Catalytic Asymmetric Synthesis of Inherently Chiral Eight‐Membered O‐Heterocycles through Cross‐[4+4] Cycloaddition 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. In this study, 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 via 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 expanded the inherently chiral library of medium‐sized rings and also contributed to the advancement of asymmetric cross‐[4+4] cycloadditions of quinone methides.