A ew Type of Bis(sulfonamide)-Diamine Ligand for a Cu(OTf) 2 -Catalyzed Asymmetric Friedel-Crafts Alkylation Reaction of Indoles with itroalkenes Jing Wu, Xincheng Li, Fan Wu, and Boshun Wan* Dalian Institute of Chemical ysics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian 116023, China. E-mail: bswan@dicp.ac.cn Supporting Information
Table of Contents 1. General information S2 2. The preparation of Bis(sulfonamide)-Diamine Ligand L1 L7 S2 3. Optimization of the model reaction S2 S3 4. Asymmetric Friedel-Craft Alkylation of indole with nitroalkene S3 5. Results of some commercially available indole analogues S3-S4 6. Analysis of the ligand L1-L7 and products S3 S10 7. Copy of MR, RMS and PLC for racemic and chiral compounds S11 S65 S1
1. General information All reactions were carried out under an atmosphere of argon using standard Schlenk techniques, unless otherwise noted. 1 MR and 13 C MR spectra were recorded on Bruker DRX 400 or Bruker DRX 500 spectrometers (400 Mz or 500 Mz for 1 MR, 100 Mz or 126 Mz for 13 C MR, see details of each compound) using CDCl 3 or CD 3 COCD 3 as solvent. Tetramethylsilane (δ = 0) or CDCl 3 (δ = 7.27) or CD 3 COCD 3 (2.05 ppm) serves as the internal standard for 1 MR and CDCl 3 (77.16 ppm) and CD 3 COCD 3 (29.84 ppm) for 13 C MR. Coupling constants (J) are reported in z and refer to apparent peak multiplications. Optical rotations were measured with JASCO P 1010 polarimeter. RMS data were obtained with Micromass PLC-Q-TOF mass spectrometer Flash column chromatography was performed on silica gel (300 400 mesh). TLC analysis was performed using glass-backed plates coated with 0.2 mm silica. Commercially available reagents were used throughout without further purification. All solvents were purified according to the standard procedures. 2. The preparation of Bis(sulfonamide)-Diamine Ligand L1 L7 R 1 R 1 O R 2 TsCl, K 2 CO 3 2 C 3 C Ts R 2 1,2-diamines, reflux C 3 C or C 3 O R 2 Ts Ts R 2 L1-L7 were synthesized by the same procedure in the literature 1,2,3. 3. Optimization of model reaction Table 1. Screening of Lewis acids for the reaction Entry Metal salt Yield (%) Ee (%) 1 Cu(OTf) 2 68 21 2 FeCl 3 88 2 3 Ag(OTf) 52 0 4 Zn(OTf) 2 94 0 5 Cu(OTf). C 6 6 38 0 6 CuCl 2 29 3 7 Cu(OAc) 2 23 8 1 Jin, W.; Li, X. C.; uang, Y. B.; Wu, F.; Wan, B. S. Chem. Eur. J. 2010, 16, 8259. 2 Jin, W.; Li, X. C.; Wan, B. S. J. Org. Chem. 2011, 76, 484. 3 Pei, Y.; Brule, E.; Moberg, C. Org. Biomol. Chem. 2006, 4, 544. S2
Table 2. Optimization of the solvents Entry Solvent Isolated yield (%) Ee (%) 1 toluene 94 91 2 C 2 Cl 2 99 86 3 CCl 3 99 85 4 DCE 97 81 5 Et 2 O 23 40 6 TF 7 7 7 C 3 C 8 0 9 p-xylene 91 85 10 CF 3 99 92 11 benzene 86 88 4. Asymmetric 1,4-addition of arylboronic acids to 2-cyclohexenone Under argon atmosphere, a mixture of Cu(OTf) 2 (4.5 mg, 0.0125 mmol) and L6 (9.5 mg, 0.0125mmol) in CF 3 (3 ml) was stirred at room temperature in a 25 ml Schlenk tube for 2 h to give the catalyst. After putting it into a freezer with the temperature of 0 C, this mixture was added nitroalkene (0.375 mmol). After stirred for 10 min, indole (0.25 mmol) was added. The reaction was stirred at 0 C and monitored by TLC. When the reaction was over, the reaction mixture was directly charged onto a column (silica gel) and flash chromatograph with a mixture of petroleum ether/c 3 CO 2 Et to afford the product. 5. Results of some commercially available indole analogues S3
