SUPPLEMETARY IFRMATI DI: 10.1038/CEM.1406 ighly enantioselective trapping of zwitterionic intermediates by imines uang Qiu,a, Ming Li,a, Li-Qin Jiang a, Feng-Ping Lv a, Li Zan a, Chang-Wei Zhai a, Michael. P. Doyle b and Wen-ao u*,a a Shanghai Engineering Research Center of Molecular Therapeutics and ew Drug Development, East China ormal University, Shanghai 200062, China b Department of Chemistry and Biochemistry, University of Maryland,College Park, MD 20742, USA CTETS: 1. Typical Procedures for the Reactions 3 2. Complementary Reaction ptimization Data 5 3. Analytical Data for the Products 6 4. MR Spectra for the Products 24 5. PLC Charts of the Products 55 6. X-ray Diffraction Parameters and Data 86 7. References 88 1 ATURE CEMISTRY www.nature.com/naturechemistry 1
DI: 10.1038/CEM.1406 SUPPLEMETARY IFRMATI General Information: All solvent were purified and dried using standard procedures. Diazo compounds 3 were prepared according to literature procudures 1 and 1 were prepared according to similar literature procedures. 2 Aldimines 2 were prepared from condensation of the corresponding aromatic aldehydes with anilines according to the literature method. 3 Indoles 4 were either commercial available or prepared according to literature procedures. 4 Chiral phosphoric acids 7a-7i were prepared according to literatures. 5-9 All reactions were carried out under argon atmosphere in a well-dried glassware. All MR spectra were recorded on a uker spectrometer at 500 Mz ( 1 MR) and 125 Mz ( 13 C MR) or a uker spectrometer at 400 Mz ( 1 MR) and 100 Mz ( 13 C MR). Chemical shifts (δ value) were reported in ppm down field from internal tetramethylsilane (TMS). ptical rotations were determined using a polaar 3005 polarimeter and were reported as [α] 10 D (concentration in grams/100ml solvent). Melting points were determined on a microscopic apparatus and were uncorrected. IR spectra were recorded using uker Tensor27 spectrometer. RMS (ESI) Mass Spectra were recorded on IonSpec FT-ICR mass spectrometer. Enantiomeric excesses (ee) of the products were determined by igh Performance Liquid Chromatography (PLC) on Shimadazu SPD-20AV UW-VIS Detector and LC-20AT Liquid Chromatography Pump. Chiralpad IA, AD, D- columns were purchased from Daicel Chemical Industries, LTD. The racemic standards used in PLC studies were prepared according to the general procedure without using BIL derived phosphoric acids or using racemic BIL derived phosphoric acids. 2 ATURE CEMISTRY www.nature.com/naturechemistry 2
DI: 10.1038/CEM.1406 SUPPLEMETARY IFRMATI 1. Typical Procedure for the Reaction 1.1 General procedure for the reactions of diazoacetamides with imines A mixture of Rh 2 (Ac) 4 (0.002 mmol), imine 2 (0.1 mmol), PPAs 7b (0.01 mmol) in 1.0 ml C 2 Cl 2 under an argon atmosphere was stirred at the -20 C. Diazo compound 1 (0.2 mmol) in 1.0 ml C 2 Cl 2 was added over 1hr via a syringe pump. After the completion of the addition, the reaction was stirred at -20 C for another 1hr and evaporated under reduced pressure to give the crude product. The crude product was purified by flash chromatography on silica gel (eluent: EtAc/light petroleum ether = 1:15 ~ 1:5) to give the pure product. Diastereoselectivity was determined either by 1 MR spectroscopy or PLC analysis of the crude reaction mixture and enantioselectivity was determined by chiral PLC analysis. The analytical data for the products are listed below. 1.2 General procedure for the reactions of α-phenyl-α-diazoacetates and indoles with imines A mixture of Rh 2 (Ac) 4 (0.0025 mmol), imine 2 (0.3 mmol), indole 4 (0.25 mmol), PPAs 7b (0.005 mmol) and 4 Å MS (100 mg) in 2.0 ml toluene under an argon atmosphere was stirred at the -10 C. Diazo compound 3 (0.3 mmol) in 2.0 ml toluene was added over 1hr via a syringe pump. After the completion of the addition, the reaction was stirred at the -10 C for another 6hr and evaporated under reduced pressure to give the crude product. The crude product was purified by flash chromatography on silica gel (eluent: EtAc/light petroleum ether = 1:100 ~ 1:40) to give the pure product. Diastereoselectivity was determined by 1 MR spectroscopy of the crude reaction mixture and enantioselectivity was determined by chiral PLC analysis. The analytical data for the products are listed below. 1.3 Procedure for controlled deuterium labeling experiment (Figure 3-b) A mixture of Rh 2 (Ac) 4 (0.002 mmol) and PPA (S)-7b (0.01 mmol) in 1.0 ml C 2 Cl 2 (C 2 Cl 2 containing 300 ppm 2 determined by a Karl-Fishier titrimeter) was stirred 3 ATURE CEMISTRY www.nature.com/naturechemistry 3
DI: 10.1038/CEM.1406 SUPPLEMETARY IFRMATI at 25 o C under an argon atmosphere. Diazo compound d 5-1a (0.1 mmol) in 1.0 ml C 2 Cl 2 was added over 1hr via a syringe pump. After completion of the addition, the reaction solution was stirred at 25 C overnight and the solvent was evaporated under reduced pressure to give a crude product as oil. The crude product was purified by flash chromatography on silica gel (eluent: EtAc/light petroleum ether = 1:10 ~ 1:5) to give the pure product. The deuterium content was determined by 1 MR spectroscopy of the pure product. 4 ATURE CEMISTRY www.nature.com/naturechemistry 4
DI: 10.1038/CEM.1406 SUPPLEMETARY IFRMATI 2. Complementary Reaction ptimization Data Table S1. Catalysts screening and optimization of reaction conditions for the reaction of methyl phenyldiazoacetate and indole with imine Ph 2 + + Ph C 2 Me Ph Me 3a 4a 2b Rh 2 (Ac) 4 Catlyst 7 Solvent Tempreture Ph Ph * * Ph 6a Entry Catalyst 7 Solvent T( o C) yield (%) a dr b ee (%) c 1 / Toluene 25 60 >20:1 0 2 (S)-7a Toluene 0 69 >20:1 63 3 (S)-7b Toluene 0 90 >20:1 97 4 (S)-7c Toluene 0 82 >20:1 45 5 (S)-7d Toluene 0 70 >20:1 36 6 (S)-7e Toluene 0 80 >20:1 75 7 (S)-7f Toluene 0 72 >20:1 82 8 (S)-7g Toluene 0 79 >20:1 40 9 (S)-7h Toluene 0 79 >20:1 55 10 (S)-7i Toluene 0 64 >20:1 38 11 (S)-7b DCM 0 86 >20:1 31 12 (S)-7b DCE 0 74 >20:1 20 13 (S)-7b TF 0 56 >20:1 13 14 (S)-7b Toluene 25 56 >20:1 92 15 (S)-7b Toluene -10 94 >20:1 97 16 (S)-7b Toluene -20 90 >20:1 98 17 d (S)-7a Toluene 0 63 >20:1 24 Reaction conditions: 2b/3a/4a/7/Rh 2 (Ac) 4 = 0.25/0.3/0.3/0.005/0.0025mmol, 3a in 2mL solvent was added to a solution of 4Å MS (100mg), 2b,,4a and Rh 2 (Ac) 4 in 2mL solvent under an argon atmosphere for 1 hr and stirred for another 6hr; a Isolated yield; b Determined by 1 MR spectroscopy of the reaction mixture; c Determined by chiral PLC analysis; d Without 4Å MS. 5 ATURE CEMISTRY www.nature.com/naturechemistry 5
