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Samarium(II) Iodide Mediated Sequential Reactions

Samarium(II) Iodide Mediated Sequential Reactions. Roy Bowman January 16, 2004. Sequential Reactions. Multiple bonds formed in a one pot process No need to collect and purify intermediates Access to elaborate products

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Samarium(II) Iodide Mediated Sequential Reactions

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  1. Samarium(II) Iodide MediatedSequential Reactions Roy Bowman January 16, 2004

  2. Sequential Reactions • Multiple bonds formed in a one pot process • No need to collect and purify intermediates • Access to elaborate products • Although conceptually attractive, design of sequential reactions can be overwhelming • Cationic, anionic, radical, pericyclic, carbenoid, and transition metal catalyzed sequential processes have been realized Molander, G. A.; Harris, C. R. Tetrahedron 1998, 54, 3321-3354.

  3. Samarium(II) Iodide Totleben, M. J.; Curran, D. P.; Wipf, P. Journal of Organic Chemistry 1992, 57, 1740-4. Concellon, J. M.; Rodriguez-Solla, H.; Bardales, E.; Huerta, M. European Journal of Organic Chemistry 2003, 1775-1778 • Typically generated and utilized in situ • Most stable as Sm(III)

  4. Samarium(II) Iodide Girard, P.; Namy, J. L.; Kagan, H. B. Journal of the American Chemical Society 1980, 102, 2693-8.

  5. Samarium(II) Iodide Promotes several individual reactions important in synthesis: - Radical Cyclizations - Ketyl-Olefin Coupling - Pinacolic Coupling - Barbier Type Reactions - Aldol Type Reactions - Reformatsky Type Reactions - Conjugate Additions - Nucleophilic Acyl Substitutions -Cycloadditions

  6. Samarium(II) Iodide Ability to promote both one and two electron processes • Radical/Anionic • Anionic/Radical • Anionic/Anionic • Radical/Radical

  7. Reactivity Reactivity can be manipulated using: • Co-solvents: HMPA, TMG, DBU • Additives: Ni(II), Fe(III) • Irradiation of the reaction mixture • Allows for highly selective and efficient sequential reactions to be effective Molander, G. A.; McKie, J. A. Journal of Organic Chemistry 1992, 57, 3132-9. Cabri, W.; Candiani, I.; Colombo, M.; Franzoi, L.; Bedeschi, A. Tetrahedron Letters 1995, 36, 949-52. Ogawa, A.; Sumino, Y.; Nanke, T.; Ohya, S.; Sonoda, N.; Hirao, T. Journal of the American Chemical Society 1997, 119, 2745-2746. Machrouhi, F.; Hamann, B.; Namy, J. L.; Kagan, H. B. Synlett 1996, 633-634.

  8. Radical Cyclization/Carbonyl Addition • Unclear how carbonyl addition proceeded • Barbier or Grignard type reaction? Curran, D. P.; Totleben, M. J. Journal of the American Chemical Society 1992, 114, 6050-8.

  9. Formation of Organosamarium Curran, D. P.; Totleben, M. J. Journal of the American Chemical Society 1992, 114, 6050-8.

  10. Formation of Organosamarium Samarium-Barbier Conditions: Addition of O-Allyl-iodobenzene and acetophenone to a THF solution containing Samarium diiodide and HMPA Samarium-Grignard Conditions: Iodobenzene was added to a solution of SmI2/HMPA after; 5 minutes acetophenone was added Curran, D. P.; Totleben, M. J. Journal of the American Chemical Society 1992, 114, 6050-8.

  11. Radical Cyclization/Carbonyl Addition Molander, G. A.; Harring, L. S. Journal of Organic Chemistry 1990, 55, 6171-6.

  12. Radical Cyclization/Carbonyl Addition Curran, D. P.; Totleben, M. J. Journal of the American Chemical Society 1992, 114, 6050-8.

  13. Radical Cyclization/Carbonyl Addition • Pendent ester activates ketone • Control of three stereocenters • Forming radical is trans to ketyl oxygen Molander, G. A.; Kenny, C. Journal of Organic Chemistry 1991, 56, 1439-45.

  14. Radical Cyclization/Carbonyl Addition Molander, G. A.; Kenny, C. Journal of Organic Chemistry 1991, 56, 1439-45.

  15. Radical Cyclization/Nucleophilic Addition • Facile cyclization was achieved with unactivated ketones Molander, G. A.; McKie, J. A. Journal of Organic Chemistry 1992, 57, 3132-9.

