Reversal of polarity by catalytic SET oxidation: synthesis of azabicyclo[m.n.0]alkanes via chemoselective reduction of amidines

Abstract

A one-pot catalytic method has been developed for the stereoselective synthesis of cyclopropane-fused cyclic amidines using CuBr₂/K₂S₂O₈ as an efficient single electron transfer (SET) oxidative system. The generality of this mild method is demonstrated with a wide variety of substrates to furnish pharmaceutically important amidines containing aza-bicyclic and novel aza-tricyclic frameworks in very good yields. A chemoselective reduction of cyclic amidines to 2-/3-azabicyclo[m.n.0]alkanes and octahydroindoles has been developed using a NaBH₄/I₂ reagent system. The synthetic scope of the chemoselective reduction of the amidine functionality has been exemplified in the stereoselective synthesis of an iminosugar based (±)-epiquinamide analogue.