DI: 10.1038/CEM.1406 SUPPLEMETARY IFRMATI 3. Analytical Data for the Products (R)-3-((S)-((4-chlorophenyl)amino)(phenyl)methyl)-3-ethyl-1-methylindolin-2-on e (5ba) White solid; mp: 119-125 o C; 77% yield; 1 MR Cl (500Mz, CDCl 3 ): δ 7.28-7.26 (m, 3 ), 7.19 (t, J = 6.9 5ba z, 1 ), 7.09 (t, J = 7.3 z, 1 ), 7.01-6.96 (m, 6 ), 6.96-6.54 (m, 3 ), 6.15 (d, J = 8.6 z, 1 ), 4.76 (d, J = 8.8 z, 1 ), 2.99 (s, 3 ), 2.49-2.45 (m, 1 ), 2.00-1.95 (m, 1 ), 0.63 (t, J = 7.4 z, 3 ); 13 C MR (100Mz, CDCl 3 ): δ 178.67, 145.74, 144.00, 138.04, 131.71, 129.34, 128.27, 127.69, 127.33, 127.23, 123.84, 123.35, 114.84, 108.61, 107.92, 62.65, 57.38, 27.94, 25.79, 8.77; IR (neat): υ 3393, 2963, 2923, 2853, 1698, 1601, 1498, 1468, 1401, 1353, 1318, 1259, 1089, 1076, 1020, 824, 804, 753, 726, 704 cm -1 ; dr (syn:anti) = 98:2; RMS (ESI) Calcd for [C 24 23 Cl 2 a, M + a] + : 413.1397; found: 413.1377; 96% ee (PLC condition: Chiralcel IA column, n-exane/i-pr = 95:5, flow rate = 1.0 ml/min, wave length 10 = 254nm, t R = 9.97 min for minor isomer, t R = 12.58 min for major isomer); [α] D +68.9 (c 1.14, C 2 Cl 2 ). (R)-3-ethyl-1-methyl-3-((S)-phenyl(phenylamino)methyl)indolin-2-one (5bb) Colorless oil; 84% yield; 1 MR (500Mz, CDCl 3 ): δ 7.25 (d, J = 7.5 z, 1 ), 7.19 (t, J = 7.7 z, 1 ), 7.10-7.00 (m, 8 5bb ), 6.59-6.52 (m, 4 ), 5.61 (d, J = 7.9 z, 1 ), 4.77 (d, J = 8.5 z, 1 ), 3.00 (s, 3 ), 2.51-2.46 (m, 1 ), 1.98-1.93 (m, 1 ), 0.61 (t, J = 7.4 z, 3 ); 13 C MR (100Mz, CDCl 3 ): δ 178.77, 146.73, 144.09, 138.60, 129.57, 129.02, 128.17, 127.76, 127.03, 123.87, 122.25, 116.97, 113.20, 107.83, 62.60, 57.57, 27.95, 25.78, 8.80; IR (neat): υ 3366, 3055, 2875, 1691, 1505, 1469, 1377, 1354, 1320, 1250, 1155, 1077, 1022, 917, 793, 695 cm -1 ; dr (syn:anti) = 99:1; RMS (ESI) Calcd for [C 24 24 2 a, M + a] + : 379.1781; found: 379.1797; 97% ee (PLC condition: Chiralcel IA column, n-exane/i-pr = 98:2, flow rate = 1.0 ml/min, wave length = 254nm, t R = 11.34 6 ATURE CEMISTRY www.nature.com/naturechemistry 6
DI: 10.1038/CEM.1406 SUPPLEMETARY IFRMATI min for minor isomer, t R = 13.74 min for major isomer); [α] D 10 +87.3 (c 1.20, C 2 Cl 2 ). (R)-3-((S)-((4-bromophenyl)amino)(phenyl)methyl)-3-ethyl-1-methylindolin-2-on e (5bc) Colorless oil; 75% yield; 1 MR (500Mz, CDCl 3 ): δ 7.23 (d, J = 7.1 z, 1 ), 7.19 (t, J = 7.7 z, 1 ), 5bc 7.11-7.06 (m, 3 ), 7.01-7.00 (m, 3 ), 6.96-6.95 (m, 2 ), 6.56 (d, J = 7.8 z, 1 ), 6.40 (d, J = 8.8 z, 2 ), 5.71 (d, J = 9.0 z, 1 ), 4.70 (d, J = 9.2 z, 1 ), 2.99 (s, 3 ), 2.48-2.43 (m, 1 ), 1.97-1.93 (m, 1 ), 0.61 (t, J = 7.4 z, 3 ); 13 C MR (100Mz, CDCl 3 ): δ 178.67, 145.74, 144.00, 138.04, 131.71, 129.34, 128.27, 127.69, 127.33, 127.23, 123.84, 122.35, 114.84, 108.61, 107.92, 62.65, 57.38, 27.94, 25.79, 8.77; IR (neat): υ 3366, 3058, 2928, 1692, 1611, 1593, 1495, 1469, 1377, 1355, 1320, 1249, 1179, 1112, 1074, 1021, 1001, 916, 812, 736, 699 cm -1 ; dr (syn:anti) = 99:1; RMS (ESI) Calcd for [C 24 23 2 a, M + a] + : 457.0881; found: 457.0886; 97% ee (PLC condition: Chiralcel IA column, n-exane/i-pr = 95:5, flow rate = 1.0 ml/min, wave length = 254nm, t R = 11.68 min for minor isomer, t R = 14.13 min for major isomer); [α] 10 D +56.8 (c 1.16, C 2 Cl 2 ). (R)-3-ethyl-1-methyl-3-((S)-phenyl((4-(trifluoromethyl)phenyl)amino)methyl)ind olin-2-one (5bd) Colorless oil; 57% yield; 1 MR (500Mz, CDCl 3 ): δ CF 3 7.29-7.26 (m, 3 ), 7.19 (t, J = 7.6 z, 1 ), 7.09 (t, J = 5bd 7.5 z, 1 ), 7.01-6.96 (m, 5 ), 6.56-6.53 (m, 3 ), 6,15 (d, J = 8.7 z, 1 ), 4.76 (d, J = 8.8 z, 1 ), 3.00 (s, 3 ), 2.49-2.22 (m, 1 ), 1.99-1.95 (m, 1 ), 0.63 (t, J = 7.4 z, 3 ); 13 C MR (100Mz, CDCl 3 ): δ 179.00, 149.30, 143.93, 137.83, 129.29, 128.36, 127.60, 127.41, 127.37, 126.46, 123.79, 122.45, 112.32, 108.00, 62.37, 57.24, 27.97, 25.80, 8.78; IR (neat): υ 3367, 2933, 1693, 1613, 1532, 1494, 7 ATURE CEMISTRY www.nature.com/naturechemistry 7
DI: 10.1038/CEM.1406 SUPPLEMETARY IFRMATI 1470, 1379, 1319, 1261, 1187, 1158, 1106, 1062, 823, 749, 700 cm -1 ; dr (syn:anti) = 99:1; RMS (ESI) Calcd for [C 25 23 F 3 2 a, M + a] + : 447.1655; found: 447.1663; 95% ee (PLC condition: Chiralcel AD column, n-exane/i-pr = 95:5, flow rate = 1.0 ml/min, wave length = 254nm, t R = 8.97 min for minor isomer, t R = 10.46 min for major isomer); [α] 10 D +69.3 (c 0.70, C 2 Cl 2 ). (R)-3-((S)-((3-bromophenyl)amino)(phenyl)methyl)-3-ethyl-1-methylindolin-2-on e (5be) Colorless oil; 65% yield; 1 MR (500Mz, CDCl 3 ): δ 7.24 (d, J = 7.3 z, 1 ), 7.18 (t, J = 7.6 z, 1 ), 7.08 (t, 5be J = 7.6 z, 1 ), 7.02-7.01 (m, 3 ), 6.98-6.96 (m, 2 ), 6.87 (t, J = 8.0 z, 1 ), 6.69-6.67 (m, 2 ), 6.56 (d, J = 7.8 z, 1 ), 6.44 (d, J = 8.3 z, 1 ), 5.78 (d, J = 8.8 z, 1 ), 4.71 (d, J = 9.1 z, 1 ), 2.99 (s, 3 ), 2.47-2.43 (m, 1 ), 1.97-1.92 (m, 1 ), 0.61 (t, J = 7.4 z, 3 ); 13 C MR (100Mz, CDCl 3 ): δ 178.62, 148.10, 144.00, 138.00, 130.31, 129.31, 128.28, 127.66, 127.36, 127.26, 123.85, 123.05, 122.36, 119.83, 115.84, 111.83, 107.92, 62.48, 57.38, 27.96, 25.78, 8.76; IR (neat): υ 3383, 3024, 2976, 1694, 1609, 1598, 1512, 1498, 1391, 1324, 1247, 1169, 1138, 1094, 1011, 796, 712 cm -1 ; dr (syn:anti) = 99:1; RMS (ESI) Calcd for [C 24 23 2 a, M + a] + : 457.0886; found: 457.0889; 96% ee (PLC condition: Chiralcel AD column, n-exane/i-pr = 97:3, flow rate = 1.0 ml/min, wave length = 254nm, t R = 9.69 min for minor isomer, t R = 11.14 min for major isomer); [α] 10 D +70.8 (c 1.00, C 2 Cl 2 ). (R)-3-((S)-(4-chlorophenyl)(phenylamino)methyl)-3-ethyl-1-methylindolin-2-one (5bf) Colorless oil; 78% yield; 1 MR (500Mz, CDCl 3 ): δ 7.26-7.24 (d, J = 7.1 z, 1 ), 7.20 (t, J = 7.7 z, 1 ), 7.11-7.02 (m, 3 ), 6.97 (d, J = 8.5 z, 2 ), 6.91 (d, J = 8.6 z, 2 ), 6.61-6.59 (m, 2 ), 6.50 (d, J = 8.5 z, 2 ), 5.69 (d, J = 8.8 z, 1 ), 4.75 (d, J = 9.1 z, 1 ), 3.00 (s, 3 ), 2.51-2.46 (m, 1 ), 1.99-1.95 (m, 1 ), 0.62 (t, J = 8 ATURE CEMISTRY www.nature.com/naturechemistry 8
