Highly diastereoselective synthesis of an octahydro-1H-cyclpenta[c]pyridine skeleton via a Pd/Au-relay catalyzed reaction of (Z)-1-iodo-1,6-diene and alkyne

Abstract

The octahydro-1H-cyclopenta[c]pyridine skeletons exist in a broad spectrum of bioactive natural products, and the development of efficient and convenient protocols to construct this skeleton remains a challenging task. Herein, we report a novel diastereoselective synthesis strategy to produce octahydro-1H-cyclopenta[c]pyridine skeleton from (Z)-1-iodo-1,6-diene and alkyne via Pd/Au-relay catalyzed sequential intramolecular Heck-type cyclization, Sonogashira coupling and 1,5-enyne cyclization. The Heck/Sonogashira sequential coupling was achieved with low palladium catalyst loading without copper to deliver a variety of piperidines bearing 1,5-enyne motifs, which could furnish the octahydro-1H-cyclopenta[c]pyridine derivates with excellent diastereoselectivity (>99.5 : 1) in the presence of IPrAuCl/AgBF₄.