Regio- and Stereoselective Ring Openings of 3-Aza-2-oxabicyclo[2.2.1]hept-5-ene Systems with Copper Catalyst-Modified Grignard Reagents:  Application to the Synthesis of an Inhibitor of 5-Lipoxygenase

Abstract

Treatment of acylnitroso hetero Diels-Alder cycloadducts 2 with organomagnesium reagents in the presence of a catalytic amount of copper induces ring opening to afford predominantly monocyclic anti-1,2-hydroxamic acids 12. Alkylmagnesium reagents were found to give superior regio- and stereoselectivities compared with vinyl and arylmagnesium reagents. This cycloadduct ring opening methodology was applied to the synthesis of a unique cyclopentenyl hydroxamic acid-based inhibitor of 5-lipoxygenase.