Scheme 5.11: Plausible mechanism for the formation of 3a
F. General procedure for the synthesis of compounds 8 This compound was prepared according to literature procedure. 20
5.7 Characterization Data of Products
(S)-2-(nitromethyl)-4-oxo-4-phenylbutyl benzoate (3a)
This compound was prepared according to the general procedure D. Reaction was completed after 2 d. Analytical TLC on silica gel using 12% ethyl acetate/hexane. White solid (30.5 mg, 93% yield); Mp: 71-73 °C; 1H NMR (600 MHz, CDCl3): δ 8.00 (d, J = 7.2 Hz, 2H), 7.96 (d, J = 7.3 Hz, 2H), 7.59 (q, J = 7.5 Hz, 2H), 7.47 (dt, J = 15.8, 7.8 Hz, 4H), 4.72 (d, J = 6.0 Hz, 2H), 4.53 – 4.47 (m, 2H), 3.42 (dt, J = 12.0, 6.0 Hz, 1H), 3.28 (d, J = 6.5 Hz, 2H); 13C NMR (125 MHz, CDCl3): δ 196.9, 166.3, 136.5, 133.9, 133.6, 129.9, 129.6, 129.0, 128.8, 128.3, 76.4, 64.8, 37.2, 33.4; FT-IR (thin film): 1719, 1678, 1539, 1451, 1385, 1283, 1178, 1111, 1070 1002, 760, 711, 688 cm-1; HRMS (+ESI): Calcd for C18H18NO5 [M+H]+ 328.1179; found:
328.1181; The ee value 96% (tminor = 62.7 min, tmajor = 68.3 min) was determined by HPLC analysis using Daicel Chiralpak ID with hexane/iPrOH (90:10) as the eluent, flow:
1.0 mL/min, 254 nm, 25 oC.
(S)-2-(nitromethyl)-4-oxo-4-(p-tolyl)butyl benzoate (3b)
This compound was prepared according to the general procedure D. Reaction was completed after 3 d.
Analytical TLC on silica gel using 12% ethyl acetate/hexane. White solid (26 mg, 76% yield); Mp:
80-82 °C; 1H NMR (600 MHz, CDCl3): δ 7.96 (d, J = 7.3 Hz, 2H), 7.88 (d, J = 8.2 Hz, 2H), 7.60 (t, J = 7.4 Hz, 1H), 7.48 (t, J = 7.8 Hz, 2H), 7.25 (d, J = 8.1 Hz, 2H), 4.71 (d, J
= 6.3 Hz, 2H), 4.51 – 4.45 (m, 2H), 3.41 (dt, J = 11.9, 6.1 Hz, 1H), 3.27 (d, J = 6.4 Hz, 2H), 2.42 (s, 3H);13C NMR (125 MHz, CDCl3): δ 196.6, 166.3, 144.9, 134.0, 133.6, 129.8, 129.7, 129.6, 128.7, 128.4, 76.5, 64.9, 37.1, 33.5, 21.9; FT-IR (thin film): 1712, 1682, 1549, 1363, 1279, 1224, 1180, 1110, 1000, 755, 639 cm-1; HRMS (+ESI): Calcd for C19H20NO5 [M+H]+ 342.1336; found: 342.1346; The ee value 96% (tminor = 66.9 min, tmajor = 76.5 min) was determined by HPLC analysis using Daicel Chiralpak ID with hexane/iPrOH (90:10) as the eluent, flow: 1.0 mL/min, 254 nm, 25 oC.
(S)-4-(4-(tert-butyl)phenyl)-2-(nitromethyl)-4-oxobutyl benzoate (3c)
This compound was prepared according to the general procedure D. Reaction was completed after 3 d.
Analytical TLC on silica gel using 12% ethyl acetate/hexane. White solid (24 mg, 63% yield); Mp:
80-82 °C; 1H NMR (600 MHz, CDCl3): δ 7.99 (d, J = 7.2 Hz, 2H), 7.90 (d, J = 8.5 Hz, 2H), 7.58 (t, J = 7.5 Hz, 1H), 7.49 (d, J = 8.5 Hz, 2H), 7.45 (t, J = 7.8 Hz, 2H), 4.71 (d, J
= 6.0 Hz, 2H), 4.53 – 4.46 (m, 2H), 3.41 (dt, J = 11.9, 6.1 Hz, 1H), 3.25 (d, J = 6.5 Hz, 2H), 1.34 (s, 9H); 13C NMR (150 MHz, CDCl3): δ 196.6, 166.3, 157.9, 133.9, 133.6, 129.8, 129.6, 128.7, 128.3, 125.9, 76.5, 64.9, 37.1, 35.4, 33.5, 31.3; FT-IR (thin film):
1708, 1676, 1604, 1547, 1279, 1216, 1114, 1002, 825, 713, 581 cm-1; HRMS (+ESI):
Calcd for C22H26NO5 [M+H]+ 384.1805; found: 384.1801; The ee value 96% (tminor = 20.5 min, tmajor = 25.3 min) was determined by HPLC analysis using Daicel Chiralpak ID with hexane/iPrOH (80:20) as the eluent, flow: 1.0 mL/min, 254 nm, 25 oC.
