The Journal of Organic Chemistry
FEATURED ARTICLE
yellow solid; 89% ee by HPLC analysis (Chiralcel OD-H column, 1 mL/
NMR (400 MHz, CDCl3) δ 7.14 (d, J = 1.0 Hz, 1H), 5.96 (dd, J = 7.9,
1.4 Hz, 1H), 4.89 (dd, J = 7.8, 5.2 Hz, 1H), 3.55-3.41 (m, 2H), 2.57-
2.42 (m, 2H), 1.60 (ddd, J = 13.3, 8.5, 6.6 Hz, 2H), 1.45 (dt, J = 20.6, 7.2
Hz, 1H), 1.40-1.31 (m, 2H), 1.31-1.27 (m, 1H), 1.27 (d, J = 1.0 Hz,
3H), 1.25 (d, J = 1.1 Hz, 3H), 0.92 (t, J = 7.3 Hz, 3H), 0.79 (t, J = 7.5 Hz,
3H); 13C NMR (101 MHz, CDCl3) δ 198.2, 140.2, 125.1, 112.1, 109.5,
54.9, 36.3, 32.6, 29.8, 28.4, 22.8, 22.0, 21.8, 14.2, 9.0; HRMS (ESI) calcd
for [M þ H]þ (C15H25NO)þ requires 236.2009, found 236.2009.
(R)-1-(4-Butyl-1-isopropyl-1,4-dihydropyridin-3-yl)pentan-
1-one 3g (Table 2, entry 7): 82% (108 mg) yield as yellow oil; 96%
ee by HPLC analysis (Chiralcel OJ-H column, 1 mL/min, 2% i-PrOH in
hexane, 254 nm), (S) tR = 4.75 (minor) and (R) tR = 5.21 (major);
[R]25D -603 (c 0.28 in MeOH); IR ν = 3060, 2958, 2930, 2872, 1666,
1626, 1577, 1465, 1425, 1389, 1179, 1157, 732 cm-1; MS m/z 263, 248,
234, 220, 206, 164; 1H NMR (400 MHz, CDCl3) δ 7.12 (d, J = 0.9 Hz,
1H), 5.93 (dd, J = 7.9, 1.4 Hz, 1H), 4.92 (dd, J = 7.8, 5.2 Hz, 1H), 3.55-
3.43 (m, 2H), 2.52-2.46 (m, 2H), 1.60 (ddd, J = 13.1, 8.4, 6.4 Hz, 3H),
1.34 (dt, J = 22.2, 7.3 Hz, 4H), 1.25 (dd, J = 13.6, 8.2 Hz, 11H), 0.92 (t,
J = 7.3 Hz, 4H), 0.86 (t, J = 6.9 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ
198.2, 140.0, 124.9, 112.7, 110.1, 54.8, 37.6, 36.3, 31.5, 28.4, 27.2, 23.0,
22.8, 22.0, 21.8, 14.4, 14.2; HRMS (ESI) calcd for [M þ H]þ (C17H29-
NO)þ requires 264.2322, found 264.2318.
min, 10% i-PrOH in hexane, 254 nm), (S) tR = 9.53 (major) and (R) tR =
11.21 (minor); [R]25 -538 (c 0.11 in MeOH); IR ν = 3073, 2956,
D
1669, 1510, 1343, 820 cm-1; MS m/z 328, 285, 243, 206, 164; 1H NMR
(400 MHz, CDCl3) δ 8.14-8.10 (m, 2H), 7.45-7.39 (m, 2H), 7.28 (d,
J = 1.4 Hz, 1H), 6.08 (d, J = 7.8 Hz, 1H), 4.97 (dd, J = 7.8, 4.9 Hz, 1H),
4.80 (d, J = 4.9 Hz, 1H), 3.62 (hept, J = 6.7 Hz, 1H), 2.45 (ddq, J = 22.5,
15.1, 7.5 Hz, 2H), 1.56-1.47 (m, 2H), 1.36 (d, J = 1.4 Hz, 3H), 1.35 (d,
J = 1.4 Hz, 3H), 1.31-1.19 (m, 2H), 0.86 (t, J = 7.3 Hz, 3H); 13C NMR
(101 MHz, CDCl3) δ 197.3, 155.2, 146.4, 139.3, 128.6, 125.0, 123.8,
112.0, 108.9, 55.4, 38.6, 36.1, 27.7, 22.7, 22.1, 22.0, 14.1; HRMS (ESI)
calcd for [M þ H]þ (C19H24N2O3)þ requires m/z 329.1860, found
329.1855.
