利用有機催化串聯反應同時建構出五個四級碳立體中心

Abstract

本篇是以本實驗室開發的四取代烯烴作為親電試劑，以不同結構和反應特性的親核試劑利用金雞納鹼的衍生物作為催化劑，進行有機催化串聯反應建構出含有五個四級碳立體中心的產物。

第一部分為利用 1,3-茚二酮衍生物 119 和 3-亞烷基羥吲哚衍生物 120 使用接有硫脲片段的奎寧催化劑，在溫和的反應條件下，可進行 Vinylogous Michael addition / Acetalization / oxa-Michael addition / Michael addition 的不對稱串聯反應，產率最好可達 91%，鏡像超越值有 80%，產物結構具有六個立體中心，其中的五個為四級碳結構。

第二部分為利用鄰羥基芳醛亞胺衍生物 135 和 1,3-茚二酮衍生物 119 使用接有方醯胺基片段的奎尼丁催化劑作用下，可先進行一個 [3+2] 環加成後再進行 Double acetalization / Lactonization 的串聯反應，可以得到單一非鏡像異構物且產率可達 99%，而鏡像超越值也達 99%，和第一部分的結構一樣具有六個立體中心，其中五個為四級碳結構。

The tetra-substituted olefins were developed by our laboratory as electrophile, reacted with different nucleophiles and cinchona alkaloid derivatives as a catalyst for organocatalytic cascade reactions to establish six stereogenic centers including five quaternary stereocenters.

Part I：A sequential vinylogous Michael / acetalization / oxa-Michael / Michael cascade is presented for the synthesis of product 121 employing 3-alkylidene oxindole pronucleophile 120 and 1,3-indnadionederived electrophile 119. The cacade product 121 was obtained in excellent yield and good entantioselectivity (up to 91%, yield, up to 80% ee).

Part II：A sequential [3+2] cycloaddition then double acetalization and lactonization resulting in the cascade product 158, bearing six including five quaternary stereocenters was obtained as a single diasteromer in good yields and enantioselectivities.