1
070
Z. Wang et al. / Tetrahedron Letters 56 (2015) 1067–1071
O
O
O
+
-
Ph
N
Ph
N
cat. Q X
O
*
O
+
RX
Ph
solvent. MOH
Ph
R
O
Q+
asymmetric
induction
O
Ph
N
Ph
N
*
O
RX
Ph
R
Ph
H O
2
+
Q X-
+
-
Q OH
O
Ph
N
organic phase
interface
O
Ph
_
__________________________________________________________________________________________
aqueous phase
+
Q X-
+
-
MOH
+
MX
+
Q OH
Scheme 1. Possible mechanism of asymmetric alkylation of glycine Schiff base.
+
À
formed and the catalysts Q X were reformed and re-transferred to
the aqueous layer to form the catalytic cycle.
mixture was further refluxed for 12 h and the reaction was monitored by
TLC. After the completion of the reaction, the solvent was evaporated and the
residue was purified with silica gel (chloroform/methanol = 30:1) to give the
We successfully designed and synthesized a series of new chiral
phase-transfer catalysts with the structure of 8-atom cycle derived
from cinchona alkaloids. These new catalysts were applied in the
asymmetric alkylation of glycine derivatives with high yields and
moderate to excellent enantioselectivity. Further work is
under way to understand the mechanism and improve the
enantioselectivity.
product (0.24 g, 70% yield).
H NMR (500 MHz, CDCl ): 8.9188–8.9043 (m, 1H), 8.2234–8.1656 (m, 2H),
3
1
7
6
.7959–7.6351 (m, 2H), 7.4242–7.4097 (m, 1H), 6.4735–6.4328 (m, 1H),
.1463–6.0199 (m,1H), 5.8805 (s, 1H), 5.7594–5.6443 (m, 2H), 5.0114–4, 9213
(
m, 3H), 4.8283–4.7940 (m, 1H), 3.4942–3.4170 (m, 1H), 3.2820–3.1826 (m,
2H), 2.8837–2.7382 (m, 2H), 2.3971 (s, 1H), 1.9077–1.8730 (m, 3H),1.6735–
1
.5299 (m, 2H) 13C NMR (500 MHz, CDCl
3
): 150.0278, 147.9949, 146.0408,
1
1
6
42.1767, 133.1039, 129.8867, 129.0374, 126.5786, 125.8792, 123.8068,
19.5861, 114.1071, 111.9291, 109.5361, 107.8249, 82.5908, 81.2770,
0.2081, 55.8686, 41.6474, 27.2226, 24.6763.
22
D 2 2
ES-MS: 347.2 (M); [a] +95.5° (c 0.2, CH Cl ) elemental analysis: calculated: C,
Acknowledgments
79.5; H, 7.8; N, 8.1. Found: C, 79.39; H, 7.89; N, 7.95.
(
1R,7R,10S,E)-1-(6-Methoxyquinolin-4-yl)-9-vinyl-1,3,6,8,9,10,11,11a-octahydro-
1
We were thankful to the National Natural Science Foundation of
China for their financial support (No. 21102180).
7,10-ethanopyrido[2,1-c][1,4]oxazocin-7-ium bromide (4b): 63% yield, H NMR
500 MHz, CDCl ): 8.7290–8.7204 (m,1H), 8.0506–8.0238 (m,1H), 7.3945–
.3349 (m,2H), 7.2528–7.2218 (m,1H), 6.4336–6.4090 (m, 1H), 6.0792–6.0454
m, 1H), 5.7119–5.6122 (m, 2H), 5.5391–5.5336 (m,1H), 4.9527–4.8838 (m,
2H), 4.7799–4.7595 (m, 1H), 3.9461–3.9340 (m, 3H), 3.3115 (s, 1H), 3.1652–
(
7
(
3
Supplementary data
3
1
(
.0853 (m, 2H), 2.7290–2.6179 (m, 2H), 2.2770 (s, 1H), 2.1537 (s, 2H), 1.8751–
.7688 (m, 4H), 1.5377–1.5175 (m, 3H), 1.2454–1.2100 (m, 1H) 13C NMR
3
500 MHz, CDCl ): 157.8505, 148.6980, 147.3576, 143.9983, 141.5296,
139.6108, 138.8185, 132.7581, 129.2598, 126.1965, 121.9891, 119.2893,
1
3
0
02.0956, 78.5066, 76.8134, 65.8451, 58.7737, 56.7155, 54.0146, 42.7227,
22
7.3716, 26.7743, 24.7174, 20.4527, 18.0087 ES-MS: 377.2 (M); [
D
a] +100° (c
.2, CH Cl ) elemental analysis: calculated: C, 76.4; H, 7.7; N, 7.4; found: C,
2
2
References and notes
76.28; H, 7.92; N, 7.58.