DI: 10.1038/CEM.1406 SUPPLEMETARY IFRMATI Cl 7.4 z, 3 ); 13 C MR (100Mz, CDCl 3 ): δ 178.53, 146.42, 143.95, 137.40, 132.73, 129.39, 129.09, 129.06, 128.40, 127.46, 123.64, 122.40, 117.23, 113.13, 108.10, 61.97, 57.34, 5bf 27.92, 25.79, 8.75; IR (neat): υ 3365, 2965, 1695, 1602, 1507, 1377, 1276, 1260, 1092, 1014, 823, 750, 693 cm -1 ; dr (syn:anti) = 99:1; RMS (ESI) Calcd for [C 24 23 Cl 2 a, M + a] + : 413.1391; found: 413.1382; 97% ee (PLC condition: Chiralcel IA column, n-exane/i-pr = 95:5, flow rate = 1.0 ml/min, wave length = 254nm, t R = 9.41 min for minor isomer, t R = 11.94 min for major isomer); [α] 10 D +81.6 (c 1.20, C 2 Cl 2 ). (R)-3-((S)-(3-bromophenyl)(phenylamino)methyl)-3-ethyl-1-methylindolin-2-one (5bg) Colorless oil; 68% yield; 1 MR (500Mz, CDCl 3 ): δ 7.27-7.24 (m, 3 ), 7.20 (t, J = 7.7 z, 1 ), 7.12-7.09 (m, 3 5bg ), 7.07-7.04 (m, 2 ), 6.61 (t, J = 7.3 z, 1 ), 6.56 (d, J = 7.8 z, 1 ), 6.50 (d, J = 8.3 z, 2 ), 5.73 (d, J = 8.8 z, 1 ), 4.82 (d, J = 9.1 z, 1 ), 2.98 (s, 3 ), 2.52-2.48 (m, 1 ), 2.00-1.96 (m, 1 ), 0.63 (t, J = 7.4 z, 3 ); 13 C MR (100Mz, CDCl 3 ): δ 178.36, 146.29, 143.91, 143.14, 129.16, 128.57, 128.08, 124.21, 123.66, 122.50, 117.40, 113.08, 108.13, 62.27, 57.27, 27.92, 25.77, 8.75; IR (neat): υ 3349, 3054, 2942, 1696, 1601, 1498, 1320, 1105, 1079, 995, 780, 759, 733, 698 cm -1 ; dr (syn:anti) = 99:1; RMS (ESI) Calcd for [C 24 23 2 a, M + a] + : 457.0886; found: 457.0882; 90% ee (PLC condition: Chiralcel IA column, n-exane/i-pr = 95:5, flow rate = 1.0 ml/min, wave length = 254nm, t R = 8.62 min for minor isomer, t R = 10.86 min for major isomer); [α] 10 D +66.2 (c 1.18, C 2 Cl 2 ). (R)-3-((S)-((4-chlorophenyl)amino)(3,4,5-trimethoxyphenyl)methyl)-3-ethyl-1-me thylindolin-2-one (5bh) Semi-solid; 77% yield; 1 MR (500Mz, CDCl 3 ): δ 7.29 (d, J = 7.2 z, 1 ), 7.18 9 ATURE CEMISTRY www.nature.com/naturechemistry 9
DI: 10.1038/CEM.1406 SUPPLEMETARY IFRMATI Me Me Me Cl (t, J = 7.6 z, 1 ), 7.08 (t, J = 7.4 z, 1 ), 7.02 (d, J = 8.8 z, 2 ), 6.56 (d, J = 7.7 z, 1 ), 6.47 (d, J = 8.8 z, 2 ), 6.12 (s, 2 ), 5.78 (d, J = 8.7 z, 1 ), 4.58 (d, J = 5bh 8.8 z, 1 ), 3.67 (s, 3 ), 3.59 (s, 6 ), 2.96 (s, 3 ), 2.46-2.42 (m, 1 ), 2.00-1.95 (m, 1 ), 0.62 (t, J = 7.4 z, 3 ); 13 C MR (100Mz, CDCl 3 ): δ 178.62, 152.18, 145.40, 144.09, 133.74, 129.87, 128.93, 128.36, 123.55, 122.11, 121.62, 114.17, 108.19, 104.85, 62.92, 60.61, 57.50, 55.98, 27.70, 25.73, 8.82; IR (neat): υ 3391, 3187, 2901, 2836, 1702, 1622, 1535, 1478, 1399, 1367, 1252, 1130, 1023, 944, 811, 782, 715, 694 cm -1 ; dr (syn:anti) = 99:1; RMS (ESI) Calcd for [C 27 29 Cl 2 a 4, M + a] + : 503.1708; found: 503.1707; 45% ee (PLC condition: Chiralcel IA column, n-exane/i-pr = 95:5, flow rate = 1.0 ml/min, wave length = 254nm, t R = 17.22 min for major isomer, t R = 28.02 min for minor isomer); [α] 10 D +18.2 (c 1.48, C 2 Cl 2 ). (R)-3-((S,E)-1-((4-bromophenyl)amino)-3-phenylallyl)-3-ethyl-1-methylindolin-2- one (5bi) Colorless oil; 57% yield; 1 MR (500Mz, CDCl 3 ): δ 7.35 (t, J = 7.7 z, 1 ), 7.30-7.27 (m, 1 ), 7.25-7.15 5bi (m, 6 ), 7.13-7.11 (m, 2 ), 6.86 (d, J = 7.8 z, 1 ), 6.49 (d, J = 8.8 z, 2 ), 6.42 (d, J = 15.9 z, 1 ), 5.80 (dd, J 1 = 15.9 z, J 2 = 6.3 z, 1 ), 4.70 (br, 1 ), 4.43 (m, 1 ), 3.16 (s, 3 ), 2.28-2.25 (m, 1 ), 1.98-1.94 (m, 1 ), 0.61 (t, J = 7.4 z, 3 ); 13 C MR (125Mz, CDCl 3 ): δ 178.65, 145.98, 144.55, 136.37, 132.77, 131.80, 128.58, 128.41, 127.59, 126.36, 125.69, 123.35, 122.74, 115.11, 108.90, 108.22, 60.25, 57.10, 28.06, 26.04, 8.46; IR (neat): υ 3368, 3056, 2926, 1698, 1611, 1594, 1493, 1469, 1377, 1179, 1156, 1120, 1073, 1020, 1002, 967, 812, 745, 695 cm -1 ; dr (syn:anti) = 99:1; RMS (ESI) Calcd for [C 26 25 2 a, M + a] + : 483.1042; found: 483.1040; 65% ee (PLC condition: Chiralcel IA column, n-exane/i-pr = 95:5, flow rate = 1.0 ml/min, wave length = 254nm, t R = 13.65 min for minor isomer, 10 ATURE CEMISTRY www.nature.com/naturechemistry 10
DI: 10.1038/CEM.1406 SUPPLEMETARY IFRMATI t R = 32.73 min for major isomer); [α] D 10-21.6 (c 0.50, C 2 Cl 2 ). (R)-3-((S)-(4-bromophenyl)(phenylamino)methyl)-1,3-dimethylindolin-2-one (5ab) Colorless oil; 81% yield; 1 MR (500Mz, CDCl 3 ): δ 7.24-7.19 (m, 2 ), 7.13 (d, J = 8.4 z, 2 ), 7.09-7.04 (m, 3 ), 6.86 (d, J = 8.4 z, 2 ), 6.61 (d, J = 7.5 z, 2 ), 6.49 (d, 5ab J = 8.4 z, 2 ), 5.58 (d, J = 8.8 z, 1 ), 4.70 (d, J = 9.2 z, 1 ), 3.00 (s, 3 ), 1.62 (s, 3 ); 13 C MR (100Mz, CDCl 3 ): δ 179.08, 146.38, 143.12, 137.68, 131.41, 130.46, 129.36, 129.09, 128.48, 123.37, 122.49, 121.08, 117.36, 113.22, 108.24, 62.91, 51.81, 25.89, 21.27; IR (neat): υ 3382, 3054, 2933, 1693, 1601, 1521, 1376, 1312, 1120, 1012, 889, 820, 749, 698 cm -1 ; dr (syn:anti) = 98:2; RMS (ESI) Calcd for [C 23 21 2 a, M + a] + : 443.0729; found: 443.0727; 90% ee (PLC condition: Chiralcel IA column, n-exane/i-pr = 95:5, flow rate = 1.0 ml/min, wave length = 254nm, t R = 15.44 min for minor isomer, t R = 28.18 min for major isomer); [α] 10 D +48.7 (c 1.36, C 2 Cl 2 ). (R)-3-((R)-(4-bromophenyl)(phenylamino)methyl)-1-methylindolin-2-one (5cb) Yellow solid; mp: 129-133 o C; 57% yield; 1 MR (500Mz, CDCl 3 ): δ 7.30-7.26 (m, 3 ), 7.13-7.02 (m, 6 ), 6.71 (d, J = 5cb 7.8 z, 1 ), 6.66 (t, J = 7.3 z, 1 ), 6.54 (d, J = 7.6 z, 2 ), 5.35 (d, J = 9.2 z, 1 ), 5.19 (dd, J 1 = 9.2 z, J 2 = 3.9 z, 1 ), 3.99 (d, J = 3.8 z, 1 ), 3.05 (s, 3 ); 13 C MR (100Mz, CDCl 3 ): δ 175.61, 145.99, 144.68, 137.81, 131.15, 129.16, 128.87, 128.80, 124.77, 122.49, 121.17, 117.90, 113.68, 108.37, 57.49, 51.06, 26.00; IR (neat): υ 3330, 3052, 2924, 1696, 1602, 1493, 1468, 1376, 1351, 1263, 1154, 1125, 1092, 1009, 869, 810, 748, 691 cm -1 ; dr (syn:anti) = 93:7; RMS(ESI) Calcd for [C 22 19 2 a, M + a] + : 429.0573, found: 429.0555; 89% ee (PLC condition: Chiralpad IA column, n-exane/i-pr = 95:5, flow rate = 1.0mL/min, wave length = 254nm, t R = 14.0 11 ATURE CEMISTRY www.nature.com/naturechemistry 11
