of (R)-BINAP, reactions of substrates with electronically and sterically different substitu-

Scheme 12. Enantioselective Intramolecualr C−H Arylation of N-(2-Haloaryl)ferrocenecarboxamides

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Accounts of Chemical Research Scheme 13. Highly Enantioselective Synthesis of Planar Chiral Ferrocenylpyridine Derivatives

accompany asymmetric C−H arylation reactions proceeding by way of a CMD mechanism. The results of DFT calculations showed that the Gibbs free energy of the transition state TSCMD-S (Figure 4), leading to the planar chiral ferrocenes with a S configuration, is 8.8 kcal/mol higher in energy than the transition state TS-CMD-R, leading to the R product. This difference is a consequence of the fact that significant steric interactions exist between the ferrocene moiety and one phenyl group of (R)-BINAP in quadrant II in TS-CMD-S, while this unfavorable interaction is absent in TS-CMD-R where the ferrocene moiety is located in an open quadrant. Therefore, biased interactions between the chiral ligand and the ferrocene moiety in the two diastereomeric transition states lead to an excellent level of stereochemical control in the C−H arylation step (Figure 4).

ents present on the pyridine ring react smoothly. Of particular note, this methodology enables efficient and rapid access to planar chiral DMAP and PPY (4-pyrrolidin-1-ylpyridine) analogues (Scheme 13A). Interestingly, the catalyst loading can be lowered to 0.2 mol % in reaction of an 8 mmol scale of substrate 27a. This represents the highest catalytic efficiency reported to date for Pd-catalyzed asymmetric C−H bond activation (TON up to 495) (Scheme 13B). Furthermore, pyridine N-oxide 29, bearing a pentaethyl Cp ring, was used as the catalyst for the asymmetric opening reaction of a mesoepoxide. The process generated the desired product in 95% yield and 66% ee (Scheme 13C). This new method provides a foundation for future designs of methods to prepare planar chiral ferrocenylpyridine catalysts. Computational investigations were conducted to understand the basis for the excellent levels of enantioselectivity that 359


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crystallographic analysis. Additionally, the secondary propargylic alcohol 35 is efficiently synthesized by alkynylation reaction of 1-naphthaldehyde catalyzed by 34 (Scheme 14B).

5. ENANTIOSELECTIVE SYNTHESIS OF PLANAR CHIRAL FERROCENES VIA Ir- OR Rh-CATALYZED DIRECT C−H BOND FUNCTIONALIZATION Compared with the development of Pd-catalyzed asymmetric C−H bond functionalization, work on analogous reactions using rhodium or iridium catalytic systems has progressed slowly, especially when used for the introduction of planar chirality. Recently, Shibata and Shizuno reported an Ir/chiral diene-catalyzed asymmetric C−H alkylation of ferrocenes using an isoquinolin-2-yl directing group to suppress secondary alkylation reactions.33 Several alkenes including allylbenzene, oct-1-ene, methyl methacrylate, and norbornene react under these conditions in good yields and moderate to good levels of enantioselectivity. When styrene is used as the alkylating reagent, the linear substance 37e is formed as the major product (L/B = 3:1) in 96% yield and 89% ee (Scheme 15). The results of a preliminary investigation showed that in the mechanistic pathway for this process C−H bond cleavage and insertion of alkene is likely reversible. Given the fundamental importance of silicon-containing compounds, the development of enantioselective C−H silylation reactions to generate planar chiral ferrocenes bearing the silole unit is highly desirable. In 2015, three groups independently described rhodium-catalyzed asymmetric intramolecular C−H silylation reactions and their use in the construction of planar chiral benzosiloloferrocenes.34 In Shibata’s work,34a the chiral diene ligand L5 was employed in a dehydrogenative coupling reaction that leads to formation of silylation products in moderate to good yields and levels of enantioselectivity (Scheme 16). Almost at the same time, He34b and Murai and Takai34c independently carried out systematic exploratory studies that demonstrated that chiral bisphosphine ligands can be utilized in the dehydrogenative silylation reactions that occur with satisfactory yields and chiral induction. Also, they discovered that substituents R and X in 39 have dramatic effects on the reactivity of the substrates and enantioselectivity of the process (Scheme 16). Moreover, these reactions do not require severe conditions or oxidants, and therefore, they are practical and environmentally friendly methods to synthesize functionalized planar chiral metallocenes. In 2014, Wang discovered a Pd-catalyzed annulation reaction of ferrocenecarboxamides with internal alkynes.35 The lack of a requirement for ligands in this process presents a formidable challenge for developing a chiral version. We developed a Rhcatalyzed annulation reaction of N-methoxyferrocenecarboxamides with internal alkynes that does not require an external oxidant.36 Notably, an asymmetric version of this annulation reaction was initially demonstrated by using chiral Cp*Rh complex (Ra)-Rh1. The process produces 43 in 37% yield and 46% ee (Scheme 17). This study serves as a proof-of-concept of the new strategy for the asymmetric synthesis of planar chiral ferrocenes.

