29. Total synthesis of crenulatan diterpenes: Strategy and stereocontrolled construction of a bicyclic keto-lactone building block

Article abstract of DOI:10.1002/hlca.19950780210

The bicyclic keto lactone 26 was synthesized for the purpose of developing a viable route to marine diterpenes of the crenulatan type. Following the efficient conversion of (S)-citronellol (5) to the allylated alcohol 9a, the α,β -unsaturated lactone 12 was efficiently accessed in preparation for stereocontrolled conjugate addition. The hydroxymethyl equivalent most suited to this task was (i-PrO)Me₂SiCH₂MgCl, which gave 13 predominantly in the presence of CuI and Me₃SiCl. Once the OH group was deprotected (→14), it proved an easy matter to implement acid-catalyzed isomerization to lactone 15, oxidation of which gave the pivotal aldehyde 16. Condensation of 16 with PhSeCH₂Li led via 21 to 22. Once the OH group was protected (→22b), it proved possible to effect aldolization with crotonaldehyde (→23). Exposure of 23 to acid gave the sub-target compound 25. Its subsequent oxidation and thermal activation resulted in sequential selenoxide elimination with Claisen rearrangement (→26). The structural features of 26 require that a chair-like transition state be adopted during the [3.3]sigmatropic event. With the clarification of these issues, a highly serviceable and more advanced assault on the crenulatans should prove capable of being mounted.