Supporting Information

© Wiley-VCH 2007

69451 Weinheim, Germany

S-1

Enesulfonamides as Nucleophiles in Catalytic Asymmetric Reactions

Ryosuke Matsubara, Takashi Doko, Ryosuke Uetake, and Shu_ Kobayashi*

Graduate School of Pharmaceutical Sciences, The University of Tokyo,

Hongo, Bunkyo-ku, Tokyo 113-0033, Japan

Experimental

General. Melting points are uncorrected. 1H and 13C NMR spectra were recorded on a JEOL JNM-ECX-400 or JNM-ECX-600 spectrometer in CDCl3 or C6D6 unless otherwise noted. Tetramethylsilane (TMS) served as internal standard (δ = 0) for 1H NMR, and CDCl3 (δ = 77.0) and C6D6 (δ = 128.0) were used as internal standard for 13C NMR. IR spectra were measured on a JASCO FT/IR-610 spectrometer. Optical rotations were measured with a JASCO P-1010 polarimeter. High-performance liquid chromatography was carried out using following apparatus; SHIMADZU LC-10AT (liquid chromatograph), SHIMADZU SPD-10A (UV detector), and SHIMADZU C-R6A Chromatopac. Preparative high-performance liquid chromatography was carried out using following apparatus; SHIMADZU LC-8A (liquid chromatograph), SHIMADZU SPD-20A (UV detector), RID-10A (refractive index detector), SCL-10A (system controller), FRC-10A (fraction collector), YMC pack SIL-06 column (250x 20 mm, 5µm, 60A), and phenomenex Luna (250 x 50 mm, 15µm, 100A). Column chromatography was conducted on Silica gel 60 (Merck) and preparative thin-layer chromatography was carried out using Wakogel B-5F. X-ray diffraction analysis was

performed on a Rigaku-RAXIS-RAPID diffractometer. All reactions were carried out under argon atmosphere in dried glassware. All solvents were dried and distilled by standard procedures. Ethyl glyoxylate was freshly distilled before use according to the previously reported method.1 Diimine ligand 5 was prepared from commercially

1 Matsubara, R.; Vital, P.; Nakamura, Y.; Kiyohara, H.; Kobayashi, S. Tetrahedron 2004, 60, 9769.

S-2

available (1R, 2R)-(+)-1,2-diaminocyclohexane L-tartrate according to the reported method.2 CuClO4•4CH3CN was synthesized according to the reported method.3 All the ensulfonamides used in this report were synthesized from the corresponding ketones by following the reported method.4 Most of the products obtained in this reaction are literature known compounds.1,5 Preparation of Enesulfonamides. To a solution (suspension) of ketone (33 mmol) and sulfonamide (33 mmol) in DCM or DCE (30 mL) was added TiCl4 (33 mmol) in DCM or DCE (15 mL) in one portion at 0 °C. The color of the mixture was changed to dark red or black. Et3N (72.6 mmol) was added to the reaction mixture at 0 °C, then the reaction mixture was allowed to warm to rt. The reaction was kept stirred for 12 h, then poured into cooled sat. NaHCO3 aq. at 0 °C with stirring. The formed precipitate was filtered off and the filtrate was extracted with AcOEt twice. The organic layer was dried over anhydrous Na2SO4, filtered, then concentrated in vacuo. In some cases, enesulfonamide is a major product, in that case the following isomerization step could be skipped. Azeotropic removal of water by benzene evaporation was conducted for the crude material, then the residue was dissolved (or suspended) in THF (80 mL). To the mixture was added KOtBu (66 mmol) at 0 °C, and the reaction was kept stirred for 15 min at 0 °C. Water was added and the mixture was extracted with AcOEt three times. The combined organic layer was washed with brine, dried over anhydrous Na2SO4, and filtered. The filtrate was concentrated in vacuo to afford the residue, which was purified on neutral SiO2 column chromatography to afford a geometric mixture of enesulfonamide. The geometric isomers could be separated by recrystallization (Z isomers are generally more crystalline than E isomers.) or using preparative HPLC (silica gel-based column).

