Supporting Information

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1 Electronic Supplementary Material (ESI) for rganic Chemistry Frontiers. This journal is the Partner rganisations 2016 Supporting Information Fangyi Li, Changgui Zhao, and Jian Wang* Department of Pharmacology and Pharmaceutical Sciences, School of dicine, Tsinghua University, Beijing, , China. Contents: 1. General Information S2 2. Experimental Procedure S3 3. MR Spectra S22

2 1. General Information Unless otherwise stated, all commercial reagents were used as received. Reactions were conducted in dry glassware using anhydrous solvents (pass through activated alumina columns). Reaction temperatures were controlled using IKAmag temperature modulator, and unless stated otherwise, reactions were performed at room temperature (rt, approximately, 24 o C). Thin-layer chromatography (TLC) was conducted on plates (GF254) supplied by Yantai Chemicals (China) and visualized using a combination of UV, anisaldehyde, iodine, and potassium permanganate staining. Silica gel ( mesh) supplied by Tsingdao aiyang Chemicals (China) was used for flash column chromatography. 1, 13 C and 19 F MR spectra were recorded on Bruker spectrometers (400 Mz). Chemical shifts were reported in parts per million (ppm), and the residual solvent peak was used as an internal reference: proton (chloroform δ 7.26), carbon (chloroform δ 77.16) or tetramethylsilane (TMS δ 0.00) was used as a reference. Multiplicity was indicated as follows: s (singlet), d (doublet), t (triplet), q (quartet), m (multiplet), dd (doublet of doublet), bs (broad singlet). Coupling constants were reported in ertz (z). All high resolution mass spectra were obtained from the Tsinghua University Mass Spectrometry Facility. S2

3 2. Experimental Procedure The C precatalyst C (0.02 mmol), KC 3 (0.04 mmol) and compound 1a (0.2 mmol) were placed in an oven-dried Schlenk tube equipped with a magnetic stir bar. The tube was closed with a septum, evacuated and refilled with argon. Dry TF (4.0 ml) were added. The reaction mixture stirred at room temperature till the starting material was completely consumed (monitored by TLC or GC-MS). The mixture was concentrated under reduced pressure and purified by flash chromatography eluted with hexane/etac = 10:1 to afford the corresponding desired product 2a as white solid (33 mg, 87% yield). 1-Acetyl-4-phenylazet-2(1)-one (2a): 33mg, 87% yield; white solid; 1 MR (400 Mz, CDCl 3 ) δ (ppm): 7.96 (d, J = 6 z, 1), (m, 3), 6.52 (s, 1), 2.50 (s, 3); 13 C MR (100 Mz, CDCl 3 ) δ (ppm): , , , , , , , , 21.94; RMS (ESI) exact mass calculated for [M+a] + (C a) requires m/z , found m/z t Bu 4-Phenyl-1-pivaloylazet-2(1)-one (2b): 35mg, 77% yield; white solid; 1 MR (400 Mz, CDCl 3 ) δ (ppm): 8.01 (d, J = 7.2 z, 2), (m, 3), 6.51 (s, 1), 1.42 (s, 9); 13 C MR (100 Mz, CDCl 3 ) δ (ppm): , , , , , , , , 38.70, 27.82; RMS (ESI) exact mass calculated for [M+a] + (C a) requires m/z , found m/z S3