Figure 4. (a) The structures of the two transition states, TS-CMD-R and TS-CMD-S. (b) The quadrant analysis of the two transition states. The unsubstituted Cp ring of ferrocene moiety is omitted in the front views for the sake of clarity. The bond distances are in angstroms. The dihedral angles are in degrees. The relative Gibbs free energies are in kcal/mol. Reprinted with permission from ref 30. Copyright 2015 American Chemical Society.

Transition-metal-catalyzed C−H alkenylation has become a common method for the formation of C−C bonds. The development of protocols to bring about chiral induction in C− H alkenylation reactions has mainly concentrated on intermolecular examples and the use of desymmetrization or kinetic resolution strategies. Limited success has been achieved in developing Pd(0)-catalyzed intramolecular C−H alkenylation, as exemplified by the single example arising from work by the Cramer group, in which TADDOL-derived phosphoramidite was employed as the ligand.31 Recently, we developed an intramolecular C−H alkenylation that is useful for the expedient synthesis of planar chiral ferrocenes.32 Substrates bearing either electron-donating or electron-withdrawing substituents on the Cp ring are well tolerated in this process, which gives rise to planar chiral ferrocenes in high yields and excellent levels of enantioselectivity. Planar chiral ruthenocene can also be synthesized in this manner under optimized conditions. Notably, the enantioselective and diastereoselective synthesis of planar chiral ferrocenes was accomplished by using a cascade C−H arylation and alkenylation protocol, which produces the desired product with good yields and levels of dr and enantioselectivity (Scheme 14A). It is noteworthy that the new methodology can be applied to the efficient synthesis of planar chiral ligands. For example, the N,O-bidentate ferrocenyl ligand 34 was easily prepared by addition reaction of phenylmagnesium bromide to 33e in 84% yield with perfect diastereoselectivity. The absolute configuration of 34 was unambiguously determined to be (Rp,S) by using X-ray 360


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Accounts of Chemical Research Scheme 14. Highly Enantioselective Synthesis of Planar Chiral Ferrocenes via Pd(0)-Catalyzed C−H Alkenylation

6. ENANTIOSELECTIVE SYNTHESIS OF PLANAR CHIRAL FERROCENES VIA Au/Pt-CATALYZED DIRECT C−H BOND FUNCTIONALIZATION

in this reaction, which occurs efficiently and with satisfactory levels of chiral induction. This process is the first example in which planar chiral ferrocenes are prepared using gold catalysis. Soon after this effort, Shibata and co-workers developed a cycloisomerization reaction to synthesize planar chiral ferrocenes that utilizes Pt/(S,S)-Ph-BPE as the catalytic system (Scheme 18).38

Gold-catalyzed intramolecular cycloisomerization has emerged as a powerful tool for the synthesis of phenanthrenes and helicenes. However, the enantioselective version of the cycloisomerization reaction has not been explored thoroughly. Urbano and Carreño developed an asymmetric cycloisomerization process for the synthesis of aromatic tricyclic ferrocenes that takes place by enantioselective Au(I)-catalyzed C−H bond functionalization.37 Substituents having varied electronic properties and locations on the phenyl ring are well tolerated

7. CONCLUSION AND OUTLOOK In this Account, we summarized recent advances that have been made in transition-metal-catalyzed asymmetric C−H bond functionalization of ferrocenes. The examples presented demonstrate that these processes can be utilized to prepare a 361


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Accounts of Chemical Research Scheme 15. Ir-Catalyzed Enantioselective C−H Alkylation

