The pot-economical synthesis of clinprost is reported, in which the core bicyclo[3.3.0]octenone structure was synthesized by two key steps: an asymmetric domino Michael/Michael reaction catalyzed by diphenylprolinol silyl ether and an intramolecular Horner-Wadsworth-Emmons reaction. The trisubstituted endocyclic alkene was selectively introduced by 1,4-reduction followed by trapping of the generated enolate with Tf2NPh and subsequent utilization of the Suzuki-Miyaura coupling reaction. Chiral, nonracemic clinprost was synthesized in seven pots with a 17% total yield and excellent enantioselectivity.
ASJC Scopus subject areas
- Physical and Theoretical Chemistry
- Organic Chemistry