VanadiumCatalyzed Selenide Oxidation

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Vanadium-Catalyzed Selenide Oxidation with in
situ 2,3 Sigmatropic Rearrangement Scope and
Asymmetric Applications Campbell
Bourland February 6, 2002
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List of Abbreviations
e.e. d.e. TBHP CHP m-CPBA acac TBAF SOS
ASOS
enantiomeric excess ( major enantiomer - minor
enantiomer) diastereomeric excess ( major
diastereomer - minor diastereomer) tert-butyl
hydroperoxide cumene hydroperoxide meta-chlorope
rbenzoic acid acetyl acetonate tetrabutyl
ammoniumfluoride selenide oxidation with in situ
2,3 sigmatropic rearrangement asymmetric
selenide oxidation in situ 2,3 sigmatropic
rearrangement
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Importance of Allylic Alcohols
prostaglandins
Rapamycin
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Allylic Alcohols Useful as Precursors in Synthesis
Henbest and Wilsons Asymmetric Epoxdiation
Coreys Asymmetric Epoxidation
Henbest, H. B. Wilson, R. A. L. J. Chem. Soc.
1959, 1958. Corey, E. J. Dittami, J. P. J. Am.
Chem. Soc. 1985, 107, 256.
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Application of Selenides to Synthesis
The SOS reaction
Selenoxide Syn-Elmination to form alkene
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Traditional Methods for Selenide Oxidation
Wirth, T. Tetrahedron 1999, 55, 1.
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Selenoxide vs. Sulfoxide
Reich, H. J. et. al. J. Am. Chem. Soc. 1983, 105,
2503.
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Standard Protocol for Synthesis of the Allylic
Selenides
90-99
70-90
lt 95
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Development of Vanadium-Catalyzed SOS Reaction
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Utility of the Vanadium-Catazlyed SOS Reaction on
(E)-Substrates
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Carter, R. G. Bourland, T. C. J. Chem. Soc.
Chemm. Commun. 2000, 2031.
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Utility of the Vanadium-Catazlyed SOS Reaction on
Tri-Substituted and (Z) Substrates
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Effects of a Stereocenter on SOS Reaction
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Conclusion from Racemic SOS Reaction

• Conditions optimized for racemic series of
  Vanadium-catalyzed SOS reaction.
• System works on a wide variety of substrates.
• Good yields, short reaction times.
• Stereocenter does not effect SOS reaction.

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Fujitas Asymmetric Oxidation of Sulfides with
Salen-VO(acac)2
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Nokijima, K. Kojima, M. Fujita, J. Chem. Lett.
1986, 1433.
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Bolms Ligand-Based for Asymmetric Oxidation of
Sulfides
Bolm, C. Bienwald, F. Angew. Chem. Int. Ed.
Engl. 1995, 34, 2640.
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Two Chiral Events Occurring in SOS Reaction
Oxidation of selenide to chiral selenoxide
Rearrangement of chiral selenoxide to alcohol
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Endo vs. Exo Pathways

• Endo pathway appears to be favored by
  calculations and experimental results

Reich, H. J. et. al. J. Am. Chem. Soc. 1983, 105,
2503.
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Davis Oxidation of Selenides
oxaziridine
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Davis, F. A. Reddy, T. R. J. Org. Chem. 1992,
57, 2599.
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Davis Work in SOS Reaction

• Chiral induction from selenoxide to selenenate
  only 70-80 efficient.
• (Z)-Olefin geometry gives higher selectivity.
• Stereochemical outcome consistent with an endo
  transition state.

Davis, F. A. Reddy, T. R. J. Org. Chem. 1992,
57, 2599.
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Vanadium-Catalyzed ASOS Reaction
Ligand-Based Approach
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Selected Examples of Ligand-Based ASOS Reaction
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Problems with Ligand-Based System
L Chiral Schiff base ligand LB Chiral
Auxiliary containing a Lewis Base
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Auxiliary-Based System Used to Understand
Ligand-Based Systems
Auxiliary Approach
Ligand Approach
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Evans, D. A. et. al. J. Am. Chem. Soc. 1999,
121, 686.
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Williams Use of Auxiliary for Asymmetric
Oxidation of Sulfides
Williams, J. M. J. et. al. J. Chem. Soc. Perkin
Trans. 1 1996, 331.
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Examples of Auxiliaries Utilized in ASOS Reactions
(t-BuOCl instead of m-CPBA)
Reich, H. J. Yelm, K. E. J. Org. Chem. 1991, 56,
5672
Fujita, K. et. al. Synlett 1998, 987.
Uemura, S. et. al. J. Org. Chem. 1995, 60, 4114.
Koizumi, N. et. al. Tetrahedron 1997, 53, 12115
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Synthesis of Monodentate Auxiliaries Applied to
Vanadium-Catalyzed ASOS Reaction
50-74
50-74
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61-73
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ASOS Reaction with Mondentate Auxiliaries
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Results From Monodentate ASOS Reaction
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Camphor Based Monodentate Oxazoles
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Monodentate Auxillary with m-CPBA
Only 4 d.e.
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Williams Use of Auxiliary for Asymmetric
Oxidation of Sulfides
Williams, J. M. J. et. al. J. Chem. Soc. Perkin
Trans. 1 1996, 331.
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Synthesis of Bidentate Auxiliary System
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ASOS Reaction with Bidentate Auxiliary
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Methylated Serine-based Auxillary ASOS Reaction
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Bidentate Auxillary ASOS Reaction with Different
Metal Catalysts
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Threonine-Based Auxillary ASOS Reaction
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Synthesis of Epimeric Selenides
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Synthesis of Iso-Propyl Selenides
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ASOS Reaction with Iso-propyl Selenides
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Possible Explanation of Stereochemistry
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Conclusion
Racemic SOS reaction Developed the first
catalytic, metal-based method. Requires only
10 mol VO(acac)2 and applicable to a wide
range of substrates.
Vanadium-catalyzed, Auxiliary-Based ASOS
reaction Achieved up to 70 diastereomeric
excess (d.e.) with an oxazole-based
auxiliary. Laid the foundation for the
development of a ligand- based ASOS reaction
system.
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Acknowledgements
Committee Members
Lab Group
Dr. Rich Carter Dr. Mitch Avery Dr. Dan Mattern
Wei Zhang David Weldon Melissa Gronemeyer
Chrissy Castrichini Dr. and Mrs. Walter
Bourland Rachel Graves The Graves Clan Stacy
Jones Qun Zhu G-Flo and Big Serge Dr. Ismail
Ahmed Dr. Linda Spargo The University of
Mississippi
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