Organocatalyzed double dearomatization reaction of non-functionalized phenols and propargylic alcohols: the important regulating effect of steric hindrance

Abstract

While Friedel–Crafts (F–C) reaction has been widely used for the preparation of functionalized benzylic compounds, the interrupted F–C reaction that allows for the synthesis of stable dearomatized cyclic systems has rarely been reported. We demonstrate herein that the introduction of an appropriate steric hindrance group around the reactive site of the arene could enable an interrupted F–C reaction by retarding the rearomatization process of the corresponding dearomatized intermediate. Utilizing such a concept, an organocatalyzed dearomative 1,8-addition and formal dearomative Diels–Alder cascade between polycyclic phenols and propargylic alcohols was realized to give efficient access to a series of structurally and stereochemically complex polycyclic diketones. This double dearomatization reaction features a broad substrate scope, exclusive diastereoselectivity, operational simplicity and mild reaction conditions. The preference of the current protocol to undergo a double dearomatization reaction instead of a [3 + 3] cycloaddition was rationalized by DFT calculations.