title: Mechanistic investigation of enediyne-connected amino ester rearrangement. Theoretical rationale for the exclusive preference for 1,6- or 1,5-hydrogen atom transfer depending on the substrate. A potential route to chiral naphthoazepines.
abstract: Memory of chirality (MOC) and deuterium-labeling studies were used to demonstrate that the cascade rearrangement of enediyne-connected amino esters 1a and 1b evolved through exclusive 1,5- or 1,6-hydrogen atom transfer, subsequent to 1,3-proton shift and Saito-Myers cyclization, depending on the structure of the starting material. These results were independently confirmed by DFT theoretical calculations performed on model monoradicals. These calculations clearly demonstrate that in the alanine series, 1,5-hydrogen shift is kinetically favored over 1,6-hydrogen shift because of its greater exergonicity. In the valine series, the bulk of the substituent at the nitrogen atom has a major influence on the fate of the reaction. N-Tosylation increases the barrier to 1,5-hydrogen shift to the benefit of 1,6-hydrogen shift. The ready availability of 1,6-hydrogen atom transfer was explored as a potential route for the enantioselective synthesis of naphthoazepines.
authors.affiliation: Institut de Chimie Radicalaire, CNRS UMR 7273, Equipes CMO and CTM, Aix-Marseille Université, 13397 Cedex 20, Marseille, France.
authors.forename: Damien
authors.initials: D
authors.lastname: Campolo
authors.forename: Anouk
authors.initials: A
authors.lastname: Gaudel-Siri
authors.forename: Shovan
authors.initials: S
authors.lastname: Mondal
authors.forename: Didier
authors.initials: D
authors.lastname: Siri
authors.forename: Eric
authors.initials: E
authors.lastname: Besson
authors.forename: Nicolas
authors.initials: N
authors.lastname: Vanthuyne
authors.forename: Malek
authors.initials: M
authors.lastname: Nechab
authors.forename: Michèle P
authors.initials: MP
authors.lastname: Bertrand