Efficient one-pot synthesis of tryptamines and tryptamine homologues by amination of chloroalkynes

A new method was developed for the one-pot synthesis of substituted 3-(2-aminoethyl)- and 3-(3-aminopropyl)indoles from commercially available aryl hydrazines and chloroalkylalkynes. Various tryptamine derivatives were prepared directly in good yield with excellent regioselectivity. The method involves a new domino reaction sequence consisting of a titanium-catalyzed amination of the chloroalkylalkyne, [3+3]-rearrangement of the resulting aryl hydrazone, and nucleophilic substitution of the chloride by ammonia.