DI: 10.1038/CEM.1406 SUPPLEMETARY IFRMATI min for minor isomer, t R = 23.8 min for major isomer); [α] D 10 +59.4 (c 1.10, C 2 Cl 2 ). (R)-3-((S)-(4-bromophenyl)(phenylamino)methyl)-1,3-diethylindolin-2-one (5bj) Colorless oil; 70% yield; 1 MR (500Mz, CDCl 3 ): δ 7.25-7.20 (m, 2 ), 7.13-7.10 (m, 2 ), 7.09-7.04 (m, 3 ), 6.87 (d, J = 8.4 z, 2 ), 6.63 (d, J = 7.9 z, 1 ), 6.60 (t, J = 5bj 7.3 z, 1 ), 6.48 (d, J = 8.4 z, 2 ), 6.70 (d, J = 9.2 z, 1 ), 4.74 (d, J = 9.2 z, 1 ), 3.70-3.66 (m, 1 ), 3.53-3.48 (m, 1 ), 2.49-2.45 (m, 1 ), 1.97-1.92 (m, 1 ), 1.01 (t, J = 7.2 z, 3 ), 0.60 (t, J = 7.4 z, 3 ); 13 C MR (100Mz, CDCl 3 ): δ 178.14, 146.42, 143.10, 137.90, 132.45, 130.95, 130.49, 129.12, 128.39, 123.89, 122.21, 120.94, 117.22, 113.08, 108.30, 61.85, 56.94, 34.37, 28.22, 12.25, 8.62; IR (neat): υ 3398, 2971, 2923, 1690, 1601, 1506, 1487, 1371, 1314, 1236, 1180, 1072, 1008, 821, 782, 693 cm -1 ; dr (syn:anti) = 98:2; RMS (ESI) Calcd for [C 25 25 2 a, M + a] + : 471.1042; found: 471.1033; 88% ee (PLC condition: Chiralcel IA column, n-exane/i-pr = 98:2, flow rate = 1.0 ml/min, wave length = 254nm, t R = 16.12 min for minor isomer, t R = 18.45 min for major isomer); [α] 10 D +53.3 (c 0.98, C 2 Cl 2 ). (R)-1-benzyl-3-((S)-(4-bromophenyl)(phenylamino)methyl)-3-ethylindolin-2-one (5bk) Colorless oil; 67% yield; 1 MR (500Mz, CDCl 3 ): δ 7.26-7.24 (m, 4 ), 7.16-7.12 (m, 3 ), 7.10-7.05 (m, 3 ), Bn 5bk 6.95-6.91 (m, 4 ), 6.62 (t, J = 7.3 z, 1 ), 6.53-6.49 (m, 3), 5.55 (d, J = 6.4 z, 1 ), 4.93 (d, J = 15.8 z, 1 ), 4.84 (d, J = 9.4 z, 1 ), 4.62 (d, J = 15.8 z, 1 ), 2.51-2.47 (m, 1 ), 2.00-1.96 (m, 1 ), 0.64 (t, J = 7.4 z, 3 ); 13 C MR (100Mz, CDCl 3 ): δ 178.72, 146.26, 143.40, 137.84, 135.24, 130.80, 129.77, 129.23, 129.14, 128.69, 128.45, 127.52, 127.28, 127.07, 123.92, 122.43, 121.11, 117.37, 113.20, 109.39, 61.53, 57.22, 43.61, 28.80, 8.67; IR (neat): υ 3369, 3052, 2919, 1694, 12 ATURE CEMISTRY www.nature.com/naturechemistry 12
DI: 10.1038/CEM.1406 SUPPLEMETARY IFRMATI 1601, 1486, 1402, 1295, 1268, 1175, 1032, 952, 810, 784, 757, 697 cm -1 ; dr (syn:anti) = 98:2; RMS (ESI) Calcd for [C 30 27 2 a, M + a] + : 533.1199; found: 533.1180; 91% ee (PLC condition: Chiralcel IA column, n-exane/i-pr = 95:5, flow rate = 1.0 ml/min, wave length = 254nm, t R = 7.89 min for minor isomer, t R = 10.14 min for major isomer); [α] 10 D +40.0 (c 0.94, C 2 Cl 2 ). (R)-5-bromo-3-((S)-(4-bromophenyl)((4-bromophenyl)amino)methyl)-3-ethyl-1- methylindolin-2-one (5bl) Semi-solid; 80% yield; 1 MR (500Mz, CDCl 3 ): δ 7.38 (s, 1 ), 7.33 (d, J = 8.3 z, 1), 7.17-7.12 (m, 4 5bl ), 6.83 (d, J = 8.2 z, 2 ), 6.47 (d, J = 8.3 z, 1 ), 6.37 (d, J = 8.6 z, 2 ), 5.74 (br, 1 ), 4.63 (s, 1), 2.98 (s, 3 ), 2.49-2.45 (m, 1 ), 1.96-1.92 (m, 1 ), 0.63 (t, J = 7.4 z, 3 ); 13 C MR (100Mz, CDCl 3 ): δ 177.87, 145.22, 142.89, 137.03, 131.99, 131.86, 131.49, 131.39, 130.73, 129.25, 126.77, 121.44, 116.67, 115.24, 114.82, 109.64, 109.18, 62.10, 57.41, 27.88, 25.93, 8.74; IR (neat): υ 2294, 2984, 2842, 1694, 1608, 1497, 1434, 1387, 1365, 1276, 1123, 1087, 1015, 812, 743, 696 cm -1 ; dr (syn:anti) = 98:2; RMS (ESI) Calcd for [C 24 21 3 2 a, M + a] + : 612.9096; found: 612.9116; 98% ee (PLC condition: Chiralcel IA column, n-exane/i-pr = 98:2, flow rate = 1.0 ml/min, wave length = 254nm, t R = 19.54 min for minor isomer, t R = 21.19 min for major isomer); [α] 10 D +122.9 (c 1.58, C 2 Cl 2 ). (2R,3R)-methyl-2-(1-methyl-1-indol-3-yl)-2,3-diphenyl-3-(phenylamino)propan oate (6a) White solid; mp: 145-148 o C; 94% yield; 1 MR (400Mz, CDCl 3 ): δ 7.36-7.30 (m, 3 ), 7.23-7.20 (m, 3 ), 7.16-7.10 (m, 4 ), 7.03-6.99 (m, 3 ), 6.87-6.85 (m, 3 ), 6.56-6.51 (m, 2 ), 6.40 (d, J = 7.8 z, 2 ), 5.82 (d, J = 9.2 z, 1 ), 5.04 (d, J = 9.0 z, 1 ), 3.73 (s, 3 ), 3.62 (s, 3 ); 13 C MR (100z, CDCl 3 ): δ 173.18, 146.26, 141.18, 139.44, 132.86, 129.28, 129.16, 129.03, 128.16, 127.47, 127.13, 121.41, 13 ATURE CEMISTRY www.nature.com/naturechemistry 13
DI: 10.1038/CEM.1406 SUPPLEMETARY IFRMATI 121.19, 119.44, 117.05, 113.10, 109.51, 62.00, 61.15, 52.20, 32.95; IR (neat): υ 3411, 3025, 2954, 1718, 1603, 1507, 1469, 1365, 1252, 1157, 1089, 836, 800, 743, 698 6a cm -1 ; dr (anti:syn) > 20:1; RMS (ESI) Calcd for [C 31 28 2 a 2, M + a] + : 483.2043; found: 483.2048; 97% ee (PLC condition: Chiralcel D- column, n-exane/i-pr = 100:1, flow rate = 1.0 ml/min, wave length = 254nm, t R = 10.45 min for minor isomer, t R = 11.77 min for major isomer); [α] D 10 +74.9 (c 0.37, C 2 Cl 2 ). (2R,3R)-methyl-3-(4-bromophenyl)-2-(1-methyl-1-indol-3-yl)-2-phenyl-3-(phen ylamino)propanoate (6b) White solid; mp: 85-90 o C; 93% yield; 1 MR (400Mz, CDCl 3 ): δ 7.25-7.23 (m, 3 ), 7.18-7.13 (m, 5 ), 7.08 (dd, J 1 = 6.7 z, J 2 = 7.9 z, 1 ), 6.93-6.97 (m, 3 ), 6.78 (dd, 6b J 1 = 6.8 z, J 2 = 8.3 z, 1 ), 6.67 (d, J = 8.4 z, 2 ), 6.51 (t, J = 7.3 z, 1 ), 6.45 (d, J = 8.2 z, 1), 6.30 (d, J = 7.3 z, 2 ), 5.69 (d, J = 8.9 z, 1 ), 4.98 (d, J = 8.5 z, 1 ), 3.68 (s, 3 ), 3.55 (s, 3 ); 13 C MR (100z, CDCl 3 ): δ 172.97, 145.85, 140.70, 138.64, 136.40, 132.46, 131.00, 130.45, 129.14, 128.88, 128.15, 127.81, 127.20, 121.38, 119.46, 117.29, 113.03, 109.49, 61.74, 60.80, 52.20, 32.94; IR (neat): υ 2954, 2929, 2856, 1963, 1717, 1602, 1507, 1469, 1252, 1156, 1089, 1066, 835, 777, 743, 698 cm -1 ; dr (anti:syn) > 20:1; RMS (ESI) Calcd for [C 31 27 2 a 2, M + a] + : 561.1148; found: 561.1138; 99% ee (PLC condition: Chiralcel IA column, n-exane/i-pr = 90:10, flow rate = 1.0 ml/min, wave length = 254nm, t R = 7.40 min for major isomer, t R = 8.59 min for minor isomer); [α] 10 D +4.3 (c 0.68, C 2 Cl 2 ). (2R,3R)-methyl-2-(1-methyl-1-indol-3-yl)-2-phenyl-3-(phenylamino)-3-(4-(triflu oromethyl)phenyl)propanoate (6c) Semi-solid; 76% yield; 1 MR (400Mz, CDCl 3 ): δ 7.29-7.23 (m, 5 ), 7.11-7.18 (m 3 ), 7.09 (t, J = 8.0 z, 1 ), 6.99-6.81 (m, 5 ), 6.77 (t, J = 7.2 z, 1 ), 6.53 (t, 14 ATURE CEMISTRY www.nature.com/naturechemistry 14