2 Mimoun, H.; Laumer, J. Y. S.; Giannini, L.; Scopelliti, R.; Floriani, C. J. Am. Chem. Soc. 1999, 121, 6158. 3 Kubas, G. J. Inorganic Synthesis; Shriver, D. F., Ed.; Plenum: New York, 1979; Vol. XIX, p 90. 4 Kato, S.; Igami, S. JP 63250303 A2 19881018 CAN 111:96854 1988. 5 R. Matsubara, S. Kobayashi, Angew. Chem. Int. Ed. 2006, 45, 7993; Angew. Chem. 2006, 118, 8161.

S-3

N-(benzenesulfonyl)-(E)-1-phenylprop-1-en-1-amine (E-4a): Mp. 107-108 °C; 1H NMR (CDCl3) δ = 1.60 (d, 3H, J = 7.3 Hz), 5.68 (q, 1H, J = 7.2 Hz), 6.03 (s, 1H), 6.95-7.10 (m, 2H), 7.20-7.30 (m, 3H), 7.45-7.63 (m, 3H), 7.82 (d, 2H, J = 7.8 Hz); 13C NMR (CDCl3) δ =

13.9, 115.7, 127.4, 128.3, 128.3, 128.8, 128.9, 132.8, 133.8, 135.4, 139.7; IR (neat) 3347, 3255, 2978, 1685, 1596, 1447, 1332, 1219, 1159, 1090, 951, 754, 688, 592, 536

cm-1; HRMS (FAB); Exact mass calcd for [M+H]+, 274.0902. Found 274.0911.

N-(benzenesulfonyl)-(Z)-1-phenylprop-1-en-1-amine (Z-4a): Mp. 104-104.5 °C; 1H NMR (CDCl3); δ = 1.47 (d, 3H, J = 6.8 Hz), 5.68 (q, 1H, J = 7.0 Hz), 6.18 (s, 1H), 7.20-7.27 (m, 3H),

7.30-7.37 (m, 2H), 7.38-7.45 (m, 2H), 7.50-7.55 (m, 1H); 13C NMR (CDCl3) δ = 13.0, 121.4, 126.8, 127.4, 128.1, 128.2, 128.9, 132.9, 135.1, 137.8, 139.8; IR (neat) 3258, 3082, 3062, 3020, 2919, 1644, 1585, 1491, 1480, 1446, 1402, 1326, 1268, 1165, 1091, 1043, 1025, 997, 970, 904, 844, 787, 748, 727, 696, 685, 645, 620, 571, 532, 440 cm-1; HRMS (FAB); Exact mass calcd for [M+H]+, 274.0902. Found 274.0903.

N-((p-methoxy)-benzenesulfonyl)-(E)-1-phenylprop-1-en-1-a

mine (E-4b): Mp. 52-54 °C;1H NMR (CDCl3); δ = 1.59 (d, 3H, J = 7.3 Hz), 3.87 (s, 3H), 5.65 (q, 1H, J = 7.2 Hz), 5.95-6.02 (brs,

1H), 6.94 (d, 2H, J = 8.7 Hz), 7.00-7.07 (m, 2H), 7.22-7.27 (m, 3H), 7.70-7.78 (m, 2H); 13C NMR (CDCl3) δ = 13.9, 55.6, 114.0, 115.0, 128.3, 128.8, 129.6, 131.3, 134.0, 135.6, 163.0; IR (neat) 3647, 3266, 3057, 2942, 2840, 1595, 1578, 1497, 14434, 1415, 1378, 1357, 1312, 1260, 1224, 1180, 1157, 1091, 1025, 960, 877, 834, 802, 781, 767, 700,

628, 577, 553 cm-1; HRMS (FAB); Exact mass calcd for [M+H]+, 304.1007. Found 304.0996.

N-((p-methoxy)-benzenesulfonyl)-(Z)-1-phenylprop-1-en-1-amine (Z-4b): Mp. 142.5-143.5 °C; 1H NMR (CDCl3) δ =