Entry R Yield (%) Ee (%) 1 1-Me 51 17 2 2-Me 87 0 3 2-47 9 4 7-Me 68 1 6. Analysis of the ligand L1-L7 and product L1 white solid; m.p. = 159 161 C; yield 92%; R f = 0.33 Ts Ts (C 2 Cl 2 /C 3 O = 30/1); [α] 23 D = +35.7 (c 0.63, CCl 3 ); MR (500 Mz, CDCl 3 ) δ 7.81 (d, J = 8.3 z, 4), 7.29 (d, J = 8.0 z, 4), 7.18 7.03 (m, 6), 7.02 6.91 (m, 4), 5.78 (s, 2), 3.52 (s, 2), 3.18 3.04 (m, 2), 2.54 (dd, J = 12.6, 5.0 z, 2), 2.48 2.39 (m, 9), 1.85 1.66 (m, 1), 0.68 (d, J = 6.7 z, 6), 0.64 (d, J = 6.8 z, 6); 13 C MR (126 Mz, CDCl 3 ) δ 143.0, 141.5, 139.0, 129.6, 128.0, 127.9, 127.1, 126.9, 69.0, 60.0, 48.0, 30..0, 21.6, 19.4, 18.9; RMS Calculated for C 38 51 4 O 4 S 2 [M+] + 691.3352, found 691.335. 1 Ts Ts L2 white solid; m.p. = 205 207 C; yield 83%; R f = 0.40 (C 2 Cl 2 /C 3 O = 30/1); [α] 25 D = +44.2 (c 0.75, CCl 3 );. 1 MR (500 Mz, CDCl 3 ) δ 7.68 (d, J = 8.1 z, 4), 7.20 (d, J = 8.1 z, 4), 7.16 7.07 (m, 6), 6.97 (d, J = 6.4 z, 4), 5.56 (s, 2), 3.49 (s, 2), 3.14 (s, 2), 2.46 (dd, J = 11.6, 7.2 z, 2), 2.42 2.35 (m, 8), 1.70 1.61 (m, 3), 0.73 (d, J = 6.8 z, 6), 0.68 (d, J = 6.8 z, 6). 13 C MR (126 Mz, CDCl 3 ) δ 142.9, 141.4, 139.0, 129.6, 128.1, 128.0, 127.0, 69.4, 60.0, 48.5, 30.7, 21.6, 19.2, 18.6; RMS Calculated for C 38 51 4 O 4 S 2 [M+] + 691.3352, found 691.3356. Ts L3: known compond 3 white foam; m.p. = 62 64 C; yield 80%; R f = 0.35 (C 2 Cl 2 /C 3 O = 30/1); [α] 25 D = 12.3 (c 1.09, CCl 3 ); 1 MR (400 Mz, CDCl 3 ) δ 7.81 (d, J = 8.2 z, 4), 7.28 (d, J = 8.1 z, 4), 5.83 (s, 1), 3.14 3.02 (m, 2), 2.87 Ts (dd, J = 12.1, 5.0 z, 2), 2.59 (dd, J = 12.1, 3.5 z, 2), 2.41 (s, 6), 2.23 2.13 (m, 2), 1.99 (d, J = 12.4 z, 2), 1.73 (m, 4), 1.30 1.14 (m, 2), 1.02 (dd, J = 13.1, 6.1 z, 2), 0.76 (d, J = 6.7 z, 6), 0.67 (d, J = 6.7 z, 6); 13 C MR (101 Mz, CDCl 3 ) δ 142.9, 138.8, 129.6, 127.0, 61.4, 60.2, 47.4, 32.1, 29.9, 25.3, 21.6, 19.4, 19.0. Ts Ts L4: white foam; m.p. = 71 73 C; yield 79%; R f = 0.23 (C 2 Cl 2 /C 3 O = 30/1); [α] 25 D = +13.8 (c 1.28, CCl 3 ); 1 MR (500 Mz, CDCl 3 ) δ 7.83 (d, J = 8.3 z, 4), 7.30 (d, J = 8.2 z, 4), 7.15 7.03 (m, 6), 6.92 (dd, J = 7.6, 1.6 z, 4), 5.66 (s, 2), 3.53 (s, 2), 3.48 (m, 2), 2.55 (s, 2), 2.45 2.38 (m, 8), 2.34 (dd, J = 12.8, 7.1 z, 2), 0.92 (d, J = 6.6 z, 6); 13 C MR (126 Mz, CDCl 3 ) δ 143.1, 141.1, 138.7, 129.7, 128.0, 127.2, 127.0, 68.0, 51.8, 48.9, 21.6, 19.1; RMS Calculated for C 34 43 4 O 4 S 2 [M+] + 635.2726, found 635.2721. S4
