title: Theory of 1,3-dipolar cycloadditions: distortion/interaction and frontier molecular orbital models.
abstract: Quantum chemical calculations of activation barriers and reaction energies for 1,3-dipolar cycloadditions by the high-accuracy CBS-QB3 method reveal previously unrecognized quantitative trends in activation barriers. The distortion/interaction model of reactivity explains why (1) there is a monotonic decrease of approximately 6 kcal/mol in the activation energy along the series oxides, imine, and ylide for the diazonium, nitrilium, and azomethine betaine classes of 1,3-dipoles; (2) nitrilium and azomethine betaines with the same trio of atoms have almost identical cycloaddition barrier heights; (3) barrier heights for the cycloadditions of a given 1,3-dipole with ethylene and acetylene have the same activation energies (mean absolute deviation of 0.6 kcal/mol) in spite of very different reaction thermodynamics (Delta DeltaH(rxn) range = 14-43 kcal/mol) and frontier molecular orbital (FMO) energy gaps. The energy to distort the 1,3-dipole and dipolarophile to the transition state geometry, rather than FMO interactions or reaction thermodynamics, controls reactivity for cycloadditions of 1,3-dipoles with alkenes or alkynes. A distortion/interaction energy analysis was also carried out on the transition states for the cycloadditions of diazonium dipoles with a set of substituted alkenes (CH2CHX, X = OMe, Me, CO 2Me, Cl, CN) and reveals that FMO interaction energies between the 1,3-dipole and the dipolarophile differentiate reactivity when transition state distortion energies are nearly constant.
authors.affiliation: Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095, USA.
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Ess
authors.forename: K N
authors.initials: KN
authors.lastname: Houk
mesh_terms: D006571:Heterocyclic Compounds / Q000138:chemical synthesis*; D008956:Models, Chemical; D008958:Models, Molecular; D011789:Quantum Theory; D013816:Thermodynamics
chemical_list: D006571:Heterocyclic Compounds