Study on the base-catalyzed reverse vinylogous aldol reaction of (4a beta,5 beta)-4,4a,5,6,7,8-hexahydro5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-one under Robinson annulation conditions

摘要

We have proposed a pathway for the base-catalyzed reverse vinylogous aldol reaction of (-)-(4a beta,5 beta)-4,4a,5,6,7,8-hexahydro-5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-one [(-)-8] under Robinson annulation conditions. For confirmation, 4-(2,6-dimethyl-3-oxocyclohex-1-enyl)butanal (11) and 4-(2,6-dimethyl-5-oxocyclohex-1-enyl)butanal (12), both of which potentially produce enolate 1, were synthesized regioselectively. Unexpectedly, 11 gave a complex mixture, including only a trace amount of (+/-)-8 (less than 5% yield), under these basic conditions. To the contrary, 12 cleanly afforded (+/-)-8 in 66% yield. This result provides evidence for our proposed mechanism of the above reaction.