Yao et al.
FULL PAPER
over Na2SO4. After removal of the solvent, the residue
was purified by column chromatography on silica gel
(10% MeOH in CH2Cl2) to afford 3a-3b.
monitored by conducting thin layer chromatography on
silica gel. After completion of the reaction, target com-
pound was separated from the reacting system by
preparative thin layer chromatography on silica gel (pe-
troleum ether/EtOAc=5/1) to afford final product.
Preparation of chiral Brønsted acid catalyst 3c
Method A From 2c, by following the same route
as for chiral Brønsted acid catalysts 3a-3b, 3c (0.03 g,
11%) was obtained as a white solid.
Dimethyl 2-((4-methylbenzo[d]thiazol-2-ylamino)(4-
fluorophenyl)-methyl)malonate
20
As a colorless oil; yield: 0.041 g, 92%; [α]D –19.9
Method B Under argon, to a solution of 2d (0.26 g,
0.38 mmol) in pyridine (5 mL), NaH (0.01 g, 0.45 mmol)
was added and stirred at 0 ℃. After 30 min, phosphorus
oxychloride (0.2 mL) was added dropwise at 0 ℃, and
the reaction mixture was allowed to warm up to room
temperature and stirred for 6 h. The reaction mixture
was quenched with water (10 mL) at 0 ℃, and stirred
for 4 h at 35 ℃. CH2Cl2 (10 mL) was added to dissolve
the precipitate, and pyridine was removed by reverse
extraction with aqueous 3 mol/L HCl (30 mL×3). The
organic phase was dried over Na2SO4. After removal of
the solvent, the residue was purified by column chro-
matography on silica gel (10% MeOH in CH2Cl2) to
afford 3c (0.14 g, 52%) as a white solid.
(c 0.55, CHCl3); ee 91%. HPLC: Chiracpak, IA (Hex-
ane/Ethanol=75/25), Flow rate=1 mL/min, UV=254
nm, tR(major)=5.2 min, tR(minor)=6.0 min. 1H NMR
(500 MHz CDCl3) δ: 7.37-7.44 (m, 3H), 7.13-6.96
(m, 4H), 5.61 (d, J=5.7 Hz, 1H), 3.99 (d, J=5.2 Hz,
1H), 3.85 (d, J=1.2 Hz, 1H), 3.69 (s, 6H), 2.50 (s, 3H).
13C NMR (125 MHz, CDCl3) δ: 168.31, 167.16, 165.07,
151.11, 134.41, 130.54, 129.31, 128.56 (d, J=8.3 Hz),
126.77, 121.89, 118.32, 115.86 (d, J=21.4 Hz), 57.68,
56.98, 53.20 (d, J=29.8 Hz), 18.41; 19F NMR (470
MHz, CDCl3) δ: –113.80. Anal. calcd for C20H19N2O4FS:
C 59.69, H 4.76, N 6.96; found C 59.45, H 4.20, N 6.87.
ESI-MS m/z: 403.1[M+H]+.
Chiral Brønsted acid catalyst 3a (C44H31O6P3)
White solid. Yield 0.17 g, 60%. m.p. 212-214 ℃.
Dimethyl 2-(1-((4-chlorobenzo[d]thiazol-2-yl)amino)-
3-phenylallyl)malonate
1
[α]2D0 +161.3 (c 1.00, CHCl3); H NMR (500 MHz,
As a colorless oil; yield: 90%; [α]D20 −15.1 (c 0.52,
CHCl3); ee 95%. HPLC: Chiracpak, IA (hexane/
ethanol=85/15), flow rate=1 mL/min, UV=254 nm,
CDCl3) δ: 6.87 (s, 1H, OH), 7.18-7.35 (m, 4H), 7.40-
7.86 (m, 26H); 31P NMR (200 MHz, CDCl3) δ: –1.46,
31.82, 35.12 (t, 3P). ESI-MS m/z: 749.2 [M+H]+.
Chiral Brønsted acid catalyst 3b (C38H23N2O4P)
White solid. Yield 0.13 g, 57%. m.p.>250 ℃. [α]D20
–487.88 (c 0.99, CHCl3); 1H NMR (500 MHz, DMSO) δ:
9.25 (s, 2H), 8.84 (s, 2H), 8.70 (d, J=8.6 Hz, 2H),
8.41 (d, J=8 Hz, 2H), 8.29-8.34 (m, 3H), 8.15 (t, J=
7.4 Hz, 2H), 8.08 (t, J=6.3 Hz, 2H), 7.96 (t, J=7.4 Hz,
2H), 7.67 (t, J=7.4 Hz, 2H), 7.56 (t, J=8 Hz, 2H), 7.35
(d, J=8.6 Hz, 2H); 13C NMR (125 MHz, CDCl3) δ:
155.31, 152.60, 142.02, 135.08, 132.88, 127.76, 126.36,
125.62, 125.22, 125.02, 124.81, 124.19, 123.99, 121.96,
120.56, 118.73, 115.70, 115.36; 31P NMR (200 MHz,
CDCl3) δ: 8.49 (s, 1P). ESI-MS m/z: 601.2 [M–H]+.
