Frustrated Lewis Pairs Catalyzed Asymmetric Metal-Free

Article pubs.acs.org/accounts

Cite This: Acc. Chem. Res. 2018, 51, 191−201

Frustrated Lewis Pairs Catalyzed Asymmetric Metal-Free Hydrogenations and Hydrosilylations Wei Meng, Xiangqing Feng, and Haifeng Du* Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Molecular Recognition and Function, CAS Research/Education Center for Excellence in Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China School of Chemical Sciences, University of Chinese Academy of Sciences, Beijing 100049, China CONSPECTUS: The use of frustrated Lewis pairs is an extremely important approach to metal-free hydrogenations. In contrast to the rapid growth of catalytic reactions, asymmetric hydrogenations are far less developed due to a severe shortage of readily available chiral frustrated Lewis pair catalysts with high catalytic activities and selectivities. Unlike the stable Lewis base component of frustrated Lewis pairs, the moisturesensitive boron Lewis acid component is difficult to prepare. The development of convenient methods for the quick construction of chiral boron Lewis acids is therefore of great interest. In this Account, we summarize our recent studies on frustrated Lewis pair-catalyzed, asymmetric metal-free hydrogenations and hydrosilylations. To address the shortage of highly active and selective catalysts, we developed a novel strategy for the in situ preparation of chiral boron Lewis acids by the hydroboration of chiral dienes or diynes with Piers’ borane without further purification, which allows chiral dienes or diynes to act like ligands. This strategy ensures the construction of a useful toolbox of catalysts for asymmetric metal-free hydrogenations and hydrosilylations is rapid and operationally simple. Another strategy is using combinations of readily available Lewis acids and bases containing hydridic and acidic hydrogen atoms, respectively, as a novel type of frustrated Lewis pairs. Such systems provide a great opportunity for using simple chiral Lewis bases as the origins of asymmetric induction. With chiral diene-derived boron Lewis acids as catalysts, a broad range of unsaturated compounds, such as imines, silyl enol ethers, 2,3-disubstituted quinoxalines, and polysubstituted quinolines, are all viable substrates for asymmetric metal-free hydrogenations and give the corresponding products in good yields with high enantioselectivities and/or stereoselectivities. These chiral catalysts are very effective for bulky substrates, and the substrate scope for these metal-free asymmetric hydrogenations has been dramatically expanded. Chiral alkenylboranes were designed to enhance the rigidity of the framework and modify the Lewis acidity through the resulting double bonds. Frustrated Lewis pairs of chiral alkenylboranes and phosphines are a class of highly effective catalysts for asymmetric Piers-type hydrosilylations of 1,2-dicarbonyl compounds, and they give the desired products in high yields and enantioselectivities. Moreover, asymmetric transfer hydrogenations of imines and quinoxalines with ammonia borane as the hydrogen source have been achieved with frustrated Lewis pair of Piers’ borane and (R)-tert-butylsulfinamide as the catalyst. Mechanistic studies have suggested that the hydrogen transfer occurs via an 8-membered ring transition state, and regeneration of the reactive frustrated Lewis pair with ammonia borane occurs through a concerted 6-membered ring transition state.

1. INTRODUCTION

bonds involves synergistic interactions of the vacant orbital of the Lewis acid and the lone-pair electron orbital of the Lewis base with the σ bonding and σ* antibonding orbitals of H2, respectively. This pioneering work opened up a new field of chemistry referred to as frustrated Lewis pairs (FLPs), which has attracted substantial attention in the past decade.2 The great success of metal-free hydrogenations can clearly be attributed to the major advances in the field of FLPs. A broad range of unsaturated compounds have been hydrogenated using

In 2006, Stephan and co-workers discovered that sterically hindered Lewis acid and Lewis base pairs could reversibly activate H2 (Scheme 1).1 The heterolytic cleavage of H−H Scheme 1. Seminal Work on Reversible Activation of H2 by FLPs

Received: October 24, 2017 Published: December 15, 2017 © 2017 American Chemical Society

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DOI: 10.1021/acs.accounts.7b00530 Acc. Chem. Res. 2018, 51, 191−201

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Accounts of Chemical Research

Figure 1. Representative catalysts for asymmetric hydrogenation and hydrosilylation.

FLP catalysis.3 In sharp contrast, asymmetric metal-free hydrogenations are far less developed.4 The first example was reported in 2008 and employed an α-pinene-derived chiral borane as the catalyst for the hydrogenation of an imine to give 13% ee (Figure 1).5 Subsequently, several chiral FLPs were designed and synthesized for asymmetric hydrogenations and Piers-type hydrosilylations (Figure 1).6−13 However, except for enamines,10 the substrate scope for these asymmetric hydrogenations was limited to imines and 2-phenylquinoline, and less than 90% ee was usually obtained.4 Therefore, the development of chiral FLP-catalyzed, highly enantioselective, metal-free hydrogenations with wide substrate scopes still remains a formidable challenge. The syntheses of the chiral FLP catalysts listed in Figure 1 can be generally categorized into two protocols. The first group were prepared through the hydroboration of chiral alkenes with Piers’ borane HB(C6F5)2,14 which, when an internal alkene is used, often generates a mixture of diastereoisomers. The other group were prepared via the substitution of (C6F5)nBCl3−n with chiral organometallic reagents. Of the two components of the FLPs, the Lewis bases are stable and readily available, but boron Lewis acids are very sensitive to moisture and difficult to access. The lack of convenient and reliable methods for the quick construction of chiral boron Lewis acids seems to be a major obstacle to progress in the field. Based on our previous work involving the development of acyclic chiral diene ligands for transition-metal catalysis,15 we proposed a novel strategy for generating chiral boranes in situ by the hydroboration of chiral terminal dienes or diynes with Piers’ borane without further purification (Scheme 2). In other words, chiral dienes or diynes can act like ligands. This strategy avoids the production of mixtures of diastereoisomers in the case of internal alkenes or alkynes and ensures a rapid and operationally simple preparation. Moreover, inspired by the classical FLPs, we developed a novel type of FLP containing acidic and hydridic hydrogen atoms (Scheme 2). This Account summarizes our studies on asymmetric metal-free hydrogenations and hydrosilylations.

