Chiral Cinchona Alkaloid-Thiourea Catalyzed Mannich Reaction
N 7.56; found C 64.92, H 5.32, N 7.68.
as determined by HPLC [Daicel Chiralpak IA, hexane/
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1
EtOH=99/1, 1.0 mL•min , λ=270 nm, tR(major)=
3-{(2-Chlorophenyl)[(4-methylbenzo[d]thiazol-2-yl)-
amino]methyl}pentane-2,4-dione (3b)
16.91 min, tR(minor)=18.46 min], [α]2D5 +93.2 (c 1.03,
1
CHCl3); H NMR (CDCl3, 500 MHz) δ: 7.39 (t, J=8.0
White solid, 94% yield, m.p. 126—127 ℃; 80% ee
Hz, 1H, ArH), 7.36 (dd, J=1.8, 8.1 Hz, 1H, ArH), 7.25
(dd, J=1.2, 7.5 Hz, 1H, ArH), 7.08 (d, J=6.9 Hz, 1H,
ArH), 6.98 (t, J=7.5 Hz, 1H, ArH), 6.93—6.90 (m, 2H,
ArH), 6.59 (d, J=10.3 Hz, 1H, NH), 5.77 (t, J=9.8 Hz,
1H, CH), 4.62 (d, J=8.0 Hz, 1H, CH), 3.97 (s, 3H,
OCH3), 2.53 (s, 3H, CH3), 2.19 (s, 3H, CH3), 2.13 (s,
3H, CH3); 13C NMR (CDCl3, 125 MHz) δ: 204.1, 202.3,
165.4, 156.5, 151.1, 130.4, 130.0, 129.4, 129.1, 126.6,
125.8, 121.7, 121.0, 118.2, 110.9, 70.5, 56.8, 55.6, 30.2,
29.9, 18.3; IR (KBr) ν: 3306, 3022, 1722, 1701, 1541,
as determined by HPLC [Daicel Chiralpak IA, hexane/
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1
EtOH=99/1, 1.0 mL•min , λ=270 nm, tR(major)=
13.77 min, tR(minor)=15.05 min], [α]2D5 +81.6 (c 1.02,
1
CHCl3); H NMR (CDCl3, 500 MHz) δ: 7.49 (t, J=4.6
Hz, 1H, ArH), 7.40 (t, J=8.6 Hz, 2H, ArH), 7.23 (t, J=
4.0 Hz, 2H, ArH), 7.08 (d, J=6.9 Hz, 2H, ArH), 6.98 (t,
J=7.5 Hz, 1H, NH), 6.13 (dd, J=4.6, 9.2 Hz, 1H, CH),
4.51 (d, J=4.6 Hz, 1H, CH), 2.50 (s, 3H, CH3), 2.41 (s,
3H, CH3), 2.07 (s, 3H, CH3); 13C NMR (CDCl3, 125
MHz) δ: 206.0, 202.7, 164.6, 151.3, 136.4, 132.6, 130.8,
130.1, 129.6, 129.5, 129.4, 127.6, 126.9, 122.1, 118.5,
67.5, 55.6, 32.4, 29.5, 18.5; IR (KBr) ν: 3422, 2914,
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1
1244, 766, 752 cm . Anal. calcd for C21H22N2O3S: C
65.95, H 5.80, N 7.32; found C 66.26, H 5.91, N 7.62.
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1721, 1705, 1539, 1472, 1200, 770, 744 cm . Anal.
calcd for C20H19ClN2O2S: C 62.09, H 4.95, N 7.24;
found C 62.13, H 5.21, N 7.34.
