title: A Theoretical Mechanistic Study of the Asymmetric Desymmetrization of a Cyclic meso-Anhydride by a Bifunctional Quinine Sulfonamide Organocatalyst.
abstract: Cinchona alkaloids and their derivatives are widely used as organocatalysts in asymmetric synthesis. In particular, sulfonamide derivatives of cinchona alkaloids are highly enantioselective desymmetrization catalysts in the ring opening of a variety of cyclic anhydrides. To better understand the mechanism of catalysis, as well as to identify the basis for enantioselectivity by this catalyst, we have performed DFT calculations of this reaction with a cyclic meso anhydride. Herein, we report calculations for two reaction pathways, one concerted and one stepwise, for the production of each enantiomer of the desymmetrized product using the complete sulfonamide catalyst I. Our results are consistent with both the enantioselectivity of this transformation and the catalytic role of the quinuclidine moiety. We find that the stepwise pathway is the relevant pathway in the production of the major enantiomer. Our calculations highlight the role of differential distortion of the anhydride-methanol complex in the transition state as the factor leading to stereoselectivity.
authors.affiliation: Department of Chemistry, Carleton College , Northfield, Minnesota 55057, United States.
authors.forename: Katie
authors.initials: K
authors.lastname: Blise
authors.affiliation: Department of Chemistry, Carleton College , Northfield, Minnesota 55057, United States.
authors.forename: Milan W
authors.initials: MW
authors.lastname: Cvitkovic
authors.affiliation: Department of Chemistry, Carleton College , Northfield, Minnesota 55057, United States.
authors.forename: Nolly J
authors.initials: NJ
authors.lastname: Gibbs
authors.affiliation: Department of Chemistry, Carleton College , Northfield, Minnesota 55057, United States.
authors.forename: Sean F
authors.initials: SF
authors.lastname: Roberts
authors.affiliation: Department of Chemistry, Carleton College , Northfield, Minnesota 55057, United States.
authors.forename: Reid M
authors.initials: RM
authors.lastname: Whitaker
authors.affiliation: Department of Chemistry, Carleton College , Northfield, Minnesota 55057, United States.
authors.forename: Gretchen E
authors.identifier: 0000-0002-7858-2528
authors.initials: GE
authors.lastname: Hofmeister
authors.affiliation: Department of Chemistry, Carleton College , Northfield, Minnesota 55057, United States.
authors.forename: Daniela
authors.identifier: 0000-0001-7900-1660
authors.initials: D
authors.lastname: Kohen