Me

Ph

HNS

O O

Ph

HNS

O O

Me

Me

Ph

HNS

OMe

O O

Ph

HNS

O O

MeOMe

S-4

1.49 (d, 3H, J = 6.9 Hz), 3.84 (s, 3H), 5.64 (q, 1H, J = 7.1 Hz), 6.12 (s, 1H), 6.85-6.88 (m, 2H), 7.22-7.26 (m, 3H), 7.34-7.37 (m, 2H), 7.61-7.64 (m, 2H); 13C NMR (CDCl3) δ = 12.9, 55.6, 113.9, 120.7, 126.7, 127.9, 128.0, 129.4, 131.4, 135.3, 137.7, 163.0; IR (neat) 3255, 1643, 1595, 1576, 1496, 1457, 1442, 1395, 1326, 1263, 1181, 1159, 1112, 1094, 1041, 1024, 968, 904, 833, 802, 785, 748, 695, 645, 612, 558, 539, 504, 448 cm-1; HRMS (FAB); Exact mass calcd for [M+H]+, 304.1007. Found 304.0995. A crystal suitable for X-ray diffraction analysis was prepared by recrystallization from AcOEt/hexane solvent system. CCDC-629330 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge from www.ccdc.cam.ac.uk/conts/retrieving.html, from the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB21EZ, UK; fax: (+44)1223-336-033; or deposit@ccdc.cam.ac.uk.

N-((p-methyl)-benzenesulfonyl)-(Z)-1-phenylprop-1-en-1-amine (Z-4c): Mp. 132-134 °C; 1H NMR (CDCl3) δ = 1.47 (d, 3H, J = 6.9 Hz), 2.41 (s, 3H), 5.66 (q, 1H, J = 7.2 Hz), 6.10 (s, 1H), 7.20-7.27 (m, 5H), 7.34-7.38 (m, 2H), 7.58-7.63 (m, 2H);

13C NMR (CDCl3) δ = 12.9, 21.5, 120.8, 126.7, 127.3, 127.9, 128.0, 129.4, 135.2, 136.7, 137.7, 143.6; IR (neat) 3263, 3032, 1646, 1596, 1492, 1444, 1395, 1326, 1164, 1091, 1040, 1025, 899, 834, 813, 783, 748, 693, 609, 549, 531 cm-1; HRMS (FAB); Exact mass calcd for [M+H]+, 288.1058. Found 288.1059.

N-((p-chloro)-benzenesulfonyl)-(E)-1-phenylprop-1-en-1-amine (E-4d): 1H NMR (C6D6) δ = 1.34 (d, 3H, J = 7.4 Hz), 5.45-5.55 (m, 1H), 5.75-6.05 (m, 1H), 6.80-6.85 (m, 2H), 6.85-7.00 (m, 5H), 7.43-7.50 (m, 2H); 13C NMR (C6D6) δ = 13.7, 116.0, 127.9,

128.0, 128.1, 128.3, 128.4, 129.0, 129.1, 129.2, 134.5, 135.7, 138.8, 139.4; IR (neat) 3266, 3088, 3059, 2919, 2857, 1911, 1700, 1650, 1585, 1493, 1476, 1443, 1396, 1379, 1359, 1317, 1278, 1223, 1164, 1091, 1027, 1014, 960, 883, 828, 781, 755, 700, 619, 564, 533, 482 cm-1; HRMS (FAB); Exact mass calcd for [M+H]+, 308.0512. Found 308.0514.

Ph

HNS

O O

MeMe

Me

Ph

HNS

Cl

O O

S-5

N-((p-chloro)-benzenesulfonyl)-(Z)-1-phenylprop-1-en-1-amine (Z-4d): Mp. 152-155 °C; 1H NMR (CDCl3) δ = 1.54 (d, 3H, J = 6.9 Hz), 5.70 (q, 1H, J = 6.9 Hz), 6.21 (s, 1H), 7.20-7.25 (m, 3H), 7.28-7.32 (m, 2H), 7.35-7.38 (m, 2H),

7.60-7.63 (m, 2H); 13C NMR (CDCl3) δ = 13.0, 121.7, 126.7, 128.1, 128.7, 129.0, 134.8, 137.3, 138.3, 139.3; IR (neat) 3265, 1557, 1471, 1394, 1331, 1167, 1089, 1010, 900,

824, 784, 756, 667, 642, 593, 530, 482, 419 cm-1; HRMS (FAB); Exact mass calcd for [M+H]+, 308.0512. Found 308.0524.

