Boshun Wan (???)

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Recent Advances for the Selective Synthesis of
Heterocycles
Boshun Wan (???) E-mail bswan_at_dicp.ac.cn
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Heterocycles for Sustainable Chemistry
Natural products
Pharmaceuticals
Heterocycles
Chemicals for RD
Polymer Materials
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Top 100 Brand Name Drugs by US Retail Sales in
2010
Heterocycles 50 Pyridine/Pyrrole 10
http//cbc.arizona.edu/njardarson/group/top-pharma
ceuticals-poster
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Overview of My Group
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Why Cycloadditon?
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Developed Catalytic Systems
Louie, J.
Saá, C.
Vollhardt
Takahashi, T.
CpCo
Ni/NHC
Zr/Ni
Generic description of the 6 factors
Metal-catalyzed 2 2 2 cycloaddition
Urabe, H.
Tanaka, K.
Ti(OiPr)4/iPrMgCl
Rh/P-P
Yamamoto, Y.
Guerchais, V.
Saá, C.
Zenneck, U.
CpRu
Fe(0)
Fe(I)
(a) Varela, J. A. Saá, C. Chem. Rev. 2003, 103,
3787. (b) Chopade, P. R. Louie, J. Adv. Synth.
Catal. 2006, 348, 2307. (c) Heller, B. Hapke, M.
Chem. Soc. Rev. 2007, 36, 1085. (d) Varela, J.
A. Saá, C. Synlett 2008, 2571. (e) Wang, C. X.
Li, X. C. Xu, F. Wan, B. S. Prog. Chem. 2010,
22, 610.
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Why Iron?
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Iron Catalytic System
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Problems and Solutions
Three crucial problems 1. Low-valent metal 2.
Substrate Coordination
Product Dissociation 3. Benzene byproducts
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Problems and Solutions
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Cycloaddition of Diynes and Unactivated Nitriles
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Cycloaddition of Diynes and Unactivated Nitriles
(Continued)
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Cycloaddition of Tetrayne
All-intramolecular Cycloaddition
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Cycloaddition of Alkynenitrile and Alkyne
Louie, J.
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Control Experiments
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Possible Pathways to Form Pyridines
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Iron-Catalyzed Cycloaddition
With Wang, C. X. Angew. Chem. Int. Ed. 2011, 50,
7162
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Cycloaddition of Alkynes and Nitriles in Water
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Ruthenium-catalyzed 222 Cycloaddition in Pure
Water
With Xu, F. ChemSusChem. 2012, 5, 854 (IF 6.325)
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Synthesis of Pyrroles via Cyclization
Entry R1 R2 R3 Yield ()
1 C6H5 C6H5 4-MeC6H4 97
2 3-MeC6H4 C6H5 4-MeC6H4 67
3 4-MeC6H4 C6H5 4-MeC6H4 89
4 4-FC6H4 C6H5 4-MeC6H4 97
5 2-CF3C6H4 C6H5 4-MeC6H4 82
6 2-ClC6H4 C6H5 4-MeC6H4 98
7 2-BrC6H4 C6H5 4-MeC6H4 96
8 C6H5 4-MeC6H4 4-MeC6H4 93
9 C6H5 4-FC6H4 4-MeC6H4 96
10 4-FC6H4 C6H5 C6H5 94
11 2-BrC6H4 C6H5 C6H5 95
12 C6H5 C6H5 4-MeC6H4 98
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Synthesis of Pyrroles via Cyclization
Entry R1 R2 R3 Yield ()
1 C6H5 C6H5 4-MeC6H4 97
2 3-MeC6H4 C6H5 4-MeC6H4 82
3 4-MeC6H4 C6H5 4-MeC6H4 95
4 4-FC6H4 C6H5 4-MeC6H4 94
5 2-CF3C6H4 C6H5 4-MeC6H4 94
6 2-ClC6H4 C6H5 4-MeC6H4 93
7 2-BrC6H4 C6H5 4-MeC6H4 90
8 C6H5 4-MeC6H4 4-MeC6H4 92
9 C6H5 4-FC6H4 4-MeC6H4 94
10 4-FC6H4 C6H5 C6H5 95
11 2-BrC6H4 C6H5 C6H5 88
12 C6H5 C6H5 4-MeC6H4 84
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Mechanism Study
"a" Migration
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Mechanism Study
Crossover Experiment
anticipated products
new products
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Mechanism Study
"ß" Migration
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Crossover Experiment
Competition Experiment
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Highly Regioselective Sulfonyl-Group Migration
Reactions
With Xin, X. Y. Angew. Chem. Int. Ed. 2012, 51,
1693.
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Summary
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