Pd-Catalyzed Decarbonylative Suzuki–Miyaura Cross-Coupling of Pyramidalized N-Mesyl Amides by a Tandem N–C(O)/C–C Bond Activation

Abstract

The Suzuki–Miyaura biaryl cross-coupling is the pivotal technology for carbon–carbon coupling in pharmaceutical, polymer, and agrochemical fields. A long-standing challenge has been the development of efficient precursors for the decarbonylative cross-coupling of amide bonds. Herein, we report a highly chemoselective palladium-catalyzed Suzuki–Miyaura cross-coupling of N-mesyl amides for the synthesis of biaryls by a tandem N–C(O)/C–C bond activation with high selectivity for decarbonylative cleavage. The results demonstrate the first example of a decarbonylative coupling (−CO) of amide bonds activated by an atom-economic, low-cost, and benign N-pyramidalized mesyl group (>30 examples). The reaction shows high generality and functional group tolerance and can be applied in late-stage functionalization of pharmaceuticals. Notably, N-mesyl amides are significantly more reactive than other classes of amides in the decarbonylative Suzuki cross-coupling manifold. Density functional theory (DFT) studies demonstrate considerably lower barrier for rate-limiting transmetalation using N-mesyl amides. The study establishes N-mesyl amides as versatile precursors for Suzuki–Miyaura cross-coupling to afford valuable biaryls and opens the door to deploy N-mesyl amides in challenging cross-couplings of amides by decarbonylation.