Scheme 2. Our Strategy for Developing Chiral Boron Lewis Acids or a Novel Type of FLP

compounds 2 (Scheme 3). Subsequent reduction with LiAlH4 and oxidation with PCC afforded chiral dialdehydes 3. Chiral Scheme 3. Synthesis of Chiral Dienes

dienes 4 can then be conveniently accessed via Wittig reactions.16 A valuable toolbox of diverse chiral dienes 4 was thus rapidly constructed for asymmetric metal-free hydrogenations. 2.1. Hydrogenation of Imines and Silyl Enol Ethers

2. CHIRAL DIENE-DERIVED BORON LEWIS ACIDS With binaphthyl-based dicarboxylate 1 as a starting material, a variety of substituents can be easily incorporated onto the binaphthyl framework via Suzuki coupling reactions to give

A variety of chiral boron Lewis acids generated in situ from chiral dienes 4 and HB(C6F5)2 were investigated for the asymmetric hydrogenation of imine 5a (Scheme 4).17 The substituents of chiral dienes 4 had significant impacts on the 192


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Accounts of Chemical Research Scheme 4. Asymmetric Hydrogenation of Imine 5a with Selected Chiral Dienes 4a−h

Scheme 6. Asymmetric Hydrogenation of 1,4-Benzoxazines 7

deactivation of the metal catalysts. We found that highly stereoselective hydrogenations of vicinal diimines 9 could be realized using 5−10 mol % of B(C6F5)3 under mild conditions (Scheme 7).21 A variety of 1,2-diamines 10 were obtained in

enantioselectivities of the reaction. Chiral diene 4h, bearing very bulky substituents, gave a promising 60% ee. After a further optimization, a variety of imines 5 containing both electron-donating and electron-withdrawing substituents were shown to be effective substrates for this reaction and gave the desired products 6 in 63−99% yields with 74−89% ee’s (Scheme 5). The catalyst loading can be reduced to as low as

Scheme 7. Stereoselective Hydrogenation of 1,2-Diimines

Scheme 5. Asymmetric Hydrogenation of Imines 5

92−99% yields as purely the cis isomers. The asymmetric hydrogenation of diimine 9j was further studied by using a diene 4i-derived chiral borane catalyst (Scheme 8). Unfortunately, only 10% ee was obtained in this reaction. Despite the low enantioselectivity, the chemistry of FLPs may provide a potential solution for this challenge. 1.25 mol %. Significantly, a sensitive alkyne group (6c) was well tolerated in this metal-free catalytic system. Moreover, diene 4h-derived chiral borane was also effective for the asymmetric Piers-type hydrosilylation of imines.18 Although chiral boron Lewis acids have not been isolated, NMR studies indicate that they are cleanly generated by the treatment of chiral dienes 4 with HB(C6F5)2 at room temperature for several minutes. Cyclic imines were seldom employed as substrates for FLPcatalyzed metal-free hydrogenations. Using B(C6F5)3 (2.5 mol %) as the catalyst, 3-substituted 2H-1,4-benzoxazines 7 were successfully hydrogenated to furnish desired products 8 in high yields.19 The asymmetric hydrogenation of 1,4-benzoxazines 7 with diene 4h-derived chiral boron Lewis acid afforded the corresponding products 8 in high yields and up to 42% ee (Scheme 6). More effective chiral catalysts still need to be identified for this reaction. Vicinal diamines are present in a wide range of biologically active compounds and chiral catalysts. Catalytic hydrogenation of vicinal diimines is likely a straightforward approach to the synthesis of vicinal diamines. However, such transformations are not common20 possibly because of steric hindrance and/or

Scheme 8. Asymmetric Hydrogenation of 1,2-Diimine 9j

In recent years, important advances have been made in FLPcatalyzed hydrogenations of ketones,22 but its asymmetric version has not been reported and remains a challenge. Erker et al. and Paradies et al. reported the hydrogenation of silyl enol ethers,23 respectively, which provides an alternative method for the synthesis of optically active secondary alcohols using chiral FLPs. Diene 4g-derived chiral borane could not promote the 193


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co-workers reported a hydrogenation of pyridines with one equivalent of B(C6F5)3.26 We were inspired to develop a catalytic reaction using boranes generated in situ from alkenes as catalysts. After testing a variety of commercially available alkenes, the pentafluorostyrene-derived borane was found to be highly effective for the hydrogenation of pyridines 13 and gave the desired piperidines 14 in high yields with excellent cis selectivity (Scheme 11).27,28 Pyridines containing 2-aryl, 2,6-

hydrogenation of silyl enol ether 11a without a Lewis base (Scheme 9). Lewis bases were essential for this reaction and Scheme 9. Asymmetric Hydrogenation of Silyl Enol Ether 11a with Selected Lewis Bases

Scheme 11. Stereoselective Hydrogenation of Pyridines

had substantial effects on both the reactivity and enantioselectivity. tBu3P proved to be the optimal Lewis base and gave the desired products in 98% ee. Interestingly, when using chiral diene 4f, the absolute configuration of alcohol 12a was reversed with 94% ee. A variety of silyl enol ethers 11 were suitable substrates for the asymmetric hydrogenation and afforded the desired secondary alcohols in 93−99% yields with 88−99% ee’s (Scheme 10).24 Notably, carbon−carbon double bonds (such as the one in 12i) are stable under the current reaction conditions.