DI: 10.1038/CEM.1406 SUPPLEMETARY IFRMATI J = 7.2 z, 1 ), 6.46 (d, J = 8.2 z, 1 ), 6.33 (d, J = 8.3z, 2 ), 5.78 (d, J = 8.7 z, 1 ), 5.08 (d, J = 7.9z, 1 ), 3.69 (s, 3 ), 3.57 (s, 3 ); 13 C MR (100z, CF 3 6c CDCl 3 ): δ 172.97, 145.76, 143.92, 140.49, 136.62, 132.20, 129.60, 128.89, 128.15, 127.73, 127.29, 124.24, 121.36, 119.48, 117.43, 112.98, 109.53, 61.76, 61.14, 52.26, 32.91; IR (neat): υ 3416, 3049, 2914, 1739, 1602, 1504, 1428, 1325, 1224, 1164, 1123, 1066, 847, 751, 698 cm -1 ; dr (anti:syn) > 20:1; RMS (ESI) Calcd for [C 32 27 F 3 2 a 2, M + a] + : 551.1917; found: 551.1906; 97% ee (PLC condition: Chiralcel IA column, n-exane/i-pr = 90:10, flow rate = 1.0 ml/min, wave length = 254nm, t R = 6.94 min for major isomer, t R = 8.37 min for minor isomer); [α] 10 D +48.1 (c 2.20, C 2 Cl 2 ). (2R,3R)-methyl-2-(1-methyl-1-indol-3-yl)-2-phenyl-3-(phenylamino)-3-(p-tolyl) propanoate (6d) Semi-solid; 85% yield; 1 MR (400Mz, CDCl 3 ): δ 7.37-7.32 (m, 3 ), 7.17-7.13 (m, 3 ), 7.04-7.00 (m, 1 ), 6.94-6.91 (m, 3 ), 6.87-6.83 (m, 1 ), 6.74 (d, J = 7.8 z, 6d 2 ), 6.56 (t, J = 7.3 z, 2 ), 6.50 (d, J = 8.2 z, 2 ), 6.39 (d, J = 8.4 z, 2 ), 5.81 (s, 1 ), 4.95 (d, J = 2.0 z, 1 ), 3.77 (s, 3 ), 3.64 (s, 3 ), 2.26 (s, 3 ); 13 C MR (100z, CDCl 3 ): δ 173.13, 146.21, 141.24, 136.89, 136.51, 136.15, 129.06, 132.89, 128.92, 128.08, 127.00, 121.32, 121.05, 119.32, 116.87, 113.01, 109.39, 61.91, 60.61, 52.08, 32.89, 21.08; IR (neat): υ 3406, 3024, 2947, 1738, 1602, 1511, 1334, 1253, 1089, 835, 748, 696 cm -1 ; dr (anti:syn) > 20:1; RMS (ESI) Calcd for [C 32 30 2 a 2, M + a] + : 497.2199; found: 497.2159; 67% ee (PLC condition: Chiralcel IA column, n-exane/i-pr = 90:10, flow rate = 1.0 ml/min, wave length = 254nm, t R = 5.68 min for major isomer, t R = 6.46 min for minor isomer); [α] 10 D +7.5 (c 1.71, C 2 Cl 2 ). (2R,3R)-methyl-3-(3-bromophenyl)-2-(1-methyl-1-indol-3-yl)-2-phenyl-3-(phen ylamino)propanoate (6e) 15 ATURE CEMISTRY www.nature.com/naturechemistry 15
DI: 10.1038/CEM.1406 SUPPLEMETARY IFRMATI White solid; mp: 74-78 o C; 58% yield; 1 MR (400Mz, CDCl 3 ): δ 7.36-7.21 (m, 7 ), 7.16 (t, J = 7.4 z, 1 ), 7.06-6.99 (m, 4 ), 6.93-6.85 (m, 3 ), 6.60 (t, J = 7.3 z, 6e 1 ), 6.49 (d, J = 8.2 z, 1 ), 6.39 (d, J = 7.8 z, 2 ), 5.80 (d, J = 8.8 z, 1 ), 4.98 (d, J = 8.5 z, 1 ), 3.78 (s, 3 ), 3.63 (s, 3 ), 13 C MR (100z, CDCl 3 ): δ 172.97,, 145.90, 142.13, 140.74, 136.67, 132.87, 130.58, 129.24, 128.31, 128.95, 127.93, 127.34, 121.60, 121.37, 121.21, 119.61, 117.41, 113.05, 109.69, 109.14, 62.02, 60.83, 52.29, 30.00; IR (neat): υ 3421, 3396, 3055, 2951, 1739, 1600, 1503, 1371, 1250, 1128, 1067, 854, 776, 693 cm -1 ; dr (anti:syn) > 20:1; RMS (ESI) Calcd for [C 31 27 2 a 2, M + a] + : 561.1148; found: 561.1138; 93% ee (PLC condition: Chiralcel IA column, n-exane/i-pr = 90:10, flow rate = 1.0 ml/min, wave length = 254nm, t R = 5.52 min for major isomer, t R = 6.22 min for minor isomer); [α] 10 D +45.2 (c 1.93, C 2 Cl 2 ). (2R,3S)-methyl-3-(2-bromophenyl)-2-(1-methyl-1-indol-3-yl)-2-phenyl-3-(phen ylamino)propanoate (6f) Semi-solid; 75% yield; 1 MR (400Mz, CDCl 3 ): δ 7.56 (s, 1 ), 7.38-7.31 (m, 3 ), 7.22-7.18 (m, 3 ), 7.15-7.03 (m, 7 ), 6.99-6.90 (m, 2 ), 6.65-6.62 (m, 3 ), 5.94 (s, 1 6f ), 3.82 (s, 3 ), 3.72 (s, 3 ); 13 C MR (100z, CDCl 3 ): δ 174.15, 146.04, 139.27, 136.94, 132.23, 131.31, 130.27, 129.28, 128.92, 127.36, 127.14, 127.09, 126.85, 121.93, 121.41, 119.26, 117.19, 113.25, 109.31, 61.02, 52.31, 33.04; IR (neat): υ 3414, 3054, 2948, 1735, 1600, 1503, 1432, 1373, 1326, 1227, 1192, 1152, 1072, 1018, 811, 740, 696 cm -1 ; dr (anti:syn) > 20:1; RMS (ESI) Calcd for [C 31 27 2 a 2, M + a] + : 561.1148; found: 561.1147; 99% ee (PLC condition: Chiralcel IA column, n-exane/i-pr = 90:10, flow rate = 1.0 ml/min, wave length = 254nm, t R =5.00 min for major isomer, t R = 5.45 min for minor isomer); [α] 10 D +101.7 (c 1.86, C 2 Cl 2 ). (2R,3R)-methyl-3-((4-chlorophenyl)amino)-2-(1-methyl-1-indol-3-yl)-2,3-diphe 16 ATURE CEMISTRY www.nature.com/naturechemistry 16
DI: 10.1038/CEM.1406 SUPPLEMETARY IFRMATI nylpropanoate (6g) Semi-solid; 98% yield; 1 MR (400Mz, CDCl 3 ): δ Cl 7.33-7.35 (m, 3 ), 7.24-7.26 (m, 3 ), 7.17 (t, J = 7.5z, 1 ), 7.02-7.10 (m, 5 ), 6.87 (t, J = 7.4 z, 1 6g ), 6.81 (d, J = 8.4 z, 2 ), 6.50 (t, J = 7.3 z, 1 ), 6.53 (d, J = 8.2 z, 1 ), 6.39 (d, J = 8.0 z, 2 ), 5.79 (d, J = 8.2 z, 1 ), 5.06 (br, 1 ), 3.78 (s, 3 ) 3.65 (s, 3 ); 13 C MR (100z, CDCl 3 ): δ 173.04, 146.19, 141.08, 139.39, 136.56, 132.69, 129.18, 129.05, 128.96, 128.01, 128.26, 127.01, 121.33, 121.09, 119.32, 116.98, 113.02, 109.63, 109.38, 61.94, 61.18, 52.00, 32.77; IR (neat): υ 3417, 3057, 2948, 1735, 1598, 1496, 1372, 1330, 1223, 1153, 1071, 1020, 814, 767, 700 cm -1 ; dr (anti:syn) > 20:1; RMS (ESI) Calcd for [C 32 27 F 3 2 a 2, M + a] + : 551.1917; found: 551.1919; 94% ee (PLC condition: Chiralcel IA column, n-exane/i-pr = 95:5, flow rate = 1.0 ml/min, wave length = 254nm, t R = 5.90 min for major isomer, t R = 6.89 min for minor isomer); [α] 10 D +18.4 (c 2.73, C 2 Cl 2 ). (2R,3R)-methyl-2-(4-methoxyphenyl)-2-(1-methyl-1-indol-3-yl)-3-phenyl-3-(phe nylamino)propanoate (6h) Me White solid; mp: 110-115 o C; 85% yield; 1 MR (400Mz, CDCl 3 ): δ 7.22-7.25 (m, 3 ), 7.07-7.16 (m, 4 ), 6.98-7.02 (m, 2 ), 6.94 (s, 1 ), 6.84-6.89 (m, 3 ), 6h 6.75 (d, J = 9.0 z, 2 ), 6.60 (d, J = 8.2 z, 1 ), 6.55 (t, J = 11.3 z, 1 ), 6.39 (d, J = 7.8 z, 2 ), 5.80 (d, J = 9.0 z, 1 ), 5.02 (d, J = 8.8 z, 1 ), 3.73 (s, 3 ), 3.69 (s, 3 ), 3.61 (s, 3 ); 13 C MR (100z, CDCl 3 ): δ 173.38, 158.58, 146.38, 139.61, 136.67, 133.17, 132.80, 130.24, 129.34, 129.21, 128.11, 127.48, 127.43, 121.51, 121.22, 119.49, 117.06, 113.51, 113.09, 109.78, 109.56, 61.43, 61.27, 55.23, 52.20, 32.94; IR (neat): υ 3431, 3054, 2932, 1735, 1602, 1507, 1458, 1250, 1224, 1182, 1135, 865, 794, 752, 698 cm -1 ; dr (anti:syn) > 20:1; RMS (ESI) Calcd for [C 32 30 2 a 2, M + a] + : 513.2149; found: 513.2133; 95% ee (PLC condition: Chiralcel IA column, n-exane/i-pr = 17 ATURE CEMISTRY www.nature.com/naturechemistry 17
DI: 10.1038/CEM.1406 SUPPLEMETARY IFRMATI 98:2, flow rate = 1.0 ml/min, wave length = 254nm, t R = 15.54 min for minor isomer, t R = 17.64 min for major isomer); [α] D 10 +69.7 (c 1.98, C 2 Cl 2 ). (2R,3R)-methyl-2-(4-bromophenyl)-2-(1-methyl-1-indol-3-yl)-3-phenyl-3-(phen ylamino)propanoate (6i) White solid; mp: 124-126 o C; 98% yield; 1 MR (400Mz, CDCl 3 ): δ 7.33-7.36 (m, 3 ), 7.10-7.22 (m, 6 ), 7.00-7.05 (m, 3 ), 6.91 (t, J = 7.2 z, 1 ), 6.83 (d, J 6i = 6.9 z, 2 ), 6.56-6.60 (m, 2 ), 6.40 (d, J = 7.7 z, 2 ), 5.75 (d, J = 7.4 z, 1 ), 5.04 (br, 1 ), 3.76 (s, 3 ), 3.65 (s, 3 ); 13 C MR (100z, CDCl 3 ): δ 172.64, 145.99, 140.19, 139.03, 136.57, 132.69, 131.10, 130.87, 129.12, 129.08, 127.51, 127.41, 121.28, 121.17, 119.55, 117.22, 113.06, 109.54, 109.04, 61.59, 61.14, 52.22, 32.86; IR (neat): υ 3401, 3058, 2927, 1735, 1601, 1503, 1486, 1431, 1222, 1153, 1075, 1009, 820, 741, 701 cm -1 ; dr (anti:syn) > 20:1; RMS (ESI) Calcd for [C 31 27 2 a 2, M + a] + : 561.1148; found: 561.1152; 84% ee (PLC condition: Chiralcel IA column, n-exane/i-pr = 95:5, flow rate = 1.0 ml/min, wave length = 254nm, t R = 8.47 min for minor isomer, t R = 9.66 min for major isomer); [α] 10 D +57.8 (c 1.81, C 2 Cl 2 ). (2R,3R)-methyl-2-(3-methoxyphenyl)-2-(1-methyl-1-indol-3-yl)-3-phenyl-3-(phe nylamino)propanoate (6j) Me Semi-solid; 76% yield; 1 MR (400Mz, CDCl 3 ): δ 7.37 (d, J = 8.2 z, 1 ), 7.22-7.17 (m, 5 ), 7.10-7.05 (m, 3 ), 6.99-6.92 (m, 5 ), 6.85 (d, J = 7.6 z, 1 ), 6.65-6.62 (m, 6j 2 ), 6.47 (d, J = 7.7 z, 2 ), 5.85 (d, J = 7.4 z, 1 ), 5.08 (d, J = 7.1 z, 1 ), 3.80 (s, 3 ), 3.70 (s, 3 ), 3.58 (s, 3 ); 13 C MR (100z, CDCl 3 ): δ 173.01, 159.36, 146.35, 142.73, 139.56, 136.59, 132.77, 129.26, 129.18, 128.98, 128.04, 127.47, 127.39, 121.61, 121.35, 121.17, 119.47, 117.02, 114.44, 113.16, 112.94, 109.45, 62.05, 61.84, 55.08, 52.19, 32.92; IR (neat): υ 3427, 3089, 2947, 1734, 1602, 1521, 1489, 1235, 1176, 1062, 834, 787, 775, 18 ATURE CEMISTRY www.nature.com/naturechemistry 18
