The Journal of Organic Chemistry
Article
(C42H43N3O3+Na)+ requires m/z 660.3197, found m/z 660.3201;
enantiomeric ratio 94:6, determined by HPLC (Daicel Chirapak IA,
hexane/2-propanol = 70/30, flow rate 1.0 mL/min, T = 30 °C, 254
nm) tR = 5.900 min (minor), tR = 7.523 min (major).
6.92 (d, J = 7.8 Hz, 1H), 6.61 (d, J = 8.8 Hz, 2H), 6.47 (dd, J = 16.5,
5.2 Hz, 2H), 6.04 (d, J = 8.7 Hz, 2H), 4.90 (d, J = 16.1 Hz, 1H), 4.75
(d, J = 16.1 Hz, 1H), 3.70 (s, 3H), 2.33 (d, J = 16.6 Hz, 1H), 2.29 (s,
3H), 2.24−2.13 (m, 2H), 2.07 (d, J = 16.7 Hz, 1H), 1.15 (s, 3H), 0.95
(s, 3H); 13C NMR (100 MHz, CDCl3) δ 193.9, 178.6, 161.5, 158.0,
141.4, 137.8, 137.2, 133.3, 131.2, 131.2, 128.6, 128.3, 127.9, 127.4,
127.0, 126.8, 124.0, 123.3, 122.8, 120.4, 115.3, 114.3, 112.1, 109.2,
108.7, 55.6, 52.8, 50.3, 44.3, 41.5, 31.9, 29.5, 27.7, 21.6; IR (KBr) ν
3551, 3414, 3312, 3057, 2958, 2927, 2053, 1868, 1688, 1616, 1561,
1510, 1395, 1382, 1247, 1188, 1031, 1009, 823, 733, 698 cm−1; ESI
FTMS exact mass calcd for (C39H37N3O3 + Na)+ requires m/z
618.2727, found m/z 618.2721; enantiomeric ratio 88:12, determined
by HPLC (Daicel Chirapak IA, hexane/2-propanol = 70/30, flow rate
1.0 mL/min, T = 30 °C, 254 nm) tR = 7.217 min (minor), tR = 9.113
min (major).
Compound 3ha: flash column chromatography eluent, petroleum
ether/ethyl acetate = 2/1; reaction time = 16 h; yield: 52% (32.2 mg);
white solid; mp 135−136 °C; [α]20D = +22.3 (c 1.5, CHCl3); 1H NMR
(400 MHz, CDCl3) δ 8.38 (d, J = 7.9 Hz, 1H), 8.24 (s, 1H), 7.34 (d, J
= 8.1 Hz, 1H), 7.28 (d, J = 7.0 Hz, 1H), 7.26−7.25 (m, 2H), 7.24−
7.18 (m, 5H), 7.18−7.13 (m, 1H), 6.96 (dd, J = 7.8, 1.8 Hz, 1H),
6.63−6.60 (m, 3H), 6.51 (d, J = 2.5 Hz, 1H), 6.05 (d, J = 8.8 Hz, 2H),
4.98 (d, J = 16.1 Hz, 1H), 4.75 (d, J = 16.1 Hz, 1H), 3.71 (s, 3H), 2.40
(d, J = 16.4 Hz, 1H), 2.20 (dd, J = 16.6, 5.7 Hz, 2H), 2.10 (d, J = 16.7
Hz, 1H), 1.18 (s, 3H), 0.97 (s, 3H; 13C NMR (100 MHz, CDCl3) δ
178.0, 158.0, 144.9, 137.5, 136.3, 133.4, 131.4, 130.7, 128.6, 127.8,
127.2, 127.1, 126.4, 123.8, 123.6, 122.7, 122.6, 121.6, 120.6, 115.0,
114.2, 111.6, 109.8, 108.0, 55.4, 52.1, 50.0, 44.1, 41.3, 31.9, 29.0, 27.8;
IR (KBr) ν 3443, 3383, 2958, 2925, 1705, 1650, 1607, 1510, 1398,
1329, 1248, 1221, 1103, 913, 803, 745, 699 cm−1; ESI FTMS exact
mass calcd for (C38H34ClN3O3 + H)+ requires m/z 616.2376, found
m/z 616.2343; enantiomeric ratio 94:6, determined by HPLC (Daicel
Chirapak IA, hexane/2-propanol = 70/30, flow rate 1.0 mL/min, T =
30 °C, 254 nm) tR = 6.717 min (minor), tR = 9.007 min (major).
