The Palladium-Catalyzed Aerobic Kinetic Resolution of Secondary Alcohols: Reaction Development, Scope, and Applications

Handle URI:
http://hdl.handle.net/10754/599944
Title:
The Palladium-Catalyzed Aerobic Kinetic Resolution of Secondary Alcohols: Reaction Development, Scope, and Applications
Authors:
Ebner, Davidâ C.; Bagdanoff, Jeffreyâ T.; Ferreira, Ericâ M.; McFadden, Ryanâ M.; Caspi, Danielâ D.; Trend, Raissaâ M.; Stoltz, Brianâ M.
Abstract:
The 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.
Citation:
Ebner 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.
Publisher:
Wiley-Blackwell
Journal:
Chemistry - A European Journal
KAUST Grant Number:
KUS-I1-006–02
Issue Date:
7-Dec-2009
DOI:
10.1002/chem.200902172
PubMed ID:
19904777
PubMed Central ID:
PMC2862982
Type:
Article
ISSN:
0947-6539; 1521-3765
Sponsors:
The 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.
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Full metadata record

DC FieldValue Language
dc.contributor.authorEbner, Davidâ C.en
dc.contributor.authorBagdanoff, Jeffreyâ T.en
dc.contributor.authorFerreira, Ericâ M.en
dc.contributor.authorMcFadden, Ryanâ M.en
dc.contributor.authorCaspi, Danielâ D.en
dc.contributor.authorTrend, Raissaâ M.en
dc.contributor.authorStoltz, Brianâ M.en
dc.date.accessioned2016-02-28T06:32:59Zen
dc.date.available2016-02-28T06:32:59Zen
dc.date.issued2009-12-07en
dc.identifier.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.en
dc.identifier.issn0947-6539en
dc.identifier.issn1521-3765en
dc.identifier.pmid19904777en
dc.identifier.doi10.1002/chem.200902172en
dc.identifier.urihttp://hdl.handle.net/10754/599944en
dc.description.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.en
dc.description.sponsorshipThe 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.en
dc.publisherWiley-Blackwellen
dc.subjectAlcoholsen
dc.subjectAsymmetric catalysisen
dc.subjectOxidationen
dc.subjectPalladiumen
dc.subjectSynthetic methodsen
dc.titleThe Palladium-Catalyzed Aerobic Kinetic Resolution of Secondary Alcohols: Reaction Development, Scope, and Applicationsen
dc.typeArticleen
dc.identifier.journalChemistry - A European Journalen
dc.identifier.pmcidPMC2862982en
dc.contributor.institutionThe Arnold and Mabel Beckman Laboratories of Chemical Synthesis, Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 E. California Blvd., MC 164-30, Pasadena, CA 91125, USA.en
kaust.grant.numberKUS-I1-006–02en
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