Aza-Prins type cyclisation of vinyl bis-sulfide-tethered amines for the collective syntheses of piperidine, indolizidine and isoindolone natural products

Abstract

Herein, we report a Brønsted acid-mediated inter- and intramolecular aza-Prins cyclisation of vinyl bis-sulfide substituted amines, providing an efficient and highly stereoselective approach to synthesize piperidine, indolizidine, and isoindolone frameworks. This methodology offers a concise and versatile platform for the rapid assembly of multiple piperidine alkaloids such as (±)-coniine, (±)-conmaculatin, (±)-anabasine and (−)-dihydropinidine as well as indolizidine alkaloids viz. δ-coniceine, (±)-epi-indolizidine 167B, (±)-epi-indolizidine 209D, and (±)-epi-indolizidine 223AB. Furthermore, the developed methodology is applied in the synthesis of the valmerin core.