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

Davidâ  C. Ebner; Jeffreyâ  T. Bagdanoff; Ericâ  M. Ferreira; Ryanâ  M. McFadden; Danielâ  D. Caspi; Raissaâ  M. Trend; Brianâ  M. Stoltz

doi:10.1002/chem.200902172

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

Davidâ C. Ebner, Jeffreyâ T. Bagdanoff, Ericâ M. Ferreira, Ryanâ M. McFadden, Danielâ D. Caspi, Raissaâ M. Trend, Brianâ M. Stoltz

Research output: Contribution to journal › Article › peer-review

66 Scopus citations

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.

Original language	English (US)
Pages (from-to)	12978-12992
Number of pages	15
Journal	Chemistry - A European Journal
Volume	15
Issue number	47
DOIs	https://doi.org/10.1002/chem.200902172
State	Published - Dec 7 2009
Externally published	Yes

Bibliographical note

KAUST Repository Item: Exported on 2020-10-01
Acknowledged KAUST grant number(s): KUS-I1-006–02
Acknowledgements: 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.
This publication acknowledges KAUST support, but has no KAUST affiliated authors.

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

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.",

author = "Ebner, {David{\^a} C.} and Bagdanoff, {Jeffrey{\^a} T.} and Ferreira, {Eric{\^a} M.} and McFadden, {Ryan{\^a} M.} and Caspi, {Daniel{\^a} D.} and Trend, {Raissa{\^a} M.} and Stoltz, {Brian{\^a} M.}",

note = "KAUST Repository Item: Exported on 2020-10-01 Acknowledged KAUST grant number(s): KUS-I1-006–02 Acknowledgements: 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. This publication acknowledges KAUST support, but has no KAUST affiliated authors.",

year = "2009",

month = dec,

day = "7",

doi = "10.1002/chem.200902172",

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T1 - The Palladium-Catalyzed Aerobic Kinetic Resolution of Secondary Alcohols: Reaction Development, Scope, and Applications

AU - Ebner, Davidâ C.

AU - Bagdanoff, Jeffreyâ T.

AU - Ferreira, Ericâ M.

AU - McFadden, Ryanâ M.

AU - Caspi, Danielâ D.

AU - Trend, Raissaâ M.

AU - Stoltz, Brianâ M.

N1 - KAUST Repository Item: Exported on 2020-10-01 Acknowledged KAUST grant number(s): KUS-I1-006–02 Acknowledgements: 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. This publication acknowledges KAUST support, but has no KAUST affiliated authors.

PY - 2009/12/7

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N2 - 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.

AB - 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.

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DO - 10.1002/chem.200902172

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JO - Chemistry - A European Journal

JF - Chemistry - A European Journal

IS - 47

ER -

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

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