Synthesis of Alkylidenemalonates and α,β-Unsaturated Esters
1
pale-yellow oil. H NMR: δ = 7.02 (t, J = 7.5 Hz, 1 H), 3.96 (d, J
(163 mg, 45%) was obtained as a pale-yellow oil. 1H NMR: δ =
6.91 (s, 1 H), 3.95 (d, J = 6.5 Hz, 2 H), 3.81 (s, 3 H), 1.94 (m, 1
= 6.5 Hz, 2 H), 3.82, (s, 3 H), 2.30 (q, J = 7.5 Hz, 2 H), 1.97 (nonet,
J = 6.5 Hz, 1 H), 1.50–1.44 (m, 2 H), 1.40–1.23 (m, 6 H), 0.94 (d, H), 1.13 (s, 9 H), 0.93 (d, J = 6.5 Hz, 6 H) ppm. 13C NMR: δ =
J = 6.5 Hz, 6 H), 0.88 (t, J = 7.0 Hz, 3 H) ppm. 13C NMR: δ =
166.1 (C), 164.0 (C), 150.1 (CH), 128.2 (C), 71.2 (CH2), 52.1 (CH3), 34.2 (CH), 28.8 (CH ), 27.7 (C), 18.9 (CH ) ppm. IR (KBr): ν =
167.5 (C), 164.4 (C), 155.4 (CH), 128.3 (C), 71.3 (CH2), 52.1 (CH3),
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31.5 (CH2), 29.8 (CH2), 28.9 (CH2), 28.2 (CH2), 27.7 (CH), 22.5 2961, 2934, 2874, 1732, 1643, 1246, 1196, 1070, 1001 cm–1. MS
(CH ), 19.0 (CH ), 14.0 (CH ) ppm. IR (neat): ν = 2955, 2928,
(EI): m/z = 186 [M – isobutene]+, 171, 136, 105, 91. HRMS (ESI):
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1724, 1643, 1605, 1246, 1227, 1065 cm–1. MS (EI): m/z = 271 [M
calcd. for C13H22O4Na 265.1410 [M + Na]+; found 265.1406. The
+ H]+, 239 [M – OMe]+. HRMS (ESI): calcd. for C15H27O4 E geometry was assigned by analogy.
271.1904 [M + H]+; found 271.1906. The E geometry was assigned
Methyl (Z)-3-Phenyl-2-(tributylstannyl)acrylate (4a): Compound 1a
by analogy.
(1.5 mL, 10 mmol) was placed in a dry 100-mL round-bottomed
flask. THF (10 mL), Bu3SnH (3.0 mL, 11 mmol), and AIBN
(25 mg, 0.15 mmol) were added to the flask. The mixture was
stirred for 3 h and then concentrated in vacuo. The residue was
purified by column chromatography (hexane to hexane/AcOEt,
50:1) to afford the title compound (3.13 g, 69%) as a colorless oil.
1H NMR: δ = 8.37 (s, 1 H), 7.40–7.20 (m, 5 H), 3.78 (s, 3 H), 1.10–
1.51 (m, 12 H), 0.90–0.70 (m, 15 H) ppm. 13C NMR: δ = 172.3 (C),
153.8 (CH), 139.2 (C), 138.7 (C), 128.5 (CH), 128.1 (CH), 127.9
(CH), 51.7 (CH3), 28.8 (CH2), 27.1 (CH2), 13.6 (CH3), 11.7
[(1R,2S,5R)-2-Isopropyl-5-methylcyclohexyl] Methyl (Z)-2-Benzyl-
idenemalonate (3ka): Purified by column chromatography (hexane
to hexane/AcOEt, 20:1). From 2.2 mmol 4a, the title compound
(370 mg, 48%) was obtained as a white solid, m.p. 92–94 °C. [α]2D5
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= –40.2 (c = 1.00, CHCl3). H NMR: δ = 7.72 (s, 1 H), 7.52–7.47
(m, 2 H), 7.43–7.34 (m, 3 H), 4.88 (td, J = 11.0, 4.5 Hz, 1 H), 3.83
(s, 3 H), 2.16 (m, 1 H), 1.85 (sextd, J = 7.0, 2.5 Hz, 1 H), 1.72–
1.65 (m, 2 H), 1.52 (m, 1 H), 1.39 (ddt, J = 12.5, 11.0, 1.0 Hz, 1
H), 1.13–0.95 (m, 2 H), 0.93 (d, J = 6.5 Hz, 3 H), 0.88 (m, 1 H),
0.82 (d, J = 7.0 Hz, 3 H), 0.77 (d, J = 3.0 Hz, 3 H) ppm. 13C NMR:
δ = 166.4 (C), 164.7 (C), 141.8 (CH), 132.8 (C), 130.5 (CH), 129.5
(CH), 128.7 (CH), 126.5 (C), 76.1 (CH), 52.4 (CH3), 46.8 (CH3),
40.0 (CH2), 34.1 (CH2), 31.4 (CH), 25.5 (CH), 23.0 (CH2), 22.0
(CH ) ppm. IR (neat): ν = 2955, 2922, 2870, 2853, 1710, 1695,
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1230, 1194, 1074 cm–1. MS (EI): m/z = 451 [M]+, 395 [M – Bu]+.
