Developing P-Stereogenic Phosphine Ligand for Transition Metal Catalyzed Asymmetric Hydrogenation

This dissertation focusses on the discussion of how empirical ligand design works on the development of chiral pincer ligands in the field of asymmetric hydrogenation. Although the design art of bisphosphine ligands was well-established, this empirical guide for pincer ligand design is still ambiguous. Developing a ligand design guide based on the nature of metals enables synthetic chemists to improve the catalytic performance without investing large numbers of time, develop highly efficient catalysts for industrial uses, or explore new areas and mechanistic insights.

Learning from the history of chiral pincer ligand development, over 14 categories of pincer ligands were reported according to the coordinating atoms by the time that this dissertation was prepared. Firstly, the ligand design and relevant catalytic performance of different ligand categories were summarized and discussed in prevalent noble metal catalysis such as Ru(II), Ir(III). Based on the nature of Fe(II) with respect to noble metals, a novel PNP-type ligand HengPNP (L) was designed and successfully synthesized. Empirical design perspectives were discussed, and the ligand was characterized by NMR, HRMS. Its corresponding Fe(II) complex was studied by X-ray crystallographic technique. However, the Fe(II) carbonyl complex was thermodynamically unstable under decent pressure.

To better understand the catalytic performance and enantioselectivity of HengPNP (L), its corresponding Ir(III) complex was employed in the asymmetric hydrogenation of various ketone substrates. A C-H bond activation Ir(III) compound was successfully isolated. The Ir(III)/HengPNP was efficient on the asymmetric hydrogenation of orthosubstituted benzophenones with excellent ee and up to 500 TON. The catalyst was superior on the hydrogenation of bis-ortho-substituted benzophenones, excellent ee was achieved over the state-of-the-art Ir/f-amphox. DFT studies was conducted to shed light on the enantio-induction model of Ir/HengPNP. A novel enantio-induction mechanism was established-the change of rotation energy of ketone substrate under the steric pressure from rigid Ir/HengPNP, was responsible for the enantioselectivity. IrH/NH bifunctional mechanism was proposed for this protocol.

[1. Blaser, H.; Spindler, F.; Studer, M., Enantioselective catalysis in fine chemicals production. Applied Catalysis A: General 2001, 221 (1-2), 119-143.2. Blaser, H. U.; Pugin, B.; Spindler, F.; Saudan, L. A., Hydrogenation. Applied Homogeneous Catalysis with Organometallic Compounds: A Comprehensive Handbook in Four Volumes 2017, 621-690.3. Osborn, J.; Wilkinson, G.; Mrowca, J., Tris(triphenylphosphine)halorhodium (I). Inorg. Synth. 1967, 10, 67-71.4. Knowles, W. S.; Sabacky, M. J.; Vineyard, B., Catalytic asymmetric hydrogenation. J.Chem. Soc, Chem. Commun. 1972, (1), 10-11.5. Knowles, W. S., Asymmetric hydrogenations (Nobel lecture). Angew. Chem. Int. Ed.2002, 41 (12), 1998-2007.6. Dang, T.; Kagan, H., The asymmetric synthesis of hydratropic acid and amino-acids by homogeneous catalytic hydrogenation. J. Chem. Soc., Chem. Commun., 1971, (10), 481-481.7. Knowles, W. S.; Sabacky, M. J.; Vineyard, B.; Weinkauff, D., Asymmetric hydrogenation with a complex of rhodium and a chiral bisphosphine. J. Am. Chem. Soc. 1975, 97 (9), 2567-2568.8. Miyashita, a. A.; Yasuda, A.; Takaya, H.; Toriumi, K.; Ito, T.; Souchi, T.; Noyori, R.,Synthesis of 2, 2'-bis(diphenylphosphino)-1,1'-binaphthyl (BINAP), an atropisomericchiral bis(triaryl)phosphine, and its use in the rhodium(I)-catalyzed asymmetrichydrogenation of. alpha.-(acylamino)acrylic acids. J. Am. Chem. Soc. 1980, 102 (27),7932-7934.9. Noyori, R.; Tomino, I.; Tanimoto, Y., Virtually complete enantioface differentiation incarbonyl group reduction by a complex aluminum hydride reagent. J. Am. Chem. Soc. 1979, 101 (11), 3129-3131.10. Cram, D. J.; Cram, J. M., Design of complexes between synthetic hosts and organicguests. Acc. Chem. Res. 1978, 11 (1), 8-14.11. Tang, W. J.; Zhang, X. M., New chiral phosphorus ligands for enantioselectivehydrogenation. Chem. Rev. 2003, 103 (8), 3029-3069.12. Zhang, W.; Chi, Y.; Zhang, X., Developing chiral ligands for asymmetrichydrogenation. Acc. Chem. Res. 2007, 40 (12), 1278-1290.13. Wang, D. S.; Chen, Q. A.; Lu, S. M.; Zhou, Y. G., Asymmetric hydrogenation ofheteroarenes and arenes. Chem. Rev. 2012, 112 (4), 2557-90.14. Andrushko, N.; Andrushko, V., Asymmetric Hydrogenation of C=O and C=N Bondsin Stereoselective Synthesis. Stereoselective Synthesis of Drugs and Natural Products2013, 1-52.15. Hopmann, K. H.; Bayer, A., Enantioselective imine hydrogenation with iridiumcatalysts: Reactions, mechanisms and stereocontrol. Coord. Chem. Rev. 2014, 268, 59-82.16. Li, W.; Zhang, X. M., Asymmetric Hydrogenation of Imines. In StereoselectiveFormation of Amines, Li, W.; Zhang, X., Eds. 2014; Vol. 343, pp 103-144.17. Yoshimura, M.; Tanaka, S.; Kitamura, M., Recent topics in catalytic asymmetrichydrogenation of ketones. Tetrahedron Lett. 2014, 55 (27), 3635-3640.18. Kuwano, R., Transition-Metal-Catalyzed Asymmetric Hydrogenation of Aromatics.Asymmetric Dearomatization Reactions., 2016.19. Zhang, Z.; Butt, N. A.; Zhang, W., Asymmetric Hydrogenation of Nonaromatic CyclicSubstrates. Chem. Rev. 2016, 116 (23), 14769-14827.20. Gajewy, J.; Łowicki, D.; Kwit, M., From Noble Metals to Fe-, Co-, and Ni-basedCatalysts: A Case Study of Asymmetric Reductions. Chiral Lewis Acids in OrganicSynthesis., 2017, 183.21. Xie, X.; Lu, B.; Li, W.; Zhang, Z., Coordination determined chemo- andenantioselectivities in asymmetric hydrogenation of multi-functionalized ketones. Coord. Chem. Rev., 2018, 355, 39-53.22. Zhang, Z.; Butt, N. A.; Zhou, M.; Liu, D.; Zhang, W., Asymmetric Transfer andPressure Hydrogenation with Earth-Abundant Transition Metal Catalysts. Chin. J. Chem.2018, 36 (5), 443-454.23. Wan, F.; Tang, W., Phosphorus ligands from the Zhang lab: Design, asymmetrichydrogenation, and industrial applications. Chin. J. Chem. 2021, 39 (4), 954-968.24. Zhao, Q.; Chen, C.; Wen, J.; Dong, X.