An Extremely Simple Route to a Prostaglandin Precursor: Hexamethylphosphoric-Triamide-Mediated Conjugate Addition of 1-(Phenylthio)Oct-2-Enyllithium to 4-Tert-Butoxycyclopent-2-Enone and Triphenyltin-Chloride-Assisted Reaction of the Enolate With Methyl 7-Iodohept-5-Ynoate

Abstract

Reaction of 4-t-butoxycyclopent-2-enone with (E)-1-(pheny1thio)oct-2-enyllithium in tetrahydrofuran containing 1.5 equivalents of hexamethylphosphoric triamide at - 78� followed by treatment of the resulting enolate with one equivalent of triphenyltin chloride and then with methyl 7-iodohept-5-ynoate at - 20� gives the vicinally dialkylated cyclopentanone, methyl (a-9-oxo-1l-t-butoxy-13-(phenylthio)prost-14-en-5-ynoate, as a 1 : 1 mixture of diastereomers epimeric at C13, in 70-72% overall yields from the octenyllithium reagent. Stereoselective reduction of the C9 carbonyl, conversion of the sulfide into the allylically transposed alcohol, and removal of the t-butyl group by means of iron(III) chloride in acetic anhydride at 0� provides a triacetate which is converted into racemic methyl 5,6-didehydroprostaglandin F2a methyl ester as a 1 : 1 mixture of diastereomers epimeric at C15.

Regioselectivity of the Reactions of Heteroatom-Stabilized Allyl Anions with Electrophiles

“…Conjugate addition to allyl phenyl sulfides, e.g., 146 also gave α-products 147 and 148 (Scheme ). This route can eventually furnish a prostaglandin, whereby the key step involves the reaction of the lithium enolates of 147 and 148 , produced in the initial conjugate addition step, with triphenyltin followed by alkylation − or a stereoselective steroid synthesis by subsequent trapping of the enolates with benzyl bromide 24 …”