Catalytic Asymmetric Synthesis of Inherently Chiral Eight‐Membered O‐Heterocycles through Cross‐[4+4] Cycloaddition of Quinone Methides

作者：Da Xu, Guojie Zhou, Bangli Liu, Shiqi Jia, Yidong Liu, Yidong Liu, Hailong Yan · 发表于：Angewandte Chemie International Edition · 年份：2024 · DOI：10.1002/anie.202416873 · 被引用次数：20 · 研究领域：Synthesis of Indole Derivatives、Bioactive Compounds and Antitumor Agents

Inherently chiral eight-membered rings embedded in tetraphenylene derivatives and hetero-analogues exhibit unique properties and allow diverse applications. A conceptually viable and straightforward approach to these frameworks is [4+4] cycloaddition, which still remains elusive. Herein, we describe the stereoselective cross-[4+4] cycloaddition of quinone methides (QMs), leading to the formation of oxa-analogues of tetraphenylene with exceptional chemo-, diastereo-, and enantioselectivity. The structures of these novel rigid eight-membered O-heterocycles were explored by single-crystal X-ray diffraction, and their stereochemical stability was elaborated through both density functional theory (DFT) calculations and thermal racemization experiments. The developed methodology exhibited broad substrate scope and the resulting cross-[4+4] cycloadducts could be readily transformed into valuable chiral building blocks. Our findings expand the library of inherently chiral medium-sized rings and also contribute to the advancement of asymmetric cross-[4+4] cycloadditions of quinone methides.