6
Y. Lou et al. / Tetrahedron xxx (2015) 1e8
ꢁ
27
1
solid, mp 95e98 C. 40% yield. [
400 MHz, CDCl ):
a]
D
ꢀ57.8 (c 0.5, MeOH). H NMR
1H), 3.83e3.89 (m, 2H), 3.69e3.77 (m, 2H), 3.37 (s, 3H), 2.14e2.31
(m, 1H), 1.69e1.84 (m, 1H); C NMR (100 MHz, DMSO-d ): d 158.1,
6
149.2, 144.6, 139.4, 132.0, 131.8, 129.8,128.4,127.7, 124.0, 106.2, 83.4,
55.6, 51.5, 49.9, 47.1, 38.1, 37.8. HRMS-ESI (m/z): calcd for
13
(
3
d
8.54 (br s, 1H), 7.62 (d, J¼7.2 Hz, 1H), 7.29 (d,
J¼8.0 Hz, 1H), 6.14 (br, 1H), 5.08 (d, J¼15.6 Hz, 1H), 4.80 (br s, 1H),
4
3
0
1
3
.55 (d, J¼15.6 Hz, 1H), 4.21e4.28 (m, 1H), 3.92e3.99 (m, 1H),
3
5
.44e3.60 (m, 2H), 3.29 (t, J¼4.4 Hz, 1H), 1.47e1.73 (m, 7H),
C
20
H
20
N
4
O
3
Cl
excess: 26% for major diastereoisomer, 30% for minor di-
astereoisomer. HPLC analysis; PC-2, MeOH/H
O¼90/10, 0.7 mL/
min, 254 nm, major diastereoisomer,
¼11.7 min (major),
¼12.7 min (minor); minor diastereoisomer, t ¼22.1 min (major),
¼36.7 min (minor). IR (Neat):2930, 1557, 1490, 1459, 1323, 1272,
2
(Mþ): 435.0985; found: 435.0975. Enantiometric
.87e1.25 (m, 6H); 13C NMR (100 MHz, CDCl
): d 158.8, 151.0, 149.6,
3
38.6, 130.6, 124.1, 107.7, 77.5, 51.8, 48.7, 44.5, 40.7, 39.4, 33.0, 31.5,
2
3
5
0.2, 26.3, 26.2. HRMS-ESI (m/z): calcd for C19
15.1507; found: 415.1509. Enantiometric excess: 95%. HPLC anal-
ysis; PC-2, MeCN/H ¼11.2 min
O¼90/10, 0.7 mL/min, 214 nm, t
major), t
¼16.3 min (minor). IR (Neat):3218, 2925, 2851, 1553,
H
25
N
4
O
3
Cl (Mþ):
t
R
4
t
t
R
R
2
R
R
ꢀ
1
(
R
1148, 1082, 1023 cm
.
ꢀ
1
1
462, 1393, 1281, 1209, 1132, 1025 cm
.