1S,7R,10S,E)-1-(6-Methoxyquinolin-4-yl)-9-vinyl-1,3,6,8,9,10,11,11a-octahydro-
,10-ethanopyrido[2,1-c][1,4]oxazocin-7-ium bromide (4c): 53.1% yield, 1H NMR
500 MHz, CDCl ): 8.7204–8.7193 (m,1H), 8.0601–8.0294 (m, 1H), 7.4040–
.3413 (m, 2H), 7.2626–7.2166 (m,1H), 6.4454–6.4046 (m, 1H), 6.1093–6.0400
(
7
(
7
1
2
3
4
5
6
.
.
.
.
.
.
3
(
m, 2H), 5.6780–5.5472 (m, 2H), 5.1599–5.0716 (m, 2H), 4.9482–4.8920 (m,
1
2
(
H), 4.7891–4.7547 (m, 1H), 3.9442–3.9328 (m, 3H), 3.1868–3.1019 (m, 2H),
.9826–2.7679 (m, 4H), 2.2706–2.2463 (m,1H), 1.7724 (s, 1H), 1.5069–1.4824
m, 3H), 1.2527–1.1816 (m, 2H), 0.9454–0.8975 (m, 1H) 13C NMR (500 MHz,
3
CDCl ): 157.1687, 150.1687, 147.3799, 145.8176, 144.0027, 140.8254,
7
8
.
.
1
8
2
33.1505, 131.2325, 129.6808, 126.9962, 121.2880, 119.2112, 102.2112,
2.2055, 80.6039, 60.2081, 55.4593, 49.9428, 49.0488, 48.3823, 39.6256,
22
7.7150, 25.9084, 24.6867 ES-MS: 377.2 (M);
[
a
]
D
À14° (c 0.2, CH
2 2
Cl )
9
.
elemental analysis: calculated: C, 76.4; H, 7.7; N, 7.4; found: C, 76.6; H, 7.45; N,
.57.
1R,7R,10S,E)-1-(Quinolin-4-yl)-9-vinyl-1,3,6,8,9,10,11,11a-octahydro-7,10-ethan-
1
1
1
1
7
(
1
opyrido[2,1-c][1,4]oxazocin-7-ium bromide (4d): 56.9% yield, H NMR (500 MHz,
CDCl ): 8.9185–8.9043 (m, 1H), 8.1907–8.1148 (m, 2H), 7.7660–7.6210
m,2H), 7.4260–7.4120 (m, 1H), 6.4651–6.4240 (m, 1H), 6.1454–6.0176 (m,
3
(
2
4
3
0
1
1
4
H), 5.9080–5.8020 (m,1H), 5.7185–5.6410 (m, 1H), 5.1782–5.0697 (m, 2H),
.9745–4.9180 (m,1H), 4.8213–4.7874 (m,1H), 3.2700–3.1762 (m, 3H),
.0660–2.9939 (m,2H), 2.8654 (s, 1H), 2.3483–2.1630 (m, 3H), 1.8380 (s, 2H),
1
1
1
6. Typical procedure of the synthesis of the catalysts 4a to 4d:
.9761–0.8701 (m, 2H) 13
3
C NMR (500 MHz, CDCl ): 149.9942, 147.9244,
45.8366, 140.6015, 133.0530, 129.8156, 129.0673, 126.6098, 125.8520,
23.8260, 119.3837, 118.8478, 82.0510, 80.6292, 68.2785, 59.9805, 49.0344,
(
1S,7R,10S,E)-1-(Quinolin-4-yl)-9-vinyl-1,3,6,8,9,10,11,11a-octahydro-7,10-ethan-
opyrido[2,1-c][1,4]oxazocin-7-ium bromide (4a): Cinchonidine (0.294 g, 1 mmol)
was dissolved in THF (5 ml), and sodium hydride (0.048 g, 2 mmol) was added.
The reaction mixture was stirred and heated to 80 °C and refluxed for 1 h, then
22
8.1538, 27.6099, 25.6839, 24.5560, 23.5513 ES-MS: 347.2 (M); [
Cl ) elemental analysis: calculated: C, 79.5; H, 7.8; N, 8.1; found: C, 79.63;
H, 7.31; N, 8.35.
D
a] +6° (c 0.2,
CH
2
2
(E)-1,4-dibromo-2-butene (0.321 g, 1.5 mmol) was added. The reaction