Lewis acid-promoted intramolecular cyclization of ortho-prenylated chalcones: application to first total synthesis of (±) involucrasin C and its novel analogues

Abstract

This study presents a refinement of a synthetic protocol for the diastereoselective intramolecular ene-type cyclization of ortho-prenylated chalcones using ZnCl₂, leading to the corresponding tertiary alcohols sans the undesired alkene by-product. While InCl₃·4H₂O offers the best yield, ZnCl₂ with slightly diminished yield provides a cheaper alternative. To assess diastereoselectivity, the prenyl group was replaced with a cinnamyl moiety, forming a third consecutive chiral center as a single diastereomer. Additionally, total synthesis of (±) involucrasin C, along with the synthesis of several structurally related novel analogues, is presented in this work.