(S)-4-(4-methoxyphenyl)-2-(nitromethyl)-4-oxobutyl benzoate (3d)
This compound was prepared according to the general procedure D. Reaction was completed after 5 d.
Analytical TLC on silica gel using 18% ethyl acetate/hexane. White solid (19 mg, 53% yield); Mp:
87-89 °C; 1H NMR (600 MHz, CDCl3): δ 8.00 (d, J = 7.2 Hz, 2H), 7.94 (d, J = 8.9 Hz, 2H), 7.59 (t, J = 7.4 Hz, 1H), 7.45 (t, J = 7.8 Hz, 2H), 6.94 (d, J = 8.9 Hz, 2H), 4.71 (d, J
= 6.0 Hz, 2H), 4.53 – 4.45 (m, 2H), 3.88 (s, 3H), 3.41 (dt, J = 12.0, 6.1 Hz, 1H), 3.22 (d, J = 6.5 Hz, 2H); 13C NMR (150 MHz, CDCl3): δ 195.4, 166.3, 164.2, 133.6, 130.6, 129.8, 129.7, 129.6, 128.8, 114.1, 76.5, 64.9, 55.8, 36.8, 33.5; FT-IR (thin film): 1709, 1670, 1602, 1553, 1363, 1275, 1178, 1121, 1027, 996, 817, 711 cm-1; HRMS (+ESI):
Calcd for C19H20NO6 [M+H]+ 358.1285; found: 358.1293; The ee value 96% (tminor = 42.4 min, tmajor = 47.5 min) was determined by HPLC analysis using Daicel Chiralpak ID with hexane/iPrOH (70:30) as the eluent, flow: 1.0 mL/min, 254 nm, 25 oC.
(S)-4-(4-fluorophenyl)-2-(nitromethyl)-4-oxobutyl benzoate (3e)
This compound was prepared according to the general procedure D. Reaction was completed after 3 d.
Analytical TLC on silica gel using 10% ethyl acetate/hexane. White solid (25 mg, 72% yield); Mp: 75- 77 °C; 1H NMR (600 MHz, CDCl3): δ 7.99 (dd, J = 8.5, 5.4 Hz, 4H), 7.59 (t, J = 7.5 Hz, 1H), 7.46 (t, J = 7.8 Hz, 2H), 7.15 (t, J = 8.6 Hz, 2H), 4.74 – 4.69 (m, 2H), 4.50 (d, J
= 5.6 Hz, 2H), 3.41 (dt, J = 12.0, 6.0 Hz, 1H), 3.25 (d, J = 6.5 Hz, 2H); 13C NMR (125 MHz, CDCl3): δ 195.4, 167.3, 166.3 (d, J = 152.3 Hz), 133.7, 132.9 (d, J = 3.0 Hz), 131.0 (d, J = 10.5 Hz), 130.9, 129.8, 129.6, 128.8, 116.2 (d, J = 25.5 Hz), 76.4, 64.8, 37.1, 33.4; FT-IR (thin film): 1722, 1686, 1596, 1549, 1283, 1228, 1112, 1000, 841, 713 cm-1; HRMS (+ESI): Calcd for C18H17NFO5 [M+H]+ 346.1085; found: 346.1091;
The ee value 94% (tminor = 35.0 min, tmajor = 39.1 min) was determined by HPLC analysis using Daicel Chiralpak ID with hexane/iPrOH (85:15) as the eluent, flow: 1.0 mL/min, 254 nm, 25 oC.
(S)-4-(4-chlorophenyl)-2-(nitromethyl)-4-oxobutyl benzoate (3f)
This compound was prepared according to the general procedure D. Reaction was completed after 3 d.
Analytical TLC on silica gel using 10% ethyl acetate/hexane. White solid (27 mg, 75% yield); Mp:
95-97 °C; 1H NMR (600 MHz, CDCl3): δ 7.99 (d, J = 7.2 Hz, 2H), 7.90 (d, J = 8.6 Hz, 2H), 7.59 (t, J = 7.4 Hz, 1H), 7.46 (t, J = 7.4 Hz, 4H), 4.75 – 4.68 (m, 2H), 4.50 (d, J = 5.6 Hz, 2H), 3.40 (dt, J = 12.0, 6.0 Hz, 1H), 3.24 (d, J = 6.5 Hz, 2H); 13C NMR (125 MHz, CDCl3): δ 195.9, 166.3, 140.5, 134.8, 133.7, 129.8, 129.7, 129.6, 129.4, 128.8, 76.4, 64.7, 37.2, 33.4; FT-IR (thin film): 1714, 1682, 1555, 1317, 1279, 1220, 1114, 996, 817, 711 cm-1; HRMS (+ESI): Calcd for C18H17NClO5 [M+H]+ 362.0790; found:
362.0786; The ee value 94% (tminor = 36.7 min, tmajor = 42.8 min) was determined by HPLC analysis using Daicel Chiralpak ID with hexane/iPrOH (85:15) as the eluent, flow:
1.0 mL/min, 254 nm, 25 oC.
