Xiangya International Academy of Translational Medicine, Central South University, 172 Tongzipo Rd., Changsha, Hunan province, China,

Electronic Supplementary Material (ESI) for ChemComm. This journal is The Royal Society of Chemistry 2016 Supporting Information Enantioselective Oxidative Functionalization of Csp3-H Bond Adjacent to Nitrogen Atom for Rapid Access to β-hydroxyl-α-amino Acid Derivatives Lin Qiu, a,b Xin Guo, a Yu Qian, a Changcheng Jing, a Chaoqun Ma, a Shunying Liu, a * Liping Yang a and Wenhao Hu a * a Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, 3663 North Zhongshan Rd., Shanghai, China, 200062. E-mail: syliu@sist.ecnu.edu.cn; whu@chem.ecnu.edu.cn, Fax: (+86)-021-6222-1237 b Xiangya International Academy of Translational Medicine, Central South University, 172 Tongzipo Rd., Changsha, Hunan province, China, 410013 Contents pages General and Materials S2 General procedure for multi-component reaction S2 Notes and references S2 The direct oxidation of N-aryl glycine esters to imines. S3-S6 Crystal data of 3d.. S7 Characterization Data of Products S8- S14 NMR spectra for the Compounds...S15-S34 Chiral HPLC analysis figures of the Products.....S35-S52 1

General and Materials: HRMS spectra were recorded on a Bruker microtof II instrument. NMR spectra were recorded on a Brucker-400 MHz spectrometer. HPLC analysis was performed on Waters-Breeze (2487 Dual Absorbance Detector and 1525 Binary HPLC Pump) & Shimadzu (SPD-20AV UV-VIS Detector and LC-20AT Liquid Chromatograph Pump). Chiralpak IC was purchased from Daicel Chemical Industries. The racemic standards used in HPLC studies were prepared according to the general procedure by using a racemic BINOL derivatived phosphoric acid catalyst. Dichloromethane, chloroform, 1, 2-dichloroethane and toluene were commercial sources and used without further purification. Chiral phosphoric acids 4a-g 1, the diazo compound 1 2 and N-aryl glycine ester 2 3 were prepared according to the literature. The other chemicals were obtained from commercial sources and used without further purification. General procedure for multi-component reaction: A suspension of Rh2(OAc)4 (1 mol%), chiral phosphoric acid 4 (5 mol%), N-aryl glycine ester 2 (0.10 mmol, 1.0 eq), DDQ (0.10 mmol, 1.0 eq) and 0.05 ml water in 1.5 ml DCE was stirred at room temperature for 1 h, then cooled to -10 o C, and diazo compound 1 (0.15 mmol, 1.5 eq) in 0.5 ml DCE was added over 3 h via syringe pump. After completion of the addition, the reaction was stirred for additional 12 hours, and then allowed to warm to room temperature slowly. Solvent was removed and the crude products were purified by flash chromatography on silica gel (eluent : EtOAc / light petroleum ether = 1:20~ 1:5) to give the products 3. Notes and references: 1. (a) Uraguchi, D.; Terada, M.; J. Am. Chem. Soc. 2004, 126, 5356-5357; (b) Akiyama, T.; Morita, H.; Itoh, J.; uchibe, K. Org. Lett. 2005, 7, 2583-2585; (c) Storer, R. I.; Carrera, D. E.; Ni, Y.; MacMillan, D. W. C. J. Am. Chem. Soc. 2006, 128, 84-86; (d) Uraguchi, D.; Sorimachi, K.; Terada, M. Angew. Chem. Int. Ed. 2006, 45, 2254-2257; (e) Yamanaka, M.; Junji Itoh, M.; Fuchibe, K.; Akiyama, T. J. Am Chem. Soc. 2007, 129, 6756-6764; (f) Guo, Q.; Liu, H.; Luo, S.; Guo, C.; Gu, Y.; Gong, L. J. Am.Chem. Soc. 2007, 129, 3790-3791; (g) Jiang, J.; Yu, J.; Sun, X.; Rao, Q.; Gong, L. Angew. Chem., Int. Ed. 2008, 47, 2458-2462; (h) Masahiro, T.; Daisuke, U.; Keiichi, S.; Hideo, S. PCT Int. Appl. 2005 WO2005070875. 2. M. P. Doyle, M. A. McKervey, T. Ye, Modern Catalytic Methods for Organic Synthesis with Diazo Compounds, Wiley, New York, 1998, Chapter 1. 3. J. Xie and Z. Z. Huang, Angew. Chem. Int. Ed. 2010, 49, 10181-10185. 2

