Highly enantiospecific synthesis of 4-alkyl and 4,5-dialkyl substituted 4,5-dihydrofuran-2(3H)-ones from optically active (E)- and (Z)-alk-1-enyl p-tolyl sulphoxides: application to the synthesis of lignan lactones

Abstract

Stereochemically and optically pure 2-substituted ethylenic p-tolyl sulphoxides (R)-E-(4) and (R)Z-(4) undergo readily and stereospecifically an additive Pummerer rearrangement reaction with dichloroketene to give trans- and cis-β-alkyl-α,α-dichloro-γ-p-tolylthio-γ-butyrolactone derivatives (5), respectively. Sequential reductive dechlorination and desulphurization lead to (–)-(S)-, from trans-(5), and (+)-(R)-β-alkyl-γ-butyrolactones [4-alkyl-4,5-dihydrofuran-2(3H)-ones](7), from cis-(5), with a high optical purity, respectively. Reaction of the intermediate tolylthio derivatives (6) with allyltributylstannane gives β-alkyl-γ-ally-γ-butyrolactones (15) and (16). These sequential reactions can be successfully applied to the synthesis of (+)-(R)-β-piperonylbutyrolactone (20), the key intermediate for the synthesis of antileukemic lignan lactones, in high chemical and optical yields. Acylation of compound (20) with 3,4,5-trimethoxybenzoyl chloride furnishes (+)-podorhizon (21).