The Z geometry was confirmed by the H–Sn coupling constant of
the β-H (δ = 8.37 ppm, 3JH-Sn = 100 Hz).[13] The 1H and 13C NMR
data are in good agreement with the published data.[29]
(CH), 20.7 (CH ), 15.8 (CH ) ppm. IR (neat): ν = 2951, 2920, 1728,
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1628, 1454, 1258, 1200, 1065, 764 cm–1. MS (ESI): m/z = 367
[M + Na]+. HRMS (ESI): calcd. for C21H28O4Na 367.1880 [M +
Na]+; found 367.1882. The Z geometry was assigned by analogy.
4-Benzyl 2,4-Dimethyl (2SR,3SR,4SR,5SR)- and (2SR,3SR,4RS,
5SR)-3,5-Diphenylpyrrolidine-2,4,4-tricarboxylate (6): Conducted
according to the reported procedure[15] by using 3ac (0.20 mmol).
Purification of the crude material by column chromatography (hex-
ane/AcOEt, 10:1 to 1:1) gave the title compound (87 mg, 92%) as
a pale-yellow oil. 1H NMR: δ = 7.49 (td, J = 8.5, 2.0 Hz, 2 H),
7.37–7.18 (m, 11 H), 6.94 (dd, J = 7.0, 2.0 Hz, 0.72 H), 6.84 (dd,
J = 7.0, 2.0 Hz, 1.28 H), 5.37 (s, 0.36 H), 5.35 (s, 0.64 H), 4.91 (d,
J = 7.5 Hz, 0.64 H), 4.88 (d, J = 7.5 Hz, 0.36 H), 4.45 (d, J =
6.5 Hz, 0.64 H), 4.43 (d, J = 6.5 Hz, 0.36 H), 4.24–4.21 (m, 1.36
H), 4.12 (d, J = 12.5 Hz, 0.64 H), 3.77 (s, 3 H), 3.12 (s, 2.16 H),
3.10 (s, 1.08 H) ppm. 13C NMR: δ = 174.2 (minor C), 173.1 (major
C), 169.8 (minor C), 169.34 (minor C), 169.25 (major C), 169.1
(major C), 138.6 (minor C), 138.5 (major C), 138.2 (minor C),
138.1 (major C), 134.9 (minor C), 134.7 (major C), 128.9 (CH),
128.8 (CH), 128.7 (CH), 128.45 (CH), 128.36 (CH), 128.30 (CH),
128.25 (CH), 128.17 (CH), 128.15 (CH), 128.04 (CH), 127.98 (CH),
127.8 (CH), 127.68 (CH), 127.65 (CH), 127.6 (CH), 127.53 (CH),
127.46 (CH), 79.72 (major CH2), 79.66 (minor CH2), 71.3 (major
C), 71.2 (minor C), 68.23 (minor CH), 68.17 (major CH), 67.1
(major CH), 67.0 (minor CH), 66.3 (minor CH), 66.1 (major CH),
56.3 (major CH3), 56.2 (minor CH3), 52.5 (major CH3), 51.7
[(1R,2S,5R)-(2-Phenylpropan-2-yl)-5-methylcyclohexyl] Methyl (Z)-
2-Benzylidenemalonate (3la): Purified by column chromatography
(hexane to hexane/AcOEt, 10:1). From 2.2 mmol 4a, the title com-
pound (430 mg, 45%) was obtained as a colorless oil. [α]2D5 = –31.3
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(c = 1.00, CHCl3). H NMR: δ = 7.71 (s, 1 H), 7.49 (dd, J = 7.5,
2.0 Hz, 2 H), 7.41–7.17 (m, 7 H), 7.10 (dt, J = 7.0, 2.0 Hz, 1 H),
4.92 (td, J = 10.5, 4.0 Hz, 1 H), 3.84 (s, 3 H), 2.21 (ddd, J = 11.5,
5.5, 3.0 Hz, 1 H), 1.85 (ddd, J = 12.0, 9.0, 3.5 Hz, 1 H), 1.53–1.43
(m, 2 H), 1.28 (m, 1 H), 1.20 (s, 3 H), 1.17 (s, 3 H), 0.98–0.66 (m,
3 H), 0.86 (d, J = 6.5 Hz, 3 H) ppm. 13C NMR: δ = 165.8 (C),
164.4 (C), 150.7 (C), 142.1 (CH), 132.9 (C), 130.3 (CH), 129.5