Table S1. The direct oxidation of N- aryl glycine esters to imines. a Time (min) Conversion (%) b 2a 2b 2e 0 0 0 0 5 64 74 41 15 95 86 45 35 97 91 86 75 97 90 94 a The reaction was carried out in NMR tube 0.05 mmol N-aryl glycine esters and 0.05 mmol DDQ with 0.5 ml CDCl3, NMR tube keep in ultrasonic cleaner. b Determined by 1 H NMR spectroscopy of the reaction mixture in the NMR tube. 100 80 conversion(%) 60 40 2a 2b 2e 20 0 0 20 40 60 80 time(min) Figure S1. The direct oxidation of N- aryl glycine esters to imines. Scheme S1. The Mannich addition of diazoketone 1a, water and imines 5a. 3

5 min 4

15 min 35 min 5

75 min Crude NMR of 3a 6

Crystal data of (2R, 3S)-anti-3c (CCDC 918137): The relative stereochemistry of the product was confirmed by single crystal X-ray analysis of 3c, and the data for compound 3c is consistent with that reported for the same compound in our previous work.8f Reference 8f) : Y. Qian, C. Jing, S. Liu, W. Hu, Chem. Commun. 2013, 49, 2700. 7

Characterization Data of Products: Ethyl (2R, 3S)-2-((4-chlorophenyl)amino)-3-hydroxy-4-oxo-4-phenylbutanoate (anti -3a): 76% yield; 86:14 dr (anti:syn); 93% ee (anti); determined by HPLC (Daicel Chirapak IC, flow rate 0.8 ml/min, hexane/isopropanol =50:10, 254 nm, Retention time: tminor = 10.5 min, tmajor = 13.2 min); 1 H NMR (CDCl3, 400 MHz) δ 1.12 (t, J = 7.2 Hz, 3H), 3.99-4.10 (comp, 3H), 4.50 (m, 1H), 4.81 (d, J = 10.7 Hz,1H), 5.39 (m, 1H), 6.61 (d, J = 8.7 Hz, 2H), 7.14 (d, J = 8.7 Hz, 2H), 7.55 (t, J = 7.7Hz, 2H), 7.67 (t, J = 7.4 Hz, 1H), 7.94 (d, J = 7.7 Hz, 2H); 13 C NMR (CDCl3, 100 MHz) δ 13.88, 60.52, 61.62, 74.24, 115.52, 123.90, 128.28, 129.09, 129.24, 134.15, 134.21, 144.86, 169.08, 198.20; HRMS (ESI) calcd for C18H18ClNNaO4 [M+Na] + : 370.0822, found 370.0802. Ethyl (2R, 3R)-2-(4-Chlorophenylamino)-3-hydroxy-4-oxo-4-phenylbutanoate (syn -3a): 76% yield; 86:14 dr (anti:syn); 69% ee (syn); determined by HPLC (Daicel Chirapak IC, flow rate 0.8 ml/min, hexane/isopropanol =50:10, 254 nm, Retention time: tminor = 9.0 min, tmajor = 11.0 min); 1 H NMR (CDCl3, 400 MHz) δ 7.77 (d, J = 7.3 Hz, 1H), 7.65 (dd, J = 6.2, 1.8 Hz, 2H), 7.44 7.32 (m, 2H), 6.93 (d, J = 8.8 Hz, 2H), 6.21 (d, J = 8.9 Hz, 2H), 5.60 (d, J = 1.2 Hz, 1H), 4.40 (s, 1H), 4.27 (dq, J = 10.5, 3.7 Hz, 3H), 1.29 (t, J = 7.2 Hz, 4H); 13 C NMR (CDCl3, 100 MHz) δ 198.09, 170.52, 145.01, 134.34, 133.07, 129.24, 128.89, 128.46, 123.70, 115.54, 74.14, 62.10, 60.23, 14.19; HRMS (ESI) calcd for C18H18ClNNaO4 [M+Na] + : 370.0822, found 370.0801. Ethyl (2R, 3S)-2-(4-Chlorophenylamino)-3-hydroxy-4-oxo-4-p-tolylbutanoate (3b): 85% yield; 90:10 dr (anti:syn); 94% ee (anti); determined by HPLC (Daicel Chirapak IC, flow rate 0.8 ml/min, hexane/isopropanol = 50:10, 254 nm, Retention time: tminor = 11.7 min, tmajor = 13.0 min); 1 H NMR (CDCl3, 400 MHz) δ 1.03 (t, J = 8.0 Hz, 3H), 2.39 (s, 3H), 3.90-3.99 (comp, 3H), 4.40 (dd, J = 4.0, 8.0 Hz, 1H), 4.70(d, J = 12.0 Hz, 1H), 5.29 (d, J = 2.0 Hz, 1H), 6.53 (d, J = 8.0 Hz, 2H), 7.06 (d, J = 8.0 Hz, 2H), 7.27 (d, J = 8.0 Hz, 2H), 7.76 (d, J = 8.0 Hz, 2H); 13 C NMR (CDCl3, 100 MHz) δ 13.90, 21.80, 60.67, 61.59, 74.09, 115.55, 123.93, 128.41, 129.26, 129.83, 131.53, 144.92, 145.43, 169.12, 197.63; HRMS (ESI) calcd for C19H20ClNNaO4 [M+Na] + : 384.0979, found 384.0983. 8