-Q.; Zhang, X., Noncovalent interactionassistedferrocenyl phosphine ligands in asymmetric catalysis. Acc. Chem. Res. 2020, 53(9), 1905-1921.25. Moulton, C. J.; Shaw, B. L., Transition metal–carbon bonds. Part XLII. Complexes ofnickel, palladium, platinum, rhodium and iridium with the tridentate ligand 2, 6-bis [(di-tbutylphosphino)methyl] phenyl. J. Chem. Soc, Dalton Trans., 1976, (11), 1020-1024.26. Empsall, H. D.; Hyde, E. M.; Markham, R.; McDonald, W. S.; Norton, M. C.; Shaw,B. L.; Weeks, B., Synthesis and X-ray structure of an unusual iridium ylide or carbenecomplex. J. Chem. Soc., Chem. Commun., 1977, (17), 589-590.27. Crocker, C.; Errington, R. J.; Markham, R.; Moulton, C. J.; Odell, K. J.; Shaw, B.L., Large-ring and cyclometalated rhodium complexes from some medium-chain. alpha.,.omega.-diphosphines. J. Am. Chem. Soc., 1980, 102 (13), 4373-4379.28. Briggs, J. R.; Constable, A. G.; McDonald, W. S.; Shaw, B. L., Transition metal–carbon bonds. Part 53. The further chemistry of cyclometallated complexes formed fromtBu2P(CH2)5PtBu2 and PtCl2: crystal structure of [PtCl{tBu2PCH2CH2C=CHCH2PtBu2}]. Journal of the Chemical Society, Dalton Transactions 1982, (7), 1225-1230.29. Crocker, C.; Empsall, H. D.; Errington, R. J.; Hyde, E. M.; McDonald, W. S.;Markham, R.; Norton, M. C.; Shaw, B. L.; Weeks, B., Transition metal–carbon bonds.Part 52. Large ring and cyclometallated complexes formed from tBu2PCH2CH2CHRCH2CH2PtBu2 (R= H or Me) and IrCl3, or [Ir2Cl4(cyclooctene)4]: crystal structures of thecyclometallated hydride,[IrHCl(tBu2PCH2CH2CHCH2CH2PtBu2)], and the carbenecomplex [IrCl(tBu2PCH2CH2CCH2CH2PtBu2)]. J. Chem. Soc., Dalton Trans., 1982, (7),1217-1224.30. Crocker, C.; Errington, R. J.; Markham, R.; Moulton, C. J.; Shaw, B. L., Furtherstudies on the interconversion of large ring and cyclometallated complexes of rhodium,with the diphosphines tBu2P(CH2)5PtBu2 and tBu2PCH2CH=CHCH2PtBu2. J. Chem. Soc., Dalton Trans., 1982, (2), 387-395.31. Errington, R. J.; McDonald, W. S.; Shaw, B. L., Transition metal–carbon bonds. Part54. Complexes of palladium, platinum, rhodium, and iridium with tBu2PCH2CHMe(CH2)3PtBu2. Crystal structures of [PdCl(tBu2PCH2CHMeCHCH2CH2PtBu2)] and [IrH(Cl)(tBu2PCH2CHMeCHCH2CH2PtBu2)]. J. Chem. Soc., Dalton Trans., 1982, (9), 1829-1835.32. Albrecht, M.; van Koten, G., Platinum group organometallics based on "Pincer"complexes: Sensors, switches, and catalysts. Angew. Chem. Int. Ed., 2001, 40 (20), 3750-3781.33. Hao, X.; Niu, J.; Zhao, X.; Gong, J.; Song, M., Development of Pincer Catalysts withSelected Group 8～10 Metals. Chinese J. Org. Chem., 2013, 33 (4).34. van Koten, G., The Monoanionic ECE-Pincer Ligand: A Versatile Privileged LigandPlatform—General Considerations. In Organometallic pincer chemistry, Springer: 2013;pp 1-20.35. Chase, P. A.; Gossage, R. A.; van Koten, G., Modern Organometallic MultidentateLigand Design Strategies: The Birth of the Privileged “Pincer” Ligand Platform. In ThePrivileged Pincer-Metal Platform: Coordination Chemistry & Applications, 2015; pp 1-15.36. Dobereiner, G. E.; Zhang, X.; Wang, H., Phosphine Ligand Development forHomogeneous Asymmetric Hydrogenation. Comprehensive Organometallic Chemistry IV.,2021.37. Nishiyama, H.; Sakaguchi, H.; Nakamura, T.; Horihata, M.; Kondo, M.; Itoh, K.,Chiral and C2-symmetrical bis(oxazolinylpyridine)rhodium(III) complexes: effectivecatalysts for asymmetric hydrosilylation of ketones. Organometallics., 1989, 8 (3), 846-848.38. Nishiyama, H.; Itoh, Y.; Matsumoto, H.; Park, S.-B.; Itoh, K., New chiral rutheniumbis (oxazolinyl) pyridine catalyst. Efficient asymmetric cyclopropanation of olefins withdiazoacetates. J. Am. Chem. Soc., 1994, 116 (5), 2223-2224.39. Cuervo, D.; Gamasa, M. P.; Gimeno, J., New chiral ruthenium(II) catalysts containing2,6-bis(4'-(R)-phenyloxazolin-2'-yl)pyridine (Ph-pybox) ligands for highlyenantioselective transfer hydrogenation of ketones. Chem., 2004, 10 (2), 425-32.40. Menendez-Pedregal, E.; Vaquero, M.; Lastra, E.; Gamasa, P.; Pizzano, A., Highlyenantioselective hydrogenation of N-aryl imines derived from acetophenones by using Rupybox complexes under hydrogenation or transfer hydrogenation conditions in isopropanol. Chem., 2015, 21 (2), 549-53.41. Claros, M.; de Julian, E.; Diez, J.; Lastra, E.; Gamasa, M. P., Asymmetric TransferHydrogenation of Arylketones Catalyzed by Enantiopure Ruthenium(II)/PyboxComplexes Containing Achiral Phosphonite and Phosphinite Ligands. Molecules., 2020,25 (4).42. Paredes, P.; Díez, J.; Gamasa, M. P., Synthesis of enantiopure iridium (I) and iridium(III) pybox complexes and their application in the asymmetric transfer hydrogenation ofketones. Organometallics., 2008, 27 (11), 2597-2607.43. de Julián, E.; Díez, J.; Lastra, E.; Gamasa, M. P., Iridium(I) complexes bearing the (S,S)- iPr-pybox ligand in the asymmetric transfer hydrogenation of acetophenone. J MolCatal A: Chem., 2014, 394, 