Intramolecular N–H insertion of -diazocarbonyls catalyzed by Cu(acac)2: An efficient route to derivatives of 3-oxoazetidines, 3-oxopyrrolidines and 3-oxopiperidines

Along with the intramolecular C–H insertion reactions by carbenoids, intramolecular N–H insertion reactions of α-diazocarbonyl substrates catalyzed by metal complex have received considerable attention in recent years. This type of insertion reaction has been shown to be a mild and efficient route to 4-, 5-, and 6-membered aza rings. A frequently cited example of this powerful approach is the Merck industrial synthesis of the bicyclic β-lactam thienamycin, in which the intramolecular N–H insertion by Rh-carbenoid is the key step. The corresponding asymmetric N–H insertion was early exploited with a chiral-auxiliary approach, and recent efforts in this area are concentrated on the application of chiral Rh catalysts. Although N–H insertions by metallocarbenoids were originally promoted by copper-mediated diazo decomposition, most of the intramolecular N–H insertions recently reported are based on Rh-catalyzed diazo decomposition, particularly with Rh2(OAc)4 as the catalyst. 4,6 Rh complexes have been extensively used in diazo decomposition, and they have been shown to be the most efficient catalysts in intramolecular C–H insertions as well as in cyclopropanations. Despite great success demonstrated by Rh catalysts, their application in intramolecular N–H insertion has been limited by the competing C–H insertion, which is a very easily accomplished Rhmediated reaction. For example, Rapoport reported that intramolecular C–H insertion, which led to the formation of 5-membered carbocycles, was a significant by-product in the synthesis of 3-oxopiperidine by Rh2(OAc)4-catalyzed intramolecular carbenoid N–H insertion. McKervey also recently reported the competing C–H insertion in asymmetric intramolecular N–H insertions by a chiral Rh complex. This possible side reaction may be the reason that the intramolecular N–H insertion by carbenoids has still not been widely applied in the synthesis of molecules with complicated structures, except for the β-lactams syntheses by Rh-carbene intramolecular N–H insertion in which the reaction occurs in a conformationally restricted ring system. To avoid the complexity caused by this side reaction, it would be desirable to look for other metal complexes which can efficiently promote intramolecular N–H insertion but not C–H insertion. We report in this paper our investigation on the intramolecular N–H insertion catalyzed by copper(II) acetylacetonate [Cu(acac)2]. The results suggest that this catalyst can efficiently promote intramolecular N–H insertions.