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Organic Azides, an Overview Their synthesis, reactions and applications

Organic Azides, an Overview Their synthesis, reactions and applications. Literature Meeting / February 13, 2006 Guillaume Larouche Under supervision of Prof. André B. Charette Based, in part, on the review: Organic Azides: An Exploding Diversity of a Unique Class of Compounds

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Organic Azides, an Overview Their synthesis, reactions and applications

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  1. Organic Azides, an OverviewTheir synthesis, reactions and applications Literature Meeting / February 13, 2006 Guillaume Larouche Under supervision of Prof. André B. Charette Based, in part, on the review: Organic Azides: An Exploding Diversity of a Unique Class of Compounds Stefan Bräse, Carmen Gil, Kerstin Knepper and Viktor Zimmerman Angew. Chem. Int. Ed.2005, 44, 5188-5240

  2. OUTLINE 2 • Introduction, properties • Preparation of azides • Aryl azides • Alkenyl azides • Alkyl azides • Acyl azides • … • Reactivity of azides • Cycloadditions • Rearrangement • … • Conclusion

  3. INTRODUCTION 3 • Prepared first by Peter Grieß in 1864 (phenyl azide) followed by Curtius (hydrogen azide) • 1H-triazirine was the proposed structure which was rapidly revised in favor of the linear model • Most azides are explosive substances which decompose with the release of nitrogen ORTEP representation of 1,3,5-triazido-2,4,6-trinitrobenzene* *D. Adam, PhD Thesis, Ludwigs-Maximillians-Universität München (Germany), 2001

  4. INTRODUCTION 4 • Structure 1d explain the regioselectivity of the reactions with electrophiles (attacked by N1) and nucleophiles (attack on N3) • Structure 1c explain the facile decomposition into the corresponding nitrene and dinitrogen • Aromatic azides are stabilized by conjugation with the aromatic system

  5. PREPARATION OF AZIDES 5 • 1- Synthesis of Azides derivatives • In principle, 5 methods could achieve azide preparation: • Insertion of the N3 group (substitution or addition) • Insertion of an N2 group (diazo transfer) • Insertion of a nitrogen atom (diazotization) • Cleavage of triazines and analogous compounds • Rearrangement of azides

  6. PREPARATION OF AZIDES 6 1- Aryl Azides From Diazonium compounds: Drawback: preparation of the diazonium salt R. N. Butler, A. Fox, S. Collier, L. A. Burke, J. Chem. Soc. Perkin Trans. 2,1998, 2243 – 2247

  7. PREPARATION OF AZIDES 7 1- Aryl Azides From Diazonium compounds: 2 Azido-thalidomide S. M. Capitosti, T. P. Hansen, M. L. Brown, Org. Lett. 2003, 5, 2865 – 2867

  8. PREPARATION OF AZIDES 8 1- Aryl Azides From SNAr Reactions1: From Organometallic reagents2: 1C. K. Lowe-Ma, R. A. Nissan, W. S. Wilson, J. Org. Chem. 1990, 55, 3755 – 3761 2J. Gavenonis, T. D. Tilley, Organometallics,2002, 21, 5549 – 5563

  9. PREPARATION OF AZIDES 9 1- Aryl Azides From Diazo Transfer1: From Diazotization of Hydrazines3: :NH2R Also for alkyl azides2: 1Q. Liu, Y. Tor, Org. Lett.2003, 5, 2571 – 2572 2W. S. Horne, C. S. Stout, M. R. Ghadiri, J. Am. Chem. Soc. 2003, 125, 9372 – 9376 3Y. H. Kim, K. Kim, S. B. Shim, Tetrahedron Lett.1986, 27, 4749 – 4752

  10. PREPARATION OF AZIDES 10 2- Alkenyl Azides With Iodine Azide1: Addition on an aldehyde2: 1F. W. Fowler, A. Hassner, L. A. Levy, J. Am. Chem. Soc. 1967, 89, 2077 – 2082 2P. Molina, P. M. Fresneda, S. Delgado, J. Org. Chem. 2003, 68, 489 – 499

  11. PREPARATION OF AZIDES 11 3- Alkyl Azides Nucleophilic substitution: Substitution of an iodo atom with retention of configuration1 Asymmetric opening of an epoxide2 1D. Enders, D. Klein, Synlett.1999, 719 – 720 2L. E. Martínez, J. L. Leighton, D. H. Carsten, E. N. Jacobsen, J. Am. Chem. Soc. 1995, 117, 5897 – 5898

  12. PREPARATION OF AZIDES 12 3- Alkyl Azides By Mitsunobu reaction: Using DPPA: Not explosive 1S.-H. Lee, J. Yoon, S.-H. Chung, Y.-S. Lee, Tetrahedron2001, 57, 2139 – 2145 2B. Jiang, C.-G. Yang, J. Wang, J. Org. Chem. 2002, 67, 1396 – 1398

