SUPPLEMENTARY INFORMATION

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1 SUPPLEMETARY IFRMATI DI: /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 , 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 PLC Charts of the Products X-ray Diffraction Parameters and Data References 88 1 ATURE CEMISTRY 1

2 DI: /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 2

3 DI: /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 ( 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 3

4 DI: /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 4

5 DI: /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 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 >20:1 0 2 (S)-7a Toluene 0 69 >20: (S)-7b Toluene 0 90 >20: (S)-7c Toluene 0 82 >20: (S)-7d Toluene 0 70 >20: (S)-7e Toluene 0 80 >20: (S)-7f Toluene 0 72 >20: (S)-7g Toluene 0 79 >20: (S)-7h Toluene 0 79 >20: (S)-7i Toluene 0 64 >20: (S)-7b DCM 0 86 >20: (S)-7b DCE 0 74 >20: (S)-7b TF 0 56 >20: (S)-7b Toluene >20: (S)-7b Toluene >20: (S)-7b Toluene >20: 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 5

6 DI: /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: o C; 77% yield; 1 MR Cl (500Mz, CDCl 3 ): δ (m, 3 ), 7.19 (t, J = 6.9 5ba z, 1 ), 7.09 (t, J = 7.3 z, 1 ), (m, 6 ), (m, 3 ), 6.15 (d, J = 8.6 z, 1 ), 4.76 (d, J = 8.8 z, 1 ), 2.99 (s, 3 ), (m, 1 ), (m, 1 ), 0.63 (t, J = 7.4 z, 3 ); 13 C MR (100Mz, CDCl 3 ): δ , , , , , , , , , , , , , , , 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 Cl 2 a, M + a] + : ; found: ; 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 = min for major isomer); [α] D (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 ), (m, 8 5bb ), (m, 4 ), 5.61 (d, J = 7.9 z, 1 ), 4.77 (d, J = 8.5 z, 1 ), 3.00 (s, 3 ), (m, 1 ), (m, 1 ), 0.61 (t, J = 7.4 z, 3 ); 13 C MR (100Mz, CDCl 3 ): δ , , , , , , , , , , , , , , 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 a, M + a] + : ; found: ; 97% ee (PLC condition: Chiralcel IA column, n-exane/i-pr = 98:2, flow rate = 1.0 ml/min, wave length = 254nm, t R = ATURE CEMISTRY 6

7 DI: /CEM.1406 SUPPLEMETARY IFRMATI min for minor isomer, t R = min for major isomer); [α] D (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 (m, 3 ), (m, 3 ), (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 ), (m, 1 ), (m, 1 ), 0.61 (t, J = 7.4 z, 3 ); 13 C MR (100Mz, CDCl 3 ): δ , , , , , , , , , , , , , , , 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 a, M + a] + : ; found: ; 97% ee (PLC condition: Chiralcel IA column, n-exane/i-pr = 95:5, flow rate = 1.0 ml/min, wave length = 254nm, t R = min for minor isomer, t R = min for major isomer); [α] 10 D (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 (m, 3 ), 7.19 (t, J = 7.6 z, 1 ), 7.09 (t, J = 5bd 7.5 z, 1 ), (m, 5 ), (m, 3 ), 6,15 (d, J = 8.7 z, 1 ), 4.76 (d, J = 8.8 z, 1 ), 3.00 (s, 3 ), (m, 1 ), (m, 1 ), 0.63 (t, J = 7.4 z, 3 ); 13 C MR (100Mz, CDCl 3 ): δ , , , , , , , , , , , , , , 62.37, 57.24, 27.97, 25.80, 8.78; IR (neat): υ 3367, 2933, 1693, 1613, 1532, 1494, 7 ATURE CEMISTRY 7

8 DI: /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 F 3 2 a, M + a] + : ; found: ; 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 = min for major isomer); [α] 10 D (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 ), (m, 3 ), (m, 2 ), 6.87 (t, J = 8.0 z, 1 ), (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 ), (m, 1 ), (m, 1 ), 0.61 (t, J = 7.4 z, 3 ); 13 C MR (100Mz, CDCl 3 ): δ , , , , , , , , , , , , , , , , , 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 a, M + a] + : ; found: ; 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 = min for major isomer); [α] 10 D (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 (d, J = 7.1 z, 1 ), 7.20 (t, J = 7.7 z, 1 ), (m, 3 ), 6.97 (d, J = 8.5 z, 2 ), 6.91 (d, J = 8.6 z, 2 ), (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 ), (m, 1 ), (m, 1 ), 0.62 (t, J = 8 ATURE CEMISTRY 8

