Supporting Information For Synthesis of Enamides via CuI-Catalyzed Reductive Acylation of Ketoximes with NaHSO 3 Zheng-Hui Guan*, Zhi-Yuan Zhang, Zhi-Hui Ren, Yao-Yu Wang, and Xumu Zhang Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of Ministry of Education, Department of Chemistry & Materials Science, Northwest University, Xi an 710069, P. R. China (E-mail: guanzhh@nwu.edu.cn) Context 1. General information-----------------------------------------------------------------------s2 2. Typical procedure for CuI-Catalyzed Reductive Acylation of Ketoximes------S2 3. Spectroscopic data for enamides 2-------------------------------------------------S2-S6 4. Copies of 1 H NMR, 13 C NMR spectra--------------------------------------------s7-s52 S 1
General information: Column chromatography was carried out on silica gel. 1 H NMR spectra were recorded on 400 MHz in d 6 -DMSO or CDCl 3 and 13 C NMR spectra were recorded on 100 MHz in d 6 -DMSO or CDCl 3. Commercially available reagents and solvents were used without further purification. The ketoximes were in all cases prepared from the corresponding ketones according to literature procedures 1,2 and used in the reaction without further purification. (1) Bousquet, E. W.; Carothers, W. H.; McEwen, W. L. Organic Synthesis; Wiley and Sons: New York, 1943; Collect. Vol II, pp 313-315. (2) Zhao, H.; Vandenbossche, C. P.; Koenig, S. G.; Singh, S. P.; Bakale, R. P. Org. Lett. 2008, 10, 505. Typical procedure for CuI-Catalyzed Reductive Acylation of Ketoximes: R 1 OH N 10 mol%cui, 2 eq Ac 2 O, 3eq NaHSO 3 n DCE, 120 o C The mixture of ketoxime 1 (0.5 mmol), acetic anhydride (1.0 mmol, 102.0 mg), NaHSO 3 (1.5 mmol, 156.2 mg) and CuI (10 mol%, 9.1 mg) was stirred in 1,2-dichloroethane (DCE, 5.0 ml) at 120 C under Ar, After completion of the reaction (detected by TLC), the reaction mixture was cooled to room temperature, diluted with EtOAc (25 ml) and washed with NaOH (2N, 20 ml) and brine (20 ml). The organic layers were dried over anhydrous Na 2 SO 4 and evaporated in vacuo. The desired enamide 2 was obtained after purification by flash chromatography on silica gel with hexane/ethyl acetate as the eluent. Spectroscopic data for enamides 2: R 2 n 2a 1 : 1 H NMR (400 MHz, CDCl 3 ) δ 7.42-7.34 (m, 5H), 6.89 (bs, 1H), 5.87 (s, 1H), 5.09 (s, 1H), 2.13 (s, 3H). 