Bridged rings from phenolic feedstocks: regio- and diastereoselective substitution-hemiketalization cyclization of bridged benzoxocin-4-ones with Grignard reagents†‡

Abstract

The efficient and controllable generation of bridged polycycles with structural complexity and diversity from readily available feedstocks is highly important for modern organic synthesis, chemical biology and drug discovery. Here, we present a unique substitution-hemiketalization cyclization of readily available bridged benzoxocin-4-ones with Grignard reagents, which leads to a facile synthesis of a diverse portfolio of bridged benzoxocin-2-ol frameworks. The reaction features high regioselectivity and diastereoselectivity, while accommodating a broad scope of Grignard reagents. The electrophilic capture of organomagnesium intermediates generated in the reaction enables one-pot access to bridged polycyclic benzoxocin-2-ols with enhanced complexity and diversity. Collectively, this work showcases a conceptual strategy that can efficiently generate structurally rich and complex bridged ring skeletons essentially from phenolic feedstocks.