仿生启发下基于β-酮酸催化脱羧反应在有机合成中的应用拓展与深入

项目名称： 仿生启发下基于β-酮酸催化脱羧反应在有机合成中的应用拓展与深入

项目编号： No.21472137

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 数理科学和化学

项目作者： 聂晶

作者单位： 天津大学

项目金额： 85万元

中文摘要： 通过β-酮酸的催化脱羧实现对酮α-位高选择性官能团化，是一条简便有效的绿色合成途径，然而该反应在有机合成中的应用却十分有限。在生物合成聚酮的启发下，本项目拟采用价廉易得的β-酮酸为原料，系统研究其与多种亲电试剂的脱羧加成及取代反应，探索温和条件下构建碳-碳及碳-杂键的新策略。在此基础上，发展高效、高立体选择性基于β-酮酸脱羧的催化不对称反应，为合成多种天然产物及药物分子中间体提供有效的方法。具体研究内容包括：（1）催化脱羧插入及不对称反应（2）催化脱羧氟化/三氟甲基化及不对称反应（3）催化不对称脱羧烷基化反应、烯丙基化反应及炔丙基化反应（4）催化不对称脱羧氨化反应（5）催化不对称脱羧Michael加成反应（6）催化不对称脱羧Aldol反应（7）催化不对称脱羧Mannich反应（8）对机理的深入探讨。总之，本项目旨在拓展β-酮酸脱羧反应在有机合成中的应用，为此类反应提供科学的实验及理论依据

中文关键词： 有机合成化学；催化；不对称合成；脱羧反应；仿生

英文摘要： Catalytic decarboxylative reaction of β-ketoacids represents one of the most direct and efficient method to achieve the chemoselective α-functionalization of ketones. However, the synthetic utility of this reaction has rarely been explored. Inspired by the approach of biosynthesis of polyketides, a number of catalytic decarboxylative addition/substitution reactions of β-ketoacids with various electrophiles will be performed to construct C-C and C-X bonds in mild conditions. Furthermore, the corresponding asymmetric decarboxylative transformations will also be developed. This project includes: (1) catalytic decarboxylative insertion reactions and asymmetric reactions (2) catalytic decarboxylative fluorination and trifluoromethylation reactions and asymmetric reactions (3) catalytic asymmetric decarboxylative alkylation, allylic alkylation and propargylic substitution reactions (4) catalytic asymmetric decarboxylative amination reactions (5) catalytic asymmetric decarboxylative Michael addition reactions (6) catalytic asymmetric decarboxylative Aldol reactions (7) catalytic asymmetric decarboxylative Mannich reactions. Additionally, a detailed investigation of the reaction mechanism will be performed. In a word, this item is aimed at expanding the utility of decarboxylative reaction of β-ketoacids in organic synthesis, and providing new tools and ideas for the further development of this reaction.

英文关键词： organic synthesis;catalysis;asymmetric synthesis;decarboxylative reaction;biomimetic