13 C NMR (100 MHz, CDCl 3 ) δ 169.2, 140.5, 138.3, 128.6, 126.0, 102.6, 24.4. 2b 1 : 1 H NMR (400 MHz, CDCl 3 ) δ 7.31 (d, J = 8 Hz, 2H), 7.17 (d, J = 8 Hz, 2H), 6.94 (bs, 1H), 5.81 (s, 1H), 5.05 (s, 1H), 2.38 (s, 3H), 2.11 (s, 3H). 13 C NMR (100 MHz, CDCl 3 ) δ 169.0, 140.3, 138.6, 135.5, 129.3, 125.9, 101.8, 24.5, 21.1. S 2
MeO 2c 2 : 1 H NMR (400 MHz, CDCl 3 ) δ 7.34 (d, J = 8 Hz, 2H), 6.88 (d, J = 8 Hz, 2H), 5.76 (s, 1H), 5.01 (s, 1H), 3.82 (s, 3H), 2.11 (s, 3H). 13 C NMR (100 MHz, CDCl 3 ) δ 169.4, 159.6, 140.1, 130.5, 127.2, 113.5, 101.5, 55.2, 24.1. AcHN 2d: 1 H NMR (400 MHz,DMSO) δ 10.02 (s, 1H), 9.25 (s, 1H), 7.58 (d, J = 9.2 Hz, 2H), 7.37 (d, J = 8.4 Hz, 2H), 5.54 (s, 1H), 4.95 (s, 1H), 2.03 (s, 6H). 13 C NMR (100 MHz, DMSO) δ 174.2, 173.5, 146.1, 144.5, 137.6, 131.7, 123.7, 106.1, 29.1, 28.9. Br 2e 2 : 1 H NMR (400 MHz, CDCl 3 ) δ 7.45 (d, J = 8 Hz, 2H), 7.25 (m, 3H), 5.70 (s, 1H), 5.06 (s, 1H), 2.05 (s, 3H). 13 C NMR (100 MHz, CDCl 3 ) δ 169.3, 139.6, 137.0, 131.6, 127.6, 103.7, 24.2. Cl 2f 3 : 1 H NMR (400 MHz, CDCl 3 ) δ 7.37 (s, 4H), 7.00 (bs, 1H), 5.76 (s, 1H), 5.08 (s, 1H), 2.10 (s, 3H). 13 C NMR (100 MHz, CDCl 3 ) δ 169.4, 139.6, 136.4, 134.2, 128.5, 127.3, 103.7, 24.0. F 2g 4 : 1 H NMR (400 MHz, CDCl 3 ) δ 7.40 (s, 2H), 7.08-7.05 (t, J = 8.4 Hz, 2H), 6.84 (bs, 1H), 5.79 (s, 1H), 5.04 (s, 1H), 2.13 (s, 3H). 13 C NMR (100 MHz, CDCl 3 ) δ 169.7, 162.9 (d, J = 246.3 Hz), 139.8, 134.0, 127.8 (d, J = 7.7 Hz), 115.1 (d, J = 7.7 Hz), 103.3, 23.8. O 2 N 2h 2 : 1 H NMR (400 MHz, CDCl 3 ) δ 8.22 (d, J = 8.8 Hz, 2H), 7.58 (d, J= 8.4 Hz, 2H), 6.92 (bs, 1H), 5.82 (s, 1H), 5.27 (s, 1H), 2.17 (s, 3H). 13 C NMR (100 MHz, CDCl 3 ) δ 169.1, 147.6, 144.1, 139.2, 126.8, 123.9, 107.1, 24.2. S 3
MeO 2i 3 : 1 H NMR (400 MHz, DMSO) δ 9.31 (s, 1H), 7.32-7.30 (t, J = 8 Hz, 1H), 7.04-6.92 (m, 3H), 5.65 (s, 1H), 5.01 (s, 1H), 3.78 (s, 3H), 2.02 (s, 3H). 13 C NMR (100 MHz, DMSO) δ 174.3, 164.3, 146.4, 144.7, 134.5, 123.7, 118.9, 117.0, 107.0, 60.2, 28.9. 2j 5 : 1 H NMR (400 MHz, CDCl 3 ) δ 7.19-7.12 (m, 3H), 6.79 (bs, 1H), 5.84 (s, 1H), 5.05 (s, 1H), 2.27 (s, 6H), 2.14 (s, 3H). 13 C NMR (100 MHz, CDCl 3 ) δ 169.2, 140.5, 137.1, 136.7, 135.8, 129.7, 127.1, 123.3, 101.5, 24.3, 19.7, 19.4. 