Scheme 16. Rh-Catalyzed Intramolecular Asymmetric C−H Silylation

Scheme 17. Rh(III)-Catalyzed Asymmetric Annulation Reaction

variety of planar chiral ferrocene derivatives. The Pd(II)initiated reactions provide access to a broad variety of products. These processes proceed through five-membered chiral palladacycles as critical intermediates formed by enantioselective C−H bond cleavage. Redox-neutral, Pd(0)-catalyzed, intramolecular asymmetric C−H bond functionalization reactions are highly efficient and produce ferrocene derivatives with excellent levels of ee. These products can be readily transformed into chiral ligands or catalysts. In addition,

asymmetric syntheses of structurally diverse planar chiral ferrocenes via Ir-, Rh-, Au-, and Pt-catalyzed C−H bond functionalization have also been developed. These methods have impressive advantages over traditional approaches for the synthesis of functionalized planar chiral ferrocenes in terms of both step- and atom-economies. While the achievements made to date are notable, work in this field is still in its infancy. For example, enantioselective C− H functionalization of ferrocenes leading to formation of 362


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Accounts of Chemical Research Scheme 18. Enantioselective Synthesis of Planar Chiral Ferrocenes via Au/Pt-Catalyzed Cycloisomerization

organic chemistry from East China University of Science and Technology in 2005 and 2008 under the supervision of Prof. Qi-Lin Zhou and Prof. Xin-Yan Wu, respectively. He carried out his postdoctoral studies at Shanghai Institute of Organic Chemistry with Prof. Shu-Li You from 2009 to 2011 and at Georg-August-University of Göttingen with Prof. Lutz Ackermann from 2012 to 2013. In 2011, he joined the You Group at Shanghai Institute of Organic Chemistry as an associate professor. His current research interests include asymmetric catalysis and C−H bond functionalization. Chao Zheng was born in 1985 in Hubei, China, and received his B.Sc. degree in chemistry from Shanghai Jiao Tong University in 2007. He obtained his Ph.D. degree at the Shanghai Institute of Organic Chemistry under the supervision of Prof. Shu-Li You and Prof. Yu-Xue Li in 2012. He joined Prof. Shu-Li You’s group as an Assistant Professor and was promoted to Associate Professor in 2015. His current work is focused on using computational methods to gain mechanistic understanding of and design novel reactions. Shu-Li You received his B.Sc. in chemistry from Nankai University in 1996 and a Ph.D. from the Shanghai Institute of Organic Chemistry (SIOC) in 2001 under the supervision of Prof. Li-Xin Dai. He then carried out postdoctoral studies with Prof. Jeffery W. Kelly at The Scripps Research Institute, and from 2004, he worked at the Genomics Institute of the Novartis Research Foundation as a Principal Investigator before returning to SIOC in 2006. His research interests include asymmetric catalysis, synthetic methodology, natural product synthesis, and medicinal chemistry.

carbon−heteroatom bonds (C−P, C−N, C−S, etc.) has not been explored. Catalytic activities are not sufficiently high for the purposes of many practical applications, especially in the cases of Pd(II)-catalyzed intermolecular reactions. Moreover, preinstallation of directing groups is usually required for the success of C−H functionalization reactions, a factor that certainly diminishes the generality and compatibility of the processes. Further investigations of asymmetric C−H functionalization of ferrocenes with directing groups, which can be utilized directly or removed easily, are highly desirable. Finally, the development of diverse and more efficient methods for the synthesis of planar ferrocenes that involve asymmetric C−H functionalization continues to motivate our research in this area.

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ACKNOWLEDGMENTS We thank the National Basic Research Program of China from MOST (2015CB856600, 2016YFA0202900), the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB20000000), and NSFC (21332009, 21421091, 21572250) for generous financial support.