9 DI: /CEM.1406 SUPPLEMETARY IFRMATI Cl 7.4 z, 3 ); 13 C MR (100Mz, CDCl 3 ): δ , , , , , , , , , , , , , , , 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 Cl 2 a, M + a] + : ; found: ; 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 = min for major isomer); [α] 10 D (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 (m, 3 ), 7.20 (t, J = 7.7 z, 1 ), (m, 3 5bg ), (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 ), (m, 1 ), (m, 1 ), 0.63 (t, J = 7.4 z, 3 ); 13 C MR (100Mz, CDCl 3 ): δ , , , , , , , , , , , , , 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 a, M + a] + : ; found: ; 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 = min for major isomer); [α] 10 D (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 ), ATURE CEMISTRY 9

10 DI: /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 ), (m, 1 ), (m, 1 ), 0.62 (t, J = 7.4 z, 3 ); 13 C MR (100Mz, CDCl 3 ): δ , , , , , , , , , , , , , , 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 Cl 2 a 4, M + a] + : ; found: ; 45% ee (PLC condition: Chiralcel IA column, n-exane/i-pr = 95:5, flow rate = 1.0 ml/min, wave length = 254nm, t R = min for major isomer, t R = min for minor isomer); [α] 10 D (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 ), (m, 1 ), bi (m, 6 ), (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 ), (m, 1 ), (m, 1 ), 0.61 (t, J = 7.4 z, 3 ); 13 C MR (125Mz, CDCl 3 ): δ , , , , , , , , , , , , , , , , 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 a, M + a] + : ; found: ; 65% ee (PLC condition: Chiralcel IA column, n-exane/i-pr = 95:5, flow rate = 1.0 ml/min, wave length = 254nm, t R = min for minor isomer, 10 ATURE CEMISTRY 10

11 DI: /CEM.1406 SUPPLEMETARY IFRMATI t R = min for major isomer); [α] D (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 (m, 2 ), 7.13 (d, J = 8.4 z, 2 ), (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 , , , , , , , , , , , , , , , 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 a, M + a] + : ; found: ; 90% ee (PLC condition: Chiralcel IA column, n-exane/i-pr = 95:5, flow rate = 1.0 ml/min, wave length = 254nm, t R = min for minor isomer, t R = min for major isomer); [α] 10 D (c 1.36, C 2 Cl 2 ). (R)-3-((R)-(4-bromophenyl)(phenylamino)methyl)-1-methylindolin-2-one (5cb) Yellow solid; mp: o C; 57% yield; 1 MR (500Mz, CDCl 3 ): δ (m, 3 ), (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 , , , , , , , , , , , , , , 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 a, M + a] + : , found: ; 89% ee (PLC condition: Chiralpad IA column, n-exane/i-pr = 95:5, flow rate = 1.0mL/min, wave length = 254nm, t R = ATURE CEMISTRY 11

12 DI: /CEM.1406 SUPPLEMETARY IFRMATI min for minor isomer, t R = 23.8 min for major isomer); [α] D (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 (m, 2 ), (m, 2 ), (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 ), (m, 1 ), (m, 1 ), (m, 1 ), (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 , , , , , , , , , , , , , , , 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 a, M + a] + : ; found: ; 88% ee (PLC condition: Chiralcel IA column, n-exane/i-pr = 98:2, flow rate = 1.0 ml/min, wave length = 254nm, t R = min for minor isomer, t R = min for major isomer); [α] 10 D (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 (m, 4 ), (m, 3 ), (m, 3 ), Bn 5bk (m, 4 ), 6.62 (t, J = 7.3 z, 1 ), (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 ), (m, 1 ), (m, 1 ), 0.64 (t, J = 7.4 z, 3 ); 13 C MR (100Mz, CDCl 3 ): δ , , , , , , , , , , , , , , , , , , , , 61.53, 57.22, 43.61, 28.80, 8.67; IR (neat): υ 3369, 3052, 2919, 1694, 12 ATURE CEMISTRY 12

13 DI: /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 a, M + a] + : ; found: ; 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 = min for major isomer); [α] 10 D (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), (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 ), (m, 1 ), (m, 1 ), 0.63 (t, J = 7.4 z, 3 ); 13 C MR (100Mz, CDCl 3 ): δ , , , , , , , , , , , , , , , , , 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 a, M + a] + : ; found: ; 98% ee (PLC condition: Chiralcel IA column, n-exane/i-pr = 98:2, flow rate = 1.0 ml/min, wave length = 254nm, t R = min for minor isomer, t R = min for major isomer); [α] 10 D (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: o C; 94% yield; 1 MR (400Mz, CDCl 3 ): δ (m, 3 ), (m, 3 ), (m, 4 ), (m, 3 ), (m, 3 ), (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 , , , , , , , , , , , , 13 ATURE CEMISTRY 13

