A. Alexakis, A. Tomassini, O. Andrey, G. Bernardinelli
FULL PAPER
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transferred to a separating funnel, and washed twice with ice-cold
saturated aqueous NH4Cl solution. The organic phase was dried
with MgSO4, concentrated in vacuo and chromatographed (cyclo-
hexane/EtOAc, 9:1) to afford the product 9 or 10 as a colourless
opaque oil.
Methyl 2-Methoxycarbonyl-3,5-diphenylpent-4-enoate (9):[22] The
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enantiomeric excess (77%) was determined by SFC (AD column,
1
3% MeOH). H NMR (500 MHz, CDCl3): δ = 3.53 (s, 3 H), 3.72
(s, 3 H), 3.97 (d, J = 11.0 Hz, 1 H), 4.28 (dd, J = 10.8, 9.8 Hz, 1
H), 6.35 (dd, J = 15.8, 8.8 Hz, 1 H), 6.50 (d, J = 15.8 Hz, 1 H),
7.35–7.20 (m, 10 H) ppm. 13C NMR (125.8 MHz, CDCl3): δ =
49.17 (CH), 52.44 (CH3), 52.62 (CH3), 57.61 (CH), 126.36 (CH),
127.15 (CH), 127.55 (CH), 127.84 (CH), 128.45 (CH), 128.70 (CH),
129.06 (CH), 131.80 (CH), 136.78 (Cquat.), 140.13 (Cquat.), 167.75
(C=O), 168.17 (C=O) ppm.
Dimethyl Cyclohex-2-en-1-ylmalonate (10):[22] The enantiomeric ex-
cess (40%) was determined by GC (Chiraldex column, isotherm
100 °C). 1H NMR (500 MHz, CDCl3): δ = 1.37 (dddd, J = 19.6,
11.0, 8.5, 2.5 Hz, 1 H), 1.62–1.53 (m, 1 H), 1.81–1.69 (m, 2 H),
2.02–1.98 (m, 2 H), 2.95–2.88 (m, 1 H), 3.29 (d, J = 9.5 Hz, 1 H),
3.74 (s, 3 H), 3.75 (s, 3 H), 5.53 (dd, J = 10.4, 2.2 Hz, 1 H), 5.78
(dq, J = 10.1, 2.6 Hz, 1 H) ppm. 13C NMR (125.8 MHz, CDCl3):
δ = 20.84 (CH2), 24.90 (CH2), 26.60 (CH2), 35.36 (CH3), 52.36
(CH), 56.83 (CH), 127.29 (CH), 129.65 (CH), 168.84 (C=O), 168.90
(C=O) ppm.
[6]
Cu-Catalysed Conjugate Addition with Aminal 3d as Ligand:[14] Li-
gand 3d (0.0166 mmol) and 1 mL of Et2O were added to a solution
of copper thiophenecarboxylate (CuTC; 0.008 mmol) in Et2O
(1 mL) at room temperature under nitrogen. The solution was
stirred at 25 °C for 30 min and then cooled to –30 °C. Et2Zn (1 mL,
0.5 mmol 15% in hexane) was added dropwise such that the tem-
perature did not rise above –30 °C. The solution was stirred for
5 min, and the Michael acceptor (0.415 mmol) was then added
dropwise as a solution in 0.5 mL of Et2O. The reaction mixture
was stirred at –30 °C for 12 h before being quenched by addition
of 2 n HCl. Purification by flash chromatography (Rf = 0.48; silica;
hexane/AcOEt, 80:20) afforded 3-ethylcyclohexanone (11). The en-
antiomeric excess (74%) was measured by chiral GC [Lipodex E,
25 m, 50 mLs–1, T = 60 °C: tR = 24.72, major enantiomer (R); tR
= 28.15, minor enantiomer (S)]. 1H NMR: δ = 2.50–0.70 (m) ppm.
13C NMR: δ = 25.0 (C-7), 28.6 (C-8), 31.0 (C-4), 36.0 (C-5), 38.8
(C-3), 41.1 (C-6), 47.9 (C-2), 210.9 (C-1) ppm.
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[9]
Acknowledgments
The authors thank Stephane Rosset for help, Prof. E. P. Kündig for
useful discussions, Dr. S. Pache for providing the (benzaldehyde)
tricarbonylchromium complex, and the Swiss National Research
Foundation (no. 20-068095.02) and COST action D24/0003/01
(OFES contract no. C02.0027) for financial support.
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Eur. J. Org. Chem. 2005, 1332–1339