N-((p-methoxy)-benzenesulfonyl)-(E)-1-(p-methoxy)phenylprop-1-en-1-amine (E-4e): Mp. 95-96 °C; 1H NMR (CDCl3) δ = 1.59 (d, 3H, J = 7.6 Hz), 3.78 (s, 3H), 3,87 (s, 1H), 5.57 (q, 1H, J = 7.1 Hz), 5.90 (s,

1H), 6.77-6.80 (m, 2H), 6.93-6.96 (m, 2H), 6.97-7.01 (m, 2H), 7.73-7.76 (m, 2H); 13C NMR (CDCl3) δ = 13.9, 55.3, 55.6, 113.6, 114.0, 114.2, 127.9, 129.7, 130.2, 131.4, 133.8, 159.4, 163.0; IR (neat) 3263, 2975, 2939, 2839, 1671, 1596, 1555, 1510, 1498, 1459, 1441, 1418, 1377, 1356, 1315, 1260, 1176, 1150, 1088, 1026, 941, 881, 835, 803, 761, 739, 677, 628, 596, 552 cm-1; HRMS (FAB); Exact mass calcd for [M+H]+, 334.1113. Found 334.1102.

N-((p-methoxy)-benzenesulfonyl)-(Z)-1-(p-methoxy)phenylprop-1-en-1-amine (Z-4e): Mp. 151.5-152 °C; 1H NMR (CDCl3) δ = 1.45 (d, 3H, J = 7.1 Hz), 3.78 (s, 3H), 3.84 (s, 3H), 5.50 (q, 1H, J = 7.0 Hz), 5.96 (s, 1H), 6.75-6.80 (m, 2H), 6.85-6.90 (m,

2H), 7.26-7.33 (m, 2H), 7.60-7.67 (m, 2H); 13C NMR (CDCl3) δ = 12.7, 55.2, 55.6, 113.4, 113.9, 118.4, 128.0, 129.4, 130.3,

135.0, 159.5, 163.0; IR (neat) 3266, 1610, 1594, 1573, 1553, 1508, 1455, 1387, 1331,

1265, 1176, 1160, 1093, 1029, 824, 803, 702, 6116, 556, 419 cm-1; HRMS (FAB); Exact mass calcd for [M+H]+, 334.1113. Found 334.1102.

Ph

HNS

O O

MeCl

NH

OMe

MeO

S

O O

OMe

Me

HNS

OMe

O

O

S-6

N-((p-chloro)-benzenesulfonyl)-(E)-1-(p-methoxy)phenylprop-1-en-1-amine (E-4f): Mp. 116-117 °C; 1H NMR (CDCl3) δ = 1.58 (d, 3H, J = 7.4 Hz), 3.86 (s, 3H), 5.59 (q, 1H, J = 7.2 Hz), 6.05 (s, 1H), 6.92 (d, 2H, J =

8.8 Hz), 7.01 (d, 2H, J = 8.2 Hz), 7.22 (d, 2H, J = 8.2 Hz), 7.68 (d, 2H, J = 8.8 Hz); 13C NMR (CDCl3) δ = 13.9, 55.6, 114.0, 116.8, 128.4, 129.6, 130.4, 131.1, 133.2, 133.8, 134.1, 163.1; IR (neat) 3648, 3262, 2942, 2840, 1653, 1595, 1578, 1496, 1440, 1378, 1357, 1312, 1261, 1223, 1180, 1158, 1091, 1025, 961, 881, 833, 766, 720, 669, 628, 577, 555, 486 cm-1; HRMS (FAB); Exact mass calcd for [M+H]+, 338.0618. Found 338.0602.

N-((p-chloro)-benzenesulfonyl)-(Z)-1-(p-methoxy)phenylprop-1-en-1-amine (Z-4f): Mp. 175-176 °C; 1H NMR (CDCl3) δ = 1.47 (d, 3H, J = 6.9 Hz), 3.86 (s, 3H), 5.62 (q, 1H, J = 6.9 Hz), 6.02 (s, 1H), 6.87-6.90 (m, 2H), 7.19-7.22 (m, 2H), 7.28-7.32 (m, 2H) 7.60-7.63 (m, 2H); 13C NMR (CDCl3) δ = 12.8, 55.6, 114.0, 120.9, 128.1, 128.2, 129.4, 131.2, 133.8, 134.5, 136.2, 163.1; IR (neat) 3238, 1594, 1576, 1486, 1455, 1402, 1320, 1304, 1264,

1154, 1090, 1019, 822, 802, 739, 695, 679, 608, 561, 536, 420 cm-1; HRMS (FAB); Exact mass calcd for [M+H]+, 338.0618. Found 338.0612.

