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 nonenzymatic biomimetic polyene tetracyclization route. The cyclization substrate, pentaenol 3, contains a tetramethylallylic alcohol initiator, an allyltrimethylsilane terminating group, and a fluorine atom at pro-C-13 to serve as a cation-stabilizing (C-S) auxiliary controlling the regiochemistry of the C/D ring juncture. The synthesis of 3 employed lithium-halogen exchange to create alcohols 10 and 19. The Z-fluoroalkene in 3 was introduced stereoselectively 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) when it was added as a dilute solution in dichloromethane to trifluoroacetic acid at -45 degrees C to afford tetracyclic fluoro diene 24 possessing the trans-anti-trans-anti-trans ring stereochemistry of the dammaranes. Replacement of the fluorine atom of 24 with hydrogen with complete retention of configuration 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 give the SP-alcohol 30. Ketal hydrolysis followed by Grignard reaction with isopentenylmagnesium bromide afforded the dammarenediols (1/3, 1a/1b).