Ethyl (2R, 3S)-2-(4-Chlorophenylamino)-3-hydroxy-4-(4-methoxyphenyl)-4-oxobutanoate (3c): 78% yield; 92:8 dr (anti:syn); 95% ee (anti); determined by HPLC (Daicel Chirapak IC, flow rate 0.8 ml/min, hexane/isopropanol = 50:10, 254 nm, Retention time: tminor = 15.8 min, tmajor = 16.8 min); 1 H NMR (CDCl3, 400 MHz) δ 1.10 (t, J = 8.0 Hz, 3H), 3.91 (s, 3H), 3.97-4.09 (comp, 3H), 4.46 (dd, J =4.0, 12.0 Hz, 1H), 4.79 (d, J = 12.0 Hz, 1H), 5.34 (d, J = 4.0 Hz, 1H), 6.60 (d, J = 8.0 Hz, 2H), 7.01 (d, J = 8.0 Hz, 2H), 7.13 (d, J = 8.0 Hz, 2H), 7.93 (d, J = 8.0 Hz, 2H); 13 C NMR (CDCl3, 100 MHz) δ 13.90, 55.60, 60.75, 61.54, 73.75, 114.38, 115.52. 123.89, 126.79, 129.24, 130.70, 144.98, 164.45, 169.21, 196.23; HRMS (ESI) calcd for C19H20ClNNaO5[M+Na] + : 400.0928, found 400.0911. Ethyl (2R, 3S)-2-(4-Chlorophenylamino)-3-hydroxy-4-(naphthalen-2-yl)-4- oxobutanoate (3d): 74% yield; 85:15 dr (anti:syn); 89% ee (anti); determined by HPLC (Daicel Chirapak IC, flow rate 0.8 ml/min, hexane/isopropanol/alcohol = 90:5:5, 254 nm, Retention time: tminor = 28.7 min, tmajor = 23.9 min); 1 H NMR (CDCl3, 400 MHz) δ 7.74 (d, J = 8.5 Hz, 2H), 7.63 (d, J = 8.5 Hz, 2H), 7.13 6.98 (m, 2H), 6.55 (d, J = 8.8 Hz, 2H), 5.25 (dd, J = 6.9, 2.9 Hz, 1H), 4.66 (d, J = 10.8 Hz, 1H), 4.39 (dd, J = 10.7, 2.9 Hz, 1H), 3.98 (dddd, J = 17.9, 10.8, 7.2, 3.6 Hz, 2H), 3.81 (d, J = 7.0 Hz, 1H), 1.06 (t, J = 7.1 Hz, 3H); 13 C NMR (CDCl3, 100 MHz) δ 197.17, 168.02, 144.30, 133.29, 133.14, 131.17, 128.16, 127.30, 114.99, 110.09, 73.24, 60.70, 59.43, 12.92; HRMS (ESI) calcd for C18H17BrClNNaO4[M+Na] + :447.9927, found 447.9942. Ethyl (2R, 3S)-2-(4-Chlorophenylamino)-3-hydroxy-4-(naphthalen-2-yl)-4- oxobutanoate (3e): 78% yield; 76:24 dr (anti:syn); 89% ee (anti); determined by HPLC (Daicel Chirapak IA, flow rate 1.0 ml/min, hexane/isopropanol/alcohol = 90:5:5, 254 nm, Retention time: tminor = 28.7 min, tmajor = 23.9 min); 1 H NMR (CDCl3, 400 MHz) δ 7.83 (d, J = 7.7 Hz, 2H), 7.47 (d, J = 7.7 Hz, 2H), 7.09 (d, J = 7.5 Hz, 2H), 6.55 (d, J = 7.7 Hz, 2H), 5.26 (s, 1H), 4.67 (d, J = 10.7 Hz, 1H), 4.39 (d, J = 10.0 Hz, 1H), 3.98 (dd, J = 12.9, 6.3 Hz, 2H), 3.82 (d, J = 6.2 Hz, 1H), 1.06 (t, J = 7.0 Hz, 3H); 13 C NMR (CDCl3, 100 MHz) δ 196.12, 168.10, 143.84, 139.86, 131.56, 128.76, 9

