Palladium-Catalyzed Alkylarylation of Acrylamides with

Transcription

1 Supporting Information Palladium-Catalyzed Alkylarylation of Acrylamides with Unactivated Alkyl Halides Hua Wang, Li-a Guo, and Xin-Hua Duan* Department of Chemistry, School of Science and ME Key Laboratory for onequilibrium Synthesis and Modulation of Condensed Matter, Xi an Jiaotong University, Xi an , China Table of Contents Investigation of the Reaction Mechanism S2 Isotope Labeling Experiment S5 Reference S8 1 H MR and 13 C MR Spectra of Products 3 S9 1 H MR and 13 C MR Spectra of Products 4 S28 1 H MR and 13 C MR Spectra of Products 6a S46 1 H MR and 13 C MR Spectra of Products 8a and 8b S47 S1

2 Investigation of the Reaction Mechanism + I standard conditions TMPE (2.5 equiv) 1a 2a 3a, trace When 2.5 equiv of TEMP was added to the reaction of 1a with 2a under the standard conditions, only trace amount of desired product 3a was detected, along with 83% of 1a recovered. The result indicates that a radical intermediate is probably involved in the catalytic cycle of the reaction. + I standard conditions BHT (2.5 equiv) 1a 2a 3a, 27% When 2.5 equiv of BHT was added to the reaction of 1a with 2a under the standard conditions, only 27% yield of desired product 3a was isolated. The result indicates that a radical intermediate is probably involved in the catalytic cycle of the reaction. S2

3 + Br standard conditions 1a 7a 8a, 3% yield 8a', ot Detected When cyclopropylmethyl bromide 7a was treated with 1a under the standard conditions, only 3% yield of the ring-opening product 8a was obtained due to the low conversion of 1a. In this case, 1a was recovered in 91%. o cyclopropylethyl substituted product 8a was detected in this reaction. 1,3-dimethyl-3-pent-4-enyl-1,3-dihydro-indol-2-one (8a): 1 H MR (400 MHz, CDCl 3 ): δ = (m, 1H), 7.17 (d, J = 7.2 Hz, 1H), (m, 1H), 6.84 (d, J = 7.6 Hz, 1H), (m, 1H), (m, 1H), (m, 1H), 3.22 (s, 3H), (m, 2H), (m, 2H), 1.35 (s, 3H), (m, 2H); 13 C MR (100 MHz, CDCl 3 ): δ = 180.7, 143.3, 138.2, 134.1, 127.6, 122.4, 114.7, 107.9, 48.3, 38.0, 33.7, 26.1, 23.7 ppm; The MR spectrum of 8a displayed relatively impurities in the aliphatic and aromatic region due to other inseparable byproducts. HRMS (ESI) calcd for C 15 H 19 a [M+a] , found standard conditions + Br 1a 7b 8b, 4% yield 8b', ot Detected When 6-bromo-1-hexene 7b was treated with 1a under the standard conditions, only 4% yield of the cyclopentylethyl substituted oxindole 8b was obtained due to the low conversion of 1a. In this case, 1a was recovered in 87%. o heptenyl substituted product 8b was detected in this reaction. 3-(2-Cyclopentyl-ethyl)-1,3-dimethyl-1,3-dihydro-indol-2-one (8b): 1 H MR (400 MHz, CDCl 3 ): δ = (m, 1H), 7.17 (d, J = 7.2 Hz, 1H), 7.07 (t, J = 7.2 Hz, 1H), 6.84 (d, J = 7.6 Hz, 1H), 3.22 (s, 3H), (m, 2H), (m, 3H), (m, 3H), 1.35 (s, 3H), (m, 1H), (m, 4H); 13 C MR (100 MHz, CDCl 3 ): δ = 180.8, 143.3, 134.3, 127.5, 122.4, 107.8, 48.4, 40.1, 37.6, 32.4, 30.6, 26.1, 25.1, 23.8 ppm; The MR spectrum of 8b displayed relatively impurities in the aliphatic and aromatic region which due to other inseparable byproducts. S3

4 HRMS (ESI) calcd for C 17 H 23 a [M+a] , found S4

5 Isotope Labeling Experiment a) Intramolecular Kinetic Isotope Effect (KIE) Experiment: [D 1 ]-1a was synthesized according the literature procedure. 1 An oven-dried sealed tube was charged with [D 1 ]-1a (0.2 mmol, 1.0 equiv), PdCl 2 (3.4 mg, 10 mol %), dppf (11.8 mg, 10 mol %), and K 3 P. 4 3H 2 (106 mg, 0.4 mmol). The tube was evacuated and backfilled with nitrogen (three times). Then, a solution of iodocyclohexane 2a (0.5 mmol, 2.5 equiv) in diglyme (2.0 ml) was injected by syringe. The tube was then sealed with a Teflon lined cap and placed into a preheated oil bath at 100 C with vigorous stirring. After 24 h, the resulting mixture was diluted with EtAc, and the organic phase was washed successively with H 2 (three times) and brine (one time) then dried (a 2 S 4 ) and concentrated in vacuo. The residue was purified by column chromatography on silica gel to give the corresponding product. The product was analyzed by 1 H MR (Figure 1). D [D 1 ]-1a + 2a standard conditions k H /k D = % yield 3a + D [D 1 ]-3a + D 3a [D 1 ]-3a Figure 1. 1 H MR spectra of the mixture of the product 3a and [D 1 ]-3a. S5

