Catalytic Asymmetric Hydrogenation

描述（由申请人提供）：本提案的目标是：1)开发新的过渡金属还原催化剂，用于实际合成手性醇、胺、酸、氨基醇、二醇、α和β -氨基酸；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，用于酮类、烯烃、亚胺和芳香化合物的不对称氢化。在Ru、Rh和ir催化的不对称氢化反应中，制备了许多优秀的配体体系，如PennPhos、BICP、Ambox、DIOP*、TunePhos、KetalPhos、f-KetalPhos、Binaphane和f-Binaphine。最近，P.l的小组发现了使用新的电子给体（TangPhos和Binapine）的高活性和对映选择性反应。在脂肪族酮类、胺类、不饱和酸类和亚胺类的不对称氢化反应方面取得了许多基准结果。对某些底物的氢化已观察到高活性（高达50,000次翻转）和对映体选择性（高达99% ee）。

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.