The Journal of Organic Chemistry
Article
13i-A. mp 102−122 °C (hexanes/ethyl acetate); IR (thin film, CH2Cl2)
νmax 3063, 2953, 1618, 1582, 1502, 1453, 1360, 1267, 1161, 1113, 1038,
993, 835, 766; 1H NMR (400 MHz, CDCl3) δ 8.60 (1H, ddd, J = 1.0, 1.5,
4.5 Hz), 7.77 (1H, ddd, J = 2.0, 8.0, 8.0 Hz), 7.69 (1H, d, J = 8.0 Hz),
7.22 (1H, ddd, J = 1.0, 5.0, 9.0 Hz), 7.10 (1H, d, J = 8.0 Hz), 6.59 (1H,
dd, J = 2.5, 8.5 Hz), 6.51 (1H, d, J = 2.5 Hz), 4.94 (1H, d, J = 3.5 Hz),
3.77 (3H, s), 3.06 (1H, d, J = 9.0 Hz), 2.55 (1H, dd, J = 3.0, 8.5 Hz), 2.16
(1H, d, J = 4.5 Hz), 1.79 (1H, d, J = 3.0 Hz), 1.58 (1H, tt, J = 4.0, 12.0
Hz), 1.28−1.47 (3H, m), 1.14−1.21 (1H, m), 0.85 (1H, d, J = 10 . 0 Hz);
13C NMR (100 MHz, CDCl3) δ 160.7, 158.9, 157.4, 149.2, 136.6, 130.4,
J = 1.0, 8.5 Hz), 6.78 (1H, ddd, J = 1.0, 7.5, 7.5 Hz), 6.67 (1H, ddd, J =
1.0, 1.0, 8.0 Hz), 4.94 (1H, d, J = 10.0 Hz), 3.85 (1H, d, J = 11.0 Hz),
2.40−2.51 (1H, m), 0.64 (3H, d, J = 6.5 Hz); 13C NMR (100 MHz,
CDCl3) δ 159.3, 155.2, 149.4, 143.8, 137.1, 130.4, 129.7, 128.7, 127.7,
126.9, 126.5, 123.5, 122.5, 120.9, 116.9, 84.9, 51.0, 40.4, 15.4; MS (ESI+)
m/z 302 (100, [M + H]+), 183 (5), 120 (5); HRMS (ESI+) calcd for
[M + H]+ C21H20NO 302.1539; found 302.1552.
2-((2S*,3R*,4S*)-3-Methyl-4-phenylchroman-2-yl)pyridine 18a-
exo-trans. isolated as a white solid, mp 96−98 °C (ether); IR (thin
film, CH2Cl2) νmax 3059, 3024, 2920, 1589, 1497, 1435, 1343, 1238,
1126, 1073, 1030, 995, 922, 813, 759, 702 cm−1; 1H NMR (400 MHz,
CDCl3) δ 8.51 (1H, ddd, J = 1.0, 2.0, 5.0 Hz), 7.76 (1H, ddd, J = 2.0, 7.5,
7.5 Hz), 7.52 (1H, d, J = 7.5 Hz), 7.32 (2H, dd, J = 7.5, 7.5 Hz), 7.12−
7.27 (5H, m), 7.09 (1H, dd, J = 1.0, 8.2 Hz), 7.04 (1H, dd, J = 1.5, 7.5
Hz), 6.93 (1H, ddd, J = 1.0, 7.5, 7.5 Hz), 5.15 (1H, d, J = 2.5 Hz), 4.04
(1H, d, J = 2.0 Hz), 2.71 (1H, tq, J = 2.5, 7.0 Hz), 0.84 (3H, d, J = 7.0
Hz); 13C NMR (100 MHz, CDCl3) δ 160.1, 154.6, 149.0, 146.5, 136.5,
132.0, 129.1, 128.7, 128.2, 126.6, 122.3, 122.2, 121.3, 121.2, 116.9, 75.5,
48.6, 38.8, 13. 9; MS (ESI+) m/z 302 (100, [M + H]+), 183 (5), 120 (5);
HRMS (ESI+) calcd for [M + H]+ C21H20NO 302.1539; found 302.1552.
18d. Flash chromatography (10% ethyl acetate/hexanes) gave 18d as
a white solid (0.144 g, 46% yield). Further purification by flash chroma-
tography (5% to 20% ethyl acetate/hexanes) afforded pure 18d-endo-
trans and 18d-exo-trans.
