A short and efficient total synthesis of (±) prostaglandin D2 methyl ester involving a new method for the cleavage of a dimethyl-t-butylsilyl ether

Abstract

Baeyer-Villiger oxidation of the bicyclo[2.2.1]heptanone (4; R = SiMe₂Bu^t) afforded a mixture of isomeric lactones (5) and (6), the minor component (6) being conveniently removed by selective hydrolysis. Reduction of the lactone (5) by di-isobutylaluminium hydride gave the corresponding lactol (8). Conversion of (8) into the 9α-silyloxyprostanoid (10) was performed so as to minimise silyl group migration. Oxidation of (10) gave the ketone (12) but the hindered siloxy-group at C-9 was extremely resistant to cleavage by the usual reagents. Satisfactory deprotection of (12) was achieved by treatment with aqueous HF in acetonitrile to give (±)-prostaglandin D₂ methyl ester (14) and (±)-15-epi-prostaglandin D₂ methyl ester (15). The high ‘silicophilicity’ and low acidity of HF make it the reagent of choice for cleavage of silyl ethers under mildly acidic conditions.