Organocuprate conjugate-addition–enolate-alkylation reactions: a new synthesis of 11-deoxyprostaglandins

Abstract

A short synthesis of a key 11-deoxyprostaglandin precursor, 6β-[(E)-3-oxo-oct-1-enyl]-cis-α-2-oxabicyclo-[3.3.0]octan-3-one (11), is reported. Important reactions in the synthesis include preparation of 2α-allyl-3β-{(E)-3-[dimethyl-(t-butyl)silyloxy]oct-1-enyl}cyclopentanone (4) by an organocuprate conjugate-addition–enolate-alkylation reaction, regiospecific epoxidation–cyclisation of the alcohol (7) to give 6β-{(E)-3-[dimethyl-(t-butyl)silyloxy]oct-1-enyl}-3-hydroxymethyl-cis-α-2-oxabicyclo[3.3.0]octane (9), and oxidative degradation of (9) with manganese dioxide to give 6β-{(E)-3-[dimethyl-(t-butyl)silyloxy]oct-1-enyl}-cis-α-2-oxabicyclo-[3.3.0]octan-3-one (10).