Theoretical study of the cycloaddition of nitrones to cinnamonitrile: effect of Lewis acid coordination on the selectivity of the reaction

A number of quantum chemical and density functional methods have been used to study the chemo- and regioselectivity of the uncatalysed and Lewis acid mediated cycloaddition of the nitrone PhCHdouble bond; length as m-dashN(Me)O with the Cdouble bond; length as m-dashC or the Ctriple bond; length of mdashN bond of (E)-cinnamonitrile. In agreement with experimental evidence, Lewis acid coordination to the nitrile strongly promotes reaction at the Ctriple bond; length of mdashN bond over reaction at the alkene moiety. The main factors responsible for this inversion of the chemoselectivity were identified as the following: (i) the Lewis acid strongly stabilises the product of Ctriple bond; length of mdashN addition and the transition state leading to it, thus favouring this reaction both kinetically and thermodynamically. Addition across the Cdouble bond; length as m-dashC bond, in contrast, only receives weak kinetic activation; (ii) the cycloaddition to the Cdouble bond; length as m-dashC or Ctriple bond; length of mdashN bonds involves different molecular orbitals at the cinnamonitrile, and the Lewis acid influences the orbital involved in Ctriple bond; length of mdashN addition to a larger extent; (iii) the Lewis acid has a stronger effect on the electron distribution of the Ctriple bond; length of mdashN bond. As an overall result, the Lewis acid not only promotes the cycloaddition, but also alters the order of functional group reactivity and brings about a complete change in chemoselectivity.