Studies on Heck and Suzuki Reactions Catalyzed by Palladium(0) and Wacker- Type Oxidative Cyclization Catalyzed by Palladium(II)

Transcription

1 Studies on eck and Suzuki Reactions Catalyzed by Palladium(0) and Wacker- Type xidative Cyclization Catalyzed by Palladium() Zuhui Zhang enmark Group Meeting 10/21/2008 1

2 Part ne: Palladium(0)-Catalyzed eck Reaction and Suzuki Reaction Part Two: Palladium()-Catalyzed Wacker xidative Cyclization to Construct Chromanone, Quinoline and Pyrrole 2

3 Section ne: eck reaction in aqueous mediums and its selectivity Scheme 1. eck reaction Mizoroki, T.; Mori, K.; zaki, A. Bull. Chem. Soc. Jpn. 1971, 44, 581. eck, R. F.; olley, Jr., J. P. J. rg. Chem. 1972, 37,

4 Previous Achievements: G. C. Fu, J.. artwig etc. T. Jeffery, M. T. Reetz etc. X + R C C Pd L L R W. A. errmann, Merritt B. Andrus etc. W. A. errmann,. Milstein, J. upont,. E. Bergbreiter, Q. W. Yao,. G. Blackmond etc. Tf + catalyst chiral ligand base T. ayashi, A. Pfaltz, L. F. Tietze, S. Uemura, X. -l. ou, M. estreich,. P. Curran etc. S. Uemura, A. Mori, M. C. White, K. W. Jung, J. L. Xiao etc. 4

5 ur Approach: 1) Choose water as solvent; 2) Room temperature; 3) Ultrasonic irradiation, in suit formed nano-palladium 4) Regioselectivity 5

6 Table 1. pitimization of base and PTC for eck reaction of odobenzene and Methyl Acrylate a + )))), r.t., 4.5h Me PdCl2, Base, PTC, 2 Me entry base PTC yield(%) b 1 a 2 C 3 TBAB 86 2 a 2 C 3 TEAB c trace 3 a 2 C 3 TMA d trace 4 a 2 C 3 TEA e trace 5 a TBAB 53 6 Et 3 TBAB 67 7 aac TBAB 40 a Reaction conditions: iodobenzene (1 mmol), methyl aceylate (2 mmol), phase transfer catalyst (PTC) (1 mmol), base (3 mmol) and PdCl 2 (0.02 mmol) in 3 ml of water, the mixtures was sonicated at ambient temperature (25 C) in running water bath for 4.5h. b solated yield. c TEAB is tetraethylammonium bromide. d TMA is tetramethylammonium iodide. e TEA is tetraethylamminium iodide. J. rg. Chem. 2006, 71,

7 Table 2. eck reaction promoted by ultrasonic aqueous media R + X rt, PdCl 2, a 2 C 3 TBAB, 2 R X entry ArX alkene product time(h) yield(%) 1 C 2 Me C 2 Me C 2 Et C 2 Et C C C C Me Me C Me C 2 Me Me 2 C 7 C 2 Me C 2 Me 8 Cl Cl C Me C 2 Me 9 Br Br C 2 Me C 2 Me J. rg. Chem. 2006, 71,

8 entry ArX alkene product time(h) yield(%) 10 C 2 Me 4 11 C 2 Me C 2 Me Me C Me 2 Me C 2 Me MM C MM 2 Me 8 76 C 2 Me 14 Me C Me Me C 2 Me C C MeC C 2 Me MeC C 2 Me 16 2 C 2 Me 2 Me 2 C C 2 Me C 2 Me 20 8

9 Study the catalyst for the reaction Figure 1. TEM image of Pd nano-particles formed under ultrasound 9

10 Study the formation of palladium(0) (a) (b) lefin as a reducer for the formation of Pd(0) (C) Figure 2. (a) XR pattern of PdCl 2 (0.1mmol), TBAB (1mmol) and 2 (3ml) under ultrasonic irradiation for 30 min; (b) XR pattern of PdCl 2 (0.1mmol), TBAB (1mmol), methyl acrylate (2mmol) and 2 (3ml) under ultrasonic irradiation for 30 min; (c) XR pattern of the reaction system (1mmol iodobenzene, 2 mmol methyl acrylate, 0.02 mmol PdCl 2, 3 mmol a 2 C 3 and 1 mmol TBAB in 3 ml of water) under ultrasonic 10 irradiation for 30 min.