6 b) Intermolecular Kinetic Isotope Effect (KIE) Experiment: Aniline (ring-d 5, 98%, cat. o. DLM-862-0) were purchased from Cambridge Isotope Laboratories. The isotope reagent was used without further purification. [D 5 ]-1a was synthesized according the literature procedure using D 5 -aniline as starting material. 1 An oven-dried sealed tube was charged with [D 5 ]-1a (0.1 mmol), 1a (0.1 mmol), PdCl 2 (3.4 mg, 10 mol %), dppf (11.8 mg, 10 mol %), and K 3 P. 4 3H 2 (106 mg, 0.4 mmol). The tube was evacuated and backfilled with nitrogen (three times). Then, a solution of iodocyclohexane 2a (0.5 mmol, 2.5 equiv) in diglyme (2.0 ml) was injected by syringe. The tube was then sealed with a Teflon lined cap and placed into a preheated oil bath at 100 C with vigorous stirring. After 24 h, the resulting mixture was diluted with EtAc, and the organic phase was washed successively with H 2 (three times) and brine (one time) then dried (a 2 S 4 ) and concentrated in vacuo. The residue was purified by column chromatography on silica gel to give the corresponding product. The product was analyzed by 1 H MR (Figure 2). D D 1a D + 2a standard conditions k H /k D = % yield 3a + D D D D D D [D 5 ]-1a [D 4 ]-3a 1a/[D 5 ]-1a = 1:1 D D + D D 3a [D 4 ]-3a Figure 2. 1 H MR spectra of the mixture of the product 3a and [D 4 ]-3a. S6

7 Proposed Mechanism According to the above control experiments, a possible mechanism is proposed in Figure 3. Fristly, carbon-centered radical I is formed by single-electron oxidative addition of the iodocyclohexane in the presence of Pd(0). Subsequently, the radical I adds to the C=C bond of acrylamide to give alkyl radical II, which undergoes an intramolecular cyclization to generate radical intermediate III. Finally, a Pd(I)-mediated single-electron oxidation of radical III into the corresponding carbocation followed by the loss of H +, leads to the desired product 3a and regenerates Pd(0). Figure 3. Proposed Mechanism 2a I LnPd(0) LnPd(I)I I 1a II base-h I + LnPd(0) base + LnPd(I)I H 3a III S7

8 References (1) (a) Wu, T.; Mu, X.; Liu, G. Angew. Chem. Int. Ed. 2011, 50, (b) Mu, X.; Wu, T.; Wang, H.-Y.; Guo, Y.-L.; Liu, G. J. Am. Chem. Soc. 2012, 134, 878. (c) Fabry, D. C.; Stodulski, M.; Hoerner, S.; Gulder, T. Chem. Eur. J. 2012, 18, (d) McMahon, C. M.; Alexanian, E. J. Angew. Chem., Int. Ed. 2014, 53, S8

9 1 H MR and 13 C MR Spectra of Products 3 3a 3a S9

10 Me 3b Me 3b S10

11 Me 3c Me 3c S11

12 CF 3 3d CF 3 3d S12

13 C 3e C 3e S13

14 C 2 Et 3f C 2 Et 3f S14

15 Cl 3g Cl 3g S15

16 Me 3i Me 3i S16

17 Me 3j Me 3j S17

18 F 3k F 3k S18

19 Ph 3l Ph 3l S19

20 Me Me 3m Me Me 3m S20

21 Me Me 3n Me Me 3n S21

22 Me Me 3o Me Me 3o S22

23 Bn 3p Bn 3p S23

24 Ph 3q Ph 3q S24

25 Bn 3r Bn 3r S25

26 Ph 3s Ph 3s S26

27 Me H 3t Me H 3t S27

28 1 H MR and 13 C MR Spectra of Products 4 4a 4a S28

29 n C 6 H 13 4b n C 6 H 13 4b S29

30 n C 4 H 9 4c n C 4 H 9 4c S30

31 n C 4 F 9 4d n C 4 F 9 4d S31

32 n C 4 F 9 4d S32

33 n C 6 F 13 4e n C 6 F 13 4e S33

34 n C 6 F 13 4e S34

35 n C 8 F 17 4f n C 8 F 17 4f S35

36 n C 8 F 17 4f S36

37 4g 4g S37

38 i Bu 4h i Bu 4h S38

39 t Bu 4i t Bu 4i S39

40 4j 4j S40

41 Ph 4k Ph 4k S41

42 Me 4l Me 4l S42

43 C 4m C 4m S43

44 C 2 Me 4n C 2 Me 4n S44

45 Cl Cl 4o Cl Cl 4o S45

46 Ph 6a Ph 6a S46

47 8a 8a S47

48 8b 8b S48