Total synthesis of optically active liverwort sesquiterpenes, trifarienolsA and B, using phenylethylamine as a chiral auxiliary

The imine of (rac)-2,3-dimethylcyclohexanone 10a with (S)-(-)-phenylethylam ine was reacted with methyl acrylate to yield methyl (1'S,6'R)-3-(1',6'-dim ethyl-2'-oxocyclohexyl)propanoate 4a in 26% (97% eel)after hydrolysis. When (2RS,3R)-2,3-dimethylcyclohexanone 10b, was used, the same product 4b was obtained in 59% yield (>99.5% ee) after hydrolysis. When (2RS,3R)-2,3-dimet hylcyclohexanone 10b and (R)-(+)-phenylethylamine were used, the reaction u nderwent in only 5% yield, the products being 4c, 12, 13, 14, and 15. Thus, the reaction of 3b with methyl acrylate is a matched case, while that of 3 c is a mismatched case. These phenomena are explained by the nonbonded inte raction of methyl acrylate with chiral phenylethylamine and the methyl grou p at the 6'-position of the cyclohexanone ring in the transition state. The propanoate product 4b was successfully transformed into liverwort sesquite rpene (+)-trifarienol A 1 and (-)-trifarienol B 2 in 10 steps. We have deve loped an HPLC method to determine the ees of 2,2-disubstituted and 2,2,3-tr isubstituted cyclohexanones using the corresponding pentafluorophenyl ester s. (C) 1999 Elsevier Science Ltd. All rights reserved.