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REFERENCES

(1) (a) Kealy, T. J.; Pauson, P. L. A New Tpye of Organo-Iron Compound. Nature 1951, 168, 1039−1040. (b) Miller, S. A.; Tebboth, J. A.; Tremaine, J. F. Dicyclopentadienyliron. J. Chem. Soc. 1952, 114, 632−635. (c) Eiland, P. F.; Pepinsky, R. X-Ray Examination of Iron Biscyclopentadienyl. J. Am. Chem. Soc. 1952, 74, 4971−4971. (d) Dunitz, J. D.; Orgel, L. E. Bis-cyclopentadienyl Iron: a Molecular Sandwich. Nature 1953, 171, 121−122. (e) Dunitz, J. D.; Orgel, L. E.; Rich, A. The Crystal Structure of Ferrocene. Acta Crystallogr. 1956, 9, 373−375. (2) (a) Fu, G. C. Enantioselective Nucleophilic Catalysis with “Planar-Chiral” Heterocycles. Acc. Chem. Res. 2000, 33, 412−420. (b) Dai, L.-X.; Tu, T.; You, S.-L.; Deng, W.-P.; Hou, X.-L. Asymmetric Catalysis with Chiral Ferrocene Ligands. Acc. Chem. Res. 2003, 36, 659−667. (c) Fu, G. C. Asymmetric Catalysis with “Planar-Chiral” Derivatives of 4-(Dimethylamino)pyridine. Acc. Chem. Res. 2004, 37, 542−547. (3) (a) Blaser, H.-U.; Brieden, W.; Pugin, B.; Spindler, F.; Studer, M.; Togni, A. Solvias Josiphos Ligands: from Discovery to Technical Applications. Top. Catal. 2002, 19, 3−16. (b) Blaser, H.-U.; Pugin, B.; Spindler, F. Progress in Enantioselective Catalysis Assessed from An Industrial Point of View. J. Mol. Catal. A: Chem. 2005, 231, 1−20. (4) For books and review, see: (a) Hayashi, T., Togni, A., Eds. Ferrocenes; VCH: Weinheim, Germany, 1995. (b) Togni, A., Haltermann, R. L., Eds. Metallocenes; VCH: Weinheim, Germany, 1998. (c) Štěpnička, P., Ed. Ferrocenes; Wiley: Chichester, U.K., 2008. (d) Dai, L.-X.; Hou, X.-L., Eds. Chiral Ferrocenes in Asymmetric Catalysis; Wiley: Weinheim, Germany, 2010. (e) Schaarschmidt, D.; Lang, H. Selective Syntheses of Planar-Chiral Ferrocenes. Organometallics 2013, 32, 5668−5704.

AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. ORCID

Chao Zheng: 0000-0002-7349-262X Shu-Li You: 0000-0003-4586-8359 Notes

The authors declare no competing financial interest. Biographies De-Wei Gao received his B.Sc. in chemistry from Northeast Forestry University in 2011 and his Ph.D. from the Shanghai Institute of Organic Chemistry (SIOC) in 2016 under the supervision of Prof. Shu-Li You. His research focused on the development of methods of asymmetric C−H bond functionalization to synthesize planar and axial chiral compounds. Since September 2016, he has been conducting postdoctoral studies in the laboratory of Prof. Keary M. Engle at The Scripps Research Institute. His research interests focus on asymmetric catalysis and synthetic methodology. Qing Gu was born in Shanghai in 1979. He graduated from East China University of Science and Technology in 2001 and received his B.Sc. degree in chemistry. He obtained his Master degree and Ph.D. in 363


