Bicyclo[3.3.0]octenones in synthesis. A new synthesis of (±)-cedrene using sequential inter- and intra-molecular Michael reactions

Abstract

A new synthetic approach to cedrene (1) based on sequential inter- and intra-molecular Michael reactions using the bicyclo[3.3.0]octenone (21) as the key intermediate is described.Michael addition of the enolate derived from (21) to 2-nitrobut-2-ene, led to a mixture of diastereoisomers of the nitro ketone (22), which was then converted into the 1,4-dione (23). Treatment of (23) with potassium t-butoxide in t-butyl alcohol resulted in smooth intramolecular Michael reaction leading to a mixture of α-(24a; major) and β-isomers of thetricyclo[5.3.1.01,5]undecanedione (24) in a combined yield of 73%. The undecanedione (24) was then converted into (±)-cedrene (1) and the corresponding methyl epimer (31a)via the intermediates (25), (26), (27) and (28).