Preparation and hydrolysis of some 4-substituted bicyclo[3.1.0]hex-2-ene-6-carbaldehydes: synthesis of the prostaglandin A2 analogue possessing a butyl group in place of the octenol side chain

Abstract

The halogenoesters (7) and (13) were treated with various nucleophiles to give a range of 4,6,7-trisubstituted bicyclo[3.2.0]heptenes (8)–(12) and (14)–(20). The esters (11), (12), and (17)–(20) were treated with hydroxide or methoxide ion to give the corresponding bicyclo[3.1.0]hexene-6-endo-carbaldehyde (21), (22), and/or the bicyclo[3.1.0] hexene-6-exo-carbaldehyde (24)–(27). The endo-aldehydes (21) and (22) were readily hydrolysed under acid catalysis to give the lactols (32) and (33) : the exo-aldehydes (24)–(26) were hydrolysed to the corresponding lactols (32)–(34) under more forcing conditions. The lactol (32) was converted into the prostaglandin A₂ analogue (5) by a Wittig reaction followed by a Jones oxidation.