Bioinspired Total Synthesis of (±)-Chaetophenol C Enabled by a Pd-Catalyzed Cascade Cyclization

A novel
Pd­(II)-catalyzed cascade reaction has been developed that
consists of a highly regio- and stereoselective oxa [4 + 2] cycloaddition
reaction of o-alkynylbenzaldehydes and an intramolecular
carboxylic group quenching of the in situ generated oxonium ion. This
new reaction provides a one-step construction of the tetracyclic core
structure of chaetophenol C from two simple starting materials. The
developed chemistry was successfully applied to the first total synthesis
of chaetophenol C and dozens of its analogues.

本研究开发了一种新型钯(II)（Pd(II)）催化级联反应，该反应由邻炔基苯甲醛的高区域及立体选择性氧杂[4+2]环加成过程，与原位生成氧鎓离子的分子内羧酸基团淬灭步骤共同构成。该新颖反应可通过两种简单起始原料一步构建壳孢酚C（chaetophenol C）的四环核心结构。所开发的合成方法已成功应用于壳孢酚C及其数十种类似物的首次全合成。