Theoretical investigation on SnCl4-catalyzed tandem dimerization/oxy-2-azonia-Cope rearrangements between β,γ-unsaturated ketones and imines

The mechanism of the Lewis acid-catalyzed oxy-2-azonia-Cope rearrangement between beta,gamma-unsaturated ketones and imines leading to the formation of homoallylic amides and lactams has been theoretically studied using the B3LYP density functional theory methods enhanced with a polarized continuum solvation model. It was predicted that the SnCl4-catalyzed tandem dimerization/oxy-2-azonia-Cope-rearrangement mechanism is highly preferred over the uncatalyzed version as well as the plausible tandem dimerization/Prins rearrangement mechanism. A two-step pathway was found for the overall reaction, involving the initial nucleophilic dimerization followed by the [3,3]-sigmatropic rearrangement. The latter phase was considered to be the rate-limiting step. Particularly, the transition states account for the experimentally observed stereoselectivities and Z/E selectivities. The high stereoselectivity and Z/E selectivity for the chiral cyclic substrates can be attributed to the relative conformational stabilities of TSs. Moreover, distortion-interaction analysis has been performed in an attempt to quantify the various contributions to the reaction transition states, and it revealed that interaction energy E-int(II) and distortion energy Delta E-d(I) I associated with the formation of the 2COM2 complex are the determining factors to define the Z/E selectivities for nine-and ten-membered ring pathway, respectively. Investigation on the ethyleneimine-involved reaction predicts a relatively very low barrier in the pathway; thus, the sequence might be a useful strategy for synthesis of macrolactams.