title: Theoretical elucidation of kinetic and thermodynamic control of radical addition regioselectivity.
abstract: The cyclizations of two structurally similar 2-oxo-5-hexenyl-type radicals have been investigated by ab initio and density functional (UB3LYP/6-31+G**//UHF/6-31G* and UB3LYP/6-31G*//UB3LYP/6-31G*) calculations. The origin of apparently contradictory reports of 6-endo and 5-exo cyclizations is determined. Kinetic control favors 6-endo cyclization, while thermodynamic control gives 5-exo cyclization, and the observation of different products from different research groups arises from the difference in experimental conditions used by the two groups. The outcome of a new cyclization reaction was predicted by using these theoretical techniques. Kinetic control is predicted to yield exclusively the products of 6-endo cyclization, while thermodynamic control would lead to an approximately equal mixture of one 6-endo and one 5-exo cyclized product. Experimental studies revealed that the reaction yields only the products of 6-endo cyclization through kinetic control.
authors.affiliation: Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095-1569, USA.
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Leach
authors.forename: Renxiao
authors.initials: R
authors.lastname: Wang
authors.forename: G Erich
authors.initials: GE
authors.lastname: Wohlhieter
authors.forename: Saeed I
authors.initials: SI
authors.lastname: Khan
authors.forename: Michael E
authors.initials: ME
authors.lastname: Jung
authors.forename: K N
authors.initials: KN
authors.lastname: Houk
mesh_terms: D000475:Alkenes / Q000737:chemistry*; D018360:Crystallography, X-Ray; D003500:Cyclization; D003510:Cyclohexanes / Q000138:chemical synthesis / Q000737:chemistry*; D005609:Free Radicals / Q000737:chemistry; D007700:Kinetics; D008956:Models, Chemical; D008958:Models, Molecular; D008968:Molecular Conformation; D013379:Substrate Specificity; D013816:Thermodynamics
chemical_list: D000475:Alkenes; D003510:Cyclohexanes; D005609:Free Radicals; C117224:1-hexene