diaryl, 2-alkyl-6-aryl, 2,6-dialkyl, and 2,4,6-triaryl substituents were all tolerated under the current reaction conditions. Moreover, in addition to H2, ammonia borane was also used as an effective hydrogen source for a similar transformation.29 Interestingly, 2,2′-bipyridines, which are often used as ligands in transition-metal catalysis, were also effective substrates for the current metal-free hydrogenations (Scheme 12).27 Both

Scheme 10. Asymmetric Hydrogenation of Silyl Enol Ethers 11

Scheme 12. Stereoselective Hydrogenation of 2,2Bipyridines

pyridine rings of the more reactive 6,6′-ditolyl-2,2′-bipyridine (13h) were reduced, and product 14h was generated in 75% yield with >99/1 dr. In contrast, only one pyridine ring was reduced for the less reactive 6,6′-dimethyl-2,2′-bipyridine (13i), which gave chiral 14i in 59% yield. Several chiral dienes were examined for the asymmetric hydrogenation of pyridine 13i. Unfortunately, less than 10% ee’s and moderate conversions were obtained. Alternatively, both enantiomers of 14i were easily prepared in >99% ee through a resolution using L- and Dtartaric acids.

2.2. Hydrogenation of N-Heteroarenes

Significant advances have been made in the catalytic hydrogenation of N-heteroarenes.25 Piperidines are privileged moieties that exist in numerous biologically active molecules. However, the synthesis of piperidines by homogeneous hydrogenation of simple pyridines is still unsolved due to the aromaticity of pyridines and their ability to potentially deactivate transition-metal catalysts. Recently, Stephan and 194


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Accounts of Chemical Research Scheme 13. Asymmetric Hydrogenation of 1,8-Naphthyridines

A pentafluorostyrene-derived borane can be used in the hydrogenation of 2,7-disubstituted 1,8-naphthyridines 15 to give 1,2,3,4-tetrahydro-1,8-naphthyridines 16 in 83−98% yields. With the diene 4j-derived chiral borane, the corresponding asymmetric hydrogenations were realized and afforded the desired products 16 in 90−96% yields with 14−74% ee’s (Scheme 13).30,31 All these reactions occurred exclusively on the alkyl-substituted rings. Asymmetric hydrogenations of polysubstituted N-heteroarenes represent an interesting but challenging field because these reactions efficiently and simultaneously generate at least two chiral centers. In sharp contrast to the well-studied monosubstituted quinoxalines,25 2,3-disubstituted quinoxalines have rarely been investigated as substrates for asymmetric hydrogenations.32 A method for the hydrogenation of 2,3-dimethyland 2,3-diphenylquinoxaline using one equivalent of B(C6F5)3 was reported by Stephan and co-workers to give decahydroinstead of tetrahydroquinoxaline derivatives.26 In fact, we found that with a catalytic amount of B(C6F5)3 (10 mol %) or B(pHC6F4)3 (5 mol %) as catalyst, the highly stereoselective hydrogenation of 2,3-disubstituted quinoxalines 17 was successfully achieved and gave a variety of tetrahydroquinoxalines 18 in 80−99% yields with excellent cis selectivities (Scheme 14).33 2,3-Diaryl-, 2,3-dialkyl-, and 2-aryl-3-alkylquinoxalines were all tolerated in this hydrogenation. Various dienes 4-derived chiral boranes were investigated for the asymmetric hydrogenation of 2-aryl-3-alkylquinoxalines 17 with n-hexane as the solvent, and diene 4k gave the best results (Scheme 15). A variety of tetrahydroquinoxalines 18 were obtained in high yields with 67−96% ee’s and excellent cis selectivities (Scheme 15).33 The asymmetric hydrogenation was also carried out on a gram scale without loss of reactivity or enantioselectivity. However, 2,3-dialkyl- and 2,3-diarylquinoxalines were not reactive under the current reaction conditions. Bulky 2,3,4-trisubstituted quinolines have never been employed as substrates for asymmetric hydrogenations. We envisioned that FLP catalysts might be compatible with these bulky substrates. A variety of chiral dienes 4 were therefore investigated for these challenging hydrogenations. Interestingly, chiral dienes 4i, 4l, and 4m, which lack substituents at the 3and 3′-positions, were found to give the desired products in 20−54% ee’s (Scheme 16).34 Chiral diene 4n gave product 20a in 28% conversion with 92% ee. Increasing the reaction concentration significantly improved the reactivity without impacting the enantioselectivity. A variety of quinolines 19

Scheme 14. Stereoselective Hydrogenation of 2,3Disubstituted Quinoxalines

Scheme 15. Asymmetric Hydrogenation of 2,3-Disubstituted Quinoxalines

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Accounts of Chemical Research Scheme 16. Asymmetric Hydrogenation of Quinoline 19a with Selected Chiral Dienes

Scheme 18. Asymmetric Hydrogenation of 2,4-Disubstituted Quinolines

were effective substrates and gave tetrahydroquinolines 20 in 76−99% yields with 82−99% ee’s (Scheme 17).34 Notably, cis, cis isomers were exclusively obtained in most cases. This work is a good example of the unique advantages of FLPs for very bulky substrates. Scheme 19. Asymmetric Hydrogenation of 2,3-Disubstituted Quinolines