L5: white solid; m.p. = 104 108 C; yield 95%; R f = 0.30 (C 2 Cl 2 /C 3 O = 30/1); [α] 25 D = +46.3 (c 1.25, CCl 3 ); 1 MR (400 Mz, CDCl 3 ) δ 7.60 (d, J = 8.2 z, 4), 7.15 (d, J Bn Bn = 8.1 z, 4), 7.13 7.04 (m, 12), 6.93 (m, 8), 5.71 (s, 2), Ts Ts 3.67 3.52 (m, 4), 2.74 (dd, J = 13.8, 7.3 z, 2), 2.69 2.57 (m, 4), 2.48 (dd, J = 12.4, 4.4 z, 3), 2.39 (s, 6); 13 C MR (101 Mz, CDCl 3 ) δ 142.9, 141.3, 138.2, 137.7, 129.7, 129.3, 128.5, 128.1, 128.0, 127.0, 127.0, 126.4, 69.2, 55.3, 50.3, 39.2, 21.7; RMS Calculated for C 46 51 4 O 4 S 2 [M+] + 787.3352, found 787.3345. L6: white foam; m.p. = 75 77 C; yield 55%; R f = 0.68 (C 2 Cl 2 /C 3 O = 30/1); [α] 25 D = +61.6 (c 1.26, CCl 3 ); 1 MR (400 Mz, CDCl 3 ) δ 7.81 (d, J = 8.3 z, 4), 7.33 (d, J = 8.1 z, 4), 7.31 7.18 (m, 10), 7.14 7.05 (m, 6), 6.96 Ts Ts (dd, J = 6.5, 3.0 z, 4), 5.73 (s, 2), 3.95 (t, J = 5.4 z, 2), 3.90 (s, 2), 3.49 (dd, J = 13.0, 4.6 z, 2), 3.12 (dd, J = 13.0, 6.4 z, 2), 2.96 (s, 1), 2.49 (s, 6); 13 C MR (101 Mz, CDCl 3 ) δ 143.3, 141.4, 141.3, 137.3, 129.8, 128.5, 127.9, 127.9, 127.4, 127.1, 127.1, 126.9, 67.4, 60.3, 47.6, 21.6; RMS Calculated for C 44 47 4 O 4 S 2 [M+] + 759.3039, found 759.3032. Ts Ts L7: white solid, m.p. = 192 196 C; yield 83%; R f = 0.48 (C 2 Cl 2 /C 3 O = 30/1); [α] 25 D = 30.9 (c 1.04, CCl 3 ); MR (400 Mz, CDCl 3 ) δ 7.77 (d, J = 7.8 z, 4), 7.27 (d, J = 7.9 z, 4), 7.13 (m, 6), 6.97 (d, J = 7.1 z, 4), 5.74 (s, 2), 3.48 (s, 2), 3.14 (s, 2), 2.55 (dd, J = 12.9, 4.4 z, 2), 2.42 (s, 8), 2.26 (dd, J = 12.8, 3.8 z, 2), 0.74 (s, 18); 13 C MR (101 Mz, CDCl 3 ) δ 142.8, 141.5, 139.1, 129.5, 128.0, 127.9, 127.1, 127.0, 69.0, 61.8, 47.0, 34.8, 27.4, 21.6; RMS Calculated for C 44 47 4 O 4 S 2 [M+] + 719.3665, found 719.3669. 3a (R)-(2-itro-1-phenylethyl)-1-indole: known compound 4 ; Following the general procedure, the compond was obtained as yellow oil in 99% yield and 95% ee; [α] 22 D = 22.3 (c 0.91, C 2 Cl 2 ); [lit. 5 : [α] 20 D = 24.9 (c O 1.06, C 2 Cl 2 ) for 96% ee;] R f = 0.3 (petroleum ether/etoac = 4/1); 1 2 MR (500 Mz, CDCl 3 ) δ 8.05 (s, 1), 7.44 (dd, J = 8.0, 0.7 z, 1), 7.37-7.22 (m, 6), 7.22-7.16 (m, 1), 7.07 (m, 1), 7.02 (dd, J = 2.4, 0.5 z, 1), 5.18 (t, J = 8.0 z, 1), 5.06 (dd, J = 12.5, 7.6 z, 1), 4.94 (dd, J = 12.5, 8.3 z, 1); 13 C MR (126 Mz, CDCl 3 ) δ 139.4, 136.7, 129.1, 127.9, 127.7, 126.3, 122.9, 121.7, 120.1, 119.1, 114.7, 111.5, 79.7, 41.7; PLC: Daicel Chiralpak AD-, hexane/i-pro = 90/10, Flow rate = 1.0 ml/min, UV = 210 nm, t R = 25.2 min (major) and t R = 27.7 min. 4 Jia, Y. X.; Zhu, S. F.; Yang, Y.; Zhou, Q. L. J. Org. Chem. 2006, 71, 75. S5
Cl 3b (R)-3-[1-(4-Chlorophenyl)-2-nitroethyl]-1-indole: known compound 4 ; yellow oil; 96% yield; 92% ee; [α] 23 D = 8.34 (c 2.11, C 2 Cl 2 ); [lit. 5 : [α] 20 D = 9.7 (c 0.79, C 2 Cl 2 ) for 91% ee;] R f = 0.28 O (petroleum ether/etoac = 4/1); 1 2 MR (400 Mz, Acetone) δ 10.28 (s, 1), 7.52 (d, J = 8.0 z, 1), 7.50-7.45 (m, 2), 7.42 (m, 2), 7.36-7.31 (m, 2), 7.17 7.09 (m, 1), 7.05-6.97 (m, 1), 5.35 5.16 (m, 3); 13 C MR (101 Mz, Acetone) δ 140.4, 137.7, 133.2, 130.6, 129.4, 127.1, 123.0, 122.8, 120.0, 119.4, 114.4, 112.4, 79.9, 41.6; PLC: Daicel Chiralcel OD- column, hexane/i-pro = 70/30, Flow rate = 1.0 ml/min, UV = 254 nm, t R = 25.6 min and t R = 34.1 min (major). Cl 3c (R)-3-[1-(3-Chlorophenyl)-2-nitroethyl]-1-indole: