Supporting Information

Supporting Information Wiley-VCH 2006 69451 Weinheim, Germany

A Highly Enantioselective Brønsted Acid Catalyst for the Strecker Reaction Magnus Rueping, * Erli Sugiono and Cengiz Azap General: Unless otherwise noted, all commercially available compounds were used as provided without further purification. Solvents for chromatography were technical grade and distilled prior to use. Toluene used in reaction was reagent grade and distilled from sodium. Analytical thin-layer chromatography (TLC) was performed on Merck silica gel aluminium plates with F-254 indicator, visualised by irradiation with UV light. Column chromatography was performed using silica gel Merck 60 (particle size 0.040-0.063 mm). Solvent mixtures are understood as volume/volume. Melting points were recorded on Büchi 530 Apparatus and uncorrected. 1 H-MR and 13 C-MR were recorded on a Bruker AM 250 spectrometer in CDCl 3. 1 H-MR were recorded at 55 C due signal broadening at room temperature. Data are reported in the following order: chemical shift (δ) in ppm; multiplicities are indicated (bs (broadened singlet), s (singlet), d (doublet), t (triplet), m (multiplet)); coupling constants (J) are in Hertz (Hz). High resolution mass spectra (HR-MS) were conducted on Micromass/ Waters Qtof Ultima 3 instrument. IR spectra were recorded on a Jasco FT/IR-420 spectrometer and are reported in terms of frequency of absorption (cm -1 ). 1

General procedure for asymmetric Strecker reaction: A flame dried flask equipped with a stir bar was charged with imine, catalyst (0,1 eq) and toluene. The reaction mixture was cooled and HC solution (1,5 eq, generated prior to the reaction from TMSC and methanol) was added. The mixture was allowed to stir at -40 C for 2-3 days. A cold solution of TFAA was then added and the resulting mixture was allowed to stir at rt for 3h. Solvents were removed in vacuo and the residue was subjected to column chromatography on silica gel to afford the corresponding acetylated product. (For HPLC analysis of the amino nitrile, before addition of TFAA, a sample was transferred into a precooled flask via a precooled pipette and the solvents were removed under reduced pressure). 1 5a: purified by chromatography on silica gel using hexane/ethyl acetate 10/1 as eluent to afford the product in 75% yield as a white solid, mp.: 83-84 C; 1 H-MR (CDCl 3, 55 C): δ = 4.77 (s, 2H, PhCH 2 ), 6.46 (s, 1H), 7.06-7.16 (m, 2H), 7.22-7.33 (m, 3H), 7.43 (d, J = 8.3 Hz, 2H), 7.57 (d, J = 8.3 Hz, 2H); 13 C-MR (CDCl 3, rt): δ = 50.0, 50.8, 107.0, 113.8, 114.0, 116.9, 118.4, 121.3, 125.6, 126.0, 128.1, 128.2, 129.0, 132.4, 134.5, 157.3; IR (KBr): 3055, 2987, 2305, 1705, 1421, 1265, 738 cm -1. HRMS-ESI: calculated for C 18 H 12 2 F 6 a ([M+a] + ): 409.0752, found: 409.0753. 1 Since no satisfactory HPLC condition could be found, compounds 5e and 5g were measured after acetylation. 2

5b: purified by chromatography on silica gel using hexane/ethyl acetate 10/1 as eluent to afford the product in 53% yield as a white solid, mp.: 87 C; 1 H-MR (CDCl 3, 55 C): δ = 3.79 (s, 3H), 4.69 (m, 2H), 6.42 (s, 1H), 6.77 (d, J = 8.5 Hz, 2H), 7.01 (d, J = 8.8 Hz, 2H), 7.38 (d, J = 8.0 Hz, 2H), 7.56 (d, J = 8.5 Hz, 2H); 13 C-MR (CDCl 3, rt): δ = 49.7, 50.5, 55.3, 114.0, 114.4, 118.5, 121.3, 124.0, 126.0, 128.0, 129.9, 134.7, 157, 9, 160.2; IR (KBr): 3055, 2986, 2305, 1702, 1421, 1265, 896, 746 cm -1. HRMS-ESI: calculated for C 19 H 14 2 2 F 6 a ([M+a] + ): 439.0857, found: 439.0852. 5c: purified by chromatography on silica gel using hexane/ethyl acetate 10/1 as eluent to afford the product in 59% yield as a white solid, mp.: 64 C; 1 H-MR (CDCl 3, 55 C): δ = 4.77 (s, 2H), 6.34 (s, 1H), 6.66-6.89 (m, 3H), 7.07-7.22 (m, 2H), 7.23-7.37 (m, 3H); 13 C-MR (CDCl 3, rt): δ = 49.7, 51.0, 104.9, 105.3, 105.7, 108.8, 110.8, 111.2, 113.7, 118.4, 128.3, 129.1, 129.2, 132.3, 134.3, 157.3, 157.9; 161.1, 165.1; IR (KBr): 3055, 2986, 2305, 1704, 1626, 1603, 1445, 1267, 1212, 1151, 740, 701; HRMS- ESI: calculated for C 17 H 11 2 F 5 a ([M+a] + ): 377.0689, found: 377.0689. 5d: purified by chromatography on silica gel using hexane/ethyl acetate 10/1 as eluent to afford the product in 85% yield as a white solid, mp.: 96 C; 1 H-MR (CDCl 3, 55 C): δ = 3.98 (d, J = 17.0 Hz, 1H), 4.73 (d, J = 17.0 Hz, 1H), 6.85 (d, J = 6.8 Hz, 3