Scheme 17. Asymmetric Hydrogenation of 2,3,4Trisubstituted Quinolines

workup with nBuLi and saturated aqueous NH4Cl (Scheme 20).36 Chiral diyne 26a (Ar = 3,5-tBu2C6H3) was found to be highly effective for the asymmetric hydrogenation of silyl enol ethers.36 In this reaction, chiral diyne 26a gave similar results to those of chiral diene 4g in terms of both reactivity and enantioselectivity (Scheme 9). Piers-type hydrosilylations of unsaturated compounds, in which a boron Lewis acid activates the Si−H bond instead of the substrates forming silylium and hydridoborate ions, have attracted the interest of both synthetic and mechanistic chemists.37,38 However, asymmetric Piers-type hydrosilylations are less developed.4b,7b,12,38b Especially for ketones,7b,12 the development of highly enantioselective catalysts is still an attractive target. We examined the asymmetric hydrosilylation of benzil (27a) using diyne 26a-derived chiral borane in the absence of a Lewis base (Scheme 21).39,40 Benzoin (28a) was obtained in 25% conversion with 22% ee. When phosphine Lewis bases were used together with chiral boranes, the enantioselectivity was greatly improved. Cy3P was the optimal Lewis base and gave benzoin (28a) with 98% ee. Substituents at the 3- and 3′-positions of chiral diynes 26a-e has obvious influences on the reactivity and enantioselectivity of the reaction. Further increasing the loading of PhMe2SiH to three equivalents led 94% conversion to the desired product in 99% ee. Notably, chiral diyne 26a was substantially better than chiral diene 4g (11% conversion with 56% ee) in this reaction.

We then turned our attention to 2,4-disubstituted quinolines, another class of compounds that are not tolerated in asymmetric hydrogenations. When using chiral diene 4k, the asymmetric hydrogenation of 2,4-disubstituted quinolines 21 proceeded smoothly to give products 22 in 75−98% yields with 86−98% ee’s (Scheme 18).35 Notably, a 4-cyclohexenyl substituent was well tolerated in this reaction and provided tetrahydroquinoline 22h in 93% yield with 86% ee. The current catalytic system was also effective for 2,3-disubstituted quinolines 23 (Scheme 19).35 A variety of cis-tetrahydroquinolines 24 were obtained in 74−99% yields with 45−80% ee’s. The relatively lower ee’s for 24 suggest that the substituents at the 4-positions of the quinolines are essential for achieving high enantioselectivity.

3. CHIRAL DIYNE-DERIVED BORON LEWIS ACIDS Chiral diynes were used to enhance the rigidity of the framework and modify the Lewis acidity of the catalyst through the resulting double bonds from the hydroboration with HB(C6F5)2. Starting from dialdehydes 3, chiral diynes 26 were synthesized through a Corey-Fuchs reaction followed by a 196


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Accounts of Chemical Research Scheme 20. Synthesis of Chiral Diynes

Scheme 21. Hydrosilylation of Benzil with Selected Lewis Bases and Chiral Diynes

Figure 2. Asymmetric hydrosilylation of α-keto esters.

asymmetric Piers-type hydrosilylation of acetophenone gave the corresponding product in 95% yield and 42% ee. In comparison, Oestrich and co-workers achieved up to 99% ee’s for simple ketone substrates with chiral boron Lewis acid catalysts.12 However, 1,2-dicarbonyl compounds were not suitable substrates in their catalytic system. Moreover, a Piers-type hydrosilylation of chromones and flavones has been realized using 0.1 mol % of borane catalyst generated from pentafluorostyrene with HB(C6F5)2, and the method gave the corresponding products in 60−99% yields.41 When the diyne 26a-derived borane was used as the chiral catalyst, various chromanones and flavanones can be obtained in good yields with 11−32% ee’s.

Various symmetrical 1,2-diketones 27 can be efficiently reduced to give the desired α-hydroxy ketones 28 in good yields with 86−99% ee’s (Scheme 22).40 Although three Scheme 22. Asymmetric Hydrosilylation of 1,2-Diketones

4. A NOVEL TYPE OF FRUSTRATED LEWIS PAIRS Inspired by the classic zwitterion species resulting from the splitting of H2 by FLPs (Figure 3), we proposed a novel type of

Figure 3. Our hypothesis for the development of novel FLPs.

FLP in which active Hδ‑ and Hδ+ are present initially in the Lewis acid and Lewis base, respectively.42 After hydrogen transfer, a covalent bond will be formed between the Lewis acid and base. A suitable hydrogen source will be used to split this newly formed bond and regenerate the reactive FLP. To achieve this goal, two key issues must be addressed; the two components of the FLP cannot rapidly release H2, and the formed covalent bond must be easy to split. Notably, this novel type of FLP would allow the use of chiral bases to control the asymmetric induction.

equivalents of PhMe2SiH were used, the over-reduction diol byproducts were not observed in all these cases. However, unsymmetrical 1,2-diketones were not effective substrates under the current reaction conditions. The substrate scope can be further extended to α-keto esters, and various α-hydroxy esters 29 were prepared in 82−96% yields with 96−99% ee’s (Figure 2).40 Under the current reaction conditions, the 197


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Accounts of Chemical Research Using a combination of Piers’ borane (1.1 equiv) and (R)tert-butylsulfinamide43 (30) (1.1 equiv), a stoichiometric asymmetric transfer hydrogenation of imines was achieved and afforded the corresponding amines in 78−96% yields with 73−96% ee’s.42 The challenge was making this reaction catalytic. Various hydrogen sources were investigated for the asymmetric transfer hydrogenation of imine 5a using 10 mol % of HB(C6F5)2 and 30 (Scheme 23). H2 was not a suitable Scheme 23. Catalytic Asymmetric Transfer Hydrogenation of Imine 5a

hydrogen source for the regeneration of the reactive FLPs. In contrast, the reaction with ammonia borane as the hydrogen source44 proceeded smoothly and gave amine 6a in 96% conversion but with a dramatic reduction in the enantioselectivity. After optimization, using the reaction conditions shown in Scheme 24, the catalytic asymmetric transfer

Figure 4. Plausible catalytic cycle.

hydrogen transfer occurs via 8-membered ring transition state TS1. 11B NMR studies on the reaction of compound 34 with ammonia borane indicated reactive complex 33 was regenerated. A DFT computational study suggested this regeneration occurs via 6-membered ring transition state TS2. A plausible catalytic cycle for this transfer hydrogenation is outlined as shown in Figure 4. This novel FLP was also effective for the asymmetric transfer hydrogenation of 2,3-disubstituted quinoxalines.45 For 2-alkyl3-arylquinoxalines 17, the reaction smoothly afforded cistetrahydroquinoxalines 18 as the major products in 72−95% yields with 77−86% ee’s (Scheme 25). Compared to the catalytic hydrogenation shown in Scheme 15, the current transfer hydrogenation method usually results in lower ee’s.