known compound 5 ; yellow oil; 94% yield; 94% ee; [α] 23 D = 18.04 (c 1.62, C 2 Cl 2 ); [lit. 5 : [α] 20 D = 18.1 (c 1.06, C 2 Cl 2 ) for 92% ee;] R f = 0.3 O (petroleum ether/etoac = 4/1); 1 2 MR (500 Mz, CDCl 3 ) δ 8.09 (s, 1), 7.42 (dd, J = 8.0, 0.8 z, 1), 7.37 7.33 (m, 1), 7.30 (d, J = 2.2 z, 1), 7.25 7.18 (m, 4), 7.08 (ddd, J = 8.0, 7.1, 0.9 z, 1), 7.01 (dd, J = 2.5, 0.6 z, 1), 5.15 (t, J = 8.0 z, 1), 5.03 (dd, J = 12.7, 7.5 z, 1), 4.90 (dd, J = 12.7, 8.4 z, 1); 13 C MR (126 Mz, CDCl 3 ) δ 141.5, 136.7, 135.0, 130.3, 128.1, 128.0, 126.1, 126.1, 123.0, 121.7, 120.3, 118.9, 113.9, 111.6, 79.3, 41.3; PLC: Daicel Chiralcel OD- column, hexane/i-pro = 70/30, Flow rate = 1.0 ml/min, UV = 254 nm, t R = 24.9 min and t R = 38.4 min (major). 3d (R)-3-[1-(2-Chlorophenyl)-2-nitroethyl]-1-indole: known Cl compound 4, yellow oil; 99% yield; 97% ee; [α] 21 D = 80.9 (c 1.51, C 2 Cl 2 ); [lit. 5 : [α] 20 D = 82.7 (c 1.12, C 2 Cl 2 ) for 91% ee;] R f = 0.28 O (petroleum ether/etoac = 4/1); 1 2 MR (400 Mz, Acetone) δ 10.31 (s, 1), 7.55 (d, J = 7.9 z, 1), 7.53 7.49 (m, 1), 7.49 7.44 (m, 1), 7.42 (m, 2), 7.31 7.20 (m, 2), 7.16 7.09 (m, 1), 7.06 6.97 (m, 1), 5.77 (t, J = 8.0 z, 1), 5.30 (dd, J = 13.2, 8.3 z, 1), 5.22 (dd, J = 13.2, 7.8 z, 1); 13 C MR (101 Mz, Acetone) δ 138.5, 137.7, 134.3, 130.6, 130.1, 129.6, 128.3, 127.3, 123.7, 122.8, 120.1, 119.2, 113.6, 112.5, 78.7, 38.5; PLC: Daicel Chiralcel OD- column, hexane/i-pro = 70/30, Flow rate = 1.0 ml/min, UV = 254 nm, t R = 16.6 min (major) and t R = 28.5 min. 3e (R)-3-[1-(4-Methylphenyl)-2-nitroethyl]-1-indole: known compound 5, yellow oil; 99% yield; 93% ee; [α] 23 D = 15.3 (c 2.10, C 2 Cl 2 ); [lit. 5 : [α] 20 D = -15.9 (c 0.83, C 2 Cl 2 ) for 96% ee;] R f = 0.25 O (petroleum ether/etoac = 4/1); 1 MR (400 Mz, Acetone) δ 10.23 (s, 2 1), 7.52 (d, J = 7.9 z, 1), 7.40 (d, J = 8.2 z, 1), 7.36 (m, 3), 7.10 (m, 3), 7.02 6.94 (m, 1), 5.27 (dd, J = 15.6, 10.8 z, 1), 5.21 5.12 (m, 2), 2.26 (s, 3); 13 C MR (101 Mz, Acetone) δ 138.4, 137.8, 137.4, 130.0, 128.7, 127.3, 122.8, 122.6, 119.9, 119.5, 115.0, 112.3, 80.3, 42.0, 21.0. PLC: 5 Guo, F. F. Lai, G. Y.; Xiong, S. S.; Wang, S. J.; Wang, Z. Y. Chem. Eur. J. 2010, 16, 6438. S6
Daicel Chiralcel OD- column, hexane/i-pro = 70/30, Flow rate = 1.0 ml/min, UV = 254 nm, t R = 17.9 min and t R = 22.2 min (major). MeO 3f (R)-3-[1-(4-Methoxyphenyl)-2-nitroethyl]-1-indole: known compound 4, white solid; m.p. 148 150 o C; 99% yield; 88% ee; [α] 23 D = 21.55 (c 2.22, C 2 Cl 2 ); [lit. 5 : [α] 20 D = 28.2 (c 1.04, C 2 Cl 2 ) for 95% ee;] R f = 0.15 (petroleum ether/etoac = 4/1); 1 MR (500 Mz, O 2 CDCl 3 ) δ 8.05 (s, 1), 7.43 (dd, J = 8.0, 0.7 z, 1), 7.34 (d, J = 8.2 z, 1), 7.26 7.21 (m, 2), 7.19 (ddd, J = 8.2, 7.2, 1.0 z, 1), 7.07 (ddd, J = 8.0, 7.1, 1.0 z, 1), 7.00 (dd, J = 2.5, 0.7 z, 1), 6.88 6.80 (m, 2), 5.13 (t, J = 8.0 z, 1), 5.03 (dd, J = 12.3, 7.5 z, 1), 4.89 (dd, J = 12.3, 8.4 z, 1), 3.76 (s, 3); 13 C MR (126 Mz, CDCl 3 ) δ 159.1, 136.7, 131.4, 129.0, 126.3, 122.8, 121.6, 120.1, 119.2, 115.0, 114.5, 111.5, 79.9, 55.4, 