2H), 7.05 7.23 (m, 3H), 7.31 (s, 1H), 7.42 (t, J = 7.8 Hz, 1 H), 7.53-7.71 (m, 4H), 7.91 (d, J = 8.0 Hz, 2H); 13 C-MR (CDCl 3, rt): δ = 48.3, 48.9, 115.5, 118.6, 121.4, 124.1, 124.8, 127.0, 127.3, 128.2, 128.4, 129.3, 129.4, 130.3, 131.7, 132.8, 133.7, 157.6, 158.2; IR (KBr): 3057, 2925, 1701, 1432, 1201, 1147, 794, 693 cm -1 ; HRMS-ESI: calculated for C 21 H 15 2 F 3 a ([M+a] + ): 391.1034, found: 391.1022. 5e: purified by chromatography on silica gel using hexane/ethyl acetate 10/1 as eluent to afford the product in 70% yield as a yellowish solid, mp.: 108-109 C; 1 H-MR (CDCl 3, 55 C): δ = 3.75 3.96 (m, 4H), 4.53 (d, J = 16.8, 1H), 6.56 (d, J = 8.0 Hz, 1H), 6.75 (d, J = 6.3 Hz, 2H), 6.92-7.18 (m, 4H), 7.27-7.58 (m, 4H), 8.18 (d, J = 7.8 Hz, 1H); 13 C-MR (CDCl 3, rt): δ = 48.0, 48.5, 55.8, 102.4, 114.0, 115.7, 118.6, 121.1, 123.4, 125.9, 126.2, 127.3, 128.3, 128.6, 130.0, 131.2, 133.0, 157.8, 158.1; IR (KBr): 3033, 2940, 1682, 1585, 1436, 1390, 1277, 1207, 1158, 741 cm -1. ; HRMS-ESI: calculated for C 22 H 17 2 2F 3 a ([M+a] + ): 491.1140, found: 421.1147. 5f: purified by chromatography on silica gel using hexane/ethyl acetate 10/1 as eluent to afford the product in 71% yield as a white solid, mp.: 88 C; 1 H-MR (CDCl 3, 55 C): δ = 4.53 (d, J = 16.0 Hz, 1H), 4.82 (d, J = 16.3 Hz, 1H), 6.61 (s, 1H), 6.95-7.14 (m, 2H), 7.17-7.25 (m, 3H), 7.31 (dd, J 1 = 1.8 Hz, J 2 = 6.8 Hz, 1H), 7.49-7.66 (m, 2H), 7.72-7.92 (m, 4 H); 13 C-MR 4

(MHz, CDCl 3, rt): δ = 50.1, 50.3, 114.0, 114.7, 118.6, 124.2, 127.2, 127.8, 128.0, 128.3, 128.8, 129.5, 132.8, 133.5, 157.5; IR (KBr): 3055, 2986, 2306, 1703, 1423, 1211, 1180, 1145, 761 cm -1. HRMS-ESI: calculated for C 21 H 15 2 F 3 a ([M+a] + ): 391.1034, found: 391.1029. 5g: purified by chromatography on silica gel using hexane/ethyl acetate 10/1 as eluent to afford the product in 88% yield as a white solid, mp.: 69 71 C; 1 H-MR (CDCl 3, 55 C): δ = 4.60 (d, J = 16.3 Hz, 1H), 4.77 (d, J = 16.3 Hz, 1H), 5.99 (d, J = 2.3 Hz, 2H), 6.35 (bs, 1H), 6.70-6.80 (m, 2H), 6.86 (d, J = 7.8 Hz, 1H), 7.04 7.20 (m, 2H), 7.24-7.40 (m, 3H); 13 C-MR (CDCl 3, rt): δ = 49.9, 101.9, 108.3, 108.5, 113.9, 114.8, 118.5, 122.3, 123.6, 127.8, 128.9, 133.1, 148.5, 149.0, 157.3, 157.9; IR (KBr): 3042, 2923, 1701, 1503, 1442, 12050, 1143, 702 cm -1. ; HRMS-ESI: calculated for C 18 H 13 2 3F 3 a ([M+a] + ): 385.0776, found: 385.0762. 5h: purified by chromatography on silica gel using hexane/ethyl acetate 10/1 as eluent to afford the product in 77% yield as a yellowish solid, mp.: 71 C; 1 H-MR (CDCl 3, 55 C): δ = 4.60 4.90 (m, 2H), 6.44 (s, 1H), 6.87-6.99 (m, 1H), 7.04-7.22 (m, 3H), 7.28-7.46 (m, 4H); 13 C-MR (CDCl 3, rt): δ = 45.1, 49.1, 112.7, 113.1, 117.3, 125.9, 126.3, 126.7, 127.6, 127.1, 127.3, 127.6, 127.8, 127.9, 128.9, 112.7, 131.2, 131.9, C= Signal fehlt; IR (film): 3055, 2986, 2305, 1701, 1422, 1270, 1211, 1156, 5

