title: Isotope Effects Reveal the Mechanism of Enamine Formation in l-Proline-Catalyzed α-Amination of Aldehydes.
abstract: The mechanism of l-proline-catalyzed α-amination of 3-phenylpropionaldehyde was studied using a combination of experimental kinetic isotope effects (KIEs) and theoretical calculations. Observation of a significant carbonyl (13)C KIE and a large primary α-deuterium KIE support rate-determining enamine formation. Theoretical predictions of KIEs exclude the widely accepted mechanism of enamine formation via intramolecular deprotonation of an iminium carboxylate intermediate. An E2 elimination mechanism catalyzed by a bifunctional base that directly forms an N-protonated enamine species from an oxazolidinone intermediate accounts for the experimental KIEs. These findings provide the first experimental picture of the transition-state geometry of enamine formation and clarify the role of oxazolidinones as nonparasitic intermediates in proline catalysis.
authors.affiliation: Department of Chemistry, Binghamton University , Binghamton, New York 13902, United States.
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Ashley
authors.affiliation: Department of Chemistry, Binghamton University , Binghamton, New York 13902, United States.
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Hirschi
authors.affiliation: Department of Chemistry, Binghamton University , Binghamton, New York 13902, United States.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Izzo
authors.affiliation: Department of Chemistry, Binghamton University , Binghamton, New York 13902, United States.
authors.forename: Mathew J
authors.initials: MJ
authors.lastname: Vetticatt