N-((p-methoxy)benzenesulfonyl)-(E)-1-phenylbut-1-en-1-amine (E-4g): 1H NMR (C6D6) δ = 0.72 (t, 3H, J = 7.5 Hz), 1.83 (quintet, 2H, J = 7.6 Hz), 3.05 (s, 3H), 5.61 (t, 1H, J = 7.8 Hz),

6.48-6.52 (m, 2H), 6.92-6.97 (m, 4H), 7.73-7.77 (m, 2H); 13C NMR (C6D6) δ = 14.5, 21.6, 54.6, 113.7, 113.9, 121.5, 127.6, 128.0, 128.9, 129.4, 129.8, 132.4, 133.6, 136.3, 162.7; IR (neat) 3267, 2963, 2930, 2871, 1595, 1578, 1497, 1444, 1362, 1317, 1260, 1217, 1180, 1155, 1091, 1025, 923, 886, 834, 803, 775, 700, 628, 579, 553 cm-1; HRMS (FAB); Exact mass calcd for [M+H]+, 318.1164. Found 318.1161.

NH

Cl

MeO

S

O O

Cl

Me

HNS

OMe

O

O

Et

Ph

HNS

O O

OMe

S-7

N-((p-methoxy)benzenesulfonyl)-(Z)-1-phenylbut-1-en-1-amine (Z-4g): Mp. 170-171 °C; 1H NMR (CDCl3) δ = 0.83 (t, 3H, J = 7.5 Hz), 1.89 (quintet, 2H, J = 7.5 Hz), 3.84 (s, 3H), 5.50 (t, 1H, J = 7.4 Hz), 6.03 (s, 1H), 6.84-6.90 (m, 2H),

7.21-7.27 (m, 3H), 7.33-7.38 (m, 2H), 7.58-7.65 (m, 2H); 13C NMR (CDCl3) δ = 13.4, 20.8, 55.6, 113.8, 126.9, 127.8, 128.0, 129.5, 131.3, 133.8, 137.6, 163.0; IR (neat) 3237, 2966, 1595, 1577, 1498, 1443, 1411, 1322, 1303, 1265, 1183, 1158, 1094, 1022, 920, 848, 802, 767, 739, 694, 624, 550 cm-1; HRMS (FAB); Exact mass calcd for [M+H]+, 318.1164. Found 318.1162.

N-((p-methoxy)benzenesulfonyl)-(E)-pent-2-en-3-amine (E-4h): Mp. 85-86 °C; 1H NMR (C6D6) δ = 0.78 (t, 3H, J = 7.3 Hz), 1.29 (d, 3H, J = 6.9 Hz), 1.94 (t, 2H, J = 7.3 Hz), 1.93 (q, 2H, J = 7.8 Hz), 3.06 (s, 3H), 5.34-5.46 (m, 1H), 6.50-6.80 (m, 3H), 7.85-7.98 (m, 2H); 13C NMR (C6D6) δ = 11.9, 12.2, 23.3, 54.9, 111.1, 114.1, 130.0, 132.3, 136.6, 163.0; IR (neat) δ = 3267, 2974, 2841, 1596, 1579, 1499, 1461, 1442, 1414, 1320,

1260, 1181, 1156, 1094, 1058, 1024, 954, 891, 833, 803, 681, 628, 593, 566, 546 cm-1; HRMS (FAB); Exact mass calcd for [M+H]+, 256.1007. Found 256.1017. A crystal suitable for X-ray diffraction analysis was prepared by recrystallization from AcOEt/hexane solvent system. CCDC-629329 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge from www.ccdc.cam.ac.uk/conts/retrieving.html, from the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB21EZ, UK; fax: (+44)1223-336-033; or deposit@ccdc.cam.ac.uk.