4 Ph 1-Benzoyl-4-phenylazet-2(1)-one (2c): 41mg, 83% yield; white solid; 1 MR (400 Mz, CDCl 3 ) δ (ppm): 8.35 (d, J = 8 z, 2), 8.09 (d, J = 6.8 z, 2), (m, 1), (m, 5), 6.59 (s, 1); 13 C MR (100 Mz, CDCl 3 ) δ (ppm): , , , , , , , , , , , ; RMS (ESI) exact mass calculated for [M+a] + (C a) requires m/z , found m/z Acetyl-4-(p-tolyl)azet-2(1)-one (2d): 31 mg, 78% yield; white solid; 1 MR (400 Mz, CDCl 3 ) δ (ppm): 7.89 (d, J = 8.4 z, 2), 7.30 (d, J = 8.4 z, 2), 6.49 (s, 1), 2.50 (s, 3), 2.44 (s, 3); 13 C MR (100 Mz, CDCl 3 ) δ (ppm): , , , , , , , , 21.91, 21.66; RMS (ESI) exact mass calculated for [M+a] + (C a) requires m/z , found m/z F 1-Acetyl-4-(4-fluorophenyl)azet-2(1)-one (2e): 36 mg, 87% yield; white solid; 1 MR (400 Mz, CDCl 3 ) δ (ppm): 7.98 (t, J = 7.6 z, 2), 7.15 (t J = 8.4 z, 2), 6.46 (s, 1), 2.49 (s, 3); 13 C MR (100 Mz, CDCl 3 ) δ (ppm): , (d, J = 252 z), , , (d, J = 3.1 z), (d, J = 8.9 z), (d, J = 21.8 z), , 21.93; 19 F MR (376 Mz, CDCl 3 ) δ (ppm): ; RMS (ESI) exact mass calculated for [M+a] + (C 11 8 F 2 a) requires m/z , S4

5 found m/z Cl 1-Acetyl-4-(4-chlorophenyl)azet-2(1)-one (2f): 37 mg, 84% yield; white solid; 1 MR (400 Mz, CDCl 3 ) δ (ppm): 7.91 (d, J = 8.4 z, 2), 7.44 (d, J = 8.4 z, 2), 6.49 (s, 1), 2.49 (s, 3); 13 C MR (100 Mz, CDCl 3 ) δ (ppm): , , , , , , , , 21.94; RMS (ESI) exact mass calculated for [M+a] + (C 11 8 Cl 2 a) requires m/z , found m/z C 2 thyl 4-(1-acetyl-4-oxo-1,4-dihydroazet-2-yl)benzoate (2g): 40 mg, 81% yield; white solid; 1 MR (400 Mz, CDCl 3 ) δ (ppm): 8.26 (d, J = 8.4 z, 2), 8.03 (d, J = 8.4 z, 2), 6.58 (s, 1), 3.95 (s, 3), 2.51 (s, 3); 13 C MR (100 Mz, CDCl 3 ) δ (ppm): , , , , , , , , , 52.56, 21.97; RMS (ESI) exact mass calculated for [M+a] + (C a 4 a) requires m/z , found m/z CF 3 1-Acetyl-4-(4-(trifluoromethyl)phenyl)azet-2(1)-one (2h): 45 mg, 88% yield; white solid; 1 MR (400 Mz, CDCl 3 ) δ (ppm): 8.08 (d, J = 8 z, 2), 7.73 (d J = 8 z, 2), 6.58 (s, 1), 2.52 (s, 3); 13 C MR (100 Mz, CDCl 3 ) δ (ppm): , , , , (q, J = 32.6 z), , S5

6 (q, J = 3.7 z), (q, J = z), , 21.96; 19 F MR (376 Mz, CDCl 3 ) δ (ppm): 63.02; RMS (ESI) exact mass calculated for [M+] + (C 12 9 F 3 2 ) requires m/z , found m/z Acetyl-4-(4-nitrophenyl)azet-2(1)-one (2i): 38 mg, 83% yield; White solid; 1 MR (400 Mz, CDCl 3 ) δ (ppm): 8.33 (d, J = 8.4 z, 2), 8.14 (d, J = 8.8 z, 2), 6.63 (s, 1), 2.53 (s, 3); 13 C MR (100 Mz, CDCl 3 ) δ (ppm): , , , , , , , , 22.01; RMS (ESI) exact mass calculated for [M+a] + (C a) requires m/z , found m/z Ph 4-([1,1'-Biphenyl]-4-yl)-1-acetylazet-2(1)-one (2j): 44 mg, 84% yield; white solid; 1 MR (400 Mz, CDCl 3 ) δ (ppm): 8.05 (d, J = 8.4 z, 2), 7.71 (d, J = 8.4 z, 2), 7.64 (d, J = 7.2 z, 2), 7.48 (t, J = 7.2 z, 2), (m, 1), 6.56 (s, 1), 2.51 (s, 3); 13 C MR (100 Mz, CDCl 3 ) δ (ppm): , , , , , , , , , , , , 21.95;; RMS (ESI) exact mass calculated for [M+a] + (C a) requires m/z , found m/z S6

