Activation of isocyanates with gold: towards Au-catalyzed C–H amidation of pyrroles

Abstract

The intermolecular hydroarylation of isocyanates with pyrroles was found to be efficiently catalyzed by the Au(I) complex IPrAuNTf₂ (IPr = N,N′-bis(2,6-diisopropylphenyl)-imidazol-2-ylidene). The transformation tolerates electron-withdrawing and electron-donating substituents both at the heterocycle and the isocyanate. It affords secondary aromatic amides in a single step under mild conditions with catalyst loadings down to 0.5 mol%. The reaction proceeds via coordination of the isocyanate to gold and outer-sphere nucleophilic attack of the heterocycle. Several gold(I) isocyanate adducts were authenticated by multinuclear NMR spectroscopy at low temperatures. ¹⁵N-labeling of the organic fragment allowed us to observe a deshielding of the ¹³C NMR NCO signal and a decrease of the associated ¹J_CN coupling constant upon coordination to gold. With further support from density functional theory (DFT) calculations, the ground state was assigned to an η¹-N-coordination isomer. The corresponding η¹-O-adduct lies ca. 8–11 kcal mol⁻¹ higher in energy. A gold(I) π-adduct involving N-methyl pyrrole as the substrate was also authenticated experimentally, including by X-ray crystallography. The latter species is involved as an off-cycle resting state in the catalytic transformation.