11 Section Two: iatomite-supported palladium nanoparticles catalyzed eck and Suzuki reactions omogeneous palladium catalysis Advantages: high reaction rate, high turnover numbers (T), high yields and the Pd catalysts can be tuned by ligands. isadvantages: the lack of reuse of the catalyst, a loss of expensive metal and ligands and to impurities in the products and the need to remove residual metals 11

12 iatomite, a type of widespread natural porous material, was first reported by us as a suitable template to supported palladium nanoparticles Scheme 2. Preparation of diatomite-supported palladium nanoparticles iatomite SnCl CF 3 C 3 2 PdCl 4 PVP iatomite supported Pd J. rg. Chem. 2006, 71,

13 Scheme 3. eck reaction of aryl halides with olefins with heterogeneous palladium Ar-X + X =, Br R iatomite-supported Pd nanoparticles MP, Et 3, 120 C Ar R Scheme 4. Suzuki reaction of aryl halides with olefins with heterogeneous palladium Ar-X + Ar'B() 2 Pd nanoparticles iatomite-supported X =, Br ME- 2, a 2 C C Ar-Ar' 13

14 Table 2. Recycling of diatomite-supported Pd for the eck reaction of iodobezene with methyl acrylate + Me iatomite-supported it t Pd nanoparticles MP, a 2 C C Me entry catalyst time isolated yield (%) 1 first cycle 20 min 96 2 second cycle 20 min 95 3 third cycle 20 min 97 4 fourth cycle 20 min 95 5 fifth cycle 40 min 96 6 sixth cycle 70 min 95 14

15 Figure 2. Catalytic model of heterogeneous palladium catalyst e Vries, A.. M.; Mulders, J. M. C. A.; Mommers, J.. M.; enderickx,. J. W.; e Vries, J. G. rg. Lett. 2003, 5,

16 Part Two: Palladium()-Catalyzed Wacker xidative Cyclization to Construct Chromanone, Quinoline and Pyrrole 16

17 riginal reports about Wacker cyclization a R PdCl 2 (PhC) 2 C 2 R R =, 31 % R =Ph, 53 % osokawa, T.; Maeda, K.; Koga, K.; Moritani,. Tetrahedron Lett. 1973, 14, PdCl R 2 (MeC) 2, TF 2 2. Et 3 R =, 5-Me, 5-C 2 Et, 6-Me R % egedus, L. S.; Allen, G. F.; Waterman, E. L. J. Am. Chem. Soc. 1976, 98,

18 Section ne: Palladium catalyzed Wacker-type reaction for the synthesis of chromanone and involving 1,5-hydride alkyl to palladium migration Scheme 5. riginal report on Wacker-type oxidative cyclization PdCl 2 (PhC) 2 a R R R A B (1) osokawa, T.; Maeda, K.; Koga, K.; Moritani,. Tetrahedron Lett. 1973, 14, Scheme 6. ur initial proposal β- 1a C (2) 2a E 18

19 Scheme 7. Wacker-type oxidative cyclization of 1a. 1a Pd(Ac) 2 (10 mol %) K 2 C 3 (1.2 equiv), 2 (1 atm) Et/ 2 (2/1), 35 C, 24 h 2a Chem. Commun. 2007,

20 Table 7. Palladium () -Catalyzed Wacker-Type Cyclization Y Pd(Ac) 2 (10 mol %) Y K 2 C 3 (1.2 equiv), 2 (1 atm) X Et/ 2 (2/1), 35 C, 24 h X Groups sensitive to palladium survived Entry X Y Yield (%) Me 80 Me 3 C 72 Me 70 Me 76 Me Cl 70 Cl 64 MeC 42 Br 43 Electron-donating group facilitate t the reaction steric effort is unclear Me 3 C Me 3 C stong electonwithdrawing group retards the reacton

21 Mechanism insight: β- elimination was excluded. Scheme 9. euterium labelling experiment of Wacker-type cyclization 3 Pd(Ac) 2 (10 mol %) 1 2 K 2 C 3 (1.2 equiv), 2 (1 atm) 4 Et/ 2 (2/1), 35 C, 24 h 1 67% Scheme 10. Cyclization of starting material without β- Pd(Ac) 2 (10 mol %) β K 2 C 3 (1.2 equiv), 2 (1 atm) Et/ 2 (2/1), 35 C, 24 h 70 % 21

22 Scheme 11. β-ydride Elimination/ydropalladation Sequences []-(S)-G Pd β- elim -Pd add []-(S)-C Pd β- elim Pd -Pd add []-(S)- Pd β- elim Pd (R)-2a (R)-E -Pd add 22