896, 736 cm -1 ; HRMS-ESI: calculated for C 15 H 11 2 F 3 Sa ([M+a] + ): 347.0442, found: 347.0426. 5i: purified by chromatography on silica gel using hexane/ethyl acetate 10/1 as eluent to afford the product in 84% yield as a red oil; 1 H-MR (CDCl 3, 55 C): δ = 4.64 4.86 (m, 2H), 6.28-6.35 (m, 2H), 6.38 (bs, 1H), 7.08-7.22 (m, 2H), 7.24-7.40 (m, 4H); 13 C-MR (CDCl 3, rt): δ = 44.5, 50.2, 111.1, 112.9, 113.3, 113.8, 118.3, 123.0, 127.3, 128.0, 128.4, 128.6, 128.7, 128.8, 133.2, 142.7, 144.5, 157.7; IR (KBr): 3020, 2400, 1703, 1433, 1226, 1206, 1177, 1151 cm -1 ; HRMS-ESI: calculated for C 15 H 11 2 2F 3 a ([M+a] + ): 331.0670, found: 331.0664. 5j: purified by chromatography on silica gel using hexane/ethyl acetate 10/1 as eluent to afford the product in 85% yield as a red oil. 1 H-MR (CDCl 3, 55 C): δ = 2.17 (s, 3H), 4.76 (bs, 2H), 5.82 5.95 (m, 1H), 6.30-6.54 (m, 2H), 7.04-7.18 (m, 2H), 7.25-7.33 (m, 3 H); 13 C-MR (CDCl 3, rt): δ = 13.4, 44.4, 49.8, 107.0, 113.6, 114.0, 127.1, 127.9, 128.0, 128.3, 128.6, 140.3, 154.7; IR (film): 3054, 2986, 2305, 1704, 1421, 1265, 896 cm -1. HRMS-ESI: calculated for C 16 H 13 2 2 F 3 a ([M+a] + ): 345.0827, found: 345.0813. 5k: purified by chromatography on silica gel using hexane/ethyl acetate 10/1 as eluent to afford the product in 87% yield as a white solid, mp.: 57-58 C; 1 H-MR (CDCl 3, 55 C): δ = 3.79 (s, 6

3H), 4.45 (d, J = 15.8 Hz, 1H), 4.73 (d, J = 16.0 Hz, 1H), 6.39 (s, 1H), 6.80 (d, J = 8.5 Hz, 2H), 7.02 (d, J = 8.5 Hz, 2H), 7.28-7.46 (m, 5H); 13 C-MR (CDCl 3, rt): δ = 49.7, 49.7, 55.5, 114.6, 114.9, 121.9, 127.8, 127.8, 128.7, 128.9, 129.6, 133.1, 160.7; IR (KBr): 3025, 2936, 2840, 1698, 1515, 1216, 1176, 1151, 759 cm -1. HRMS-ESI: calculated for C 18 H 15 2 2 F 3 a ([M+a] + ): 371.0983, found: 371.0999. 5l: purified by chromatography on silica gel using toluene/ethyl acetate 15/1 as eluent to afford the product in 97% yield as a white solid, mp.: 58 C; 1 H-MR (CDCl 3, 55 C): δ = 3.81 (s, 3H), 4.52 (d, J = 16.3 Hz, 1H), 4.75 (d, J = 16.3 Hz, 1H), 6.35 (bs, 1H), 6.78-6.94 (m, 2H), 7.02-7.14 (m, 2H), 7.18-7.38 (m, 5H); 13 C-MR (CDCl 3, rt): δ = 49.7, 55.5, 114.6, 114.9, 118.5, 121.8, 127.8, 128.9, 129.6, 133.1, 134.5, 157.3, 160.7; IR (KBr): 3054, 2986, 2305, 1702, 1422, 1265, 742, 706 cm -1. HRMS-ESI: calculated for C 18 H 15 2 2 F 3 a ([M+a] + ): 371.0983, found: 371.0980. 5m: purified by chromatography on silica gel using hexane/ethyl acetate 10/1 as eluent to afford the product in 55% yield as a white solid, mp.: 72-73 C; 1 H-MR (CDCl 3, 55 C): δ = 2.38 (s, 3H), 4.50 (d, J = 16.3 Hz, 1H), 4.79 (d, J = 16.3 Hz, 1H), 6.41 (bs, 1H), 7.02-7.42 (m, 9H). 13 C-MR (CDCl 3, rt): δ = 21.2, 49.9, 114.8, 118.5, 127.0, 127.9, 128.9, 129.9, 133.1, 140.1; IR (KBr): 3038, 2922, 1700, 1514, 1448, 1203, 1144, 698 cm -1. ; HRMS- ESI: calculated for C 18 H 15 2 F 3 a: 355.1034, found: 355.1048. 7

5n: purified by chromatography on silica gel using hexane/ethyl acetate 10/1 as eluent to afford the product in 69% yield as a white solid, mp.: 110 C; 1 H-MR (CDCl 3, 55 C): δ = 4.54 4.90 (m, 2H), 6.38 (bs, 1H), 7.06-7.18 (m, 2H), 7.20-7.42 (m, 7H); 13 C-MR (CDCl 3, rt): δ = 49.8, 50.5, 113.9, 114.3, 118.4, 128.1, 129.0, 129.2, 129.3, 132.7, 135.9; IR (KBr): 3054, 2986, 2305,1703, 1421, 1263, 896, 744 cm -1. HRMS-ESI: calculated for C 17 H 12 2 ClF 3 a ([M+a] + ): 375.0488, found: 375.0477. 5o: purified by chromatography on silica gel using hexane/ethyl acetate 10/1 as eluent to afford the product in 60% yield as a white solid, mp.: 79 C; 1 H-MR (CDCl 3, 55 C): δ = 3.80 (s, 3H), 4.55 (d, J = 16.0 Hz, 1H), 4.72 (d, J = 16.0 Hz, 1H), 6.33 (s, 1H), 6.80 (d, J = 8.8 Hz, 2H), 7.01 (d, J = 8.5 Hz, 2H), 7.19-7.26 (m, 2H), 7.29-7.37 (m, 2H); 13 C-MR (CDCl 3, rt): δ = 49.5, 50.0, 55.4, 114.3, 118.5, 124.2, 129.1, 129.3, 160.; IR (KBr): 3055, 2986, 2305,1700, 1421, 1268, 895, 734, 703 cm -1. HRMS-ESI: calculated for C 19 H 14 2 2 F 6 a ([M+a] + ): 405.0594, found: 405.0583. 6: A solution of aminonitrile 5l (92 mg, 0.25 mmol) in 2 ml of ether was added dropwise to lithium aluminum hydride (38 mg, 1 mmol) in ether (3 ml) at 0 C. After 30 minutes the solution was allowed to warm to rt and stirred for further 12 h. The reaction was quenched by slow addition of water (2mL) at 0 C. After addition of 15 % aq. ah (3 ml) the mixture was stirred for 30 8

