A new synthetic approach to the morphinan framework

Matthews, Ian Richard (1986) A new synthetic approach to the morphinan framework. University of Southampton, Doctoral Thesis.

Record type: Thesis (Doctoral)

Abstract

A new synthetic approach to morphine has been investigated using an intramolecular nitrone cycloaddition reaction as the key step. Coupling of 4-iodo-5-(2-propenyl)-1,3-benzodioxole with, alternatively 3-methoxy-cyclohex-2-enone, and 3-methoxy-5-[(phenylmethoxy)methyl]-2- cyclohexen-1-one is described. Subsequent sodium borohydride reduction and a Claisen type rearrangement using N, N-dimethylacetamide dimethyl acetal followed by selective cleavage of the double bond afforded the aldehydes (1) and (2). When the nitrone cycloaddition reaction was performed for R=H a 1:1 ratio of exo: endo adducts was obtained. However for R=CH₂OCH₂Ph the exo:endo ratio was 1:4. In both cases the exo adduct was converted through to a morphinan structure and for R=H a number of steps were carried out towards producing a synthetic sample of morphine. A number of different methods for making 4-iodo-5-(2-propenyl)-1,3-benzodioxole are also discussed. (D73967/87)