128.53, 128.34, 123.25, 114.67, 73.28, 60.75, 59.64, 12.95; HRMS (ESI) calcd for C18H17Cl2NNaO4[M+Na] + : 404.0432, found 404.0438. Ethyl (2R, 3S)-2-(4-Chlorophenylamino)-3-hydroxy-4-(naphthalen-2-yl)-4- oxobutanoate (3f): 68% yield; 84:16 dr (anti:syn); 90% ee (anti); determined by HPLC (Daicel Chirapak IA, flow rate 1.0 ml/min, hexane/isopropanol/alcohol = 90:5:5, 254 nm, Retention time: tminor = 28.7 min, tmajor = 23.9 min); 1 H NMR (CDCl3, 400 MHz) δ 7.51 (d, J = 8.4 Hz, 1H), 7.44 (s, 1H), 7.08 (d, J = 8.5 Hz, 2H), 6.90 (d, J = 8.3 Hz, 1H), 6.57 (d, J = 8.5 Hz, 2H), 5.29 (d, J = 6.9 Hz, 1H), 5.23 (s, 1H), 4.71 (d, J = 11.0 Hz, 1H), 4.44 (d, J = 10.9 Hz, 1H), 3.98 (dd, J = 16.7, 7.3 Hz, 2H), 3.93 (s, 3H), 3.89 (s, 3H), 1.07 (t, J = 7.1 Hz, 3H); 13 C NMR (CDCl3, 100 MHz) δ 195.29, 168.22, 153.35, 148.60, 143.92, 128.29, 125.90, 122.97, 121.87, 114.54, 109.43, 109.31, 72.65, 60.57, 60.00, 55.22, 55.07, 12.97; HRMS (ESI) calcd for C18H17BrClNNaO4[M+Na] + : 430.1033, found 430.1039. Ethyl (2R, 3S)-2-(4-Chlorophenylamino)-3-hydroxy-4-(naphthalen-2-yl)-4-oxobutanoate (3g): 83% yield; 82:18 dr (anti:syn); 91% ee (anti); determined by HPLC (Daicel Chirapak IC, flow rate 0.8 ml/min, hexane/isopropanol = 50:10, 254 nm, Retention time: tminor = 15.7 min, tmajor = 13.9 min); 1 H NMR (CDCl3, 400 MHz) δ 1.11 (t, J = 8.0 Hz, 3H), 3.96-4.12 (comp, 3H), 4.58 (m, 1H), 4.82 (m, 1H), 5.54 (d, J = 4.0 Hz, 1H), 6.62 (d, J = 8.0 Hz, 2H), 7.14 (d, J = 8.0 Hz, 2H), 7.62 (m, 2H), 7.92 (d, J = 8.0 Hz, 2H), 7.98 (m, 3H), 8,46 (s, 1H); 13 C NMR (CDCl3, 100 MHz) δ 13.92, 60.78, 61.65, 74.32, 115.60, 123.70, 123.98, 127.37, 127.96, 129.23, 129.29, 129.53, 130.03, 131.43, 132.37, 136.01, 144.86, 169.08, 198.06; HRMS (ESI) calcd for C22H20ClNNaO4 [M+Na] + : 420.0979, found 420.0981. Ethyl (2R, 3S)-2-(4-Chlorophenylamino)-4-cyclohexyl-3-hydroxy-4-oxobutanoate (3h): 81% yield; 76:24 dr (anti:syn); 73% ee (anti); determined by HPLC (Daicel Chirapak IC, flow rate 0.8 ml/min, hexane/isopropanol = 50:10, 254 nm, Retention time: tminor = 5.9 min, tmajor = 7.0 min); 1 H NMR (CDCl3, 400 MHz)δ 1.17 (t, J = 8.0 Hz, 3H), 1.24-1.88 (m, 12H), 2.75 (m, 1H), 3.71 (br, 1H), 4.11-4.15(m, 2H ), 4.50 (dd, J = 4.0, 12.0 Hz, 1H), 4.64 (s, 1H), 4.70 (d, J = 12.0 Hz, 1H), 6.63(d, J = 8.0 Hz, 2H), 7.15 (d, J = 8.0 Hz, 2H); 13 C NMR (CDCl3, 100 MHz) δ 14.06, 25.12, 25.64, 25.90, 27.24, 30.08, 46.74, 59.56, 61.92, 75.32, 115.25, 123.88, 129.31, 129.66, 144.75, 169.34, 211.13; 10