(S)-4-(4-bromophenyl)-2-(nitromethyl)-4-oxobutyl benzoate (3g)
This compound was prepared according to the general procedure D. Reaction was completed after 3 d.
Analytical TLC on silica gel using 10% ethyl acetate/hexane. White solid (34 mg, 84% yield); Mp:
105-107 °C; 1H NMR (600 MHz, CDCl3): δ 7.99 (d, J = 7.2 Hz, 2H), 7.82 (d, J = 8.6 Hz, 2H), 7.62 (d, J = 8.6 Hz, 2H), 7.59 (t, J = 7.4 Hz, 1H), 7.46 (t, J = 7.8 Hz, 2H), 4.74 – 4.67 (m, 2H), 4.50 (d, J = 5.6 Hz, 2H), 3.40 (dt, J = 12.0, 6.0 Hz, 1H), 3.24 (d, J = 6.5 Hz, 2H); 13C NMR (125 MHz, CDCl3): δ 195.9, 166.3, 135.2, 133.7, 132.4, 129.8, 129.7, 129.6, 129.2, 128.8, 76.4, 64.7, 37.2, 33.4; ; FT-IR (thin film): 1713, 1684, 1556, 1383, 1278, 1114, 995, 815, 713 cm-1; HRMS (+ESI): Calcd for C18H17NBrO5 [M+H]+ 406.0285; found: 406.0279; The ee value 94% (tminor = 62.6 min, tmajor = 73.7 min) was determined by HPLC analysis using Daicel Chiralpak ID with hexane/iPrOH (90:10) as the eluent, flow: 1.0 mL/min, 254 nm, 25 oC.
(S)-2-(nitromethyl)-4-oxo-4-(m-tolyl)butyl benzoate (3h)
This compound was prepared according to the general procedure D. Reaction was completed after 3 d. Analytical TLC on silica gel using 12% ethyl acetate/hexane. Colorless oil (26 mg, 76% yield); 1H NMR (600 MHz, CDCl3): δ 8.00 (d, J = 7.2 Hz, 2H), 7.75 (d, J = 9.0 Hz, 2H), 7.59 (t, J = 7.5 Hz, 1H), 7.46 (t, J = 7.8 Hz, 2H), 7.41 (d, J = 7.5 Hz, 1H), 7.36 (t, J = 7.5 Hz, 1H), 4.72 (d, J = 6.0 Hz, 2H), 4.53 – 4.46 (m, 2H), 3.41 (dt, J = 12.0, 6.0 Hz, 1H), 3.26 (d, J = 6.9 Hz, 2H), 2.41 (s, 3H); 13C NMR (150 MHz, CDCl3): δ 197.2, 166.3, 138.9, 136.5, 134.7, 133.6, 129.8, 129.6, 128.9, 128.8, 128.7, 125.5, 76.4, 64.8, 37.2, 33.4, 21.6; FT-IR (thin film): 1723, 1685, 1549, 1380, 1272, 1165, 1115, 1033, 715, cm-1; HRMS (+ESI): Calcd for C19H20NO5
[M+H]+ 342.1336; found: 342.1335; The ee value 92% (tminor = 28.8 min, tmajor = 31.9 min) was determined by HPLC analysis using Daicel Chiralpak ID with hexane/iPrOH (80:20) as the eluent, flow: 1.0 mL/min, 254 nm, 25 oC.
(S)-4-(3-methoxyphenyl)-2-(nitromethyl)-4-oxobutyl benzoate (3i)
This compound was prepared according to the general procedure D. Reaction was completed after 3 d. Analytical TLC on silica gel using 18% ethyl acetate/hexane. White solid (22 mg, 61% yield); Mp: 64-66 °C; 1H NMR (600 MHz, CDCl3): δ 8.00 (d, J = 7.4 Hz, 2H), 7.59 (t, J = 7.4 Hz, 1H), 7.53 (d, J = 7.6 Hz, 1H), 7.46 (dd, J = 14.1, 6.3 Hz, 3H), 7.38 (t, J = 7.9 Hz, 1H), 7.14 (dd, J = 8.2, 2.4 Hz, 1H), 4.71 (dd, J = 6.0, 1.2 Hz, 2H), 4.53 – 4.45 (m, 2H), 3.85 (s, 3H), 3.42 (dt, J = 11.9, 6.1 Hz, 1H), 3.26 (d, J = 6.5 Hz, 2H); 13C NMR (125 MHz, CDCl3): δ 196.8, 166.3, 160.2, 137.9, 133.6, 130.0, 129.9, 129.7, 128.7, 120.8, 120.4, 112.6, 76.4, 64.8, 55.7, 37.4, 33.6; FT-IR (thin film): 1716, 1680, 1600, 1539, 1373, 1279, 1116, 1032, 709 cm-
1; HRMS (+ESI): Calcd for C19H20NO6 [M+H]+ 358.1285; found: 358.1289; The ee value 96% (tminor = 28.8 min, tmajor = 33.8 min) was determined by HPLC analysis using Daicel Chiralpak ID with hexane/iPrOH (70:30) as the eluent, flow: 1.0 mL/min, 254 nm, 25 oC.
