Atroposelective Transfer Hydrogenation of Biaryl Aminals via Dynamic Kinetic Resolution. Synthesis of Axially Chiral Diamines

Atroposelective Transfer Hydrogenation of Biaryl Aminals via Dynamic Kinetic Resolution. Synthesis of Axially Chiral Diamines JoséA. Carmona, Carlos Rodríguez-Franco, JoaquínLópez-Serrano, Abel Ros, Javier Iglesias-Siguenza, Rosario Fernández,*JoséM. Lassaletta,*and Valentín Hornillos* Cite This: ACS Catal. 2021, 11, 4117−4124 Read Online ACCESS Metrics & More Article Recommendations * sıSupporting Information ABSTRACT: An efficient dynamic kinetic resolution (DKR) approach for the synthesis of axially chiral diamines has been developed on the basis of a ruthenium-catalyzed enantioselective transfer hydrogenation. The strategy relies on the configurational instability of cyclic biaryl aminal precursors in equilibrium with their amino-imine open forms, as supported by DFT calculations. This protocol features a broad substrate scope of aliphatic amines and biaryl scaffolds and proceeds under very mild conditions, allowing the preparation of BINAM homologues in good to high yields and nearly perfect enantioselectivities (up to 99% ee). KEYWORDS: asymmetric catalysis, dynamic kinetic resolution, transfer hydrogenation, axial chirality, diamines ■INTRODUCTION Axially chiral biaryls are frequently found as the fundamental units of many natural products, 1 pharmaceuticals, 2 and bioactive substances. 3 They are also used in materials science as stationary phases for chiral separation, 4 chiroptical molecular switches, 5 or dopants in liquid-crystalline materials, 6 among others. In asymmetric synthesis, they are versatile chiral ligands 7 and organocatalysts 8 for a vast number of enantioselective transformations. In particular, 1,1′-bi-2-naphthol (BINOL), 9 2,2′- bis(diphenylphosphino)-1,1′-binaphthyl (BINAP), 10 and their derivatives constitute privileged architectures with numerous applications, even on an industrial scale. 7a Related axially chiral diamines (e.g., 1,1′-binaphthyl-2,2′-diamines, BINAM) have also exhibited excellent ligand 11 and catalyst properties 12 but remain relatively underexplored due to the lack of efficient methods for their synthesis. 13 There is a handful of catalytic asymmetric methods for the synthesis of axially chiral diamines, in any case limited to BINAM derivatives. These comprise benzidine rearrangement catalyzed by chiral phosphoric acid (CPA) 14,15 (Scheme 1A), kinetic resolution involving imine formation and transfer hydrogenation 16 (Scheme 1B), and more recently, a redoxneutral Ni-catalyzed asymmetric cross-coupling of azonaphthalenes and 2-naphthylamines 17 (Scheme 1C). Therefore, the development of an approach to access optically active homologues of BINAM is expected to significantly expand the number of applications of these types of axially chiral derivatives in asymmetric catalysis. Among the synthetic strategies for the synthesis of axially chiral biaryls, 18,19 dynamic kinetic resolution (DKR) of configurationally unstable cyclic biaryl precursors has been exploited with success in several contexts. The “lactone concept” developed by Bringmann and co-workers 20 first exploited the lability of biaryl lactones in transesterification reactions, finding numerous applications in the synthesis of natural products and bioactive substances. 1,21 Efficient catalytic variants of this strategy made use of Co-, 22 Ir-, 23 and Cu-catalyzed 24 reductions and a transesterification reaction using a bifunctional thiourea catalyst 25 (Scheme 2A). More recently, the groups of Akiyama 26 and Wang 27 described a related DKR strategy for the asymmetric reductive ring opening of configurationally labile biaryl hemiaminal ethers (Scheme 2B). Inspired by these studies, we envisioned that related biaryl hemiaminals with the structure 1(Scheme 2C) should also be configurationally labile and, therefore, could be suitable starting materials for the atroposelective synthesis of axially chiral diamines, homologues of BINAM, after an asymmetric reductive amination process. Herein, we describe the successful implementation of this Received: February 5, 2021 Revised: March 8, 2021 Published: March 18, 2021 Research Articlepubs.acs.org/acscatalysis © 2021 American Chemical Society 4117 https://doi.org/10.1021/acscatal.1c00571 ACS Catal. 