295-302.44. Vega, E.; Lastra, E.; Gamasa, M. P., Asymmetric transfer hydrogenation of ketonescatalyzed by enantiopure osmium(II) pybox complexes. Inorg. Chem. 2013, 52 (10), 6193-8.45. de Julián, E.; Fernández, N.; Díez, J.; Lastra, E.; Gamasa, M. P., Osmium(II)/R-pyboxvs ruthenium(II)/R-pybox complexes in the catalytic asymmetric transfer hydrogenation of arylketones. Mol. Catal., 2018, 456, 75-86.46. Enthaler, S.; Hagemann, B.; Bhor, S.; Anilkumar, G.; Tse, M. K.; Bitterlich, B.;Junge, K.; Erre, G.; Beller, M., New Ruthenium Catalysts for Asymmetric TransferHydrogenation of Prochiral Ketones. Adv. Synth. Catal., 2007, 349 (6), 853-860.47. Ye, W.; Zhao, M.; Du, W.; Jiang, Q.; Wu, K.; Wu, P.; Yu, Z., Highly activeruthenium(II) complex catalysts bearing an unsymmetrical NNN ligand in the (asymmetric) transfer hydrogenation of ketones. Chem., 2011, 17 (17), 4737-41.48. Ye, W.; Zhao, M.; Yu, Z., Ruthenium(II) pyrazolyl-pyridyl-oxazolinyl complexcatalysts for the asymmetric transfer hydrogenation of ketones. Chem., 2012, 18 (35),10843-6.49. Chai, H.; Liu, T.; Yu, Z., NHTs Effect on the Enantioselectivity of Ru(II) ComplexCatalysts Bearing a Chiral Bis(NHTs)-Substituted Imidazolyl-Oxazolinyl-Pyridine Ligandfor Asymmetric Transfer Hydrogenation of Ketones. Organometallics., 2017, 36 (21),4136-4144.50. Jiang, Y.; Jiang, Q.; Zhang, X., A new chiral bis (oxazolinylmethyl) amine ligand forRu-catalyzed asymmetric transfer hydrogenation of ketones. J. Am. Chem. Soc., 1998, 120(15), 3817-3818.51. Li, W.; Hou, G.; Wang, C.; Jiang, Y.; Zhang, X., Asymmetric hydrogenation ofketones catalyzed by a ruthenium(II)-indan-ambox complex. Chem. Commun. 2010, 46(22), 3979-81.52. Johnson, T. C.; Totty, W. G.; Wills, M., Application of ruthenium complexes oftriazole-containing tridentate ligands to asymmetric transfer hydrogenation of ketones. Org. Lett., 2012, 14 (20), 5230-5233.53. Pellegrino, S.; Facchetti, G.; Gandolfi, R.; Fusè, M.; Erba, E.; Rimoldi, I.,Ruthenium(II) complexes bearing (NNN) ligand: catalytic evaluation of different solventmediated coordination modes. Can. J. Chem., 2018, 96 (1), 40-43.54. Ito, J.-i.; Nishiyama, H., Bifunctional Phebox Complexes for Asymmetric Catalysis. InBifunctional Molecular Catalysis, 2011; pp 185-205.55. Nishiyama, H.; Ito, J. I., Bis (oxazolinyl) phenyl transition metal complexes: synthesis,asymmetric catalysis, and coordination chemistry. Chem. Rec., 2007, 7 (3), 159-166.56. Ito, J.-i.; Sugino, K.; Matsushima, S.; Sakaguchi, H.; Iwata, H.; Ishihara, T.; Nishiyama, H., Synthesis of NHC-Oxazoline Pincer Complexes of Rh and Ru and Their CatalyticActivity for Hydrogenation and Conjugate Reduction. Organometallics., 2016, 35 (11),1885-1894.57. Baratta, W.; Bosco, M.; Chelucci, G.; Del Zotto, A.; Siega, K.; Toniutti, M.; Zangrando, E.; Rigo, P., Terdentate RuX (CNN)(PP)(X= Cl, H, OR) complexes: synthesis, properties, and catalytic activity in fast transfer hydrogenation. Organometallics., 2006, 25 (19), 4611-4620.58. Baratta, W.; Benedetti, F.; Del Zotto, A.; Fanfoni, L.; Felluga, F.; Magnolia, S.;Putignano, E.; Rigo, P., Chiral Pincer Ruthenium and Osmium Complexes for the Fast and Efficient Hydrogen Transfer Reduction of Ketones. Organometallics., 2010, 29 (16), 3563-3570.59. Evans, D. A.; Nelson, S. G.; Gagne, M. R.; Muci, A. R., A chiral samarium-basedcatalyst for the asymmetric Meerwein-Ponndorf-Verley reduction. J. Am. Chem. Soc., 1993, 115 (21), 9800-9801.60. Jiang, Y.; Jiang, Q.; Zhu, G.; Zhang, X., New chiral ligands for catalytic asymmetrictransfer hydrogenation of ketones. Tetrahedron Lett., 1997, 38 (37), 6565-6568.61. Jiang, Y.; Jiang, Q.; Zhu, G.; Zhang, X., Highly effective NPN-type tridentate ligandsfor asymmetric transfer hydrogenation of ketones. Tetrahedron Lett., 1997, 38 (2), 215-218.62. Braunstein, P.; Naud, F.; Pfaltz, A.; Rettig, S. J., Ruthenium complexes with noveltridentate N, P, N ligands containing a phosphonite bridge between two chiral oxazolins.Catalytic activity in cyclopropanation of olefins and transfer hydrogenation ofacetophenone. Organometallics., 2000, 19 (14), 2676-2683.63. Brunner, H.; Niemetz, M., Enantioselective Catalysis CXLI
[1]. Tridentate Ligandswith 1-(Pyridin-2-yl) ethylamine as Chiral Building Block in the Enantioselective Transfer Hydrogenation of Acetophenone. Monatshefte für Chemie/Chemical Monthly., 2002, 133(2), 115-126.64. Longmire, J. M.; Zhang, X., Synthesis of chiral phosphine ligands with aromaticbackbones and their applications in asymmetric catalysis. Tetrahedron Lett., 1997, 38 (10), 1725-1728.65. Dani, P.; Karlen, T.; Gossage, R. A.; Gladiali, S.; van Koten, C., Hydrogen-transfercatalysis with pincer-aryl ruthenium(II) complexes. Angew. Chem. Int. Ed., 2000, 39 (4),743.66. Albrecht, M.; Kocks, B. M.; Spek, A. L.; van Koten, G., Chiral platinum and palladiumcomplexes containing functionalized C2-symmetric bisaminoaryl ‘Pincer’ligands. J.Organomet. Chem., 2001, 624 (1-2), 271-286.67. Medici, S.; Gagliardo, M.; Williams, S. B.; Chase, P. A.; Gladiali, S.; Lutz, M.; Spek,A. L.; van Klink, G. P.; van Koten, G., Novel P‐Stereogenic PCP Pincer‐Aryl Ruthenium(II) Complexes and Their Use in the Asymmetric Hydrogen Transfer Reaction ofAcetophenone. Helv. Chim. Acta., 2005, 88 (3), 694-705.68. Barbaro, P.; Bianchini, C.; Togni, A., Synthesis and characterization of ruthenium(II)complexes containing chiral bis(ferrocenyl)-P-3 or -P2S ligands. Asymmetric transferhydrogenation of acetophenone. Organometallics., 1997, 16 (13), 