The Palladium-Catalyzed Aerobic Kinetic Resolution of Secondary Alcohols: Reaction Development, Scope, and Applications
AuthorsEbner, Davidâ C.
Bagdanoff, Jeffreyâ T.
Ferreira, Ericâ M.
McFadden, Ryanâ M.
Caspi, Danielâ D.
Trend, Raissaâ M.
Stoltz, Brianâ M.
KAUST Grant NumberKUS-I1-006–02
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AbstractThe first palladium-catalyzed enantioselective oxidation of secondary alcohols has been developed, utilizing the readily available diamine (-)-sparteine as a chiral ligand and molecular oxygen as the stoichiometric oxidant. Mechanistic insights regarding the role of the base and hydrogen-bond donors have resulted in several improvements to the original system. Namely, addition of cesium carbonate and tert-butyl alcohol greatly enhances reaction rates, promoting rapid resolutions. The use of chloroform as solvent allows the use of ambient air as the terminal oxidant at 23 degrees C, resulting in enhanced catalyst selectivity. These improved reaction conditions have permitted the successful kinetic resolution of benzylic, allylic, and cyclopropyl secondary alcohols to high enantiomeric excess with good-to-excellent selectivity factors. This catalyst system has also been applied to the desymmetrization of meso-diols, providing high yields of enantioenriched hydroxyketones.
CitationEbner D, Bagdanoff J, Ferreira E, McFadden R, Caspi D, et al. (2009) The Palladium-Catalyzed Aerobic Kinetic Resolution of Secondary Alcohols: Reaction Development, Scope, and Applications. Chem Eur J 15: 12978–12992. Available: http://dx.doi.org/10.1002/chem.200902172.
SponsorsThe authors are grateful to the NDSEG (predoctoral fellowship to D.C.E.), the NSF (predoctoral fellowships to D.C.E. and E.M.F.), the University of California TRDRP (predoctoral fellowship to J.T.B.), Bristol-Myers Squibb Company (predoctoral fellowship to E.M.F.), the American Chemical Society Division of Organic Chemistry and Bristol-Myers Squibb Foundation (predoctoral fellowship to R.M.T.), Eli Lilly (predoctoral fellowships to D.D.C. and R.M.M.), the NIH-NIGMS (R01 GM65961-01), King Abdullah University of Science and Technology (KAUST, Award No. KUS-I1-006–02), California Institute of Technology, A. P. Sloan Foundation, the Dreyfus Foundation, Research Corporation, Abbott, Amgen, AstraZeneca, Boehringer-Ingelheim, GlaxoSmithKline, Johnson and Johnson, Eli Lilly, Merck, Novartis, Pfizer, and Roche for generous funding.
JournalChemistry - A European Journal
PubMed Central IDPMC2862982
CollectionsPublications Acknowledging KAUST Support
- Scope of enantioselective palladium(II)-catalyzed aerobic alcohol oxidations with (-)-sparteine.
- Authors: Mandal SK, Jensen DR, Pugsley JS, Sigman MS
- Issue date: 2003 May 30
- Palladium-catalyzed enantioselective oxidation of alcohols: a dramatic rate acceleration by Cs2CO3/t-BuOH.
- Authors: Bagdanoff JT, Ferreira EM, Stoltz BM
- Issue date: 2003 Mar 20
- Highly selective palladium catalyzed kinetic resolution and enantioselective substitution of racemic allylic carbonates with sulfur nucleophiles: asymmetric synthesis of allylic sulfides, allylic sulfones, and allylic alcohols.
- Authors: Gais HJ, Jagusch T, Spalthoff N, Gerhards F, Frank M, Raabe G
- Issue date: 2003 Sep 5
- Palladium-catalyzed aerobic oxidative kinetic resolution of alcohols with an achiral exogenous base.
- Authors: Mandal SK, Sigman MS
- Issue date: 2003 Sep 19
- Dual role of (-)-sparteine in the palladium-catalyzed aerobic oxidative kinetic resolution of secondary alcohols.
- Authors: Mueller JA, Jensen DR, Sigman MS
- Issue date: 2002 Jul 17