41.0; PLC: Daicel Chiralcel OD- column, hexane/i-pro = 70/30, Flow rate = 1.0 ml/min, UV = 254 nm, t R = 24.8 min and t R = 30.3 min (major). OMe 3g (R)-3-[1-(2-Methoxyphenyl)-2-nitroethyl]-1-indole: known compound 4 ; yellow oil; 96% yield; 93% ee; [α] 21 D = 48.3 (c 1.87, C 2 Cl 2 ); [lit. 5 : [α] 20 D = 47.8 (c 1.15, C 2 Cl 2 ) for 95% ee;] R f = 0.3 O 2 (petroleum ether/etoac = 4/1); 1 MR (400 Mz, Acetone) δ 10.21 (s, 1), 7.52 (d, J = 7.9 z, 1), 7.44 7.37 (m, 2), 7.28 7.18 (m, 2), 7.15 7.07 (m, 1), 7.06 6.95 (m, 2), 6.85 m, 1), 5.64 (t, J = 8.0 z, 1), 5.18 (dd, J = 8.0, 1.2 z, 2), 3.93 (s, 3); 13 C MR (101 Mz, Acetone) δ 157.9, 137.7, 129.6, 129.2, 129.0, 127.7, 123.4, 122.7, 121.4, 119.8, 119.5, 114.4, 112.3, 111.9, 79.0, 56.0, 35.8; PLC: Daicel Chiralcel OD- column, hexane/i-pro = 70/30, Flow rate = 1.0 ml/min, UV = 254 nm, t R = 13.7 min (major) and t R = 15.7 min. Br 3h (R)-3-[1-(2-Bromophenyl)-2-nitroethyl]-1-indole: known compound 6 ; yellow oil; 97% yield; 96% ee; [α] 22 D = 99.9 (c 1.3, C 2 Cl 2 ); R f = 0.25 (petroleum ether/etoac = 4/1); 1 MR (400 Mz, CDCl 3 ) δ O 2 8.10 (s, 1), 7.64 (d, J = 7.8 z, 1), 7.44 (d, J = 7.9 z, 1), 7.35 (d, J = 8.2 z, 1), 7.24 7.17 (m, 3), 7.16 7.06 (m, 3), 5.79 5.71 (m, 1), 5.03 4.90 (m, 2); 13 C MR (126 Mz, CDCl 3 ) δ 138.2, 136.6, 133.6, 129.2, 128.0, 126.3, 124.6, 122.8, 122.1, 120.1, 119.1, 113.4, 111.5, 77.9, 40.7; PLC: Daicel Chiralcel OD- column, hexane/i-pro = 70/30, Flow rate = 1.0 ml/min, UV = 254 nm, t R = 30.8 min and t R = 17.5 min (major). Br O 2 3i (R)-3-[1-(3-Bromophenyl)-2-nitroethyl]-1-indole: known compound 4 ; yellow oil; 99% yield; 93% ee; [α] 22 D = 12.8 (c 2.0, C 2 Cl 2 ); [lit. 4 : [α] 20 D = +14.7 (c 1.3, C 2 Cl 2 ) for 86% ee;] R f = 0.23 (petroleum ether/etoac = 4/1); 1 MR (500 Mz, CDCl 3 ) δ 8.09 (s, 1), 7.46 (t, J = 1.8 z, 1), 7.42 (dd, J = 8.0, 0.7 z, 1), 7.38 (m, 1), 7.34 (d, J = 6 Lin, S. Z.; You, T. P. Tetrahedron 2009, 65, 1010. S7
8.2 z, 1), 7.29 7.15 (m, 3), 7.08 (m 1), 7.00 (dd, J = 2.5, 0.6 z, 1), 5.13 (d, J = 8.0 z, 1), 5.02 (dd, J = 12.7, 7.5 z, 1), 4.89 (dd, J = 12.7, 8.4 z, 1); 13 C MR (126 Mz, CDCl 3 ) δ 141.8, 136.6, 131.0, 130.9, 130.6, 126.6, 126.1, 123.2, 123.0, 121.7, 120.3, 118.9, 113.9, 111.6, 79.3, 41.3; Daicel Chiralcel OD- column, hexane/i-pro = 70/30, Flow rate = 1.0 ml/min, UV = 254 nm, t R = 25.5 min and t R = 39.2 min (major). 3j (R)-3-[1-(4-Bromophenyl)-2-nitroethyl]-1-indole: known Br compound 4 : yellow oil; 96% yield; 92% ee; [α] 25 D = +9.8 (c 1.85, C 2 Cl 2 ); [lit. 4 : [α] 20 D = 1.7 (c 1.0, C 2 Cl 2 ) for 90% ee;] R f = 0.28 (petroleum ether/etoac = 4/1); 1 MR (400 Mz, Acetone) δ 10.29 O 2 (s, 1), 7.54 7.45 (m, 3), 7.41 (m, 4), 7.13 (t, J = 7.6 z, 1), 7.01 (t, J = 7.5 z, 1), 5.34 5.16 (m, 3); 13 C MR (101 Mz, Acetone) δ 140.9, 137.7, 132.4, 130.9, 127.1, 123.0 122.8, 121.3, 120.0, 119.4, 114.3, 112.4, 79.8, 41.7; Daicel Chiralcel OD- column, hexane/i-pro = 70/30, Flow rate = 1.0 ml/min, UV = 254 nm, t R = 27.4 min and t R = 37.4 min (major). F 3k (R)-3-[1-(2-Fluorophenyl)-2-nitroethyl]-1-indole: