Stereoselective Total Synthesis of Copa and Ylango Sesquiterpenoids: Preparation of (−)-(1S,4S,5R,7R)-1,7-Dimethyl-4-isopropylbicyclo[3.2.1]octa-6,8-dione and(+)-(1R,4S,5S,7S)-1,7-Dimethyl-4-isopropylbicyclo[3.2.1]octa-6,8-dione

Abstract

The efficient, stereoselective syntheses of two diastereomeric bicyclo[3.2.1]octadiones (23 and 24) are described and the potential use of these materials for the synthesis of the copa (1–5) and the ylango (7–11) sesquiterpenoids, respectively, is outlined. Conversion of (+)-carvomenthone (26) into the corresponding n-butylthiomethylene derivative 28, followed by alkylation of the latter with ethyl 2-iodopropionate, gave compound 29. Removal of the blocking group from the latter was accompanied by ester hydrolysis and afforded keto acid 30. An efficient intramolecular Claisen condensation of the corresponding ester 31 yielded (−)-(1S,4S,5R,7R)-1,7-dimethyl-4-isopropylbicyclo[3.2.1]octa-6,8-dione(23). Conversion of the known octalone 39 into the cross-conjugated keto aldehyde 41 was accomplished by standard reactions. Treatment of the latter with lithium dimethylcuprate, followed by trapping of the resultant enolate anion with acetyl chloride gave compound 42. Oxidative ozonolysis of this material yielded the keto acid 43. Esterification of the latter, followed by intramolecular Claisen condensation of the resulting keto ester 45, afforded (+)-(1R,4S,5S,7S)-1,7-dimethyl-4-isopropylbicyclo[3.2.1]octa-6,8-dione (24).