Activation of Isocyanates at 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 and loading of catalyst 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 temperature. 15 N-labeling of the organic fragment allowed to observe a deshielding of the 13 C NMR N=C=O signal and a decrease of the associated 1 JCN coupling constant upon coordination to gold. With the further support of density functional theory (DFT) calculations, the ground state was assigned to an η 1 -Ncoordination isomer. The corresponding η 1 -O-adduct sits ca 8-11 kcal.mol -1 higher in energy. A gold(I) π-adduct involving Nmethyl pyrrole as substrate was also authenticated experimentally, including by X-ray crystallography. The latter species is involved as off-cycle resting state in the catalytic transformation.