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

Abstract

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 PhCH N(Me)O with the C C or the C N bond of ( E)-cinnamonitrile. In agreement with experimental evidence, Lewis acid coordination to the nitrile strongly promotes reaction at the C N 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 C N addition and the transition state leading to it, thus favouring this reaction both kinetically and thermodynamically. Addition across the C C bond, in contrast, only receives weak kinetic activation; (ii) the cycloaddition to the C C or C N bonds involves different molecular orbitals at the cinnamonitrile, and the Lewis acid influences the orbital involved in C N addition to a larger extent; (iii) the Lewis acid has a stronger effect on the electron distribution of the C N 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.