498
S. Chandrasekhar et al. / Tetrahedron: Asymmetry 19 (2008) 495–499
Table 3. Asymmetric Aldol reaction of aromatic aldehydes with 4a using organocatalyst 1
OH
O
catalyst 1
R
CHO + 4a
R
TFA, neat
7
8
0 o
C
Entry
1
Aldehyde
Time (h)
12
Product
Yielda (%)
86
anti/synb (ratio)
eec (%)
26
CHO
8a
94:6
7a
CHO
2
3
14
10
10
8b
8c
8d
91
89
93
96:4
95:5
92:8
28
28
23
7b
MeO
CHO
7c
Br
O2N
CHO
4
7d
a Isolated yields.
b Determined by 1H NMR of the crude product.
c Determined by chiral HPLC of the anti product.
4.1.3. Representative procedure for the Michael reaction
(s, 1H), 4.70 (dd, 1H, J = 5.2, 6.9 Hz), 4.56 (dd, 1H,
J = 3.4, 8.6 Hz), 3.75 (dt, 1H, J = 2.6, 7.8 Hz), 2.70–2.52
(m, 1H), 2.50–2.24 (m, 2H), 2.17–1.80 (m, 3H), 1.73–1.56
(m, 2H), 1.45–1.20 (m, 1H); 13C NMR (CDCl3,
100 MHz): d 211.2, 143.5, 140.7, 121.3, 109.1, 78.2, 51.7,
42.5, 34.5, 32.3, 28.0, 24.9; IR (KBr): m 3133, 2937, 2866,
1707, 1551, 1504, 1442, 1382, 1312 cmꢁ1; ESIMS: m/z
260 (M+Na)+; HRMS calcd for C12H15NO4Na: 260.0898
(M+Na)+, found: 260.0895.
4.1.3.1. (S)-2-((R)-1-(2,5-Dimethoxyphenyl)-2-nitroethyl)
cyclohexanone 6b. Catalyst 1 (10.8 mg, 0.047 mmol) was
added to a mixture of cyclohexanone 4a (0.39 mL,
3.8 mmol) and TFA (0.008 mmol) at room temperature
and stirred for 15 min. 2,5-Dimethoxy nitrostyrene 5b
(100 mg, 0.47 mmol) at 0 °C was then added and stirred
for 16 h at the same temperature. The reaction mixture
was directly loaded on a silica-gel column to give adduct
25
6b (140.1 mg, 96% yield) as a semi solid: ½aꢀD ¼ ꢁ25:1 (c
0.6, CHCl3); 1H NMR (CDCl3, 300 MHz): d 6.78–6.67
(m, 2H), 6.61 (d, 1H, J = 3.0 Hz), 4.77 (d, 1H,
J = 2.2 Hz), 4.75 (s, 1H), 3.90–3.83 (m, 1H), 3.81 (s, 3H),
3.73 (s, 3H), 2.97–2.86 (m, 1H), 2.50–2.30 (m, 2H), 2.12–
2.03 (m, 1H), 1.84–1.52 (m, 4H), 1.28–1.19 (m, 1H); 13C
NMR (75 MHz, CDCl3): d 212.4, 153.5, 151.7, 127.8,
126.5, 117.3, 112.7, 112.0, 55.8, 55.5, 50.6, 42.6, 41.4, 33.1,
28.4, 25.1; IR (Neat): m 2940, 2860, 1706, 1550, 1503,
1448, 1380 cmꢁ1; ESIMS: m/z 330 (M+Na)+ HRMS calcd
for C16H21NO5Na: 330.1317 (M+Na)+, found: 330.1321.
4.1.4. Representative procedure for the Aldol reaction. To
a mixture of cyclohexanone 4a (0.92 mL, 9.4 mmol) and
TFA (0.015 mmol) was added catalyst
1 (20.4 mg,
0.09 mmol) at rt. The reaction mixture was vigorously stir-
red for 15 min and benzaldehyde 7a (100 mg, 0.94 mmol)
then added at 0 °C. After stirring for 12 h at 0 °C, the reac-
tion mixture was loaded directly onto a silica-gel column to
give the pure Aldol product 8a (165.5 mg, 86% yield) as a
1
white solid. IR, H, 13C NMR and mass spectral data of
the known products were identical with the reported
data.5b,9
4.1.3.2.
(S)-2-((R)-1-(2-Chloro-5-nitrophenyl)-2-nitro-
25
ethyl) cyclohexanone 6e. ½aꢀD ¼ ꢁ8:0 (c 0.45, CHCl3);
mp 145–147 °C; 1H NMR (CDCl3, 200 MHz): d 8.19–
8.14 (m, 1H), 8.09 (dd, 1H, J = 2.9, 8.7 Hz), 7.59 (dd,
1H, J = 3.6, 8.7 Hz), 4.99–4.81 (m, 2H), 4.43–4.29 (m,
1H), 2.95–2.78 (m, 1H), 2.56–2.29 (m, 2H), 2.22–2.08 (m,
1H), 1.91–1.59 (m, 4H), 1.53–1.35 (m, 1H): 13C NMR
(CDCl3,75 MHz): d 210.6, 146.8, 141.6, 138.0, 131.2,
124.0, 123.5, 76.5, 51.7, 42.7, 40.7, 32.9, 28.3, 25.2; IR
(KBr): m 3082, 2946, 2866, 1703, 1555, 1519, 1447, 1377,
1351 cmꢁ1; ESIMS: m/z 349 (M+Na)+.
Acknowledgement
B.T. and B.B.P. thank the CSIR, New Delhi for financial
assistance.
References
1. (a) Hanessian, S.; Pham, V. Org. Lett. 2000, 2, 2975–2978; (b)
List, B.; Pojarliev, P.; Martin, H. J. Org. Lett. 2001, 3, 2423–
2425; (c) Enders, D.; Seki, A. Synlett 2002, 26–28; (d) List, B.
Tetrahedron 2002, 58, 5573–5590; (e) Li, J.-W.; Xu, L.-W.; Xia,
C.-G. Chin. J. Org. Chem. 2004, 24, 23–28; (f) Fan, J.-F.; Sun,
Y.-P.; Xiao, H.-M. Chin. J. Org. Chem. 2006, 26, 1463–1467.
4.1.3.3. (S)-2-((R)-(Furan-3-yl)-2-nitroethyl) cyclohexa-
25
1
none 6g. ½aꢀD ¼ ꢁ12:5 (c 0.75, CHCl3); mp 61–63 °C; H
NMR (CDCl3, 200 MHz): d 7.32 (d, 2H, J = 15.6 Hz), 6.23