Bifunctional Chiral ImPy-Carbene Ligands. H-Bonding Controlled Reactivity and Enantioselectivity in Au(I)-Catalysis

Abstract

Bifunctional chiral N-heterocyclic carbene ligands have been devised for enantioselective gold(I) catalysis. Based on a single C-stereogenic center derived from chiral pool α-aminoacids and connecting an imidazopyridine core to an arylurea motif, enantioselective gold(I)-catalyzed cycloisomerization reactions could be achieved. High enantioselectivities were notably observed for substrates presenting a pendant propargyl alcohol on 2-naphthol and 1,6-enyne scaffolds. In the latter case, the catalyst shows a high degree of selectivity for the unprecedented 6-endo-dig biscyclization of these substrates to give cyclopropyl-fused 6-ring heterocycles with a free OH functionality instead of the previously reported furan-fused products. This unusual selectivity was investigated by DFT studies, which suggested the dual role of the carbonyl group of the urea moiety: first as an H-bond acceptor in the catalytic cycle to direct the enantioselectivity and second as a cooperative group in the hydrogen shift leading to deauration.