Novel, Versatile Three-Step Synthesis of 1,2,3,4,10,10a-Hexahydropyrazino[1,2-a]indoles by Intramolecular Carbene-Mediated C-H Insertion

A new convenient three-step synthesis of the privileged CNS scaffold 1,2,3,4,10,10a-hexahydropyrazino[1,2-a]indoles has been developed. The method makes use of an intramolecular carbene-mediated C-H insertion in phenylpiperazine-derived tosyl­hydrazones made from 2-fluorobenzaldehydes. Notably, the piperazine can be replaced with other cyclic nitrogen bases and the methodology is successfully extended to pyrrolidine, piperidine, azepane, morpholine, and homopiperazine.