3004-3014.69. Barbaro, P.; Bianchini, C.; Giambastiani, G.; Togni, A., Ruthenium(II) Complexeswith Triphosphane Ligands Combining Planar, Phosphorus, and Carbon Chirality:Application to Asymmetric Reduction of Trifluoroacetophenone. Eur. J. Inorg. Chem.,2003, 2003 (23), 4166-4172.70. Tang, L.; Wang, Q.; Wang, J.; Lin, Z.; Wang, X.; Cun, L.; Yuan, W.; Zhu, J.; Liao,J.; Deng, J., A new chiral sulfinyl–NH–pyridine ligand for Ir-catalyzed asymmetric transfer hydrogenation reaction. Tetrahedron Lett., 2012, 53 (30), 3839-3842.71. Bao, D. H.; Wu, H. L.; Liu, C. L.; Xie, J. H.; Zhou, Q. L., Development of Chiral SpiroP-N-S Ligands for Iridium-Catalyzed Asymmetric Hydrogenation of beta-Alkyl-beta-Ketoesters. Angew. Chem. Int. Ed., 2015, 54 (30), 8791-4.72. Ohkuma, T.; Ooka, H.; Hashiguchi, S.; Ikariya, T.; Noyori, R., PracticalEnantioselective Hydrogenation of Aromatic Ketones. J. Am. Chem. Soc., 1995, 117 (9),2675-2676.73. Ohkuma, T.; Ooka, H.; Yamakawa, M.; Ikariya, T.; Noyori, R., Stereoselectivehydrogenation of simple ketones catalyzed by Ruthenium (II) complexes. J. Org. Chem.,1996, 61 (15), 4872-4873.74. Ohkuma, T.; Ikehira, H.; Ikariya, T.; Noyori, R., Asymmetric hydrogenation of cyclicα, β-unsaturated ketones to chiral allylic alcohols. Synlett., 1997, 1997 (Sup. I), 467-468.75. Doucet, H.; Ohkuma, T.; Murata, K.; Yokozawa, T.; Kozawa, M.; Katayama, E.;England, A. F.; Ikariya, T.; Noyori, R., trans‐[RuCl2(phosphane)(1, 2‐diamine)] and Chiraltrans‐[RuCl2(diphosphane)(1, 2‐diamine)]: Shelf‐Stable Precatalysts for the Rapid,Productive, and Stereoselective Hydrogenation of Ketones. Angew. Chem. Int. Ed., 1998,37 (12), 1703-1707.76. Ohkuma, T.; Doucet, H.; Pham, T.; Mikami, K.; Korenaga, T.; Terada, M.; Noyori,R., Asymmetric activation of racemic ruthenium (II) complexes for enantioselectivehydrogenation. J. Am. Chem. Soc., 1998, 120 (5), 1086-1087.77. Noyori, R.; Koizumi, M.; Ishii, D.; Ohkuma, T., Asymmetric hydrogenation viaarchitectural and functional molecular engineering. Pure Appl. Chem., 2001, 73 (2), 227-232.78. Noyori, R.; Ohkuma, T., Asymmetric catalysis by architectural and functionalmolecular engineering: practical chemo‐and stereoselective hydrogenation of ketones.Angew. Chem. Int. Ed., 2001, 40 (1), 40-73.79. Noyori, R., Asymmetric catalysis: science and opportunities (Nobel Lecture). Angew.Chem. Int. Ed., 2002, 41 (12), 2008-2022.80. Sandoval, C. A.; Shi, Q.; Liu, S.; Noyori, R., NH/pi attraction: a role in asymmetrichydrogenation of aromatic ketones with binap/1,2-diamine-ruthenium(II) complexes.Chem. Asian. J., 2009, 4 (8), 1221-4.81. Abdur-Rashid, K.; Clapham, S. E.; Hadzovic, A.; Harvey, J. N.; Lough, A. J.; Morris,R. H., Mechanism of the hydrogenation of ketones catalyzed by trans-dihydrido (diamine)ruthenium (II) complexes. J. Am. Chem. Soc., 2002, 124 (50), 15104-15118.82. Ohkuma, T.; Koizumi, M.; Yoshida, M.; Noyori, R., General asymmetrichydrogenation of hetero-aromatic ketones. Org. Lett., 2000, 2 (12), 1749-1751.83. Yamamura, T.; Nakatsuka, H.; Tanaka, S.; Kitamura, M., Asymmetric hydrogenationof tert-alkyl ketones: DMSO effect in unification of stereoisomeric ruthenium complexes. Angew. Chem. Int. Ed., 2013, 52 (35), 9313-5.84. Brunner, H.; Zettler, C.; Zabel, M., Asymmetric Catalysis. Part 149
[1]. Synthesis ofNew Chiral Tridentate Ligands for Enantioselective Catalysis. Monatsh. Chem., 2003,134 (9), 1253-1269.85. Flores-López, C. Z.; Flores-López, L. a. Z.; Aguirre, G.; Hellberg, L. H.; Parra-Hake,M.; Somanathan, R., Ruthenium(II)-assisted asymmetric hydrogen transfer reduction ofacetophenone using chiral tridentate phosphorus-containing ligands derived from (1R, 2R)-1,2-diaminocyclohexane. J Mol Catal A: Chem., 2004, 215 (1-2), 73-79.86. Clarke, M. L.; Diaz-Valenzuela, M. B.; Slawin, A. M. Z., Hydrogenation of aldehydes,esters, imines, and ketones catalyzed by a ruthenium complex of a chiral tridentate ligand. Organometallics., 2007, 26 (1), 16-19.87. Demmans, K. Z.; Olson, M. E.; Morris, R. H., Asymmetric Transfer Hydrogenation ofKetones with Well-Defined Manganese(I) PNN and PNNP Complexes. Organometallics.,2018, 37 (24), 4608-4618.88. Xie, J. H.; Liu, X. Y.; Xie, J. B.; Wang, L. X.; Zhou, Q. L., An additional coordinationgroup leads to extremely efficient chiral iridium catalysts for asymmetric hydrogenation of ketones. Angew. Chem. Int. Ed., 2011, 50 (32), 7329-32.89. 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 oxa-Spirocyclic Ligands for Ir-Catalyzed Direct Asymmetric Reduction of Bringmann's Lactones with Molecular H2. J. Am. Chem. Soc., 2018, 140 (26), 8064-8068.90. Zheng, Z.; Cao, Y.; Chong, Q.; Han, Z.; Ding, J.; Luo, C.; Wang, Z.; Zhu, D.;Zhou, Q.-L.; Ding, K., Chiral cyclohexyl-fused spirobiindanes: practical synthesis, liganddevelopment, and asymmetric catalysis. J. Am. Chem. Soc., 2018, 140 (32), 10374-1031.91. Nie, H.; Zhou, G.; Wang, Q.; Chen, W.; Zhang, S., Asymmetric hydrogenation ofaromatic ketones using an iridium(I) catalyst containing ferrocene-based P–N–N tridentate ligands. Tetrahedron: Asymmetry., 2013, 24 (24), 1567-1571.92. Hou, C. J.; Hu, X. P., Sterically Hindered Chiral Ferrocenyl P,N,N-Ligands for HighlyDiastereo-/Enantioselective Ir-Catalyzed Hydrogenation of alpha-Alkyl-beta-ketoesters via Dynamic Kinetic Resolution. Org. Lett., 2016, 18 (21), 5592-5595.93. Wu, W.; Liu, S.; Duan, M.; Tan, X.; Chen, C.; Xie, Y.; Lan, Y.; Dong, X. Q.;Zhang, X., Iridium Catalysts with f-Amphox Ligands: Asymmetric Hydrogenation ofSimple Ketones. Org. Lett., 2016, 18 (12), 2938-41.94. Zhang, F. H.; Wang, C.; Xie, J. H.; Zhou, Q. L., Synthesis of Tridentate Chiral SpiroAminophosphine−Oxazoline Ligands and Application to Asymmetric Hydrogenation of α‐Keto Amides. Adv. Synth. Catal., 2019, 361 (12), 2832-2835.95. Wei, D.