2k: 1 H NMR (400 MHz, CDCl 3 ) δ 7.17 (bs, 1H), 7.06 (s, 3H), 5.97 (s, 1H), 4.65 (s, 1H), 2.31 (s, 3H), 2.28 (s, 3H), 1.95 (s, 3H). 13 C NMR (100 MHz, CDCl 3 ) δ 168.9, 140.5, 138.3, 135.2, 132.4, 130.2, 129.7, 129.0, 102.1, 24.1, 20.7, 18.9. 2l 6 : 1 H NMR (400 MHz, CDCl 3 ) δ 7.4 (d, J = 8.4 Hz, 4H), 7.55-7.50 (m, 3H), 6.98 (bs, 1H), 5.95 (s, 1H), 5.24 (s, 1H), 2.18 (s, 3H). 13 C NMR (100 MHz, CDCl 3 ) δ 169.4, 140.4, 135.3, 133.1, 132.9, 128.2, 128.1, 127.5, 126.4, 126.3, 124.7, 124.0, 103.5, 24.2. 2m: 1 H NMR (400 MHz, CDCl 3 ) δ 7.14-7.05 (m, 3H), 6.78 (bs,1h), 5.84 (s, 1H), 5.03 (s, 1H), 2.77 (s, 4H), 2.13 (s, 3H), 1.79 (s, 4H). 13 C NMR (100 MHz, CDCl 3 ) δ 169.1, 140.5, 137.7, 137.2, 135.4, 129.2, 126.5, 123.0, 101.4, 29.3, 29.0, 24.3, 22.9. 2n 6 : 1 H NMR (400 MHz, DMSO) δ 9.11 (s, 1H), 7.40-7.36 (m, 2H), 7.32-7.26 (m, 3H), 6.05 (q, J = 6.8 Hz, 1H), 1.90 (s, 3H), 1.61 (d, J = 7.2 Hz, 3H). 13 C NMR (100 S 4
MHz, DMSO) δ 173.5, 141.8, 140.2, 133.8, 133.1, 132.6, 118.5, 28.6, 18.7. 2n 6 : 1 H NMR (400 MHz, DMSO) δ 9.12 (s, 1H), 7.38-7.22 (m, 5H), 5.90 (q, J = 6.8 Hz, 1H), 2.01 (s, 3H), 1.66 (d, J = 6.8 Hz, 3H). 13 C NMR (100 MHz, DMSO) δ 172.9, 143.5, 139.9, 133.3, 132.3, 130.2, 124.4, 27.8, 18.9. 2o 6 : 1 H NMR (400 MHz, DMSO) δ 9.03 (s, 1H), 7.33-7.20 (m, 5H), 1.89 (s, 3H), 1.71 (s, 6H), 13 C NMR (100 MHz, DMSO) δ 172.7, 144.2, 134.0, 132.9, 132.5, 131.8, 51.5, 27.8, 25.9. N H O 2p 7 : 1 H NMR (400 MHz, CDCl 3 ) δ 7.40-7.31 (m, 6H), 5.79 (s, 1H), 5.04 (s, 1H), 2.26 (q, J = 7.2 Hz, 2H), 1.14 (t, J =7.2 Hz, 2H). 13 C NMR (100 MHz, CDCl 3 ) δ 173.0, 140.5, 138.3, 128.4, 125.9, 102.3, 30.3, 9.5. 2q 1 : 1 H NMR (400 MHz, DMSO) δ 9.12 (s, 1H), 7.20-7.16 (m, 4H), 6.16 (s, 1H), 2.70-2.68 (t, J = 8 Hz, 2H), 2.27 (s, 2H), 2.01 (s, 3H). 13 C NMR (100 MHz, DMSO) δ 174.0, 141.2, 137.6, 136.9, 132.6, 132.3, 131.3, 127.3, 124.2, 32.3, 28.5, 26.9. MeO 2r 1 : 1 H NMR (400 MHz, DMSO) δ 9.05 (s, 1H), 7.14 (d, J = 8.4 Hz, 1H), 6.75 (s, 2H), 6.04 (s, 1H), 3.74 (s, 3H), 2.66 (s, 2H), 2.23 (s, 2H), 2.01 (s, 3H). 13 C NMR (100 MHz, DMSO) δ 173.9, 163.6, 143.1, 137.3, 129.8, 128.6, 121.2, 118.5, 116.1, 60.2, 32.8, 28.5, 26.9. 2s 1 : 1 H NMR (400 MHz, CDCl 3 ) δ 7.49 (d, J = 8 Hz, 1H), 7.36 (s, 1H), 7.2 (d, J = 7.6 Hz, 1H), 7.28-7.25 (m, 2H), 6.88 (s, 1H), 3.44 (s, 2H), 2.25 (s, 3H). 13 C NMR (100 MHz, CDCl 3 ) δ 169.3, 142.6, 139.7, 135.6, 125.8, 125.2, 124.0, 116.6, 115.8, 36.4, S 5
