On the Synthesis of α-Azidovinyl Ketones. Mechanism and Stereochemistry of Vinyl Bromide Substitution

A general method for the synthesis of α-azidovinyl ketones (3) involves the reaction of the dibromides of α,β-unsaturated ketones with 2 equiv of sodium azide in DMF at room temperature. Although in most cases the reaction proceeds via an α-bromovinyl ketone intermediate 2, the conversion of 2 to the vinyl azide 3 does not involve an SN2-type displacement. A detailed mechanistic study of the reaction, using nmr techniques, reveals that erythro-ethylideneacetophenone dibromide (la) reacts mainly through pathway l→-2→7→8→3, whereas erythro-benzylideneacetophenone dibromide (lb) and erythro-benzylideneacetone dibromide (lc) react by both pathways: 1→2→3 and 1→2→7→8→3. Under the same reaction conditions meso-1,2-dibenzoylethylene dibromide (13) gives the isoxazole (15) exclusively. Finally, a trans configuration is assigned to the a-azidovinyl ketones on the basis of stereochemical arguments.