(S)-1-(1-Isopropyl-4-(4-methoxyphenyl)-1,4-dihydropyri-
din-3-yl)pentan-1-one 3c (Table 2, entry 3): 86% (135 mg)
yield as yellow oil; 89% ee by HPLC analysis (Chiralcel OJ-H column,
1 mL/min, 10% i-PrOH in hexane, 254 nm), (S) tR = 11.23 (major) and
(R) tR = 18.67 (minor); [R]25D -423 (c 0.43 in MeOH); IR ν = 3060,
2959, 1666, 1575, 1508, 1176, 1035, 830 cm-1; MS m/z 313, 270, 228,
206, 164; 1H NMR (400 MHz, CDCl3) δ 7.26 (s, 1H), 7.21-7.15 (m,
2H), 6.88-6.71 (m, 2H), 5.99 (dd, J = 7.8, 1.0 Hz, 1H), 5.01 (dd, J = 7.8,
5.0 Hz, 1H), 4.60 (d, J = 5.0 Hz, 1H), 3.76 (s, 3H), 3.58 (hept, J = 6.7 Hz,
1H), 2.51-2.28 (m, 2H), 1.55-1.45 (m, 2H), 1.33 (d, J = 1.4 Hz, 3H),
1.31 (d, J = 1.4 Hz, 3H), 1.28-1.21 (m, 2H), 0.85 (t, J = 7.3 Hz, 3H);
13C NMR (101 MHz, CDCl3) δ 198.0, 158.0, 140.8, 138.6, 128.7, 123.8,
113.8, 112.8, 110.5, 55.3, 55.1, 37.5, 36.5, 27.7, 22.7, 22.1, 21.9, 14.1;
HRMS (ESI) calcd for [M þ H]þ (C20H27NO2)þ requires 314.2115,
found 314.2108.
(R)-1-(4-((Benzyloxy)methyl)-1-isopropyl-1,4-dihydropyr-
idin-3-yl)pentan-1-one 3h (Table 2, entry 8): 61% (100 mg)
yield as yellow oil; 93% ee by HPLC analysis (Chiralcel OD-H column,
1 mL/min, 10% i-PrOH in hexane, 254 nm), (R) tR = 6.28 (major) and
(S) tR = 8.41 (minor); [R]25D -522 (c 0.22 in MeOH); IR ν = 3063,
3030, 2958, 2931, 2870, 1667, 1626, 1575, 1426, 1179, 735 cm-1; MS
1
m/z 327, 298, 281, 270, 254, 220, 206, 164; H NMR (400 MHz,
(S)-1-(4-(4-Bromophenyl)-1-isopropyl-1,4-dihydropyridin-
3-yl)pentan-1-one 3d (Table 2, entry 4): 80% (145 mg) yield
as yellow oil; 89% ee by HPLC analysis (Chiralcel OD-H column,
1 mL/min, 10% i-PrOH in hexane, 254 nm), (S) tR = 5.62 (major) and
(R) tR = 6.71 (minor); [R]25D -350 (c 0.19 in MeOH); IR ν = 3061,
2960, 1667, 1632, 1577, 1178, 842 cm-1; MS m/z 364, 361, 320, 206,
164; 1H NMR (400 MHz, CDCl3) δ 7.39-7.35 (m, 2H), 7.25 (d, J = 1.4
Hz, 1H), 7.16-7.12 (m, 2H), 6.02 (dd, J = 7.8, 0.9 Hz, 1H), 4.98 (dd, J =
7.8, 5.0 Hz, 1H), 4.63 (d, J = 5.0 Hz, 1H), 3.59 (hept, J = 6.7 Hz, 1H),
2.50-2.33 (m, 2H), 1.55-1.46 (m, 2H), 1.34 (d, J = 0.9 Hz, 3H), 1.32
(d, J = 0.9 Hz, 3H), 1.29-1.20 (m, 2H), 0.86 (t, J = 7.3 Hz, 3H); 13C NMR
(101 MHz, CDCl3) δ 197.6, 147.2, 138.9, 131.4, 129.6, 124.3, 119.9, 112.4,
109.8, 55.2, 37.9, 36.3, 27.7, 22.7, 22.1, 21.9, 14.1; HRMS (ESI) calcd for
[M þ H]þ (C19H24BrNO)þ requires 362.1114, found 362.1105.