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of Ferrocene Derivatives. Dalton. Trans. 2015, 44, 10128−10135. (d) Zhu, D.-Y.; Chen, P.; Xia, J.-B. Synthesis of Planar Chiral Ferrocenes by Transition-Metal-Catalyzed Enantioselective C−H Activation. ChemCatChem 2016, 8, 68−73. (10) Xia, J.-B.; You, S.-L. Carbon-Carbon Bond Formation through Double sp2 C−H Activations: Synthesis of Ferrocenyl Oxazoline Derivatives. Organometallics 2007, 26, 4869−4871. (11) Takebayashi, S.; Shizuno, T.; Otani, T.; Shibata, T. Rh(III)Catalyzed Directed C−H Bond Amidation of Ferrocenes with Isocyanates. Beilstein J. Org. Chem. 2012, 8, 1844−1848. (12) Siegel, S.; Schmalz, H.-G. Insertion of Carbenoids into Cp-H Bonds of Ferrocenes: An Enantioselective-Catalytic Entry to PlanarChiral Fertocenes. Angew. Chem., Int. Ed. Engl. 1997, 36, 2456−2458. (13) (a) Sokolov, V. I.; Troitskaya, L. L. Asymmetric Catalysis in the Cyclometallation Reaction. Chimia 1978, 32, 122−123. (b) Sokolov, V. I.; Troitskaya, L. L.; Reutov, O. A. Asymmetric Cyclopalladation of Dimethylaminomethylferrocene. J. Organomet. Chem. 1979, 182, 537− 546. (c) Günay, M. E.; Richards, C. J. Synthesis of Planar Chiral Phosphapalladacycles by N-Acyl Amino Acid Mediated Enantioselective Palladation. Organometallics 2009, 28, 5833−5836. (14) (a) Shi, B.-F.; Maugel, N.; Zhang, Y.-H.; Yu, J.-Q. PdII-Catalyzed Enantioselective Activation of C(sp2)−H and C(sp3)−H Bonds Using Monoprotected Amino Acids as Chiral Ligands. Angew. Chem., Int. Ed. 2008, 47, 4882−4886. (b) Shi, B.-F.; Zhang, Y.-H.; Lam, J. K.; Wang, D.-H.; Yu, J.-Q. Pd(II)-Catalyzed Enantioselective C−H Olefination of Diphenylacetic Acids. J. Am. Chem. Soc. 2010, 132, 460−461. (c) Wasa, M.; Engle, K. M.; Lin, D. W.; Yoo, E. J.; Yu, J.-Q. Pd(II)Catalyzed Enantioselective C−H Activation of Cyclopropanes. J. Am. Chem. Soc. 2011, 133, 19598−19601. (d) Musaev, D. G.; Kaledin, A.; Shi, B.-F.; Yu, J.-Q. Key Mechanistic Features of Enantioselective C−H Bond Activation Reactions Catalyzed by [(Chiral Mono-N-Protected Amino Acid)−Pd(II)] Complexes. J. Am. Chem. Soc. 2012, 134, 1690− 1698. (e) Xiao, K.