(CH), 128.5 (CH), 127.8 (CH), 126.6 (C), 125.4 (CH), 125.1 (CH),
76.7 (CH), 52.3 (CH3), 50.4 (CH), 40.4 (CH2), 40.0 (CH2), 34.3
(CH3), 31.2 (CH), 28.8 (CH), 27.2 (CH2), 23.4 (CH3), 21.7
(CH ) ppm. IR (neat): ν = 2947, 1721, 1697, 1261, 1207, 1053 cm–1.
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MS (ESI): m/z = 443 [M + Na]+. HRMS (ESI): calcd. for
C27H32O4Na 443.2193 [M + Na]+; found 443.2192. The Z geome-
try was assigned by analogy.
Isobutyl Methyl (E)-2-(2-Methylpropylidene)malonate (3mb): Ac-
cording to the one-pot procedure used for the synthesis of 3ab but
by using 0.75 mmol 1m in place of 1a, the title compound (109 mg,
63%) was obtained as a pale-yellow oil. 1H NMR: δ = 6.68 (d, J
= 10.0 Hz, 1 H), 3.96 (d, J = 6.5 Hz, 2 H), 3.82 (s, 3 H), 2.67 (m,
1 H), 1.97 (nonet, J = 6.5 Hz, 1 H), 1.07 (d, J = 6.5 Hz, 6 H), 0.94
(d, J = 6.5 Hz, 6 H) ppm. 13C NMR: δ = 166.2 (C), 164.1 (C),
155.4 (CH), 126.2 (C), 71.2 (CH2), 52.1 (CH3), 29.5 (CH), 27.7
(minor CH ) ppm. IR (KBr): ν = 3435, 2954, 2927, 1719, 1630,
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1437, 1383, 1265, 1213, 905, 733, 702, 650 cm–1. MS (ESI): m/z =
474 [M + H]+. HRMS (ESI): calcd. for C28H28NO6 474.1911 [M
+ H]+; found 474.1914. The diastereomeric ratio (64:36) was deter-
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mined by the integration area of the H NMR signals at δ = 6.94
and 6.84 ppm. The relative configuration was determined after the
conversion of 6 into the known trimethyl ester with the established
stereochemistry (see below). The stereochemistry of the quaternary
carbon was not determined.
(CH), 21.8 (CH ), 19.0 (CH ) ppm. IR (KBr): ν = 2963, 2932, 2874,
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1732, 1647, 1248, 1223, 1150, 1055, 999 cm–1. MS (EI): m/z = 172
[M – isobutene]+, 155 [M – OiBu]+, 131, 122, 103, 91. HRMS
(ESI): calcd. for C12H20O4Na 251.1254 [M + Na]+; found 251.1251.
The E geometry was assigned by analogy.
Determination of the Relative Configuration of 6 Ϫ Trimethyl
(2SR,3SR,5SR)-3,5-Diphenylpyrrolidine-2,4,4-tricarboxylate:
A
mixture of (30.0 mg, 0.063 mmol) and 10% Pd/C (6 mg,
6
Isobutyl Methyl (E)-2-(2,2-Dimethylpropylidene)malonate (3nb):
According to the one-pot procedure used for the synthesis of 3ab
but by using 1.5 mmol 1n in place of 1a, the title compound
0.1 equiv.) in a 5:1 mixture of THF/MeOH (2 mL) was stirred for
4 h at room temp. under H2. The mixture was filtered through Ce-
lite, which was successively washed with THF. A 1 m THF solution
Eur. J. Org. Chem. 2015, 1264–1272
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