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

• Published in: Canadian journal of chemistry 1975-10, Vol.53 (19), p.2827-2837
• Main Authors: Piers, Edward, Britton, Ronald W, Geraghty, M. Bert, Keziere, Robert J, Smillie, R. Dean
• Format: Article
• Language: English
• ISSN: 0008-4042; 1480-3291
• DOI: 10.1139/v75-402

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 ).