複素環系不斉補助剤を基盤とした精密な不斉制御空間の構築と不斉触媒反応への展開

基于杂环不对称助剂的精确不对称控制空间的构建及其在不对称催化反应中的应用

基本信息

批准号：
10470471
负责人：
KUNIEDA Takehisa
金额：
$ 7.42万
依托单位：
Kumamoto University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B).
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 2000
项目状态：
已结题

项目摘要

The aim of this research is to establish the methodology for i) simple preparation of tricyclic 2-oxazolidinones and 2-imidazolidinones with conformational rigidity and steric congestion as extremely powerful chiral auxiliaries by catalytic resolution, and ii) excellent asymmetric reactions with bicyclic 2-amino alcohols and 1,2-diamines derived from the above tricyclic compounds.1. Easy access to highly efficient chiral auxiliaries by kinetic resolution :The optically active "roofed" 2-oxazolidinones and 2-imidazolidinones were readily obtained from kinetic resolution with oxazaborolidine catalysts, which is an alternative method for optical resolution with "MAC-acid" (2-exo-methoxy-1-apocamphanecarboxylic acid).2. Development of highly efficient chiral auxiliaries :Diastereoselectivity which is induced by the use of 2-imidazolidinone auxiliaries is greatly dependent on the N-substituents of the heterocycles, among which the bulky arenesulfonyl group is the moiety of choice. Reactions of this type afford an excellent level of diastereoselection in the methylation of N'-butyryl-2-imidazolidinones via the metal enolates.3. Development of highly efficient chiral amino alcohols :(1) chiral ligands : The chiral cis-2-aminoalcohols derived from ring-opening of the above tricyclic 2-oxazolidinones played a promising role in performing the high level of catalytic chiral discrimination (asymmetrization of meso-1,3-diacetyl-2-imidazolidinones).(2) chiral reactants : The alkoxide of the sterically congested 2-aminoalcohols served well as chiral discriminating agents for highly efficient dissymmetrization of meso-1,3-diacetyl-2-imidazolidinones.(3) C_2-symmetrical bis (oxazoline) ligands : The use of sterically congested C_2-symmetrical bis (oxazoline) ligands derived from the above amino alcohols provided the unexpected enantioselection for aldol reactions catalyzed by the Cu (II) complexes, which was an important findings for a design of new chiral synthetic processes.

本研究的目的是建立以下方法：i) 通过催化拆分简单制备具有构象刚性和空间拥挤性的三环 2-恶唑烷酮和 2-咪唑烷酮作为极其强大的手性助剂，以及 ii) 与双环 2-氨基发生优异的不对称反应由上述三环化合物衍生的醇和1,2-二胺。1．通过动力学拆分轻松获得高效手性助剂：光学活性“屋顶”2-恶唑烷酮和 2-咪唑烷酮很容易通过恶唑硼烷催化剂的动力学拆分获得，这是使用“MAC-酸”进行光学拆分的替代方法（2 -外型-甲氧基-1-阿莰甲酸).2．高效手性助剂的开发：使用2-咪唑啉酮助剂引起的非对映选择性很大程度上取决于杂环的N-取代基，其中大的芳烃磺酰基是选择的部分。这种类型的反应在N'-丁酰-2-咪唑啉酮通过金属烯醇化物的甲基化中提供了极好的非对映选择水平。3．高效手性氨基醇的开发：（1）手性配体：由上述三环2-恶唑烷酮开环衍生的手性顺-2-氨基醇在高水平催化手性辨别（内消旋不对称化）方面发挥了良好的作用。 -1,3-二乙酰基-2-咪唑啉酮).(2) 手性反应物 : 空间拥挤的醇盐2-氨基醇可以很好地用作内消旋-1,3-二乙酰基-2-咪唑啉酮的高效不对称化的手性辨别剂。(3) C_2-对称双(恶唑啉)配体：空间拥挤的C_2-对称双(恶唑啉)的使用衍生自上述氨基醇的配体为 Cu 催化的羟醛反应提供了意想不到的对映选择（II）配合物，这是设计新的手性合成过程的重要发现。