title: Kinetic study of the 7-endo selective radical cyclization of N-tert-butyl-o-bromobenzylmethacryl amides: kinetic investigation of the cyclization and 1,7-hydrogen transfer of aromatic radicals.
abstract: A kinetic investigation of the radical cyclization of N-tert-butyl-o-bromobenzylmethacryl amides to give 2-benzazepines via 7-endo selective cyclization was undertaken. The aryl radical generated from the amide precursor by treatment with Bu3SnH gave the three compounds, which are a 7-endo cyclized adduct, a 6-exocyclized adduct, and a reduced product. The cyclization reactions under various Bu3SnH concentrations were traced by GC analysis. The 7-endo/6-exo selectivity was constant irrespective of variation in Bu3SnH concentration. These results revealed that regioselectivity is controlled in a kinetic manner and that there is no possibility of a neophyl rearrangement. The use of Bu3SnD revealed that 1,7-hydrogen transfer, in which an aryl radical abstracts a hydrogen atom from the methallylic methyl group, occurs during the reaction. Hydrogen abstraction from toluene, the reaction solvent, was also observed. The 1,7-transfer rate depended on the Bu3SnX (X = H or D), and the reaction kinetics was examined. The k(H)/k(D) value for the hydrogen abstraction of aryl radical from Bu3SnX (X = H or D) was estimated using 4-bromoanisol. The utilization of these values revealed the overall reaction kinetics and relative rates for the cyclization and reduction by Bu3SnX (X = H or D). Kinetic parameters for hydrogen abstraction from toluene by aryl radicals were also estimated.
authors.affiliation: Department of Applied Molecular Bioscience, Graduate School of Medicine, Yamaguchi University, Ube 755-8611, Japan. ak10@yamaguchi-u.ac.jp
authors.forename: Akio
authors.initials: A
authors.lastname: Kamimura
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kotake
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Ishihara
authors.forename: Masahiro
authors.initials: M
authors.lastname: So
authors.forename: Takahiro
authors.initials: T
authors.lastname: Hayashi
mesh_terms: D000178:Acrylamides / Q000737:chemistry*; D001593:Benzyl Compounds / Q000737:chemistry*; D003500:Cyclization; D006859:Hydrogen / Q000737:chemistry*; D007700:Kinetics; D015394:Molecular Structure; D010084:Oxidation-Reduction; D014050:Toluene / Q000737:chemistry*
chemical_list: D000178:Acrylamides; D001593:Benzyl Compounds; D014050:Toluene; D006859:Hydrogen