23 Stereochemistry of oxypalladation: cis or trans? Trans : B ǎ ckwall, Stille, Kurosawa etc. Cis : ayashi, Wolfe, Stoltz, enry etc. Pd Pd G 4 3 Pd(MeC)4(BF4) (S,S) S)-ip-boxax (Pd/L=1/ benzoquinone (4 equiv) M, 40 C, 4h % /3/4/5=16/46/29/9 Syn-oxypalladation Pd Pd -Pd a dd A - eli im B Pd Pd- C Pd - elim -Pd add E - elim -Pd add Pd- T. ayashi, et al JACS, 2003, 126, F i-pr (S,S)-ip-boxax i-pr 23

24 Scheme 9. Proposed mechanism for the Wacker-type cyclization of (S) -1a-d1 d involving i 1,5-palladium migration. (Et) Pd 2 (S)-2a-d Pd 0 syn oxypalladation (S)-1a-d (S)--d Pd (S)-F-d Pd - Pd Pd (S)--d (S)-G-d 24

25 Further experiment to support 1,5-hydride alkyl to palladium migration Scheme 10 Chirality transfer experiment of cyclization Pd(Ac) 2 (10 mol %) (S)-1a (63 % ee) K 2 C 3 (1.2 equiv), 2 (1 atm) Et/ 2 (2/1), 35 C, 24 h 67 % Me (S)-2a (66 % ee) 25

26 Section Two: Facile synthesis of 2-methyl quinolines by aza-wacker oxidative cyclization catalyzed by palladium() Scheme 11. Aza-Wacker oxidative amination rg. Lett. 2008, 10,

27 Sh Scheme 12P 12. Proposed mechanism for the Pd-Catalyzed Ctl daza-wacker reaction to form 2-methyl-quinoline 2a 2 L n Pd(Ac) 2 2 1a + L n Pd(0) A Pd Ac L n C β- elim B L n Pd Ac 27

28 Section Three: Facile synthesis of 2-methyl pyrroles by aza-wacker oxidative cyclization catalyzed by palladium() Scheme 13. Synthesis of pyrroles by aza-wacker oxidative cyclization Pd() 2 R Boc Pd() R Boc J. rg. Chem. 2008, 73,

29 Scheme 14. General process to substrates from amino acids R 1. Me,SCl 2 R BAL Boc 2, ac 3 Boc Me Tol., -78 C 3 4 R R Br Boc Boc Zn, TF/ 4 Cl

30 Table 11. ptimazation of Aza-Wacker cyclization a Boc catalyst, solvent 30 C, 24 h Boc entry solvent catalyst (10 mol %) oxidant yield b (%) 1 Me Pd(Ac) 2 air Et i-pr TF Pd(Ac) 2 Pd(Ac) 2 Pd(Ac) 2 air air air 25 trace trace 5 Tol Pd(Ac) 2 air trace 6 7 MF MS Pd(Ac) 2 Pd(Ac) 2 air air trace trace CCl 3 Et Et Pd(Ac) 2 PdCl 2 PdCl 2 (MeC) 2 air air air trace Et PdCl 2 (PhC) 2 air Et PdCl 2 (PhC) Et PdCl 2 (PhC) 2 CuCl 2 (10 mol %) Et PdCl 2 (PhC) 2 Cu(Tf) 2 (10 mol %) Et PdCl 2 (PhC) 2 Cu(Tf) 2 (50 mol %) Et PdCl 2 (PhC) 2 Cu(Tf) 2 (100 mol %) 88 a Reaction conditions: 0.2 M of substrate in solvent. b solated yield. 30

31 Table 12. Synthesis of Pyrrole by Aza-Wacker Cyclization a entry substrate product yield b (%) 1 88 Boc Boc Boc Boc Boc Boc Boc Boc Boc Boc 6 S S 85 Boc Boc 87 31

32 entry substrate product yield b (%) Boc 7 62 Boc 4 4 Boc Boc 8 79 Boc Boc 9 76 Boc Boc Boc Boc 11 Boc Boc 26 a Reaction conditions: substrate t (1 mmol), PdCl 2 (PhC) 2 (0.1 mmol) and Cu(Tf) 2 (1 mmol) in 5mL of ethanol at 30 C for 24 h. b solated yield. 32

33 Conclusion: 1) Regioselective eck reaction at different C- bonds was first reported; 2) iatomite as a suitable template to support palladium was first developed and used to catalyze eck and Suzuki reactions; 3) 15-hydride 1,5 alkyl to palladium migration was first proposed in Wacker-type reaction and a series of chromanones were synthesized by this method; 4) Quinolines and pyrroles were obtained by aza-wacker cyclization. 33

34 Acknowledgement Prof. Zhiyong Wang Wang s Group 34