2-((2S*,3S*,4R*)-3,6-Dimethyl-4-phenylchroman-2-yl)pyridine
18d-endo-trans. isolated as a white solid, mp 149−150 °C (hexanes/
ethyl acetate); IR (thin film, CH2Cl2) νmax 3063, 3024, 2920, 2962, 1589,
1474, 1339, 1273, 1242, 1219, 1123, 1072, 1049, 883, 814, 759 cm−1; 1H
NMR (400 MHz, CDCl3) δ 8.63 (1H, ddd, J = 1.0, 1.5, 4.5 Hz), 7.75
(1H, ddd, J = 1.5, 7.5, 7.5 Hz), 7.51 (1H, d, J = 8.0 Hz), 7.32 (2H, dddd,
J = 1.0, 1.0, 7.0, 7.0 Hz), 7.24−7.28 (2H, m), 7.20 (2H, ddd, J = 1.5, 6.5,
6.5Hz), 6.91(1H, dd, J = 2.0, 8.0 Hz), 6.82 (1H, d, J = 9.0 Hz), 6.47 (1H, s),
4.89 (1H, d, J = 10.0 Hz), 3.81 (1H, d, J = 10.5 Hz), 2.48−2.50 (1H, m),
2.12 (3H, s), 0.63 (3H, d, J = 6.5 Hz); 13C NMR (100 MHz, CDCl3) δ
159.5, 153.1, 149.4, 144.0, 137.1, 130.5, 130.1, 129.7, 128.7, 128.4, 126.9,
126.1, 123.4, 122.5.2, 116.7, 84.9, 51.1, 40.7, 20.8, 15.5; MS (ESI+) m/z
316 (100, [M + H]+); HRMS (ESI+) calcd for [M + H]+ C22H22NO
316.1707; found 316.1705.
2-((2S*,3R*,4S*)-3,6-Dimethyl-4-phenylchroman-2-yl)pyridine
18d-exo-trans. isolated as a white solid, mp 93−94 °C (hexanes/ethyl
acetate); IR (thin film, CH2Cl2) νmax 3059, 3024, 2956, 1591, 1493,
1426, 1343, 1238, 1126, 1055, 1030, 926, 816, 702, 687 cm−1; 1H NMR
(400 MHz, CDCl3) δ 8.49 (1H, ddd, J = 1.0, 1.5, 4.5 Hz), 7.70 (1H, ddd,
J = 2.0, 8.0, 8.0 Hz), 7.65 (1H, ddd, J = 1.0, 1.5, 3.0 Hz), 7.28 (2H, dddd,
J = 0.5, 0.5, 7.5, 7.5 Hz), 7.19 (1H, tt, J = 1.0, 7.5 Hz), 7.10−7.15 (3H,
m), 7.02 (1H, dd, J = 2.0, 8.0 Hz), 6.96 (1H, d, J = 8.0 Hz), 6.82 (1 H, d,
J = 1.5 Hz), 5.10 (1H, d, J = 2.5 Hz), 3.97 (1H, d, J = 1.5 Hz), 2.68 (1H,
tq, J = 2.0, 7.0 Hz), 2.23 (3H, s), 0.81 (3H, d, J = 7.0 Hz); 13C δ NMR
(100 MHz, CDCl3) 160.3, 152.4, 149.0, 146.7, 136.5, 132.1, 130.3,
129.1, 129.0, 128.6, 126.6, 122.2, 121.8, 121.3, 116.6, 75.4, 48.7, 38.9,
20.8, 13.9; MS (ESI+) m/z 316 (100, [M + H]+); HRMS (ESI+) calcd for
[M + H]+ C22H22NO 316.1707; found 316.1701.
122.2, 121.7, 120.9, 109.2, 102.4, 80.8, 55.5, 48.1, 47.7, 44.7, 37.1, 34.5,
31.3, 28.2; MS (ESI+) m/z 308 (100, [M + H]+). HRMS (ESI+) calcd for
[M + H]+ C20H22NO2 308.1651 found 308.1649.