  13. PREPARATION OF AZIDES 13 3- Alkyl Azides 1,4 addition1,2: 1D. J. Guerin, T. E. Horstmann, S. J. Miller, Org. Lett. 1999, 1, 1107 – 1109 2T. Kawasaki, H. Enoki, K. Matsumura, M. Ohyama, M. Inagawa, M. Sakamoto, Org. Lett. 2000, 2, 3027 – 3029

  14. PREPARATION OF AZIDES 14 3- Alkyl Azides 1,2 addition to non-activated double bonds: Polar1: Radical2: 1L. Chabaud, Y. Landais, Tetrahedron Lett. 2003, 44, 6995 – 6998 2M. Tingoli, M. Tiecco, D. Chianelli, R. Balducci, A. Temperini, J. Org. Chem. 1991, 56, 6809 – 6813

  15. PREPARATION OF AZIDES 15 3- Alkyl Azides C-H activation1 (radical): Formation of allyl azides2: 1C. Viuf, M. Bols, Angew. Chem. Int. Ed.2001, 40, 623 – 625 2V. Atlan, S. Racouchot, M. Rubin, C. Bremer, J. Ollivier, A. de Meijere, J. SalaQn, Tetrahedron: Asymmetry.1998, 9, 1131 – 1135

  16. PREPARATION OF AZIDES 16 4- Acyl Azides: Highly reactive, used for the preparation of amides and heterocycles 1 71%-94% 2 3 1B. P. Banddgar, S. S. Pandit, Tetrahedron Lett. 2002, 43, 3413 – 3414 2A. Padwa, M. A. Brodney, B. Liu, K. Satake, T. Wu, J. Org. Chem. 1999, 64, 3595 – 3607 3H. Shao, M. Colucci, S. J. Tong, H. S. Zhang, A. L. Castelhano, Tetrahedron Lett. 1998, 39, 7235 – 7238

  17. AZIDES REACTIVITY 17 2- Reactions involving azides

  18. AZIDES REACTIVITY 18 1- Cycloadditions Triazolines: 1 18h, 40ºC 75% 2 Strained olefins and alkynes reacts readily, terminal alkenes react extremely slowly 1F. Avemaria, V. Zimmermann, S. Bräse, Synlett.2004, 1163 – 1166 2R. Ducray, M. A. Ciufolini, Angew. Chem. Int. Ed. 2002, 41, 4688 – 4691

  19. TMSOTf AZIDES REACTIVITY 19 1- Cycloadditions Triazolines: D. S. Reddy,W. R. Judd, J. Aubé, Org. Lett. 2003, 5, 3899 – 3902

  20. AZIDES REACTIVITY 20 1- Cycloadditions Enantioselective α-sulfamidation via triazolines: H. Vogt, S. Bräse, unpublished results

  21. AZIDES REACTIVITY 21 1- Cycloadditions Triazoles: T. R. Chan, R. Hilgraf, K. B. Sharpless, V. V. Fokin, Org. Lett. 2004, 6, 2853 – 2855

  22. AZIDES REACTIVITY 22 1- Cycloadditions Tetrazoles: Intermolecular1,2 Intramolecular3 1R. Huisgen, J. Org. Chem. 1968, 33, 2291 – 2297 2Z. P. Demko, K. B. Sharpless, J. Org. Chem. 2001, 66, 7945 – 7950 3Z. P. Demko, K. B. Sharpless, Org. Lett. 2001, 3, 4091 – 4094

  23. AZIDES REACTIVITY 23 1- Cycloadditions Tetrazoles: Ugi 4 component reaction Review: A. Domling, I. Ugi. Angew. Chem. Int. Ed. 2000, 39, 3168-3210

  24. AZIDES REACTIVITY 24 2- Nitrene Chemistry Azides can generate nitrenes thermally or photochemically Formation of 2H-azirines Y. S. P. alvarez, M. J. Alves, N. Z. Azoia, J. F. Bickley, T. L. Gilchrist, J. Chem. Soc. Perkin Trans. 1.2002, 1911 – 1919

  25. AZIDES REACTIVITY 25 2- Nitrene Chemistry: Asymmetric Diels-Alder with chiral auxiliary A. S. Timen, P. Somfai, J. Org. Chem. 2003, 68, 9958 – 9963

  26. AZIDES REACTIVITY 26 2- Nitrene Chemistry: Asymmetric Diels-Alder with chiral ligand Stoechiometric! A. S. Timen, P. Somfai, J. Org. Chem. 2003, 68, 9958 – 9963

  27. AZIDES REACTIVITY 27 2- Nitrene Chemistry Intramolecular cycloadditions:

  28. AZIDES REACTIVITY 28 2- Nitrene Chemistry Intramolecular cycloadditions: Biazirinyls synthesis K. Banert, F. KPhler, Angew. Chem. Int. Ed.2001, 40, 174 – 177

  29. AZIDES REACTIVITY 29 2- Nitrene Chemistry Intramolecular cycloadditions: 1 2 via 1S. C. Bergmeier,D. M. Stanchina, J. Org. Chem.1999, 64, 2852 – 2859 2Y. Naruta, N. Nagai, K. Maruyama, J. Chem. Soc. Perkin Trans. 1.1988, 1143 – 1148

