學生：洪柏楷 指導教授：于淑君 博士

1. Synthesis and Characterization of N-Heterocyclic Carbene Palladium(II)Complexes. The Catalytic Application on Strecker Synthesis ofα-aminonitriles 學生：洪柏楷 指導教授：于淑君　博士 2010 / 05 / 17 Department of Chemistry & Biochemistry Chung Cheng University

2. Phosphine Ligand • Phosphines are electronically and sterically tunable. • Expensive. • Air/water sensitive and thermally unstable. • Metal leaching. • Chemical waste - water bloom. 25 mL 211.5 USD 100 mL 31.9 USD 25 G 396 USD 10G 135.5USD

3. N-Heterocyclic Carbenes [M] • NHCs are stronger σ-donor and weaker π-acceptor than the most electron rich phosphine . • NHCs can be useful spectator ligands, because they are sterically and electronically tunable. • NHCs can promote a wide series of catalytic reactions like phosphine. • NHCs have advantages over phosphines and offer catalysts with better air-stability.

4. N-Heterocyclic Carbenes as Ligands • In the early 90's NHC were found to have bonding properties similar to • trialklyphosphanes and alkylphosphinates. • - compatible with both high and low oxidation state metals • - examples: • - reaction employing NHC's as ligands: Herrmann, W. A.; Öfele, K; Elison, M.; Kühn, F. E.; Roesky, P. W. J. Organomet. Chem.1994, 480, C7-C9. Herrmann, W. Angew. Chem. Int. Ed.2002, 41, 1290-1309.

5. The Catalytic Applications of Pd(II) • C-H Activation of Methane • Oxidation of Alcohols • Reductive Aldol Reaction • Allylation of Aldehydes • Strecker Reaction • Heck reaction • Suzuki–Miyaura Reaction • Carbon-Surfur Coupling Reactions • Buchwald-Hartwig Reactions • Etherification Reaction • Ethylene-CO copolymerization Reaction

6. Strecker AminoAcidSynthesis • The Strecker amino acid synthesis is a series of chemical reactions that synthesize an amino acid from an aldehyde (or ketone). • Adolph Strecker was the first to understand this organic reaction at 1850. • Two novel organogallium(III) complexes were tested in vitro against human tumour. Strecker, D. Ann.Chem. Pharm.1850,75, 27-45. Santiago Gomez-Ruiz , Milena R. Journal of Organometallic Chemistry 2009,694, 2191–2197.

7. The Various Modes of α-Aminonitrile Reactivity Enders, D.; Shilvock, J. P. Chem. Soc. Rev. 2000, 29, 359-373.

8. Lewis Acid-Catalyzed Strecker Reaction • Lewis acid catalysts • Et3N、InCl3、Ga(OTf)3、BiCl3 • Paraskar, A. S.; Sudalai, A. Tetrahedron Lett.2006, 47, 5759-5762. • Ranu, B. C.; Dey, S. S.; Hajra, A. Tetrahedron2002, 58, 2529-2532. • Surya Prakash, G. K.; Mathew, T. ; Panja, C.; Alconcel, S.; Vaghoo, H.; Do, C.; Olah, G. A. • PNAS 2007,104, 3703-3706. • De, S. K. ; Gibbs, R. A. Tetrahedron Lett.2004, 45, 7407-7408. • Transition metal Lewis acid catalysts • RuCl3、NiCl2、Sc(OTf)3、Cu(OTf)2 • De, S. K. Synth. Commun.2005, 35, 653-656. • De, S. K. J. Mol. Catal. A: Chem.2005, 225, 169-171. • Lanthanide Lewis acid catalysts • Pr(OTf)3、La(O-i-Pr)、Yb(OTf)3 • De, S. K. Synth. Commun.2005, 35, 961-966. • Others • KSF、I2 • Yadav, J. S.; Subba Reddy, B. V.; Eeshwaraiah B.; Srinivas, M. Tetrahedron 2004, 60, 1767-1771. • Royer, L.; De, S. K.; Gibbs, R. A. Tetrahedron Lett.2005, 46, 4595-4597.

9. Motivation • Using NHCs ligand to replace phosphine ligand in • organomatallic catalysis. • Synthesis of NHC-Pd(II) complexes with well-defined structures. • Developing a practical and effective process for the • Strecker Reaction. • Greener catalysis –solventless and microwave conditions.

10. The First Palladium(II) Carbene Complexes Toshikazu Hirao, Kenji Tsubata.Tetrahedron Letters 1978 , 18, 1535 - 1538.

11. Examples of Pd(II)-Carbene Complexes Lijin Xu, Weiping Chen Organometallics, 2000,19, 1123-1127 . Lijin Xu, Weiping, Chen, Journal of Organometallic Chemistry, 2000, 598, 409–416.