4
.3.12. (5R,7S)-7-(3-chlorophenyl)-1-((6-chloropyridin-3-yl)
4
. 3. 8. (5R, 7R)-1-benzyl-8-nitro-7-propyl-1, 2, 3, 5, 6, 7-
3h. Yellow solid, mp
20.1 (c 0.5, MeOH). H NMR (400 MHz,
7.32e7.35 (m, 2H), 7.26e7.28 (m, 3H), 6.26 (d,
J¼6.4 Hz, 1H), 4.65e4.81 (m, 3H), 3.67e3.76 (m, 2H), 3.50e3.59 (m,
H), 3.17 (t, J¼6.4 Hz, 1H), 1.86e1.89 (m, 2H), 1.40e1.44 (m, 1H),
methyl)-5-methoxy-8-nitro-1,2,3,5,6,7-hexahydroimidazo[1,2-a]pyri-
ꢁ
25
hexahydroimidazo[1,2-a]pyridin-5-ol
dine 3l. Yellow solid, mp 84e86 C. 80% yield. [
a
]
D
13.0 (c 0.5,
ꢁ
27
1
1
130e131 C. 83% yield. [
a
]
D
MeOH). H NMR (400 MHz, CDCl
3
):
d
8.37 (br s, 1H), 7.84 (d,
DMSO-d ):
6
d
J¼8.4 Hz, 1H), 7.31 (d, J¼8.4 Hz, 1H), 7.16e7.20 (m, 1H), 7.11e7.14 (m,
2H), 6.94 (d, J¼7.2 Hz, 1H), 5.06 (d, J¼14.8 Hz, 1H), 4.63 (d,
2
J¼15.2 Hz, 1H), 4.38e4.43 (m, 1H), 4.33 (dd, J
1
¼7.2 Hz, J ¼9.6 Hz,
2
13
1
(
5
C
.19e1.28 (m, 2H), 1.09e1.11 (m, 1H), 0.82 (t, J¼6.8 Hz, 1H); C NMR
100 MHz, DMSO-d ): 157.9, 136.7, 128.3, 127.6, 127.3, 107.4, 75.9,
3.3, 48.5, 44.4, 35.8, 35.5, 33.3,19.7, 14.0. HRMS-ESI (m/z): calcd for
(Mþ): 318.1812; found: 318.1809. Enantiometric ex-
O¼90/10, 0.5 mL/min,
¼13.6 min (minor). IR (Neat): 3213,
956, 2928, 2871, 1665, 1557, 1545, 1393, 1287, 1208, 1123, 1099,
1H), 3.72e3.93 (m, 2H), 3.49e3.61 (m, 2H), 3.38 (s, 3H), 2.28e2.41
13
6
d
3
(m, 1H), 1.86e1.92 (m, 1H); C NMR (100 MHz, CDCl ): d 158.5,
151.3, 149.2, 146.5, 139.4, 134.3, 130.5, 129.8, 126.6, 126.5, 124.9,
124.6, 107.4, 83.9, 55.9, 52.8, 49.7, 46.0, 38.8, 36.9. HRMS-ESI (m/z):
17
23
H N
3
O
3
3
5
cess: 66%. HPLC analysis; PC-4, MeCN/H
2
2
2
calcd for C20
tiometric excess: 51% for major diastereoisomer, 92% for minor
diastereoisomer. HPLC analysis; PC-2, MeOH/H
O¼90/10, 0.7 mL/
min, 254 nm, major diastereoisomer,
¼10.6 min (major),
¼12.1 min (minor); minor diastereoisomer, t ¼18.7 min (major),
¼39.3 min (minor). IR (Neat): 2931, 1557, 1515, 1462, 1324, 1272,
H
20
N
4
O
3
Cl
2
(Mþ): 435.0985; found: 435.0976. Enan-
30 nm, t
R
¼11.3 min (major), t
R
2
ꢀ
1
1029 cm
.
t
R
t
t
R
R
4
.3.9. (5R,7R)-1-((2-chlorothiazol-5-yl)methyl)-8-nitro-7-propyl-
R
ꢀ
1
1,2,3,5,6,7-hexahydroimidazo[1,2-a]pyridin-5-ol 3i. Yellow solid, mp
1150, 1080, 1022 cm .
