Efficient Zinc-Mediated Heteroannulation Route to 3-Amidoindoles

Significance

Reported is the synthesis of 3-aminoindoles 3 from phenylhydrazines 1 and alkynes 2 via a zinc-mediated hydroamination-Fischer cyclization approach. In general, electron-poor phenylhydrazines give higher yields of products than electron-rich substrates due to competing side ­reactions in the latter case. Importantly, unprotected phenylhydrazines participate in the reaction to give the free NH indoles, which is not ­possible using previous Ti-mediated methods (C. Cao, Y. Shi, A. L. Odom Org. Lett. 2002, 4, 2853). The reaction was extended to the use of heterocyclic propargylamides 4, for which decreasing the amount of Lewis acid was necessary to avoid decomposition of the heterocycles. Reaction times may also be reduced by performing the reaction under microwave irradiation.