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Ring Expansion Reactions of Squaric Acid Derivatives

Ring Expansion Reactions of Squaric Acid Derivatives. Mary Robert Nahm April 16, 2004. PHOTOCHEMISTRY. BIOLOGY. ORGANIC SYNTHESIS. MATERIALS SCIENCE. Utilities. BIOLOGY. PHOTOCHEMISTRY. ORGANIC SYNTHESIS. MATERIALS SCIENCE. Utilities. antitumor properties protein inhibitors

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Ring Expansion Reactions of Squaric Acid Derivatives

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  1. Ring Expansion Reactions of Squaric Acid Derivatives Mary Robert Nahm April 16, 2004

  2. PHOTOCHEMISTRY BIOLOGY ORGANIC SYNTHESIS MATERIALS SCIENCE Utilities

  3. BIOLOGY PHOTOCHEMISTRY ORGANIC SYNTHESIS MATERIALS SCIENCE Utilities • antitumor properties • protein inhibitors • proton transfer Seto, C. T. Org. Lett. 2004, 6, 83-6. Takeda, S. J. Am. Chem. Soc. 2001, 123, 10468-74.

  4. PHOTOCHEMISTRY BIOLOGY • sensitizers for ZnO photoconductors • solar energy conversion ORGANIC SYNTHESIS MATERIALS SCIENCE Utilities Law, K-Y. Chem. Rev. 1993, 93, 449-86.

  5. PHOTOCHEMISTRY BIOLOGY • conjugated polymers having low HOMO-LUMO separation MATERIALS SCIENCE ORGANIC SYNTHESIS Utilities Ajayaghosh, A. Org. Lett. 2001, 3, 2595-8.

  6. PHOTOCHEMISTRY BIOLOGY • ring expansions • natural product synthesis ORGANIC SYNTHESIS MATERIALS SCIENCE Utilities

  7. Outline • Background • Thermolysis • Transition Metals • Radical-Mediated • Ionic Mechanism • Stereochemical Control • Summary

  8. Background • decomposition point of 293 oC • pKa1 = 1.0 and pKa2 = 2.2 • symmetrical aromatic dianion • C4 synthon Cohen, S. J. Am. Chem. Soc.1959, 81, 3480.

  9. Squaric Acid Synthesis Cohen, S. J. Am. Chem. Soc. 1959, 81, 3480. West, R. J. Am. Chem. Soc. 1963, 85, 2584. Paine, A. J. Tetrahedron Lett.1984, 25, 135.

  10. Dialkyl Squarates Cohen, S. J. Am. Chem. Soc. 1966, 88, 1533-5. Liebeskind, L. S. J. Org. Chem. 1988, 53, 2482-8. Moore, H. W. In Synthetic Utility of Cyclobutenediones; Halton, B., Ed.; JAI Press: Greenwich, CT, 1995; Vol. 4, pp 81-162.

  11. Ring Expansion Products

  12. Electrocyclic Cascade Houk, K. N. J. Am. Chem. Soc. 1985, 107, 2099-111. Houk, K. N. J. Org. Chem. 1996, 61, 2813-2825.

  13. Total Synthesis of Espintanol Moore, H. W. J. Org. Chem. 1996, 61, 6009-12.

  14. Ring-Fused Quinones Liebeskind, L. S. Tetrahedron, 1989, 45, 3053-60.

  15. Total Synthesis of Khellinone · Moore, H. W. J. Org. Chem.1987, 52, 3491-2.

  16. 1,6-Addition Moore, H. W. Tetrahedron Lett.1991, 32, 1129-32.

  17. Michael Addition Precursor The monoketal can now undergo Michael additions with heteroatom or carbon nucleophiles leading to the regiospecific synthesis of ring-expanded quinones. Moore, H. W. J. Org. Chem. 1994, 59, 3284-8.

