Abstract
Two total syntheses of (±)-15-deoxy-Prostaglandin E2 and (-)-Prostaglandin E2 methyl ester are completed through heteroatom-directed conjugate addition (HADCA). The key steps in this strategy are (i) Samarium-Reformatsky asymmetric aldol reaction; (ii) substrate control HADCA reaction in highly stereoselective manner; (iii) 1,4-Brook rearrangement; (iv) intramolecular cyclization to produce cyclopentanone, especially, (ii)-(iv) were achieved in one-pot reaction. Alkylation of the α-side chain with ketosulfone then followed by desulfonylation and desilylation afforded the (±)-15-deoxy-PGE2 and (-)-PGE2 methyl ester in 34% and 24% yield respectively. Highly regioselective hydrosilylation of unsymmetric alkynes using phenylthio moiety as directing group and also discussed in this dissertation.