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Stereoselective Routes to Aziridines

Stereoselective Routes to Aziridines . Nate Bowling McMahon Group University of Wisconsin-Madison Sept. 12, 2002. Summary. Applications Uses for Optically Active Aziridines Addition of Nitrogen to Alkenes Nitrenes Atkinson-type Aziridinating Agents Asymmetric Aziridination Catalysis

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Stereoselective Routes to Aziridines

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  1. Stereoselective Routes to Aziridines Nate Bowling McMahon Group University of Wisconsin-Madison Sept. 12, 2002

  2. Summary • Applications • Uses for Optically Active Aziridines • Addition of Nitrogen to Alkenes • Nitrenes • Atkinson-type Aziridinating Agents • Asymmetric Aziridination Catalysis • Aziridinations using Already Existing Stereocenters • Sharpless Asymmetric Epoxidation and Dihydroxylation • Amino Alcohols • Other Routes to Stereoselectivity • Imines • Michael Addition • Azirines • Resolution

  3. The Basics of Aziridines • Ring Strain (SE) of 26.7 kcal/mol (R1-5 = H) • Oxirane = 26.3 kcal/mol • Cyclopropane = 27.5 kcal/mol • Inversion barrier of nitrogen (R1-5 = H) = 18.9 kcal/mol • Normal amines = 5- 6 kcal/mol • Usually only susceptible to ring opening by nuclephilic attack upon activation by: • Protonation • Quaternization • Lewis acid adduct • R5 = electron withdrawing substituent Tanner, D. Angew. Chem. Int. Ed. Engl.1994, 33, 599-619. Nielsen, I. M. B. J. Phys. Chem. A1998, 102, 3193-3201. Bach, R. D.; Dmitrenko, O. J. Org. Chem.2002, 67, 3884-3896.

  4. Uses of Optically Active Aziridines

  5. Stereocontrolled Synthesis of Alpha and Beta Amino Acids Through Aziridines Dubois, L.; Dodd, R. H. Tetrahedron1993, 49, 901-910.

  6. Stereocontrolled Formation of β-Substituted Phenyl Amino Acids Xiong, C.; Wang, W.; Cai, C.; Hruby, V. J. J. Org. Chem.2002, 67, 1399-1402.

  7. Carbapenem Antibiotics Through a β-Lactam Ring Closing Tanner, D.; Somfai, P. Tetrahedron1988, 44, 619-624.

  8. Proposed Mode of Action of Mitomycin C Na, Y.; Wang, S.; Kohn, H. J. Am. Chem. Soc.2002, 124, 4666-4677.

  9. Asymmetric Dihydroxylation with Aziridines Tanner, D.; Harden, A.; Johansson, F.; Wyatt, P.; Andersson, P. G. Acta Chem. Scand.1996, 50, 361-368.

  10. Nitrenes

  11. Nitrene Addition in Accordance with Skell’s Rule McConaghy, J. S.; Lwowski, W. J. Am. Chem. Soc.1967, 89, 2357-2364.

  12. Different Reaction Pathways of Singlet and Triplet Nitrenes Mishra, A.; Rice, S. N.; Lwowski, W. J. Org. Chem.1968, 33, 481-486.

  13. α-Elimination, Irradiation, and Thermal Syntheses of Nitrenes Fioravanti, S.; Loreto, M. A.; Pellacani, L.; Tardella, P. A. Tetrahedron Lett.1993, 34, 4353-4354. Fioravanti, S.; Pellacani, L.; Stabile, S.; Tardella, P. A. Tetrahedron1998, 54, 6169-6176. Bergmeier, S. C.; Stanchina, D. M. J. Org. Chem.1997, 62, 4449-4456. McConaghy, J. S.; Lwowski, W. J. Am. Chem. Soc.1967, 89, 2357-2364. Mishra, A.; Rice, S. N.; Lwowski, W. J. Org. Chem. 1968, 33, 481-486.

