Friedel-Crafts Benzylation of Activated and Deactivated Arenes

摘要

The Friedel-Crafts alkylation of aromatic compounds is a versatile method for C—C bond formation from unactivated C—H bonds. Despite the power and historical importance of Friedel-Crafts reactions, the poor reactivity of deactivated aromatic compounds, the difficultly of employing even modestly deactivated alkyl halides, and complications from the aluminum by-products have encouraged the development of new aromatic transformations. In the current era, new reactions for regio- and chemoselective direct functionaliza-tion of arenes through C—H bond activation, largely based on transition metal catalysis, have revolutionized the preparation of aromatic derivatives. Despite these advances, there remains an unmet synthetic need for refinements to the more economical Friedel-Crafts reaction to improve its substrate scope, operational simplicity, and sustainability, particularly for substitutions of electron-deficient substrates. Herein we document a new approach to Friedel-Crafts benzylations that operates with both electron-deficient electrophiles and nucle-ophiles, proceeds under mild, simple conditions, and does not require the use of aluminum or other metal reagents or catalysts (Scheme 1). Importantly, this method allows for the selective mono-meta-functionalization of electron-deficient nucleophiles with electron-poor electrophiles.