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Lewis Basic Chiral Phosphine Organocatalysis

Lewis Basic Chiral Phosphine Organocatalysis. John Feltenberger Hsung Group University of Wisconsin – Madison January 29, 2009. Lewis Basic Organocatalysis.

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Lewis Basic Chiral Phosphine Organocatalysis

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  1. Lewis Basic Chiral Phosphine Organocatalysis John Feltenberger Hsung Group University of Wisconsin – Madison January 29, 2009

  2. Lewis Basic Organocatalysis “Lewis base catalysis is the process by which an electron pair donor increases the rate of a given chemical reaction by interacting with an acceptor atom in one of the reagents or substrates. Furthermore, the Lewis base should not be consumed or altered during the course of the reaction.” The binding event may enhance either the electrophilic or nucleophilic character of the bound species. n-π* interactions Denmark, S. E.; Beutner, G. L. Angew. Chem. Int. Ed. 2008, 47, 1560.

  3. Mode of Activation: n-π* • Michael-type additions 1,2-addition to carbonyls Enhances electrophilic character Enhances nucleophilic character Masks electrophilic character Denmark, S. E.; Beutner, G. L. Angew. Chem. Int. Ed. 2008, 47, 1560.

  4. Why Use Phosphines as Organocatalysts? Highly Tunable Electronics Sterics Source of Chirality Within groups attached to P P-Chirality Phosphorus Ligands in Asymmetric Catalysis; Börner, A., Ed.; Wiley-VCH: Weinheim ,2008

  5. Structure: Amines and Phosphines • Barrier to inversion • Acyclic phosphines retain chirality at room temp • Trigonal pyramidal structure • Non-bonded lone pair of electrons Rapid inversion No inversion at room temp Kölmel, C.; Ochsenfeld, C.; Ahlrichs, R. Theor. Chim. Acta1991, 82, 271.

  6. Nucleophilicity vs. Basicity nMeI = log(kY/kMeOH) where kY is the rate of reaction of Y with MeI in methanol at 25 °C Methot, J. L.; Roush, W. R. Adv. Synth. Catal. 2004, 346, 1035. Pearson, R. G.; Songstad, J. J. Am. Chem. Soc. 1967, 89, 1827.

  7. Phosphine Reactivity • Soft nucleophile – easily polarizable • Trialkyl phosphines are more nucleophilic, but air sensitive • Triaryl phosphines are less nucleophilic, but typically cheap and air stable Methot, J. L.; Roush, W. R. Adv. Synth. Catal. 2004, 346, 1035. Pearson, R. G.; Songstad, J. J. Am. Chem. Soc. 1967, 89, 1827.

  8. Typical Uses of Phosphines Nucleophile – Wittig Olefination Reducing Agent – Mitsunobu Reaction Ligand – Asymmetric Hydrogenation High yields, ee Wittig, G.; Schollkopf, U. Chem. Ber.1954, 97, 1318. Mitsunobu, O., Yamada, M. Bull. Chem. Soc. Jpn. 1967, 40, 2380. Kitamura, M., Ohkuma, T., Inoue, S., Sayo, N., Kumobayashi, H., Akutagawa, S., Ohta, T., Takaya, H., Noyori, R. J. Am. Chem. Soc. 1988, 110, 629.

  9. Michael-Type Reactions • Michael-Type • Enones • Morita-Baylis-Hillman • Aza-MBH • Ynones and Allenones • Umpolung γ- addition • [3 + 2] Cycloaddition • [4 + 2] Annulation • Michael-Type • Enones • Morita-Baylis-Hillman • Aza-MBH • Ynones and Allenones • Umpolung γ- addition • [3 + 2] Cycloaddition • [4 + 2] Annulation

  10. Morita-Baylis-Hillman Reaction Discovery by Morita, 1968 Proposed Mechanism Morita, K.; Suzuki, Z.; Hirose, H. Bull. Chem. Soc. Jpn.1968, 41, 2815.

  11. First ChiralPhosphine MBH Reaction • Low yield and ee • Long reaction time • Atmospheric Pressure Hayase, T.; Shibata, T.; Soai, K.; Wakatsuki, Y. Chem. Commun. 1998, 1271.

  12. Chiral Amine Catalyzed MBH High pressures necessary for higher enantioselectivity Bifunctional catalyst – improved enantioselectivity Oishi, T.; Oguri, H.; Hirama, M. Tetrahedron: Asymmetry, 1995, 6, 1241-1244. Iwabuchi, Y.; Nakatani, M.; Yokoyama, N.; Hatakeyama, S. J. Am. Chem. Soc.1999, 121, 10219-10220.

