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

• Published in: Angewandte Chemie International Edition 2025-01, Vol.64 (4), p.e202416873
• Main Authors: Xu, Da, Zhou, Guojie, Liu, Bangli, Jia, Shiqi, Liu, Yidong, Yan, Hailong
• Format: Article
• Language: English
• ISSN: 1521-3773; 1521-3773
• DOI: 10.1002/anie.202416873

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.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.