1. Synthesis, Characterization and Catalytic Application of N-Heterocyclic Carbene Copper(I) Complexes 學生：潘慶豪 指導教授：于淑君 博士 2005 / 07 / 21 國立中正大學 化學暨生物化學系 1

2. Outline N-Heterocyclic Carbene Copper(I) Complexes A 3 coupling Synthesis of N-sulfonylamidines 2

3. The Advantage of Copper 1. Price (USD 5g, Sigma-Adrich) 2. Abundance in Earth’s crustal (ppm) 3. Global copper recyclables use CuCl 2 FeCl 2 NiCl 2 PdCl 2 PtCl 2 ReCl 3 AgClAuClRuCl 2 3.1516.824.54227661131037.1960443 FeMnCuAgAuPtPdRuRh 41000950500.0070.00110.0030.00060.0010.0002 20042005200620072008200920102011 Total copper usage (10 6 Kg) 2232321988227532390623841226642453825003 Total scrap usage (10 6 Kg) 74647475833284488611743584428643 Recycling rate 34 % 37 %35 %36 %33 %34 %35 % ( The International Copper Study Group, ICSG) 3

4. N-Heterocyclic Carbenes vs. Phosphine Ligands Phosphine Ligands Strong σ-donor ligand Electronically and sterically tunable Air sensitive Thermal sensitive Environment pollution N-Heterocyclic Carbenes (NHCs) Strong σ-donor ligand Electronically and sterically tunable Air stable Thermal stable Environment friendly 4

5. Copper(I) N-Heterocyclic Carbene Complexes First Cu-NHC complex Silvia Dez-Gonzlez and Steven P. Nolan, Angew. Chem. Int. Ed., 2008, 47, 8881 –8884. Y = Cl, Br, I Y = NHC (if anion is PF 6 -, BF 4 -, OTf - ) Structures of Cu-NHC complexes with different anion 5 A. J. Arduengo III, H. V. R. Dias, J. C. Calabrese, F. Davidson, Organometallics, 1993, 12, 3405-3409. H. G. Raubenheimer, S. Cronje, P. J. Olivier, J. G. Toerien, P. H. van Rooyen, Angew. Chem., Int. Ed., 1994, 33, 672-673.

6. Copper(I) N-Heterocyclic Carbene Complexes in Catalysis A 3 -coupling Synthesis of N-sulfonylamidines Aziridination Hydroamination Carboxylation Carbonylation Olefination of aldehydes and ketones C(sp 3 )–C(sp 3 ) Bond cleavage Hydrosilylation reaction [3+2] Cycloaddition Allylic substitutions Allene synthesis Thiolation Conjugate addition 6

7. Motivation 1. Based on economic and conservation of environment standpoint, we use copper metal as the metal center of organometallic catalyst. 2. Using N-heterocyclic carbenes to replace phosphine ligands in organometallic catalysis. 3. Synthesis of a series of Cu(I)-NHC complexes with well-defined structures. 4. Using Cu(I)-NHC complexes to catalyze A 3 -coupling and synthesis of N-sulfonylamidines. 5. The application microwave as an alternative heat source to the conventional thermal heating method. 7

8. Synthesis of Imidazolium Synthesis of (Pybim)HBr (2) Synthesis of (Mesbim)HBr (4) 8

9. Three Synthetic Pathways to CuBr(Pybim) (6) 9

10. Synthesis of CuBr(Mesbim) (7) and [Cu(Pybim) 2 ]PF 6 (8) Synthesis of CuBr(Mesbim) (7) Synthesis of [Cu(Pybim) 2 ]PF 6 (8) 10

11. 1 H-NMR Spectra of (Pybim)HBr (2) and CuBr(Pybim) (6) 11 2 6

12. 1 H-NMR Spectra of (Mesbim)HBr (4) and CuBr(Mesbim) (7) 12 4 7

13. 1 H-NMR Spectra of (Pybim)HBr (2) and [Cu(Pybim) 2 ]PF 6 (8) 13 2 8

14. Atomic Absorption Spectral Data of CuBr(Pybim) (6) 14

15. Atomic Absorption Spectral Data of CuBr(Mesbim) (7) 15

16. Atomic Absorption Spectral Data of [Cu(Pybim) 2 ]PF 6 (8) 16

17. Infrared Spectra of CuBr(Pybim) (6) and [Cu(Pybim) 2 ]PF 6 (8) 17

18. Infrared Spectra of CuBr(Mesbim) (7) 18

19. ESI-Mass Spectral of CuBr(Pybim) (6) 19 (a)(a) (b)(b)

20. ESI-Mass Spectral of CuBr(Mesbim) (7) 20 (a)(a) (b)(b) 346.33

21. ESI-Mass Spectral of [Cu(Pybim) 2 ]PF 6 (8) 21 (a)(a) (b)(b)

22. EA Analysis of CuBr(Mesbim) (7) Element Calculated value (%) Experimental value (%) Deviation (%) N 7.26 6.650.61 C49.8149.940.13 H 5.75 6.050.30 22