min after which the organic layer was separated. The aqueous layer was extracted with ether (3 x 5 ml). The combined organic layers were dried over a 2 S 4, concentrated under reduced pressure, and recrystallization from CH 2 Cl 2 - Hexane yielded the product as a white solid (37.9 mg, 54 %); mp.: 86-88 C; 1 H-MR (CDCl 3, rt): δ = 1.65 (s, 3H), 2.76-2.98(m, 2H), 3.54-3.66 (m, 2H), 3.75 (d, J = 13.2 Hz, 1H), 3.85 (s, 3H), 6.96 (d, J = 8.5 Hz, 2H), 7.21-7.33 (m, 7 H, Ar); 13 C-MR (CDCl 3, rt): δ = 48.8, 51.4, 55.3, 64.1, 114.0, 126.9, 128.2, 128.4, 128.5, 134.2, 140.7, 158.9; IR (KBr): 3358, 3229, 3020, 2934, 2860, 2832, 1609, 1584, 1511, 1494, 1465, 1246, 1174, 1031, 873, 819, 700 cm -1 ; HRMS-ESI: calculated for C 16 H 21 2 ([M] + ): 257.1654 found: 25 257.1651; [α] D = + 51.0 (c = 1.0, CCl 4, ee: 94%). HPLC conditions: Chiralcel D-H column, n-hexane/2-propanol = 90/10, flow rate = 1.0 ml min-1, major enantiomer: t R = 17,58 min; minor enantiomer: t R = 33,88 min. 9

12.000 µv ES254_DH_955_flow 06_1.DATA [Jasco UV 1] 11.000 H 10.000 9.000 8.000 7.000 6.000 29,708 34,842 racemic 5.000 4.000 3.000 2.000 1.000 0-1.000 RT [min] 28 29 30 31 32 33 34 35 36 37 Column: DH n-hexane/ 2-propanol 95/5 (0,6 ml/min) ES254_DH_955_flow06_1.DATA [Jasco UV 1] Index Start Time End Area % [%] 1 2 28,683 33,889 29,708 34,842 30,868 36,167 51,734 48,266 Total 100,000

280.000 260.000 µv ES265_DH_955_flow 06_1.DATA [Jasco UV 1] 240.000 H 220.000 200.000 180.000 160.000 140.000 120.000 100.000 29,842 80.000 60.000 40.000 20.000 0 35,067 RT [min] 27 28 29 30 31 32 33 34 35 36 37 38 39 40 Column: DH n-hexane/ 2-propanol 95/5 (0,6 ml/min) ES265_DH_955_flow06_1.DATA [Jasco UV 1] Index Start Time End Area % [%] 1 2 28,593 34,559 29,842 35,067 31,533 35,644 98,651 1,349 Total 100,000

90.000 85.000 80.000 75.000 70.000 65.000 60.000 55.000 50.000 45.000 40.000 35.000 30.000 25.000 20.000 15.000 10.000 5.000 0-5.000 µv ES287_DH_955_flow 06 1.DATA [Jasco UV 1] 32,567 37,150 H racemic RT [min] 31 32 33 34 35 36 37 38 39 40 Column: DH n-hexane/ 2-propanol 95/5 (0,6 ml/min) ES287_DH_955_flow06 1.DATA [Jasco UV 1] Index Start Time End Area % [%] 1 2 31,426 35,981 32,567 37,150 34,215 38,817 50,363 49,637 Total 100,000

450.000 µv ES268_DH_955_flow 06_1.DATA [Jasco UV 1] 400.000 H 350.000 300.000 32,992 250.000 200.000 150.000 100.000 50.000 0 37,742 RT [min] 31 32 33 34 35 36 37 38 39 40 Column: DH n-hexane/ 2-propanol 95/5 (0,6 ml/min) ES268_DH_955_flow06_1.DATA [Jasco UV 1] Index Start Time End Area % [%] 1 2 31,588 36,953 32,992 37,742 35,035 38,585 98,018 1,982 Total 100,000

100.000 95.000 90.000 85.000 80.000 75.000 70.000 65.000 60.000 55.000 50.000 45.000 40.000 35.000 30.000 25.000 20.000 15.000 10.000 5.000 0-5.000 µv ES341_DH_9010_flow 06_1.DATA [Jasco UV 1] 18,575 22,383 H F racemic F RT [min] 17 18 19 20 21 22 23 24 25 Column: DH n-hexane/ 2-propanol 90/10 (0,6 ml/min) ES341_DH_9010_flow06_1.DATA [Jasco UV 1] Index Start Time End Area % [%] 1 2 17,820 21,601 18,575 22,383 19,432 23,337 50,091 49,909 Total 100,000