ꢁ
27
1
146e147 C. 85% yield. [
a]
D
ꢀ248.1 (c 0.5, MeOH). H NMR
(
400 MHz, DMSO-d ):
6
d
7.62 (s, 1H), 6.29 (d, J¼6.8 Hz, 1H),
4.3.13. (5R,7S)-7-(2-chlorophenyl)-1-((6-chloropyridin-3-yl)
methyl)-5-methoxy-8-nitro-1,2,3,5,6,7-hexahydroimidazo[1,2-a]pyri-
4
.72e4.83 (m, 3H), 3.57e3.73 (m, 4H), 3.15 (t, J¼6.0 Hz, 1H), 1.87 (t,
ꢁ
27
J¼5.6 Hz, 1H), 1.51e1.55 (m, 1H), 1.23e1.31 (m, 2H), 1.17e1.20 (m,
dine 3m. Yellow solid, mp 103e104 C. 72% yield. [
MeOH). H NMR (400 MHz, CDCl
a
]
D
ꢀ23.5 (c 0.5,
13
1
1
H), 0.86 (t, J¼7.2 Hz, 3H); C NMR (100 MHz, DMSO-d
6
):
d
157.4,
3
):
¼8.0 Hz, 1H), 7.31 (d, J¼8.4 Hz, 1H), 7.11e7.20 (m, 3H),
6.95 (d, J¼7.2 Hz, 1H), 6.94 (d, J¼7.2 Hz, 1H), 5.06 (d, J¼15.2 Hz, 1H),
4.62 (d, J¼15.2 Hz, 1H), 4.39e4.43 (m, 1H), 4.33 (dd, J ¼7.2 Hz,
¼9.6 Hz, 1H), 3.72e3.85 (m, 2H), 3.57e3.70 (m, 2H), 3.38 (s, 3H),
d 8.37 (br s, 1H), 7.85 (dd,
151.4, 141.0, 136.2, 107.7, 75.7, 48.4, 47.2, 44.4, 35.5, 35.4, 32.8, 19.7,
J
1
¼2.0 Hz, J
1
3
5
1
4.0. HRMS-ESI (m/z): calcd for C14
found: 359.0934. Enantiometric excess: 88%. HPLC analysis; PC-4,
MeCN/H ¼10.0 min (major),
O¼90/10, 0.5 mL/min, 254 nm, t
¼10.5 min (minor). IR (Neat): 3207, 2955, 2926, 2871, 1557, 1531,
H
19
N
4
O
3
S
Cl (Mþ): 359.0939;
1
2
R
J
2
13
t
R
2.27e2.42 (m, 1H), 1.86e1.92 (m, 1H); C NMR (100 MHz, CDCl
3
):
ꢀ
1
1372, 1289, 1139, 1052 cm
.
d
158.5, 151.3, 149.2, 146.5, 139.4, 134.3, 130.5, 129.8, 126.6, 126.5,
1
24.9, 124.6, 107.4, 83.9, 55.9, 52.8, 49.7, 46.0, 38.8, 36.9. HRMS-ESI
3
5
4
7
.3.10. (5R,7S)-1-((6-chloropyridin-3-yl)methyl)-5-methoxy-8-nitro-
(m/z): calcd for C20
20
H N
4
O
3
Cl
2
(Mþ): 435.0985; found: 435.0977.
4
a
-phenyl-1,2,3,5,6,7-hexahydroimidazo[1,2-a]pyridine 3j. Yellow
Enantiometric excess: 47% for major diastereoisomer, 88% for minor
diastereoisomer. HPLC analysis; PC-2, MeOH/H
O¼90/10, 0.7 mL/
min, 254 nm, major diastereoisomer,
¼10.6 min (major),
¼12.1 min (minor); minor diastereoisomer, t ¼17.7 min (major),
¼28.2 min (minor). IR (Neat): 2927, 1557, 1462, 1269, 1143, 1078,
ꢁ
27
1
solid, mp 94e96 C. 77% yield. [
400 MHz, CDCl ):
8.36 (d, J¼1.6 Hz, 1H), 7.84 (dd, J
¼8.0 Hz, 1H), 7.28 (d, J¼8.0 Hz, 1H), 7.23 (d, J¼7.6 Hz, 2H),
.14e7.18 (m, 1H), 7.04 (d, J¼7.2 Hz, 2H), 5.01 (d, J¼15.2 Hz, 1H), 4.65
d, J¼15.2 Hz,1H), 4.36e4.42 (m, 2H), 3.72e3.85 (m, 2H), 3.54e3.64
a
]
D
2.9 (c 0.5, MeOH). H NMR
2
(
3
d
1
¼2.0 Hz,
t
R
J
2
t
t
R
R
7
R
ꢀ
1
(
(
(
1021 cm
.