DI: 10.1038/CEM.1406 SUPPLEMETARY IFRMATI 701 cm -1 ; dr (anti:syn) > 20:1; RMS (ESI) Calcd for [C 32 30 2 a 2, M + a] + : 513.2149; found: 513.2162; 94% ee (PLC condition: Chiralcel IA column, n-exane/i-pr = 90:10, flow rate = 1.0 ml/min, wave length = 254nm, t R = 7.33 min for major isomer, t R = 11.09 min for minor isomer); [α] 10 D +54.8 (c 1.91, C 2 Cl 2 ). (2S,3R)-methyl-2-(1-methyl-1-indol-3-yl)-3-phenyl-3-(phenylamino)-2-(thiophe n-2-yl)propanoate (6k) Semi-solid; 95% yield; 1 MR (500Mz, CDCl 3 ): δ 7.27 S (m, 1 ), 7.10-7.15 (m, 8 ), 6.83-6.88 (m, 6 ), 6.62 (m, 1 ), 6.47 (d, J = 6.9 z, 2 ), 5.54 (d, J = 6.4 z, 1 ), 6k 5.21 (d, J = 6.6 z, 1 ), 3.72 (s, 3 ), 3.70 (s, 3 ); 13 C MR (100z, CDCl 3 ): δ 172.25, 146.20, 144.65, 138.98, 136.66, 130.04, 129.10, 128.71, 128.10, 127.54, 127.45, 127.34, 125.86, 125.31, 121.50, 120.58, 119.51, 117.27, 113.21, 109.39, 64.24, 59.03, 52.47, 32.86; IR (neat): υ 3421, 2025, 2949, 1737, 1601, 1503, 1430, 1375, 1319, 1223, 1156, 1075, 1031, 909, 843, 774, 734, 697 cm -1 ; dr (anti:syn) > 20:1; RMS (ESI) Calcd for [C 29 26 2 a 2 S, M + a] + : 489.1607; found: 489.1601; 96% ee (PLC condition: Chiralcel AD column, n-exane/i-pr = 95:5, flow rate = 1.0 ml/min, wave length 10 = 254nm, t R = 9.53 min for major isomer, t R = 11.79 min for minor isomer); [α] D +95.2 (c 1.30, C 2 Cl 2 ). (R,E)-methyl-2-(1-methyl-1-indol-3-yl)-4-phenyl-2-((R)-phenyl(phenylamino)m ethyl)but-3-enoate (6l) Ph Semi-solid; 50% yield; 1 MR (500Mz, CDCl 3 ): δ 7.04-7.30 (m, 13 ), 6.55-6.61 (m, 3 ), 6.52 (t, J = 9.5 z, 1 ), 6.49-7.03 (m, 4 ), 6.08 (d, J = 16.2 z, 1 ), 5.61 (d, 6l J = 5.0 z, 1 ), 5.06 (d, J = 5.4 z, 1 ), 3.75 (s, 3 ), 3.73 (s, 3 ); 13 C MR (100z, CDCl 3 ): δ 173.77, 146.70, 139.72, 137.12, 131.55, 130.89, 129.15, 127.97, 127.66, 127.43, 126.91, 126.58, 19 ATURE CEMISTRY www.nature.com/naturechemistry 19
DI: 10.1038/CEM.1406 SUPPLEMETARY IFRMATI 121.64, 120.39, 119.47, 117.02, 113.08, 112.23, 109.44, 64.68, 57.43, 52.37, 32.90; IR (neat): υ 3439, 3021, 2923, 2852, 1730, 1601, 1506, 1374, 1323, 1262, 1193, 1071, 972, 742, 692 cm -1 ; dr (anti:syn) > 20:1; RMS (ESI) Calcd for [C 33 30 2 a 2, M + a] + : 509.2199; found: 509.2180; 97% ee (PLC condition: Chiralcel IA column, n-exane/i-pr = 95:5, flow rate = 1.0 ml/min, wave length = 254nm, t R = 8.72 min for major isomer, t R = 14.24 min for minor isomer); [α] 10 D +57.9 (c 0.63, C 2 Cl 2 ). (2R,3R)-methyl-2-(5-methoxy-1-methyl-1-indol-3-yl)-2,3-diphenyl-3-(phenylam ino)propanoate (6m) Semi-solid; 72% yield; 1 MR (500Mz, CDCl 3 ): Me 6m δ 7.28-7.30 (m, 2 ), 7.21-7.24 (m, 3 ), 7.08-7.15 (m, 3 ), 7.01-7.05 (m, 3 ), 6.92-6.94 (m, 1 ), 6.96 (d, J = 7.3 z, 2 ), 6.90 (m, 1 ), 6.59 (t, J =7.3 z, 1 ), 6.40 (d, J = 9.5 z, 2 ), 5.85-5.88 (m, 2 ), 4.96 (d, J = 8.3 z, 1 ), 3.72 (s, 3 ), 3.63 (s, 3 ), 3.39 (s, 3 ); 13 C MR (100z, CDCl 3 ): δ 172.94, 146.01, 140.84, 139.10, 137.41, 133.19, 129.13, 129.08, 128.87, 128.12, 127.42, 127.19, 122.78, 122.54, 117.24, 114.94, 113.18, 112.48, 61.76, 61.10, 52.16, 32.98; IR (neat): υ 3425, 3093, 2957, 1734, 1598, 1502, 1477, 1429, 1214, 1177, 885, 811, 745, 701 cm -1 ; dr (anti:syn) > 20:1; RMS (ESI) Calcd for [C 32 30 2 a 2, M + a] + : 513.2149; found: 513.2157; 98% ee (PLC condition: Chiralcel IA column, n-exane/i-pr = 98:2, flow rate = 1.0 ml/min, wave length = 254nm, t R = 15.94 min for major isomer, t R = 17.67 min for minor isomer); [α] 10 D +10.1 (c 1.34, C 2 Cl 2 ). (2R,3R)-methyl-2-(6-bromo-1-methyl-1-indol-3-yl)-2,3-diphenyl-3-(phenylamin o)propanoate (6n) White solid; mp: 149-152 o C; 75% yield; 1 MR (400Mz, CDCl 3 ): δ 7.47 (m, 1 ), 7.28-7.30 (m, 2 ), 7.21-7.24 (m, 3 ), 7.08-7.15 (m, 3 ), 7.01-7.05 (m, 3 ), 6.92-6.94 (m, 1 ), 6.85 (d, J = 7.3 z, 2 ), 6.59 (t, J = 7.3 z, 1 ), 6.42 (d, J = 8.0 20 ATURE CEMISTRY www.nature.com/naturechemistry 20
DI: 10.1038/CEM.1406 SUPPLEMETARY IFRMATI z, 2 ), 6.35 (d, J = 8.7 z, 1 ), 5.78 (d, J = 8.8 z, 1 ), 4.94 (d, J = 7.8 z, 1 ), 3.70 (s, 3 ), 3.63 (s, 3 ); 13 C MR (100z, CDCl 3 ): δ 172.94, 146.01, 6n 140.84, 139.10, 137.41, 133.19, 129.13, 129.08, 128.87, 128.12, 127.42, 127.19, 122.78, 122.54, 117.24, 114.94, 113.18, 112.48, 61.76, 61.10, 52.16, 32.98; IR (neat): υ 3383, 3021, 2948, 1733, 1601, 1499, 1451, 1430, 1315, 1225, 1190, 1128, 1072, 1015, 800, 746, 733, 701 cm -1 ; dr (anti:syn) > 20:1; RMS (ESI) Calcd for [C 31 27 2 a 2, M + a] + : 561.1148; found: 561.1173; 95% ee (PLC condition: Chiralcel IA column, n-exane/i-pr = 95:5, flow rate = 1.0 ml/min, wave length = 254nm, t R = 7.39 min for major isomer, t R = 11.84 min for minor isomer); [α] 10 D -34.8 (c 1.10, C 2 Cl 2 ). (2R,3R)-methyl-2-(1,7-dimethyl-1-indol-3-yl)-2,3-diphenyl-3-(phenylamino)pro panoate (6o) White solid; mp: 75-80 o C; 85% yield; 1 MR (400Mz, CDCl 3 ): δ 7.33-7.35 (m, 2 ), 7.21-7.23 (m, 3 ), 7.10-7.16 (m, 3 ), 7.02 (t, J = 7.9 z, 2 ), 6.82-6.89 (m, 6o 4 ), 6.70 (t, J = 7.6 z, 1 ), 6.57 (t, J = 7.3 z, 1 ), 6.36-6.42 (m, 3 ), 5.81 (s, 1 ), 5.07 (br, 1 ), 4.02 (s, 3 ), 3.64 (s, 3 ), 2.79 (s, 3 ); 13 C MR (100z, CDCl 3 ): δ 173.04, 146.19, 141.00, 139.40, 135.32, 134.61, 129.21, 129.03, 128.96, 128.90, 128.04, 127.33, 127.26, 126.97, 123.89, 121.29, 119.46, 116.88, 112.95, 109.04, 61.82, 61.14, 52.06, 37. 00, 19.92; IR (neat): υ 3425, 3017, 2965, 1737, 1601, 1504, 1454, 1431, 1320, 1223, 1107, 795, 777, 735, 697 cm -1 ; dr (anti:syn) > 20:1; RMS (ESI) Calcd for [C 32 30 2 a 2, M + a] + : 497.2199; found: 497.2202; 97% ee (PLC condition: Chiralcel IA column, n-exane/i-pr = 95:5, flow rate = 1.0 ml/min, wave length = 254nm, t R = 4.92 min for major isomer, t R = 5.81 min for minor isomer); [α] 10 D +62.8 (c 2.30, C 2 Cl 2 ). (2R,3R)-methyl-2-(1-benzyl-1-indol-3-yl)-2,3-diphenyl-3-(phenylamino)propan 21 ATURE CEMISTRY www.nature.com/naturechemistry 21