(S)-2-(nitromethyl)-4-oxo-4-(o-tolyl)butyl benzoate (3j)
This compound was prepared according to the general procedure D. Reaction was completed after 3 d. Analytical TLC on silica gel using 10% ethyl acetate/hexane. Brownish oil (22 mg, 64% yield); 1H NMR (600 MHz, CDCl3): δ 8.00 (d, J = 7.2 Hz, 2H), 7.66 (d, J = 7.7 Hz, 1H), 7.59 (t, J = 7.4 Hz, 1H), 7.46 (t, J = 7.8 Hz, 2H), 7.41 (t, J = 7.5 Hz, 1H), 7.30 – 7.26 (m, 2H), 4.71 (qd, J = 12.8, 6.0 Hz, 2H), 4.49 (d, J = 6.2 Hz, 2H), 3.39 (dt, J = 11.9, 6.0 Hz, 1H), 3.20 (d, J = 6.6 Hz, 2H), 2.52 (s, 3H);
13C NMR (150 MHz, CDCl3): δ 200.5, 166.3, 138.9, 136.9, 133.6, 132.5, 132.2, 129.8, 129.6, 128.8, 128.7, 126.1, 76.4, 64.8, 39.8, 33.6, 21.7; FT-IR (thin film): 1721, 1685, 1552, 1452, 1381, 1272, 1112, 756, 713 cm-1; HRMS (+ESI): Calcd for C19H20NO5
[M+H]+ 342.1336; found: 342.1339; The ee value 92% (tminor = 18.3 min, tmajor = 20.7 min) was determined by HPLC analysis using Daicel Chiralpak ID with hexane/iPrOH (80:20) as the eluent, flow: 1.0 mL/min, 254 nm, 25 oC.
(S)-4-(naphthalen-1-yl)-2-(nitromethyl)-4-oxobutyl benzoate (3k)
This compound was prepared according to the general procedure D. Reaction was completed after 5 d. Analytical TLC on silica gel using 15% ethyl acetate/hexane.
Brownish sticky oil (22 mg, 58% yield); 1H NMR (600 MHz, CDCl3): δ 8.64 (d, J = 8.8 Hz, 1H), 8.04 – 7.99 (m, 3H), 7.92 – 7.87 (m, 2H), 7.63 – 7.54 (m, 3H), 7.50 (dd, J = 8.1, 7.3 Hz, 1H), 7.45 (t, J = 7.8 Hz, 2H), 4.81 – 4.73 (m, 2H), 4.55 (d, J = 5.7 Hz, 2H), 3.49 (dq, J = 11.9, 6.1 Hz, 1H), 3.37 (d, J = 6.6 Hz, 2H); 13C NMR (150 MHz, CDCl3): δ 200.8, 166.3, 134.9, 134.2, 133.7, 133.6, 130.3, 129.8, 129.6, 128.8, 128.7, 128.6, 128.3, 126.9, 125.8, 124.5, 76.5, 64.8, 40.4, 33.8; FT-IR (thin film): 1721, 1681, 1552, 1381, 1272, 1176, 1111, 728, 713 cm-1; HRMS (+ESI): Calcd for C22H20NO5 [M+H]+ 378.1336; found: 378.1341; The ee value 91% (tminor = 30.4 min, tmajor = 51.6 min) was determined by HPLC analysis using Daicel Chiralpak ID with hexane/iPrOH (80:20) as the eluent, flow: 1.0 mL/min, 254 nm, 25 oC.
(S)-2-(nitromethyl)-4-oxo-4-(thiophen-2-yl)butyl benzoate (3l)
This compound was prepared according to the general procedure D. Reaction was completed after 4 d. Analytical TLC on silica gel using 15% ethyl acetate/hexane. White solid (23 mg, 72% yield); Mp: 52-54 °C; 1H NMR (600 MHz, CDCl3): δ 7.99 (d, J = 7.2 Hz, 2H), 7.74 (d, J = 3.8 Hz, 1H), 7.69 (d, J = 4.9 Hz, 1H), 7.59 (t, J = 7.4 Hz, 1H), 7.45 (t, J = 7.8 Hz, 2H), 7.14 (dd, J = 4.8, 4.0 Hz, 1H), 4.71 (d, J = 6.0 Hz, 2H), 4.52 – 4.45 (m, 2H), 3.39 (dp, J = 12.1, 6.1 Hz, 1H), 3.22 (d, J = 6.5 Hz, 2H); 13C NMR (125 MHz, CDCl3): δ 189.8, 166.3, 143.6, 134.7, 133.6, 132.6, 129.8, 129.6, 128.8, 128.6, 76.3, 64.7, 37.9, 33.7; FT-IR (thin film): 1721, 1662, 1552, 1416, 1272, 1113, 1070, 856, 713 cm-1; HRMS (+ESI): Calcd for C16H16NSO5 [M+H]+ 334.0744; found:
334.0747; The ee value 92% (tminor = 47.0 min, tmajor = 56.4 min) was determined by HPLC analysis using Daicel Chiralpak ID with hexane/iPrOH (80:20) as the eluent, flow:
1.0 mL/min, 254 nm, 25 oC.
(S)-2-(nitromethyl)-4-oxo-6-phenylhexyl benzoate (3m)
This compound was prepared according to the general procedure D. Reaction was completed after 4 d.