7 1-Acetyl-4-(m-tolyl)azet-2(1)-one (2k): 31 mg, 78% yield; white solid; 1 MR (400 Mz, CDCl 3 ) δ (ppm): (m, 2), (m, 2), 6.49 (s, 1), 2.49 (s, 3), 2.42 (s, 3); 13 C MR (100 Mz, CDCl 3 ) δ (ppm): , , , , , , , , , , 21.90, 21.56; RMS (ESI) exact mass calculated for [M+a] + (C a) requires m/z , found m/z Acetyl-4-(3-methoxyphenyl)azet-2(1)-one (2l): 32 mg, 73% yield; white solid; 1 MR (400 Mz, CDCl 3 ) δ (ppm): (m, 2), 7.37 (t, J = 8.4 z, 1), (m, 1), 6.49 (s, 1), 3.86 (s, 3), 2.48 (s, 3); 13 C MR (100 Mz, CDCl 3 ) δ (ppm): , , , , , , , , , , 55.52, 21.90; RMS (ESI) exact mass calculated for [M+a] + (C a) requires m/z , found m/z ; Cl 1-Acetyl-4-(3-chlorophenyl)azet-2(1)-one (2m): 40 mg, 91% yield; white solid; 1 MR (400 Mz, CDCl 3 ) δ (ppm): 7.99 (t, J = 2 z, 1), 7.81 (dt, J 1 = 7.6 z, J 2 = 1.2 z, 1), (m, 1) 7.41 ( t, J = 7.6 z, 1), 6.51 (s, 1), 2.50 (s, 3); 13 C MR (100 Mz, CDCl 3 ) δ (ppm): , , , , , , , , , , 21.96; RMS (ESI) exact mass calculated for [M+] + (C 11 9 Cl 2 ) requires m/z , found m/z ; Br 1-Acetyl-4-(3-bromophenyl)azet-2(1)-one (2n): 43 mg, 80% yield; white solid; 1 MR (400 Mz, S7

8 CDCl 3 ) δ (ppm): 8.14 (s, 1), 7.85 (d, J = 8 z, 1), 7.63 (d, J = 8 z, 1),7.34 (t, J = 8 z, 1), 6.50 (s, 1), 2.50 (s, 3); 13 C MR (100 Mz, CDCl 3 ) δ (ppm): , , , , , , , , , , 21.94; RMS (ESI) exact mass calculated for [M+a] + (C 11 8 Br 2 a) requires m/z , found m/z CF 3 1-Acetyl-4-(3-(trifluoromethyl)phenyl)azet-2(1)-one (2o): 44 mg, 86% yield; white solid; 1 MR (400 Mz, CDCl 3 ) δ (ppm): 8.26 (s, 1), 8.11 (d, J = 7.6 z, 1), 7.76 (d, J = 7.6 z, 1), 7.61 (t, J = 7.6 z, 1), 6.57 (s, 1), 2.52 (s, 3); 13 C MR (100 Mz, CDCl 3 ) δ (ppm): , , , , (q, J = 32.6 z), , , (q, J = 3.5 z), (q, J = 3.8 z), (q, J = z), , 21.92; 19 F MR (376 Mz, CDCl 3 ) δ (ppm): 62.94; RMS (ESI) exact mass calculated for [M+a] + (C 12 8 F 3 2 a) requires m/z , found m/z C 3-(1-Acetyl-4-oxo-1,4-dihydroazet-2-yl)benzonitrile (2p): 33 mg, 79% yield; white solid; 1 MR (400 Mz, CDCl 3 ) δ (ppm): 8.32 (s, 1), 8.15 (d, J = 8 z, 1), 7.79 (d, J = 7.6 z, 1), 7.61 (t, J = 8 z, 1), 6.55 (s, 1), 2.52 (s, 3); 13 C MR (100 Mz, CDCl 3 ) δ (ppm): , , , , , , , , , , , 21.98; RMS (ESI) exact mass calculated for [M+a] + (C a) requires m/z , found m/z S8