2021, 11, 4117−4124 Downloaded via UNIV DE SEVILLA on December 18, 2024 at 15:39:02 (UTC). See https://pubs.acs.org/sharingguidelines for options on how to legitimately share published articles. strategy through an asymmetric transfer hydrogenation (ATH) reaction under Ru catalysis. ■RESULTS AND DISCUSSION The key for success in this approach is the feasibility of ringclosing/ring-opening events, either between the open forms 1o and biaryl hemiaminals 1or, after condensation with a primary amine 2, between the corresponding imines 3oand aminals 3 (Scheme 3). Thus, substrates 1were designed with a secondary aromatic amine substituted by an easily removable electronwithdrawing group (tosyl) to facilitate the intramolecular proton shift required for the formation of the cyclic form 1, in either a stepwise (→I) or a concerted way through the transition structure TS. 28 Conversely, the tosyl group is assumed to facilitate the formation of aminals 3from the parent open forms 3o, while it prevents an undesired, irreversible aromatization into the phenanthridine derivatives III via iminium formation (→II) followed by hydrolysis. In this scenario, three different racemization pathways are envisaged. (a) Reversible transformation of (Sa)-1ointo (Ra)-1o occurs via cyclization (→(Sa,R)-1), atropoisomerization (→(Ra,R)-1), and ring opening to afford (Ra)-1′ o, a less stable conformer of (Ra)-1o. A parallel racemization pathway from the less stable (Sa)-1′ oproceeds via (Sa,S)-1and (Ra,S)-1, enantiomers of the above intermediates. (b) Interconversion between imines (Sa)-3oand (Ra)-3ooccurs following a route similar to that described for aldehydes 1o. (c) From 1or 3, acidassisted elimination of H2OorR′′NH2occurs to yield cationic intermediates II followed by atropoisomerization and regeneration of ent-1or ent-3. If any one of these racemization pathways is enabled, then a catalytic asymmetric transformation via DKR could be foreseen, provided that the racemization ability, ultimately associated with the Lewis acidity of the imine functionality, is eliminated in the products. Interestingly, 1H NMR spectroscopy of the model substrate 1A (Figure 1) confirmed that the expected equilibrium between the open (1o) and closed (1) forms is completely displaced to the latter, providing a single diastereomer in solution. The same situation holds for the corresponding imine derivative 3A (see the Supporting Information for details). The molecular structure of 1A in the solid state was also confirmed by an X-ray diffraction analysis. The analysis of this structure confirms the relative S,S/ R,R configuration of the product, stabilized by a strong πstacking interaction between the tosyl group and the naphthalene ring. A computational analysis 29 of the racemization mechanism was performed using R = Me, R′= H, and R′′ = cyclohexyl as a model case (Figure 2). The collected data agree with the higher stability of the closed forms 1and 3relative to their open counterparts 1oand 3o(by 2.44 and 4.93 kcal mol−1 respectively). Moreover, the most stable diastereomer in the hemiaminal series, (Sa,S)-1, matches the experimentally observed structure of 1A in the solid state. The racemization for 1and 3takes place through energy barriers of ca. 16 and 20 Scheme 1. Catalytic Asymmetric Synthesis of BINAM Derivatives Scheme 2. Atroposelective Dynamic Kinetic Resolution of Bridged Biaryl Systems Figure 1. X-ray diffraction structure of 1A. The Ra,Renantiomer and most hydrogen atoms are omitted for clarity. ACS Catalysis pubs.acs.org/acscatalysis Research Article https://doi.org/10.1021/acscatal.1c00571 ACS Catal. 2021, 11, 4117−4124 4118 kcal mol−1, respectively. 