Highly stereocontrolled synthesis of [3.3.3] propellane sesquiterpenes. ( ± )-Modhephene and (±)-epimodhephene

Abstract

Stereospecific total synthesis of (±)-modhephene ( 2) and (±)-epimodhephene ( 3) are reported. Conjugate addition of 1-trimethylsilyl-1-butyn-4-yl cuprate (BF 3-etherate catalysis) to bicyclic ketone 6, fluoride ion-promoted deblocking of the terminal acetylene, and ene reaction, gave tricyclic enone 11. Sequential Wittig methylenation, regiocontrolled epoxidation, and Lewis acid catalyzed isomerization afforded ketone 14 whose double bond relocation and Wolff-Kishner reduction led exclusively to 2. In a still shorter route to 3, 3-butenyl cuprate addition to 6 was utilized to gain access to 7. Thermolysis of this intermediate, methylenation, and double bond isomerization were found to deliver pure 3 successfully.