(S)-1-(1-Isopropyl-4-(naphthalen-2-yl)-1,4-dihydropyridin-
3-yl)pentan-1-one 3e (Table 2 entry 5): 63% (105 mg) yield as
yellow oil; 89% ee by HPLC analysis (Chiralcel OJ-H column, 1 mL/min,
10% i-PrOH in hexane, 254 nm), (R) tR = 15.17 (major) and (S) tR =
CDCl3) δ 7.35-7.20 (m, 5H), 7.17 (d, J = 1.3 Hz, 1H), 6.00 (dd, J = 7.9,
1.4 Hz, 1H), 5.08 (dd, J = 7.9, 5.1 Hz, 1H), 4.51 (dd, J = 30.7, 12.1 Hz,
2H), 3.82 (q, J = 5.2 Hz, 1H), 3.51 (hept, J = 6.7 Hz, 1H), 3.39 (d, J = 0.6
Hz, 1H), 3.37 (s, 1H), 3.37-3.37 (m, 1H), 2.56-2.42 (m, 2H), 1.64-
1.54 (m, 2H), 1.39-1.28 (m, 2H), 1.26 (s, 3H), 1.25 (s, 3H), 0.91 (t, J =
7.3 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 197.9, 141.0, 139.2, 128.3,
127.6, 127.4, 125.6, 109.2, 108.4, 74.8, 72.9, 55.0, 36.3, 32.9, 28.2, 22.8,
22.0, 21.8, 14.1; HRMS (ESI) calcd for [M þ H]þ (C21H29NO2)þ
requires 328.2271, found 328.2266.
(S)-1-(1-Cyclohexyl-4-phenyl-1,4-dihydropyridin-3-yl)pen-
tan-1-one 3i (Table 3, entry 1): 79% (127 mg) yield as yellow oil;
76% ee by HPLC analysis (Chiralcel OD-H column, 1 mL/min, 10%
i-PrOH in hexane, 254 nm), (S) tR = 5.94 (major) and (R) tR = 7.84
(minor); [R]25 -416 (c 0.12 in MeOH); IR ν = 3060, 3025, 2932,
D
2857, 1666, 1629, 1574, 1162, 762, 698 cm-1; MS m/z 323, 280, 246,
198, 164; 1H NMR (400 MHz, CDCl3) δ 7.29 (d, J = 1.3 Hz, 1H), 7.26
(dd, J = 3.7, 0.9 Hz, 4H), 7.13 (tt, J = 5.0, 4.0 Hz, 1H), 6.01 (dd, J = 7.8,
0.9 Hz, 1H), 5.00 (dd, J = 7.8, 5.1 Hz, 1H), 4.65 (d, J = 5.1 Hz, 1H), 3.10
(tt, J = 12.0, 3.6 Hz, 1H), 2.47-2.33 (m, 2H), 2.00-1.92 (m, 2H),
1.93-1.85 (m, 2H), 1.71 (d, J = 13.0 Hz, 1H), 1.56-1.43 (m, 4H), 1.42-
1.29 (m, 2H), 1.29-1.19 (m, 2H), 1.19-1.10 (m, 1H), 0.84 (t, J = 7.3 Hz,
3H); 13C NMR (101 MHz, CDCl3) δ 197.9, 148.3, 139.1, 128.4, 127.7,
126.1, 124.7, 112.4, 110.1, 63.3, 38.4, 36.5, 32.7, 32.5, 27.6, 25.8, 25.4,
22.7, 14.1; HRMS (ESI) calcd for [M þ H]þ (C22H29NO)þ requires
324.2322, found 324.2320.