14 DI: /CEM.1406 SUPPLEMETARY IFRMATI , , , , , 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 a 2, M + a] + : ; found: ; 97% ee (PLC condition: Chiralcel D- column, n-exane/i-pr = 100:1, flow rate = 1.0 ml/min, wave length = 254nm, t R = min for minor isomer, t R = min for major isomer); [α] D (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: o C; 93% yield; 1 MR (400Mz, CDCl 3 ): δ (m, 3 ), (m, 5 ), 7.08 (dd, J 1 = 6.7 z, J 2 = 7.9 z, 1 ), (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 , , , , , , , , , , , , , , , , , , 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 a 2, M + a] + : ; found: ; 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 (m, 5 ), (m 3 ), 7.09 (t, J = 8.0 z, 1 ), (m, 5 ), 6.77 (t, J = 7.2 z, 1 ), 6.53 (t, 14 ATURE CEMISTRY 14

15 DI: /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 , , , , , , , , , , , , , , , , , 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 F 3 2 a 2, M + a] + : ; found: ; 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 (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 (m, 3 ), (m, 3 ), (m, 1 ), (m, 3 ), (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 , , , , , , , , , , , , , , , , , 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 a 2, M + a] + : ; found: ; 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 15

16 DI: /CEM.1406 SUPPLEMETARY IFRMATI White solid; mp: o C; 58% yield; 1 MR (400Mz, CDCl 3 ): δ (m, 7 ), 7.16 (t, J = 7.4 z, 1 ), (m, 4 ), (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 ,, , , , , , , , , , , , , , , , , , , , 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 a 2, M + a] + : ; found: ; 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 (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 ), (m, 3 ), (m, 3 ), (m, 7 ), (m, 2 ), (m, 3 ), 5.94 (s, 1 6f ), 3.82 (s, 3 ), 3.72 (s, 3 ); 13 C MR (100z, CDCl 3 ): δ , , , , , , , , , , , , , , , , , , , 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 a 2, M + a] + : ; found: ; 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 (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 16

17 DI: /CEM.1406 SUPPLEMETARY IFRMATI nylpropanoate (6g) Semi-solid; 98% yield; 1 MR (400Mz, CDCl 3 ): δ Cl (m, 3 ), (m, 3 ), 7.17 (t, J = 7.5z, 1 ), (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 , , , , , , , , , , , , , , , , , , , 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 F 3 2 a 2, M + a] + : ; found: ; 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 (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: o C; 85% yield; 1 MR (400Mz, CDCl 3 ): δ (m, 3 ), (m, 4 ), (m, 2 ), 6.94 (s, 1 ), (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 , , , , , , , , , , , , , , , , , , , , , 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 a 2, M + a] + : ; found: ; 95% ee (PLC condition: Chiralcel IA column, n-exane/i-pr = 17 ATURE CEMISTRY 17

18 DI: /CEM.1406 SUPPLEMETARY IFRMATI 98:2, flow rate = 1.0 ml/min, wave length = 254nm, t R = min for minor isomer, t R = min for major isomer); [α] D (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: o C; 98% yield; 1 MR (400Mz, CDCl 3 ): δ (m, 3 ), (m, 6 ), (m, 3 ), 6.91 (t, J = 7.2 z, 1 ), 6.83 (d, J 6i = 6.9 z, 2 ), (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 , , , , , , , , , , , , , , , , , , , 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 a 2, M + a] + : ; found: ; 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 (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 ), (m, 5 ), (m, 3 ), (m, 5 ), 6.85 (d, J = 7.6 z, 1 ), (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 , , , , , , , , , , , , , , , , , , , , , , 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 18

19 DI: /CEM.1406 SUPPLEMETARY IFRMATI 701 cm -1 ; dr (anti:syn) > 20:1; RMS (ESI) Calcd for [C a 2, M + a] + : ; found: ; 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 = min for minor isomer); [α] 10 D (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 ), (m, 8 ), (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 , , , , , , , , , , , , , , , , , , , , 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 a 2 S, M + a] + : ; found: ; 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 = min for minor isomer); [α] D (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 (m, 13 ), (m, 3 ), 6.52 (t, J = 9.5 z, 1 ), (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 , , , , , , , , , , , , 19 ATURE CEMISTRY 19

20 DI: /CEM.1406 SUPPLEMETARY IFRMATI , , , , , , , 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 a 2, M + a] + : ; found: ; 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 = min for minor isomer); [α] 10 D (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 (m, 2 ), (m, 3 ), (m, 3 ), (m, 3 ), (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 ), (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 , , , , , , , , , , , , , , , , , , 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 a 2, M + a] + : ; found: ; 98% ee (PLC condition: Chiralcel IA column, n-exane/i-pr = 98:2, flow rate = 1.0 ml/min, wave length = 254nm, t R = min for major isomer, t R = min for minor isomer); [α] 10 D (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: o C; 75% yield; 1 MR (400Mz, CDCl 3 ): δ 7.47 (m, 1 ), (m, 2 ), (m, 3 ), (m, 3 ), (m, 3 ), (m, 1 ), 6.85 (d, J = 7.3 z, 2 ), 6.59 (t, J = 7.3 z, 1 ), 6.42 (d, J = ATURE CEMISTRY 20