N-((p-methoxy)benzenesulfonyl)-(Z)-pent-2-en-3-amine (Z-4h): Mp. 101-102 °C; 1H NMR (CDCl3) δ = 0.97 (t, 3H, J = 7.3 Hz), 1.30 (d, 3H, J = 6.9 Hz), 2.16 (q, 2H, J = 7.5 Hz), 3.86 (s, 3H), 5.03 (q, 1H, J = 6.9 Hz), 5.70-5.83 (m, 1H), 6.93-6.97 (m, 2H), 7.75-7.80 (m, 2H); 13C NMR (CDCl3) δ = 11.7, 12.1, 27.9, 55.6, 114.1, 115.0, 129.2, 131.8, 136.6, 162.9; IR (neat) 3275, 2969, 2938, 2841, 1671,

1596, 1578, 1498, 1461, 1442, 1396, 1321, 1260, 1180, 1156, 1094, 1063, 1024, 957, 900, 834, 803, 750, 718, 675, 629, 595, 556, 458 cm-1; HRMS (FAB); Exact mass calcd

Ph

HNS

O O

OMeEt

HN

Me

S O

O

OMe

Me

HN

Me

S O

O

OMe

Me

S-8

for [M+H]+, 256.1007. Found 256.1013. A crystal suitable for X-ray diffraction analysis was prepared by recrystallization from AcOEt/hexane solvent system. CCDC-629331 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge from www.ccdc.cam.ac.uk/conts/retrieving.html, from the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB21EZ, UK; fax: (+44)1223-336-033; or deposit@ccdc.cam.ac.uk.

N-((p-methoxy)benzenesulfonyl)-cyclohex-1-enamine (4i): Mp. 86-88 °C; 1H NMR (C6D6) δ = 1.10-1.40 (m, 4H), 1.72-2.02 (m, 4H), 3.03-3.25 (m, 3H), 5.51-5.70 (m, 1H), 6.50-6.70 m, 2H), 7.08 (s, 1H), 7.85-8.10 (m, 2H); 13C NMR (C6D6) δ = 21.9, 22.6, 24.3, 28.2, 55.0, 113.8, 114.3, 130.0, 132.4, 133.1, 163.0, 163.1;

IR (neat) 3346, 3259, 1597, 1577, 1499, 1457, 1324, 1301, 1264, 1154, 1095, 1027, 896, 836, 568, 543 cm-1; HRMS (FAB); Exact mass calcd for [M+H]+, 268.1007. Found 268.1012. General Procedure for Reaction of Enesulfonamides with Aldehydes and Following Hydrolysis providing Ketone product 7 or 10. Ligand 5 (5.0 mg, 0.011 mmol) in CH2Cl2 (1.5 mL) was added to a CuClO4•4CH3CN (3.3 mg, 0.010 mmol) flask under argon. The yellow solution was stirred for over 12 h, and cooled to 0 °C. Freshly distilled ethyl glyoxylate (40 µl, 0.40 mmol) in CH2Cl2 (1.5 mL) or freshly distilled phenyl glyoxal (32.2 mg, 0.24 mmol) in CH2Cl2 (1.5 mL) was added to the mixture, and then enesulfonamide 4 (0.20 mmol) was added. The reaction mixture was stirred at 0 °C for 24 h, and was quenched by addition of saturated aqueous NaHCO3. The reaction mixture was allowed to warm to rt, and was extracted with CH2Cl2. The organic layer was washed with brine and dried over anhydrous Na2SO4. After the solvent was evaporated, the residue was dissolved in EtOH (0.5 mL), and a 48% HBr aqueous solution (0.5 mL) was added to the solution. The mixture was stirred at rt for 2 min, and then the reaction was quenched by addition of saturated aqueous NaHCO3 at 0 °C. The reaction mixture was allowed to warm to rt. The mixture was extracted with CH2Cl2, and the organic layer was washed with brine and dried over anhydrous Na2SO4. After the solvents were evaporated, the crude product

HNS

OMe

O

O

S-9

was purified by chromatography on silica gel to afford the desired compound 7 or 10.

(2S,3R)-2-hydroxy-3-methyl-1,4-diphenylbutane-1,4-dione (syn-10): [α]22

D +80.1 (69% ee, c 1.285, CHCl3); 1H NMR (CDCl3) δ = 1.12 (d, 3H, J = 6.9 Hz), 3.72 (d, 1H, J = 6.4 Hz), 3.83 (dq, 1H,

J = 3.7, 6.9 Hz), 5.47 (dd, 1H, J = 3.7, 6.4 Hz), 7.45-7.67 (m, 6H), 7.89 (d, 2H, J = 7.3 Hz), 7.94 (d, 2H, J = 7.3 Hz); 13C NMR (CDCl3) δ = 10.4, 44.9, 73.5, 128.2, 128.6, 128.8, 129.0, 133.1, 134.0, 134.3, 136.3, 200.4, 201.3; IR

