Amination of Ketenes: Evidence for a Mechanism Involving Enols of Amides as Intermediates

The amination reaction of ketenes has been studied both theoretically and experimentally as a model reaction for amide bond formation. Calculations are performed using both ab initio molecular orbital theory (MO) and density functional theory (DFT) methods. Solvent effects are modeled by different methods:  Onsager SCRF, PCM, and SCI-PCM electrostatic continuum solvation models, as well as explicit inclusion of actively participating water molecules, representative of a polar protic solvent, at different hydrogen bond donor−acceptor sites of the solutes. Both the concerted process and the two-step reaction, via a 1-amino-1-hydroxy ene intermediate, have been investigated at high level of theory. These intermediates are formally enols of amides. A comparison with uncatalyzed amide bond formation indicates that the active participation of a second ammonia molecule reduces the energy barrier in favor of the two-step reaction. When a water molecule acts as catalyst instead of a second ammonia molecule, this e...