  16. Radical Cyclization/ Nucleophilic Addition Molander, G. A.; McKie, J. A. Journal of Organic Chemistry 1992, 57, 3132-9.

  17. Radical Cyclization/ Nucleophilic Addition Molander, G. A.; McKie, J. A. Journal of Organic Chemistry 1992, 57, 3132-9.

  18. Intramolecular Nucleophilic Acyl Substitution/Intramolecular Barbier Cyclization • Provides access to a variety of bi- and tri-cyclic ring systems Molander, G. A.; Harris, C. R. Journal of the American Chemical Society 1995, 117, 3705-16.

  19. Intramolecular Nucleophilic Acyl Substitution/Intramolecular Barbier Cyclization • Ability to sequence formation of the organosamarium species so carbon-carbon bonds may be directed • Alkyl halides are reduced in the order I > Br > Cl • Sequences where order is unimportant are performed with diiodides • Sequenced reactions in which side chain reaction order is significant are performed with alkyl iodide/alkyl chloride substrates Molander, G. A.; Harris, C. R. Journal of the American Chemical Society 1995, 117, 3705-16.

  20. Intramolecular Nucleophilic Acyl Substitution/Intramolecular Barbier Cyclization Molander, G. A.; Harris, C. R. Journal of the American Chemical Society 1995, 117, 3705-16.

  21. Nucleophilic Acyl Substitution/Ketyl Olefin Coupling for Preparation of Oxygen Heterocycles • Provides access to bi- and tricyclic furans an pyrans Molander, G. A.; Harris, C. R. Journal of Organic Chemistry 1997, 62, 2944-2956.

  22. Nucleophilic Acyl Substitution/Ketyl Olefin Coupling Molander, G. A.; Harris, C. R. Journal of Organic Chemistry 1997, 62, 2944-2956.

  23. Nucleophilic Acyl Substitution/Ketyl Olefin Coupling Molander, G. A.; Harris, C. R. Journal of Organic Chemistry 1997, 62, 2944-2956.

  24. Ketyl-Olefin Coupling/β-Elimination • Result is net addition of an alkenyl moiety to a carbonyl group • Complementary to traditional alkylation techniques Molander, G. A.; Harris, C. R. Journal of Organic Chemistry 1998, 63, 812-816.

  25. Ketyl-Olefin Coupling/β-Elimination Molander, G. A.; Harris, C. R. Journal of Organic Chemistry 1998, 63, 4374-4380.

  26. Nucleophilic Acyl Substitution/Alkenyl Transfer Reactions • Provides cyclic products from acyclic starting materials Molander, G. A.; Harris, C. R. Journal of Organic Chemistry 1998, 63, 4374-4380.

  27. Nucleophilic Acyl Transfer/Alkenyl Transfer Reactions Molander, G. A.; Harris, C. R. Journal of Organic Chemistry 1998, 63, 4374-4380.

  28. Nucleophilic Acyl Transfer/Alkenyl Transfer Reactions Molander, G. A.; Harris, C. R. Journal of Organic Chemistry 1998, 63, 4374-4380.

  29. Nucleophilic Acyl Transfer/Alkenyl Transfer Reactions Molander, G. A.; Harris, C. R. Journal of Organic Chemistry 1998, 63, 4374-4380.

  30. Epoxide Ring Opening/Ketyl Olefin Coupling • Complete selectivity was achieved through chelation of the ketyl • oxygen and the hydroxyl group Molander, G. A.; Harris, C. R. Journal of Organic Chemistry 1997, 62, 2944-2956.

  31. Domino Epoxide Ring Opening/Ketyl Olefin Coupling Reactions Molander, G. A.; Harris, C. R. Journal of Organic Chemistry 1997, 62, 2944-2956.

  32. Domino Epoxide Ring Opening/Ketyl Olefin Coupling Reactions Molander, G. A.; Harris, C. R. Journal of Organic Chemistry 1997, 62, 2944-2956.

  33. Domino Epoxide Ring Opening/Ketyl Olefin Coupling Reactions Molander, G. A.; Harris, C. R. Journal of Organic Chemistry 1997, 62, 2944-2956.