9 1-Acetyl-4-(naphthalen-1-yl)azet-2(1)-one (2q): 30 mg, 63% yield; white solid; 1 MR (400 Mz, CDCl 3 ) δ (ppm): (m, 1), 7.97 (d, J = 8 z, 1), (m, 1), 7.67 (d, J = 7.2 z, 1), (m, 3), 6.45 (s, 1), 2.55 (s, 3); 13 C MR (100 Mz, CDCl 3 ) δ (ppm): , , , , , , , , , , , , , , 29.84; RMS (ESI) exact mass calculated for [M+a] + (C a) requires m/z , found m/z acetyl-4-(naphthalen-2-yl)azet-2(1)-one (2r): 41 mg, 86% yield; white solid; 1 MR (400 Mz, CDCl 3 ) δ (ppm): 8.60 (s, 1), 7.96 (d, J = 7.6 z, 1), 7.90 (brs, 2), 7.87 (d, J = 7.6 z, 1), 7.56 (m, 2), 6.63 (s, 1), 2.53 (s, 3); 13 C MR (100 Mz, CDCl 3 ) δ (ppm): , , , , , , , , , , , , , , 21.96; RMS (ESI) exact mass calculated for [M+a] + (C a) requires m/z , found m/z Ts 1-Acetyl-4-(1-tosyl-1-indol-3-yl)azet-2(1)-one (2s): 52 mg, 69% yield; white solid; 1 MR (400 Mz, CDCl 3 ) δ (ppm): 8.42 (s, 1), 8.02 (d, J = 8 z, 1), 7.93 (d, J = 7.6 z, 1), 7.84 (d, J = 8.4z, 2), (m, 2), 7.26 (d, J = 8 z, 2), 6.49 (s, 1), 2.49 (s, 3), 2.35 (s, 3); 13 C MR S9

10 (100 Mz, CDCl 3 ) δ (ppm): , , , , , , , , , , , , , , , , 21.85, 21.75; RMS (ESI) exact mass calculated for [M+a] + (C Sa) requires m/z , found m/z Ts 1-Acetyl-4-(1-tosyl-1-pyrrol-2-yl)azet-2(1)-one (2t): 43 mg,65% yield; white solid; 1 MR (400 Mz, CDCl 3 ) δ (ppm): 7.71 (d, J = 8.4 z, 2), (m, 1), 7.30 (d, J = 8 z, 2), (m, 1), 6.41 (s, 1), 6.37 (t, J = 3.6 z, 1), 2.42 (s, 3), 2.29 (s, 3); 13 C MR (100 Mz, CDCl 3 ) δ (ppm): , , , , , , , , , , , , 21.83, 21.48; RMS (ESI) exact mass calculated for [M+a] + (C Sa) requires m/z , found m/z Acetyl-4-((3r,5r,7r)-adamantan-1-yl)azet-2(1)-one (2u): 37 mg, 76% yield; white solid; 1 MR (400 Mz, CDCl 3 ) δ (ppm): 5.90 (s, 1), 2.38 (s, 3), 2.07 (brs, 3), (m, 12); 13 C MR (100 Mz, CDCl 3 ) δ (ppm): , , , , 39.51, 38.77, 36.60, 28.15, RMS (ESI) exact mass calculated for [M+a] + (C a) requires m/z , found m/z S10

