Combined Experimental and Computational Mechanistic Investigation of the Palladium-Catalyzed Decarboxylative Cross-Coupling of Sodium Benzoates with Chloroarenes

Reported herein is a mechanistic investigation into the palladium-catalyzed decarboxylative cross-coupling of sodium benzoates and chloroarenes. The reaction was found to be first-order in Pd. A minimal substituent effect was observed with respect to chloroarene, and the reaction was zero-order with respect to chloroarene. Palladium-mediated decarboxylation was assigned as the turnover-limiting step based on an Eyring plot and density functional theory computations. Catalyst performance was found to vary based on the electrophile, which is best explained by catalyst decomposition at Pd(0). The 1,5-cyclooctadiene (COD) ligand contained in the precatalyst CODPd(CH2TMS)2 (Pd1) was shown to be a beneficial additive. The bench-stable Buchwald complex XPhosPdG2 could be used with exogenous COD and 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (XPhos) instead of complex Pd1. Adding exogenous XPhos significantly increased the catalyst turnover number and enhanced reproducibility.