HRMS (ESI) calcd for C18H24ClNNaO4 [M+Na] + :376.1292, found 376.1284. Ethyl (2R, 3R)-2-(4-fluorophenylamino)-3-hydroxy-4-oxo-4-phenylbutanoate (3i) 88% yield; 90:10 dr (anti:syn); 92% ee (anti); determined by HPLC (Daicel Chirapak IC, flow rate 0.8 ml/min, hexane/isopropanol = 50:10, 254 nm, Retention time: tminor = 25.6 min, tmajor = 29.1 min); 1 H NMR (CDCl3, 400 MHz) δ 7.99 7.78 (m, 2H), 7.67 7.52 (m, 1H), 7.48 (t, J = 7.7 Hz, 3H), 6.83 (dd, J = 11.9, 5.5 Hz, 2H), 6.61 6.49 (m, 2H), 5.32 (d, J = 2.7 Hz, 1H), 4.41 (s, 1H), 4.10 3.82 (m, 3H), 1.05 (t, J = 7.1 Hz, 3H); 13 C NMR (CDCl3, 100 MHz) δ 197.31, 168.30, 157.01, 154.65, 141.50, 133.24, 133.15, 128.12, 127.32, 115.03, 114.86, 114.79, 73.28, 60.59, 60.40, 12.91; HRMS (ESI) calcd for C18H19FNO4 [M+H] + :332.1220, found 332.1465. Ethyl (2R, 3S)-2-(4-bromophenylamino)-3-hydroxy-4-oxo-4-phenylbutanoate (3j): 82% yield; 88:12 dr (anti:syn); 93% ee (anti); determined by HPLC (Daicel Chirapak IC, flow rate 0.8 ml/min, hexane/isopropanol = 50:10, 254 nm, Retention time: tminor = 9.4 min, tmajor = 11.4 min); 1 H NMR (CDCl3, 400 MHz) δ 1.11 (t, J = 7.0 Hz, 3H), 3.99-4.09 (comp, 3H), 4.50 (dd, J = 2.5, 10.5 Hz, 1H), 4.83(d, J = 10.5 Hz, 1H), 5.39 (dd, J = 2.5, 6.5 Hz, 1H), 6.56 (d, J = 8.7 Hz, 2H), 7.27 (d, J = 8.7 Hz, 1H), 7.54 (t, J = 7.7 Hz, 2H), 7.66 (t, J = 7.0 Hz, 1H), 7.94 (d, J = 7.7 Hz, 2H); 13 C NMR (CDCl3, 100 MHz) δ 13.89, 60.36, 61.64, 74.23, 110.98, 115.94, 128.29, 129.10, 132.12, 134.15, 134.22, 145.32, 169.04, 198.19; HRMS (ESI) calcd for C18H18BrNNaO4 [M+Na] + : 414.0317, found 414.0309. Ethyl (2R, 3S)-3-hydroxy-4-oxo-4-phenyl-2-(phenylamino)butanoate (3k): 72% yield; 84:16 dr (anti:syn); 89% ee (anti); determined by HPLC (Daicel Chirapak IC, flow rate 0.8 ml/min, hexane/isopropanol = 50:10, 254 nm, Retention time: tminor = 13.4 min, tmajor = 16.8 min); 1 H NMR (CDCl3, 400 MHz)δ 1.03 (t, J = 8.0 Hz, 3H), 3.93-4.00 (comp, 3H), 4.51 (s, 1H), 4.69 (br, 1H), 5.33 (d, J = 1.6, 1H), 6.62 (d, J = 8.0 Hz, 2H), 6.72 (t, J = 8.0 Hz, 1H), 7.01 (t, J = 8.0 Hz, 1H), 7.46 (t, J = 8.0 Hz, 2H), 7.57 (t, J = 8.0 Hz, 1H), 7.87 (d, J = 8.0 Hz, 2H); 13 C NMR (CDCl3, 100 MHz) δ 13.90, 60.50, 61.51, 74.37, 114.44, 119.27, 128.31, 129.06, 129.40, 134.13, 134.24, 146.14, 169.31, 198.42; HRMS (ESI) calcd for C18H19NNaO4 [M+Na] + : 336.1212, found 336.1210. 11

