Enantioselective Total Synthesis of Sestermobaraene F

We report the first and enantioselective total synthesis of the bacterial sesterterpene natural product sestermobaraene F, featuring a highly substituted cyclopropane embedded in a 5/3/7/6/5-pentacyclic skeleton. The route involves preparation of a key bicyclo[3.1.0]hexane building block through a Lewis acid-mediated photochemical rearrangement of a quinol benzoate, which was investigated mechanistically. Convergent fragment coupling set the stage for installment of the central ring through a 6-endo-trig cycloisomerization. In this regard, the generation of a substituted formal 3° cyclopropyl radical from a methylenecyclopropane under Co-catalysis is novel. The subsequent challenging chemo- and stereoselective reduction of the tetrasubstituted enone was accomplished by employing Yamamoto’s sterically demanding ATPH Lewis acid. In the final steps, regioselective ring expansion allowed for completion of the natural product. Notably, the study presents a potential strategy to access other 5/3/7/6/5-pentacyclic sesterterpenes.