Analytical TLC on silica gel using 15% ethyl acetate/hexane. Colorless oil (18 mg, 51% yield); 1H NMR (600 MHz, CDCl3) δ 7.96 (dd, J = 8.3, 1.2 Hz, 2H), 7.57 (t, J = 7.4 Hz, 1H), 7.44 (t, J = 7.8 Hz, 2H), 7.24 (d, J = 8.4 Hz, 2H), 7.15 (dd, J = 18.5, 7.2 Hz, 3H), 4.54 (qd, J = 12.7, 6.1 Hz, 2H), 4.33 (d, J = 5.6 Hz, 2H), 3.16 (dt, J = 12.1, 6.1 Hz, 1H), 2.89 (t, J = 7.5 Hz, 2H), 2.75 (t, J = 7.5 Hz, 2H), 2.62 (d, J = 7.0 Hz, 2H); 13C NMR (125 MHz, CDCl3): δ 207.0, 166.2, 140.6, 133.7, 129.8, 129.5, 128.8, 128.7, 128.5, 126.5, 76.2, 64.5, 44.8, 41.4, 32.9, 29.9; FT-IR (thin film): 1718, 1602, 1552, 1452, 1380, 1272, 1112, 1026, 713 cm-1; HRMS (+ESI): Calcd for C20H25N2O5 [M+NH4]+ 373.1758;
found: 373.1755; The ee value 62% (tminor = 12.5 min, tmajor = 14.0 min) was determined by HPLC analysis using Daicel Chiralpak ID with hexane/iPrOH (85:15) as the eluent, flow: 1.0 mL/min, 254 nm, 25 oC.
(S)-2-(nitromethyl)-4-oxo-4-phenylbutyl 4-methylbenzoate (3n)
This compound was prepared according to the general procedure D. Reaction was completed after 2 d.
Analytical TLC on silica gel using 12% ethyl acetate/hexane. White solid (29 mg, 85% yield); Mp: 77-79 °C; 1H NMR (600 MHz, CDCl3): δ 7.96 (d, J = 7.3 Hz, 2H), 7.88 (d, J = 8.1 Hz, 2H), 7.60 (t, J = 7.4 Hz, 1H), 7.48 (t, J = 7.8 Hz, 2H), 7.25 (d, J = 8.0 Hz, 2H), 4.71 (d, J = 6.3 Hz, 2H), 4.51 – 4.45 (m, 2H), 3.41 (dt, J = 12.0, 6.0 Hz, 1H), 3.27 (d, J = 6.5 Hz, 2H), 2.42 (s, 3H); 13C NMR (125 MHz, CDCl3): δ 197.0, 166.4, 144.4, 136.5, 133.9, 129.9, 129.5, 129.0, 128.3, 126.9, 76.4, 64.6, 37.2, 33.4, 21.9; FT-IR (thin film): 1720, 1681, 1610, 1556, 1383, 1275, 1211, 1180, 1111, 1002, 753, 688 cm-1; HRMS (+ESI): Calcd for C19H20NO5
[M+H]+ 342.1336; found: 342.1338; The ee value 96% (tminor = 64.1 min, tmajor = 77.5 min) was determined by HPLC analysis using Daicel Chiralpak ID with hexane/iPrOH (90:10) as the eluent, flow: 1.0 mL/min, 254 nm, 25 oC.
(S)-2-(nitromethyl)-4-oxo-4-phenylbutyl 4-isopropylbenzoate (3o)
This compound was prepared according to the general procedure D. Reaction was completed after 2 d.
Analytical TLC on silica gel using 12% ethyl acetate/hexane. White solid (33.5 mg, 90% yield); Mp:
82-84 °C; 1H NMR (600 MHz, CDCl3): δ 7.96 (d, J = 7.3 Hz, 2H), 7.92 (d, J = 8.3 Hz, 2H), 7.60 (t, J = 7.4 Hz, 1H), 7.48 (t, J = 7.8 Hz, 2H), 7.30 (d, J = 8.2 Hz, 2H), 4.71 (d, J
= 6.2 Hz, 2H), 4.51 – 4.46 (m, 2H), 3.41 (dt, J = 12.1, 6.1 Hz, 1H), 3.27 (d, J = 6.4 Hz, 2H), 2.97 (dt, J = 13.8, 6.9 Hz, 1H), 1.27 (d, J = 6.9 Hz, 6H); 13C NMR (125 MHz, CDCl3): δ 197.0, 166.3, 155.2, 136.5, 133.9, 130.0, 129.0, 128.3, 127.2, 126.9, 76.4, 64.6, 37.2, 34.5, 33.5, 23.9; FT-IR (thin film): 1710, 1678, 1608, 1551, 1449, 1417, 1371, 1269, 1228, 1186, 1118, 1006, 851, 749, 685 cm-1; HRMS (+ESI): Calcd for C21H24NO5 [M+H]+ 370.1649; found: 370.1653; The ee value 94% (tminor = 24.2 min, tmajor = 34.3 min) was determined by HPLC analysis using Daicel Chiralpak ID with hexane/iPrOH (80:20) as the eluent, flow: 1.0 mL/min, 254 nm, 25 oC.
