PAPER
Michael Addition of Ketone Enolates to a,b-Unsaturated Esters
(1R,3R)-3-(3-Methoxy-3-oxopropyl)camphor (3f)
237
+
+
MS (EI, 70 eV): m/z (%) = 200 (M , 15), 169 (M – OMe, 22), 141
+
(
M – CO Me, 11), 129 (41), 97 (42), 71 (100), 43 (47).
According to the general procedure, this compound was prepared
from 1f and 2a to give the product as a colorless liquid after chro-
matography (hexane–EtOAc, 7:3). Further purification was accom-
plished by distillation; bp 150 °C/0.08 mmHg.
2
HRMS (EI, 70 eV): m/z calcd for C H O : 200.1412; found:
1
1
20
3
+
2
00.1426 (M ).
Anal. Calcd for C H O : C, 65.97; H, 10.07. Found: C, 65.80; H,
1
1
20
3
IR (neat): 1735 cm–1.
9
.79.
1
H NMR (600 MHz, CDCl ): d = 3.68 (s, 3 H, OCH ), 2.54–2.43 (m,
3
3
A
Methyl 3-(1-Oxo-1,2,3,4-tetrahydronaphthalen-2-yl)propi-
onate (3d)
According to the general procedure, this compound was prepared
from 1d and 2a to give the product as a colorless liquid after chro-
matography (hexane–EtOAc, 7:3). Further purification was accom-
plished by distillation; bp 130 °C/0.030 mmHg.
2 H, 3-CH CH ), 2.14–2.07 (m, 1 H, 3-CH ), 2.06–1.97 (m, 1 H, 5-
2 2
H ), 1.92 (d, J = 3.9 Hz, 1 H, 4-H), 1.81 (dd, J = 8.1, 5.6 Hz, 1 H, 3-
x
B
H), 1.75–1.67 (m, 1 H, 3-CH ), 1.64 (ddd, J = 14.1, 11.1, 3.6 Hz, 1
H, 6-H ), 1.47 (ddd, J = 14.1, 9.0, 5.0 Hz, 1 H, 6-H ), 1.34 (ddd,
x
n
A
J = 12.3, 9.0, 3.6 Hz, 1 H, 5-H ), 0.93 (s, 3 H, 7-CH ), 0.90 (s, 3 H,
1-CH ), 0.85 (s, 3 H, 7-CH ) (x = exo, n = endo). The decoupling
n
3
B
3
3
–
1
NMR experiment shows that the coupling constant between 3-H
and 4-H is less than 1 Hz (ca. 0 Hz). The double doublet signal at 3-
IR (neat): 1735, 1681 cm .
1
H NMR (270 MHz, CDCl ): d = 8.02 (d, J = 7.83 Hz, 1 Harom),
.48–7.43 (m, 1 H ), 7.33–7.20 (m, 2 H
.02 (dd, 2 H, 4¢-CH ), 2.61–2.47 (m, 1 H, 2¢-H), 2.51 (t, J = 7.56
Hz, 2 H, 2-CH ), 2.33–2.17 (m, 2 H, 3-H and 3¢-H ), 1.99–1.79 (m,
3
H is caused by 3-CH . This small value suggests that 3-H is located
2
7
3
arom
), 3.68 (s, 3 H, OCH3),
arom
at endo position.
2
13C NMR (67.9 MHz, CDCl
57.63 (C-1), 54.05 (C-3, +), 51.58 (OCH
C-7), 33.86 (3-CH CH , –), 29.32 (C-6, –), 29.22 (C-5, –), 27.03
A
A
3
): d = 221.00 (C-2), 173.71 (COO),
, +), 47.63 (C-4, +), 46.74
2
B
B
3
2
H, 3-H and 3¢-H ).
(
2
2
1
3
C NMR (67.9 MHz, CDCl ): d = 199.46 (s, C=O), 173.83 (s,
COO), 143.67 (s, Ar), 133.15 (d, Ar), 132.31 (s, Ar), 128.59 (d, Ar),
27.31 (d, Ar), 126.52 (d, Ar), 51.56 (q, OCH ), 46.69 (d, C-2¢),
1.63 (t, C-2), 28.74 (t), 28.59 (t, C-4¢), 25.13 (t).
A
B
3
(3-CH , –), 21.71 (7-CH , +), 20.45 (7-CH , +), 9.39 (1-Me, +).
2 3 3
+
MS (EI, 70 eV): m/z (%) = 238 (M , 36), 210 (100), 178 (75), 95
89).
1
3
3
(
+
HRMS (EI, 70 eV): m/z calcd for C14H O : 238.1569; found:
22 3
MS (EI, 70 eV): m/z (%) = 232 (M , 30), 200 (51), 146 (100), 118
+
2
38.1598, 238.1577 (M ).
(
54), 90 (44).
Anal. Calcd for C H O : C, 70.56; H, 9.30. Found: C, 70.35; H,
9.38.
1
4
22
3
HRMS (EI, 70 eV): m/z calcd for C H O : 232.1099; found:
1
4
16
3
+
2
32.1078, 232.1106, 232.1098 (M ).
Anal. Calcd for C H O : C, 72.39; H, 6.94. Found: C, 72.27; H,
14
16
3
Methyl 3-Methyl-5-oxo-5-phenylpentanoate (3g)
According to the general procedure, this compound was prepared
6
.79.
from 1g and 2b to give the product as a colorless liquid after chro-
(
2R*,4R*)-4-tert-Butyl-2-(3-methoxy-3-oxopropyl)cyclohex-
matography (hexane–Et O, 5:1). Further purification was accom-
2
anone (3e)
plished by distillation; bp 130 °C/2 mmHg.