  34. Epoxide Fragmentation/Tandem Radical Cyclizations Molander, G. A.; Del Pozo Losada, C. Tetrahedron 1998, 54, 5819-5832.

  35. Epoxide Fragmentation/Tandem Radical Cyclizations Molander, G. A.; Del Pozo Losada, C. Tetrahedron 1998, 54, 5819-5832.

  36. Epoxide Fragmentation/Tandem Radical Cyclizations Molander, G. A.; Del Pozo Losada, C. Tetrahedron 1998, 54, 5819-5832.

  37. Epoxide Fragmentation/Tandem Radical Cyclizations Molander, G. A.; Del Pozo Losada, C. Tetrahedron 1998, 54, 5819-5832.

  38. Intramolecular Barbier Cyclization/Grob Fragmentation • Stereospecific with regard to the leaving group • Stereochemistry of the alkoxide plays no role in • the stereochemistry of the fragmentation • Fragmentation proceeds under mild conditions Molander, G. A.; Le Huerou, Y.; Brown, G. A. Journal of Organic Chemistry 2001, 66, 4511-4516.

  39. Ring Expansion by Grob Fragmentation Mediated by SmI2 Molander, G. A.; Le Huerou, Y.; Brown, G. A. Journal of Organic Chemistry 2001, 66, 4511-4516.

  40. Ring Expansion by Grob Fragmentation Mediated by SmI2 Molander, G. A.; Le Huerou, Y.; Brown, G. A. Journal of Organic Chemistry 2001, 66, 4511-4516.

  41. Reformatsky/Nucleophilic Acyl Substitution • Provides an efficient route to functionalized 8 and 9 membered carbocycles Molander Gary, A.; Brown Giles, A.; Storch de Gracia, I. Journal of Organic Chemistry 2002, 67, 3459-63.

  42. Reformatsky/Nucleophilic Acyl Substitution • Diastereoselectivity of sequential process originates in the initial • Reformatsky reaction • Selectivity results from highly organized transition state Molander Gary, A.; Brown Giles, A.; Storch de Gracia, I. Journal of Organic Chemistry 2002, 67, 3459-63.

  43. Reformatsky/Nucleophilic Acyl Substitution Molander Gary, A.; Brown Giles, A.; Storch de Gracia, I. Journal of Organic Chemistry 2002, 67, 3459-63.

  44. Reformatsky/Nucleophilic Acyl Substitution Molander Gary, A.; Brown Giles, A.; Storch de Gracia, I. Journal of Organic Chemistry 2002, 67, 3459-63.

  45. Transformation of Carbohydrate Derivatives into Cyclopentanols Grove, J. J. C.; Holzapfel, C. W.; Williams, D. B. G. Tetrahedron Letters 1996, 37, 5817-5820.

  46. Transformation of Carbohydrate Derivatives into Cyclopentanols Grove, J. J. C.; Holzapfel, C. W.; Williams, D. B. G. Tetrahedron Letters 1996, 37, 5817-5820.

  47. Insertion of Isocyanides into Organic Halides Preparation of a-Hydroxy Ketones • Facile synthesis of a-hydroxy ketones by samarium mediated coupling of • organic halides , 2,6-xylyl isocyanide, and carbonyl compounds • a-Addition of organosamarium to isocyanide forms an (a-iminoalkyl)samarium • complex which can act as an acyl anion equivalent • Compatibility with a variety of functional groups under mild conditions Murakami, M.; Kawano, T.; Ito, Y. Journal of the American Chemical Society 1990, 112, 2437-9. Murakami, M.; Kawano, T.; Ito, H.; Ito, Y. Journal of Organic Chemistry 1993, 58, 1458-65.

  48. Insertion of Isocyanides into Organic Halides Preparation of a-Hydroxy Ketones Murakami, M.; Kawano, T.; Ito, H.; Ito, Y. Journal of Organic Chemistry 1993, 58, 1458-65.

  49. Insertion of Isocyanides into Organic Halides Preparation of a-Hydroxy Ketones Murakami, M.; Kawano, T.; Ito, H.; Ito, Y. Journal of Organic Chemistry 1993, 58, 1458-65.

  50. Insertion of Isocyanides into Organic Halides Preparation of a-Hydroxy Ketones Murakami, M.; Kawano, T.; Ito, H.; Ito, Y. Journal of Organic Chemistry 1993, 58, 1458-65.

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