23. Cu(I) N-Heterocyclic Carbene Catalyzed A 3 Coupling 23

24. Cu(I) N-Heterocyclic Carbene Catalyzed A 3 Coupling 24

25. Mechanism of A 3 coupling 25

26. Decomposition of Propargylamine 1.2 eq amine With cat. 0.2 eq amine With cat. 0.2 eq. amine Without cat. 26

27. Cu(I) N-Heterocyclic Carbene Catalyzed A 3 Coupling under MW Irradiation 27

28. Cu(I) N-Heterocyclic Carbene Catalyzed A 3 Coupling under MW Irradiation 28

29. Decomposition of Propargylamine 29

30. Cu(I) N-Heterocyclic Carbene Catalyzed Synthesis of N-sulfonylamidines 30

31. Cu(I) N-Heterocyclic Carbene Catalyzed Synthesis of N-sulfonylamidines 31

32. Mechanism of Synthesis of N-sulfonylamidines 32

33. Cu(I) N-Heterocyclic Carbene Catalyzed Synthesis of N-sulfonylamidines under MW Irradiation 33

34. Cu(I) N-Heterocyclic Carbene Catalyzed Synthesis of N-sulfonylamidines under MW Irradiation 34

35. Correlation of Amines pK b and Catalytic Yields 35

36. Correlation of Amines pK b and Catalytic Yields 36

37. Conclusions 1. We have successfully synthesized CuBr(Pybim) (6), CuBr(Mesbim) (7) and [Cu(Pybim) 2 ]PF 6 (8) complexes. Their structures were characterized by using NMR, AA, IR, EA and ESI-mass. 2. We have successfully demonstrated the catalytic activity of CuBr(Pybim) (6), CuBr(Mesbim) (7)and [Cu(Pybim) 2 ]PF 6 (8)on the A 3 -coupling and synthesis of N-sulfonylamidines. 3. Further acceleration of the Cu(I)-catalyzed the A 3 -coupling and synthesis of N-sulfonylamidines was achieved under microwave irradiation conditions. 37

38. 謝誌 指導老師 : 于淑君 博士 口試老師 : 梁 孟 博士 曾炳墝 博士 實驗室成員 : 張朝欽、陳盈源、蔡俊偉、李岳峰、 陳思婷、王建舜、林羲尹、葉蒨瑜 無機組全體成員 38

39. Phenylacetaldehyde react with CuBr(Pybim) (6) at catalytic condition 39

40. 1 H-NMR Spectra of Synthesis Test a b a b c c d d e e f f f f g g h h DCM b a c d e g h ff a b + d-CHCl 3 f e g h d c Acetone 40

41. Stability of Cu(I)-NHC Complexes 41

42. Three Way to The Form Byproduct ─ Urea 1. 2. 3. 42

43. Synthetic Utility of The A 3 -Coupling 1. A 3 -coupling as a key step in the synthesis of various imidazole derivatives A 3 -coupling Vsevolod A. Peshkov, Olga P. Pereshivko and Erik V. Van der Eycken, Chem. Soc. Rev., 2012, 41, 3790–3807. 43

44. Synthetic Utility of The A 3 -Coupling 2. Total synthesis of naamine family alkaloids A 3 -coupling Vsevolod A. Peshkov, Olga P. Pereshivko and Erik V. Van der Eycken, Chem. Soc. Rev., 2012, 41, 3790–3807. Nicholas S. Aberle, Guillaume Lessene, and Keith G. Watson, Org. Lett., 2006, 8, 419-421. Denis S. Ermolatev, Erik V. Van der Eycken, etc., Angew. Chem. Int. Ed., 2010, 49, 9465 –9468. 44

45. Application of Amidines As the backbone of drug and pesticide a As the precursor for heterocyclic ring b 45 a. Rauws, T. R. M.; Maes, B. U. W. Chem. Soc. Rev. 2012, 41, 2463. b. Connolly, D. J.; Cusack, D.; O'Sullivan, T. P.; Guiry, P. J. Tetrahedron 2005, 61, 10153.

46. Mechanism of Synthesis of N-sulfonylamidines 46

47. Microwave vs. Thermal Heating Antonio de la Hoz,A´ngel Dı´az-Ortiz and Andre´s Moreno, Chem. Soc. Rev., 2005, 34,164–178. Thermal heatingMicrowave 47