yellow oil, 98% yield; 96% ee; [α] 22 D = +4.4 (c 2.3, C 2 Cl 2 ); R f = 0.3 (petroleum ether/etoac = 8/1); 1 MR (400 Mz, Acetone) δ 10.30 (s, 1), 7.60 (d, O 2 J = 8.0 z, 1), 7.54 7.39 (m, 3), 7.28 (m, 1), 7.19 7.09 (m, 3), 7.08 7.01 (m, 1), 5.56 (t, J = 8.1 z, 1), 5.31 (m, 2); 13 C MR (101 Mz, Acetone) δ 161.4 (d, J C-F = 244.9 z), 137.6, 130.4 (d, J C-F = 3.9 z), 129.9 (d, J C-F = 8.5 z), 128.2 (d, J C-F = 13.9 z), 127.2, 125.4 (d, J C-F = 3.5 z), 123.4 (d, J C-F = 1.3 z), 122.8, 120.1, 119.1, 116.4 (d, J C-F = 22.5 z), 113.5, 112.5, 78.7 (d, J C-F = 1.8 z), 35.3 (d, J C-F = 3.3 z); PLC: Daicel Chiralpak AD-, hexane/i-pro = 90/10, Flow rate = 1.0 ml/min, UV = 210 nm, t R = 20.4 min (major) and t R = 28.0 min; RMS Calculated for C 16 12 2 O 2 F [M-] + 283.0883, found 283.0882. CF 3 3l 3-[1-(3-trifluoromethylphenyl)-2-nitroethyl]-1-indole: yellow oil; 99% yield; 94% ee; [α] 21 D = 5.7 (c 0.76, C 2 Cl 2 ); R f = 0.23 (petroleum ether/etoac = 4/1); 1 MR (500 Mz, CDCl 3 ) δ 8.13 (s, 1), 7.62 (s, 1), 7.55 (d, J = 8.2 z, 2), 7.38 (d, J = 8.2 z, 1), 7.25 7.21 (m, 1), O 2 7.14 7.09 (m, 1), 7.03 (d, J = 2.1 z, 1), 5.27 (t, J = 8.0 z, 1), 5.09 (dd, J = 12.8, 7.4 z, 1), 4.96 (dd, J = 12.8, 8.5 z, 1); 13 C MR (126 Mz, CDCl 3 ) δ 140.36, 136.54, 131.19 (d, J C-F = 32.8 z), 129.46, 125.86, 124.56 (d, J C-F = 3.8 z), 123.93 (d, J C-F = 273.4 z), 122.97, 121.66, 120.22, 118.63, 113.59, 111.54, 79.08, 41.32; Daicel Chiralpak AD-, hexane/i-pro = 80/20, Flow rate = 1.0 ml/min, UV = 220 nm, t R = 6.3 min (major) and t R = 7.2 min; RMS Calculated for C 17 12 2 O 2 F 3 [M-] + 333.0851, found 283.0856. O O 2 3m (R)-3-(1-Furan-2-yl-2-nitroethyl)-1-indole: known compound 4 ; yellow oil; 98% yield; 88% ee; [α] 22 D = +40.6 (c 1.64, C 2 Cl 2 ); [lit. 5 : [α] 20 D = + 38.2 (c 1.05, C 2 Cl 2 ) for 95% ee;]. R f = 0.33 (petroleum ether/etoac = 4/1); 1 MR (400 Mz, Acetone) δ 10.28 (s, 1), 7.63 (d, S8
J = 8.0 z, 1), 7.48 (dd, J = 1.8, 0.7 z, 1), 7.44 (d, J = 8.1 z, 1), 7.36 (d, J = 2.5 z, 1), 7.19 7.11 (m, 1), 7.10 7.01 (m, 1), 6.36 (dd, J = 3.2, 1.9 z, 1), 6.29 (d, J = 3.2 z, 1), 5.33 5.19 (m, 2), 5.15 (dd, J = 12.3, 7.3 z, 1); 13 C MR (101 Mz, Acetone) δ 154.2, 143.0, 137.7, 126.96, 124.1, 122.7, 120.1, 119.4, 112.5, 112.0, 111.2, 107.5, 78.6, 36.4; Daicel Chiralcel OD- column, hexane/i-pro = 70/30, Flow rate = 1.0 ml/min, UV = 254 nm, t R = 15.4 min (major) and t R = 21.8 min. 3n (R)-3-(1-(aphthalen-1-yl)-2-nitroethyl)-1-indole: known compound 4 : yellow oil; 95% yield; 95% ee; [α] 22 D = 22.5 (c 1.46, C 2 Cl 2 ); [lit. 5 : [α] 20 D = 25.8 (c 1.14, C 2 Cl 2 ) for 94% ee;] R f = 0.3 (petroleum ether/etoac = 4/1); 1 MR (400 Mz, CDCl 3 ) δ 8.29 (d, J = 8.3 z, 1), O 2 8.04 (s, 1), 7.95 7.87 (m, 1), 7.80 (m, 1), 7.61 7.49 (m, 2), 7.46 (d, J = 8.0 z, 1), 7.42 7.30 (m, 3), 7.23 7.16 (m, 1), 7.13 7.03 (m, 1), 7.00 (m, 1), 6.09 (t, J = 7.8 z, 1), 5.22 5.02 (m, 2); 13 C MR (126 Mz, CDCl 3 ) δ 136.7, 134.8, 134.3, 131.3, 129.3, 128.5, 127.0, 126.3, 126.1, 125.5, 124.8, 122.8, 122.8, 120.1, 119.0, 114.5, 111.6, 78.7, 37.2; Daicel