Asymmetric synthesis of lignans using oxazolidinones as chiral auxiliaries

A simple procedure for the asymmetric synthesis of lignans via chiral beta-benzyl-gamma-butyrolactones has been developed. The key benzylbutyrolactone intermediates were efficiently synthesized using a six-step procedure, starting from 3,4-(methylenedioxy)cinnamic acid. The key step in this sequence was a highly diastereoselective alkylation of an N-acyloxazolidinone enolate. The resulting beta-benzyl-gamma-butyrolactones were subsequently transformed into the benzylidene lignans gossypifan and savinin (hibalactone) via aldol condensation-dehydration reactions, and into the dibenzylbutyrolactone lignan 4'-demethylyatein, through alkylation. Oxidation of 4'-demethylyatein with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) afforded cis-and trans-benzylidenebenzylbutyrolactones, whereas oxidation with DDQ/TFA gave 4'-demethyldeoxyisopodophyllotoxin.