N-Heterocyclic-Carbene-Catalyzed C-H Heteroarylation of Aldehydes for the Rapid Synthesis of Aryl Heteroaryl Ketones.

The N-heterocyclic carbene (NHC)-catalyzed C-H heteroarylation of aromatic aldehydes for the synthesis of aryl heteroaryl ketones under mild and metal-free conditions is reported. This operationally simple strategy proceeds via the nucleophilic substitution of aldehyde-derived Breslow intermediates with 2-chloro-substituted heteroarenes in an addition-elimination pathway following the irreversible formation of benzoin. Moreover, the reaction exhibited good functional group tolerance, providing access to a diverse range of heteroaryl ketones in moderate to high yields. In addition, the synthetic utility of the method is demonstrated through the preparation of pharmaceutically relevant molecules.