Chiralcel OD- column, hexane/i-pro = 70/30, Flow rate = 1.0 ml/min, UV = 254 nm, t R = 26.1 min (major) and t R = 31.5 min. 3o (R)-3-(2-aphthalen-1-yl-2-nitroethyl)-1-indole: known compond 7 ; white solid; m.p. 139 140 o C; 90% yield; 93% ee; [α] 26 D = +20.6 (c 1.00, C 2 Cl 2 ); [lit. 7 : [α] 20 D = 18.9 (c 1.0, C 2 Cl 2 ) for 97% ee;] R f = 0.2 (petroleum ether/etoac = 4/1); 1 MR (400 Mz, Acetone) δ 10.30 (s, O 1), 8.03 (s, 1), 7.93 7.75 (m, 3), 7.70 7.54 (m, 2), 7.53 7.38 (m, 2 4), 7.13 (t, J = 7.6 z, 1), 7.00 (t, J = 7.5 z, 1), 5.49 5.24 (m, 3); 13 C MR (101 Mz, Acetone) δ138.9, 137.8, 134.4, 133.6, 129.2, 128.6, 128.4, 127.3, 127.02, 126.97, 126.69, 123.1, 122.7, 112.0 119.5, 114.7, 112.4, 80.1, 42.5; Daicel Chiralpak AD-, hexane/i-pro = 90/10, Flow rate = 1.0 ml/min, UV = 210 nm, t R = 37.7 min and t R = 40.7 min (major). 3p (R)-3-(1-nitrohexan-2-yl)-1-indole: known compond 7 ; yellow oil; 65% yield; 70% ee; [α] 21 D = +9.7 (c 0.23, C 2 Cl 2 ); [lit. 7 : [α] D 20 = 30.6 O 2 (c 1.0, C 2 Cl 2 ) for 91% ee;] R f = 0.33 (petroleum ether/etoac = 8/1); 1 MR (400 Mz, Acetone) δ 10.17 (s, 1), 7.67 (d, J = 7.9 z, 1), 7.41 (d, J = 8.1 z, 1), 7.28 (s, 1), 7.12 (t, J = 7.5 z, 1), 7.04 (t, J = 7.5 z, 1), 4.83 (d, J = 7.6 z, 2), 3.80 (m, 1), 1.97 1.74 (m, 2), 1.39 1.20 (m, 4), 0.83 (t, J = 6.5 z, 3);. 13 C MR (101 Mz, Acetone) δ 137.8, 127.5, 123.5, 122.4, 119.8, 119.4, 114.5, 112.5, 81.3, 37.0, 33.2, 30.1, 23.2, 14.2; PLC: Daicel Chiralcel OD- column, hexane/i-pro = 90/10, Flow rate = 1.0 ml/min, UV = 254 nm, t R = 35.7 min (major) and t R = 39.3 min. O 2 3q (R)-5-Methyl-3-(2-nitro-1-phenylethyl)-1-indole: known compond 8 ; white solid; m.p. 140 141 o C; 99% yield; 94% ee; [α] 26 D = +27.4 (c 1.38, C 2 Cl 2 ); [lit. 8 : [α] 20 D = +9.7 (c 0.92, C 2 Cl 2 ) for 97% ee;] R f = 0.27 (petroleum ether/etoac = 4/1); 1 MR (400 Mz, Acetone) δ 7 Ganesh, M.; Seidel, D. J. Am. Chem. Soc. 2008, 130, 16464. 8 Liu,.; Du, D.-M. Adv. Synth. Catal. 2010, 352, 1113. S9
10.11 (s, 1), 7.52 7.44 (m, 2), 7.39 7.27 (m, 5), 7.26 7.19 (m, 1), 6.97 (dd, J = 8.3, 1.4 z, 1), 5.35 5.10 (m, 3), 2.37 (s, 3); 13 C MR (101 Mz, Acetone) δ 141.5, 136.1, 129.4, 128.8, 127.9, 127.6, 124.3, 123.0, 119.0, 114.3, 112.1, 80.2, 42.3, 21.6; PLC: Daicel Chiralpak AD-, hexane/i-pro = 80/20, Flow rate = 1.0 ml/min, UV = 254 nm, t R = 25.9 min (major) and t R = 30.9 min. MeO O 2 3r (R)-5-Methoxy-3-(2-nitro-1-phenylethyl)-1-indole: known compound 5 ; white solid; m.p. 139 140 o C; 99% yield; 95% ee; [α] 20 D = +27.0 (c 1.96, C 2 Cl 2 ); [lit. 5 : [α] 20 D = +30.2 (c 1.02, C 2 Cl 2 ) for 96% ee;] R f = 0.21 (petroleum ether/etoac = 4/1); 1 MR (500 Mz, CDCl 3 ) δ 7.99 (s, 1), 7.36 7.29 (m, 4), 7.28 7.22 (m, 2), 7.00 (d, J = 2.3 z, 1), 6.84 (dt, J = 5.8, 2.4 z, 2), 5.14 (t, J = 8.0 z, 1), 5.04 (dd, J = 12.5, 7.6 z, 1), 4.93 (dd, J = 12.5, 8.4 z, 1), 3.77 (s, 3); 13 C MR (126 Mz, CDCl 3 ) δ 154.3, 139.3, 131.7, 129.1, 127.9, 127.7, 126.7, 122.4, 114.2, 112.9, 112.2, 100.9, 79.6, 56.0, 41.7. Daicel Chiralpak AD-, hexane/i-pro = 90/10, Flow rate = 1.0 