12. Examples of Pd(II)-Carbene Complexes Yuan Han, Han Vinh Huynh, Journal of Organometallic Chemistry, 2007, 692, 3606–3613.

13. Synthesis of Palladium(Il) Carbene Complexes hmim = 1-hexyl-3-methylimidazolium

14. Synthesis of Pd(Il) Carbene Complex Catalyst

15. 1H NMRSpectraof(Hmim)HI (1),PdI2(hmim)2 (2),andPd(hmim)2(OOCCF3)2 (3) *CDCl3 CH3 2H H

16. 13C NMRSpectraof (Hmim)HI (1), PdI2(hmim)2 (2), andPd(hmim)2(OOCCF3)2 (3) *CDCl3 C C C

17. 19F NMRof Pd(hmim)2(OOCCF3)2 (3) F

18. IRSpectraof (Hmim)HI (1), PdI2(hmim)2 (2), andPd(hmim)2(OOCCF3)2 (3) Pd(hmim)2(OOCCF3)2 (3) 1576 3133, 3162 2957, 2933, 2861 1868 (C=O) 1190 PdI2(hmim)2 (2) 1219 3113, 3149 1566 2954, 2928, 2857 imidazole ν (ring stretching) (Hmim)HI (1) 1166 2953,2930,2857 1569 imidazole H–C–C & H–C–N bending 3079,3140 aliphatic ν (C–H) imidazole ring ν (C–H)

19. Single-Crystal StructureofPdI2(hmim)2 (2) dihedral angle 8.20 °

20. Selective Bond lengths and Bond Angles of PdI2(hmim)2 (2) Bond lengths [Å] Pd(1)-C(1) 2.024(5) Pd(1)-I(1) 2.6066(5) N(1)-C(1) 1.352(7) N(1)-C(2) 1.387(7) C(2)-C(3) 1.341(8) Bond angles [deg] C(1)-Pd(1)-I(1) 90.27(14) C(11)-Pd(1)-C(1) 179.8(2) I(2)-Pd(1)-I(1) 179.22(2) N(2)-C(1)-N(1) 105.2(4) C(1)-N(1)-C(2) 110.6(4) C(3)-C(2)-N(1) 107.0(5) Lijin Xu, Weiping, Chen, Journal of Organometallic Chemistry, 2000, 598, 409–416.

21. N-Heterocyclic Carbene Complexes of palladium ---- Isolation of cis and trans Isomers cis (yield : 8 %) + trans (yield : 82%) trans-syn : trans-anti = 1: 2.6 trans-anti could be dissolved in Et2O. trans-syn was not soluble in Et2O. Dieter Enders, Heike Gielen.Chem. Ber, 1996, 129, 1483–1488.

22. N-Heterocyclic Carbene Complexes of Palladium ---- cis / trans-isomerization cis (white solid) Yield : 19 % Rt ,24 h trans (Yellow solid) Yield : 55 % trans-anti : trans-syn =5:1 d-CDCl3 trans-anti : trans-syn =1:1 1H NMR(trans-anti) 4.09 (s, 6H, NCH3) 4.46 (t ,4H,NCH2 ) 1H NMR(trans-syn ) 4.06(s, 6H, NCH3) 4.44 (t ,4H,NCH2 ) Lijin Xu, Weiping Chen Organometallics, 2000,19, 1123-1127 .

23. PdI2(hmim)2 (2) trans-syn and trans-anti isomerization PdI2(hmim)2 (2) recrystalized from toluene + hexane (1:15) 4.363 4.325 4.287 + 3.952 4.380 4.362 4.330 4.301 4.285 + 3.951 3.935 trans-anti trans-syn + trans-anti Rt ,12h 200 NMR 50 °C,12h d-CDCl3 PdI2(hmim)2(2)

24. NHC-Pd(II) Complex-Catalyzed StreckerReaction Entry 1~14 TOF(h-1) = 1.38 a Reaction condition: 3 mol % Pd catalyst , 0.2 mmol benzaldehyde, 0.2 mmol aniline,0.4 mmol TMSCN, sodium sulfate 0.7 mmol, room temperature stirring in 1 mL of CH2Cl2 b Isolated yield. Jamie Jarusiewicz, Yvonne Choe. J. Org. Chem. 2009, 74, 2873–2876.

25. NHC-Pd(II) Complex-Catalyzed StreckerReaction TOF (h-1) 1.18 0.68 0.80 0.86 0.94 TOF (h-1) 1.38 1.19 1.31 0.23 0.61 a Reaction condition: 3 mol % Pd catalyst , 0.2 mmol benzaldehyde, 0.2 mmol aniline,0.4 mmol TMSCN, sodium sulfate 0.7 mmol, room temperature stirring in 1 mL of CH2Cl2 b Isolated yield. Jamie Jarusiewicz, Yvonne Choe. J. Org. Chem. 2009, 74, 2873–2876.