  13. BifunctionalPhosphine Activated Aza-MBH with MS 4Å Shi, M.; Chen, L.-H.; Li, C.-Q. J. Am. Chem. Soc.2005, 127, 3790.

  14. Modification of BifunctionalPhosphine (R)-2,2’ disubstituted 1,1’ binapthyl Shi, M.; Chen, L.-H.; Li, C.-Q. J. Am. Chem. Soc.2005, 127, 3790.

  15. Proposed Mechanism for the Aza-MBH Shi, M.; Chen, L.-H.; Li, C.-Q. J. Am. Chem. Soc.2005, 127, 3790.

  16. 31P NMR Analysis -13.16 ppm LB1 +25.30 ppm -13.16 ppm LB1 with MVK Phosphonium salt A +26.07 ppm Shi, M.; Chen, L.-H.; Li, C.-Q. J. Am. Chem. Soc.2005, 127, 3790.

  17. Michael-Type Reactions • Michael-Type • Enones • Morita-Baylis-Hillman • Aza-MBH • Ynones and Allenones • Umpolung γ- Addition • [3 + 2] Cycloaddition • [4 + 2] Annulation • Michael-Type • Enones • Morita-Baylis-Hillman • Aza-MBH • Ynones and Allenones • Umpolung γ- Addition • [3 + 2] Cycloaddition • [4 + 2] Annulation

  18. Alkyne to 1,3-Diene Isomerization Trost, B. M.; Kazmaier, U. J. Am. Chem. Soc.1992, 114, 7933. Guo, C.; Lu, X. J. Chem. Soc., Perkin Trans. 1 1993, 1921.

  19. Isomerization Reactivity • Catalytic acetic acid and higher temps necessary for esters and amides • Reactivity order: ketone > ester > amide • PBu3 was faster, but considerable oligomerization • No reaction was observed with tertiary amines Trost, B. M.; Kazmaier, U. J. Am. Chem. Soc.1992, 114, 7933.

  20. Phosphine-Catalyzed Umpolungγ-Additions Trost, B. M.; Li, C.-J. J. Am. Chem. Soc.1994, 116, 3167.

  21. Enantioselectiveγ-Addition to Ynoate Chen, Z.; Zhu, G.; Jiang, Q.; Xiao, D.; Cao, P.; Zhang, X. J. Org. Chem. 1998, 63, 5631.

  22. Enantioselective γ-Addition to Allenoate Chen, Z.; Zhu, G.; Jiang, Q.; Xiao, D.; Cao, P.; Zhang, X. J. Org. Chem. 1998, 63, 5631.

  23. Phosphine-Catalyzed [3 + 2] Cycloaddition No reaction with Et3N Zhang, C.; Lu, X. J. Org. Chem. 1995, 60, 2906.

  24. Amine Catalyzed Pathway Evans, C. A.; Miller, S. J. J. Am. Chem. Soc.2003, 125, 12394.

  25. Asymmetric [3 + 2] Cycloaddition Zhu, G.; Chen, Z.; Jiang, Q.; Xiao, D.; Cao, P.; Zhang, X. J. Am. Chem. Soc.1997, 119, 3836.

  26. Another Asymmetric [3 + 2] Cycloaddition Wilson, J. E.; Fu, G. C. Angew. Chem. Int. Ed. 2006, 45, 1426.

  27. Asymmetric Spirocyclization Wilson, J. E.; Fu, G. C. Angew. Chem. Int. Ed. 2006, 45, 1426.

  28. Phosphine-Containing α-Amino Acid Cowen, B. J.; Miller, S. J. J. Am. Chem. Soc.2007, 129, 10988.

  29. Deracemization of (±) Allenic Ester Cowen, B. J.; Miller, S. J. J. Am. Chem. Soc.2007, 129, 10988.

  30. Phosphine Catalyzed [4 + 2] Annulation Zhu, X-F.; Lan, J.; Kwon, O. J. Am. Chem. Soc.2003, 125, 4716.

  31. [4 + 2] Annulation Pathway Zhu, X-F.; Lan, J.; Kwon, O. J. Am. Chem. Soc.2003, 125, 4716.

  32. Asymmetric [4 + 2] Annulation Wurz, R. P.; Fu, G. C. J. Am. Chem. Soc. 2005, 127, 12234.

  33. Asymmetric [4 + 2] Annulation - Applications Wurz, R. P.; Fu, G. C. J. Am. Chem. Soc. 2005, 127, 12234.

  34. Conclusions • Advantages of Phosphine Catalysts • Tunability • Diversity of possible reactions • Source of chirality • Limitations • Air sensitive • Long reaction times • High catalyst loadings

  35. Acknowledgements • Professor Richard Hsung • Hsung group members • Practice talk attendees • -Andrew Lohse • - Grant Buchanan • - Jin Haek Yang • - Lauren Carlson • - Aaron Almeida • - Mike Giuliano • - Jay Steinkruger • - Christle Guevarra • - Dr. Ryuji Hayashi • Kat Myhre • Ashley Feltenberger

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