Compound 3ia: flash column chromatography eluent, petroleum
Compound 3da: flash column chromatography eluent, petroleum
ether/ethyl acetate = 2/1; reaction time = 16 h; yield: 99% (59 mg);
white solid; mp 162−163 °C; [α]20D = +67.6 (c 1.8, CHCl3); 1H NMR
(400 MHz, CDCl3) δ 8.76 (d, J = 2.0 Hz, 1H), 8.36 (d, J = 7.9 Hz,
1H), 7.36−7.28 (m, 2H), 7.27−7.25 (m, 1H), 7.22−7.16 (m, 1H),
7.12 (td, J = 7.8, 1.0 Hz, 2H), 7.05−6.93 (m, 4H), 6.89 (d, J = 6.3 Hz,
1H), 6.62 (t, J = 8.4 Hz, 3H), 6.40 (d, J = 2.5 Hz, 1H), 6.05 (d, J = 8.8
Hz, 2H), 4.95 (d, J = 16.0 Hz, 1H), 4.65 (d, J = 16.0 Hz, 1H), 3.69 (s,
3H), 2.34 (d, J = 16.4 Hz, 1H), 2.27−2.22 (m, 1H), 2.15 (s, 3H),
2.14−2.12 (m, 1H), 2.07 (d, J = 16.7 Hz, 1H), 1.13 (s, 3H), 0.93 (s,
3H); 13C NMR (100 MHz, CDCl3) δ 193.7, 178.4, 161.6, 157.9,
143.5, 137.9, 137.6, 136.8, 133.1, 130.9, 128.3, 127.9, 127.8, 127.8,
127.7, 126.5, 124.3, 123.1, 123.0, 122.5, 121.7, 120.2, 114.8, 114.1,
111.9, 109.2, 108.3, 55.4, 52.5, 50.1, 43.9, 41.2, 31.9, 29.0, 27.8, 21.4;
IR (KBr) ν 3552, 3478, 3413, 3302, 3053, 2953, 2925, 2866, 1698,
1637, 1566, 1510, 1396, 1246, 1222, 1171, 1038, 907, 743, 617 cm−1;
ESI FTMS exact mass calcd for (C39H37N3O3 + Na)+ requires m/z
618.2727, found m/z 618.2747; enantiomeric ratio 93:7, determined
by HPLC (Daicel Chirapak IA, hexane/2-propanol = 70/30, flow rate
1.0 mL/min, T = 30 °C, 254 nm) tR = 6.717 min (minor), tR = 8.590
min (major).
Compound 3ea: flash column chromatography eluent, petroleum
ether/ethyl acetate = 2/1; reaction time = 16 h; yield: 74% (44.2 mg);
1
white solid; mp 180−182 °C; [α]20 = +468.5 (c 0.4, CHCl3); H
D
NMR (400 MHz, CDCl3) δ 8.39 (d, J = 7.8 Hz, 1H), 8.25 (s, 1H),
7.34−7.28 (m, 4H), 7.25−7.20 (m, 2H), 7.16 (d, J = 8.6 Hz, 1H),
7.14−7.07 (m, 3H), 7.00 (t, J = 7.3 Hz, 1H), 6.63−6.58 (m, 3H), 6.46
(d, J = 2.4 Hz, 1H), 6.07 (d, J = 8.8 Hz, 2H), 4.97 (d, J = 16.3 Hz,
1H), 4.74 (d, J = 16.3 Hz, 1H), 3.71 (s, 3H), 2.39 (d, J = 16.4 Hz, 1H),
2.24−2.08 (m, 3H), 1.19 (s, 3H), 0.96 (s, 3H); 13C NMR (100 MHz,
acetone-d6) δ 193.1, 178.2, 161.6, 159.0, 144.3, 141.1, 139.0, 134.8,
134.6, 132.1, 130.8, 128.7, 128.5, 128.2, 127.9, 127.8, 126.8, 124.4,
124.0, 123.5, 122.5, 120.1, 115.9, 114.9, 112.8, 109.4, 109.0, 55.8, 53.4,
51.0, 43.5, 41.9, 32.6, 28.2; IR (KBr) ν 3552, 3479, 3414, 3308, 3237,
3118, 2956, 2933, 2836, 1688, 1574, 1512, 1487, 1396, 1251, 1169,
1038, 682 cm−1; ESI FTMS exact mass calcd for (C38H34ClN3O3 +
Na)+ requires m/z 638.2181, found m/z 638.2172; enantiomeric ratio
94:6, determined by HPLC (Daicel Chirapak IA, hexane/2-propanol =
70/30, flow rate 1.0 mL/min, T = 30 °C, 254 nm) tR = 7.670 min
(minor), tR = 9.513 min (major).
