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Ashley M. Berman

Transition-Metal Catalyzed Asymmetric Conjugate Addition of Organometallic Reagents. Ashley M. Berman. Introduction to the Asymmetric Conjugate Addition (ACA) of Organometallic Reagents. Powerful tool for the construction of C-C bonds

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Ashley M. Berman

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  1. Transition-Metal Catalyzed Asymmetric Conjugate Addition of Organometallic Reagents Ashley M. Berman

  2. Introduction to the Asymmetric Conjugate Addition (ACA) of Organometallic Reagents • Powerful tool for the construction of C-C bonds • Wide availability of Michael acceptors and organometallic reagents • Possibility to set multiple stereocenters in a single synthetic operation Pertinent Reviews: 1) Rossiter, B. E.; Swingle, N. Chem. Rev.1992, 92, 771. 2) Sibi, M. P.; Manyem, S. Tetrahedron2000, 56, 8033. 3) Krause, N.; Hoffmann-Röder, A. Synthesis2001, 2, 171. 4) Hayashi, T.; Yamasaki, K. Chem. Rev.2003, 103, 2829.

  3. A. Covalently Bound Chiral Auxiliaries Strategies for ACA Oppolzer, W.; Poli, G.; Kingma, A.; Starkemann, C.; Bernardinelli, G. Helv. Chim. Acta.1987, 70, 2201.

  4. B. Heterocuprates Preparation of Heterocuprates Corey, E. J.; Naef, R.; Hannon, F. J. J. Am. Chem. Soc.1986, 108, 7114.

  5. C. External Chiral Ligands Organocuprates RLi 1) Kanai, M.; Tomioko, K. TetrahedronLett.1994, 35, 895. 2) Asano, Y.; Iida, A.; Tomioko, K. Tetrahedron Lett.1997, 38, 8973.

  6. D. Transition-Metal Catalysis Cu/RMgX Catalytic System Strangeland, E. L.; Sammakia, T. Tetrahedron1997, 53, 16503.

  7. The Cu/R2Zn and Rh/RB(OH)2 catalytic systems have been the most thoroughly examined • These systems offer complimentary methods to 1,4 adducts

  8. The Cu/R2Zn Catalytic System A. Mechanistic Considerations

  9. Theoretical analysis of R2CuLi·LiCl conjugate addition FMO Interaction Nakamura, E.; Mori, S. Angew. Chem. Int. Ed.2000, 39, 3750.

  10. B. Ligand Development Pertinent Review: Alexakis, A.; Benhaim, C. Eur. J. Org. Chem.2002, 3221.

  11. 1. Trivalent Phosphorus Ligands Feringa’s Phosphoramidites De Vries, A. H. M; Meetsma, A.; Feringa, B. L. Angew. Chem. Int. Ed.1996, 35, 2374.

  12. 1) Feringa, B. L.; Pineschi, M.; Arnold, L. A.; Imbos, R.; de Vries, A. H. M.. Angew. Chem. Int. Ed.1997, 36, 2620. 2) Feringa, B. L. Acc. Chem. Res.2000, 33, 346.

  13. Ligands for ACA to cyclopentenone 1) Mandoli, A.; Arnold, L. A.; Salvadori, P.; Feringa, B. L. Tetrahedron Asymmetry2001, 12, 1929. 2) Escher, I. H.; Pfaltz, A. Tetrahedron2000, 56, 2879. 3) Liang, L.; Au-Yeung, T. L.; Chan, A. S. Org. Lett.2002, 4, 3799.

  14. TADDOL Derived Ligands Alexakis, A.; Burton, J.; Vastra, J.; Benhaim, C.; et. al. Eur. J. Org. Chem.2000, 4011.

  15. Miscellaneous Phosphorus Ligands 1) Reetz, M. T.; Gosberg, A.; Moulin, D. Tetrahedron Lett.2002, 43, 1189. 2) Yamanoi, Y.; Imamoto, T. J. Org. Chem. 1999, 64, 2988.

  16. 2. Peptide-Based Ligands Ligand for ACA to aliphatic enones (a) Absolute configuration not determined Mizutani, H.; Degrado, S. J.; Hoveyda, A. H. J. Am. Chem. Soc.2002, 124, 779.

  17. Ligand for ACA to Cyclic Trisubstituted Enones (a) Following base induced isomerization of 1,4 adduct Mizutani, H.; Degrado, S. J.; Hoveyda, A. H. J. Am. Chem. Soc.2002, 124, 13362.

  18. Other Peptide-Based Ligands Developed by Hoveyda 1) Degrado, S. J.; Mizutani, H.; Hoveyda, A. H. J. Am. Chem. Soc.2001, 123, 755. 2) Hird, A. W.; Hoveyda, A. H. Angew. Chem. Int. Ed.2003, 42, 1276.

  19. C. ACA to other Michael Acceptors 1. Nitroalkenes (Acyclic Substrates) Duursma, A.; Minnaard, A. J.; Feringa, B. L. J. Am. Chem. Soc.2003, 125, 3700.

  20. Conversion of 1,4 adducts into versatile chiral building blocks Duursma, A.; Minnaard, A. J.; Feringa, B. L. J. Am. Chem. Soc.2003, 125, 3700.

  21. Cyclic Substrates (a) Base induced isomerization to anti 1,4 adduct proceeds without lowering of enantiomeric excess Luchaco-Cullis, C. A.; Hoveyda, A. H. J. Am. Chem. Soc.2002, 124, 8192.