Scheme 24. Asymmetric Transfer Hydrogenation of Imines 31 with Ammonia Borane

Scheme 25. Asymmetric Transfer Hydrogenation of 2-Alkyl3-arylquinoxalines

hydrogenation of imines 31 afforded the desired amine products 32 in good yields with 84−95% ee’s.42 Pyridine additive may prevent the HB(C6F5)2-catalyzed racemic reaction of imines with ammonia borane by trapping the free Piers’ borane. The mechanism for this reaction was investigated using both experimental and theoretical techniques. When Piers’ borane and sulfinamide 30 were mixed, NMR studies and DFT calculations suggested formation of B/O complex 33 was preferred (Figure 4). The 11B NMR study of the reaction of complex 33 with imine 31 showed that the intensity of the signal for complex 33 gradually decreased, while the intensity of the signal for compound 34 increased as the reaction progressed. Further DFT calculations suggested that this

Notably, 2,3-dialkylquinoxalines 17, which are not reactive in the asymmetric hydrogenation with H2, were reactive in the asymmetric transfer hydrogenation with ammonia borane. Unlike the reactions with 2-alkyl-3-arylquinoxalines, the reactions of 2,3-dialkylquinoxalines usually favor the trans products. A variety of tetrahydroquinoxalines 18 were obtained 198


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Accounts of Chemical Research Scheme 26. Asymmetric Transfer Hydrogenation of 2,3-Dialkylquinoxalines

react smoothly under FLP catalysis. These features provide great opportunities for future in-depth studies.

in 58−93% yields with 28:72−75:25 dr (trans/cis) and 89−99% ee’s (for the trans isomer) (Scheme 26). In contrast, the ee’s for the corresponding cis isomers were much lower.

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5. CONCLUSION The chemistry of FLPs offers new methods of metal-free hydrogenations. However, chiral FLP-catalyzed, asymmetric hydrogenations are still in their infancy due to a severe shortage of readily available chiral catalysts with high catalytic activities and selectivities. As summarized in this Account, we developed a strategy for using chiral dienes or diynes like ligands for the in situ generation of novel chiral boron Lewis acids by hydroboration with HB(C6F5)2. The convenient method for the generation of diverse, chiral boranes allows the rapid construction of a valuable toolbox of catalysts for asymmetric metal-free hydrogenations. A wide range of unsaturated compounds, such as imines, silyl enol ethers, 2,3-disubstituted quinoxalines, and polysubstituted quinolines, were effective substrates for these asymmetric hydrogenations and furnished the corresponding products in good yields with high enantioselectivities and/or stereoselectivities. Notably, the FLP catalysts have been shown to be well suited to bulky substrates. Moreover, the challenging asymmetric Piers-type hydrosilylations of 1,2-dicarbonyl compounds have been successfully realized using chiral diyne-derived alkenylboranes coupled with phosphine Lewis bases, which provide with high reactivities and enantioselectivities. Significantly, inspired by classic FLPs, a novel type of FLPs that use a combination of active H δ‑ - and H δ+ -containing Lewis acid and base, respectively, has been developed. Using the simple FLP of Piers’ borane and (R)-tert-butylsulfinamide, a catalytic highly enantioselective transfer hydrogenation of imines and 2,3disubstituted quinoxalines with ammonia borane has been successfully achieved. The FLP-catalyzed asymmetric hydrogenations and hydrosilylations described in this Account have various advantages. (1) Chiral catalysts with diverse structures are easily obtained. (2) Highly enantioselective and/or stereoselective hydrogenations and hydrosilylations have been realized, and these reactions represent a formidable challenge in this field. (3) A broad range of substrates are well tolerated. (4) Some substrates that are challenging for transition-metal catalysts

AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. ORCID

Wei Meng: 0000-0002-1555-3738 Haifeng Du: 0000-0003-0122-3735 Notes

The authors declare no competing financial interest. Biographies Wei Meng was born in Hebei, China. He received his B.Sc. from Shanxi University in 2006 and Ph.D. from Tianjin University in 2012 under Prof. Jun-An Ma. He joined Peking University as a postdoctoral fellow in 2012 under Prof. Zhi-Xiang Yu. He joined Institute of Chemistry, Chinese Academy of Sciences, as an Assistant Professor in 2014 and was promoted to Associate Professor in 2017. Xiangqing Feng was born in 1983. She received her B.Sc. from Xinyang Normal University in 2006, her M.Sc. in 2009 from Nankai University, and her Ph.D. from Institute of Chemistry, Chinese Academy of Sciences, under Professor Haifeng Du in 2012. She joined Institute of Chemistry, Chinese Academy of Sciences, as an Assistant Professor in 2012. Haifeng Du was born in 1974. He received his B.Sc. in 1998 from Nankai University, M.Sc. from Nankai University and Shanghai Institute of Organic Chemistry with Professors Jiben Meng and Kuiling Ding in 2001, and Ph.D. from Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, under Professor Kuiling Ding in 2004. He joined Colorado State University as a postdoctoral fellow with Professor Yian Shi in 2004. In 2008, he joined Institute of Chemistry, Chinese Academy of Sciences, as a Professor. His interests include the development of novel catalysts for asymmetric catalysis and selective synthesis.

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ACKNOWLEDGMENTS We are deeply indebted to all co-workers whose names are listed in the relevant references. We are also grateful for 199


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Accounts of Chemical Research financial support from the National Natural Science Foundation of China (21222207, 21572231, and 21521002).