Ethyl (2R, 3S)-2-(3,4-difluorophenylamino)-3-hydroxy-4-oxo-4-phenylbutanoate (3l): 86% yield; 95:5 dr (anti:syn); 95% ee (anti); determined by HPLC (Daicel Chirapak IC, flow rate 0.8 ml/min, hexane/isopropanol = 50:10, 254 nm, Retention time: tminor = 8.2 min, tmajor = 9.1 min); 1 H NMR (CDCl3, 500 MHz) δ 1.12 (t, J = 7.0 Hz, 3H), 3.98-4.10 (comp, 3H), 4.31 (d, J = 2.5 Hz, 1H), 5.39 (s, 1H), 6.37 (m, 1H), 6.47 (m, 1H), 6.97 (m, 2H), 7.56 (t, J = 7.5 Hz, 2H), 7.68 (t, J = 7.5 Hz, 1H), 7.93 (d, J = 8.0 Hz, 2H); 13 C NMR (CDCl3, 100 MHz) δ 13.94, 60.88, 61.80, 74.26, 103.28, 103.48, 109.76, 117.66, 117.84, 128.31, 129.22, 134.06, 134.39, 143.24, 169.00, 198.10; HRMS (ESI) calcd for C18H17F2NNaO4[M+Na] + : 372.1023, found 372.1036. Ethyl (2R, 3S)-2-(3-chloro-4-fluorophenylamino)-3-hydroxy-4-oxo-4-phenylbutanoate (3m): 79% yield; 90:10 dr (anti:syn); 95% ee (anti); determined by HPLC (Daicel Chirapak IC, flow rate 0.8 ml/min, hexane/isopropanol = 50:10, 254 nm, Retention time: tminor = 19.0 min, tmajor = 22.1 min); 1 H NMR (CDCl3, 400 MHz) δ 7.87 (d, J = 7.5 Hz, 2H), 7.61 (d, J = 7.3 Hz, 1H), 7.50 (t, J = 7.4 Hz, 2H), 6.90 (t, J = 8.7 Hz, 1H), 6.63 (d, J = 3.1 Hz, 1H), 6.54 6.34 (m, 1H), 5.31 (d, J = 4.2 Hz, 1H), 4.63 (d, J = 10.4 Hz, 1H), 4.37 (d, J = 10.5 Hz, 1H), 3.98 (dd, J = 15.3, 7.3 Hz, 2H), 3.88 (d, J = 6.7 Hz, 1H), 1.07 (t, J = 7.1 Hz, 3H); 13 C NMR (CDCl3, 100 MHz) δ 197.11, 167.92, 142.17, 133.35, 133.09, 128.21, 127.28, 116.20, 115.98, 114.68, 113.09, 113.02, 73.21, 60.78, 59.89, 12.92; HRMS (ESI) calcd for C18H17NO4FNaCl [M+Na] + : 388.0728, found 388.0733. Ethyl (2R, 3S)-2-(3,4-dichlorophenylamino)-3-hydroxy-4-oxo-4-phenylbutanoate (3n): 85% yield; 84:16 dr (anti:syn); 94% ee (anti); determined by HPLC (Daicel Chirapak IA, flow rate 1.0 ml/min, hexane/isopropanol/alcohol = 240:15:50, 254 nm, Retention time: tminor = 16.3 min, tmajor = 13.9 min); 1 H NMR (CDCl3, 500 MHz) δ 7.87 (dd, J = 8.3, 1.2 Hz, 1H), 7.62 (d, J = 7.5 Hz, 1H), 7.52 (t, J = 7.7 Hz, 2H), 7.36 (m, 1H), 7.16 (d, J = 8.7 Hz, 1H), 6.68 (d, J = 2.8 Hz, 1H), 6.50 6.41 (m, 1H), 5.31 (dd, J = 6.5, 2.7 Hz, 1H), 4.78 (d, J = 10.5 Hz, 1H), 4.40 (dd, J = 10.5, 2.7 Hz, 1H), 4.09 3.83 (m, 3H), 1.08 (t, J = 7.2 Hz, 3H); 13 C NMR (CDCl3, 100 MHz) δ 197.01, 167.68, 144.76, 133.38, 133.06, 132.01, 129.87, 128.24, 127.25, 120.86, 114.32, 113.12, 73.15, 60.87, 59.18, 12.92; 12