ether/ethyl acetate = 2/1; reaction time = 16 h; yield 50% (33.2 mg);
1
white solid; mp 136−137 °C; [α]20 = +428.6 (c 0.1, CHCl3); H
D
NMR (400 MHz, CDCl3) δ 8.41 (d, J = 7.8 Hz, 1H), 8.21 (s, 1H),
7.37 (d, J = 8.1 Hz, 1H), 7.33−7.30 (m, 1H), 7.29−7.27 (m, 1H),
7.26−7.22 (m, 5H), 7.22−7.17 (m, 2H), 7.14 (dd, J = 7.8, 1.7 Hz,
1H), 6.79 (d, J = 1.6 Hz, 1H), 6.64 (d, J = 8.9 Hz, 2H), 6.54 (d, J = 2.5
Hz, 1H), 6.07 (d, J = 8.8 Hz, 2H), 5.00 (d, J = 16.1 Hz, 1H), 4.77 (d, J
= 16.1 Hz, 1H), 3.74 (s, 3H), 2.42 (d, J = 16.5 Hz, 1H), 2.25−2.10 (m,
3H), 1.21 (s, 3H), 0.99 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
193.7, 177.9, 161.6, 158.0, 145.1, 137.5, 136.3, 132.0, 130.7, 128.6,
127.8, 127.2, 126.4, 124.5, 124.2, 123.6, 122.7, 122.5, 121.3, 120.6,
114.9, 114.2, 112.5, 111.6, 107.9, 55.4, 52.1, 50.0, 44.1, 41.3, 31.9, 29.0,
27.8; IR (KBr) ν 3552, 3414, 3236, 2955, 2036, 1705, 1638, 1617,
1566, 1510, 1487, 1397, 1329, 1247, 1221, 1104, 1034, 767, 743, 620
cm−1; ESI FTMS exact mass calcd for (C38H34BrN3O3 + Na)+ requires
m/z 684.1663, found m/z 684.1635; enantiomeric ratio 93:7,
determined by HPLC (Daicel Chirapak IA, hexane/2-propanol =
70/30, flow rate 1.0 mL/min, T = 30 °C, 254 nm) tR = 6.700 min
(minor), tR = 9.123 min (major).