-Q.; Chen, X.-S.; Hou, C.-J.; Hu, X.-P., Iridium-catalyzed asymmetrichydrogenation of β-keto esters with new phenethylamine-derived tridentate P,N,N-ligands. Synth. Commun., 2019, 49 (2), 237-243.96. Liang, Z.; Yang, T.; Gu, G.; Dang, L.; Zhang, X., Scope and Mechanism on Iridiumf-Amphamide Catalyzed Asymmetric Hydrogenation of Ketones. Chin. J. Chem., 2018, 36(9), 851-856.97. Yu, J.; Long, J.; Yang, Y.; Wu, W.; Xue, P.; Chung, L. W.; Dong, X. Q.; Zhang,X., Iridium-Catalyzed Asymmetric Hydrogenation of Ketones with Accessible andModular Ferrocene-Based Amino-phosphine Acid (f-Ampha) Ligands. Org. Lett., 2017,19 (3), 690-693.98. Yu, J.; Duan, M.; Wu, W.; Qi, X.; Xue, P.; Lan, Y.; Dong, X. Q.; Zhang, X., ReadilyAccessible and Highly Efficient Ferrocene-Based Amino-Phosphine-Alcohol (f-Amphol)Ligands for Iridium-Catalyzed Asymmetric Hydrogenation of Simple Ketones. Chem.,2017, 23 (4), 970-975.99. Zeng, L.; Yang, H.; Zhao, M.; Wen, J.; Tucker, J. H. R.; Zhang, X., C1-SymmetricPNP Ligands for Manganese-Catalyzed Enantioselective Hydrogenation of Ketones:Reaction Scope and Enantioinduction Model. ACS Catal., 2020, 10 (23), 13794-13799.100. Ling, F.; Nian, S.; Chen, J.; Luo, W.; Wang, Z.; Lv, Y.; Zhong, W., Developmentof Ferrocene-Based Diamine-Phosphine-Sulfonamide Ligands for Iridium-CatalyzedAsymmetric Hydrogenation of Ketones. J. Org. Chem., 2018, 83 (18), 10749-10761.101. Ling, F.; Hou, H.; Chen, J.; Nian, S.; Yi, X.; Wang, Z.; Song, D.; Zhong, W.,Highly Enantioselective Synthesis of Chiral Benzhydrols via Manganese CatalyzedAsymmetric Hydrogenation of Unsymmetrical Benzophenones Using an Imidazole-Based Chiral PNN Tridentate Ligand. Org. Lett., 2019, 21 (11), 3937-3941.102. Ling, F.; Chen, J.; Nian, S.; Hou, H.; Yi, X.; Wu, F.; Xu, M.; Zhong, W.,Manganese-Catalyzed Enantioselective Hydrogenation of Simple Ketones Using anImidazole-Based Chiral PNN Tridentate Ligand. Synlett., 2020, 31 (03), 285-289.103. Zhang, L.; Tang, Y.; Han, Z.; Ding, K., Lutidine-Based Chiral Pincer ManganeseCatalysts for Enantioselective Hydrogenation of Ketones. Angew. Chem. Int. Ed., 2019,58 (15), 4973-4977.104. Császár, Z.; Szabó, E. Z.; Bényei, A. C.; Bakos, J.; Farkas, G., Chelate ring sizeeffects of Ir(P,N,N) complexes: Chemoselectivity switch in the asymmetric hydrogenation of α,β-unsaturated ketones. Catal. Commun., 2020, 146.105. Yang, H.; AlvarezGressier, M.; Lugan, N.; Mathieu, R., Ruthenium(II) complexescontaining optically active hemilabile P,N,O-tridentate ligands. Synthesis and evaluationin catalytic asymmetric transfer hydrogenation of acetophenone by propan-2-ol.Organometallics., 1997, 16 (7), 1401-1409.106. Kwong, H. L.; Lee, W. S.; Lai, T. S.; Wong, W. T., Ruthenium catalyzed asymmetrictransfer hydrogenation based on chiral P,N,O Schiff base ligands and crystal structure of a ruthenium(II) complex bearing chiral P,N,O Schiff base ligands. Inorg. Chem. Commun., 1999, 2 (2), 66-69.107. Alvarez, M.; Lugan, N.; Mathieu, R., Synthesis and evaluation of the bondingproperties of a potentially tridentate ligand: 1-(diphenylphosphino)-2-ethoxy-1-(2-pyridyl)ethane. J. Chem. Soc, Dalton Trans., 1994, (19), 2755-2760.108. Dai, H.; Hu, X.; Chen, H.; Bai, C.; Zheng, Z., New efficient P,N,O-tridentate ligandsfor Ru-catalyzed asymmetric transfer hydrogenation. Tetrahedron: Asymmetry., 2003, 14(11), 1467-1472.109. Phillips, S. D.; Fuentes, J. A.; Clarke, M. L., On the NH effect in ruthenium-catalysed hydrogenation of ketones: rational design of phosphine-amino-alcohol ligands forasymmetric hydrogenation of ketones. Chem., 2010, 16 (27), 8002-5.110. Altan, O.; Yılmaz, M. K., New phosphine-amino-alcohol tridentate ligands forruthenium catalyzed asymmetric transfer hydrogenation of ketones. J. Organomet. Chem., 2018, 861, 252-262.111. Junge, K.; Beller, M., Homogeneous Cobalt‐Catalysed Hydrogenation Reactions.Cobalt Catalysis in Organic Synthesis: Methods and Reactions., 2020, 25-66.112. Agbossou-Niedercorn, F.; Michon, C., Bifunctional homogeneous catalysts based on first row transition metals in asymmetric hydrogenation. Coord. Chem. Rev., 2020, 425.113. Dub, P. A.; Gordon, J. C., The role of the metal-bound N–H functionality in Noyoritype molecular catalysts. Nat. Rev. Chem., 2018, 2 (12), 396-408.114. Alig, L.; Fritz, M.; Schneider, S., First-row transition metal (de) hydrogenationcatalysis based on functional pincer ligands. Chem. Rev., 2018, 119 (4), 2681-2751.115. Wei, D.; Darcel, C., Iron catalysis in reduction and hydrometalation reactions. Chem.Rev., 2018, 119 (4), 2550-2610.116. Burk, M. J.; Feaster, J. E.; Harlow, R. L., New chiral phospholanes; Synthesis,characterization, and use in asymmetric hydrogenation reactions. Tetrahedron:Asymmetry., 1991, 2 (7), 569-592.117. Abdur-Rashid, K., Transfer hydrogenation processes and catalysts. 