26. StreckerReactionCatalyzed by K2PdCl4 TOF (h-1) 50 20 20 20 10 14.2 10 10 TOF (h-1) 20 20 20 10 10 8.3 10 10 13.3 a Reaction condition: 1.0 mmol aldehyde, 1.0 mmol aniline, 1.3 mmol TMSCN, 10 mol % K2PdCl4, room temperature stirring. b Isolated yield. B. Karmakar, J. Banerji.Tetrahedron Letters. 2010, xx, xxx–xxx.

27. Fe(Cp)2PF6Catalyzed Strecker Reaction TOF (h-1) 56.4 55.2 49.2 51.6 48.6 54 53.4 TOF (h-1) 56.4 51 51.6 49.2 40.8 50.4 52.2 a Reaction condition: 5 mol % Fe(Cp)2PF6 , 1 mmol aldehyde or ketone , 1 mmol aniline and1.3mmol TMSCN, reaction time 20 min. b isolated yields. Noor-ul H. Khan, Santosh Agrawal .Tetrahedron Letters. 2008,49, 640–644.

28. Fe(Cp)2PF6Catalyzed Strecker Reaction Noor-ul H. Khan, Santosh Agrawal .Tetrahedron Letters. 2008,49, 640–644.

29. ProposedMechanism for the Strecker Reaction

30. Pd(Hmim)2(OOCCF3)2 (3) Catalyzed Strecker Reaction Reaction condition: 0.2 mmol benzaldehyde, 0.2 mmol aniline 0.4 mmol TMSCN, sodium sulfate 0.7 mmol, 0.2mL solvent, RT, 3mol % Pd (Hmim)2(OOCCF3)2 . The conversion is determined by 1H NMR.

31. Pd(Hmim)2(OOCCF3)2 (3)-Catalyzed Strecker Reaction Condition: 0.2 mmol benzaldehyde, 0.2 mmol aniline, 0.4 mmol TMSCN, RT, 3mol % Pd (Hmim)2(OOCCF3)2 . The conversion is determined by 1H NMR.

32. Pd(Hmim)2(OOCCF3)2 (3)-Catalyzed Strecker Reaction-(1) Condition: 0.2 mmol benzaldehyde, 0.2 mmol aniline 0.4 mmol TMSCN, RT, 3mol % Pd (Hmim)2(OOCCF3)2 . The conversion is determined by 1H NMR.

33. Pd(Hmim)2(OOCCF3)2 (3)-Catalyzed Strecker Reaction-(2) Condition: 0.2 mmol benzaldehyde, 0.2 mmol aniline, 0.4 mmol TMSCN, RT, 3mol % Pd (Hmim)2(OOCCF3)2 . The conversion is determined by 1H NMR.

34. Pd(Hmim)2(OOCCF3)2 (3)-Catalyzed Strecker Reaction Condition: 0.2 mmol benzaldehyde, 0.2 mmol aniline, 0.4 mmol TMSCN, RT, 3mol % Pd (Hmim)2(OOCCF3)2 . The conversion is determined by 1H NMR.

35. Pd(Hmim)2(OOCCF3)2 (3)-Catalyzed Strecker Reaction Time (h) TOF(h-1) 1.38 Condition: 0.2 mmol acetophenone, 0.2 mmol aniline, 0.4 mmol TMSCN, RT, 3mol % Pd (Hmim)2(OOCCF3)2 . The conversion is determined by 1H NMR.

36. Pd(Hmim)2(OOCCF3)2 (3) Catalyzed Strecker Reaction under Microwave Irradiation Conditions Time (sec) (bmim)HPF6 600 w Time (sec) TOF(h-1) 1420 (bmim)HPF6 450 w Condition: 0.2 mmol acetophenone, 0.2 mmol aniline, 0.4 mmol TMSCN, RT, 3mol % Pd (Hmim)2(OOCCF3)2 . The conversion is determined by 1H NMR.

37. Conclusions • We have successfully synthesized NHC-carbene Pd(II) • complexes (2) and (3), and characterized them by using 1H- • ,13C , 19F-NMR, IR spectrocopies. • We have successfully demonstrated the highly effective activity • of the Pd(II) complex catalyst towards the Strecker reactions. • Not many successful synthetic protocols for Strecker reactions • of ketones has been reported. We have demonstrated in this study • that our target Pd(II) carbene catalyst (3) is highly active for the • Strecker reactions of ketones. • The Strecker reactions of ketones can be further accelerated • under microwave irradiation conditions.