Catalytic Asymmetric Hydrogenation

描述(申请人提供)：本建议的目标是：1)开发新型过渡金属还原催化剂，用于手性醇、胺、酸、氨基醇、二醇、α和β-氨基酸的实际合成；2)了解控制对映体选择性的基本因素。该项目涉及配体设计的各种方法、催化不对称反应的新方案和机理理解。P.I.开发了一个手性配体工具箱，用于酮、烯烃、亚胺和芳香族化合物的不对称氢化。PennPhos、BICPs、Ambox、Diop*、TunePhos、KetalPhos、f-KetalPhos、Binaphane和f-Binaffine等许多优良的配体体系已被合成用于Ru、Rh和Ir催化的不对称氢化反应。最近，P.L的团队发现了使用新的电子供体配体(TangPhos和Binapine)进行的高活性和不对称反应。P.I.在脂肪酮、烯胺、不饱和酸和亚胺的不对称氢化领域取得了许多基准结果。对于某些底物的氢化，观察到了高活性(高达50,000转化率)和对映体选择性(高达99%ee)。 S研究的具体目标包括：1)开发单酮和功能酮还原的新型催化剂，2)探索烯烃的不对称氢化，3)亚胺的不对称氢化和酮的直接还原胺化，4)芳香族和杂芳族化合物的不对称还原，5)继续开发新的手性配体。这些方法的发展对人类健康有直接的影响。他们提出了重要药物的实用合成方法，如立普妥、依那普利、司特拉林、帕罗西汀、右旋吗啡和普瑞他林的合成。

DESCRIPTION (provided by applicant): 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.