TOTAL SYNTHESIS OF CRENULATAN DITERPENES - STRATEGY AND STEREOCONTROLLED CONSTRUCTION OF A BICYCLIC KETO-LACTONE BUILDING-BLOCK

The bicyclic keto lactone 26 was synthesized for the purpose of develo ping a viable route to marine diterpenes of the crenulatan type. Follo wing the efficient conversion of(S)-citronellol (5) to the allylated a lcohol 9a (Scheme 2), the alpha beta-unsaturated lactone 12 was effici ently accessed in preparation for stereocontrolled conjugate addition. The hydroxymethyl equivalent most suited to this task was (i-PrO)Me(2 )SiCH(2)MgCl, which gave 13 predominantly in the presence of CuI and M e(3)SiCl. Once the OH group was deprotected (--> 14), it proved an eas y matter to implement acid-catalyzed isomerization to lactone 15, oxid ation of which gave the pivotal aldehyde 16. Condensation of 16 with P hSeCH(2)Li led via 21 to 22 (Scheme 3). Once the OH group was protecte d (--> 22b), it proved possible to effect aldolization with crotonalde hyde (--> 23). Exposure of 23 to acid gave the sub-target compound 25. Its subsequent oxidation and thermal activation resulted in sequentia l selenoxide elimination with Claisen rearrangement (--> 26). The stru ctural features of 26 require that a chair-like transition state be ad opted during the [3.3]sigmatropic event. With the clarification of the se issues, a highly serviceable and more advanced assault on the crenu latans should prove capable of being mounted.