-J.; Lin, D. W.; Miura, M.; Zhu, R.-Y.; Gong, W.; Wasa, M.; Yu, J.-Q. Palladium(II)-Catalyzed Enantioselective C(sp3)− H Activation Using a Chiral Hydroxamic Acid Ligand. J. Am. Chem. Soc. 2014, 136, 8138−8142. (f) Chu, L.; Xiao, K.-J.; Yu, J.-Q. RoomTemperature Enantioselective C−H Iodination via Kinetic Resolution. Science 2014, 346, 451−455. (g) Xiao, K.-J.; Chu, L.; Chen, G.; Yu, J.Q. Kinetic Resolution of Benzylamines via Palladium(II)-Catalyzed C−H Cross-Coupling. J. Am. Chem. Soc. 2016, 138, 7796−7800. (15) Gao, D.-W.; Shi, Y.-C.; Gu, Q.; Zhao, Z.-L.; You, S.-L. Enantioselective Synthesis of Planar Chiral Ferrocenes via PalladiumCatalyzed Direct Coupling with Arylboronic Acids. J. Am. Chem. Soc. 2013, 135, 86−89. (16) Cheng, G.-J.; Chen, P.; Sun, T.-Y.; Zhang, X.; Yu, J.-Q.; Wu, Y.D. A Combined IM-MS/DFT Study on [Pd(MPAA)]-Catalyzed Enantioselective C−H Activation: Relay of Chirality through a Rigid Framework. Chem. - Eur. J. 2015, 21, 11180−11188. (17) Pi, C.; Li, Y.; Cui, X.; Zhang, H.; Han, Y.; Wu, Y. Redox of Ferrocene Controlled Asymmetric Dehydrogenative Heck Reaction via Palladium-Catalyzed Dual C−H Bond Activation. Chem. Sci. 2013, 4, 2675−2679. (18) Zhang, H.; Cui, X.; Yao, X.; Wang, H.; Zhang, J.; Wu, Y. Directly Fused Highly Substituted Naphthalenes via Pd-Catalyzed Dehydrogenative Annulation of N,N-Dimethylaminomethyl Ferrocene Using a Redox Process with a Substrate. Org. Lett. 2012, 14, 3012− 3015. (19) Shi, Y.-C.; Yang, R.-F.; Gao, D.-W.; You, S.-L. Enantioselective Synthesis of Planar Chiral Ferrocenes via Palladium-Catalyzed Annulation with Diarylethynes. Beilstein J. Org. Chem. 2013, 9, 1891−1896. (20) Ackermann, L., Eds. Modern Arylation Methods; Wiley: Weinheim, Germany, 2009. (21) Gao, D.-W.; Gu, Q.; You, S.-L. An Enantioselective Oxidative C−H/C−H Cross-Coupling Reaction: Highly Efficient Method to Prepare Planar Chiral Ferrocenes. J. Am. Chem. Soc. 2016, 138, 2544− 2547. (22) Pi, C.; Cui, X.; Liu, X.; Guo, M.; Zhang, H.; Wu, Y. Synthesis of Ferrocene Derivatives with Planar Chirality via Palladium-Catalyzed