According to the general procedure, this compound was prepared
from 1e and 2a to give the product as a colorless liquid after chro-
matography (hexane–Et O, 3:1). Further purification was accom-
plished by distillation; bp 135 °C/0.014 mmHg.
–
1
IR (neat): 1730, 1690 cm .
1
H NMR (270 MHz, CDCl ): d = 7.99–7.95 (m, 2 Harom), 7.60–7.43
2
3
(m, 3 H ), 3.67 (s, 3 H, OCH ), 3.12 (dd, J = 16.1, 5.9 Hz, 1 H, 4-
H ), 2.86 (dd, J = 16.1, 7.3 Hz, 1 H, 4-H ), 2.68 (m, 1 H, 3-H), 2.46
(
arom
3
A
B
–
1
IR (neat): 1739, 1716 cm .
A
dd, J = 15.1, 6.4 Hz, 1 H, 2-H ), 2.33 (dd, J = 15.1, 6.8 Hz, 1 H, 2-
1
H NMR (600 MHz, CDCl ): d = 3.66 (s, 3 H, OCH ), 2.46–2.23 (m,
B
3
3
H ), 1.05 (d, J = 6.8 Hz, 3 H, 3-CH ).
3
5
2
1
1
0
1
H,6-CH , 2-H , and 2-CH CH ), 2.13–2.02 (m, 3 H, 3-H , 5-H ,
2 ax 2 2 eq eq
13C NMR (67.9 MHz, CDCl
137.07 (s, ipso-Carom), 133.00 (d, p-CHarom), 128.55 (d, Ar), 128.08
d, Ar), 51.42 (q, OCH ), 44.81 (t, C-4), 40.86 (t, C-2), 26.82 (d, C-
A
B
): d = 199.16 (s, C-5), 172.96 (s, C-1),
3
-CH H CH ), 1.60 (dddd, 1 H, J = 12.6, 12.6, 3.0, 3.0 Hz, 4-H ),
2
ax
A
B
.55–1.49 (m, 1 H, 2-CH H CH ), 1.43 (dddd, 1 H, J = 12.6, 12.6,
2
(
3
2.6, 4.8 Hz, 5-H ), 1.17 (ddd, 1 H, J = 12.6, 12.6, 12.6 Hz, 3-H ),
ax
ax
3
), 20.08 (q, 3-CH3).
.93 (s, 9 H, t-C H ). The signal for 4-H at 1.60 (dddd, J = 12.6,
4
9
+
+
2.6, 3.0, 3.0 Hz) suggests that it is located at the axial position. The
MS (EI, 70 eV): m/z (%) = 220 (M , 0.6), 189 (M – OCH , 5), 161
3
+
coupling constant between 2-H and 3-H is 12.6 Hz because of the
(M – CO Me, 1.7), 147 (6), 120 (30), 105 (100), 77 (41).
ax
2
multiplicity of 3-H and decoupling NMR experiment. This large
value suggests that 2-H is located at the axial position.
HRMS (EI, 70 eV): m/z calcd for C H O : 220.1110; found:
1
3
16
3
+
2
20.1081, 220.1136, 220.1116 (M ).
1
3
C NMR (67.9 MHz, CDCl ): d = 212.82 (s, C-1), 174.08 (s, COO),
3
Anal. Calcd for C H O : C, 70.89; H, 7.32. Found: C, 70.84; H,
1
3
16
3
5
3
1.47 (q, OCH ), 48.69 (d, C-2), 47.00 (d, C-4), 41.64 (t, C-6),
3
7
.46.
5.30 (t, C-3), 32.38 (s, CMe ), 31.63 (t, 2-CH CH CO Me), 28.75
3
2
2
2
(
t, C-5), 27.59 [q, C(CH ) ], 24.87 (t, 2-CH CH CO Me).
3 3 2 2 2
Methyl 3,4-Dimethyl-5-oxo-5-phenylpentanoate (3h)
According to the general procedure, this compound was prepared
from 1b and 2b to give the product (diastereomeric mixture, 70:30)
+
MS (EI, 70 eV): m/z (%) = 240 (M , 43), 208 (100), 124 (68), 57
78).
(
as a colorless liquid after chromatography (hexane–Et O, 5:1). Fur-
ther purification was done by distillation; bp 120 °C/2 mmHg.
2
HRMS (EI, 70 eV): m/z calcd for C H O 240.1725; found:
1
4
24
3
+
2
40.1738, 240.1725, 240.1726 (M ).
–
1
IR (neat): 1735, 1682 cm .
Anal. Calcd for C H O : C, 69.96; H, 10.07. Found: C, 69.79; H,
1
4
24
3
+
+
1
0.28.
MS (EI, 70 eV): m/z (%) = 234 (M , 8), 203 (M – OCH , 8), 175
(
3
+
+
M – CO Me, 2), 161 (M – CH CO Me, 12), 133 (4), 105 (100),
2 2 2
trans-3e
77 (21).
This compound was a minor product in Scheme 5 and was not iso-
lated pure. The selected signal in the crude mixture:
HRMS (EI, 70 eV): m/z calcd for C H O : 234.1256; found:
1
4
18
3
+
2
34.1251, 234.1237 (M ).
1
3
C NMR (67.9 MHz, CDCl ): d = 51.39 (OCH ).
3
3
Synthesis 2005, No. 2, 233–239 © Thieme Stuttgart · New York