2007. US Patent: US 20050107638 A1.118. Garbe, M.; Junge, K.; Walker, S.; Wei, Z.; Jiao, H.; Spannenberg, A.; Bachmann,S.; Scalone, M.; Beller, M., Manganese(I)-Catalyzed Enantioselective Hydrogenation ofKetones Using a Defined Chiral PNP Pincer Ligand. Angew. Chem. Int. Ed., 2017, 56 (37), 11237-11241.119. Garbe, M.; Wei, Z.; Tannert, B.; Spannenberg, A.; Jiao, H.; Bachmann, S.; Scalone,M.; Junge, K.; Beller, M., Enantioselective Hydrogenation of Ketones using DifferentMetal Complexes with a Chiral PNP Pincer Ligand. Adv. Synth. Catal., 2019, 361 (8),1913-1920.120. Arenas, I.; Boutureira, O.; Matheu, M. I.; Díaz, Y.; Castillón, S., Synthesis of aPStereogenic PNPtBu,PhRuthenium Pincer Complex and Its Application in AsymmetricReduction of Ketones. Eur. J. Org. Chem., 2015, 2015 (17), 3666-3669.121. Yang, Z.; Wei, X.; Liu, D.; Liu, Y.; Sugiya, M.; Imamoto, T.; Zhang, W., PStereogenicpincer iridium complexes: Synthesis, structural characterization andapplication in asymmetric hydrogenation. J. Organomet. Chem., 2015, 791, 41-45.122. Huber, R.; Passera, A.; Mezzetti, A., Iron(II)-Catalyzed Hydrogenation ofAcetophenone with a Chiral, Pyridine-Based PNP Pincer Ligand: Support for an Outer-Sphere Mechanism. Organometallics., 2018, 37 (3), 396-405.123. Huber, R.; Passera, A.; Gubler, E.; Mezzetti, A., P-Stereogenic PN(H)P Iron(II)Catalysts for the Asymmetric Hydrogenation of Ketones: The Importance of Non-Covalent Interactions in Rational Ligand Design by Computation. Adv. Synth. Catal., 2018, 360 (15), 2900-2913.124. Bianchini, C.; Farnetti, E.; Glendenning, L.; Graziani, M.; Nardin, G.; Peruzzini,M.; Rocchini, E.; Zanobini, F., Synthesis of the New Chiral Aminodiphosphine Ligands(R)- and (S)-(.alpha.-Methylbenzyl)bis(2-(diphenylphosphino)ethyl)amine and Their Usein the Enantioselective Reduction of .alpha.,.beta.-Unsaturated Ketones to Allylic Alcohols by Iridium Catalysis. Organometallics 1995, 14 (3), 1489-1502.125. Jiang, Q. Z.; VanPlew, D.; Murtuza, S.; Zhang, X. M., Synthesis of (1R,1R')-2,6-bis1-(diphenylphosphino)ethyl pyridine and its application in asymmetric transferhydrogenation. Tetrahedron Lett., 1996, 37 (6), 797-800.126. Dai, H.; Hu, X.; Chen, H.; Bai, C.; Zheng, Z., New chiral ferrocenyldiphosphineligand for catalytic asymmetric transfer hydrogenation. J. Mol. Catal. A: Chem.2004, 209(1-2), 19-22.127. Kuriyama, W.; Matsumoto, T.; Ino, Y.; Ogata, O. Novel ruthenium carbonyl complexhaving a tridentate ligand and manufacturing method and usage therefor. Patent, WO2011048727A1.128. Lagaditis, P. O.; Sues, P. E.; Sonnenberg, J. F.; Wan, K. Y.; Lough, A. J.; Morris,R. H., Iron(II) complexes containing unsymmetrical P-N-P' pincer ligands for the catalytic asymmetric hydrogenation of ketones and imines. J. Am. Chem. Soc., 2014, 136 (4), 1367-80.129. Sonnenberg, J. F.; Lough, A. J.; Morris, R. H., Synthesis of Iron P-N-P′ and P-NHP′Asymmetric Hydrogenation Catalysts. Organometallics., 2014, 33 (22), 6452-6465.130. Smith, S. A. M.; Lagaditis, P. O.; Lupke, A.; Lough, A. J.; Morris, R. H.,Unsymmetrical Iron P-NH-P' Catalysts for the Asymmetric Pressure Hydrogenation ofAryl Ketones. Chem., 2017, 23 (30), 7212-7216.131. Zirakzadeh, A.; Kirchner, K.; Roller, A.; Stöger, B.; Widhalm, M.; Morris, R. H.,Iron(II) Complexes Containing Chiral Unsymmetrical PNP′ Pincer Ligands: Synthesis andApplication in Asymmetric Hydrogenations. Organometallics., 2016, 35 (21), 3781-3787.132. Zhang, F.-H.; Zhang, F.-J.; Li, M.-L.; Xie, J.-H.; Zhou, Q.-L., Enantioselectivehydrogenation of dialkyl ketones. Nat. Catal., 2020, 3 (8), 621-627.133. Wang, H.; Wen, J.; Zhang, X., Chiral tridentate ligands in transition metal-catalyzedasymmetric hydrogenation. Chem. Rev., 2021, 121 (13), 7530-7567.134. Baratta, W.; Chelucci, G.; Magnolia, S.; Siega, K.; Rigo, P., Highly productive CNNpincer ruthenium catalysts for the asymmetric reduction of alkyl aryl ketones. Chem., 2009, 15 (3), 726-32.135. Baratta, W.; Chelucci, G.; Gladiali, S.; Siega, K.; Toniutti, M.; Zanette, M.;Zangrando, E.; Rigo, P., Ruthenium(II) terdentate CNN complexes: superlative catalystsfor the hydrogen-transfer reduction of ketones by reversible insertion of a carbonyl group into the Ru-H bond. Angew. Chem. Int. Ed., 2005, 44 (38), 6214-9.136. Baratta, W.; Siega, K.; Rigo, P., Catalytic transfer hydrogenation with terdentateCNN ruthenium complexes: the influence of the base. Chem., 2007, 13 (26), 7479-86.137. Baratta, W.; Ballico, M.; Baldino, S.; Chelucci, G.; Herdtweck, E.; Siega, K.;Magnolia, S.; Rigo, P., New benzo[h]quinoline-based ligands and their pincer Ru and Oscomplexes for efficient catalytic transfer hydrogenation of carbonyl compounds. Chem.,2008, 14 (30), 9148-60.138. Baratta, W.; Baldino, S.; Calhorda, M. J.; Costa, P. J.; Esposito, G.; Herdtweck,E.; Magnolia, S.; Mealli, C.; Messaoudi, A.; Mason, S. A.; Veiros, L. F., CNN pincerruthenium catalysts for hydrogenation and transfer hydrogenation of ketones: experimental and computational studies. Chem., 2014, 20 (42), 13603-17.139. Baratta, W.; Ballico, M.; Chelucci, G.; Siega, K.; Rigo, P., Osmium(II) CNN pincercomplexes as efficient catalysts for both asymmetric transfer and H2 hydrogenation ofketones. Angew. Chem. Int. Ed., 2008, 47 (23), 4362-5.140. Clarke, Z. E.; Maragh, P. T.; Dasgupta, T. P.; Gusev, D. G.; Lough, A. J.; Abdur-Rashid, K., A family of active iridium catalysts for transfer hydrogenation of ketones.Organometallics., 2006, 25 (17), 4113-4117.141. Zirakzadeh, A.; de Aguiar, S. R. M. M.; Stöger, B.; Widhalm, M.; Kirchner, K.,Enantioselective Transfer Hydrogenation of Ketones Catalyzed by a Manganese Complex Containing an Unsymmetrical Chiral PNP′ Tridentate Ligand. ChemCatChem., 2017, 9(10), 1744-1748.142. Ito, J.