3-{(2-Nitrophenyl)[(4-methylbenzo[d]thiazol-2-yl)-
amino]methyl}pentane-2,4-dione (3f)
Light yellow solid, 94% yiled, m.p. 118—120 ℃;
80% ee as determined by HPLC [Daicel Chiralpak IA,
hexane/EtOH =99/1, 1.0 mL•min - 1, λ =270 nm,
tR(major)=26.21 min, tR(minor)=30.80 min], [α]D25
-223.3 (c 1.10, CHCl3); 1H NMR (CDCl3, 500 MHz) δ:
8.03 (dd, J=1.7, 8.6 Hz, 1H, ArH), 7.72 (dd, J=1.2 Hz,
J=8.1 Hz, 1H, ArH), 7.58—7.54 (m, 1H, ArH), 7.44—
7.41 (m, 1H, ArH), 7.36 (d, J=8.0 Hz, 1H, ArH), 7.29
(t, J=8.0 Hz, 1H, ArH), 7.05 (d, J=7.5 Hz, 1H, ArH),
6.98 (t, J=7.5 Hz, 1H, NH), 6.41 (dd, J=4.0, 9.2 Hz,
1H, CH), 4.61 (d, J=3.5 Hz, 1H, CH), 2.48 (s, 3H,
CH3), 2.41 (s, 3H, CH3), 2.12 (s, 3H, CH3); 13C NMR
(CDCl3, 125 MHz) δ: 206.8, 202.9, 163.6, 150.8, 148.8,
135.3, 133.9, 130.5, 129.9, 129.7, 128.8, 126.6, 125.0,
122.1, 118.2, 67.2, 53.6, 32.9, 29.0, 18.0; IR (KBr) ν:
3-{(4-Fluorophenyl)[(4-methylbenzo[d]thiazol-2-yl)-
amino]methyl}pentane-2,4-dione (3c)
White solid, 94% yield, m.p. 120—121 ℃; 79% ee
as determined by HPLC [Daicel Chiralpak IA, hexane/
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1
EtOH=99/1, 1.0 mL•min , λ=270 nm, tR(major)=
20.59 min, tR(minor)=23.25 min], [α]2D5 +46.1 (c 1.06,
CHCl3); 1H NMR (CDCl3, 500 MHz) δ: 7.40—7.37 (m,
3H, ArH), 7.09—6.97 (m, 4H, ArH), 6.57 (brs, 1H, NH),
5.72 (d, J=8.0 Hz, 1H, CH), 4.36 (d, J=8.1 Hz, 1H,
CH), 2.50 (s, 3H, CH3), 2.21 (s, 3H, CH3), 2.19 (s, 3H,
CH3); 19F NMR (CDCl3, 470 MHz) δ: -113.6; 13C
NMR (CDCl3, 125 MHz) δ: 204.1, 204.0, 201.8, 164.5,
163.3, 161.3, 134.8, 130.5, 130.4, 129.3, 128.7, 128.6,
126.7, 122.0, 118.3, 115.9, 115.7, 72.3, 57.4, 30.4, 30.2,
18.3; IR (KBr) ν: 3314, 2913, 1724, 1694, 1537, 1508,
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3387, 2914, 1719, 1705, 1541, 1524, 1342, 745 cm .
Anal. calcd for C20H19N3O4S: C 60.44, H 4.82, N 10.57;
found C 60.85, H 4.93, N 10.78.
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1
1246, 843, 771 cm . Anal. calcd for C20H19FN2O2S: C
64.85, H 5.17, N 7.56; found C 64.96, H 5.32, N 7.68.
3-{(4-Chlorophenyl)[(4-methylbenzo[d]thiazol-2-yl)-
amino]methyl}pentane-2,4-dione (3d)
Conclusions
We have developed an efficient catalytic Mannich
reaction of heterocyclic imines derived from benzothia-
zole with acetylacetone in the presence of a chiral bi-
functional organocatalyst Q-1. The resulting novel
β-amino ketones bearing benzothiazole moiety are ob-
tained in high yields (90%—95%) and good enantiose-
lectivities (72%—84% ee). We anticipate that this
method would be useful in the preparation of bioactive
chiral β-amino ketone derivatives containing benzothi-
azole group, the availability of which should aid me-
dicinal and chemical studies. Further studies on the
scope of the new catalyst Q-1 in other asymmetric
transformations and anti-plant viral activity of the Man-
nich products are currently underway.
White solid, 91% yiled, m.p. 110—111 ℃; 72% ee
as determined by HPLC [Daicel Chiralpak IA, hexane/
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1
EtOH=99/1, 1.0 mL•min , λ=270 nm, tR(major)=
21.00 min, tR(minor)=24.14 min], [α]2D5 -176.8 (c
1
1.08, CHCl3); H NMR (CDCl3, 500 MHz) δ: 7.39—
7.26 (m, 5H, ArH), 7.09—6.97 (m, 2H, ArH), 6.52 (brs,
1H, NH), 5.77 (d, J=7.5 Hz, 1H, CH), 4.35 (d, J=7.5
Hz, 1H, CH), 2.50 (s, 3H, CH3), 2.21 (s, 3H, CH3), 2.21
(s, 3H, CH3); 13C NMR (CDCl3, 125 MHz) δ: 204.3,
202.0, 164.7, 151.1, 137.8, 134.2, 130.7, 129.6, 129.2,
128.6, 127.0, 122.3, 118.5, 72.3, 57.6, 30.7, 30,4, 18.6;
IR (KBr) ν: 3360, 2916, 1722, 1697, 1533, 1487, 1200,
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761, 745 cm . Anal. calcd for C20H19ClN2O2S: C 62.09,
H 4.95, N 7.24; found C 62.36, H 5.11, N 7.32.
3-{(2-Methoxyphenyl)[(4-methylbenzo[d]thiazol-2-yl)-
amino]methyl}pentane-2,4-dione (3e)
References
1
(a) Huguenot, F.; Brigaud, T. J. Org. Chem. 2006, 71, 2159.
White solid, 90% yiled, m.p. 119—120 ℃; 75% ee
Chin. J. Chem. 2011, 29, 2433— 2438
© 2011 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
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