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 benzylbut yrolactone intermediates were efficiently synthesized using a six-step procedure, starting from 3,4-(methylenedioxy)cinnamic acid. The key s tep in this sequence was a highly diastereoselective alkylation of an N-acyloxazolidinone enolate. The resulting beta-benzyl-gamma-butyrolac tones were subsequently transformed into the benzylidene lignans gossy pifan and savinin (hibalactone) via aldol condensation-dehydration rea ctions, and into the dibenzylbutyrolactone lignan 4'-demethylyatein, t hrough alkylation. Oxidation of 4'-demethylyatein with 2,3-dichloro-5, 6-dicyano-1,4-benzoquinone (DDQ) afforded cis-and trans-benzylideneben zylbutyrolactones, whereas oxidation with DDQ/TFA gave 4'-demethyldeox yisopodophyllotoxin.