  14. Highly Diastereoselective Nitrene Addition Fioravanti, S.; Morreale, A.; Pellacani, L.; Tardella, P. A. J. Org. Chem.2002, 67, 4972-4974.

  15. The Thermolysis of Several Different Species Gives One Common Nitrene Atkinson, R. S.; Jones, D. W.; Kelly, B. J. J. Chem. Soc., Perkin Trans. 11991, 1344-1346.

  16. Atkinson-type Aziridinating Agents Atkinson, R. S.; Rees, C. W. J. Chem. Soc. (C)1969, 772-778. Anderson, D. J.; Gilchrist, T. L.; Horwell, D. C.; Rees, C. W. J. Chem. Soc. (C), 1970, 576-579.

  17. Oxidation of Atkinson-type Aziridinating Agents Gives Stereospecific Addition Atkinson, R. S.; Rees, C. W. J. Chem. Soc. (C)1969, 772-778. Anderson, D. J.; Gilchrist, T. L.; Horwell, D. C.; Rees, C. W. J. Chem. Soc. (C), 1970, 576-579.

  18. Invertomers When X is electron withdrawing, the inversion barrier is decreased. When X is electron donating, the inversion barrier is increased. Atkinson, R. S.; Malpass, J. R. J. Chem. Soc., Perkin Trans. 11977, 2242-2249.

  19. Kinetic v. Thermodynamic Invertomer Formation Atkinson, R. S. Tetrahedron1999, 55, 1519-1559.

  20. Non-bonding Interactions Atkinson, R. S.; Grimshire, M. J.; Kelly, B. J. Tetrahedron1989, 45, 2875-2886.

  21. Alternative Intermediate • Oxidation with Pb(OAc)4 at –20oC, and subsequent examination by NMR spectroscopy at -30oC revealed no presence of aziridine, but amino protons had disappeared. • Removal of Pb(OAc)4 from solution revealed the presence of a methyl singlet that had previously been overshadowed by the Pb(OAc)4 acetate signal. • Surmised that the reacting intermediate may not be nitrene, but acetoxyamino group instead. Atkinson, R. S.; Grimshire, M. J.; Kelly, B. J. Tetrahedron1989, 45, 2875-2886.

  22. Mechanistic Pathway from Proposed Intermediate Atkinson, R. S.; Williams, P. J. J. Chem. Soc., Perkin Trans. 11996, 1951-1956.

  23. Support for the Proposed Mechanism Atkinson, R. S.; Williams, P. J. J. Chem. Soc., Perkin Trans. 11996, 1951-1956.

  24. Stereochemical Control with the Aziridinating Agent Atkinson, R. S.; Coogan, M. P.; Lochrie, I. S. T. Tetrahedron Lett.1996, 37, 5179-5182.

  25. Diastereoselectivity Using Oppolzer’s Auxiliary Kapron, J. T.; Santarsiero, B. D.; Vederas, J. C. J. Chem. Soc., Chem. Commun.1993, 1074-1076.

  26. Asymmetric Aziridination Catalysts

  27. Catalytic Aziridination via Nitrenoid Intermediate ØNitrenoid intermediate allows for asymmetric aziridination under the influence of L* Li, Z.; Quan, R. W.; Jacobsen, E. N. J. Am. Chem. Soc.1995, 117, 5889-5890.

  28. Jacobsen Asymmetric Aziridination Catalyst Li, Z.; Quan, R. W.; Jacobsen, E. N. J. Am. Chem. Soc.1995, 117, 5889-5890.

