Synthesis, olfactory evaluation, and determination of the absolute configuration of the 3,4-didehydroionone stereoisomers

The synthesis of 3,4-didehydroionone isomers 4, (+)-6, and (-)-6 and of 3,4-didehydro-7,8-dihydroionone isomers 5, (+)-7, and (-)-7 was accomplished starting from commercially available racemic a-ionone (1). Their preparation of the racemic forms 4-7 was first achieved by mean of a number of chemo- and regioselective reactions (Schemes 1 and 2). The enantio- and diastereoselective lipase-mediated kinetic acetylation of 4-hydroxy-gamma-ionone (10a/10b) provided 4-hydroxy-gamma-ionone (+)-10a/(+/-)-10b and (+)-4-(acetyloxy)-gamma-ionone ((+)12b) (Scheme 3). The latter compounds were used as starting materials to prepare the 3,4-didehydro-gamma-ionones (+)- and (-)-6 and the 3,4-didehydro-7,8-dihydro-gamma-ionones (+)- and (-)-7 in enantiomer-enriched form. The absolute configuration of (+)-12b was determine by chemical correlation with (+)-(6S)-gamma-ionone ((+)-3) and with (-)-(6S)-alpha-ionone ((-)-1) therefore allowing to assign the (S)-configuration to (+)-6 and (+)-7. Olfactory evaluation of the above described 3,4-didehydroionone isomers shows a significant difference between the enantiomers and regioisomers both in fragrance feature and in detection threshold (Table).