DI: 10.1038/CEM.1406 SUPPLEMETARY IFRMATI oate (6p) Semi-solid; 80% yield; 1 MR (400Mz, CDCl 3 ): δ 7.14-7.47 (m, 14 ), 7.04-7.10 (m, 4 ), 6.90-6.94 (m, 3 ), 6.60-6.65 (m, 2 ), 6.46 (d, J = 7.6 z, 2 ), 5.94 (d, J Bn 6p = 8.8 z, 1 ), 5.26-5.40 (m, 2 ), 5.03 (d, J = 8.8 z, 1 ), 3.69 (s, 3 ); 13 C MR (100z, CDCl 3 ): δ 172.99, 146.22, 141.20, 139.28, 137.39, 136.17, 132.54, 129.14, 128.84, 128.25, 127.73, 127.46, 127.43, 127.16, 127.04, 121.39, 119.70, 117.07, 113.04, 110.04, 62.03, 60.79, 52.18, 50.27, 29.73; IR (neat): υ 3422, 3054, 2972, 1737, 1601, 1502, 1453, 1392, 1320, 1222, 1179, 1057, 731, 695 cm -1 ; dr (anti:syn) > 20:1; RMS (ESI) Calcd for [C 37 32 2 a 2, M + a] + : 559.2356; found: 559.2347; 95% ee (PLC condition: Chiralcel IA column, n-exane/i-pr = 95:5, flow rate = 1.0 ml/min, wave length 10 = 254nm, t R = 5.64 min for major isomer, t R = 6.39 min for minor isomer); [α] D +50.8 (c 1.20, C 2 Cl 2 ). (2R,3R)-methyl-2,3-diphenyl-2-(1-phenyl-1-indol-3-yl)-3-(phenylamino)propan oate (6q) White solid; mp: 170-173 o C; 75% yield; 1 MR (400Mz, CDCl 3 ): δ 7.43-7.58 (m, 7 ), 7.29-7.32 (m, 4 ), 7.16-7.19 (m, 5 ), 7.03 (d, J = 8.0 z, 2 ), 6.93-6.95 6q Ph (m, 3 ), 6.58 (t, J = 7.5 z, 2 ), 6.43 (d, J = 8.0 z, 2 ), 5.97 (d, J = 9.5 z, 1 ), 4.98 (d, J = 9.0 z, 1 ), 3.67 (s, 3 ); 13 C MR (100z, CDCl 3 ): δ 172.79, 146.16, 140.75, 139.28, 139.39, 135.72, 132.12, 129.52, 129.21, 129.10, 128.99, 128.25, 127.56, 127.47, 127.22, 126.63, 124.57, 121.93, 121.46, 120.37, 117.17, 113.04, 110.76, 62.09, 60.95, 52.22, 26.89; IR (neat): υ 3412, 3052, 2977, 1739, 1597, 1501, 1456, 1379, 1323, 1260, 1215, 1181, 1076, 912, 751, 697 cm -1 ; dr (anti:syn) > 20:1; RMS (ESI) Calcd for [C 36 30 2 a 2, M + a] + : 545.2205; found: 545.2221; 86% ee (PLC condition: Chiralcel IA column, n-exane/i-pr = 95:5, flow rate = 1.0 ml/min, wave length 10 = 254nm, t R = 5.13 min for minor isomer, t R = 6.04 min for major isomer); [α] D 22 ATURE CEMISTRY www.nature.com/naturechemistry 22
DI: 10.1038/CEM.1406 SUPPLEMETARY IFRMATI -38.4 (c 2.10, C 2 Cl 2 ). 23 ATURE CEMISTRY www.nature.com/naturechemistry 23
DI: 10.1038/CEM.1406 SUPPLEMETARY IFRMATI 4. MR Spectra for ew Compounds (R)-3-((S)-((4-chlorophenyl)amino)(phenyl)methyl)-3-ethyl-1-methylindolin-2-on e (5ba) Cl 5ba Cl 5ba 24 ATURE CEMISTRY www.nature.com/naturechemistry 24
DI: 10.1038/CEM.1406 SUPPLEMETARY IFRMATI (R)-3-ethyl-1-methyl-3-((S)-phenyl(phenylamino)methyl)indolin-2-one (5bb) 5bb 5bb 25 ATURE CEMISTRY www.nature.com/naturechemistry 25
DI: 10.1038/CEM.1406 SUPPLEMETARY IFRMATI (R)-3-((S)-((4-bromophenyl)amino)(phenyl)methyl)-3-ethyl-1-methylindolin-2-on e (5bc) 5bc 5bc 26 ATURE CEMISTRY www.nature.com/naturechemistry 26
DI: 10.1038/CEM.1406 SUPPLEMETARY IFRMATI (R)-3-ethyl-1-methyl-3-((S)-phenyl((4-(trifluoromethyl)phenyl)amino)methyl)ind olin-2-one (5bd) CF 3 5bd CF 3 5bd 27 ATURE CEMISTRY www.nature.com/naturechemistry 27
DI: 10.1038/CEM.1406 SUPPLEMETARY IFRMATI (R)-3-((S)-((3-bromophenyl)amino)(phenyl)methyl)-3-ethyl-1-methylindolin-2-on e (5be) 5be 5be 28 ATURE CEMISTRY www.nature.com/naturechemistry 28
DI: 10.1038/CEM.1406 SUPPLEMETARY IFRMATI (R)-3-ethyl-1-methyl-3-((S)-(phenylamino)(4-(trifluoromethyl)phenyl)methyl)ind olin-2-one (5bf) Cl 5bf Cl 5bf 29 ATURE CEMISTRY www.nature.com/naturechemistry 29
DI: 10.1038/CEM.1406 SUPPLEMETARY IFRMATI (R)-3-((S)-(3-bromophenyl)(phenylamino)methyl)-3-ethyl-1-methylindolin-2-one (5bg) 5bg 5bg 30 ATURE CEMISTRY www.nature.com/naturechemistry 30
DI: 10.1038/CEM.1406 SUPPLEMETARY IFRMATI (R)-3-((S)-((4-chlorophenyl)amino)(3,4,5-trimethoxyphenyl)methyl)-3-ethyl-1-me thylindolin-2-one (5bh) Me Me Me Cl 5bh Me Me Me Cl 5bh 31 ATURE CEMISTRY www.nature.com/naturechemistry 31
DI: 10.1038/CEM.1406 SUPPLEMETARY IFRMATI (R)-3-((S,E)-1-((4-bromophenyl)amino)-3-phenylallyl)-3-ethyl-1-methylindolin-2- one (5bi) 5bi 5bi 32 ATURE CEMISTRY www.nature.com/naturechemistry 32
DI: 10.1038/CEM.1406 SUPPLEMETARY IFRMATI (R)-3-((S)-(4-bromophenyl)(phenylamino)methyl)-1,3-dimethylindolin-2-one (5ab) 5ab 5ab 33 ATURE CEMISTRY www.nature.com/naturechemistry 33
DI: 10.1038/CEM.1406 SUPPLEMETARY IFRMATI (R)-3-((R)-(4-bromophenyl)(phenylamino)methyl)-1-methylindolin-2-one (5cb) 5cb 5cb 34 ATURE CEMISTRY www.nature.com/naturechemistry 34
DI: 10.1038/CEM.1406 SUPPLEMETARY IFRMATI (R)-3-((S)-(4-bromophenyl)(phenylamino)methyl)-1,3-diethylindolin-2-one (5bj) 5bj 5bj 35 ATURE CEMISTRY www.nature.com/naturechemistry 35
DI: 10.1038/CEM.1406 SUPPLEMETARY IFRMATI (R)-1-benzyl-3-((S)-(4-bromophenyl)(phenylamino)methyl)-3-ethylindolin-2-one (5bk) Bn 5bk Bn 5bk 36 ATURE CEMISTRY www.nature.com/naturechemistry 36
DI: 10.1038/CEM.1406 SUPPLEMETARY IFRMATI (R)-5-bromo-3-((S)-(4-bromophenyl)((4-bromophenyl)amino)methyl)-3-ethyl-1- methylindolin-2-one (5bl) 5bl 5bl 37 ATURE CEMISTRY www.nature.com/naturechemistry 37
DI: 10.1038/CEM.1406 SUPPLEMETARY IFRMATI (2R,3R)-methyl-2-(1-methyl-1-indol-3-yl)-2,3-diphenyl-3-(phenylamino)propan oate (6a) 6a 6a 38 ATURE CEMISTRY www.nature.com/naturechemistry 38
DI: 10.1038/CEM.1406 SUPPLEMETARY IFRMATI (2R,3R)-methyl-3-(4-bromophenyl)-2-(1-methyl-1-indol-3-yl)-2-phenyl-3-(phen ylamino)propanoate (6b) 6b 6b 39 ATURE CEMISTRY www.nature.com/naturechemistry 39
DI: 10.1038/CEM.1406 SUPPLEMETARY IFRMATI (2R,3R)-methyl-2-(1-methyl-1-indol-3-yl)-2-phenyl-3-(phenylamino)-3-(4-(triflu oromethyl)phenyl)propanoate (6c) CF 3 6c CF 3 6c 40 ATURE CEMISTRY www.nature.com/naturechemistry 40
DI: 10.1038/CEM.1406 SUPPLEMETARY IFRMATI (2R,3R)-methyl-2-(1-methyl-1-indol-3-yl)-2-phenyl-3-(phenylamino)-3-(p-tolyl) propanoate (6d) 6d 6d 41 ATURE CEMISTRY www.nature.com/naturechemistry 41
DI: 10.1038/CEM.1406 SUPPLEMETARY IFRMATI (2R,3R)-methyl-3-(3-bromophenyl)-2-(1-methyl-1-indol-3-yl)-2-phenyl-3-(phen ylamino)propanoate (6e) 6e 6e 42 ATURE CEMISTRY www.nature.com/naturechemistry 42
