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 of structural complexity and diversity from readily avaialbe feedstocks is highly important for morden organic synthesis, chemical biology and drug discovery. Here we present a unique substitution-hemiketalization cyclization of the 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, meanwhile accomadating a broad scope of Grignard reagents. The electrophilic capture of organomagnesium intermediates generated in the reaction enables the one-pot access to bridged polycyclic benzoxocin-2-ols with enhanced complexity and diversity. Collectively, this work showcases a conceptional strategy that can efficiently generate structurally rich and complex bridged ring skeletons essentially from phenolic feedstocks.