13
m, 2H), 3.36 (s, 3H), 2.34e2.40 (m,1H),1.95e2.02 (m,1H); C NMR
100 MHz, CDCl ): 158.4, 151.2, 149.2, 143.8, 139.4, 130.7, 128.1,
26.5, 126.3, 124.5, 107.9, 84.1, 55.6, 52.6, 49.8, 45.8, 39.0, 36.5.
3
d
4.3.14. (5R,7S)-1-((6-chloropyridin-3-yl)methyl)-7-(4-fluorophenyl)-
5-methoxy-8-nitro-1,2,3,5,6,7-hexahydroimidazo[1,2-a]pyridine
1
3
5
ꢁ
27
HRMS-EI (m/z): calcd for C20
4
5
H
21
N
4
O
3
Cl (Mþ): 400.1302; found:
3n. Yellow solid, mp 160e163 C. 67% yield. [
a]
D
23.5 (c 0.5,
1
00.1329. Enantiometric excess: 78% for major diastereoisomer,
8% for minor diastereoisomer. HPLC analysis; PC-2, MeOH/
MeOH). H NMR (400 MHz, DMSO-d
6
):
¼8.0 Hz, 1H), 7.53 (d, J¼8.4 Hz, 1H), 6.98e7.02 (m,
4H), 4.90 (d, J¼15.6 Hz, 1H), 4.71 (d, J¼15.6 Hz, 1H), 4.60 (m, 1H),
4.01 (dd, J ¼11.6 Hz, 1H), 3.76e4.04 (m, 4H), 3.37 (s, 3H),
¼6.8 Hz, J
2.18e2.32 (m, 1H), 1.71e1.78 (m, 1H); C NMR (100 MHz, DMSO-
):
160.7 (d, JCeF¼239.4 Hz), 158.7, 149.7, 142.0 (d, JCeF¼2.5 Hz),
39.8, 132.3, 128.7 (d, JCeF¼7.6 Hz), 124.5, 114.9 (d, JCeF¼21.0 Hz),
106.9, 83.9, 56.0, 52.0, 50.3, 47.6, 38.5, 38.4. HRMS-ESI (m/z): calcd
d
8.42 (d, J¼1.6 Hz, 1H), 7.89
(dd, J
1
¼2.0 Hz, J
2
H
2
O¼90/10, 0.5 mL/min, 254 nm, major diastereoisomer,
¼15.74 min (major), t ¼17.7 min (minor); minor diastereoisomer,
¼30.3 min (major), t ¼51.8 min (minor). IR (Neat): 2931, 2891,
t
t
R
R
1
2
13
R
R
ꢀ
1
1561, 1460, 1249, 1145, 1080, 1022 cm
.
d
6
d
1
4
5
.3.11. (5R,7S)-7-(4-chlorophenyl)-1-((6-chloropyridin-3-yl)methyl)-
-methoxy-8-nitro-1,2,3,5,6,7-hexahydroimidazo[1,2-a]pyridine
3
5
for C20
metric excess: 36% for major diastereoisomer, 37% for minor di-
astereoisomer. HPLC analysis; PC-2, MeOH/H
O¼90/10, 0.7 mL/
min, 254 nm, major diastereoisomer,
¼9.6 min (major),
¼10.4 min (minor); minor diastereoisomer, t ¼17.2 min (major),
H
20
N
4
O
3
ClF (Mþ): 419.1281; found: 419.1274. Enantio-
ꢁ
27
3
k. Yellow solid, mp 192e195 C. 77% yield. [
a
]
D
3.2 (c 0.5, MeOH).
8.42 (br, 1H), 7.88e7.90 (m, 1H),
.53 (d, J¼8.4 Hz, 1H), 7.21e7.25 (m, 2H), 6.98e7.01 (m, 2H), 4.89 (d,
J¼15.6 Hz, 1H), 4.60e4.74 (m, 2H), 4.00 (dd, J ¼6.8 Hz, J ¼11.2 Hz,
1
H NMR (400 MHz, DMSO-d
6
):
d
2
7
t
R
1
2
t
R
R