ml/min, UV = 210 nm, t R = 28.0 min (major) and t R = 42.5 min. F O 2 3s (R)-5-Fluoro-3-(2-nitro-1-phenylethyl)-1-indole: known compond 9 ; yellow oil; 88% yield; 94% ee; [α] 20 D = 21.14 (c 1.79, C 2 Cl 2 ); R f = 0.25 (petroleum ether/etoac = 8/1); 1 MR (400 Mz, Acetone) δ 10.37 (s, 1), 7.54 7.45 (m, 3), 7.41 (dd, J = 8.8, 4.5 z, 1), 7.33 (m, 2), 7.23 (ddd, m, 2), 6.92 (td, J = 9.1, 2.5 z, 1), 5.37 5.13 (m, 3); 13 C MR (101 Mz, Acetone) δ 158.4 (d, J C-F = 232.5 z), 141.2, 134.3, 129.5, 128.8, 128.0, 127.6 (d, J C-F = 9.8 z), 125.0, 115.1 (d, J C-F = 4.8 z), 113.4 (d, J C-F = 9.8 z), 110.8 (d, J C-F = 26.4 z), 104.2 (d, J C-F = 23.8 z), 80.0, 42.1; Daicel Chiralpak AD-, hexane/i-pro = 90/10, Flow rate = 1.0 ml/min, UV = 210 nm, t R = 19.1 min (major) and t R = 22.7 min. Br O 2 3t (R)-5-Bromo-3-(2-nitro-1-phenylethyl)-1-indole: known compound 5 ; yellow oil; 99% yield; 94% ee; [α] 26 D = +43.3 (c 1.58, C 2 Cl 2 ); [lit. 5 : [α] 20 D = +41.0 (c 1.11, C 2 Cl 2 ) for 93% ee;] R f = 0.17 (petroleum ether/etoac = 8/1); 1 MR (400 Mz, CDCl 3 ) δ 8.12 (s, 1), 7.54 (d, J = 1.6 z, 1), 7.36 7.17 (m, 7), 7.04 (d, J = 2.4 z, 1), 5.11 (t, J = 8.0 z, 1), 5.01 (dd, J = 12.5, 8.0 z, 1), 4.90 (dd, J = 12.5, 8.0 z, 1); 13 C MR (101 Mz, CDCl 3 ) δ 138.8, 135.2, 129.2, 128.0, 127.9, 127.8, 125.8, 122.9, 121.6, 114.2, 113.4, 113.0, 79.5, 41.4; Daicel Chiralpak AD-, hexane/i-pro = 90/10, Flow rate = 1.0 ml/min, UV = 254 nm, t R = 18.0 min (major) and t R = 19.6 min. 9 Singh, P. K.; Bisai, A.; Singh, V. K. Tetrahedron Lett. 2007, 48, 1127. S10
Copy of MR Ts L1 Ts Ts Ts L1 S11
Ts L2 Ts Ts L2 Ts S12
Ts L3 Ts Ts L3 Ts S13
Ts L4 Ts Ts L4 Ts S14
Bn Ts Ts L5 Bn Bn Ts Ts L5 Bn S15
Ts Ts L6 Ts Ts L6 S16
Ts L7 Ts Ts L7 Ts S17
O 2 3a O 2 3a S18
Cl O 2 3b Cl O 2 3b S19
Cl O 2 3c Cl O 2 3c S20
Cl O 2 3d Cl O 2 3d S21
O 2 3e O 2 3e S22
MeO O 2 3f MeO O 2 3f S23
OMe O 2 3g OMe O 2 3g S24
Br O 2 3h Br O 2 3h S25
Br O 2 3i Br O 2 3i S26
Br O 2 3j Br O 2 3j S27
F O 2 3k F O 2 3k S28
CF 3 O 2 3l CF 3 O 2 3l S29
O O 2 3m O O 2 3m S30
O 2 3n O 2 3n S31
O 2 3o O 2 3o S32
O 2 3p O 2 3p S33
O 2 3q O 2 3q S34
MeO O 2 3r MeO O 2 3r S35
F O 2 3s F O 2 3s S36
Br O 2 3t Br O 2 3t S37
Copy of PLC for racemic and chiral compounds O 2 (+/-) 3aa O 2 3aa 95% ee S38
Cl Cl O 2 O 2 (+/-) 3ab 3ab 92% ee S39
Cl Cl O 2 O 2 (+/-) 3ac 3ac 94% ee S40
Cl Cl O 2 O 2 (+/-) 3ad 3ad 97% ee S41
O 2 O 2 (+/-) 3ae 3ae 93% ee S42
MeO MeO O 2 (+/-) 3af O 2 3af 88% ee S43
OMe OMe (+/-) 3ag O 2 3ag 93% ee O 2 S44
Br Br O 2 O 2 (+/-) 3ah 3ah 96% ee S45
Br Br O 2 O 2 (+/-) 3ai 3ai 93% ee S46
Br Br O 2 O 2 (+/-) 3aj 3aj 92% ee S47
F F O 2 O 2 (+/-) 3ak 3ak 96% ee S48
CF 3 CF 3 O 2 O 2 (+/-) 3al 3al 94% ee S49
O O 2 O O 2 (+/-) 3am 3am 88% ee S50
O 2 O 2 (+/-) 3an 3an 95% ee S51
O 2 O 2 (+/-) 3ao 3ao 93% ee S52
O 2 O 2 (+/-) 3ap 3ap 70% ee S53
O 2 O 2 (+/-) 3ba 3ba 94% ee S54
MeO O 2 MeO (+/-) 3ca O 2 3ca 95% ee S55
F O 2 F O 2 (+/-) 3da 3da 94% ee S56
Br O 2 Br O 2 (+/-) 3ea 3ea 94% ee S57
Ts Ts S58
Ts Ts S59
Ts Ts S60
Bn Ts Ts Bn S61
Ts Ts S62
Ts Ts S63
F O 2 S64
CF 3 O 2 S65