24.28 (minor); [R]25 -427 (c 0.25 in MeOH); IR ν = 3054, 2959,
D
1666, 1631, 1573, 1178, 817 cm-1; MS m/z 333, 290, 248, 206, 164; 1H
NMR (400 MHz, CDCl3) δ 7.76 (dd, J = 8.0, 4.1 Hz, 3H), 7.65 (d, J =
1.0 Hz, 1H), 7.46 (dd, J = 8.5, 1.8 Hz, 1H), 7.43-7.35 (m, 2H), 7.33 (d,
J = 1.4 Hz, 1H), 6.04 (dd, J = 7.8, 0.9 Hz, 1H), 5.08 (dd, J = 7.8, 5.0 Hz,
1H), 4.84 (d, J = 5.0 Hz, 1H), 3.62 (hept, J = 6.7 Hz, 1H), 2.49-2.34 (m,
2H), 1.53-1.44 (m, 2H), 1.37 (d, J = 1.6 Hz, 3H), 1.35 (d, J = 1.6 Hz,
3H), 1.28-1.18 (m, 2H), 0.82 (t, J = 7.3 Hz, 3H); 13C NMR (101 MHz,
CDCl3) δ 197.9, 145.5, 138.9, 133.7, 132.4, 128.1, 128.0, 127.7, 126.7,
125.9, 125.8, 125.2, 124.2, 112.4, 110.2, 55.2, 38.6, 36.5, 27.6, 22.7, 22.1,
22.0, 14.1; HRMS (ESI) calcd for [M þ H]þ (C23H27NO)þ requires
334.2165, found 334.2153.
(S)-1-(1-Benzyl-4-phenyl-1,4-dihydropyridin-3-yl)pentan-
1-one 3j (Table 3, entry 2): 54% (90 mg) yield as yellow oil; 87% ee
by HPLC analysis (Chiralcel OD-H column, 1 mL/min, 10% i-PrOH in
hexane, 254 nm), (S) tR = 12.73 (major) and (R) tR = 20.16 (minor);
[R]25D -241 (c 0.20 in CHCl3); IR ν = 3061, 3027, 2957, 2931, 2871,
1668, 1629, 1578, 1176, 730, 698 cm-1; MS m/z 331, 314, 302, 288, 254,
240, 91; 1H NMR (400 MHz, CDCl3) δ 7.43-7.24 (m, 11H), 7.18-
7.11 (m, 1H), 5.97-5.91 (m, 1H), 5.02 (dd, J = 7.7, 5.0 Hz, 1H), 4.67 (d,
J = 5.0 Hz, 1H), 4.49 (s, 2H), 2.47-2.31 (m, 2H), 1.53-1.41 (m, 2H),
1.27-1.15 (m, 2H), 0.82 (t, J = 7.3 Hz, 3H); 13C NMR (101 MHz,
(R)-1-(4-Ethyl-1-isopropyl-1,4-dihydropyridin-3-yl)pentan-
1-one 3f (Table 2, entry 6): 69% (81 mg) yield as yellow oil, 93% ee
by HPLC analysis (Chiralcel OD-H column, 1 mL/min, 2% i-PrOH
in hexane, 254 nm), (R) tR = 6.28 (major) and (S) tR = 9.76 (minor);
[R]25D -675 (c 0.19 in MeOH); IR ν = 3060, 2960, 1666, 1626, 1576,
1
1462, 1425, 1179, 1158, 727 cm-1; MS m/z 235, 220, 206, 164; H
1543
dx.doi.org/10.1021/jo200095e |J. Org. Chem. 2011, 76, 1538–1545