The fluorine atom as a cation-stabilizing auxiliary in biomimetic polyene cyclizations: Total synthesis of dl-dammarenediol

Dammarenediols I (1a) and II (1b) were prepared by an efficient nonenzymati c biomimetic polyene tetracyclization route. The cyclization substrate, pen taenol 3, contains a tetramethylallylic alcohol initiator, an allyltrimethy lsilane terminating group, and a fluorine atom at pro-C-13 to serve as a ca tion-stabilizing (C-S) auxiliary controlling the regiochemistry of the C/D ring juncture. The synthesis of 3 employed lithium-halogen exchange to crea te alcohols 10 and 19. The Z-fluoroalkene in 3 was introduced stereoselecti vely via the Trost palladium-catalyzed alkylation of allylic acetate 11 (Z/ E: 4.6/1). The cyclization of 3 was most efficient (62% isolated yield) whe n it was added as a dilute solution in dichloromethane to trifluoroacetic a cid at -45 degrees C to afford tetracyclic fluoro diene 24 possessing the t rans-anti-trans-anti-trans ring stereochemistry of the dammaranes. Replacem ent of the fluorine atom of 24 with hydrogen with complete retention of con figuration was accomplished using the Ohsawa-Oishi reagent (Na/K alloy and crown ether). Wacker oxidation of the resulting hydrocarbon provided ketone 28, which after ketalization was ozonolyzed with a reductive workup to giv e the SP-alcohol 30. Ketal hydrolysis followed by Grignard reaction with is opentenylmagnesium bromide afforded the dammarenediols (1/3, 1a/1b).