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Borane Adducts: Precursors for Borenium Catalysts for Asymmetric FLP Hydrogenations. Dalton Trans. 2016, 45, 15303−15316. (14) Parks, D. J.; Piers, W. E.; Yap, G. P. A. Synthesis, Properties, and Hydroboration Activity of the Highly Electrophilic Borane Bis(pentafluorophenyl)borane, HB(C6F5)2. Organometallics 1998, 17, 5492−5503. (15) (a) Feng, X.; Du, H. Synthesis of Novel Chiral Olefin Ligands and Their Application in Asymmetric Catalysis. Asian J. Org. Chem. 2012, 1, 204−213. (b) Feng, X.; Du, H. Application of Chiral Olefin Ligands in Asymmetric Catalysis. Youji Huaxue 2015, 35, 259−272. (16) Cao, Z.; Du, H. Development of Binaphthyl-Based Chiral Dienes for Rh(I)-Catalyzed Asymmetric Arylation of N,N-Dimethylsulamoyl-Protected Aldimines. Org. Lett. 2010, 12, 2602−2605. (17) Liu, Y.; Du, H. Chiral Dienes as “Ligands” for Borane-Catalyzed Metal-Free Asymmetric Hydrogenation of Imines. J. Am. Chem. Soc. 2013, 135, 6810−6813. (18) Zhu, X.; Du, H. A Chiral Borane Catalyzed Asymmetric Hydrosilylation of Imines. Org. Biomol. Chem. 2015, 13, 1013−1016. (19) Wei, S.; Feng, X.; Du, H. A Metal-Free Hydrogenation of 3Substituted 2H-1,4-Benzoxazines. Org. Biomol. Chem. 2016, 14, 8026− 8029. (20) Stephan, D. W.; Greenberg, S.; Graham, T. W.; Chase, P.; Hastie, J. J.; Geier, S. J.; Farrell, J. M.; Brown, C. C.; Heiden, Z. M.; Welch, G. C.; Ullrich, M. Metal-Free Catalytic Hydrogenation of Polar Substrates by Frustrated Lewis Pairs. Inorg. Chem. 2011, 50, 12338− 12348. (21) Zhu, X.; Du, H. A Highly Stereoselective Metal-Free Hydrogenation of Diimines for the Synthesis of Cis-Vicinal Diamines. Org. Lett. 2015, 17, 3106−3109. (22) (a) Mahdi, T.; Stephan, D. W. Enabling Catalytic Ketone Hydrogenation by Frustrated Lewis Pairs. J. Am. Chem. Soc. 2014, 136, 15809−15812. (b) Scott, D. J.; Fuchter, M. J.; Ashley, A. E. Nonmetal Catalyzed Hydrogenation of Carbonyl Compounds. J. Am. Chem. Soc. 2014, 136, 15813−15816. (c) Nyhlén, J.; Privalov, T. On the Possibility of Catalytic Reduction of Carbonyl Moieties with Tris(pentafluorophenyl)borane and H2: A Computational Study. Dalton Trans. 2009, 5780−5786. (23) (a) Wang, H.; Fröhlich, R.; Kehr, G.; Erker, G. Heterolytic Dihydrogen Activation with the 1,8-Bis(diphenylphosphino)naphthalene/B(C6F5)3 Pair and Its Application for Metal-Free Catalytic Hydrogenation of Silyl Enol Ethers. Chem. Commun. 2008, 5966−5968. (b) Greb, L.; Oña-Burgos, P.; Kubas, A.; Falk, F. C.; Breher, F.; Fink, K.; Paradies, J. [2.2]Paracyclophane Derived Bisphosphines for the Activation of Hydrogen by FLPs: Application in Domino Hydrosilylation/Hydrogenation of Enones. Dalton Trans. 2012, 41, 9056−9060. (24) Wei, S.; Du, H. A Highly Enantioselective Hydrogenation of Silyl Enol Ethers Catalyzed by Chiral Frustrated Lewis Pairs. J. Am. Chem. Soc. 2014, 136, 12261−12264. (25) For selected reviews, see: (a) Glorius, F. Asymmetric Hydrogenation of Aromatic Compounds. Org. Biomol. Chem. 2005, 3, 4171−4175. (b) Zhou, Y.-G. Asymmetric Hydrogenation of Heteroaromatic Compounds. Acc. Chem. Res. 2007, 40, 1357−1366. (c) Kuwano, R. Catalytic Asymmetric Hydrogenation of 5-Membered Heteroaromatics. Heterocycles 2008, 76, 909−922. (d) Wang, D.-S.; Chen, Q.-A.; Lu, S.-M.; Zhou, Y.-G. Asymmetric Hydrogenation of Heteroarenes and Arenes. Chem. Rev. 2012, 112, 2557−2590. (e) Chen, Q.-A.; Ye, Z.-S.; Duan, Y.; Zhou, Y.-G. Homogeneous Palladium-Catalyzed Asymmetric Hydrogenation. Chem. Soc. Rev. 2013, 42, 497−511. (26) Mahdi, T.; del Castillo, J. N.; Stephan, D. W. Metal-Free Hydrogenation of N-Based Heterocycles. Organometallics 2013, 32, 1971−1978. (27) Liu, Y.; Du, H. Metal-Free Borane-Catalyzed Highly Stereoselective Hydrogenation of Pyridines. J. Am. Chem. Soc. 2013, 135, 12968−12971. (28) For a related mechanistic study, see: Zhao, J.; Wang, G.; Li, S. Mechanistic Insight into the Full Hydrogenation of 2,6-Disubstituted