(S)-2-(nitromethyl)-4-oxo-4-phenylbutyl 4-(tert-butyl)benzoate (3p)
This compound was prepared according to the general procedure D. Reaction was completed after 2 d.
Analytical TLC on silica gel using 12% ethyl acetate/hexane. White solid (32 mg, 83% yield); Mp:
97-99 °C; 1H NMR (600 MHz, CDCl3): δ 7.94 (dd, J = 19.3, 7.9 Hz, 4H), 7.60 (t, J = 7.4 Hz, 1H), 7.48 (dd, J = 12.6, 8.2 Hz, 4H), 4.71 (d, J = 6.0 Hz, 2H), 4.51 – 4.46 (m, 2H), 3.41 (dd, J = 12.0, 6.0 Hz, 1H), 3.27 (d, J = 6.5 Hz, 2H), 1.34 (s, 9H); 13C NMR (100 MHz, CDCl3): δ 197.0, 166.3, 157.4, 136.5, 133.9, 129.7, 128.9, 128.3, 126.8, 125.7, 76.5, 64.6, 37.2, 35.3, 33.5, 31.3; FT-IR (thin film): 1707, 1679, 1610, 1544, 1284, 1211, 1120, 1002, 852, 746, 688 cm-1; HRMS (+ESI): Calcd for C22H26NO5
[M+H]+ 384.1805; found: 384.1812; The ee value 94% (tminor = 18.7 min, tmajor = 26.0 min) was determined by HPLC analysis using Daicel Chiralpak ID with hexane/iPrOH (80:20) as the eluent, flow: 1.0 mL/min, 254 nm, 25 oC.
(S)-2-(nitromethyl)-4-oxo-4-phenylbutyl 4-methoxybenzoate (3q)
This compound was prepared according to the general procedure D. Reaction was completed after 2 d.
Analytical TLC on silica gel using 18% ethyl acetate/hexane. White solid (32.5 mg, 91% yield); Mp: 116-118 °C; 1H NMR (600 MHz, CDCl3): δ 7.96 (dd, J = 8.0, 6.4 Hz, 4H), 7.60 (t, J = 7.4 Hz, 1H), 7.48 (t, J = 7.8 Hz, 2H), 6.93 (d, J = 8.9 Hz, 2H), 4.71 (d, J = 6.3 Hz, 2H), 4.50 – 4.44 (m, 2H), 3.87 (s, 3H), 3.41 (dt, J = 12.0, 6.1 Hz, 1H), 3.27 (d, J = 6.5 Hz, 2H); 13C NMR (125 MHz, CDCl3): δ 197.0, 166.0, 163.9, 136.5, 133.9, 131.9, 129.0, 128.3, 121.9, 114.0, 76.5, 64.6, 55.7, 37.2, 33.5; FT-IR (thin film): 1750, 1600, 1553, 1510, 1379, 1320, 1256, 1165, 1109, 1008, 848, 768, 690, 611 cm-1; HRMS (+ESI): Calcd for C19H20NO6
[M+H]+ 358.1285; found: 358.1286; The ee value 96% (tminor = 57.3 min, tmajor = 75.6 min) was determined by HPLC analysis using Daicel Chiralpak ID with hexane/iPrOH (80:20) as the eluent, flow: 1.0 mL/min, 254 nm, 25 oC.
(S)-2-(nitromethyl)-4-oxo-4-phenylbutyl 4-fluorobenzoate (3r)
This compound was prepared according to the general procedure D. Reaction was completed after 3 d.
Analytical TLC on silica gel using 12% ethyl acetate/hexane. Semi solid (28.5 mg, 82% yield); 1H NMR (600 MHz, CDCl3): δ 8.00 (dd, J = 8.7, 5.4 Hz, 2H), 7.96 (d, J = 7.7 Hz, 2H), 7.60 (t, J = 7.4 Hz, 1H), 7.48 (t, J = 7.8 Hz, 2H), 7.12 (t, J = 8.6 Hz, 2H), 4.71 (d, J = 6.0 Hz, 2H), 4.52 – 4.46 (m, 2H), 3.41 (dq, J = 12.1, 6.1 Hz, 1H), 3.27 (dd, J = 6.5, 1.2 Hz, 2H); 13C NMR (125 MHz, CDCl3):
δ 196.9, 167.3, 165.3 (d, J = 18.0 Hz), 136.5, 134.0, 132.5 (d, J = 10.5 Hz), 129.1, 128.3, 125.9, 116.0 (d, J = 27.0 Hz), 76.5, 65.1, 37.2, 33.5; FT-IR (thin film): 1719, 1686, 1602, 1549, 1509, 1377, 1276, 1231, 1121, 1002, 853, 763, 688, 608 cm-1; HRMS (+ESI): Calcd for C18H17NFO5 [M+H]+ 346.1085; found: 346.1080; The ee value 90%
(tminor = 23.7 min, tmajor = 27.6 min) was determined by HPLC analysis using Daicel Chiralpak ID with hexane/iPrOH (80:20) as the eluent, flow: 1.0 mL/min, 254 nm, 25 oC.