260.000 µv ES373_DH_9010_flow 06_1.DATA [Jasco UV 1] 240.000 220.000 200.000 180.000 160.000 18,858 F H 140.000 120.000 F 100.000 80.000 60.000 40.000 20.000 0 22,767-20.000 RT [min] 18 19 20 21 22 23 Column: DH n-hexane/ 2-propanol 90/10 (0,6 ml/min) ES373_DH_9010_flow06_1.DATA [Jasco UV 1] Index Start Time End Area % [%] 1 2 18,068 21,849 18,858 22,767 19,928 22,996 99,145 0,855 Total 100,000

22.000 20.000 18.000 16.000 14.000 µv ES381_DH_7525_flow 06_1.DATA [Jasco UV 3] H racemic 12.000 10.000 8.000 6.000 4.000 2.000 0 RT [min] 14 15 16 17 18 19 20 21 22 23 24 25 Column: DH n-hexane/ 2-propanol 75/25 (0,6 ml/min) ES381_DH_7525_flow06_1.DATA [Jasco UV 3] Index Start Time End Area % [%] 1 2 13,393 21,617 14,158 22,458 14,956 23,504 49,266 50,734 Total 100,000

220.000 µv ES378_DH_7525_flow 06_1.DATA [Jasco UV 3] 200.000 180.000 160.000 H 140.000 120.000 100.000 80.000 60.000 40.000 20.000 0 RT [min] 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 Column: DH n-hexane/ 2-propanol 75/25 (0,6 ml/min) ES378_DH_7525_flow06_1.DATA [Jasco UV 3] Index Start Time End Area % [%] 1 2 12,400 22,400 13,125 22,942 13,952 23,572 99,888 0,112 Total 100,000

130.000 µv ES310-Ac_DH_9010_flow 1_1.DATA [Jasco UV 1] 120.000 110.000 8,550 100.000 90.000 80.000 racemic 14,342 70.000 60.000 50.000 40.000 30.000 TI FF 20.000 10.000 0 RT [min] 8 9 10 11 12 13 14 15 16 Column: DH n-hexane/ 2-propanol 90/10 (1,0 ml/min) ES310-Ac_DH_9010_flow1_1.DATA [Jasco UV 1] Index Start Time End Area % [%] 1 2 8,213 13,853 8,550 14,342 9,081 15,000 50,387 49,613 Total 100,000

600.000 550.000 µv ES370_DH_9010_flow 1_1.DATA [Jasco UV 1] 8,442 500.000 450.000 400.000 350.000 300.000 250.000 200.000 150.000 100.000 50.000 14,275 0 RT [min] 7 8 9 10 11 12 13 14 15 16 17 Column: DH n-hexane/ 2-propanol 90/10 (1,0 ml/min) ES370_DH_9010_flow1_1.DATA [Jasco UV 1] Index Start Time End Area % [%] 1 2 7,810 13,884 8,442 14,275 9,174 14,752 97,089 2,911 Total 100,000

40.000 µv ES280_DH_955_flow 06 1.DATA [Jasco UV 1] 35.000 H 30.000 25.000 racemic 20.000 15.000 36,142 39,092 10.000 5.000 0-5.000 RT [min] 34 35 36 37 38 39 40 41 Column: DH n-hexane/ 2-propanol 95/5 (0,6 ml/min) ES280_DH_955_flow06 1.DATA [Jasco UV 1] Index Start Time End Area % [%] 1 2 34,912 38,027 36,142 39,092 37,655 40,584 50,197 49,803 Total 100,000

340.000 320.000 300.000 280.000 260.000 240.000 220.000 200.000 180.000 160.000 140.000 120.000 100.000 80.000 60.000 40.000 20.000 0 µv ES267_DH_955_flow 06_1.DATA [Jasco UV 1] H 35,742 38,775 RT [min] 34 35 36 37 38 39 40 41 Column: DH n-hexane/ 2-propanol 95/5 (0,6 ml/min) ES267_DH_955_flow06_1.DATA [Jasco UV 1] Index Start Time End Area % [%] 1 2 34,384 37,827 35,742 38,775 37,444 40,027 92,551 7,449 Total 100,000

10.000 9.500 9.000 8.500 8.000 7.500 7.000 6.500 6.000 5.500 5.000 4.500 4.000 3.500 3.000 2.500 2.000 1.500 1.000 500 0-500 -1.000 µv ES377rac_DH_982_flow 06_1.DATA [Jasco UV 2] 39,317 47,725 racemic RT [min] 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 Column: DH n-hexane/ 2-propanol 98/2 (0,6 ml/min) ES377rac_DH_982_flow06_1.DATA [Jasco UV 2] Index Start Time End Area % [%] 1 2 37,301 45,990 39,317 47,725 41,953 50,554 49,835 50,165 Total 100,000

65.000 µv ES397_DH_982_flow 06_1.DATA [Jasco UV 2] 60.000 55.000 50.000 45.000 40.000 35.000 30.000 37,775 25.000 20.000 15.000 10.000 5.000 0 46,592 RT [min] 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 Column: DH n-hexane/ 2-propanol 98/2 (0,6 ml/min) ES397_DH_982_flow06_1.DATA [Jasco UV 2] Index Start Time End Area % [%] 2 1 36,483 45,538 37,775 46,592 40,194 47,965 96,514 3,486 Total 100,000

90.000 85.000 80.000 75.000 70.000 65.000 60.000 55.000 50.000 45.000 40.000 35.000 30.000 25.000 20.000 15.000 10.000 5.000 0-5.000 µv ES336_DH_955_flow 06_0.DATA [Jasco UV 1] H 23,025 25,192 S racemic RT [min] 22 23 24 25 26 27 Column: DH n-hexane/ 2-propanol 95/5 (0,6 ml/min) ES336_DH_955_flow06_0.DATA [Jasco UV 1] Index Start Time End Area % [%] 1 2 22,285 24,325 23,025 25,192 23,974 26,174 49,952 50,048 Total 100,000