21 DI: /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 , , 6n , , , , , , , , , , , , , , , , 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 a 2, M + a] + : ; found: ; 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 = min for minor isomer); [α] 10 D (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: o C; 85% yield; 1 MR (400Mz, CDCl 3 ): δ (m, 2 ), (m, 3 ), (m, 3 ), 7.02 (t, J = 7.9 z, 2 ), (m, 6o 4 ), 6.70 (t, J = 7.6 z, 1 ), 6.57 (t, J = 7.3 z, 1 ), (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 , , , , , , , , , , , , , , , , , , , , 61.82, 61.14, 52.06, , 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 a 2, M + a] + : ; found: ; 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 (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 21

22 DI: /CEM.1406 SUPPLEMETARY IFRMATI oate (6p) Semi-solid; 80% yield; 1 MR (400Mz, CDCl 3 ): δ (m, 14 ), (m, 4 ), (m, 3 ), (m, 2 ), 6.46 (d, J = 7.6 z, 2 ), 5.94 (d, J Bn 6p = 8.8 z, 1 ), (m, 2 ), 5.03 (d, J = 8.8 z, 1 ), 3.69 (s, 3 ); 13 C MR (100z, CDCl 3 ): δ , , , , , , , , , , , , , , , , , , , , 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 a 2, M + a] + : ; found: ; 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 (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: o C; 75% yield; 1 MR (400Mz, CDCl 3 ): δ (m, 7 ), (m, 4 ), (m, 5 ), 7.03 (d, J = 8.0 z, 2 ), q 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 , , , , , , , , , , , , , , , , , , , , , , , 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 a 2, M + a] + : ; found: ; 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 22

23 DI: /CEM.1406 SUPPLEMETARY IFRMATI (c 2.10, C 2 Cl 2 ). 23 ATURE CEMISTRY 23

24 DI: /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 24

25 DI: /CEM.1406 SUPPLEMETARY IFRMATI (R)-3-ethyl-1-methyl-3-((S)-phenyl(phenylamino)methyl)indolin-2-one (5bb) 5bb 5bb 25 ATURE CEMISTRY 25

26 DI: /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 26

27 DI: /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 27

28 DI: /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 28

29 DI: /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 29

30 DI: /CEM.1406 SUPPLEMETARY IFRMATI (R)-3-((S)-(3-bromophenyl)(phenylamino)methyl)-3-ethyl-1-methylindolin-2-one (5bg) 5bg 5bg 30 ATURE CEMISTRY 30

31 DI: /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 31

32 DI: /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 32

33 DI: /CEM.1406 SUPPLEMETARY IFRMATI (R)-3-((S)-(4-bromophenyl)(phenylamino)methyl)-1,3-dimethylindolin-2-one (5ab) 5ab 5ab 33 ATURE CEMISTRY 33

34 DI: /CEM.1406 SUPPLEMETARY IFRMATI (R)-3-((R)-(4-bromophenyl)(phenylamino)methyl)-1-methylindolin-2-one (5cb) 5cb 5cb 34 ATURE CEMISTRY 34

35 DI: /CEM.1406 SUPPLEMETARY IFRMATI (R)-3-((S)-(4-bromophenyl)(phenylamino)methyl)-1,3-diethylindolin-2-one (5bj) 5bj 5bj 35 ATURE CEMISTRY 35

36 DI: /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 36

37 DI: /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 37

38 DI: /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 38

39 DI: /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 39

40 DI: /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 40

41 DI: /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 41

42 DI: /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 42

43 DI: /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 43

44 DI: /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 44

45 DI: /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 45

46 DI: /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 46

47 DI: /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 47

48 DI: /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 48

49 DI: /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 49

50 DI: /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 50

51 DI: /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 51

52 DI: /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 52

53 DI: /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 53

54 DI: /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 54

55 DI: /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 55

56 DI: /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 56

57 DI: /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 57

58 DI: /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 58

59 DI: /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 59

60 DI: /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 60

61 DI: /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 61

62 DI: /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 62

63 DI: /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 63

64 DI: /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 64

65 DI: /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 65

66 DI: /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 66

67 DI: /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 67

68 DI: /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 68

69 DI: /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 69

70 DI: /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 70

71 DI: /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 71

72 DI: /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 72