(neat) 3448, 2925, 1681, 1596, 1578, 1448, 1252, 1219, 971, 701 cm-1; HRMS (FAB); Exact mass calcd for [M+H]+, 269.1178. Found 269.1166; Chiral HPLC; Daicel Chiralcel AD-H; hexane/iPrOH = 4/1, flow rate = 1.0 mL/min: tR = 9.6 min (2S,3R), tR

= 13.1 min (2R,3S). (2S,3S)-2-hydroxy-3-methyl-1,4-diphenylbutane-1,4-dione (anti-10): [α]22

D +76.5 (78% ee, c 0.685, CHCl3); 1H NMR (CDCl3) δ = 1.35 (d, 3H, J = 7.3 Hz), 3.95-4.04 (m, 1H), 4.37 (s, 1H), 5.20 (d, 1H, J = 4.1 Hz), 7.42-7.50 (m, 4H), 7.54-7.62 (m, 2H), 7.92 (d, 2H, J = 7.3 Hz),

7.98 (d, 2H, J = 7.3 Hz); 13C NMR (CDCl3) δ = 14.9, 42.7, 76.6, 128.4, 128.6, 128.7, 129.1, 133.5, 133.7, 135.1, 136.1, 200.2, 204.7; IR

(neat) 3069, 2929, 1682, 1595, 1448, 1218, 974, 838, 702, 420 cm-1; HRMS (FAB); Exact mass calcd for [M+H]+, 269.1178. Found 269.1183; Chiral HPLC; Daicel Chiralcel AS-H; hexane/iPrOH = 4/1, flow rate = 1.0 mL/min: tR = 9.1 min (2S,3S), tR = 22.9 min (2R,3R).

EtO

O

H

O

+ MePMP

NHSO2PMPEtO

O

OH

PMP

Me

NSO2PMP

Cu(I)-diimine 5

NaBH4

MeOH, –78 °C, 3 h

EtO

O

OH

PMP

Me

HNSO2PMP

EtO

O

OH

PMP

Me

HNSO2PMP

Z-4e 6e

9a (X-ray) 9b

+

93% yield (2 steps)9a/9b = 92/8

99% ee (9a), 97% ee (9b)

Ph

O

OH

Me

Ph

O

Ph

O

OH

Me

Ph

O

S-10

Procedure for Synthesis of sulfonamide 9a. Ligand 5 (5.0 mg, 0.011 mmol) in CH2Cl2 (1.5 mL) was added to the CuClO4•4CH3CN (3.3 mg, 0.010 mmol) flask under argon. The yellow solution was stirred for over 12 h, and cooled to 0 °C. Freshly distilled ethyl glyoxylate (40 µl, 0.40 mmol) in CH2Cl2 (1.5 mL) was added to the mixture, and then enesulfonamide Z-4e (0.20 mmol) was added. The reaction mixture was stirred at 0 °C for 24 h, and was quenched by addition of saturated aqueous NaHCO3. The reaction mixture was allowed to warm to rt, and was extracted with CH2Cl2. The organic layer was washed with brine and dried over anhydrous Na2SO4. The crude material was dissolved in MeOH (2.5 mL), and was cooled to –78 °C. To the solution was added NaBH4 (15.2 mg, 0.4 mmol), and the mixture was stirred for 3 h at –78 °C. NH4Cl aq. was added to quench the reaction, and the mixture was extracted with CH2Cl2 three times. The combined organic layer was washed with brine and dried over Na2SO4. The solution was concentrated in vacuo, and the obtained residue was purified on silica gel chromatography to afford 9a/9b mixture (81 mg, 93% yield, 9a/9b = 92/8, 99% ee (9a), 97% ee (9b)). Recrystallization of the 9a/9b mixture from hexane/AcOEt afforded pure 9a. Pure 9a thus obtained was again recrystallized from hexane/CHCl3 to give the single crystal suitable for X-ray diffraction analysis. The absolute and relative configuration was unambiguously determined.