320.000 300.000 µv ES346_DH_955_flow 06_1.DATA [Jasco UV 1] 280.000 260.000 23,117 H 240.000 220.000 200.000 180.000 160.000 140.000 120.000 100.000 80.000 60.000 S 40.000 20.000 25,333 0 21 22 23 24 25 26 27 RT [min] 28 Column: DH n-hexane/ 2-propanol 95/5 (0,6 ml/min) ES346_DH_955_flow06_1.DATA [Jasco UV 1] Index Start Time End Area % [%] 1 2 22,231 24,777 23,117 25,333 24,280 25,942 97,318 2,682 Total 100,000

80.000 75.000 70.000 65.000 60.000 55.000 50.000 45.000 40.000 35.000 30.000 25.000 20.000 15.000 10.000 5.000 0-5.000 µv ES334_DH_955_flow 06_0.DATA [Jasco UV 1] H 23,350 24,550 racemic RT [min] 22 23 24 25 26 Column: DH n-hexane/ 2-propanol 95/5 (0,6 ml/min) ES334_DH_955_flow06_0.DATA [Jasco UV 1] Index Start Time End Area % [%] 1 2 22,524 24,016 23,350 24,550 24,016 25,623 52,466 47,534 Total 100,000

190.000 180.000 170.000 160.000 150.000 140.000 130.000 120.000 110.000 100.000 90.000 80.000 70.000 60.000 50.000 40.000 30.000 20.000 10.000 0-10.000 µv ES345_DH_955_flow 06_3.DATA [Jasco UV 1] 24,617 H RT [min] 23 24 25 26 27 25,900 Column: DH n-hexane/ 2-propanol 95/5 (0,6 ml/min) ES345_DH_955_flow06_3.DATA [Jasco UV 1] Index Start Time End Area % [%] 1 2 23,729 25,479 24,617 25,900 25,479 26,770 94,709 5,291 Total 100,000

38.000 36.000 34.000 32.000 30.000 28.000 26.000 24.000 22.000 20.000 18.000 16.000 14.000 12.000 10.000 8.000 6.000 4.000 2.000 0-2.000 µv ES306_DH_955_flow 06_1.DATA [Jasco UV 1] H 17,192 18,317 racemic RT [min] 17 18 19 Column: DH n-hexane/ 2-propanol 95/5 (0,6 ml/min) ES306_DH_955_flow06_1.DATA [Jasco UV 1] Index Start Time End Area % [%] 1 2 16,581 17,882 17,192 18,317 17,758 19,091 50,229 49,771 Total 100,000 Seite

550.000 µv ES307_DH_955_flow 06_1.DATA [Jasco UV 1] 500.000 450.000 17,100 H 400.000 350.000 300.000 250.000 200.000 150.000 100.000 50.000 18,267 0 RT [min] 15 16 17 18 19 20 Column: DH n-hexane/ 2-propanol 95/5 (0,6 ml/min) ES307_DH_955_flow06_1.DATA [Jasco UV 1] Index Start Time End Area % [%] 1 2 16,472 17,851 17,100 18,267 17,821 18,789 96,160 3,840 Total 100,000

460.000 440.000 420.000 400.000 380.000 360.000 340.000 320.000 300.000 280.000 260.000 240.000 220.000 200.000 180.000 160.000 140.000 120.000 100.000 80.000 60.000 40.000 20.000 0 µv CA-155_DH_991_flow 066.DATA [Jasco UV 1] 32,600 34,717 H racemic RT [min] 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 Column: DH n-hexane/ 2-propanol 99/1 (1,0 ml/min) CA-155_DH_991_flow066.DATA [Jasco UV 1] Index Start Time End Area % [%] 1 2 29,833 33,844 32,600 34,717 33,844 39,192 49,341 50,659 Total 100,000

210.000 200.000 190.000 180.000 170.000 160.000 150.000 140.000 130.000 120.000 110.000 100.000 90.000 80.000 70.000 60.000 50.000 40.000 30.000 20.000 10.000 0-10.000 µv ES244_DH_991_flow 1_1.DATA [Jasco UV 1] 32,008 34,892 H RT [min] 30 31 32 33 34 35 36 37 38 Column: DH n-hexane/ 2-propanol 99/1 (1,0 ml/min) ES244_DH_991_flow1_1.DATA [Jasco UV 1] Index 1 2 Start 30,754 33,899 Time 32,008 34,892 End 33,688 36,092 Area % [%] 94,341 5,659 Total 100,000

130.000 µv ES253_DH_955_flow 1_1.DATA [Jasco UV 1] 120.000 110.000 17,825 19,950 H 100.000 90.000 racemic 80.000 70.000 60.000 50.000 40.000 30.000 20.000 10.000 0 RT [min] 16 17 18 19 20 21 22 23 Column: DH n-hexane/ 2-propanol 95/5 (1,0 ml/min) ES253_DH_955_flow1_1.DATA [Jasco UV 1] Index Start Time End Area % [%] 1 2 17,142 19,014 17,825 19,950 18,886 21,055 49,553 50,447 Total 100,000

120.000 µv ES361_DH_955_flow 1_1.DATA [Jasco UV 1] 110.000 100.000 17,808 H 90.000 80.000 70.000 60.000 50.000 40.000 30.000 20.000 10.000 20,033 0 RT [min] 16 17 18 19 20 21 22 Column: DH n-hexane/ 2-propanol 95/5 (1,0 ml/min) ES361_DH_955_flow1_1.DATA [Jasco UV 1] Index Start Time End Area % [%] 1 2 17,088 19,451 17,808 20,033 18,939 20,650 96,523 3,477 Total 100,000