11 1-Acetyl-3,4-dihydronaphtho[1,2-b]azet-2(1)-one (2v): 13 mg, 31% yield; white solid; 1 MR (400 Mz, CDCl 3 ) δ (ppm): 8.07 (d, J = 7.2 z, 1), (m, 2), 7.22 (d, J = 7.2 z, 1), 2.92 (t, J = 8 z, 2), 2.77 (t, J = 8 z, 2), 2.46 (s, 3); 13 C MR (100 Mz, CDCl 3 ) δ (ppm): , , , , , , , , , , 26.85, 21.69, 19.69; RMS (ESI) exact mass calculated for [M+a] + (C a) requires m/z , found m/z acetyl-1-indeno[1,2-b]azet-2(3)-one (2w): 15 mg, 38% yield; white solid; 1 MR (400 Mz, CDCl 3 ) δ (ppm): 7.89 (d, J = 7.2 z, 1), 7.60 (d, J = 7.6 z, 1), (m, 2), 3.80 (s, 2), 2.55 (s, 3); 13 C MR (100 Mz, CDCl 3 ) δ (ppm): , , , , , , , , , , 33.15, 21.91; RMS (ESI) exact mass calculated for [M+a] + (C a) requires m/z , found m/z S11

12 3. MR Spectra: 1-Acetyl-4-phenylazet-2(1)-one (2a): S12

13 4-Phenyl-1-pivaloylazet-2(1)-one (2b): t Bu S13

14 t Bu 1-Benzoyl-4-phenylazet-2(1)-one (2c): Ph S14

15 Ph 1-Acetyl-4-(p-tolyl)azet-2(1)-one (2d): S15

16 1-Acetyl-4-(4-fluorophenyl)azet-2(1)-one (2e): F S16

17 F F 1-Acetyl-4-(4-chlorophenyl)azet-2(1)-one (2f): S17

18 Cl Cl thyl 4-(1-acetyl-4-oxo-1,4-dihydroazet-2-yl)benzoate (2g): S18

19 C 2 C 2 1-Acetyl-4-(4-(trifluoromethyl)phenyl)azet-2(1)-one (2h) S19

20 CF 3 CF 3 S20

21 CF 3 1-Acetyl-4-(4-nitrophenyl)azet-2(1)-one (2i): 2 S21

22 2 4-([1,1'-biphenyl]-4-yl)-1-acetylazet-2(1)-one (2j): Ph S22

23 Ph 1-Acetyl-4-(m-tolyl)azet-2(1)-one (2k): S23

24 1-Acetyl-4-(3-methoxyphenyl)azet-2(1)-one (2l) S24

25 1-Acetyl-4-(3-chlorophenyl)azet-2(1)-one (2m): F Cl S25

26 Cl 1-Acetyl-4-(3-bromophenyl)azet-2(1)-one (2n): Br S26

27 Br 1-Acetyl-4-(3-(trifluoromethyl)phenyl)azet-2(1)-one (2o): CF 3 S27

28 CF 3 CF 3 3-(1-Acetyl-4-oxo-1,4-dihydroazet-2-yl)benzonitrile (2p): S28

29 C C 1-Acetyl-4-(naphthalen-1-yl)azet-2(1)-one (2q) S29

30 1-Acetyl-4-(naphthalen-2-yl)azet-2(1)-one (2r) S30

31 1-Acetyl-4-(1-tosyl-1-indol-3-yl)azet-2(1)-one (2s): S31

32 Ts Ts 1-Acetyl-4-(1-tosyl-1-pyrrol-2-yl)azet-2(1)-one (2t): S32

33 Ts Ts 1-Acetyl-4-((1s,3s)-adamantan-1-yl)azet-2(1)-one (2u) S33

34 1-Acetyl-3,4-dihydronaphtho[1,2-b]azet-2(1)-one (2v): S34

35 1-Acetyl-1-indeno[1,2-b]azet-2(3)-one (2w): S35

36 S36