A synthetic approach to zoapatanol and related bicyclic analogues

Abstract

A Ni⁰-catalysed coupling of MeMgBr with dihydrofuran (4) and addition of Grignard reagent (7) to a butyne-1,4-diol derivative (8) were key steps in the highly stereoselective construction of the trisubstituted double bonds in (10) which is a precursor to the oxepane ring system (12) of zoapatanol (1); subsequent elaboration of (12) gave (1R*,4S*,5R*)-4-[5-oxo-8-methylnon-7-enyl]-3,8-dioxabicyclo[3.2.1]octane-1-acetic acid (18), a demethyl analogue of the potent antigestational agent ORF 13811 (2).