Compound 3fa: Flash column chromatography eluent, petroleum
ether/ethyl acetate = 2/1; reaction time = 16 h; yield 62% (40.2 mg);
1
white solid; mp 170−171 °C; [α]20 = +398.3 (c 0.3, CHCl3); H
D
NMR (400 MHz, CDCl3) δ 8.42 (d, J = 1.9 Hz, 1H), 8.37 (d, J = 7.9
Hz, 1H), 7.32 (dd, J = 7.3, 3.5 Hz, 2H), 7.29 (s, 1H), 7.26−7.24 (m,
2H), 7.22 (dd, J = 6.2, 1.3 Hz, 1H), 7.19 (dd, J = 8.4, 2.0 Hz, 2H), 7.14
(dd, J = 7.7, 1.1 Hz, 1H), 7.03−6.99 (m, 1H), 6.64−6.59 (m, 2H),
6.56 (d, J = 7.7 Hz, 1H), 6.43 (d, J = 2.5 Hz, 1H), 6.06 (d, J = 8.8 Hz,
2H), 4.83 (d, J = 16.3 Hz, 1H), 4.72 (d, J = 16.3 Hz, 1H), 3.71 (s, 3H),
2.36 (d, J = 16.5 Hz, 1H), 2.19 (t, J = 17.6 Hz, 2H), 2.10 (d, J = 16.7
Hz, 1H), 1.17 (s, 3H), 0.95 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
193.7, 178.1, 161.7, 158.0, 142.8, 137.6, 137.3, 133.0, 132.3, 130.9,
130.8, 130.5, 129.0, 127.9, 127.8, 126.8, 126.4, 123.5, 123.2, 122.8,
122.6, 122.1, 120.4, 115.1, 114.1, 111.8, 108.9, 108.1, 55.4, 52.5, 50.1,
42.7, 41.2, 31.9, 29.0, 27.8; IR (KBr) ν 3553, 3413, 3231, 3035, 2958,
2881, 1688, 1638, 1609, 1572, 1397, 1330, 1272, 1168, 1047, 940, 829,
684 cm−1; ESI FTMS exact mass calcd for (C38H33Cl2N3O3 + Na)+
requires m/z 672.1791, found m/z 672.1778; enantiomeric ratio 93:7,
determined by HPLC (Daicel Chirapak IA, hexane/2-propanol = 70/
30, flow rate 1.0 mL/min, T = 30 °C, 254 nm) tR = 7.777 min (minor),
tR = 10.300 min (major).
Compound 3ja: flash column chromatography eluent, petroleum
ether/ethyl acetate = 2/1; reaction time = 16 h; yield 85% (50.7 mg);
1
white solid; mp 141−142 °C; [α]20 = +410.9 (c 0.4, CHCl3); H
D
NMR (400 MHz, CDCl3) δ 8.47 (s, 1H), 8.38 (d, J = 7.9 Hz, 1H),
7.28 (d, J = 7.9 Hz, 2H), 7.25−7.14 (m, 3H), 7.12−7.11 (m, 4H),
7.08−6.99 (m, 1H), 6.94−6.90 (m, 2H), 6.65−6.58 (m, 2H), 6.45 (d, J
= 2.5 Hz, 1H), 6.05 (d, J = 8.8 Hz, 2H), 5.22 (d, J = 16.4 Hz, 1H), 4.99
(d, J = 16.4 Hz, 1H), 3.71 (s, 3H), 2.42−2.30 (m, 2H), 2.24 (s, 3H),
2.18−2.11 (m, 1H), 1.15 (s, 3H), 0.95 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 193.7, 179.2, 161.5, 157.9, 141.6, 139.4, 137.6, 133.8, 131.8,
131.0, 128.9, 128.4, 127.8, 126.6, 126.4, 125.9, 125.8, 123.2, 123.1,
122.7, 121.9, 121.1, 120.3, 119.6, 115.7, 114.1, 111.7, 108.6, 55.4, 52.1,
50.1, 45.1, 41.2, 31.9, 28.9, 27.9, 19.0; IR (KBr) ν 3351, 3414, 3236,
2953, 2867, 2037, 1715, 1694, 1638, 1616, 1510, 1418, 1395, 1248,
1182, 1036, 1010, 846, 766, 617 cm−1; ESI FTMS exact mass calcd for
(C39H37N3O3 + H)+ requires m/z 596.2913, found m/z 596.2935;
Compound 3ga: flash column chromatography eluent, petroleum
ether/ethyl acetate = 2/1; reaction time = 16 h; yield 70.5% (42 mg);
white solid; mp 249−250 °C; [α]20D = +22.4 (c 1.8, CHCl3); 1H NMR
(400 MHz, CDCl3) δ 8.74 (d, J = 1.7 Hz, 1H), 8.37 (d, J = 7.9 Hz,
1H), 7.31−7.23 (m, 4H), 7.21−7.16 (m, 1H), 7.16−7.04 (m, 5H),
4640
dx.doi.org/10.1021/jo500644v | J. Org. Chem. 2014, 79, 4635−4643