DI: 10.1038/CEM.1406 SUPPLEMETARY IFRMATI (2R,3S)-methyl-3-(2-bromophenyl)-2-(1-methyl-1-indol-3-yl)-2-phenyl-3-(phen ylamino)propanoate (6f) 6f 6f 43 ATURE CEMISTRY www.nature.com/naturechemistry 43
DI: 10.1038/CEM.1406 SUPPLEMETARY IFRMATI (2R,3R)-methyl-3-((4-chlorophenyl)amino)-2-(1-methyl-1-indol-3-yl)-2,3-diphe nylpropanoate (6g) Cl 6g Cl 6g 44 ATURE CEMISTRY www.nature.com/naturechemistry 44
DI: 10.1038/CEM.1406 SUPPLEMETARY IFRMATI (2R,3R)-methyl-3-((4-methoxyphenyl)amino)-2-(1-methyl-1-indol-3-yl)-2,3-diph enylpropanoate (6h) Me 6h Me 6h 45 ATURE CEMISTRY www.nature.com/naturechemistry 45
DI: 10.1038/CEM.1406 SUPPLEMETARY IFRMATI (2R,3R)-methyl-2-(4-bromophenyl)-2-(1-methyl-1-indol-3-yl)-3-phenyl-3-(phen ylamino)propanoate (6i) 6i 6i 46 ATURE CEMISTRY www.nature.com/naturechemistry 46
DI: 10.1038/CEM.1406 SUPPLEMETARY IFRMATI (2R,3R)-methyl-2-(3-methoxyphenyl)-2-(1-methyl-1-indol-3-yl)-3-phenyl-3-(phe nylamino)propanoate (6j) Me 6j Me 6j 47 ATURE CEMISTRY www.nature.com/naturechemistry 47
DI: 10.1038/CEM.1406 SUPPLEMETARY IFRMATI (2S,3R)-methyl-2-(1-methyl-1-indol-3-yl)-3-phenyl-3-(phenylamino)-2-(thiophe n-2-yl)propanoate (6k) S 6k S 6k 48 ATURE CEMISTRY www.nature.com/naturechemistry 48
DI: 10.1038/CEM.1406 SUPPLEMETARY IFRMATI (R,E)-methyl-2-(1-methyl-1-indol-3-yl)-4-phenyl-2-((R)-phenyl(phenylamino)m ethyl)but-3-enoate (6l) Ph 6l Ph 6l 49 ATURE CEMISTRY www.nature.com/naturechemistry 49
DI: 10.1038/CEM.1406 SUPPLEMETARY IFRMATI (2R,3R)-methyl-2-(5-methoxy-1-methyl-1-indol-3-yl)-2,3-diphenyl-3-(phenylam ino)propanoate (6m) Me 6m Me 6m 50 ATURE CEMISTRY www.nature.com/naturechemistry 50
DI: 10.1038/CEM.1406 SUPPLEMETARY IFRMATI (2R,3R)-methyl-2-(6-bromo-1-methyl-1-indol-3-yl)-2,3-diphenyl-3-(phenylamin o)propanoate (6n) 6n 6n 51 ATURE CEMISTRY www.nature.com/naturechemistry 51
DI: 10.1038/CEM.1406 SUPPLEMETARY IFRMATI (2R,3R)-methyl-2-(1,7-dimethyl-1-indol-3-yl)-2,3-diphenyl-3-(phenylamino)pro panoate (6o) 6o 6o 52 ATURE CEMISTRY www.nature.com/naturechemistry 52
DI: 10.1038/CEM.1406 SUPPLEMETARY IFRMATI (2R,3R)-methyl-2-(1-benzyl-1-indol-3-yl)-2,3-diphenyl-3-(phenylamino)propan oate (6p) Bn 6p Bn 6p 53 ATURE CEMISTRY www.nature.com/naturechemistry 53
DI: 10.1038/CEM.1406 SUPPLEMETARY IFRMATI (2R,3R)-methyl-2,3-diphenyl-2-(1-phenyl-1-indol-3-yl)-3-(phenylamino)propan oate (6q) Ph 6q Ph 6q 54 ATURE CEMISTRY www.nature.com/naturechemistry 54
DI: 10.1038/CEM.1406 SUPPLEMETARY IFRMATI 5. PLC Charts of the Products (R)-3-((S)-((4-chlorophenyl)amino)(phenyl)methyl)-3-ethyl-1-methylindolin-2-on e (5ba) Cl (3S*, 1'R*)-5ba Cl (3S, 1'R)-5ba 55 ATURE CEMISTRY www.nature.com/naturechemistry 55
DI: 10.1038/CEM.1406 SUPPLEMETARY IFRMATI (R)-3-ethyl-1-methyl-3-((S)-phenyl(phenylamino)methyl)indolin-2-one (5bb) (3S*, 1'R*)-5bb (3S, 1'R)-5bb 56 ATURE CEMISTRY www.nature.com/naturechemistry 56
DI: 10.1038/CEM.1406 SUPPLEMETARY IFRMATI (R)-3-((S)-((4-bromophenyl)amino)(phenyl)methyl)-3-ethyl-1-methylindolin-2-on e (5bc) (3S*, 1'R*)-5bc (3S, 1'R)-5bc 57 ATURE CEMISTRY www.nature.com/naturechemistry 57
DI: 10.1038/CEM.1406 SUPPLEMETARY IFRMATI (R)-3-ethyl-1-methyl-3-((S)-phenyl((4-(trifluoromethyl)phenyl)amino)methyl)ind olin-2-one (5bd) CF 3 (3S*, 1'R*)-5bd CF 3 (3S, 1'R)-5bd 58 ATURE CEMISTRY www.nature.com/naturechemistry 58
DI: 10.1038/CEM.1406 SUPPLEMETARY IFRMATI (R)-3-((S)-((3-bromophenyl)amino)(phenyl)methyl)-3-ethyl-1-methylindolin-2-on e (5be) (3S*, 1'R*)-5be (3S, 1'R)-5be 59 ATURE CEMISTRY www.nature.com/naturechemistry 59
DI: 10.1038/CEM.1406 SUPPLEMETARY IFRMATI (R)-3-((S)-(4-chlorophenyl)(phenylamino)methyl)-3-ethyl-1-methylindolin-2-one (5bf) Cl (3S*, 1'R*)-5bf Cl (3S, 1'R)-5bf 60 ATURE CEMISTRY www.nature.com/naturechemistry 60
DI: 10.1038/CEM.1406 SUPPLEMETARY IFRMATI (R)-3-((S)-(3-bromophenyl)(phenylamino)methyl)-3-ethyl-1-methylindolin-2-one (5bg) (3S*, 1'R*)-5bg (3S, 1'R)-5bg 61 ATURE CEMISTRY www.nature.com/naturechemistry 61
DI: 10.1038/CEM.1406 SUPPLEMETARY IFRMATI (R)-3-((S)-((4-chlorophenyl)amino)(3,4,5-trimethoxyphenyl)methyl)-3-ethyl-1-me thylindolin-2-one (5bh) Me Me Me Cl (3S*, 1'R*)-5bh Me Me Me Cl (3S, 1'R)-5bh 62 ATURE CEMISTRY www.nature.com/naturechemistry 62
DI: 10.1038/CEM.1406 SUPPLEMETARY IFRMATI (R)-3-((S,E)-1-((4-bromophenyl)amino)-3-phenylallyl)-3-ethyl-1-methylindolin-2- one (5bi) (3S*, 1'R*)-5bi (3S, 1'R)-5bi 63 ATURE CEMISTRY www.nature.com/naturechemistry 63
DI: 10.1038/CEM.1406 SUPPLEMETARY IFRMATI (R)-3-((S)-(4-bromophenyl)(phenylamino)methyl)-1,3-dimethylindolin-2-one (5ab) (3S*, 1'R*)-5ab (3S, 1'R)-5ab 64 ATURE CEMISTRY www.nature.com/naturechemistry 64
DI: 10.1038/CEM.1406 SUPPLEMETARY IFRMATI (R)-3-((R)-(4-bromophenyl)(phenylamino)methyl)-1-methylindolin-2-one (5cb) (3R*, 1'R*)-5cb (3R, 1'R)-5cb 65 ATURE CEMISTRY www.nature.com/naturechemistry 65
DI: 10.1038/CEM.1406 SUPPLEMETARY IFRMATI (R)-3-((S)-(4-bromophenyl)(phenylamino)methyl)-1,3-diethylindolin-2-one (5bj) (3S*, 1'R*)-5bj (3S, 1'R)-5bj 66 ATURE CEMISTRY www.nature.com/naturechemistry 66
DI: 10.1038/CEM.1406 SUPPLEMETARY IFRMATI (R)-1-benzyl-3-((S)-(4-bromophenyl)(phenylamino)methyl)-3-ethylindolin-2-one (5bk) Bn (3S*, 1'R*)-5bk Bn (3S, 1'R)-5bk 67 ATURE CEMISTRY www.nature.com/naturechemistry 67
DI: 10.1038/CEM.1406 SUPPLEMETARY IFRMATI (R)-5-bromo-3-((S)-(4-bromophenyl)((4-bromophenyl)amino)methyl)-3-ethyl-1- methylindolin-2-one (5bk) (3S*, 1'R*)-5bl (3S, 1'R)-5bl 68 ATURE CEMISTRY www.nature.com/naturechemistry 68
DI: 10.1038/CEM.1406 SUPPLEMETARY IFRMATI (2R,3R)-methyl-2-(1-methyl-1-indol-3-yl)-2,3-diphenyl-3-(phenylamino)propan oate (6a) (2R*, 3R*)-6a (2R, 3R)-6a 69 ATURE CEMISTRY www.nature.com/naturechemistry 69
DI: 10.1038/CEM.1406 SUPPLEMETARY IFRMATI (2R,3R)-methyl-3-(4-bromophenyl)-2-(1-methyl-1-indol-3-yl)-2-phenyl-3-(phen ylamino)propanoate (6b) (2R*, 3R*)-6b (2R, 3R)-6b 70 ATURE CEMISTRY www.nature.com/naturechemistry 70
DI: 10.1038/CEM.1406 SUPPLEMETARY IFRMATI (2R,3R)-methyl-2-(1-methyl-1-indol-3-yl)-2-phenyl-3-(phenylamino)-3-(4-(triflu oromethyl)phenyl)propanoate (6c) CF 3 (2R*, 3R*)-6c CF 3 (2R, 3R)-6c 71 ATURE CEMISTRY www.nature.com/naturechemistry 71
DI: 10.1038/CEM.1406 SUPPLEMETARY IFRMATI (2R,3R)-methyl-2-(1-methyl-1-indol-3-yl)-2-phenyl-3-(phenylamino)-3-(p-tolyl) propanoate (6d) (2R*, 3R*)-6d (2R,3R)-6d 72 ATURE CEMISTRY www.nature.com/naturechemistry 72