REFERENCES

(1) Welch, G. C.; San Juan, R. R.; Masuda, J. D.; Stephan, D. W. Reversible, Metal-Free Hydrogen Activation. Science 2006, 314, 1124− 1126. (2) Stephan, D. W. “Frustrated Lewis Pairs”: A Concept for New Reactivity and Catalysis. Org. Biomol. Chem. 2008, 6, 1535−1539. (3) For leading reviews, see: (a) Stephan, D. W.; Erker, G. Frustrated Lewis Pairs: Metal-Free Hydrogen Activation and More. Angew. Chem., Int. Ed. 2010, 49, 46−76. (b) Soós, T. Design of Frustrated Lewis Pair Catalysts for Metal-Free and Selective Hydrogenation. Pure Appl. Chem. 2011, 83, 667−675. (c) Erker, G. Frustrated Lewis Pairs: Some Recent Developments. Pure Appl. Chem. 2012, 84, 2203−2217. (d) Stephan, D. W. “Frustrated Lewis Pair” Hydrogenations. Org. Biomol. Chem. 2012, 10, 5740−5746. (e) Paradies, J. Metal-Free Hydrogenation of Unsaturated Hydrocarbons Employing Molecular Hydrogen. Angew. Chem., Int. Ed. 2014, 53, 3552−3557. (f) Stephan, D. W. Frustrated Lewis Pairs: From Concept to Catalysis. Acc. Chem. Res. 2015, 48, 306−316. (g) Stephan, D. W.; Erker, G. Frustrated Lewis Pair Chemistry: Development and Perspectives. Angew. Chem., Int. Ed. 2015, 54, 6400−6441. (h) Stephan, D. W. The Broadening Reach of Frustrated Lewis Pair Chemistry. Science 2016, 354, aaf7229. (4) For leading reviews, see: (a) Liu, Y.; Du, H. Frustrated Lewis Pair Catalyzed Asymmetric Hydrogenation. Huaxue Xuebao 2014, 72, 771−777. (b) Feng, X.; Du, H. Metal-Free Asymmetric Hydrogenation and Hydrosilylation Catalyzed by Frustrated Lewis Pairs. Tetrahedron Lett. 2014, 55, 6959−6964. (c) Shi, L.; Zhou, Y.-G. Enantioselective Metal-Free Hydrogenation Catalyzed by Chiral Frustrated Lewis Pairs. ChemCatChem 2015, 7, 54−56. (d) Paradies, J. Chiral Borane-Based Lewis Acids for Metal Free Hydrogenations. In Topics in Organometallic Chemistry; Springer: Berlin, Heidelberg, 2017; DOI: 10.1007/3418_2016_173. (5) Chen, D.; Klankermayer, J. Metal-Free Catalytic Hydrogenation of Imines with Tris(perfluorophenyl)borane. Chem. Commun. 2008, 2130−2131. (6) Chen, D.; Wang, Y.; Klankermayer, J. Enantioselective Hydrogenation with Chiral Frustrated Lewis Pairs. Angew. Chem., Int. Ed. 2010, 49, 9475−9478. (7) (a) Ghattas, G.; Chen, D.; Pan, F.; Klankermayer, J. Asymmetric Hydrogenation of Imines with a Recyclable Chiral Frustrated Lewis Pair Catalyst. Dalton Trans. 2012, 41, 9026−9028. (b) Chen, D.; Leich, V.; Pan, F.; Klankermayer, J. Enantioselective Hydrosilylation with Chiral Frustrated Lewis Pairs. Chem. - Eur. J. 2012, 18, 5184− 5187. (8) Ye, K.-Y.; Wang, X.; Daniliuc, C. G.; Kehr, G.; Erker, G. A Ferrocene-Based Phosphane/Borane Frustrated Lewis Pair for Asymmetric Imine Reduction. Eur. J. Inorg. Chem. 2017, 2017, 368− 371. (9) Sumerin, V.; Chernichenko, K.; Nieger, M.; Leskelä, M.; Rieger, B.; Repo, T. Highly Active Metal-Free Catalysts for Hydrogenation of Unsaturated Nitrogen-Containing Compounds. Adv. Synth. Catal. 2011, 353, 2093−2110. (10) Lindqvist, M.; Borre, K.; Axenov, K.; Kόtai, B.; Nieger, M.; Leskelä, M.; Pápai, I.; Repo, T. Chiral Molecular Tweezers: Synthesis and Reactivity in Asymmetric Hydrogenation. J. Am. Chem. Soc. 2015, 137, 4038−4041. (11) (a) Mewald, M.; Fröhlich, R.; Oestreich, M. An Axially Chiral, Electron-Deficient Borane: Synthesis, Coordination Chemistry, Lewis Acidity, and Reactivity. Chem. - Eur. J. 2011, 17, 9406−9414. (b) Mewald, M.; Oestreich, M. Illuminating the Mechanism of the Borane-Catalyzed Hydrosilylation of Imines with Both an Axially Chiral Borane and Silane. Chem. - Eur. J. 2012, 18, 14079−14084. (12) Süsse, L.; Hermeke, J.; Oestreich, M. The Asymmetric Piers Hydrosilylation. J. Am. Chem. Soc. 2016, 138, 6940−6943. (13) For an example on chiral borenium ions, see: Lam, J.; Günther, B. A. R.; Farrell, J. M.; Eisenberger, P.; Bestvater, B. P.; Newman, P. D.; Melen, R. L.; Crudden, C. M.; Stephan, D. W. Chiral Carbene200