(5) Selected examples: (a) Battelle, L. F.; Bau, R.; Gokel, G. W.; Oyakawa, R. T.; Ugi, I. K. Absolute Configuration of a 1,2Disubstituted Ferrocene Derivative with Planar and Central Elements of Chirality and the Mechanism of the Stereoselective Metalations of Optically Active α-Ferrocenyl Tertiary Amines. J. Am. Chem. Soc. 1973, 95, 482−486. (b) Rebière, F.; Riant, O.; Ricard, L.; Kagan, H. B. Asymmetric Synthesis and Highly Diastereoselective ortho-Lithiation of Ferrocenyl Sulfoxides. Application to the Synthesis of Ferrocenyl Derivatives with Planar Chirality. Angew. Chem., Int. Ed. Engl. 1993, 32, 568−570. (c) Richards, C. J.; Damalidis, T.; Hibbs, D. E.; Hursthouse, M. B. Synthesis of 2-[2-(Diphenylphosphino)ferrocenyl]oxazoline Ligands. Synlett 1995, 74−76. (d) Tsukazaki, M.; Tinkl, M.; Roglans, A.; Chapell, B. J.; Taylor, N. J.; Snieckus, V. Direct and Highly Enantioselective Synthesis of Ferrocenes with Planar Chirality by (−)-Sparteine-Mediated Lithiation. J. Am. Chem. Soc. 1996, 118, 685−686. (e) Enders, D.; Peters, R.; Lochtman, R.; Raabe, G. Asymmetric Synthesis of Novel Ferrocenyl Ligands with Planar and Central Chirality. Angew. Chem., Int. Ed. 1999, 38, 2421−2423. (f) Laufer, R. S.; Veith, U.; Taylor, N. J.; Snieckus, V. C2-Symmetric Planar Chiral Ferrocene Diamides by (−)-Sparteine-Mediated Directed ortho-Lithiation. Synthesis and Catalytic Activity. Org. Lett. 2000, 2, 629−631. (g) Bolm, C.; Kesselgruber, M.; Muñiz, K.; Raabe, G. Diastereoselective Synthesis of Ferrocenyl Sulfoximines with Planar and Central Chirality. Organometallics 2000, 19, 1648−1651. (h) Bolm, C.; Kesselgruber, M.; Raabe, G. The First Planar-Chiral Stable Carbene and Its Metal Complexes. Organometallics 2002, 21, 707−710. (i) Genet, C.; Canipa, S. J.; O’Brein, P.; Taylor, S. Catalytic Asymmetric Synthesis of Ferrocenes and P-Stereogenic Bisphosphines. J. Am. Chem. Soc. 2006, 128, 9336−9337. For a review on kinetic resolution: (j) Alba, A.-N. R.; Rios, R. Kinetic Resolution: A Powerful Tool for the Synthesis of Planar-Chiral Ferrocenes. Molecules 2009, 14, 4747−4757. (6) (a) Mercier, A.; Yeo, W. C.; Chou, J.; Chaudhuri, P. D.; Bernardinelli, G.; Kündig, E. P. Synthesis of Highly Enantiomerically Enriched Planar Chiral Ruthenium Complexes via Pd-catalysed Asymmetric Hydrogenolysis. Chem. Commun. 2009, 5227−5229. (b) Mercier, A.; Urbaneja, X.; Yeo, W. C.; Chaudhuri, P. D.; Cumming, G. R.; House, D.; Bernardinelli, G.; Kündig, E. P. Asymmetric Catalytic Hydrogenolysis of Aryl-Halide Bonds in Fused Arene Chromium and Ruthenium Complexes. Chem. - Eur. J. 2010, 16, 6285−6299. (7) Ogasawara, M.; Arae, S.; Watanabe, S.; Nakajima, K.; Takahashi, T. Kinetic Resolution of Planar-Chiral 1,2-Disubstituted Ferrocenes by Molybdenum-Catalyzed Asymmetric Intraannular Ring-Closing Metathesis. Chem. - Eur. J. 2013, 19, 4151−4154. (8) For reviews and book, see: (a) Giri, R.; Shi, B.-F.; Engle, K. M.; Maugel, N.; Yu, J.-Q. Transition Metal-Catalyzed C−H Activation Reactions: Diastereoselectivity and Enantioselectivity. Chem. Soc. Rev. 2009, 38, 3242−3272. (b) Peng, H. M.; Dai, L.-X.; You, S.-L. Enantioselective Palladium-Catalyzed Direct Alkylation and Olefination Reaction of Simple Arenes. Angew. Chem., Int. Ed. 2010, 49, 5826−5828. (c) Wencel-Delord, J.; Colobert, F. Asymmetric C(sp2) − H Activation. Chem. - Eur. J. 2013, 19, 14010−14017. (d) Engle, K. M.; Yu, J.-Q. Developing Ligands for Palladium(II)-Catalyzed C−H Functionalization: Intimate Dialogue between Ligand and Substrate. J. Org. Chem. 2013, 78, 8927−8955. (e) Zheng, C.; You, S.-L. Recent Development of Direct Asymmetric Functionalization of Inert C−H Bonds. RSC Adv. 2014, 4, 6173−6214. (f) Ye, B.; Cramer, N. Chiral Cyclopentadienyls: Enabling Ligands for Asymmetric Rh(III)-Catalyzed C−H Functionalizations. Acc. Chem. Res. 2015, 48, 1308−1318. (g) You, S.-L., Ed. Asymmetric Functionalization of C−H Bonds; RSC: Cambridge, U.K., 2015. (9) (a) Wang, Y.; Zhang, A.; Liu, L.; Kang, J.; Zhang, F.; Ma, W. Recent Advances in Transition-Metal-Catalyzed Enantioselective Syntheses of Planar Chiral Ferrocenes. Youji Huaxue 2015, 35, 1399−1406. (b) Arae, S.; Ogasawara, M. Catalytic Asymmetric Synthesis of Planar-Chiral Transition-Metal Complexes. Tetrahedron Lett. 2015, 56, 1751−1761. (c) López, L. A.; López, E. Recent Advances in Transition Metal-catalyzed C−H Bond Functionalization 364


