Catalytic Asymmetric Hydrogenation

催化不对称加氢

• 批准号: 6822980
• 负责人: Xumu Zhang
• 金额: $ 26.88万
• 依托单位: PENNSYLVANIA STATE UNIVERSITY, THE
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-08-01 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6822980
• 关键词: alcohols; alkenes; aminoacid; catalyst; chemical synthesis; conformation; cyclic compound; cyclization; diol; drug design /synthesis /production; heavy metals; heterocyclic compounds; imines; ketones; metal complex; oxidation reduction reaction; protonation; stereochemistry

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.

描述（由申请人提供）：该提案的目标是：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.开发了用于酮、烯烃、亚胺和芳香族化合物不对称氢化的手性配体工具箱。已经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，用于 Ru、Rh 和 Ir 催化的不对称氢化。最近，P.l 的研究小组发现了使用新的给电子配体（TangPhos 和 Binapine）的高活性和对映选择性反应。 P.I. 已取得许多基准测试结果。脂肪酮、烯酰胺、不饱和酸和亚胺的不对称氢化领域。某些底物的氢化反应具有高活性（高达 50,000 次转换）和对映选择性（高达 99% ee）。 P.l.研究的具体目标涉及以下转变：1）开发用于还原简单酮和功能化酮的新型催化剂，2）探索烯烃的不对称氢化，3）研究亚胺的不对称氢化和酮的直接还原胺化，4）研究芳香族和杂芳香族化合物的不对称还原，5）继续研究 开发新的手性配体。这些方法的发展对人类健康有直接影响。 P. I 提出了重要药物化合物的实际合成。例子包括立普妥、依那普利、司曲林、帕罗西汀、右吗啡烷和普瑞巴林的合成。