150.000 140.000 130.000 120.000 110.000 100.000 90.000 80.000 70.000 60.000 50.000 40.000 30.000 20.000 10.000 0-10.000 µv ES302_DH_955_flow 06_1.DATA [Jasco UV 1] H racemic 18,267 20,300 RT [min] 17 18 19 20 21 22 Column: DH n-hexane/ 2-propanol 95/5 (0,6 ml/min) ES302_DH_955_flow06_1.DATA [Jasco UV 1] Index Start Time End Area % [%] 1 2 17,644 19,630 18,267 20,300 19,002 21,055 49,966 50,034 Total 100,000

110.000 105.000 100.000 95.000 90.000 85.000 80.000 75.000 70.000 65.000 60.000 55.000 50.000 45.000 40.000 35.000 30.000 25.000 20.000 15.000 10.000 5.000 0 µv ES303_DH_955_flow 06_1.DATA [Jasco UV 1] 18,300 20,300 H RT [min] 17 18 19 20 21 22 Column: DH n-hexane/ 2-propanol 95/5 (0,6 ml/min) ES303_DH_955_flow06_1.DATA [Jasco UV 1] Index Start Time End Area % [%] 1 2 17,727 19,680 18,300 20,300 19,091 21,012 93,284 6,716 Total 100,000

26.000 24.000 µv ES258_DH_955_flow 06 1.DATA [Jasco UV 1] 22.000 H 20.000 18.000 16.000 27,158 Cl racemic 14.000 12.000 31,700 10.000 8.000 6.000 4.000 2.000 0-2.000 RT [min] 26 27 28 29 30 31 32 33 34 Column: DH n-hexane/ 2-propanol 95/5 (0,6 ml/min) ES258_DH_955_flow06 1.DATA [Jasco UV 1] Index Start Time End Area % [%] 1 2 26,219 30,775 27,158 31,700 28,218 33,146 50,072 49,928 Total 100,000

180.000 170.000 160.000 150.000 140.000 130.000 120.000 110.000 100.000 90.000 80.000 70.000 60.000 50.000 40.000 30.000 20.000 10.000 0-10.000 µv ES271_DH_955_flow 06_1.DATA [Jasco UV 1] 26,550 H Cl RT [min] 25 26 27 28 29 30 31 32 33 31,042 Column: DH n-hexane/ 2-propanol 95/5 (0,6 ml/min) ES271_DH_955_flow06_1.DATA [Jasco UV 1] Index Start Time End Area % [%] 1 2 25,345 30,128 26,550 31,042 27,949 32,094 92,592 7,408 Total 100,000

18.000 17.000 16.000 15.000 14.000 13.000 12.000 11.000 10.000 9.000 8.000 7.000 6.000 5.000 4.000 3.000 2.000 1.000 µv ES286_DH_991_flow 1_2.DATA [Jasco UV 1] 54,800 60,400 H Cl racemic RT [min] 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 Column: DH n-hexane/ 2-propanol 99/1 (1,0 ml/min) ES286_DH_991_flow1_2.DATA [Jasco UV 1] Index Start Time End Area % [%] 1 2 52,531 58,032 54,800 60,400 57,567 63,843 49,524 50,476 Total 100,000

42.000 40.000 38.000 36.000 34.000 32.000 30.000 28.000 26.000 24.000 22.000 20.000 18.000 16.000 14.000 12.000 10.000 8.000 6.000 4.000 2.000 0-2.000 µv Es272_DH_991_flow 1_1.DATA [Jasco UV 1] 57,875 63,375 H Cl RT [min] 55 56 57 58 59 60 61 62 63 64 65 66 67 68 Column: DH n-hexane/ 2-propanol 99/1 (1,0 ml/min) Es272_DH_991_flow1_1.DATA [Jasco UV 1] Index Start Time End Area % [%] 1 2 55,553 61,530 57,875 63,375 60,893 65,356 92,886 7,114 Total 100,000

160.000 150.000 140.000 130.000 µv ca255_dh_9010_flow 1_8.DATA [Jasco UV 1] 17,550 28,033 H 120.000 110.000 100.000 90.000 80.000 70.000 60.000 50.000 40.000 30.000 20.000 10.000 H 2 racemic 0 RT [min] 15 20 25 30 35 40 45 50 55 Column: DH n-hexane/ 2-propanol 90/10 (1,0 ml/min) ca255_dh_9010_flow1_8.data [Jasco UV 1] Index Start Time End Area % [%] 1 2 14,791 26,657 17,550 28,033 26,657 43,036 49,504 50,496 Total 100,000

320.000 300.000 280.000 260.000 240.000 220.000 200.000 180.000 160.000 140.000 120.000 100.000 80.000 60.000 40.000 20.000 0 µv ca264-1_dh_9010_flow 1_4.DATA [Jasco UV 1] 17,583 33,875 H H 2 RT [min] 15 20 25 30 35 40 45 50 55 60 Column: DH n-hexane/ 2-propanol 90/10 (1,0 ml/min) ca264-1_dh_9010_flow1_4.data [Jasco UV 1] Index Start Time End Area % [%] 1 2 15,460 31,504 17,583 33,875 31,504 52,145 97,231 2,769 Total 100,000

2.00 7.00 5.00 6.50 Seite 6.00 5.50 1.02 2.28 3.55 7.50 2.13 2.06 ppm (t1)

