Connecting remote C-H bond functionalization and decarboxylative coupling using simple amines.

A catalytic para-selective alkylation reaction connects C-H functionalization and decarboxylative coupling strategies using simple bases to trap a previously hidden intermediate. This reaction exploits an 'inverted sequence' that forms the C-C bond prior to C-H bond cleavage and provides a new entry into C-H functionalization reactions. Transition metal-catalysed C-H functionalization and decarboxylative coupling are two of the most notable synthetic strategies developed in the past 30 years. Here, we connect these two reaction pathways using bases and a simple Pd-based catalyst system to promote a para-selective C-H functionalization reaction from benzylic electrophiles. Experimental and computational mechanistic studies suggest a pathway that involves an uncommon Pd-catalysed dearomatization of the benzyl moiety followed by a base-enabled rearomatization through a formal 1,5-hydrogen migration. This reaction complements 'C-H activation' strategies that convert inert C-H bonds into C-metal bonds prior to C-C bond formation. Instead, this reaction exploits an inverted sequence and promotes C-C bond formation prior to deprotonation. These studies provide an opportunity to develop general para-selective C-H functionalization reactions from benzylic electrophiles and show how new reactive modalities may be accessed with careful control of the reaction conditions.