The goals of this proposal are: 1) to develop novel transition metal reduction catalysts for the practical synthesis of chiral alcohols, amines, acids, amino alcohols, diols, alpha and beta-amino acids; 2) to understand the fundamental factors controlling enantioselectivity. This project involves various approaches to ligand design, new protocols for catalytic asymmetric reactions and mechanistic understanding. The P.I. has developed a chiral ligand toolbox for asymmetric hydrogenation of ketones, alkenes, imines and aromatic compounds. A number of excellent ligands systems such as PennPhos, BICP, Ambox, DIOP*, TunePhos, KetalPhos, f-KetalPhos, Binaphane and f-Binaphine have been prepared for Ru, Rh and Ir-catalyzed asymmetric hydrogenation. Recently, the P.l's group has discovered highly active and enantioselective reactions using new electron-donating ligands (TangPhos and Binapine). Many benchmark results have been achieved by the P.I. in area of asymmetric hydrogenation of aliphatic ketones, enamides, unsaturated acids and imines. High activity (up to 50,000 turnovers) and enantioselectivity (up to 99% ee) have been observed for hydrogenation of some substrates.
The specific aims of the P.l.'s research involve following transformations: 1) to develop new catalysts for reduction of simple ketones and functionalized ketones, 2) to explore asymmetric hydrogenation of alkenes, 3) to investigate asymmetric hydrogenation of imines and direct reductive amination of ketones, 4) to study asymmetric reduction of aromatic and hetereoaromatic compounds, and 5) to continue the research of developing new chiral ligands. Development of these methods have a direct impact to human health. Practical synthesis of important pharmaceutical compounds are proposed by P. I. Examples include synthesis of lipitor, enalapril, setraline, paxil, dextromorphans and pregabalin.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
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Medicinal Chemistry Study Section (MCHA)
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Schwab, John M
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Pennsylvania State University
Schools of Arts and Sciences
University Park
United States
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Li, Shengkun; Huang, Kexuan; Zhang, Xumu (2014) Enantioselective hydrogenation of ?,?-disubstituted nitroalkenes. Chem Commun (Camb) 50:8878-81
Chang, Mingxin; Huang, Yuhua; Liu, Shaodong et al. (2014) Asymmetric hydrogenation of pyridinium salts with an iridium phosphole catalyst. Angew Chem Int Ed Engl 53:12761-4
Li, Shengkun; Huang, Kexuan; Zhang, Jiwen et al. (2013) Rhodium-catalyzed highly regioselective hydroaminomethylation of styrenes with tetraphosphorus ligands. Org Lett 15:3078-81
Liu, Tang-Lin; Li, Wei; Geng, Huiling et al. (2013) Catalytic enantioselective desymmetrization of meso cyclic anhydrides via iridium-catalyzed hydrogenation. Org Lett 15:1740-3
Li, Shengkun; Huang, Kexuan; Zhang, Jiwen et al. (2013) Rh-catalyzed highly enantioselective hydrogenation of nitroalkenes under basic conditions. Chemistry 19:10840-4
Huang, Kexuan; Li, Shengkun; Chang, Mingxin et al. (2013) Rhodium-catalyzed enantioselective hydrogenation of oxime acetates. Org Lett 15:484-7
Li, Shengkun; Huang, Kexuan; Zhang, Jiwen et al. (2013) Cascade synthesis of fenpiprane and related pharmaceuticals via rhodium-catalyzed hydroaminomethylation. Org Lett 15:1036-9
Li, Shengkun; Huang, Kexuan; Cao, Bonan et al. (2012) Highly enantioselective hydrogenation of ýý,ýý-disubstituted nitroalkenes. Angew Chem Int Ed Engl 51:8573-6
Chang, Mingxin; Li, Wei; Zhang, Xumu (2011) A highly efficient and enantioselective access to tetrahydroisoquinoline alkaloids: asymmetric hydrogenation with an iridium catalyst. Angew Chem Int Ed Engl 50:10679-81
Geng, Huiling; Huang, Kexuan; Sun, Tian et al. (2011) Enantioselective synthesis of optically pure ýý-amino ketones and ýý-aryl amines by Rh-catalyzed asymmetric hydrogenation. J Org Chem 76:332-4

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