New Methods for Catalytic Asymmetric Synthesis of Valuable Chemicals

本项目旨在通过激活碳-碳pi键，制备有价值的对映体富集的无环和杂环分子，以供外部杂原子亲核试剂攻击。定义了钯环钴恶唑啉（COP）配合物催化的不对称富集对映体支链烯丙胺、酯和醚的合成范围。将定义利用这种化学构造环状分子，如内酯、环醚和氮杂环。将进行cop催化合成对映体富集的烯丙基酯和酚的机理研究，以促进发现改进的催化剂，并允许合理设计通过类似途径进行的新反应。提出的研究的一个重要目标是确定更简单、更便宜的催化剂。利用不对称Pd（II）和相关催化剂，通过级联成环工艺进行立体控制构建杂环也将被探索。为了提高选择性和安全性，引入临床实践的新药越来越多地以单对映体形式销售的复杂手性分子。通过这个奖项，有机和大分子化学项目支持加州大学欧文分校化学系的Larry E. Overman博士的研究。Overman教授和他的学生正在研究使用含有钯的化合物来影响手性有机分子的选择性合成。该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.