-i.; Ujiie, S.; Nishiyama, H., New Bis (oxazolinyl) phenyl− Ruthenium (II)Complexes and Their Catalytic Activity for Enantioselective Hydrogenation and TransferHydrogenation of Ketones. Organometallics., 2009, 28 (2), 630-638.143. Ito, J.; Teshima, T.; Nishiyama, H., Enhancement of enantioselectivity by alcoholadditives in asymmetric hydrogenation with bis(oxazolinyl)phenyl ruthenium catalysts.Chem. Commun., 2012, 48 (8), 1105-7.144. Phillips, S. D.; Andersson, K. H. O.; Kann, N.; Kuntz, M. T.; France, M. B.;Wawrzyniak, P.; Clarke, M. L., Exploring the role of phosphorus substituents on theenantioselectivity of Ru-catalysed ketone hydrogenation using tridentate phosphinediamine ligands. Catal. Sci. Technol., 2011, 1 (8).145. Choualeb, A.; Lough, A. J.; Gusev, D. G., Hemilabile pincer-type hydride complexesof iridium. Organometallics., 2007, 26 (21), 5224-5229.146. Prokopchuk, D. E.; Smith, S. A.; Morris, R. H., Ligands for iron-based homogeneouscatalysts for the asymmetric hydrogenation of ketones and imines. Ligand Design in Metal Chemistry: Reactivity and Catalysis., 2016, 205-236.147. Wen, J.; Wang, F.; Zhang, X., Asymmetric hydrogenation catalyzed by first-rowtransition metal complexes. Chem. Soc. Rev., 2021, 50, 3211-3237.148. Wang, Y.; Wang, M.; Li, Y.; Liu, Q., Homogeneous manganese-catalyzedhydrogenation and dehydrogenation reactions. Chem., 2020, 7(5), 1180-1223.149. Agbossou-Niedercorn, F.; Michon, C., Bifunctional homogeneous catalysts based on first row transition metals in asymmetric hydrogenation. Coord. Chem. Rev., 2020, 425, 213523.150. Liu, W.; Sahoo, B.; Junge, K.; Beller, M., Cobalt complexes as an emerging class ofcatalysts for homogeneous hydrogenations. Acc. Chem. Res., 2018, 51 (8), 1858-1869.151. Hirsekorn, K. F.; Hulley, E. B.; Wolczanski, P. T.; Cundari, T. R., Olefin Substitutionin (silox) 3M (olefin)(silox= tBu3SiO; M= Nb, Ta): The Role of Density of States in Second vs Third Row Transition Metal Reactivity. J. Am. Chem. Soc., 2008, 130 (4), 1183-1196.152. Sui‐Seng, C.; Freutel, F.; Lough, A. J.; Morris, R. H., Highly efficient catalystsystems using iron complexes with a tetradentate PNNP ligand for the asymmetrichydrogenation of polar bonds. Angew. Chem. Int. Ed., 2008, 47 (5), 940-943.153. Mikhailine, A.; Lough, A. J.; Morris, R. H., Efficient asymmetric transferhydrogenation of ketones catalyzed by an iron complex containing a P−N−N−Ptetradentate ligand formed by template synthesis. J. Am. Chem. Soc., 2009, 131 (4), 1394-1395.154. Lagaditis, P. O.; Lough, A. J.; Morris, R. H., Low-valent ene–amido iron complexesfor the asymmetric transfer hydrogenation of acetophenone without base. J. Am. Chem.Soc., 2011, 133 (25), 9662-9665.155. Sues, P. E.; Lough, A. J.; Morris, R. H., Stereoelectronic factors in iron catalysis:synthesis and characterization of aryl-substituted iron (II) carbonyl P–N–N–P complexes and their use in the asymmetric transfer hydrogenation of ketones. Organometallics., 2011, 30 (16), 4418-4431.156. Mikhailine, A. A.; Maishan, M. I.; Lough, A. J.; Morris, R. H., The Mechanism ofEfficient Asymmetric Transfer Hydrogenation of Acetophenone Using an Iron (II)Complex Containing an (S, S)-Ph2PCH2CH=NCHPhCHPhN=CHCH2PPh2 Ligand: Partial Ligand Reduction Is the Key. Journal of the American Chemical Society 2012, 134 (29),12266-12280.157. Prokopchuk, D. E.; Morris, R. H., Inner-sphere activation, outer-sphere catalysis:theoretical study on the mechanism of transfer hydrogenation of ketones using iron (II)PNNP eneamido complexes. Organometallics., 2012, 31 (21), 7375-7385.158. Prokopchuk, D. E.; Sonnenberg, J. F.; Meyer, N.; Zimmer-De Iuliis, M.; Lough, A.J.; Morris, R. H., Spectroscopic and DFT Study of Ferraaziridine Complexes Formed inthe Transfer Hydrogenation of Acetophenone Catalyzed Using trans-[Fe(CO)(NCMe)(PPh2C6H4CH=NCH2−)2-κ4 P, N, N, P](BF4)2. Organometallics., 2012, 31(8), 3056-3064.159. Zuo, W.; Lough, A. J.; Li, Y. F.; Morris, R. H., Amine (imine) diphosphine ironcatalysts for asymmetric transfer hydrogenation of ketones and imines. Science., 2013, 342(6162), 1080-1083.160. Sonnenberg, J. F.; Wan, K. Y.; Sues, P. E.; Morris, R. H., Ketone AsymmetricHydrogenation Catalyzed by P-NH-P′ Pincer Iron Catalysts: An Experimental andComputational Study. ACS Catal., 2016, 7 (1), 316-326.161. Elangovan, S.; Garbe, M.; Jiao, H.; Spannenberg, A.; Junge, K.; Beller, M.,Hydrogenation of esters to alcohols catalyzed by defined manganese pincer complexes.Angew. Chem. Int. Ed., 2016, 128 (49), 15590-15594.162. Elangovan, S.; Topf, C.; Fischer, S.; Jiao, H.; Spannenberg, A.; Baumann, W.;Ludwig, R.; Junge, K.; Beller, M., Selective catalytic hydrogenations of nitriles, ketones,and aldehydes by well-defined manganese pincer complexes. J. Am. Chem. Soc., 2016, 138(28), 8809-8814.163. Widegren, M. B.; Harkness, G. J.; Slawin, A. M. Z.; Cordes, D. B.; Clarke, M. L.,A Highly Active Manganese Catalyst for Enantioselective Ketone and EsterHydrogenation. Angew. Chem. Int. Ed., 2017, 56 (21), 5825-5828.164. Passera, A.; Mezzetti, A., Mn(I) and Fe(II)/PN(H)P Catalysts for the Hydrogenationof Ketones: A Comparison by Experiment and Calculation. Adv. Synth. Catal., 2019, 361(20), 4691-4706.165. Zhang, Q.-Q.; Xie, J.-H.; Yang, X.-H.; Xie, J.-B.; Zhou, Q.-L., Iridium-CatalyzedAsymmetric Hydrogenation of alpha-Substituted alpha,beta-Unsaturated Acyclic Ketones: Enantioselective Total Synthesis of (-)-Mesembrine. Org. Lett., 2012, 14 (24), 6158-6161.166. Liu, Y. T.; Chen, J. Q.; Li, L. P.; Shao, X. Y.; Xie, J. H.; Zhou, Q. L., AsymmetricHydrogenation of Tetrasubstituted Cyclic Enones to Chiral Cycloalkanols with ThreeContiguous Stereocenters. Org. Lett., 2017, 19 (12), 3231-3234.167. Zuo, X. D.; Guo, S. M.; Yang, R.; Xie, J. H.; Zhou, Q. L., Asymmetric TotalSynthesis of Gracilamine and Determination of Its Absolute Configuration. Org. Lett.,2017, 19 (19), 5240-5243.168. Zuo, X. D.; Guo, S. M.; Yang, R.; Xie, J. H.; Zhou, Q. L., Bioinspiredenantioselective synthesis of crinine-type alkaloids via iridium-catalyzed asymmetrichydrogenation of enones. Chem. Sci., 2017, 8 (9), 6202-6206.169. Yan, P.