(S)-2-(nitromethyl)-4-oxo-4-phenylbutyl 4-chlorobenzoate (3s)
This compound was prepared according to the general procedure D. Reaction was completed after 3 d.
Analytical TLC on silica gel using 12% ethyl acetate/hexane. White solid (29.5 mg, 81% yield); Mp: 81-83 °C; 1H NMR (600 MHz, CDCl3): δ 7.96 (d, J = 7.4 Hz, 2H), 7.92 (d, J = 8.6 Hz, 2H), 7.61 (t, J = 7.4 Hz, 1H), 7.49 (t, J = 7.8 Hz, 2H), 7.43 (d, J = 8.6 Hz, 2H), 4.71 (d, J = 6.0 Hz, 2H), 4.53 – 4.46 (m, 2H), 3.42 (dt, J = 11.9, 6.0 Hz, 1H), 3.27 (dd, J = 6.4, 2.1 Hz, 2H); 13C NMR (100 MHz, CDCl3): δ 196.9, 165.5, 140.1, 136.5, 134.0, 131.2, 129.1, 129.0, 128.3, 128.1, 76.5, 65.2, 37.2, 33.4; FT-IR (thin film): 1714, 1682, 1592, 1551, 1377, 1273, 1108, 998, 761, 687 cm-1; HRMS (+ESI): Calcd for C18H17NClO5 [M+H]+ 362.0790; found:
362.0788; The ee value 95% (tminor = 25.7 min, tmajor = 32.2 min) was determined by HPLC analysis using Daicel Chiralpak ID with hexane/iPrOH (80:20) as the eluent, flow:
1.0 mL/min, 254 nm, 25 oC.
(S)-2-(nitromethyl)-4-oxo-4-phenylbutyl 4-bromobenzoate (3t)
This compound was prepared according to the general procedure D. Reaction was completed after 3 d.
Analytical TLC on silica gel using 12% ethyl acetate/hexane. Yellow crystalline solid (31.5 mg, 78% yield); Mp: 101-103 °C; 1H NMR (600 MHz, CDCl3): δ 7.95 (d, J = 7.4 Hz, 2H), 7.84 (d, J = 8.5 Hz, 2H), 7.60 (dd, J = 12.4, 8.0 Hz, 3H), 7.49 (t, J = 7.8 Hz, 2H), 4.71 (d, J = 6.0 Hz, 2H), 4.53 – 4.45 (m, 2H), 3.42 (dt, J = 11.8, 6.0 Hz, 1H), 3.27 (dd, J = 6.4, 2.3 Hz, 2H); 13C NMR (100 MHz, CDCl3): δ 196.9, 165.6, 136.5, 134.0, 132.1, 131.3, 129.1, 128.8, 128.5, 128.3, 76.5, 65.2, 37.2, 33.4; FT-IR (thin film): 1716, 1683, 1589, 1552, 1378, 1277, 1228, 1104, 1010, 847, 758, 692 cm-1; HRMS (+ESI): Calcd for C18H17NBrO5 [M+H]+ 406.0285;
found: 406.0282; The ee value 96% (tminor = 28.8 min, tmajor = 37.3 min) was determined by HPLC analysis using Daicel Chiralpak ID with hexane/iPrOH (80:20) as the eluent, flow: 1.0 mL/min, 254 nm, 25 oC.
(S)-2-(nitromethyl)-4-oxo-4-phenylbutyl 3-methylbenzoate (3u)
This compound was prepared according to the general procedure D. Reaction was completed after 2 d. Analytical TLC on silica gel using 12% ethyl acetate/hexane. White solid (28 mg, 82% yield); Mp: 53-55 °C; 1H NMR (600 MHz, CDCl3): δ 7.96 (d, J = 7.4 Hz, 1H), 7.79 (d, J = 10.4 Hz, 1H), 7.60 (t, J = 7.4 Hz, 1H), 7.48 (t, J = 7.7 Hz, 1H), 7.39 (d, J = 7.6 Hz, 1H), 7.34 (t, J = 7.6 Hz, 1H), 4.72 (d, J
= 6.0 Hz, 1H), 4.49 (d, J = 5.6 Hz, 1H), 3.42 (dt, J = 12.0, 6.1 Hz, 1H), 3.28 (d, J = 6.0 Hz, 1H), 2.40 (s, 1H); 13C NMR (150 MHz, CDCl3): δ 196.9, 166.5, 138.6, 136.5, 134.4, 133.9, 130.4, 129.5, 129.0, 128.6, 128.3, 126.9, 76.4, 64.7, 37.2, 33.4, 21.5; FT- IR (thin film): 1716, 1680, 1555, 1383, 1281, 1206, 1110, 998, 741, 687 cm-1; HRMS (+ESI): Calcd for C19H20NO5 [M+H]+ 342.1336; found: 342.1342; The ee value 92%
(tminor = 16.7 min, tmajor = 17.9 min) was determined by HPLC analysis using Daicel Chiralpak IA with hexane/iPrOH (90:10) as the eluent, flow: 1.0 mL/min, 254 nm, 25 oC.
