The acetoxyfulvene synthesis of prostaglandins. Part 1. Synthesis of the corey aldehyde

Abstract

A short and practical alternative synthesis of the Corey aldehyde (2), a key intermediate in prostaglandin synthesis, is described. 6-Acetoxyfulvene (7) underwent a Diels–Alder reaction with 2-chloroacrylonitrile to give 7-acetoxymethylene-2-chlorobicyclo[2.2.1]hept-5-ene-2-carbonitrile (8) which was converted sequentially into 2-chloro-7-anti-formylbicyclo[2.2.1]hept-5-ene-2-carbonitrile (10) and its 7-syn-isomer (11). The factors controlling the stereochemistry at C(7) in the anti- and syn-aldehydes (10) and (11) are discussed in detail.