Total synthesis of (±)-prostaglandin E2 methyl ester from exo-2-bromo-endo-3-hydroxybicyclo[3.2.0]heptan-6-one using dimethyl-t-butylsilyl protected intermediates

Abstract

Peracetic acid oxidation at –78 °C of the dihydroxybicyclo[3.2.0]heptan-6-one (23) afforded the dihydroxylactone (24) which was protected as its bisdimethyl-t-butylsilyl ether (26) and reduced to the corresponding lactol (27). A Wittig reaction on (27), carried out in benzene with a short reaction time, gave mainly the required 11α-silyl ether (28) together with a trace of the 9α-silyl ether (29) which results from 1,5-migration of the silyl group. Oxidation of (28) followed by quantitative deprotection using aqueous HF in acetonitrile afforded (±)-PGE₂ methyl ester (20). This short stereo-and regio-selective total synthesis proceeds in an overall yield of 10% starting from cyclopentadiene.