title: The Nitrilimine-Alkene Cycloaddition Regioselectivity Rationalized by Density Functional Theory Reactivity Indices.
abstract: Conventional frontier molecular orbital theory is not able to satisfactorily explain the regioselectivity outcome of the nitrilimine-alkene cycloaddition. We considered that conceptual density functional theory (DFT) could be an effective theoretical framework to rationalize the regioselectivity of the title reaction. Several nitrilimine-alkene cycloadditions were analyzed, for which we could find regioselectivity data in the literature. We computed DFT reactivity indices at the B3LYP/6-311G(2d,p)//B3LYP/6-31G(d,p) and employed the grand potential stabilization criterion to calculate the preferred regioisomer. Experimental and calculated regioselectivity agree in the vast majority of cases. It was concluded that predominance of a single regioisomer can be obtained by maximizing (i) the chemical potential difference between nitrilimine and alkene and (ii) the local softness difference between the reactive atomic sites within each reactant. Such maximization can be achieved by carefully selecting the substituents on both reactants.
authors.affiliation: Dipartimento di Chimica, Università degli Studi di Milano, via C. Golgi 19, 20133 Milano, Italy. giorgio.molteni@unimi.it.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Molteni
authors.affiliation: Istituto di Scienze e Tecnologie Molecolari, Consiglio Nazionale delle Ricerche, via C. Golgi 19, 20133 Milano, Italy. alessandro.ponti@istm.cnr.it.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Ponti
mesh_terms: D000465:Algorithms; D000475:Alkenes / Q000737:chemistry*; D003198:Computer Simulation; D061565:Cycloaddition Reaction; D008956:Models, Chemical
chemical_list: D000475:Alkenes
keywords: 1,3-dipolar cycloaddition; alkene; conceptual density functional theory; nitrilimine; reactivity indices; regioselectivity; softness