30 As expected, the barrier calculated for the aminal model is higher, but this appears to be offset by their higher stability relative to the hemiaminals (by ca. 5 kcal mol−1). On the other hand, the calculated energy of N-sulfonyliminium intermediates II makes them unaffordable (ΔG= ca. 400 kcal mol−1for the reaction 1+ HCO2H→II+HCO2 −+H 2O). Together, the collected information confirms the initial hypothesis for the labilization through a bridged hemiaminal structure, thus enabling the envisaged DKR. Preliminary experiments (Table 1) started with the asymmetric reductive amination of hemiaminal 1A with n-propylamine 2a in CH2Cl2 (C= 0.07 M), using 5 mol % of Noyori’s catalyst RuCl(pcymene)[(S,S)-Ts-DPEN] 31 in the presence of a large excess of a formic acid/trimethylamine mixture (FA/TEA 5/2, 30 equiv). Under these conditions, the desired diamine 4Aa was formed, although in a negligible conversion (<10%) and with low enantioselectivity (40% ee, entry 1), together with amino alcohol 5A resulting from the direct reduction of 1A (30% conversion, 24% ee). Gratifyingly, the desired product 4Aa was efficiently obtained in 93% conversion and 94% ee by reducing Scheme 3. Racemization Routes a a The absolute configuration is assigned assuming that R, R′=CorH. Figure 2. DFT-calculated free energy profile (kcal mol−1) for the racemization of imines 3o(see the Supporting Information for additional details). ACS Catalysis pubs.acs.org/acscatalysis Research Article https://doi.org/10.1021/acscatal.1c00571 ACS Catal. 2021, 11, 4117−4124 4119 the amount of FA/TEA to 6.0 equiv (entry 2). Solvent effects were examined at this point, showing a significant influence on reactivity and enantioselectivity, with dioxane giving the best results (91% conversion, 97% ee, entry 9). We found that the enantioselectivity was also highly dependent on the concentration, dropping to 92% and 80% ee in reactions performed at c = 0.1 and 0.2 M, respectively. Nonetheless, when the reaction mixture was further diluted (c= 0.05 M), the enantiomeric excess was not affected in comparison to the optimal value. With the optimized conditions in hand, we next moved to explore the scope of the methodology. Initially, amines 2a−i were studied in combination with 1A. As shown in Scheme 4, primary amines bearing different linear or cyclic aliphatic substituents provide the desired products in high yields and enantioselectivities. Product 4Ab was obtained with results similar to those for the model substrate, while exocyclic amines provided excellent enantioselectivities regardless of the nature of the cyclic structure (3Ac−g). An amino aldehyde protected as 1,3-dioxolane (2g) was well tolerated, furnishing the axially chiral diamine 4Ag in good yield with high enantioselectivity. The reaction also proceeded very successfully with allylamine 2h, thus introducing an easily removable protecting group to access the free axially chiral primary diamine compounds (vide infra). This DKR methodology is also suitable for the use of pyrrolidine 2j,affording the desired axially chiral diamine 4Aj in 84% yield and 92% ee, although a slightly longer reaction time Table 1. Screening of Reaction Conditions a entry solvent conversn (%) b ee (%) c 1CH 2Cl2 d <10 40 2CH 2Cl293 94 3 toluene 85 94 4 DCE 64 94 5 DMSO 77 40 6 THF 91 85 7 MeCN 78 73 8 DMF 81 50 9 1,4-dioxane 91 97 a Conditions unless specified otherwise: 0.1 mmol of 1A, 1.1 mmol of 2a. b Determined by 1H NMR spectroscopy of the crude reaction mixture. c Determined by chiral HPLC analysis. d 30 equiv of FA/TEA (5/2) was added. Scheme 4. Reaction Scope a a Reactions were performed on a 0.1 mmol scale in 1.5 mL of 1,4-dioxane. Isolated yields after chromatography are given. ee values were determined by HPLC on chiral stationary phases. b The condensation reaction did not proceed to completion. ACS Catalysis pubs.acs.org/acscatalysis Research Article https://doi.org/10.1021/acscatal.1c00571 ACS Catal. 2021, 11, 4117−4124 4120 (36 h) was required to complete the reaction. Considering this result, we found it surprising that when piperidine or morpholine was used instead, the desired diamines were not detected. In fact, the corresponding aminals were quantitatively formed but, after addition of the catalyst and FA/TEA, aminoalcohol 5A was the only observed product. The absolute Rconfiguration of 4Aa was determined by a single-crystal X-ray diffraction analysis and that of the other products 4was assigned by analogy. The methodology can also be applied to other biaryl scaffolds. Thus, biaryl hemiaminals bearing electron-donating or -withdrawing substituents such as 1B and 1C afforded the corresponding axially chiral diamines 4Ba,4Ca,4Cc, and 4Cf with excellent enantioselectivity. Very similar results were observed for the asymmetric reductive amination of hemiaminal 1D, featuring