  22. Cyclic Substrates (continued) Luchaco-Cullis, C. A.; Hoveyda, A. H. J. Am. Chem. Soc.2002, 124, 8192.

  23. 2. N-Acyloxazolidinones Hird, A. W.; Hoveyda, A. H. Angew. Chem. Int. Ed.2003, 42, 1276.

  24. N-Acyloxazolidinones (continued) Hird, A. W.; Hoveyda, A. H. Angew. Chem. Int. Ed.2003, 42, 1276.

  25. D. Tandem Reactions • Following ACA, a chiral zinc enolate is generated • While commonly quenched with H2O, this enolate can likewise be trapped with other electrophiles

  26. 1. Alkylation of Zinc Enolates Mizutani, H.; Degrado, S. J.; Hoveyda, A. H. J. Am. Chem. Soc.2002, 124, 779.

  27. Alkylation of Zinc Enolates - Application in the Enantioselective Synthesis of Clavularin B Degrado, S. J.; Mizutani, H.; Hoveyda, A. H. J. Am. Chem. Soc.2001, 123, 755.

  28. 2. Allylation of Zinc Enolates Naasz, R.; Arnold, L. A.; Minnaard, A. J.; Feringa, B. L. Chem. Commun.2001, 735.

  29. 3. Silylation of Zinc Enolates Knopff, O.; Alexakis, A. Org. Lett.2002, 4, 3835.

  30. 4. Tandem 1,4 Addition/Aldol Reaction Arnold, L. A.; Naasz, R.; Minnaard, A. J.; Feringa, B. L. J. Org. Chem.2002, 67, 7244.

  31. Application in the Enantioselective Synthesis of (-) Prostaglandin E1 Methyl Ester Arnold, L. A.; Naasz, R.; Minnaard, A. J.; Feringa, B. L. J. Org. Chem.2002, 67, 7244.

  32. The Rh/RB(OH)2 Catalytic System A. Mechanistic Considerations

  33. Preparation of Key Intermediates in Catalytic Cycle Hayashi, T.; Takahashi, M.; Takaya, Y.; Ogasawara, M. J. Am. Chem. Soc.2002, 124, 5052.

  34. Model of Stereoinduction (BINAP System) Takaya, Y.; Ogasawara, M.; Hayashi, T. J. Am. Chem. Soc.1998, 120, 5579.

  35. B. Ligand Development 1) Reetz, M. T.; Moulin, D.; Gosberg, A. Org. Lett.2001, 3, 4083. 2) Boiteau, J.; Imbos, R.; Minnaard, A. J.; Feringa, B. L. Org. Lett.2003, 5, 681. 3) Kuriyama, M.; Nagai, K.; Yamada, K.; Miwa, Y.; Taga, T.; Tomioko, K. J. Am. Chem. Soc.2002, 124, 8932. 4) Hayashi, T.; Ueyama, K.; Tokunaga, N.; Yoshida, K.; J. Am. Chem. Soc.2003, 125, 11508.

  36. C. ACA to Enones Takaya, Y.; Ogasawara, M.; Hayashi, T. J. Am. Chem. Soc.1998, 120, 5579.

  37. Other cyclic enones Acyclic enones Takaya, Y.; Ogasawara, M.; Hayashi, T. J. Am. Chem. Soc.1998, 120, 5579.

  38. D. ACA to other Michael Acceptors 1. Nitroalkenes (Cyclic Substrates) Hayashi, T.; Senda, T.; Ogasawara, M. J. Am. Chem. Soc.2000, 122, 10716.

  39. Acyclic substrates Hayashi, T.; Senda, T.; Ogasawara, M. J. Am. Chem. Soc.2000, 122, 10716.

  40. Conversion of 1,4 adducts into versatile chiral building blocks Hayashi, T.; Senda, T.; Ogasawara, M. J. Am. Chem. Soc.2000, 122, 10716.

  41. 2. 1-Alkenylphosphonates Conversion to Optically Active Alkenes Hayashi, T.; Senda, T.; Takaya, Y.; Ogasawara, M. J. Am. Chem. Soc.1999, 121, 11591.

  42. 3. ,-Unsaturated Esters Takaya, Y.; Senda, T.; Kurushima, H.; Ogasawara, M.; Hayashi, T. Tetrahedron Asymmetry1999, 10, 4047.

  43. 4. ,-Unsaturated Amides Sakuma, S.; Miyaura, N. J. Org. Chem.2001, 66, 8944.

  44. Enantioselective Synthesis of 4-Aryl-2-Piperidinones Senda, T.; Ogasawara, M.; Hayashi, T. J. Org. Chem.2001, 66, 6852.

  45. E. ACA in the Absence of Water; Chiral Boron Enolates Yoshida, K.; Ogasawara, M.; Hayashi, T. J. Org. Chem.2003, 68, 1901.

  46. Mechanistic Considerations Yoshida, K.; Ogasawara, M.; Hayashi, T. J. Org. Chem.2003, 68, 1901.

  47. Chiral Titanium Enolates Hayashi, T.; Tokunaga, N.; Yoshida, K.; Han, J. W. J. Am. Chem. Soc.2002,124, 12102.

  48. Titanium Enolates (continued) Hayashi, T.; Tokunaga, N.; Yoshida, K.; Han, J. W. J. Am. Chem. Soc.2002,124, 12102.

  49. Conclusion • Numerous strategies have been developed for the ACA of organometallic reagents, including transition-metal catalysis • The Cu/R2Zn and Rh/RB(OH)2 catalytic systems offer complimentary methods to 1,4 adducts

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