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Accounts of Chemical Research Enantioselective C−H Bond Activation. Org. Lett. 2014, 16, 5164− 5167. (23) Gao, D.-W.; Yin, Q.; Gu, Q.; You, S.-L. Enantioselective Synthesis of Planar Chiral Ferrocenes via Pd(0)-Catalyzed Intramolecular Direct C−H Bond Arylation. J. Am. Chem. Soc. 2014, 136, 4841−4844. (24) Fukuzawa, S.-i.; Yamamoto, M.; Hosaka, M.; Kikuchi, S. Preparation of Chiral Homoannularly Bridged N,P-Ferrocenyl Ligands by Intramolecular Coupling of 1,5-Dilithioferrocenes and Their Application in Asymmetric Allylic Substitution Reactions. Eur. J. Org. Chem. 2007, 5540−5545. (25) Nottingham, C.; Müller-Bunz, H.; Guiry, P. J. A Family of Chiral Ferrocenyl Diols: Modular Synthesis, Solid-State Characterization, and Application in Asymmetric Organocatalysis. Angew. Chem., Int. Ed. 2016, 55, 11115−11119. (26) Deng, R.; Huang, Y.; Ma, X.; Li, G.; Zhu, R.; Wang, B.; Kang, Y.B.; Gu, Z. Palladium-Catalyzed Intramolecular Asymmetric C−H Functionalization/Cyclization Reaction of Metallocenes: An Efficient Approach toward the Synthesis of Planar Chiral Metallocene Compounds. J. Am. Chem. Soc. 2014, 136, 4472−4475. (27) Zhang, S.; Lu, J.; Ye, J.; Duan, W.-L. Asymmetric C−H Arylation for the Synthesis of Planar Chiral Ferrocenes: Controlling Enantioselectivity Using Chiral Phosphoric Acids. Youji Huaxue 2016, 36, 752−759. (28) Ma, X.; Gu, Z. Palladium-Catalyzed Intramolecular Cp−H Bond Functionalization/Arylation: An Enantioselective Approach to Planar Chiral Quinilinoferrocenes. RSC Adv. 2014, 4, 36241−36244. (29) Liu, L.; Zhang, A.-A.; Zhao, R.-J.; Li, F.; Meng, T.-J.; Ishida, N.; Murakami, M.; Zhao, W.-X. Asymmetric Synthesis of Planar Chiral Ferrocenes by Enantioselective Intramolecular C−H Arylation of N(2-Haloaryl)ferrocenecarboxamides. Org. Lett. 2014, 16, 5336−5338. (30) Gao, D.-W.; Zheng, C.; Gu, Q.; You, S.-L. Pd-Catalyzed Highly Enantioselective Synthesis of Planar Chiral Ferrocenylpyridine Derivatives. Organometallics 2015, 34, 4618−4625. (31) Albicker, M. R.; Cramer, N. Enantioselective PalladiumCatalyzed Direct Arylations at Ambient Temperature: Access to Indanes with Quaternary Stereocenters. Angew. Chem., Int. Ed. 2009, 48, 9139−9142. (32) Gao, D.-W.; Gu, Y.; Wang, S.-B.; Gu, Q.; You, S.-L. Palladium(0)-Catalyzed Asymmetric C−H Alkenylation for Efficient Synthesis of Planar Chiral Ferrocenes. Organometallics 2016, 35, 3227−3233. (33) Shibata, T.; Shizuno, T. Iridium-Catalyzed Enantioselective C− H Alkylation of Ferrocenes with Alkenes Using Chiral Diene Ligands. Angew. Chem., Int. Ed. 2014, 53, 5410−5413. (34) (a) Shibata, T.; Shizuno, T.; Sasaki, T. Enantioselective Synthesis of Planar-Chiral Benzosiloloferrocenes by Rh-Catalyzed Intramolecular C−H Silylation. Chem. Commun. 2015, 51, 7802− 7804. (b) Zhang, Q.-W.; An, K.; Liu, L.-C.; Yue, Y.; He, W. RhodiumCatalyzed Enantioselective Intramolecular C−H Silylation for the Syntheses of Planar-Chiral Metallocene Siloles. Angew. Chem., Int. Ed. 2015, 54, 6918−6921. (c) Murai, M.; Matsumoto, K.; Takeuchi, Y.; Takai, K. Rhodium-Catalyzed Synthesis of Benzosilolometallocenes via the Dehydrogenative Silylation of C(sp2)−H Bonds. Org. Lett. 2015, 17, 3102−3105. (35) Xie, W.; Li, B.; Xu, S.; Song, H.; Wang, B. Palladium-Catalyzed Direct Dehydrogenative Annulation of Ferrocenecarboxamides with Alkynes in Air. Organometallics 2014, 33, 2138−2141. (36) Wang, S.-B.; Zheng, J.; You, S.-L. Synthesis of Ferrocene-Based Pyridinones through Rh(III)-Catalyzed Direct C−H Functionalization Reaction. Organometallics 2016, 35, 1420−1425. (37) Urbano, A.; Hernández-Torres, G.; del Hoyo, A. M.; MartínezCarrión, A.; Carreño, M. C. Mild Access to Planar-Chiral orthoCondensed Aromatic Ferrocenes via Gold(I)-Catalyzed Cycloisomerization of ortho-Alkynylaryl Ferrocenes. Chem. Commun. 2016, 52, 6419−6422. (38) Shibata, T.; Uno, N.; Sasaki, T.; Kanyiva, K. S. Pt-Catalyzed Enantioselective Cycloisomerization for the Synthesis of Planar-Chiral Ferrocene Derivatives. J. Org. Chem. 2016, 81, 6266−6272. 365


Synthesis of Planar Chiral Ferrocenes via Transition-Metal-Catalyzed

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