1. Recent Advances for the Selective Synthesis of Heterocycles
Boshun Wan (万伯顺)

2. Heterocycles for Sustainable Chemistry
Natural products
Pharmaceuticals
Heterocycles
Chemicals for R&D
Polymer Materials

3. Heterocycles: ~50%; Pyridine/Pyrrole: ~10%
Top 100 Brand Name Drugs by US Retail Sales in 2010
Heterocycles: ~50%; Pyridine/Pyrrole: ~10%

4. Overview of My Group

5. Why Cycloadditon?

6. Generic description of the 6 factors
Developed Catalytic Systems
Saá, C.
Vollhardt
Takahashi, T.
Louie, J.
“CpCo”
“Zr/Ni”
“Ni/NHC”
Generic description of the 6 factors
Metal-catalyzed
[ ]
cycloaddition
Tanaka, K.
Urabe, H.
“Rh/P-P”
“Ti(OiPr)4/iPrMgCl”
Yamamoto, Y.
Saá, C.
Zenneck, U.
Guerchais, V.
“Cp*Ru”
“Fe(0)”
“Fe(+I)”
(a) Varela, J. A.; Saá, C. Chem. Rev. 2003, 103, (b) Chopade, P. R.; Louie, J. Adv. Synth. Catal. 2006, 348, (c) Heller, B.; Hapke, M. Chem. Soc. Rev. 2007, 36, (d) Varela, J. A.; Saá, C. Synlett 2008, (e) Wang, C. X.; Li, X. C.; Xu, F.; Wan, B. S. Prog. Chem. 2010, 22, 610.

7. Why Iron? 2011 Iron (0.02 US$/mol) Iron(I) complex Iron(0) complex
US$ per mol
Iron(I) complex
Iron(0) complex
2011

8. Iron Catalytic System

9. Problems and Solutions
Three crucial problems:
1. Low-valent metal
2. Substrate Coordination
&
Product Dissociation
3. Benzene byproducts

10. Problems and Solutions

11. Cycloaddition of Diynes and Unactivated Nitriles

12. Cycloaddition of Diynes and Unactivated Nitriles
(Continued)

13. Cycloaddition of Tetrayne
All-intramolecular Cycloaddition

14. Cycloaddition of Alkynenitrile and Alkyne
Louie, J.

15. Control Experiments

16. Possible Pathways to Form Pyridines

17. Iron-Catalyzed Cycloaddition
With Wang, C. X. Angew. Chem. Int. Ed. 2011, 50, 7162

18. Cycloaddition of Alkynes and Nitriles in Water

19. Ruthenium-catalyzed [2+2+2] Cycloaddition in Pure Water
With Xu, F. ChemSusChem. 2012, 5, 854 (IF 6.325)

20. Synthesis of Pyrroles via Cyclization
Entry R1 R2 R3
Yield (%) 1
C6H5
4-MeC6H4 97 2
3-MeC6H4 67 3 89 4
4-FC6H4 5
2-CF3C6H4 82 6
2-ClC6H4 98 7
2-BrC6H4 96 8 93 9 10 94 11 95 12

21. Synthesis of Pyrroles via Cyclization
Entry R1 R2 R3
Yield (%) 1
C6H5
4-MeC6H4 97 2
3-MeC6H4 82 3 95 4
4-FC6H4 94 5
2-CF3C6H4 6
2-ClC6H4 93 7
2-BrC6H4 90 8 92 9 10 11 88 12 84

22. Mechanism Study
"α" Migration

23. Mechanism Study
Crossover Experiment
anticipated products
new products

24. Mechanism Study
"β" Migration

25. Crossover Experiment
Competition Experiment

26. Highly Regioselective Sulfonyl-Group Migration Reactions
With Xin, X. Y. Angew. Chem. Int. Ed. 2012, 51, 1693.

27. Summary

28. 苯并恶唑与不同磺酰肼的氧化偶联

29. 苯并恶唑与不同磺酰肼的氧化偶联