a naphthyl ring at the upper fragment of the biaryl skeleton. For instance, the reactions with n-propylamine 2a,nbutylamine 2b, cyclohexylamine 2c, or cyclohexylmethylamine 2f afforded the expected products in high yields and excellent enantioselectivities in all cases. However, lower reactivity was observed in the reaction with 1,3-dioxolane derivative 2g or allylamine 2h, though the enantiomeric excesses were slightly higher than those shown for 4Ag or 4Ah. The use of systems such as 1E and 1F also resulted in the isolation of the desired products with excellent enantioselectivities. To explore the preparative utility of the method, the enantioselective reductive amination of 1A with 2h was repeated on a 2 mmol scale, delivering the desired product 4Ah in 65% yield with the same enantioselectivity (99% ee) as that obtained in the small-scale reaction. Further deprotection of an allylic amine was then carried out with N,N′-dimethylbarbituric acid and Pd(PPh)4as the catalyst to afford the desired primary amine (R)-6A almost quantitatively while the stereochemical integrity was preserved (Scheme 5). 32 This product, an axially chiral analogue of the widely employed N-(p-tosyl)-1,2-diphenyl- ethylene-1,2-diamine (TsDPEN), was then treated with 3,5- bis(trifluoromethyl)phenyl isothiocyanate to deliver thiourea (R)-7A, featuring an appealing structure as a bifunctional organocatalyst. Additionally, detosylation in the presence of TFA afforded the BINAM homologue (R)-8A in 87% yield and without significant racemization. ■CONCLUSION In conclusion, an efficient strategy for the enantioselective synthesis of axially chiral homologues of BINAM has been developed. The ring-opening−ring-closing equilibrium between amino-imine structures 3oand biaryl aminals 3and the low atropoisomerization barriers in the latter, as supported by DFT calculations, enable a dynamic kinetic resolution by Rucatalyzed asymmetric transfer hydrogenation. Notably, the reactions are operationally simple, proceed at room temperature, and give excellent enantioselectivity in nearly all cases. The resulting products are also direct precursors for the synthesis of diverse bifunctional derivatives with appealing structures for their application in asymmetric catalysis. ■ASSOCIATED CONTENT * sıSupporting Information The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acscatal.1c00571. Experimental details, spectroscopic and analytical data for new compounds, computational details, and HPLC traces (PDF) Crystallographic data of 1A (CIF) Crystallographic data of 4Aa (CIF) XYZ coordinates of calculated species (XYZ) ■AUTHOR INFORMATION Corresponding Authors Rosario Fernández −Departamento de Química Orgánica, Universidad de Sevilla and Centro de Innovación en Química Avanzada (ORFEO-CINQA), 41012 Sevilla, Spain; orcid.org/0000-0002-1755-1525; Email: ff[email protected] JoséM. Lassaletta −Instituto de Investigaciones Químicas (CSIC-US), 41092 Sevilla, Spain; Centro de Innovación en Química Avanzada (ORFEO-CINQA), 41092 Sevilla, Spain; orcid.org/0000-0003-1772-2723; Email: [email protected] Valentín Hornillos −Departamento de Química Orgánica, Universidad de Sevilla and Centro de Innovación en Química Avanzada (ORFEO-CINQA), 41012 Sevilla, Spain; Instituto de Investigaciones Químicas (CSIC-US), 41092 Sevilla, Spain; orcid.org/0000-0002-6181-9146; Email: [email protected] Authors JoséA. Carmona −Instituto de Investigaciones Químicas (CSIC-US), 41092 Sevilla, Spain; Centro de Innovación en Química Avanzada (ORFEO-CINQA), 41092 Sevilla, Spain; orcid.org/0000-0003-0358-7874 Carlos Rodríguez-Franco −Instituto de Investigaciones Químicas (CSIC-US), 41092 Sevilla, Spain; Centro de Innovación en Química Avanzada (ORFEO-CINQA), 41092 Sevilla, Spain; orcid.org/0000-0002-9218-9685 JoaquínLópez-Serrano −Departamento de Química Inorgánica, Universidad de Sevilla and Centro de Innovación Química Avanzada (ORFEO-CINQA), 41092 Sevilla, Spain; Scheme 5. Representative Transformations from 3Ah ACS Catalysis pubs.acs.org/acscatalysis Research Article https://doi.org/10.1021/acscatal.1c00571 ACS Catal. 