Synthesis of β-Lactams by Ag+-Induced Ring Expansion of 1-Hydroxycyclopropylamines:  A Theoretical Analysis

• Published in: The journal of physical chemistry. A, Molecules, spectroscopy, kinetics, environment, & general theory Vol. 109; no. 34; pp. 7822 - 7831
• Main Authors: Campomanes, Pablo, Menéndez, M. Isabel, Cárdenas-Jirón, Gloria I, Sordo, Tomás L
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 01.09.2005
• Subjects: beta-Lactams - chemical synthesis; Cyclopropanes - chemistry; Silver - chemistry
• ISSN: 1089-5639; 1520-5215
• DOI: 10.1021/jp052291+

A theoretical analysis of the silver-induced ring expansion of N-chloro-N-methyl-1-hydroxycyclopropylamine to form N-methyl-2-azetidinone, and of the Cl- elimination from this substrate without Ag+ assistance, was performed using the B3LYP method and the 6-31+G(d) basis set for C, N, O, H, and Cl atoms and the relativistic effective core pseudopotential LANL2DZ complemented with one set of f polarization functions (ζf = 0.473) for the Ag atom. The partial Ag+-assisted extrusion of Cl- at the rate-determining transition state provokes an important change in the nodal properties of the frontier molecular orbitals of the H3CClNCOHAg+ fragment, thus making very stabilizing HOMO−LUMO interactions between this fragment and the C2H4 moiety possible. This interaction leads to the ring opening and release of most of the strain energy, giving rise to a low energy barrier for the process. Also, by assisting the Cl- extrusion, Ag+ avoids the elimination of the hydroxyl hydrogen atom, which would provoke the fragmentation of the system instead of the formation of the β-lactam.