A Systematic Study of Functionalized Oxiranes as Initiating Groups for Cationic Polycyclization Reactions

Three different methods have been developed that effectively utilize chiral oxiranes derived from Katsuki–Sharpless epoxidation of allylic alcohols as initiating groups for cationic cyclization of unsaturated substrates to form chiral polycycles. This type of transformation has previously been problematic. These employ either epoxy-methoximes, vinyl-substituted oxiranes, or hydroxymethyl oxiranes. All three approaches are described in detail. In addition, this research has led to possible explanations for previously encountered difficulties in this area and provided two new insights into the Lewis acid activation of oxiranes. The methodology described herein constitutes a valuable link between two powerful synthetic constructions, enantioselective Katsuki–Sharpless epoxidation and cationic polycyclization reactions.

已开发出三种不同方法，可有效利用由烯丙醇经香月-夏普莱斯（Katsuki–Sharpless）环氧化反应制备得到的手性环氧乙烷（chiral oxiranes）作为引发基团，用于不饱和底物的阳离子环化反应，以构建手性多环化合物。此前该类转化反应长期存在技术难题。这三种策略分别采用环氧甲氧肟类（epoxy-methoximes）、乙烯基取代环氧乙烷（vinyl-substituted oxiranes）以及羟甲基环氧乙烷（hydroxymethyl oxiranes）作为引发基团，本文将对这三种方法进行详细阐述。此外，本研究还为该领域此前遇到的相关难题提供了合理解释，并针对环氧乙烷的路易斯酸（Lewis acid）活化机制提出了两项全新的研究见解。本文所报道的合成方法，搭建了对映选择性香月-夏普莱斯环氧化反应与阳离子多环化反应这两种高效合成策略之间的宝贵桥梁。