Recent Advances for the Selective Synthesis of Heterocycles Boshun Wan (万伯顺) E-mail: bswan@dicp.ac.cn

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

Heterocycles: ~50%; Pyridine/Pyrrole: ~10% Top 100 Brand Name Drugs by US Retail Sales in 2010 Heterocycles: ~50%; Pyridine/Pyrrole: ~10% http://cbc.arizona.edu/njardarson/group/top-pharmaceuticals-poster

Overview of My Group

Why Cycloadditon?

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 [2 + 2 + 2] 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, 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.

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

Iron Catalytic System

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

Problems and Solutions

Cycloaddition of Diynes and Unactivated Nitriles

Cycloaddition of Diynes and Unactivated Nitriles (Continued)

Cycloaddition of Tetrayne All-intramolecular Cycloaddition

Cycloaddition of Alkynenitrile and Alkyne Louie, J.

Control Experiments

Possible Pathways to Form Pyridines

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

Cycloaddition of Alkynes and Nitriles in Water

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

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

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

Mechanism Study "α" Migration

Mechanism Study Crossover Experiment anticipated products new products

Mechanism Study "β" Migration

Crossover Experiment Competition Experiment

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

Summary

苯并恶唑与不同磺酰肼的氧化偶联

苯并恶唑与不同磺酰肼的氧化偶联