Method A Chiral Brønsted acid catalyst 3c
1
tR(major)=8.5 min, tR(minor)=9.9 min. H NMR (500
MHz CDCl3) δ: 7.22-7.53 (m, 9H), 6.70 (d, J=16 Hz,
1H), 6.25-6.31 (dd, J=30 Hz, 1H), 5.26-5.29 (m,
1H), 3.94 (d, J=4.6 Hz, 1H), 3.72 (s, 3H), 3.78 (s, 3H);
13C NMR (125 MHz, CDCl3) δ: 168.4, 167.5, 166.1,
150.8, 135.8, 133.5, 132.0, 128.6, 128.3, 127.1, 126.8,
126.4, 125.1, 120.5, 120.0, 56.4, 55.3, 53.1, 52.9. Anal.
calcd for C21H18N2O4ClS: C 58.67, H 4.22, N 6.52;
found C 58.16, H 3.98, N 6.21. ESI-MS m/z: 431.3
[M+H]+.
Dimethyl 2-(1-(benzo[d]thiazol-2-ylamino)-3-phenyl-
allyl)malonate
20
As a colorless oil; yield: 86%; [α]D –13.5 (c 0.55,
(C46H33O6P), white solid. m.p.>250 ℃. [α]20
CHCl3); ee 93%. HPLC: Chiracpak, IA (hexane/ethanol
=85/15), flow rate=1 mL/min, UV=254 nm, tR(major)
D
+203.2 (c 1.00, CHCl3); 1H NMR (500 MHz, DMSO) δ:
7.64 (d, J=8.6 Hz, 2H), 7.49-7.51 (m, 4H), 7.27-
7.38 (m, 16H), 7.14-7.17 (m, 7H), 7.04-7.11 (m, 4H);
13C NMR (125 MHz, CDCl3) δ: 149.60, 146.76, 139.14,
132.41, 131.18, 130.52, 129.75, 129.07, 128.25 (d, J=
13.1 Hz), 127.37 (d, J=16.6 Hz), 126.41, 126.10,
125.90, 124.20, 79.65; 31P NMR (200 MHz, CDCl3) δ:
5.98 (s, 1P). ESI-MS m/z: 711.3 [M–H]+.
1
=7.8 min, tR(minor)=8.5 min. H NMR (500 MHz,
CDCl3) δ: 7.56 (t, J=7.15 Hz, 2H), 7.22-7.36 (m, 6H),
7.09 (t, J=8.0 Hz, 1H), 6.71 (d, J=16 Hz, 1H), 6.27-
6.31 (dd, J=20 Hz, 1H), 5.28 (s, 1H), 4.09-4.14 (q,
J=7.45 Hz, 1H), 3.96 (d, J=4.6 Hz, 1H), 3.78 (s, 3H),
3.72 (s, 3H); 13C NMR (125 MHz, CDCl3) δ: 168.4,
167.5, 166.0, 135.9, 133.2, 130.4, 128.6, 128.2, 126.8,
126.0, 125.3, 122.0, 120.9, 119.3, 56.5, 55.4, 53.1, 52.9.
Anal. calcd for C21H19N2O4S: C 63.78, H 4.84, N 7.08;
found C 63.36, H 5.26, N 7.11. ESI-MS m/z: 397.4 [M
+H]+.
General procedure for asymmetric Mannich reaction
A mixture of imines (0.11 mmol) and catalyst 3c
loading 10 mol% (0.0078 g, 0.011 mmol) in m-xylene (2
mL) was stirred for 30 min at room temperature. The
system was then cooled down to –40 ℃ and stirred for
5 min; dimethyl malonate 4 (0.02 g, 0.17 mmol) was
added dropwise and the progress of the reaction was
Dimethyl 2-((benzo[d]thiazol-2-ylamino)(thiophen-2-
yl)methyl)malonate
As a white solid; yield: 83%; [α]2D0 +18.9 (c 0.51,
604
© 2015 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2015, 33, 601—609