Palladium-Catalyzed Carbonylative Synthesis of Acrylamides from Alkenyl Thianthrenium Salts

Abstract

Covalent drugs have emerged as powerful tools in modern therapeutics, with acrylamide being one of the most widely used electrophilic warheads in recent years. Herein, we report a practical and selective strategy for synthesizing acrylamides via Pd-catalyzed carbonylative amidation of vinyl thianthrenium salts with arylamines. These salts serve as stable and safe surrogates for alkynes or activated alkenes. The reaction proceeds under mild conditions using only 0.1 mol% Pd catalyst and 1 atm of CO, delivering a broad range of N-aryl acrylamides in high yields (>90%) with excellent chemoselectivity and functional group tolerance. Furthermore, the method is readily scalable to the gram level without compromising efficiency.This work demonstrates the synthetic potential of vinyl thianthrenium salts in carbonylation chemistry and offers a general, robust, and scalable approach for the preparation of functionalized acrylamides under mild conditions.