(2S,3R,4R)-ethyl 4-(p-methoxyphenyl)sulfonylamino-2-hydroxy-4-(4-methoxyphenyl)-3-methylbutanoate (9a/9b mixture): [α]22

D +106.9 (9a, >99% ee, c 0.475, CHCl3); Mp (9a).

100-101 °C; 1H NMR (CDCl3) 9a: δ = 0.84 (d, 3H, J = 6.9 Hz), 1.17 (t, 3H, J = 6.9 Hz), 2.05-2.11 (m, 1H), 2.90 (s, 1H), 3.67 (s, 1H), 3.68 (s, 3H), 3.75 (s, 3H), 4.02-4.20 (m, 3H), 5.29 (d, 1H, J = 6.2 Hz), 6.65 (d, 2H, J = 8.7 Hz), 6.73 (d, 2H, J = 8.7 Hz), 6.99 (d, 2H, J = 8.7 Hz), 7.54 (d, 2H, J = 8.7 Hz); Distinguishable peaks derived from 9b: δ =

0.74(d, 3H, J = 6.9 Hz), 2.13-2.18 (m, 1H), 5.84 (d, 1H, J = 8.9 Hz); 13C NMR (CDCl3) 9a: δ = 9.5, 14.1, 42.5, 55.1, 55.4, 60.6, 61.9, 71.0, 113.6, 113.6, 128.1, 129.2, 131.6, 131.7, 15

8.6, 162.4, 174.3; IR (9a) (neat) 3497, 3275, 2969, 2942, 2838, 1729, 1613, 1596, 1583, 1513, 1498, 1463, 1442, 1321, 1302, 1257, 1179, 1154, 1095, 1058, 102, 965, 942, 914, 830, 802, 758, 669, 562 cm-1; HRMS (FAB); Exact mass calcd for [M+H]+, 438.1586.

EtO

O

OH

PMP

Me

HNSO2PMP

S-11

Found 438.1594; Chiral HPLC; Daicel Chiralcel AD-H; hexane/iPrOH = 4/1, flow rate = 1.0 mL/min: tR = 26.0 min (2R,3S,4R), tR = 33.9 min (2S,3R, 4R), tR = 40.8 min (2S,3R,4S), tR = 69.5 min (2R,3S,4S). CCDC-629328 contains the supplementary

crystallographic data for this paper. These data can be obtained free of charge from www.ccdc.cam.ac.uk/conts/retrieving.html, from the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB21EZ, UK; fax: (+44)1223-336-033; or deposit@ccdc.cam.ac.uk. General Procedure for Amination Reaction of Enesulfonamides E-4b and Following Hydrolysis Providing Ketone 12. Cu(OTf)2 (7.2 mg, 0.02 mmol) was added to a dried flask, and diamine ligand 11 (9.9 mg, 0.022 mmol) in toluene (1.5 ml) was added and the reaction mixture was kept stirred for 12 h at rt. The solution was cooled to –20 °C. MS 3A (20 mg), azodicarboxylate (0.22 mmol) in toluene (0.3 ml) and enesulfonamide E-4b (0.2 mmol) in toluene (1.2 ml) were added successively. The reaction mixture was stirred for 4.5 h, then a saturated NaHCO3 aqueous solution was added to quench the reaction. The mixture was extracted with CH2Cl2, and the organic extracts were dried over Na2SO4. Filtration and evaporation of the solvents afforded the crude acylimine product. EtOH (0.5 ml) and 48% HBr (0.5 ml) were added to the crude product at rt, then stirred for 1.5 min. At 0 °C a saturated NaHCO3 aqueous solution was added to the mixture, then the mixture was extracted with CH2Cl2. Drying of the organic extracts over Na2SO4, evaporation of the solvents, and purification of the residue on silica gel chromatography afforded ketone 12 (47 mg, 70% yield, 91% ee).5

Explanation for diastereoselectivity observed in this reaction. Hydrogen atom on nitrogen atom of enecarbamates should play an important role for diastereselection on the analogy of enecarbamate nucleophilic addition. Concerted 6-membered ring transition state model shown below does not contradict the experimental results.

Me

O

HN

H

Me

PhSO2Ar

O

HN

H

PhSO2Ar

EtO

O

OH

Me

NSO2Ar

PhEtO

O

OH

Me

NSO2Ar

Ph

anti syn

E-enesulfonamide Z-enesulfonamide

OEtO O

EtO

CuCu **