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 PhCHth the CC (E)-cinnamonitrile. In agreement with experimental evidence, Lewis acid coordination to the nitrile strongly promotes reaction at the Cer 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 Cn and the transition state leading to it, thus favouring this reaction both kinetically and thermodynamically. Addition across the Cn contrast, only receives weak kinetic activation; (ii) the cycloaddition to the C:glyph name="tbnd" />N bonds involves different molecular orbitals at the cinnamonitrile, and the Lewis acid influences the orbital involved in Cn to a larger extent; (iii) the Lewis acid has a stronger effect on the electron distribution of the Cs 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. [Copyright &y& Elsevier]