23.9. Cl 2t 8 : 1 H NMR (400 MHz, DMSO) δ 9.80 (s, 1H), 7.77 (d, J = 8 Hz, 1H), 7.52 (s, 1H), 7.40 (d, J = 8 Hz, 1H), 6.76 (s, 1H), 3.39-3.34 (m, 2H), 2.10 (s, 3H). 13 C NMR (100 MHz, DMSO) δ 174.1, 149.7, 144.1, 141.2, 135.2, 131.1, 129.3, 124.7, 119.7, 41.1, 28.6. 2u 9 : 1 H NMR (400 MHz, CDCl 3 ) δ 6.31 (bs, 1H), 6.06 (s,1h), 2.11-2.04 (m, 4H), 2.01 (s, 3H), 1.70-1.65 (m, 2H), 1.59-1.54 (m, 2H). 13 C NMR (100 MHz, CDCl 3 ) δ 168.7, 132.7, 113.1, 27.7, 24.0, 23.8, 22.3, 21.7. 2v 9 : 1 H NMR (400 MHz, DMSO) δ 9.38 (s, 1H), 5.74 (s, 1H), 2.37-2.33 (m, 2H), 2.28 (s, 2H), 1.99-1.89 (m, 3H), 1.75-1.70 (m, 2H). 13 C NMR (100 MHz, DMSO) δ 172.9, 142.2, 113.2, 38.1, 35.7, 28.5, 25.9. References: (1) Guan, Z.-H.; Huang, K.; Yu, S.; Zhang, X. Org. Lett. 2009, 11, 481. (2) Tang, W.; Capacci, A.; Sarvestani, M.; Wei, X.; Yee, N. K.; Senanayake, C. H. J. Org. Chem. 2009, 74, 9528. (3) Gridnev, I. D.; Yasutake, M.; Higashi, N.; Imamoto, T. J. Am. Chem. Soc. 2001, 123, 5268 (4) Shi, L.; Wang, X.; Sandoval, C. A.; Wang, Z.; Li, H.; Wu, J.; Yu, L.; Ding, K. Chem. Eur. J. 2009, 15, 9855. (5) Jia, Y.-X.; Zhong, J; Zhu, S-F; Zhang, C-M; Zhou, Q-L. Angew. Chem., Int. Ed. 2007, 46, 5565. (6) Zhao, H.; Vandenbossche, C. P.; Koenig, S. G.; Singh, S. P.; Bakale, R. P. Org. Lett. 2008, 10, 505. (7) Baudequin, C; Zamfir, A; Tsogoeva, S. B. Chem. Commun. 2008, 38, 4637. (8) Sklarz, B; Cohen, S; Speiser, T.; Nachman, R. PCT Int. Appl. (2000), 70 pp. WO 2000038673 A1 20000706 CAN 133:73867 AN 2000:456874 (9) Gilmore, C. D.; Allan, K. M.; Stoltz, B. M. J. Am. Chem. Soc. 2008, 130, 1558 S 6
2a: S 7
2a: S 8
2b: S 9
2b: S 10
2c: MeO S 11
2c: MeO S 12
2d: AcHN S 13
2d: AcHN S 14
2e: Br S 15
2e: Br S 16
2f: Cl S 17
2f: Cl S 18
2g: F S 19
2g: F S 20
2h: O 2 N S 21
2h: O 2 N S 22
MeO 2i: S 23
MeO 2i: S 24
2j: S 25
2j: S 26
2k: S 27
2k: S 28
2l: S 29
2l: S 30
2m: S 31
2m: S 32
2n: S 33
2n: S 34
2n: S 35
2n: S 36
2o: S 37
2o: S 38
O 2p: N H S 39
O 2p: N H S 40
2q: S 41
2q: S 42
2r: MeO S 43
2r: MeO S 44
2s: S 45
2s: S 46
2t: Cl S 47
2t: Cl S 48
2u: S 49
2u: S 50
2v: S 51
2v: S 52