Au(I)-catalyzed Hydroaminative Cyclization Leading to 2,5-Dihydroisoxazoles

Abstract

Isoxazoles have attracted considerable synthetic and medicinal interest and are frequently used in drug design. Typically, these heterocycles are assembled by 1,3-dipolar cycloaddition of nitrile oxides and nitrones with C-C -bonds, drawback of which is the poor regioselectivity. On the other hand, intramolecular hydroamination would be a conceptually simple alternative to these traditional methods, given an appropriate transition metal catalyst. Thus, a catalytic conversion of propargylic N-hydroxylamine into 2,5-dihydroisoxazole have been demonstrated for the first time employing Au(I)-catalyst. The N-O bond in substrates survives the current gold catalyzed condition and delivers a variety of dihydroisoxazoles. Interestingly, a cleavage of N-O bond was observed in one example, presumably formed through the generation of Au-carbenoid. The latter result indicates possible usage of amine oxides as oxidants in the regioselective generation of Au-carbenoid from triple bond precursors.