HRMS (ESI) calcd for C18H17Cl2NNaO4 [M+Na] + : 404.0432, found 404.0430. Methyl (2R, 3R)-2-(4-chlorophenylamino)-3-hydroxy-4-oxo-4-phenylbutanoate (3o) 86% yield; 80:20 dr (anti:syn); 80% ee (anti); determined by HPLC (Daicel Chirapak IC, flow rate 0.8 ml/min, hexane/isopropanol = 50:10, 254 nm, Retention time: tminor = 10.6min, tmajor = 12.0 min); 1 H NMR (CDCl3, 400 MHz) δ 7.87 (d, J = 7.2 Hz, 2H), 7.60 (t, J = 7.4 Hz, 1H), 7.49 (t, J = 7.7 Hz, 2H), 7.08 (d, J = 8.8 Hz, 2H), 6.54 (d, J = 8.8 Hz, 2H), 5.32 (dd, J = 7.0, 2.9 Hz, 1H), 4.67 (d, J = 10.7 Hz, 1H), 4.45 (dd, J = 10.8, 2.9 Hz, 1H), 3.86 (d, J = 7.0 Hz, 1H), 3.50 (s, 3H); 13 C NMR (CDCl3, 100 MHz) δ 197.21, 168.67, 143.78, 133.31, 133.15, 128.31, 128.17, 127.25, 123.06, 114.50, 73.14, 59.76, 51.12; HRMS (ESI) calcd for C17H16NO4NaCl [M+Na] + : 356.0666, found 356.0666. Benzyl (2R, 3S)-2-(4-chlorophenylamino)-3-hydroxy-4-oxo-4-phenylbutanoate (anti-3p) 68% yield; 79:21 dr (anti:syn); 85% ee (anti); determined by HPLC (Daicel Chirapak IC, flow rate 0.8 ml/min, hexane/isopropanol/alcohol = 90:5:5, 254 nm, Retention time: tminor = 15.0 min, tmajor = 23.9 min); 1 H NMR (CDCl3, 400 MHz) δ 7.71 (d, J = 7.9 Hz, 2H), 7.55 (m, 1H), 7.40 (t, J = 7.5 Hz, 3H), 7.23 (m, 3H), 7.05 (m, 4H), 6.53 (d, J = 8.3 Hz, 2H), 5.32 (s, 1H), 4.92 (s, 2H), 4.72 (d, J = 10.8 Hz, 1H), 4.47 (d, J = 10.8 Hz, 1H), 3.90 (s, 1H); 13 C NMR (CDCl3, 100 MHz) δ 197.02, 168.09, 143.81, 133.50, 133.20, 132.93, 128.29, 128.04, 127.77, 127.65, 127.53, 127.46, 127.32, 123.07, 114.59, 73.21, 66.48, 59.67; HRMS (ESI) calcd for C23H20NO4NaCl [M+Na] + : 432.0979, found 432.0981. Benzyl (2R, 3R)-2-(4-chlorophenylamino)-3-hydroxy-4-oxo-4-phenylbutanoate (syn-3p) 68% yield; 79:21 dr (anti:syn); 78% ee (syn); determined by HPLC (Daicel Chirapak IC, flow rate 0.8 ml/min, hexane/isopropanol/alcohol = 90:5:5, 254 nm, Retention time: tminor = 15.7 min, tmajor = 26.0 min); 1 H NMR (CDCl3, 400 MHz) δ 7.98 (dd, J = 8.5, 7.2 Hz, 2H), 7.73 7.63 (m, 3H), 7.51 7.46 (m, 1H), 7.39 7.31 (m, 3H), 7.13 (d, J = 8.7 Hz, 2H), 7.01 6.90 (m, 3H), 6.21 (dd, J = 8.9, 2.4 Hz, 2H), 5.60 (d, J = 7.4 Hz, 1H), 5.33 5.18 (m, 2H), 4.53 (s, 1H), 4.34 4.25 (m, 2H), 4.25 4.17 (m, 1H); 13 C NMR (CDCl3, 100 MHz) δ 197.87, 169.47, 143.77, 133.38, 133.26, 132.91, 128.17, 128.03, 127.93, 127.59, 127.44, 127.40, 127.38, 122.73, 114.58, 72.52, 66.64, 61.27; HRMS (ESI) calcd for C23H20NO4NaCl [M+Na] + : 432.0979, found 432.0978. 13