2021, 11, 4117−4124 4121 Instituto de Investigaciones Químicas (CSIC-US), 41092 Sevilla, Spain; orcid.org/0000-0003-3999-0155 Abel Ros −Instituto de Investigaciones Químicas (CSIC-US), 41092 Sevilla, Spain; Centro de Innovación en Química Avanzada (ORFEO-CINQA), 41092 Sevilla, Spain; orcid.org/0000-0002-3455-5675 Javier Iglesias-Siguenza −Departamento de Química Orgánica, Universidad de Sevilla and Centro de Innovación en Química Avanzada (ORFEO-CINQA), 41012 Sevilla, Spain; orcid.org/0000-0001-8846-2303 Complete contact information is available at: https://pubs.acs.org/10.1021/acscatal.1c00571 Author Contributions The manuscript was written through contributions of all authors. All authors have given approval to the final version of the manuscript. Notes The authors declare no competing financial interest. ■ACKNOWLEDGMENTS We thank the Spanish Ministerio de Ciencia e Innovación (Grants PID2019-106358GB-C21, PID2019-106358GB-C22, contract RYC-2017-22294 for V.H., fellowship FPU18/02677 for C.R.-F.), European funding (ERDF), and Junta de Andalucía (Grants P18-FR-3531, P18-FR-644, US-1262867, US-1260906, and fellowship for J.A.C.). The use of the computational facilities at the Centro de Supercomputación de Galicia (CESGA) is gratefully acknowledged. ■REFERENCES (1) Bringmann, G.; Gulder, T.; Gulder, T. A. M.; Breuning, M. Atroposelective Total Synthesis of Axially Chiral Biaryl Natural Products. Chem. Rev. 2011,111, 563−639. (2) (a) Toenjes, S. T.; Gustafson, J. L. Atropisomerism in Medicinal Chemistry: Challenges and Opportunities. Future Med. Chem. 2018,10, 409−422. (b) Clayden, J.; Moran, W. J.; Edwards, P. J.; LaPlante, S. R. The Challenge of Atropisomerism in Drug Discovery. Angew. Chem., Int. Ed. 2009,48, 6398−6401. (3) (a) Smyth, J. E.; Butler, N. M.; Keller, P. A. A Twist of Nature-The Significance of Atropisomers in Biological Systems. Nat. Prod. Rep. 2015,32, 1562−1583. (b) Kozlowski, M. C.; Morgan, B. J.; Linton, E. C. Total synthesis of chiral biaryl natural products by asymmetric biaryl coupling. Chem. Soc. Rev. 2009,38, 3193−3207. (4) Dotsevi, G.; Sogah, Y.; Cram, D. J. Total Chromatographic Optical Resolution of α-Amino Acid and Ester Salts through Chiral Recognition by a Host Covalently Bound to Polystyrene Resin. J. Am. Chem. Soc. 1976,98, 3038−3041. (5) Takaishi, K.; Yasui, M.; Ema, T. Binaphthyl-Bipyridyl Cyclic Dyads as a Chiroptical Switch. J. Am. Chem. Soc. 2018,140, 5334−5338. (6) Li, Q.; Green, L.; Venkataraman, N.; Shiyanovskaya, I.; Khan, A.; et al. Reversible Photoswitchable Axially Chiral Dopants with High Helical Twisting Power. J. Am. Chem. Soc. 2007,129, 12908−12909. (7) (a) Privileged Chiral Ligands and Catalysts; Zhou, Q.-L., Ed.; Wiley-VCH: Weinheim, Germany, 2011. (b) Li, Y.-M.; Kwong, F.-Y.; Yu, W.-Y.; Chan, A. S.C. Recent Advances in Developing New Axially Chiral Phosphine Ligands for Asymmetric Catalysis. Coord. Chem. Rev. 2007,251, 2119. (c) Chen, Y.; Yekta, S.; Yudin, A. K. Modified BINOL Ligands in Asymmetric Catalysis. Chem. Rev. 2003,103, 3155−3212. (8) For selected reviews, see: (a) Parmar, D.; Sugiono, E.; Raja, S.; Rueping, M. Complete Field Guide to Asymmetric BINOL-Phosphate Derived Brønsted Acid and Metal Catalysis: History and Classification by Mode of Activation; Brønsted Acidity, Hydrogen Bonding, Ion Pairing, and Metal Phosphates. Chem. Rev. 2014,114, 9047−9153. (b) Min, C.; Seidel, D. Asymmetric Brønsted Acid Catalysis with Chiral Carboxylic Acids. Chem. Soc. Rev. 2017,46, 5889−5902. (9) Brunel, J. M. Update 1 of: BINOL: A Versatile Chiral Reagent. Chem. Rev. 2007,107, PR1−PR45. (10) Noyori, R.; Takaya, H. BINAP: An Efficient Chiral Element for Asymmetric Catalysis. Acc. Chem. Res. 1990,23, 345−350. (11) For selected examples of BINAM-based metal catalysts, see: (a) Wang, C.; Yamamoto, H. Nickel-Catalyzed Regio-and Enantioselective Aminolysis of 3,4-Epoxy Alcohols. J. Am. Chem. Soc. 2015,137, 4308−4311. (b) Alamsetti, S. K.; Sekar, G. Chiral Cobalt-Catalyzed Enantioselective Aerobic Oxidation of α-Hydroxy Esters. Chem. Commun. 2010,46, 7235−7237. (c) Sudo, Y.; Shirasaki, D.; Harada, S.; Nishida, A. Highly Enantioselective Diels−Alder Reactions of Danishefsky Type Dienes with Electron-Deficient Alkenes Catalyzed by Yb(III)-BINAMIDE Complexes. J. Am. Chem. Soc. 2008,130, 12588−12589. (d) Huang, H.; Okuno, T.; Tsuda, K.; Yoshimura, M.; Kitamura, M. Enantioselective Hydrogenation of Aromatic Ketones Catalyzed by Ru Complexes of Goodwin−Lions-type sp2N/sp3N Hybrid Ligands R-BINAN-R‘-Py. J. Am. Chem. Soc. 2006,128, 8716− 8717. (12) For selected examples of BINAM-based organocatalysts, see: (a) Reddi, Y.; Tsai, C.