Chroman 13i-B. mp 95−96 °C (hexanes/ethyl acetate); IR (thin
film, CH2Cl2) νmax 3059, 2953, 2909, 2970, 2834, 1591, 1483, 1453,
1333, 1264, 1221, 1188, 1109, 1094, 1084, 991, 837, 774, 741; 1H NMR
(400 MHz, CDCl3) δ 8.59 (1H, ddd, J = 1.0, 2.0, 5.0 Hz), 7.76 (1H, ddd,
J = 2.0, 8.0, 8.0 Hz), 7.69 (1H, d, J = 8.0 Hz), 7.22 (1H, ddd, J = 1.0, 5.0,
7.0 Hz), 7.08 (1H, dd, J = 8.0, 8.0 Hz), 6.60 (1H, d, J = 8.0 Hz), 6.53 (1H,
d, J = 8.0 Hz), 4.90 (1H, d, J = 4.0 Hz), 3.86 (3H, s), 3.24 (1H, d, J =
9.0 Hz), 2.56 (1H, dd, J = 4.0, 9.0 Hz), 2.28 (1H, d, J = 4.5 Hz), 1.78 (1H,
d, J = 3.0 Hz), 1.57 (1H, tt, J = 4.0, 12.0 Hz), 1.40−1.44 (2H, m), 1.33
(1H, tt, J = 4.5, 12.0 Hz), 1.20 (1H, tt, J = 3.5, 8.0 Hz), 0.85 (1H, d, J =
10.0 Hz); 13C NMR (100 MHz, CDCl3) δ 160.8, 158.2, 157.7, 149.1,
136.6, 126.7, 122.2, 120.9, 118.4, 110.5, 103.8, 80.6, 55.7, 47.6, 45.2,
40.2, 37.3, 35.2, 31.3, 28.5; MS (ESI+) m/z 308 (100, [M + H]+); HRMS
(ESI+) calcd for [M + H]+ C20H22NO2 308.1651 found 308.1656.
Chroman 13j. Flash chromatography (20% ethyl acetate/hexanes)
gave 13j as a white solid (0.199 g, 65% yield). mp 113−115 °C (hexanes/
ethyl acetate); IR (thin film, CH2Cl2) νmax 3053, 2953, 2924, 2870, 1593,
1572, 1472, 1435, 1362, 1338, 1288, 1252, 1213, 1155, 1103, 991, 812,
764, 747; 1H NMR (400 MHz, CDCl3) δ 8.59 (1H, ddd, J = 1.0, 2.0, 5.0
Hz), 7.76 (1 H, ddd, J = 2.0, 8.0, 8.0 Hz), 7.69 (1H, d, J = 8.0), 7.20 (1H,
ddd, J = 1.0, 5.0, 7.5 Hz), 6.87 (1H, d, J = 9.0 Hz), 6.76 (1H, d, J = 3.0
Hz), 6.68 (1H, dd, J = 3.0, 9.0 Hz), 4.88 (1H, d, J = 4.0 Hz), 3.19 (3H, s),
3.07 (1H, d, J = 9.0 Hz), 2.56 (1H, dd, J = 3.5, 9.0 Hz), 2.23 (1H, d, J =
4.5 Hz), 1.79 (1H, d, J = 3.0 Hz), 1.60 (1H, tt, J = 4.0, 12.5 Hz), 1.51
(1H, dt, J = 2.0, 10.0 Hz), 1.30−1.46 (2H, m), 1.20 (1H, tt, J = 3.0, 9.0
Hz), 0.87 (1 H, d, J = 10.0 Hz); 13C NMR (100 MHz, CDCl3) δ 160.8,
154.7, 150.7, 149.1, 136.6, 130.3, 122.1, 120.9, 118.2, 114.3, 112.8, 80.8,
55.8, 48.2, 47.8, 45.9, 37.1, 34.7, 31.2, 28.5; MS (ESI+) m/z 308 (100,
[M + H]+). HRMS (ESI+) calcd for [M + H]+ C20H22NO2 308.1651
found 308.1651.
