STEREOSPECIFIC CONSTRUCTION OF MULTIPLE CONTIGUOUS QUATERNARY CARBONS- TOTAL SYNTHESIS OF (PLUS-OR-MINUS)-CIS, ANTI, TETRAMETHYL-4-OXATRICYCLO[6.4.0.02,6]DODECAN-3-OL, A THAPSANE ISOLATED FROM THAPSIA-VILLOSAVAR MINOR

The details of the first total synthesis of a natural thapsane 1g cont aining three contiguous quaternary carbon atoms, starting from cycloge raniol (9) is described. The Claisen rearrangement of 9 with methoxypr opene in the presence of acatalytic amount of propionic acid produced ketone 10. Rhodium acetate-catalyzed intramolecular cyclopropanation o f alpha-diazo-beta-keto ester 12, obtained from 10 via beta-keto ester 8, furnished cyclopropyl keto ester 7. Lithium in liquid ammonia redu ctive cleavage of cyclopropyl compound 7 gave a 1:1 mixture of hydrind anone 6 and ketol 13. Wittig methylenation of 6 furnished ester 21. Ep oxidation of 21, followed by BF3-OEt2-catalyzed rearrangement of epoxi de 23 afforded hemiacetal 25. Treatment of hemiacetal 25 with triethyl silane in trifluoroacetic acid furnished lactone 22, a degradation pro duct of various thapsanes. Finally, DIBAH reduction of lactone 22 gene rated the thapsane 1g.