1. Transition-Metal-Catalyzed Denitrogenative Transannulation: Converting Triazoles into Other Heterocyclic Systems 杜宇鎏 2012.10.13

2. Page  2 2 1. Introduction  In this PPT, recent progress of the transition metal catalyzed denitrogenative transannulation of a triazole ring, which was discovered in 2007, is discussed.  1,2,3-Triazoles are important heterocyclic units endowed with a broad spectrum of biological activities. They have been extensively used in medicinal chemistry, biochemistry, and in material science.

3. Page  3 3 ◆ The Dimroth rearrangement 1)Otto Dimroth, Justus Liebig’s Annalen der Chemie, 1909, 364, 183-226. 2)Otto Dimroth, Walter Michaelis, Justus Liebig’s Annalen der Chemie, 1927, 459, 39-46.

4. Page  4 4  The position of this equilibrium depends upon several factors, such as temperature, solvent, and the nature of the substituent (R 1 ) at C 7 of the triazole ring.  The introduction of a halogen atom at C7 shifts the equilibrium to the right, which has been explained in terms of nonbonding repulsion between the lone pair of electrons on the halogen and nitrogen atom in the peri-position of the left. 1)G. Labb, Bull. Soc. Chim.Belg. 1990, 99, 281; 2)B. Abarca-Gonzlez, R. Ballesteros, F. Mojarred, G. Jones, D. J. Mouat, J. Chem. Soc. Perkin Trans. 1 1987, 1865.

5. Page  5 5 2. Transannulation of Pyridotriazoles 1) S. Chuprakov, Frank, W. Hwang, V. Gevorgyan, Angew. Chem. 2007, 119, 4841; Angew. Chem. Int. Ed. 2007, 46, 4757. 2) V. Bagheri, M. P. Doyle, J. Taunton, E. E. Claxton, J. Org. Chem. 1988, 53, 6158.

6. Page  6 6 S. Chuprakov, Frank, W. Hwang, V. Gevorgyan, Angew. Chem. 2007, 119, 4841; Angew. Chem. Int. Ed. 2007, 46, 4757. ◆ Transannulation with Alkynes and Nitriles

7. Page  7 7

8. Page  8 8 Proposed mechanism for transannulation of pyridotriazoles with alkynes and nitriles

9. Page  9 9 3. Transannulation of N-Sulfonyl-1,2,3-triazoles 3.1. Transannulation with Alkynes, Nitriles, and Alkenes T. Horneff, S. Chuprakov, N. Chernyak, V. Gevorgyan, V. V. Fokin, J. Am. Chem. Soc. 2008, 130, 14972.

10. Page  10 10 T. Miura, M. Yamauchi, M. Murakami, Chem. Commun. 2009, 1470. ◆ Nickel-catalyzed denitrogenative transannulation reaction of Nsulfonyl-1,2,3- triazoles with internal alkynes.

11. Page  11 11 ◆ Proposed reaction pathway ◆ Possible role of the Lewis acid: A promotion of the ring–chain tautomerization, or an acceleration of the reductive elimination of nickel.

12. Page  12 12 ◆ Transannulation of monocyclic triazoles with terminal alkynes into pyrroles B. Chattopadhyay, V. Gevorgyan, Org. Lett. 2011, 13, 3746.

13. Page  13 13 ◆ Unique spot ◆ Deuterium labeling experiment

14. Page  14 14 ◆ Proposed Mechanism

15. Page  15 15 ◆ An efficient three-component semi-one-pot synthesis of the pyrrole

16. Page  16 16 3.2 Synthesis of Rhodium(II) N-Triflyl Azavinyl Carbenes ◆ Sulfonylation reaction of 4-phenyl-NH-1,2,3-triazole N. Grimster, L. Zhang, V. V. Fokin, J. Am. Chem. Soc. 2010, 132, 2510.

17. Page  17 17 ◆ Larock’s indole synthesis 1) I. Nakamura, T. Nemoto, N. Shiraiwa, M. Terada, Org. Lett. 2009, 11, 1055 2) R. C. Larock, E. K. Yum, J. Am. Chem. Soc. 1991, 113, 6689 4. Transannulation of N-Aroylbenzotriazoles

18. Page  18 18 ◆ Proposed Mechanism

19. Page  19 19 5. Transannulation of 1,2,3-Benzotriazinones T. Miura, M. Yamauchi, M. Murakami, Org. Lett. 2008, 10, 3085

20. Page  20 20

21. Page  21 21 ◆ Transannulation of 1,2,3-benzotriazinones with allenes M. Yamauchi, M. Morimoto, T. Miura, M. Murakami, J. Am. Chem. Soc. 2010, 132, 54.

22. Page  22 22 ◆ The nature of the product varied depending upon the type of the phosphine ligand

23. Page  23 23 ◆ Asymmetric version

24. Page  24 24 ◆ Transannulation of benzotriazinones with 1,3-dienes and activated alkenes T. Miura, M. Morimoto, M. Yamauchi, M. Murakami, J. Org. Chem. 2010, 75, 5359.

25. Page  25 25 ◆ With symmetrical 1,3-dienes ◆ With unsymmetrical 1,3-dienes

26. Page  26 26 ◆ Transannulation with Isocyanides T. Miura, Y. Nishida, M. Morimoto, M. Yamauchi, M. Murakami, Org. Lett. 2011, 13, 1429.

27. Page  27 27 6. Transannulation of 1,2,3,4-Benzothiazinones ◆ Transannulation with Allenes T. Miura, M. Yamauchi, A. Kosaka, M. Murakami, Angew. Chem. 2010, 122, 5075; Angew. Chem. Int. Ed. 2010, 49, 4955.

28. Page  28 28 ◆ Highly diastereo- and enantioselective Rh(II)-catalyzed cyclopropanation Stepan Chuprakov, Sen Wai Kwok, Li Zhang, Lukas Lercher, and Valery V. Fokin, J. Am. Chem. Soc., 2009, 131, 18034–18035.

29. Page  29 29 ◆ Catalytic Asymmetric C-H Insertions of Rhodium(II) Azavinyl Carbenes Stepan Chuprakov, Jamal A. Malik, Mikhail Zibinsky, and Valery V. Fokin, J. Am. Chem. Soc. 2011, 133, 10352-10355

30. Page  30 30 ◆ Reactivity of N-(1,2,4-Triazolyl)-Substituted 1,2,3-Triazoles Mikhail Zibinsky and Valery V. Fokin, Org. Lett. 2011, 13, 4870-4872

31. Page  31 31 Conclusion ◆ The PPT highlights the increasing interest in the development of transition metal catalyzed transannulation reactions. ◆ Triazoles serves as a complimentary methodology for construction of heterocycles as it allows a general and highly efficient synthesis of complex and highly functionalized aromatic nitrogen heterocycles with diverse substitution patterns. ◆ Unsymmetrical approaches in this area have not been developed as complete as the symmetrical ones, which require more attentions and researches.

32. Thank You For Your Attention

33. Page  33 33 ◆ Proposed mechanism for transannulation of pyridotriazoles with alkynes and nitriles

34. Page  34 34 ◆ Proposed mechanism for the transannulation of N-sulfonyl-1,2,3-triazoles 17 with nitriles