Ru(II)-Catalyzed Annulation of Benzamidines and Alkynes by C-H/N-H Activation: A Facile Synthesis of 1- Aminoisoquinolines. Supporting Information

Transcription

1 Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry. This journal is The Royal Society of Chemistry 2017 Ru(II)-Catalyzed Annulation of Benzamidines and Alkynes by C-H/N-H Activation: A Facile Synthesis of 1- Aminoisoquinolines Partha Pratim Kaishap a, Gauri Duarah a, Dipak Chetia b and Sanjib Gogoi a * *Corresponding author, Tel.: ; Fax: ; skgogoi1@gmail.com a Applied Organic Chemistry, Chemical Sciences & Technology Division, CSIR-North East Institute of Science and Technology, Jorhat , AcSIR, India, Fax: Tel.: ; skgogoi1@gmail.com, b Department of Pharm. Sciences, Dibrugarh University, Dibrugarh Supporting Information 1

2 Contents Page Mechanistic Experiments 3-4 NMR spectra

3 1. Mechanistic Experiments 1.1 Intermolecular competition experiments: (a) A solution of benzamidine hydrochloride 1a (78 mg, 0.5 mmol), alkyne 2a (178 mg, 1.0 mmol), alkyne 2l (110 mg, 1.0 mmol), [RuCl 2 (p-cymene)] 2 (8 mg, 2.5 mol %), Cu(OAc) 2.H 2 O (100 mg, 0.5 mmol ) and K 2 CO 3 (65 mg, 0.5 mmol) in t AmOH (6.0 ml) was stirred in at 85 o C for 12 hours. The solvent was removed under vacuo and the crude reaction mixture was poured into water and extracted with ethylacetate (25 ml x 2). The ethylacetate layer was then washed with brine and water. Finally, it was dried over anhydrous Na 2 SO 4 and removed under vacuo. The 1 H NMR of the crude product showed the formation of 3aa and 3al in the ratio of 3.5:1. (b) A solution of benzamidine hydrochloride 1a (78 mg, 0.5 mmol), alkyne 2b (206 mg, 1.0 mmol), alkyne 2d (214 mg, 1.0 mmol), [RuCl 2 (p-cymene)] 2 (8 mg, 2.5 mol %) Cu(OAc) 2.H 2 O (100 mg, 0.5 mmol ) and K 2 CO 3 (65 mg, 0.5 mmol) in t AmOH (6.0 ml) was stirred at 85 o C for 12 hours. The solvent was removed under vacuo and the crude reaction mixture was poured into water and extracted with ethylacetate (25 ml x 2). The ethylacetate layer was then washed with brine and water. Finally, it was dried over anhydrous Na 2 SO 4 and the solvent was removed under vacuo. The 1 H NMR of the crude product showed the formation of 3ab and 3ad in the ratio of 1:1.8. (c) 3

4 A solution of 1b (170 mg, 1.0 mmol), 1c (174 mg, 1.0 mmol), alkyne 2a (89 mg, 0.5 mmol), [RuCl 2 (p-cymene)] 2 (8 mg, 2.5 mol %), Cu(OAc) 2.H 2 O (100 mg, 0.5 mmol) and K 2 CO 3 (65 mg, 0.5 mmol) in t AmOH (6.0 ml) was stirred at 85 o C for 12 hours. The solvent was removed under vacuo and the crude reaction mixture was poured into water and extracted with ethylacetate (25 ml x 2). The ethylacetate layer was then washed with brine and water. Finally, it was dried over anhydrous Na 2 SO 4 and the solvent was removed under vacuo. The 1 H NMR of the crude product showed the formation of 3ba and 3ca in the ratio of 1: Isotopically labelled experiments A solution of benzamidine hydrochloride 1a (78 mg, 0.5 mmol), diphenylacetylene 2a (55 mg, 0.5 mmol), [RuCl 2 (p-cymene)] 2 (8 mg, 2.5 mol %), Cu(OAc) 2 (91 mg, 0.5 mmol ) and K 2 CO 3 (65 mg, 0.5 mmol) in CD 3 OD (4.0 ml) was stirred at 64 o C for 12 hours. The solvent was evaporated and the crude product obtained was purified by silica gel ( mesh) column chromatography using EtOAc/Hexane (7:3) as the eluant to afford 3aa-D (60 mg, 42%). The deuterium incorporation was found to be 20% at C-8 of 3aa-D. 4

5 2. NMR spectra 5

6 6

7 7

8 8

9 9

10 10

11 11

12 12

13 13

14 14

15 15

16 16

17 17

18 18

19 19

20 20

21 21

22 22

23 23

24 24

25 25

26 26

27 27

28 28

29 29

30 30

31 31

32 32

33 33

34 34

35 35

36 Intermolecular competition experiments: 36

37 Isotopically labelled experiment (Scheme 2) Structure determination of compound 3ae by spectroscopic studies 37

38 38

39 39

40 40

41 Structure determination of compound 3ag by spectroscopic studies 41

42 42

43 43

44 44

45 Structure determination of compound 3ag by spectroscopic studies 45

46 46

47 47

48 48

49 49

50 Structure determination of compound 3aj by spectroscopic studies 50

51 51

52 52

53 53

54 Structure determination of compound 3ao by NOESY Structure determination of compound 3as by spectroscopic studies 54

55 55

56 56

57 57

58 58