1.00 4.0 Seite 0.56 8.0 ppm (t1) 6.0 5.0 0.29 0.63 0.64 7.0 0.61 0.69

F F 2.00 0.91 2.87 1.98 3.05 ppm (t1) 7.50 7.00 6.50 6.00 5.50 5.00 4.50 Seite

1.00 0.99 ppm (t1) 4.0 Seite 7.0 6.0 5.0 8.0 1.81 2.68 0.81 1.00 3.74 1.97

4.16 1.00 ppm (f1) 8.0 6.0 4.0 Seite 5.0 0.97 2.01 7.0 4.13 4.25 1.08

1.00 1.00 ppm (f1) 4.50 5.00 8.00 6.00 Seite 5.50 0.90 6.50 1.91 7.00 2.74 7.50 1.03 2.00 3.90

1.00 1.01 ppm (t1) 7.50 7.00 4.50 6.50 5.00 Seite 5.50 6.00 2.02 0.93 1.92 0.97 2.02 3.16

S 1.00 0.43 0.46 1.36 1.98 ppm (f1) 7.50 7.00 6.50 6.00 5.50 5.00 4.50 Seite

2.00 ppm (t1) 7.00 6.00 5.00 Seite 5.50 0.94 0.72 0.90 6.50 1.86 4.04

3.00 2.0 3.0 ppm (f1) Seite 5.0 4.0 2.02 0.96 6.0 1.77 7.0 1.97 3.53

3.00 0.95 1.01 0.89 1.92 2.00 4.79 ppm (t1) 7.50 7.00 6.50 6.00 5.50 5.00 4.50 4.00 3.50 Seite

3.00 1.01 4.00 4.50 Seite 0.99 7.50 ppm (t1) 6.50 6.00 5.50 5.00 7.00 0.85 1.96 1.94 5.03

1.00 ppm (f1) 7.0 6.0 3.0 5.0 4.0 Seite 0.34 0.35 0.30 3.03

Cl 2.00 0.90 1.94 6.64 7.50 ppm (t1) 7.00 6.50 6.00 5.50 5.00 4.50 Seite

3.00 3.50 4.00 1.04 0.98 ppm (f1) 4.50 7.00 7.50 6.50 6.00 5.50 Cl 5.00 Seite 0.89 1.93 1.96 1.82 1.88

H H 2 3.00 1.94 8.0 ppm (f1) 2.0 6.0 5.0 4.0 7.0 3.0 1.96 0.99 2.72 1.87 6.56

ppm (t1) 150 100 50 157.314 134.501 132.361 129.049 128.216 128.125 125.996 125.610 121.280 118.409 116.943 113.984 113.833 107.023 50.830 50.028 Seite

ppm (t1) 150 100 50 160.216 157.911 134.747 129.910 127.995 125.963 123.952 121.326 118.453 114.387 113.996 55.279 50.459 49.736 Seite

ppm (t1) 150 100 50 165.113 161.117 157.869 157.260 134.300 132.310 129.230 129.067 128.278 118.376 113.711 111.221 110.789 108.830 105.702 105.307 104.903 50.968 49.685 F F Seite

ppm (f1) 150 100 50 158.200 157.613 133.730 132.795 131.667 130.305 129.447 129.277 128.394 128.232 127.338 126.957 124.805 124.120 121.422 118.583 115.483 48.875 48.273 Seite

ppm (t1) 150 100 50 158.148 157.761 133.020 131.182 130.048 128.553 128.308 127.331 126.168 125.873 123.416 121.123 118.582 115.711 114.006 102.449 55.787 48.516 48.006 Seite

ppm (f1) 150 100 50 157.461 133.502 132.777 129.506 128.848 128.320 127.992 127.772 127.602 127.213 124.214 124.185 118.575 114.736 113.997 50.325 50.108 Seite

ppm (t1) 150 100 50 157.898 157.288 148.965 148.450 133.127 128.871 127.810 123.642 122.330 118.489 114.762 113.914 108.546 108.294 101.856 49.942 Seite

ppm (t1) 150 100 50 131.913 131.199 128.939 127.940 127.832 127.585 127.275 127.104 126.730 126.260 125.948 117.289 113.090 112.712 49.133 45.122 S Seite

ppm (t1) 150 100 50 157.713 144.462 142.716 133.166 128.828 128.676 128.557 128.384 127.992 127.288 122.979 118.346 113.768 113.323 112.871 111.124 50.215 44.451 Seite

ppm (t1) 150 100 50 154.725 140.322 128.603 128.318 128.041 127.872 127.118 114.027 113.575 107.025 49.805 44.445 13.426 Seite

ppm (f1) 150 100 50 160.725 133.140 129.622 128.869 128.739 127.806 127.781 121.920 114.913 114.568 55.466 49.743 49.698 Seite

ppm (t1) 150 100 50 160.726 157.299 134.524 133.144 129.624 128.865 127.801 121.878 118.507 114.934 114.563 55.453 49.728 Seite

ppm (f1) 150 100 50 140.193 133.095 129.933 128.883 127.925 127.061 118.514 49.944 21.190 Seite

ppm (f1) 150 100 50 136.028 132.674 129.358 129.246 129.004 128.079 118.437 114.294 113.861 50.488 49.807 Cl Seite

ppm (t1) 150 100 50 160.256 129.730 129.280 129.129 124.220 118.470 114.295 77.578 77.070 76.562 55.376 50.080 49.544 Cl Seite

ppm (t1) 150 100 50 158.913 140.672 134.185 128.475 128.399 128.236 126.900 113.988 77.669 77.160 76.652 64.104 55.306 51.376 48.822 H H 2 Seite