A NOVEL CYCLOADDITION REACTION OF ALPHA-DIAZO-GAMMA-AMIDO KETONES CATALYZED BY RHODIUM(II) ACETATE - SCOPE AND MECHANISTIC DETAILS OF THE PROCESS

alpha-Diazo ketones containing an amido group in the gamma-position ha ve been found to undergo a novel rhodium(II)-catalyzed cycloaddition r eaction. Intramolecular cyclization of the keto carbenoid onto the oxy gen atom of the amide group generates a carbonyl ylide dipole as a tra nsient species. This highly stabilized dipole does not readily undergo 1,3-dipolar cycloaddition but rather transfers a proton to produce a cyclic ketene N,O-acetal. The ketene acetal is unstable to moisture an d upon standing is readily hydrolyzed to a gamma-keto delta-lactone an d an amine. In the absence of any significant amount of water, the ket ene N,O-acetal undergoes conjugate addition with the activated st-bond of the dipolarophile to give a zwitterion intermediate. The anionic p ortion of the zwitterion adds to the neighboring carbonyl group. This is followed by epoxide ring formation with charge dissipation leading to an amido-substituted spiro cyclopentyl epoxide. In certain cases a hydroxy lactone was also isolated and its formation can be attributed to the competitive hydrolysis of the zwitterionic intermediate. The Rh (II)-catalyzed reaction of the diazo ketoamide derived from N-benzylpi peridone with DMAD afforded two different types of cycloadducts. In ad dition to the spiro cyclopentyl epoxide, a product derived from trappi ng of the carbonyl ylide dipole was also obtained, thereby providing a dditional support for the proposed mechanism.