-C.; Avila, C. M.; Toste, F. D.; Sunoj, R. B. Harnessing Noncovalent Interactions in Dual-Catalytic Enantioselective Heck-Matsuda Arylation. J. Am. Chem. Soc. 2019,141, 998−1009. (b) Denmark, S. E.; Kornfilt, D. J. P. J. Org. Chem. 2017,82, 3192− 3222. (c) Tan, B.; Candeias, N. R.; Barbas, C. F. Construction of Bispirooxindoles Containing Three Quaternary Stereocentres in a Cascade Using a Single Multifunctional Organocatalyst. Nat. Chem. 2011,3, 473−477. (d) Uraguchi, D.; Nakashima, D.; Ooi, T. Chiral Arylaminophosphonium Barfates as a New Class of Charged Brønsted Acid for the Enantioselective Activation of Nonionic Lewis Bases. J. Am. Chem. Soc. 2009,131, 7242−7243. (e) Hatano, M.; Ikeno, T.; Matsumura, T.; Torii, S.; Ishihara, K. Chiral Lithium Salts of Phosphoric Acids as Lewis Acid-Base Conjugate Catalysts for the Enantioselective Cyanosilylation of Ketones. Adv. Synth. Catal. 2008, 350, 1776−1780. (13) For the resolution of BINAM, see: Brown, K. J.; Berry, M. S.; Murdoch, J. R. J. Synthesis of Optically Active 2,2’-Dihalo-1,1’- Binaphthyls via Stable Diazonium salts. J. Org. Chem. 1985,50, 4345− 4349. (14) Li, G.-Q.; Gao, H.; Keene, C.; Devonas, M.; Ess, D. H.; Kurti, L. Organocatalytic Aryl−Aryl Bond Formation: An Atroposelective [3,3]- Rearrangement Approach to BINAM Derivatives. J. Am. Chem. Soc. 2013,135, 7414−7417. (15) De, C. K.; Pesciaioli, F.; List, B. Catalytic Asymmetric Benzidine Rearrangement. Angew. Chem., Int. Ed. 2013,52, 9293−9295. (16) Cheng, D.-J.; Yan, L.; Tian, S.-K.; Wu, M.-Y.; Wang, L.-X.; Fan, Z.-L.; Zheng, S.-C.; Liu, X.-Y.; Tan, B. Highly Enantioselective Kinetic Resolution of Axially Chiral BINAM Derivatives Catalyzed by a Brønsted Acid. Angew. Chem., Int. Ed. 2014,53, 3684−3687. (17) Qi, L.-W.; Li, S.; Xiang, S.-H.; Wang, J.; Tan, B. Asymmetric Construction of Atropisomeric Biaryls via a Redox Neutral Cross- Coupling Strategy. Nat. Catal. 2019,2, 314−323. (18) (a) Lassaletta, J. M. Atropisomerism and Axial Chirality, 1st ed.; World Scientific: 2019. Selected reviews: (b) Zhang, D.; Wang, Q. Palladium Catalyzed Asymmetric Suzuki-Miyaura Coupling Reactions to Axially Chiral Biaryl Compounds: Chiral Ligands and Recent Advances. Coord. Chem. Rev. 2015,286,1−16. (c) Loxq, P.; Manoury, E.; Poli, R.; Deydier, E.; Labande, A. Synthesis of Axially Chiral Biaryl Compounds by Asymmetric Catalytic Reactions with Transition Metals. Coord. Chem. Rev. 2016,308, 131−190. (d) Ma, G.; Sibi, M. P. Catalytic Kinetic Resolution of Biaryl Compounds. Chem. - Eur. J. 2015,21, 11644−11657. (e) Wencel-Delord, J.; Panossian, A.; Leroux, F. R.; Colobert, F. Recent Advances and New Concepts for the Synthesis of Axially Stereoenriched Biaryls. Chem. Soc. Rev. 2015,44, 3418−3430. (f) Zilate, B.; Castrogiovanni, A.; Sparr, C. Catalyst- Controlled Stereoselective Synthesis of Atropisomers. ACS Catal. 2018,8, 2981−2988. (g) Wang, Y.-B.; Tan, B. Construction of Axially Chiral Compounds via Asymmetric Organocatalysis. Acc. Chem. Res. ACS Catalysis pubs.acs.org/acscatalysis Research Article https://doi.org/10.1021/acscatal.1c00571 ACS Catal. 2021, 11, 4117−4124 4122 2018,51, 534−547. (h) Liao, G.; Zhou, T.; Yaoa, Q.-J.; Shi, B.-F. Recent Advances in the Synthesis of Axially Chiral Biaryls via Transition Metal-catalysed Asymmetric C−H Functionalization. Chem. Commun. 2019,55, 8514−8523. (i) Carmona, J. A.; Rodríguez-Franco, C.; Fernandez, R.; Hornillos, V.; Lassaletta, J. M. Atroposelective transformation of axially chiral (hetero)biaryls. From desymmetrization to modern resolution strategies. Chem. Soc. Rev. 2021,50, 2968−2983. (19) Selected recent examples: (a) Coombs, G.; Sak, M. H.; Miller, S. J. Peptide-Catalyzed Fragment Couplings that Form Axially Chiral Non-C2-Symmetric Biaryls. Angew. Chem., Int. Ed. 2020,59, 2875− 2880. (b) Hornillos, V.; Carmona, J. A.; Ros, A.; Iglesias-Siguenza, J.; Lopez-Serrano, J.; Fernández, R.; Lassaletta, J. M. Dynamic Kinetic Resolution of Heterobiaryl Ketones by Zinc-Catalyzed Asymmetric Hydrosilylation. Angew. Chem., Int. Ed. 2018,57, 3777−3781. (c) Xue, F.; Hayashi, T. Asymmetric Synthesis of Axially Chiral 2-Aminobiaryls by