ANNULATIONS LEADING TO DIENE SYSTEMS - TOTAL SYNTHESES OF THE DOLASTANE-TYPE DITERPENOIDS (+/-)-(5S,12R,14S)-DOLASTA-1(15),7,9-TRIEN-14-OL AND (+/-)-AMIJITRIENOL

Alkylation of the substituted cycloalkanones 14a-d and 30 with (Z)-1-bromo-4-methyl-3-trimethylstannyl-2-pentene (13) produced compounds 15a-d and 33, which were readily converted into the corresponding enol trifluoromethanesulfonates (triflates) 16a-d and 34. Intramolecular Pd(O)-catalyzed coupling of the vinylstannane and enol triflate functions in 16a-d and 34 provided the dienes 17a-d and 35. The annulation product 35 served as a suitable starting material for the total syntheses of the dolastane diterpenoids (+/-)-(5S,12R,14S)-dolasta-1(15),7,9-trien-14-ol (2) and (+/-)-amijitrienol (3). The key steps of the synthesis of (+/-)-2 involved the stereoselective methylation of the ketone 44 (readily derived from 35) to provide 46 and the Barbier type ring closure of 47 to provide the target compound. For the synthesis of (+/-)-3, the notable conversions included the reductive transformation of the diene 35 into the alkene 53, the aldol condensation of the ketone 54 with 4-trimethylstannyl-4-pentenal (55), the chemo- and stereoselective reduction of the dione 58, and the one-pot conversion of the keto vinylstannane 63 into the triene 65, via the intermediate 64.