Catalytic Performance of Silica Supported Cinchona Alkaloids
1683
Table 1 Screening reaction conditions for the organocatalytic
asymmetric conjugate addition of 1a to maleimide 2 catalyzed by
Cat.I and Cat.II
Entry Solvent
T (d) Catalyst Yield dr
(%)a
ee
(%)
(syn)b
(syn/
anti)b
1
Toluene
CH2Cl2
4
4
4
4
4
4
4
5
4
4
4
4
4
4
CatI
CatI
CatI
CatI
CatI
CatI
CatI
CatI
CatI
CatII
CatII
CatII
CatII
CatII
83
86
82
74
93
52
71
61
87
87
86
82
74
93
82:18
80:20
78:22
77:23
64:36
49:51
45:55
84:16
75:25
75:25
63:37
68:32
63:37
62:38
84
80
74
78
71
45
45
80
75
78
70
71
69
67
2
3
Pseudocumene
CHCl3
4
5
CH3CN
Fig. 1 FT-IR spectra of silica-SH (a), silica-supported quinine
catalyst (b) and silica-supported cinchonine catalyst (c)
6
NMP
7
MeOH
8
Toluenec
Toluened
Toluene
CH2Cl2
smajor = 17.2 min, sminor = 20.1 min; minor diastereomer:
1
9
smajor = 21.8 min, sminor = 24.2 min]. H NMR(CDCl3):
10
11
12
13
14
d = 1.22 (t, J = 7.2, 3H), 1.93–2.03 (m, 2H), 2.08–2.20 (m,
1H), 2.35–2.50 (m, 3H), 2.60 (dd, J = 6.0, 18.0, 1H), 2.80 (dd,
J = 9.2, 18.0, 1H), 3.46 (dd, J = 6.0, 9.2, 1H), 4.17 (q, J = 7.2,
2H), 4.57 (AB, J = 14.2, 2H), 7.18–7.35 (m, 5H). 13C NMR
(CDCl3): d = 13.9 (CH3), 19.1 (CH2), 31.6 (CH2), 32.6 (CH2),
37.9 (CH2), 42.1 (CH), 42.2(CH2), 60.6 (C), 62.0 (CH2), 127.7
(CH), 128.3 (CH, 2C), 128.5 (CH, 2C), 135.4 (C), 169.5 (C),
175.0 (C), 177.0 (C), 213.5 (C). HRMS: m/z calcd for
C19H21NO5: 343.14197; found: 343.14173.
Pseudocumene
CHCl3
CH3CN
Experimental conditions (0.2 mmol scale): The reactions were stirred
at ambient temperature in 1 mL undistilled solvent with a 1:1.2 ratio
of 1a–2 and a certain amount of catalyst
a
Isolated yield
b
Determined by HPLC analysis
c
Reaction is performed in the presence of 5 mol% catalyst
2.3.2 3-(3-acetyl-2-oxotetrahydrofuran-3-yl)-1-
d
Reaction is performed in the presence of 20 mol% catalyst
benzylpyrrolidine-2,5-dione, 3b
White solid. [Daicel ChiralpakAD-H, hexane/i-PrOH = 80/
20, 0.75 mL/min, k 214 nm, major diastereomer: smi-
nor = 27.9 min, smajor = 33.2 min; minor diastereomer:
smajor = 20.0 min, sminor = 23.8 min]. 1H NMR
(CDCl3): d = 2.27 (s, 3H), 2.40–2.49 (m, 1H), 2.53 (dd,
J = 6.4, 18.4, 1H), 2.68–2.75 (m, 1H), 2.81 (dd, J = 9.2,
18.4, 1H), 3.35 (dd, J = 6.4, 9.2, 1H), 4.27–4.34 (m, 2H),
4.64 (AB, J = 14.4, 2H), 7.23–7.33 (m, 3H), 7.32–7.36 (m,
2H). 13C NMR (CDCl3): d = 25.9 (CH3), 28.7 (CH2), 31.7
(CH2), 42.1 (CH), 42.6 (CH2), 61.6 (C), 65.9 (CH2), 127.9
(CH), 128.5 (CH, 2C), 128.6 (CH, 2C), 135.3 (C), 173.6 (C),
174.4 (C), 176.1 (C), 200.7 (C). HRMS: m/z calcd for
C17H17NO5: 315.11067; found: 315.11085.
sminor = 32.7 min, smajor = 38.3 min]. 1H NMR (CDCl3):
d = 1.22 (t, J = 7.2, 3H), 1.50 (s, 3H), 2.24 (s, 3H), 2.44 (dd,
J = 6.0, 18.4, 1H), 2.85 (dd, J = 9.2, 18.4, 1H), 3.37 (dd,
J = 6.0, 9.2, 1H), 4.18 (q, J = 7.2, 2H), 4.64 (AB,
J = 14.0, 2H), 7.23-7.40 (m, 5H). 13C NMR (CDCl3):
d = 13.9 (CH3), 18.9 (CH3), 26.8 (CH3), 32.4 (CH2), 42.4
(CH2), 44.9(CH), 61.2 (C), 62.2 (CH2), 127.8 (CH), 128.5
(CH, 2C), 128.7 (CH, 2C), 135.6 (C), 170.7 (C), 175.2 (C),
177.0 (C), 204.2(C). HRMS: m/z calcd for C18H21NO5:
331.14197; found: 331.14163.
2.3.4 3-(1-acetyl-2-oxocyclopentyl)-1-benzylpyrrolidine-
2,5-dione, 3d
2.3.3 Ethyl 2-(1-benzyl-2,5-dioxopyrrolidin-3-yl)-2-
White foam. [Daicel Chiralpak AD-H, hexane/i-
PrOH = 75/25, 0.75 mL/min, k 214 nm, major diastereo-
mer: sminor = 15.2 min, smajor = 22.7 min; minor dia-
stereomer: sminor = 11.4 min, smajor = 13.8 min]. 1H
NMR (CDCl3): d = 1.80–2.00 (m, 3H), 2.19 (s, 3H), 2.35
(dd, J = 6.4, 18.4, 1H), 2.40–2.57 (m, 3H), 2.74 (dd,
methyl-3-oxobutanoate, 3c
White foam. [Daicel Chiralpak AS-H column, hexane/i-
PrOH = 80/20, 0.75 mL/min, k 214 nm, major diastereomer:
sminor = 21.3 min, smajor = 26.2 min; minor diastereomer:
123