The formation of amide bonds represents one of the most fundamental processes in organic synthesis. Transition-metal-catalyzed activation of acyclic twisted amides has emerged as an increasingly powerful platform in synthesis. Herein, we report the transamidation of N-activated twisted amides by selective N-C(O) cleavage mediated by air- and moisture-stable half-sandwich Ni(II)-NHC (NHC = N-heterocyclic carbenes) complexes. We demonstrate that the readily available cyclopentadienyl complex, [CpNi(IPr)Cl] (IPr = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene), promotes highly selective transamidation of the N-C(O) bond in twisted N-Boc amides with non-nucleophilic anilines. The reaction provides access to secondary anilides via the non-conventional amide bond-forming pathway. Furthermore, the amidation of activated phenolic and unactivated methyl esters mediated by [CpNi(IPr)Cl] is reported. This study sets the stage for the broad utilization of well-defined, air- and moisture-stable Ni(II)-NHC complexes in catalytic amide bond-forming protocols by unconventional C(acyl)-N and C(acyl)-O bond cleavage reactions.
Keywords: Buchwald–Hartwig; N-heterocyclic carbenes; NHCs; N–C activation; [CpNi(NHC)X]; amidation; amide bonds; cyclopentadienyl; nickel; nickel–NHCs; transamidation; twisted amides.