Rhodium-Catalyzed Benzannulation of 1-Arylalkynes with 2- (Cyanomethyl) phenylboronates. Angew. Chem., Int. Ed. 2018,57, 10368−10372. (d) Zheng, S. C.; Wang, Q.; Zhu, J. Catalytic Kinetic Resolution by Enantioselective Aromatization: Conversion of Racemic Intermediates of the Barton-Zard Reaction into Enantioenriched 3- Arylpyrroles. Angew. Chem., Int. Ed. 2019,58, 9215−9219. (e) Carmona, J. A.; Hornillos, V.; Ramírez-Lopez, P.; Ros, A.; Iglesias-Siguenza, J.; Gomez-Bengoa, E.; Fernández, R.; Lassaletta, J. M. Dynamic Kinetic Asymmetric Heck Reaction for the Simultaneous Generation of Central and Axial Chirality. J. Am. Chem. Soc. 2018,140, 11067−11075. (f) Yao, Q. J.; Zhang, S.; Zhan, B. B.; Shi, B. F. Atroposelective Synthesis of Axially Chiral Biaryls by Palladium- Catalyzed Asymmetric C-H Olefination Enabled by a Transient Chiral Auxiliary. Angew. Chem., Int. Ed. 2017,56, 6617−6621. (g) Wang, Q.; Cai, Z.-J.; Liu, C.-X.; Gu, Q.; You, S.-L. Rhodium-Catalyzed Atroposelective C-H Arylation: Efficient Synthesis of Axially Chiral Heterobiaryls. J. Am. Chem. Soc. 2019,141, 9504−9510. (h) Deng, R.; Xi, J.; Li, Q.; Gu, Z. Enantioselective Carbon-Carbon Bond Cleavage for Biaryl Atropisomers Synthesis. Chem. 2019,5, 1834−1846. (i) Tian, M.; Bai, D.; Zheng, G.; Chang, J.; Li, X. Rh (III)-Catalyzed Asymmetric Synthesis of Axially Chiral Biindolyls by Merging C-H Activation and Nucleophilic Cyclization. J. Am. Chem. Soc. 2019,141, 9527−9532. (j) Romero-Arenas, A.; Hornillos, V.; Iglesias-Siguenza, J.; Fernández, R.; López-Serrano, J.; Ros, A.; Lassaletta, J. M. Ir-Catalyzed Atroposelective Desymmetrization of Heterobiaryls: Hydroarylation of Vinyl Ethers and Bicycloalkenes. J. Am. Chem. Soc. 2020,142, 2628− 2639. (k) Zhao, K.; Duan, L.; Xu, S.; Jiang, J.; Fu, Y.; Gu, Z. Enhanced Reactivity by Torsional Strain of Cyclic Diaryliodonium in Cu- Catalyzed Enantioselective Ring-Opening Reaction. Chem. 2018,4, 599−612. (l) Munday, E.; Grove, M.; Feoktistova, T.; Breukner, A.; Walden, D.; Young, C.; Slawin, A.; Campbell, A.; Cheong, P. H.-Y.; Smith, A. D. Isothiourea-Catalyzed Atroposelective Acylation of Biaryl Phenols via Sequential Desymmetrization/Kinetic Resolution. Angew. Chem., Int. Ed. 2020,59, 7897−7905. (m) Luo, J.; Zhang, T.; Wang, L.; Liao, G.; Yao, Q.-J.; Wu, Y.-J.; Zhan, B.-B.; Lan, Y.; Lin, X.-F.; Shi, B.-F. Enantioselective Synthesis of Biaryl Atropisomers via Pd-Catalyzed C− H Olefination using Chiral Spiro Phosphoric Acid Ligands. Angew. Chem., Int. Ed. 2019,58, 6708−6712. (n) Zhan, B.-B.; Wang, L.; Luo, J.; Lin, X.-F.; Shi, B.- F. Synthesis of Axially Chiral Biaryl-2-amines by PdII- Catalyzed Free Amine-Directed Atroposelective C-H Olefination. Angew. Chem., Int. Ed. 2020,59, 3568−3572. (o) Liu, Z. S.; Hua, Y.; Gao, Q.; Ma, Y.; Tang, H.; Shang, Y.; Cheng, H. G.; Zhou, Q. Construction of Axial Chirality Via Palladium/Chiral Norbornene Cooperative Catalysis. Nat. Catal. 2020,3, 727−733. (20) (a) Bringmann, G.; Reuscher, H. Atropodiastereoselective Ring Opening of Bridged, “Axial-Prostereogenic”Biaryls: Directed Synthesis of (+)-Ancistrocladisine. Angew. Chem., Int. Ed. Engl. 1989,28, 1672− 1673. (b) Bringmann, G.; Walter, R.; Ewers, C. L. Diastereoselective Ring Opening of Achiral Bridged Biaryls Using Chiral O-and N- Nucleophiles: First Atropo-Enantioselective Synthesis of (−)-4, 4’-Bis (orcinol). Synlett 1991,1991, 581−583. (c) Bringmann, G.; Pabst, T.; Busemann, S.; Peters, K.; Peters, E.-M. Atropo-enantioselective Synthesis of a Simplified Analog of Mastigophorenes A and B. Tetrahedron 1998,54, 1425−1438. (d) Bringmann, G.; Mortimer, A. J. P.; Keller, P. A.; Gresser, M. J.; Garner, J.; Breuning, M. Atroposelective Synthesis of Axially Chiral Biaryl Compounds. Angew. Chem., Int. Ed. 2005,44, 5384−5427. (21) Bringmann, G.; Menche, D. Stereoselective Total Synthesis of Axially Chiral Natural Products Via Biaryl Lactones. Acc. Chem. Res. 2001,34, 615−624. (22) Ashizawa, T.; Tanaka, S.; Yamada, T. Catalytic Atropo- Enantioselective Reduction of Biaryl Lactones to Axially Chiral Biaryl Compounds. Org. Lett. 2008,10, 2521−2524. (23) Chen, G.-Q.; Lin, B.-J.; Huang, J.-M.; Zhao, L.-Y.; Chen, Q.-S.; Jia, S.-P.; Yin, Q.; Zhang, X. Design and Synthesis of Chiral Oxaspirocyclic Ligands for Ir-Catalyzed Direct Asymmetric Reduction of Bringmann’s Lactones With Molecular H2.J. Am. Chem. Soc. 2018,140, 8064−8068. (24) Hu, L.; Zhang, Y.; Chen, G.