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

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