  29. Enantioselective Katsuki Aziridination Catalyst Nishikori, H.; Katsuki, T. Tetrahedron Lett.1996, 37, 9245-9248.

  30. Stereoselective Routes to Aziridines Using Sharpless Asymmetric Epoxidation and Asymmetric Dihydroxylation Catalysts

  31. Sharpless Asymmetric Epoxidation Tanner, D. Angew. Chem. Int. Ed. Engl.1994, 33, 599-619.

  32. Epoxide to Aziridine via Staudinger reaction Sommerdijk, N. A. J. M.; Buynsters, P. J. J. A.; Akdemir, H.; Geurts, D. G.; Nolte, R. J. M.; Zwanenburg, B. J. Org. Chem.1997, 62, 4955-4960.

  33. Epoxide to Aziridine via Aza-Payne Reaction Urabe, H.; Aoyama, Y.; Sato, F. Tetrahedron1992, 48, 5639-5646. Moulines, J.; Charpentier, P.; Bats, J.-P.; Nuhrich, A.; Lamidey, A.-M. Tetrahedron Lett.1992, 33, 487-490.

  34. Retention of Epoxide Configuration Toshimitsu, A.; Abe, H.; Hirosawa, C.; Tamao, K. J. Chem. Soc., Perkin Trans. 11994, 3465-3471.

  35. Sharpless Asymmetric Dihydroxylation Tanner, D. Angew. Chem. Int. Ed. Engl.1994, 33, 599-619.

  36. Different Pathways From Homochiral 1,2-Cyclic Sulfates Lohray, B. B.; Gao, Y.; Sharpless, K. B. Tetrahedron Lett.1989, 30, 2623-2626.

  37. Chiral Aziridines from Amino Alcohols

  38. Okawa’s Aziridination Procedure From Amino Alcohols Nakajima, K.; Takai, F.; Tanaka, T.; Okawa, K. Bull. Chem. Soc. Jpn.1978, 51, 1577-1578.

  39. R1 R2 R3 R4 time/solvent Yield (%) C6H5CH2 H H CH3 2 h/ether 90 C6H5CH2 CH3 CH3 H 18 h/ether 89 Mitsunobu Reaction: Amino-Alcohol to Aziridine Pfister, J. R. Synthesis1984, 969-970.

  40. Preparation of Aziridines from the Mitsunobu Reaction of 1,2-Aminoalcohols Wipf, P.; Miller, C. P. Tetrahedron Lett.1992, 33, 6267-6270.

  41. Stereoselective Formation of Aziridines from Imines

  42. General Mechanism of Aziridine Formation from Imines

  43. High Diastereoselectivities From Sulfinimines in an Aza-Darzens Reaction Davis, F. A.; Liu, H.; Zhou, P.; Fang, T.; Reddy, G. V.; Zhang, Y. J. Org. Chem.1999, 64, 7559-7567.

  44. Rationale for Diastereoselectivity Davis, F. A.; Liu, H.; Zhou, P.; Fang, T.; Reddy, G. V.; Zhang, Y. J. Org. Chem.1999, 64, 7559-7567.

  45. Enantioselectivity Using the Imino Corey-Chaykovsky Reaction Saito, T.; Sakairi, M.; Akiba, D. Tetrahedron Lett.2001, 42, 5451-5454.

  46. Highly Diastereoselective Aziridination of Imines with Trimethylsilyldiazomethane Aggarwal, V. K.; Alonso, E.; Ferrara, M.; Spey, S. E. J. Org. Chem.2002, 67, 2335-2344.

  47. Ring Closing Pathway Aggarwal, V. K.; Alonso, E.; Ferrara, M.; Spey, S. E. J. Org. Chem.2002, 67, 2335-2344.

  48. Rationale for Cis-Selectivity Aggarwal, V. K.; Alonso, E.; Ferrara, M.; Spey, S. E. J. Org. Chem.2002, 67, 2335-2344.

  49. Utilization of Michael Addition in Aziridine Synthesis

  50. Highly Diastereoselective, Auxiliary Mediated, Gabriel-Cromwell reaction Garner, P.; Dogan, O.; Pillai, S. Tetrahedron Lett.1994, 35, 1653-1656.

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