  30. AZIDES REACTIVITY 30 2- Nitrene Chemistry Insertion into sp3 C-H bonds: 1 2 3 1H. Nozaki, S. Fujita, H. Takaya, R. Noyori, Tetrahedron. 1967, 23, 45 – 49 2D. F. Berndt, P. Norris, Tetrahedron Lett. 2002, 43, 3961 – 3962 3C. J. Moody, J. G. Ward, J. Chem. Soc. Perkin Trans. 1. 1984, 2895 – 2901

  31. AZIDES REACTIVITY 31 2- Nitrene Chemistry Rearrangement of Nitrenes: 1 2 1W. L. Karney, W. T. Borden, J. Am. Chem. Soc.1997, 119, 1378 – 1387 2K. Knepper, S. Bräse, unpublished results

  32. AZIDES REACTIVITY 32 3- Nucleophilic addition The Staudinger reduction: :PR3 1 Hydrogenation2: 1P. T. Nyffeler, C.-H. Liang, K. M. Koeller, C.-H. Wong, J. Am. Chem. Soc.2002, 124, 10 773 – 10778 2Y. Gaoni, J. Org. Chem. 1994, 59, 6853 – 6855

  33. AZIDES REACTIVITY 33 3- Nucleophilic addition Aza-Wittig reaction:

  34. AZIDES REACTIVITY 34 3- Nucleophilic addition Aza-Wittig reaction: Humm ??? P. Langer, I. Freifeld, H. Shojaei, Chem. Commun.2003, 3044 – 3045

  35. AZIDES REACTIVITY 35 3- Nucleophilic addition The iminophosphorane can also react with other electrophiles (ex: epoxides) In that case, an azetidine was created under Staudinger conditions S. Obika, J.-i. Andoh, M. Onoda, O. Nakagawa, A. Hiroto, T. Sugimoto, T. Imanishi, Tetrahedron Lett.2003, 44, 5267 – 5270

  36. AZIDES REACTIVITY 36 3- Nucleophilic addition Improved diazo transer method developed in the group R. P. Wurz, W. Lin, A. B. Charette, Tetrahedron Lett. 2003, 44, 8845 – 8848

  37. AZIDES REACTIVITY 37 4- Curtius and related rearrangement Curtius rearrangement:

  38. AZIDES REACTIVITY 38 4- Curtius and related rearrangement Curtius rearrangement: F. M. Menger, J. Bian, V. A. Azov, Angew. Chem. Int. Ed. 2002, 41, 2581 – 2584

  39. AZIDES REACTIVITY 39 4- Curtius and related rearrangement Curtius rearrangement: 34-75 % 56-70 % Robert T. Yu, Tomislav Rovis, J. Am. Chem. Soc.2006, ASAP

  40. AZIDES REACTIVITY 40 4- Curtius and related rearrangement Schmidt rearrangement: G. F. Alberici, J. Andrieux, G. Adam, M. M. Plat, Tetrahedron Lett.1983, 24, 1937 – 1940

  41. AZIDES REACTIVITY 41 5- Reactions of Azides with electrophiles Schmidt and Boyer reactions: Electrophile L. Kürti, B. Czakó, Strategic Applications of Named Reactions in Organic Synthesis, Elsevier Academic Press.2005, 758 p.

  42. AZIDES REACTIVITY 42 5- Reactions of Azides with electrophiles Schmidt and Boyer reactions: See Alex Lemire Literature meeting (Nov 8, 2004) for extended explanations on Aubé’s work 1J. Aubé, G. L. Milligan, J. Am. Chem. Soc. 1991, 113, 8965 – 8966 2K. Sahasrabudhe, V. Gracias, K. Furness, B. T. Smith, C. E. Katz, S. D. Reddy, J. Aubé, J. Am. Chem. Soc. 2003, 125, 7914 – 7922

  43. AZIDES REACTIVITY 43 5- Reactions of Azides with electrophiles Schmidt and Boyer reactions: Humm… again!? S. Lang, A. R. Kennedy, J. A. Murphy, A. H. Payne, Org. Lett.2003, 5, 3655 – 3658

  44. AZIDES REACTIVITY 44 6- Transformation into nitro and cyano group 1 80% - 98% yield On non-functionalized alkyl or aryl 2 Up to 60% yield 1S. Rozen, M. Carmeli, J. Am. Chem. Soc.2003, 125, 8118 – 8119 2R. Sasson, S. Rozen, Org. Lett,2005, 7, 2177 - 2179

  45. AZIDES REACTIVITY 45 7- Radical reactions 1D. S. Hays, G. C. Fu, J. Org. Chem. 1998, 63, 2796 – 2797 2S. Kim, G. H. Joe, J. Y. Do, J. Am. Chem. Soc.1993, 115, 3328 –3329

  46. AZIDES REACTIVITY 46 8- Azides for labelling Ex: Azido-thalidomide C. A. Gartner, Curr. Med. Chem. 2003, 10, 671 – 689

  47. CONCLUSION 47 Examples, from my bench… DPPA:

  48. CONCLUSION 48 Airbags… A useful application of azides

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