(S)-2-(nitromethyl)-4-oxo-4-phenylbutyl 3-methoxybenzoate (3v)
This compound was prepared according to the general procedure D. Reaction was completed after 2 d. Analytical TLC on silica gel using 18% ethyl acetate/hexane. White solid (31 mg, 86% yield); Mp: 63-65 °C; 1H NMR (600 MHz, CDCl3): δ 7.96 (d, J = 7.3 Hz, 2H), 7.60 (dd, J = 14.7, 7.4 Hz, 2H), 7.49 (dd, J = 14.3, 6.5 Hz, 3H), 7.36 (t, J = 8.0 Hz, 1H), 7.12 (dd, J = 8.2, 2.1 Hz, 1H), 4.71 (d, J = 6.0 Hz, 2H), 4.53 – 4.46 (m, 2H), 3.85 (s, 3H), 3.42 (dt, J = 11.9, 6.1 Hz, 1H), 3.28 (d, J = 6.5 Hz, 2H); 13C NMR (125 MHz, CDCl3): δ 196.9, 166.2, 159.9, 136.4, 133.9, 130.9, 129.7, 129.0, 128.3, 122.2, 120.1, 114.3, 76.5, 65.0, 55.7, 37.2, 33.4; FT-IR (thin film):
1711, 1680, 1596, 1541, 1490, 1371, 1279, 1229, 1072, 1004, 754, 688, cm-1; HRMS (+ESI): Calcd for C19H20NO6 [M+H]+ 358.1285; found: 358.1292; The ee value 98%
(tminor = 44.9 min, tmajor = 47.5 min) was determined by HPLC analysis using Daicel Chiralpak IA with hexane/iPrOH (95:5) as the eluent, flow: 1.0 mL/min, 254 nm, 25 oC.
(S)-2-(nitromethyl)-4-oxo-4-phenylbutyl 3-chlorobenzoate (3w)
This compound was prepared according to the general procedure D. Reaction was completed after 3 d. Analytical TLC on silica gel using 12% ethyl acetate/hexane. Pale yellow sticky oil (24 mg, 66% yield); 1H NMR (600 MHz, CDCl3): δ 7.96 (d, J = 6.9 Hz, 3H), 7.87 (d, J = 7.8 Hz, 1H), 7.61 (t, J = 7.4 Hz, 1H), 7.56 (dd, J = 8.0, 1.0 Hz, 1H), 7.49 (t, J = 7.8 Hz, 2H), 7.40 (t, J = 7.9 Hz, 1H), 4.72 (d, J
= 6.0 Hz, 2H), 4.53 – 4.48 (m, 2H), 3.42 (dq, J = 12.0, 6.1 Hz, 1H), 3.28 (d, J = 6.5 Hz, 2H); 13C NMR (125 MHz, CDCl3): δ 196.9, 165.1, 136.4, 134.9, 133.9, 133.6, 131.4, 130.1, 129.9, 129.0, 128.3, 127.9, 76.4, 65.3, 37.2, 33.4; FT-IR (thin film): 1724, 1685, 1553, 1427, 1378, 1256, 1129, 1000, 749, 690 cm-1; HRMS (+ESI): Calcd for C18H17NClO5 [M+H]+ 362.0790; found: 362.0793; The ee value 96% (tminor = 27.8 min, tmajor = 29.7 min) was determined by HPLC analysis using Daicel Chiralpak ID with hexane/iPrOH (80:20) as the eluent, flow: 1.0 mL/min, 254 nm, 25 oC.
(S)-2-(nitromethyl)-4-oxo-4-phenylbutyl 2-methylbenzoate (3x)
This compound was prepared according to the general procedure D. Reaction was completed after 2 d. Analytical TLC on silica gel using 12% ethyl acetate/hexane. Sticky oil (28.5 mg, 83% yield); 1H NMR (600 MHz, CDCl3): δ 7.96 (d, J = 7.4 Hz, 2H), 7.86 (d, J = 8.3 Hz, 1H), 7.60 (t, J = 7.4 Hz, 1H), 7.48 (t, J = 7.8 Hz, 2H), 7.43 (t, J = 7.5 Hz, 1H), 7.28 – 7.25 (m, 2H), 4.71 (d, J = 6.0 Hz, 2H), 4.50 – 4.44 (m, 2H), 3.40 (dt, J = 12.0, 6.0 Hz, 1H), 3.27 (d, J = 7.1 Hz, 2H), 2.59 (s, 3H); 13C NMR (150 MHz, CDCl3):
δ 196.9, 167.0, 140.8, 136.5, 133.9, 132.7, 132.1, 130.7, 129.0, 128.9, 128.3, 126.1, 76.4, 64.5, 37.3, 33.4, 22.0; FT-IR (thin film): 1720, 1686, 1553, 1451, 1381, 1253, 1078, 741, 691 cm-1; HRMS (+ESI): Calcd for C19H20NO5 [M+H]+ 342.1336; found:
342.1338; The ee value 97% (tminor = 39.7 min, tmajor = 47.0 min) was determined by HPLC analysis using Daicel Chiralpak ID with hexane/iPrOH (90:10) as the eluent, flow:
1.0 mL/min, 254 nm, 25 oC.