Article

Accounts of Chemical Research Pyridines Catalyzed by the Lewis Acid C6F5(CH2)2B(C6F5)2. Dalton Trans. 2015, 44, 9200−9208. (29) Zhou, Q.; Zhang, L.; Meng, W.; Feng, X.; Yang, J.; Du, H. Borane-Catalyzed Transfer Hydrogenations of Pyridines with Ammonia Borane. Org. Lett. 2016, 18, 5189−5191. (30) For a related work, see: Ma, W.; Chen, F.; Liu, Y.; He, Y.-M.; Fan, Q.-H. Ruthenium-Catalyzed Enantioselective Hydrogenation of 1,8-Naphthyridine Derivatives. Org. Lett. 2016, 18, 2730−2733. (31) Wang, W.; Feng, X.; Du, H. Borane-Catalyzed Metal-Free Hydrogenation of 2,7-Disubstituted 1,8-Naphthyridines. Org. Biomol. Chem. 2016, 14, 6683−6686. (32) For one example, see: Qin, J.; Chen, F.; Ding, Z.; He, Y.-M.; Xu, L.; Fan, Q.-H. Asymmetric Hydrogenation of 2- and 2,3-Substituted Quinoxalines with Chiral Cationic Ruthenium Diamine Catalysts. Org. Lett. 2011, 13, 6568−6571. (33) Zhang, Z.; Du, H. A Highly Cis-Selective and Enantioselective Metal-Free Hydrogenation of 2,3-Disubstituted Quinoxalines. Angew. Chem., Int. Ed. 2015, 54, 623−626. (34) Zhang, Z.; Du, H. Cis-Selective and Highly Enantioselective Hydrogenation of 2,3,4-Trisubstituted Quinolines. Org. Lett. 2015, 17, 2816−2819. (35) Zhang, Z.; Du, H. Enantioselective Metal-Free Hydrogenations of Disubstituted Quinolines. Org. Lett. 2015, 17, 6266−6269. (36) Ren, X.; Li, G.; Wei, S.; Du, H. Facile Development of Chiral Alkenylboranes from Chiral Diynes for Asymmetric Hydrogenation of Silyl Enol Ethers. Org. Lett. 2015, 17, 990−993. (37) For a pioneering work, see: Parks, D. J.; Piers, W. E. Tris(pentafluorophenyl)boron-Catalyzed Hydrosilylation of Aromatic Aldehydes, Ketones, and Esters. J. Am. Chem. Soc. 1996, 118, 9440− 9441. (38) For leading reviews, see: (a) Piers, W. E.; Marwitz, A. J. V.; Mercier, L. G. Mechanistic Aspects of Bond Activation with Perfluoroarylboranes. Inorg. Chem. 2011, 50, 12252−12262. (b) Oestreich, M.; Hermeke, J.; Mohr, J. A Unified Survey of Si−H and H−H Bond Activation Catalysed by Electron-Deficient Boranes. Chem. Soc. Rev. 2015, 44, 2202−2220. (c) Lipke, M. C.; Liberman-Martin, A. L.; Tilley, T. D. Electrophilic Activation of Silicon-Hydrogen Bonds in Catalytic Hydrosilylations. Angew. Chem., Int. Ed. 2017, 56, 2260− 2294. (39) For a diastereoselective example, see: Skjel, M. K.; Houghton, A. Y.; Kirby, A. E.; Harrison, D. J.; McDonald, R.; Rosenberg, L. SilaneControlled Diastereoselectivity in the Tris(pentafluorophenyl)boraneCatalyzed Reduction of α-Diketones to Silyl-Protected 1,2-Diols. Org. Lett. 2010, 12, 376−379. (40) Ren, X.; Du, H. Chiral Frustrated Lewis Pairs Catalyzed Highly Enantioselective Hydrosilylations of 1,2-Dicarbonyl Compounds. J. Am. Chem. Soc. 2016, 138, 810−813. (41) Ren, X.; Han, C.; Feng, X.; Du, H. A Borane-Catalyzed MetalFree Hydrosilylation of Chromones and Flavones. Synlett 2017, 28, 2421−2424. (42) Li, S.; Li, G.; Meng, W.; Du, H. A Frustrated Lewis Pair Catalyzed Asymmetric Transfer Hydrogenation of Imines Using Ammonia Borane. J. Am. Chem. Soc. 2016, 138, 12956−12962. (43) For leading reviews, see: (a) Ellman, J. A.; Owens, T. D.; Tang, T. P. N-tert-Butanesulfinyl Imines: Versatile Intermediates for the Asymmetric Synthesis of Amines. Acc. Chem. Res. 2002, 35, 984−995. (b) Robak, M. T.; Herbage, M. A.; Ellman, J. A. Synthesis and Applications of tert-Butanesulfinamide. Chem. Rev. 2010, 110, 3600− 3740. (44) For selected examples, see: (a) Ménard, G.; Stephan, D. W. Room Temperature Reduction of CO2 to Methanol by Al-Based Frustrated Lewis Pairs and Ammonia Borane. J. Am. Chem. Soc. 2010, 132, 1796−1797. (b) Yang, X.; Zhao, L.; Fox, T.; Wang, Z.-X.; Berke, H. Transfer Hydrogenation of Imines with Ammonia−Borane: A Concerted Double-Hydrogen-Transfer Reaction. Angew. Chem., Int. Ed. 2010, 49, 2058−2062. (c) Chong, C. C.; Hirao, H.; Kinjo, R. A Concerted Transfer Hydrogenolysis: 1,3,2-Diazaphospholene-Catalyzed Hydrogenation of NN Bond with Ammonia−Borane. Angew. Chem., Int. Ed. 2014, 53, 3342−3346. (d) Fu, S.; Chen, N.-Y.; Liu, X.;

Shao, Z.; Luo, S.-P.; Liu, Q. Ligand-Controlled Cobalt-Catalyzed Transfer Hydrogenation of Alkynes: Stereodivergent Synthesis of Zand E-Alkenes. J. Am. Chem. Soc. 2016, 138, 8588−8594. (45) Li, S.; Meng, W.; Du, H. Asymmetric Transfer Hydrogenations of 2,3-Disubstituted Quinoxalines with Ammonia Borane. Org. Lett. 2017, 19, 2604−2606.

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