  18. Heteroatom Nucleophiles Moore, H. W. J. Org. Chem. 1994, 59, 3284-8.

  19. Natural Product Synthesis Moore, H. W. J. Org. Chem. 1994, 59, 3284-8.

  20. Squaric Acid Chloride Maahs, G. Angew. Chem.1966, 78, 927. De Selms, R-C. Tetrahedron Lett. 1970, 781.

  21. Allylsilane Addition Eguchi, S. J. Chem. Soc., Perkin Trans. 11991, 2272.

  22. Silyl Enol Ether Addition Eguchi, S. J. Chem. Soc., Perkin Trans. 11991, 2272.

  23. Allyl Substituents Eguchi, S. Tetrahedron, 1994, 50, 7783-98.

  24. Acyl Substituents Eguchi, S. Tetrahedron, 1994, 50, 7783-98.

  25. Acyl Substituents X Eguchi, S. Tetrahedron, 1994, 50, 7783-98.

  26. Possible Mechanisms Eguchi, S. Tetrahedron, 1994, 50, 7783-98.

  27. Total Synthesis of (E)-Basidalin Eguchi, S. Tetrahedron, 1994, 50, 7783-98.

  28. Zwitterion Intermediate • proceed further to ring-contracted products due to instability of initially formed macrocycles Moore, H. W. J. Org. Chem. 1995, 60, 735-738.

  29. Spirocycles · Moore, H. W. J. Org. Chem. 1995, 60, 735-738.

  30. Cyclopentenediones Must protect hydroxyl group to avoid fragmentation: Moore, H. W. J. Org. Chem. 1995, 60, 735-738.

  31. Transition Metal Complexes Insertion-elimination sequence by reaction with low-valent cobalt reagent Liebeskind, L. S. Tetrahedron, 1989, 45, 3053-60. Liebeskind, L. S. Pure and Appl. Chem. 1988, 60, 27-34.

  32. Maleoylcobalt Mechanism Liebeskind, L. S. Pure and Appl. Chem. 1988, 60, 27-34.

  33. Cobalt Mediated Liebeskind, L. S. Tetrahedron, 1989, 45, 3053-60.

  34. Palladium(II)-Catalyzed Liebeskind, L. S. Tetrahedron, 1989, 45, 3053-60. Liebeskind, L. S. Pure and Appl. Chem. 1988, 60, 27-34.

  35. Observed Stereoselectivity X • Two factors: • reaction path proceeding through the most stabilized cationic intermediate • trans addition across the double bond Liebeskind, L. S. Tetrahedron, 1989, 45, 3053-60. Liebeskind, L. S. Pure and Appl. Chem. 1988, 60, 27-34.

  36. Rhodium(I)-Catalyzed Liebeskind, L.S. J. Am. Chem. Soc. 1993, 115, 4895-6.

  37. Proposed Mechanism

  38. Medium-Sized-Ring Synthesis Liebeskind, L.S. J. Am. Chem. Soc. 1993, 115, 4895-6.

  39. Radical Mediated Possible mechanism: · · · Eguchi, S. J. Org. Chem.1994, 59, 4707-9.

  40. Radical Mediated Will the phenyl group participate in a 6-exo-trig reaction? Possible mechanism: · · · Eguchi, S. J. Org. Chem.1994, 59, 4707-9.

  41. Examination of 5-exo-trig Case #1: Case #2: Eguchi, S. J. Am. Chem. Soc. 1995, 117, 9653-61.

  42. Other Oxidants Free radical mechanism undoubtedly participates Eguchi, S. J. Am. Chem. Soc. 1995, 117, 9653-61.

  43. Hypoiodites Eguchi, S. Tetrahedron Lett.1995, 36, 5539-42.

  44. Ionic Mechanism Eguchi, S. Tetrahedron Lett.1995, 36, 5539-42.

  45. Dimethyl Gloiosiphone A · · Paquette, L.A. J. Am. Chem. Soc. 1996, 118, 9456-7.

  46. Two-Fold Vinyl Anion Addition Paquette, L. A. J. Am. Chem. Soc. 1993, 115, 12189-90.

  47. Two-Fold Vinyl Anion Addition Paquette, L. A. J. Am. Chem. Soc. 1993, 115, 12189-90.

  48. Cis Addition [3,3] 1,2-addition [3,3] leading to the dianionic oxy-Cope pathway Paquette, L. A. J. Am. Chem. Soc. 1993, 115, 12189-90.

  49. 4p 8p Trans Addition leading to the electrocylic reaction channel 1,2-addition Paquette, L. A. J. Am. Chem. Soc. 1993, 115, 12189-90.

  50. 4p 8p trans addition is preferred Transannular Bonding 1,2-addition Paquette, L. A. J. Am. Chem. Soc. 1995, 117, 1451-2. Paquette, L. A. J. Am. Chem. Soc. 1993, 115, 12189-90.

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