Palladium catalyzed reductive Heck coupling and its application in total synthesis of (−)-17-nor-excelsinidine

Abstract

Monoterpene indole alkaloids, bearing a highly substituted piperidine ring, are a structurally diverse class of bioactive natural products, found in various parts of the world. Herein, we reported the construction of the key piperidine ring via palladium catalyzed reductive Heck coupling with a good syn selective manner, avoiding the usage of stoichiometric, highly toxic, air sensitive and moisture sensitive Ni(COD)₂. To further showcase the value of this methodology, we realized the total synthesis of the structurally unique zwitterionic monoterpene indole alkaloid (−)-17-nor-excelsinidine in 9 steps, in which the key ammonium–acetate connection (N4–C16) of (−)-17-nor-excelsinidine was constructed via oxidative coupling in excellent yield and high regioselectivity under NBS/pyridine from the enolate of geissoschizine.