The synthesis of angular methyl substituted bicyclic enones via a unique regioselective enamine annulation reaction

Abstract

Enamines of 2,4,4-trimethylcyclopentanone 5 and of 2,5,5-trimethylcyclohexanone 14 react with methyl vinyl ketone to afford the bicyclic enones 9 and 15 in yields up to 70%. The formation of these products bearing an angular Me group is the result of an anomalous enamine Robinson annulation reaction, due to an alkylation of the enamine in the first step at its most substituted α-position. The effect of substitution in the α- and β′-position in the cycloalkanone, its ringsize, the structure of the Michael acceptor (alkyl vinyl ketone) was illustrated in reactions of the enamines of 2,5-dimethylcyclohexanone 22, carvomenthone 19, menthone 26, dihydrocarvone 28 and tetrahydroeucarvone 32 with methyl- and/or ethyl vinyl ketone.