-Q.; Lin, B.-J.; Zhang, Q.-W.; Yin, Q.; Zhang, X. CuH-Catalyzed Atropoenantioselective Reduction of Bringmann’s Lactones via Dynamic Kinetic Resolution. Org. Lett. 2019,21, 5575−5580. (25) Yu, C.; Huang, H.; Li, X.; Zhang, Y.; Wang, W. Dynamic Kinetic Resolution of Biaryl Lactones via a Chiral Bifunctional Amine Thiourea-Catalyzed Highly Atropo-Enantioselective Transesterification. J. Am. Chem. Soc. 2016,138, 6956−6959. (26) Mori, K.; Itakura, T.; Akiyama, T. Enantiodivergent Atroposelective Synthesis of Chiral Biaryls by Asymmetric Transfer Hydrogenation: Chiral Phosphoric Acid Catalyzed Dynamic Kinetic Resolution. Angew. Chem., Int. Ed. 2016,55, 11642−11646. (27) (a) Zhang, J.; Wang, J. Atropoenantioselective Redox-Neutral Amination of Biaryl Compounds through Borrowing Hydrogen and Dynamic Kinetic Resolution. Angew. Chem., Int. Ed. 2018,57, 465−469. (b) Guo, D.; Zhang, J.; Zhang, B.; Wang, J. Ruthenium-Catalyzed Atropoenantioselective Synthesis of Axial Biaryls via Reductive Amination and Dynamic Kinetic Resolution. Org. Lett. 2018,20, 6284−6288. (28) (a) This assumption is supported by the remarkable acidity of sulfonyl anilines, slightly higher than that of phenol: Bordwell pKa Table, http://www.chem.wisc.edu/areas/reich/pkatable/. (b) Bordwell, F. G. J.; McCallum, R.; Olmstead, W. N. Acidities and Hydrogen Bonding of Phenols in Dimethyl Sulfoxide. J. Org. Chem. 1984,49, 1424−1427. (29) Calculations were performed at the DFT SMD-B3LYP-d3bj/6- 31+g(d,p) level, including, during optimization, bulk solvent effects (1,4-dioxane) and the D3 version of Grimme’s empirical dispersion with Becke−Johnson damping. Preliminary geometry optimizations and analysis of the potential energy surface of the calculated species, in addition to a thorough conformational analysis, were carried out with the semiempirical quantum mechanics extended tight binding XTB and CREST programs by the Grimme group. The model system studied consisted of the different diasteromers of the hemiaminal 1and the aminal 3and the corresponding open forms without simplifications. See the Supporting Information for further details. (30) For a related study see: Bringmann, G.; Vitt, D.; Kraus, J.; Breuning, M. The ortho-Hydroxy-ortho’-Formyl Biaryl/Lactol Equilibrium: Quantum Chemical Studies on Structure and Dynamics. Tetrahedron 1998,54, 10691−10698. (31) (a) Fujii, A.; Hashiguchi, S.; Uematsu, N.; Ikariya, T.; Noyori, R. Ruthenium(II)-Catalyzed Asymmetric Transfer Hydrogenation of Ketones Using a Formic Acid-Triethylamine Mixture. J. Am. Chem. Soc. 1996,118, 2521−2522. (c) Uematsu, N.; Fujii, A.; Hashiguchi, S.; Ikariya, T.; Noyori, R. Asymmetric Transfer Hydrogenation of Imines. J. Am. Chem. Soc. 1996,118, 4916−4917. For a review see: (d) Foubelo, F.; Yus, M. Catalytic Asymmetric Transfer Hydrogenation of Imines: Recent Advances. Chem. Rec. 2015,15, 907−924. For some selected examples of Ru(II)/TsDPEN-catalyzed ATH of imines, see: (e) Ros, A.; Magriz, A.; Dietrich, H.; Ford, M.; Fernández, R.; Lassaletta, J. M. Transfer Hydrogenation of α-Branched Ketimines: Enantioselective Synthesis of Cycloalkylamines via Dynamic Kinetic Resolution. Adv. Synth. Catal. 2005,347, 1917−1920. (f) Wu, Z.; Perez, M.; Scalone, M.; Ayad, T.; Ratovelomanana-Vidal, V. Ruthenium- ACS Catalysis pubs.acs.org/acscatalysis Research Article https://doi.org/10.1021/acscatal.1c00571 ACS Catal. 2021, 11, 4117−4124 4123 Catalyzed Asymmetric Transfer Hydrogenation of 1-Aryl-Substituted Dihydroisoquinolines: Access to Valuable Chiral 1-Aryl-Tetrahydroi- soquinoline Scaffolds. Angew. Chem., Int. Ed. 2013,52, 4925−4928. (32) Garro-Helion, F.; Merzouk, A.; Guibé, F. Mild and Selective Palladium(0)-Catalyzed Deallylation of Allylic Amines. Allylamine and Diallylamine as Very Convenient Ammonia Equivalents for the Synthesis of Primary Amines. J. Org. Chem. 1993,58, 6109−6113. ■NOTE ADDED AFTER ASAP PUBLICATION This paper was originally published on March 18, 2021. Figure 2 was missing 3D structures, and the corrected version was reposted on April 2, 2021. ACS Catalysis pubs.acs.org/acscatalysis Research Article https://doi.org/10.1021/acscatal.1c00571 ACS Catal. 2021, 11, 4117−4124 4124