Mechanism of AlIII-Catalyzed Transamidation of Unactivated Secondary Carboxamides

• Published in: Journal of the American Chemical Society 2006-04, Vol.128 (15), p.5177-5183
• Main Authors: Hoerter, Justin M, Otte, Karin M, Gellman, Samuel H, Stahl, Shannon S
• Format: Article
• Language: English
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja060331x

The carbon−nitrogen bond of secondary carboxamides is generally thermodynamically and kinetically unreactive; however, we recently discovered that the trisamidoaluminum(III) dimer Al2(NMe2)6 catalyzes facile transamidation between simple secondary carboxamides and primary amines under moderate conditions. The present report describes kinetic and spectroscopic studies that illuminate the mechanism of this unusual transformation. The catalytic reaction exhibits a bimolecular rate law with a first-order dependence on the AlIII and amine concentrations. No rate dependence on the carboxamide concentration is observed. Spectroscopic studies (1H and 13C NMR, FTIR) support a catalyst resting state that consists of a mixture of tris-(κ2-amidate)aluminum(III) complexes. These results, together with the presence of a significant kinetic isotope effect when deuterated amine substrate (RND2) is used, implicate a mechanism in which the amine undergoes preequilibrium coordination to aluminum and proton transfer to a κ2-amidate ligand to yield an Al(κ2-amidate)2(κ1-carboxamide)(NHR) complex, followed by rate-limiting intramolecular delivery of the amido ligand (NHR) to the neutral AlIII-activated κ1-carboxamide. Noteworthy in this mechanism is the bifunctional character of AlIII, which is capable of activating both the amine nucleophile and the carboxamide electrophile in the reaction.