Chroman 13l. Flash chromatography (15% ethyl acetate/hexanes)
gave 13l as a white solid (0.200 g, 66% yield). IR (thin film, CH2Cl2) νmax
3055, 3005, 2959, 2924, 2870, 1590, 1573, 1489, 1474, 1439, 1366,
1335, 1242, 1227, 1126, 1012, 995, 889, 814, 746, 721, 698, 650, 621; 1H
NMR (400 MHz, CDCl3) δ 8.58 (1H, ddd, J = 1.0, 2.0, 5.0 Hz), 7.75
(1H, ddd, J = 2.0, 2.0, 7.5 Hz), 7.69 (1H, ddd, J = 0.5, 1.5, 3.0 Hz), 7.19
(1H, dddd, J = 0.5, 1.3, 5.0, 6.5 Hz), 6.66 (2H, d, J = 12.0 Hz), 4.84 (1H,
d, J = 4.0 Hz), 3.07 (1H, d, J = 9.0 Hz), 2.59 (1H, ddd, J = 1.0, 4.0, 8.0
Hz), 2.32 (3H, s), 2.25 (3H, s), 2.18 (1H, d, J = 4.5 Hz), 1.78 (1H, d,
J = 1.5 Hz), 1.51−1.59 (2H, m), 1.31−1.45 (2H, m), 1.20 (1H, tt, J = 3.0,
8.5 Hz), 0.86 (1H, d, J = 10.0 Hz); 13C NMR (100 MHz, CDCl3) δ
160.8, 156.8, 149.1, 137.2, 136.6, 136.2, 125.1, 125.0, 122.1, 120.9, 116.1,
80.6, 48.4, 45.6, 42.7, 37.4, 35.2, 31.1, 28.7, 21.1, 16.0; MS (ESI+) m/z
306 (100, [M + H]+); HRMS (ESI+) calcd for [M + H]+ C21H24NO
306.1858; found 306.1866.
18j. Flash chromatography (20% ethyl acetate/hexanes) gave 18j as a
white solid (0.207 g, 63% yield). Further purification by flash
chromatography (10% to 25% ethyl acetate/hexanes) afforded pure
18j-endo-trans, 18a-exo-trans, and 18j-endo-cis.
2-((2S*,3S*,4R*)-6-Methoxy-3-methyl-4-phenylchroman-2-yl)-
pyridine 18j-endo-trans. isolated as a white solid, mp 124−125 °C
(hexanes/ethyl acetate); IR (thin film, CH2Cl2) νmax 3063, 2964, 2927,
18a. Flash chromatography (15% ethyl acetate/hexanes) gave 18a as
a white solid (0.087 g, 29% yield). Further purification by flash chroma-
tography (5% to 20% ethyl acetate/hexanes) afforded pure 18a-endo-
trans and 18a-exo-trans.
2-((2S*,3S*,4R*)-3-Methyl-4-phenylchroman-2-yl)pyridine 18a-
endo-trans. isolated as a white solid, mp 140−141 °C (ether); IR
(thin film, CH2Cl2) νmax 3063, 3013, 2963, 2924, 1589, 1466, 1435,
1335, 1300, 1261, 1211, 1180, 1084, 1045, 995, 914, 787, 768 cm−1; 1H
NMR (400 MHz, CDCl3) δ 8.64 (1H, ddd, J = 0.5, 1.5, 5.0 Hz), 7.76
(1H, ddd, J = 2.0, 7.5, 7.5 Hz), 7.52 (1H, ddd, J = 1.0, 1.0, 8.0 Hz), 7.32
(2H, dddd, J = 1.0, 1.0, 7.0, 7.0 Hz), 7.24−7.28 (2H, m), 7.20 (2H, dd,
J = 1.5, 8.5 Hz), 7.11 (1H, dddd, J = 1.0, 1.5, 7.0, 7.0 Hz), 6.92 (1H, dd,
1
1591, 1490, 1342, 1270, 1214, 1151, 1028, 819, 700 cm−1; H NMR
(400 MHz, CDCl3) δ 8.63 (1H, ddd, J = 1.0, 2.0, 5.0 Hz), 7.75 (1H, ddd,
J = 2.0, 7.5, 7.5 Hz), 7.50 (1H, d, J = 8.0 Hz), 7.18−7.33 (6H, m), 6.86
(1H, d, J = 9.0 Hz), 6.68 (1H, ddd, J = 1.0, 3.0, 9.0 Hz), 6.21 (1H, dd, J =
1.0, 3.0 Hz), 4.87 (1H, d, J = 10.0 Hz), 3.82 (1H, d, J = 11.0 Hz), 3.59
(3H, s), 2.39−2.49 (1H, m), 0.63 (3H, d, J = 6.5 Hz); 13C NMR (100
MHz, CDCl3) δ 159.4, 153.8, 149.5, 149.4, 143.7, 137.1, 129.7, 128.7,
127.2, 127.0, 123.4, 125.5, 117.5, 115.2, 113.6, 84.9, 55.8, 51.4, 40.6,
15.5; MS (ESI+) m/z 332 (100, [M + H]+); HRMS (ESI+) calcd for
[M + H]+ C22H22NO2 332.1656; found 332.1655.
1418
dx.doi.org/10.1021/jo302328s | J. Org. Chem. 2013, 78, 1404−1420