Isopropyl (2R, 3S)-2-((4-chlorophenyl)amino)-3-hydroxy-4-oxo-4-phenylbutanoate (anti-3q) 76% yield; 72:28 dr (anti:syn); 89% ee (anti); determined by HPLC (Daicel Chirapak IC, flow rate 0.8 ml/min, hexane/isopropanol/alcohol = 90:5:5, 254 nm, Retention time: tminor = 10.6 min, tmajor = 14.7 min); 1 H NMR (CDCl3, 400 MHz) δ 7.96 7.81 (m, 2H), 7.61 (t, J = 7.4 Hz, 1H), 7.50 (t, J = 7.7 Hz, 2H), 7.13 7.01 (m, 2H), 6.62 6.45 (m, 2H), 5.48 (d, J = 3.4 Hz, 1H), 5.30 (dd, J = 6.3, 2.7 Hz, 1H), 4.84 (dt, J = 12.5, 6.3 Hz, 1H), 4.70 (d, J = 10.6 Hz, 1H), 4.40 (d, J = 7.9 Hz, 1H), 3.89 (d, J = 6.6 Hz, 1H), 1.04 (dd, J = 7.5, 6.4 Hz, 6H); 13 C NMR (CDCl3, 100 MHz) δ 197.17, 167.51, 143.94, 133.22, 133.18, 128.28, 128.13, 127.36, 122.96, 114.61, 73.32, 69.02, 59.51, 20.69, 20.45; HRMS (ESI) calcd for C23H20NO4NaCl [M+Na] + : 384.0974, found 384.0962. Isopropyl (2R, 3R)-2-((4-chlorophenyl)amino)-3-hydroxy-4-oxo-4-phenylbutanoate (syn-3q) 76% yield; 72:28 dr (anti:syn); 9% ee (syn); determined by HPLC (Daicel Chirapak IC, flow rate 0.8 ml/min, hexane/isopropanol/alcohol = 90:5:5, 254 nm, Retention time: tmajor = 9.8 min, tminor = 10.8 min); 1 H NMR (CDCl3, 400 MHz) δ 7.89 7.85 (m, 2H), 7.60 (tt, J = 3.1, 2.4 Hz, 1H), 7.52 7.46 (m, 2H), 6.88 (d, J = 8.9 Hz, 2H), 6.23 6.09 (m, 2H), 5.49 (d, J = 1.6 Hz, 1H), 5.05 (dt, J = 12.5, 6.3 Hz, 1H), 4.36 (s, 1H), 4.22 (s, 1H), 1.19 (d, J = 6.1 Hz, 6H); 13 C NMR (CDCl3, 100 MHz) δ 197.15, 169.01, 144.03, 133.35, 132.10, 128.17, 127.90, 127.50, 122.78, 114.58, 73.08, 69.06, 59.35, 20.83, 20.68; HRMS (ESI) calcd for C23H20NO4NaCl [M+Na] + : 384.0974, found 384.0960. 14

NMR spectra for the Compounds: 15

16

17

18

19

20

21

22

23

24

25

26

27

28

29

30

31

32

33

34

35

Chiral HPLC analysis figures of the Products: 36

37

38

39

40

41

42

43

44

45

46

47

48

49

50

51

52

53