-C.; Zhu, G.-L.; Xie, J.-H.; Zhang, X.-D.; Zhou, Q.-L.; Li, Y.-Q.; Shen,W.-H.; Che, D.-Q., Industrial Scale-Up of Enantioselective Hydrogenation for theAsymmetric Synthesis of Rivastigmine. Org. Process Res. Dev., 2013, 17 (2), 307-312.170. Qian, J.-Q.; Yan, P.-C.; Che, D.-Q.; Zhou, Q.-L.; Li, Y.-Q., A novel approach forthe synthesis of Crizotinib through the key chiral alcohol intermediate by asymmetrichydrogenation using highly active Ir-Spiro-PAP catalyst. Tetrahedron Lett., 2014, 55 (9),1528-1531.171. Yan, P. C.; Xie, J. H.; Zhang, X. D.; Chen, K.; Li, Y. Q.; Zhou, Q. L.; Che, D. Q.,Direct asymmetric hydrogenation of alpha-keto acids by using the highly efficient chiralspiro iridium catalysts. Chem. Commun., 2014, 50 (100), 15987-90.172. Yang, X.-H.; Xie, J.-H.; Zhou, Q.-L., Chiral spiro iridium catalysts with SpiroPAPligands: highly efficient for asymmetric hydrogenation of ketones and ketoesters.Org. Chem. Front., 2014, 1 (2).173. Yang, X. H.; Xie, J. H.; Liu, W. P.; Zhou, Q. L., Catalytic asymmetric hydrogenationof delta-ketoesters: highly efficient approach to chiral 1,5-diols. Angew. Chem. Int. Ed.,2013, 52 (30), 7833-6.174. Yang, X. H.; Wang, K.; Zhu, S. F.; Xie, J. H.; Zhou, Q. L., Remote ester group leadsto efficient kinetic resolution of racemic aliphatic alcohols via asymmetric hydrogenation. J. Am. Chem. Soc., 2014, 136 (50), 17426-9.175. Zhang, Y. M.; Yuan, M. L.; Liu, W. P.; Xie, J. H.; Zhou, Q. L., Iridium-CatalyzedAsymmetric Transfer Hydrogenation of Alkynyl Ketones Using Sodium Formate andEthanol as Hydrogen Sources. Org. Lett., 2018, 20 (15), 4486-4489.176. Zhu, G.-L.; Zhang, X.-D.; Yang, L.-J.; Xie, J.-H.; Che, D.-Q.; Zhou, Q.-L.; Yan,P.-C.; Li, Y.-Q., Ir/SpiroPAP Catalyzed Asymmetric Hydrogenation of a Key Intermediate of Montelukast: Process Development and Potential Impurities Study. Org. Process Res. Dev., 2015, 20 (1), 81-85.177. Hua, Y. Y.; Bin, H. Y.; Wei, T.; Cheng, H. A.; Lin, Z. P.; Fu, X. F.; Li, Y. Q.;Xie, J. H.; Yan, P. C.; Zhou, Q. L., Iridium-Catalyzed Asymmetric Hydrogenation ofgamma- and delta-Ketoacids for Enantioselective Synthesis of gamma- and delta-Lactones. Org. Lett., 2020, 22 (3), 818-822.178. Lin, H.; Xiao, L. J.; Zhou, M. J.; Yu, H. M.; Xie, J. H.; Zhou, Q. L., EnantioselectiveApproach to (-)-Hamigeran B and (-)-4-Bromohamigeran B via Catalytic AsymmetricHydrogenation of Racemic Ketone To Assemble the Chiral Core Framework. Org. Lett.,2016, 18 (6), 1434-7.179. Yang, X. H.; Yue, H. T.; Yu, N.; Li, Y. P.; Xie, J. H.; Zhou, Q. L., Iridium-catalyzedasymmetric hydrogenation of racemic alpha-substituted lactones to chiral diols. Chem. Sci., 2017, 8 (3), 1811-1814.180. Gu, X. S.; Yu, N.; Yang, X. H.; Zhu, A. T.; Xie, J. H.; Zhou, Q. L., EnantioselectiveHydrogenation of Racemic alpha-Arylamino Lactones to Chiral Amino Diols with Site-Specifically Modified Chiral Spiro Iridium Catalysts. Org. Lett., 2019, 21 (11), 4111-4115.181. Gu, G.; Yang, T.; Yu, O.; Qian, H.; Wang, J.; Wen, J.; Dang, L.; Zhang, X.,Enantioselective Iridium-Catalyzed Hydrogenation of alpha-Keto Amides to alpha-Hydroxy Amides. Org. Lett., 2017, 19 (21), 5920-5923.182. Hu, Y.; Wu, W.; Dong, X.-Q.; Zhang, X., Efficient access to chiral 1,2-aminoalcohols via Ir/f-amphox-catalyzed asymmetric hydrogenation of α-amino ketones.Org. Chem. Front., 2017, 4 (8), 1499-1502.183. Wu, W.; Xie, Y.; Li, P.; Li, X.; Liu, Y.; Dong, X.-Q.; Zhang, X., Asymmetrichydrogenation of α-hydroxy ketones with an iridium/f-amphox catalyst: efficient access to chiral 1,2-diols. Org. Chem. Front., 2017, 4 (4), 555-559.184. Wu, W.; You, C.; Yin, C.; Liu, Y.; Dong, X. Q.; Zhang, X., Enantioselective andDiastereoselective Construction of Chiral Amino Alcohols by Iridium-f-Amphox-Catalyzed Asymmetric Hydrogenation via Dynamic Kinetic Resolution. Org. Lett., 2017,19 (10), 2548-2551.185. Hu, Y.; Yin, X.; Chen, Z.; Dong, X.-Q.; Zhang, X., Highly enantioselective Ir/famphox-catalyzed hydrogenation of ketoamides: efficient access to chiral hydroxy amides.Org. Chem. Front., 2018, 5 (12), 2000-2003.186. Qin, C.; Chen, X.-S.; Hou, C.-J.; Liu, H.; Liu, Y.-J.; Huang, D.-Z.; Hu, X.-P.,Iridium-catalyzed asymmetric hydrogenation of β-keto esters with f-amphox ligands. Synth. Commun., 2018, 48 (6), 672-676.187. Yin, C.; Dong, X.-Q.; Zhang, X., Iridium/f-Amphol-catalyzed Efficient AsymmetricHydrogenation of Benzo-fused Cyclic Ketones. Advanced Synthesis & Catalysis 2018, 360(22), 4319-4324.188. Yin, C.; Wu, W.; Hu, Y.; Tan, X.; You, C.; Liu, Y.; Chen, Z.; Dong, X.-Q.; Zhang,X., Iridium-Catalyzed Asymmetric Hydrogenation of Halogenated Ketones for theEfficient Construction of Chiral Halohydrins. Adv. Synth. Catal., 2018, 360 (11), 2119-2124.189. Zhang, X.; Wen, J.; Wang, S.; Yu, Y., Iridium/f-Amphox-Catalyzed AsymmetricHydrogenation of Styrylglyoxylamides. Synlett 2018, 29 (16), 2203-2207.190. Wang, J.; Shao, P. L.; Lin, X.; Ma, B.; Wen, J.; Zhang, X., Facile Synthesis ofEnantiopure Sugar Alcohols: Asymmetric Hydrogenation and Dynamic Kinetic ResolutionCombined. Angew. Chem. Int. Ed., 2020, 59 (41), 18166-18171.191. Gong, Q.; Wen, J.; Zhang, X., Desymmetrization of cyclic 1,3-diketones via Ircatalyzed hydrogenation: an efficient approach to cyclic hydroxy ketones with a chiralquaternary carbon. Chem. Sci., 2019, 10 (25), 6350-6353.