New Methods for Catalytic Asymmetric Synthesis of Valuable Chemicals

本项目致力于鉴定新的催化剂和催化方法，通过激活碳-碳pi键来制备有价值的富含对映体的无环和杂环分子，以备外部杂原子亲核剂的攻击。定义了手性环钴恶唑啉(COP)配合物催化的富对映体支链烯丙基胺、酯和醚的不对称合成的范围。将定义使用这种化学来构建环状分子，例如内酯、环醚和氮杂环。将对CoP催化合成对映体富烯丙基酯和苯酚进行机理研究，以便于发现改进的催化剂，并允许合理设计以类似途径进行的新反应。拟议调查的一个重要目标是寻找更简单、更便宜的催化剂。不对称Pd(II)及其相关催化剂用于通过级联成环过程立体控制杂环的构建也将被探索。为了提高选择性和安全性，引入临床实践的新药物是越来越复杂的手性分子，作为单一对映体上市。通过这个奖项，有机和高分子化学项目支持了加州大学欧文分校化学系的拉里·E·奥弗曼博士的研究。奥弗曼教授和他的学生正在研究使用含有钯的化合物来实现手性有机分子的选择性合成。拟议的研究计划有望为制药业提供合成和发现单一对映体药物的新工具。

This project addresses the identification of new catalysts and catalytic methods for preparing valuable enantioenriched acyclic and heterocyclic molecules through the activation of carbon-carbon pi bonds for attack by external heteroatom nucleophiles. The scope of the asymmetric synthesis of enantioenriched branched allylic amines, esters and ethers catalyzed by palladacyclic cobalt oxazoline (COP) complexes will be defined. The use of this chemistry for constructing cyclic molecules such as lactones and cyclic ethers and nitrogen heterocycles will be defined. Mechanistic investigations of the COP-catalyzed synthesis of enantioenriched allylic esters and phenols will be undertaken in order to facilitate discovery of improved catalysts and allow the rational design of new reactions that proceed by similar pathways. An important objective of the proposed investigations is to identify simpler, less expensive catalysts. The use of asymmetric Pd(II) and related catalysts for stereocontrolled construction of heterocycles by cascade ring-forming processes will also be explored.To increase selectivity and safety, new pharmaceuticals introduced into clinical practice are increasingly complex chiral molecules marketed as single enantiomers. With this award, the Organic and Macromolecular Chemistry Program is supporting the research of Dr. Larry E. Overman, of the Department of Chemistry at the University of California at Irvine. Professor Overman and his students are studying the use of compounds containing palladium to effect the selective synthesis of chiral organic molecules. The proposed program of research is expected to provide the pharmaceutical industry with new tools for the synthesis and discovery of single enantiomer drugs.