Enantioselective Indole N–H Functionalization Enabled by Addition of Carbene Catalyst to Indole Aldehyde at Remote Site

An
enantioselective functionalization of the indole NH group is
developed. The reaction stereoselectivity is controlled by an N-heterocyclic
carbene catalyst that adds to an aldehyde moiety at the C7-carbon
of indole. The NH group participating in the carbene-catalyzed reaction
is part of the heteroaromatic rings of the indole substrate. Our reactions
afford multicyclic products bearing pyrroloquinazoline or oxazinoindole
scaffolds widely present in bioactive molecules. Our study will encourage
further exploration of carbene-catalyzed reactions of aromatic molecules
and asymmetric transformation of heteroatoms in various functional
molecules.