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Synlett 2010(2): 317-320  
DOI: 10.1055/s-0029-1219171
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© Georg Thieme Verlag Stuttgart ˙ New York

Copper-Catalysed Kinetic Resolution of Cyclic Alkenyl Cyclopropane Malonates with Organoaluminium and Grignard Reagents

Chehla Ladjel, Nicolas Fuchs, Ludovic Gremaud, Alexandre Alexakis*
Department of Organic Chemistry, University of Geneva, 30 Quai Ernest Ansermet, 1211 Geneva 4, Switzerland
Fax: +41(22)3793215; e-Mail: alexandre.alexakis@unige.ch;
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Publication History

Received 5 October 2009
Publication Date:
04 January 2010 (online)

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Abstract

We report herein the first copper-catalysed kinetic resolution of alkenyl cyclopropane malonates with organoaluminium and Grignard reagents. The conjugate products were exclusively obtained on five- and six-membered-ring substrates. After optimization of the reaction conditions, we observed good conversions and enantiomeric excesses using ferrocene-based ligands on five-membered-ring substrates, and phosphoramidite ligands on six-membered rings.

Key words

kinetic resolution - alkenyl cyclopropane malonates - conjugate addition - Grignard reagents - copper

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16

General Procedure (Chiral Version): In a dried Schlenk tube flushed under nitrogen, was placed the copper catalyst (0.04 mmol) and the specified ligand (0.08 mmol). Anhydrous CH2Cl2 (1 mL) was then added and the mixture was stirred at room temperature for 15 min. The Schlenk tube was then placed in a bath at -78 ˚C, and the indicated Grignard reagent (1 equiv) was added. The starting material (1 mmol), solubilised in the indicated solvent (0.5 mL), was added dropwise. The mixture was stirred for 4 h at this temperature. Aq HCl (1N, 1 mL) was added and the reaction was allowed to warm to r.t. The organic layer was separated and the aqueous phase was extracted with Et2O. The organic phases were dried over MgSO4 and the solvent was evaporated under reduced pressure. The crude compound was purified by chromatography on silica gel (cyclohexane-Et2O, 70:30) and the product was isolated as an oil.
Dimethyl 2-(4-ethylcyclopent-2-enyl)malonate (4b): ¹H NMR (400 MHz, CDCl3): δ = 0.88 (t, J = 7 Hz, 3 H), 1.25-1.45 (m, 2 H), 1.69-1.81 (m, 2 H), 2.62 (br s, 1 H), 3.25 (m, 1 H), 3.36 (br s, 1 H), 3.73 (s, 6 H), 5.62 (d, J = 5 Hz, 1 H), 5.79 (d, J = 5 Hz, 1 H). ¹³C NMR (100 MHz, CDCl3): δ = 169.4, 169.3, 137.8, 130.9, 57, 52.6, 46.5, 45.2, 34.4, 28.6, 12.3.
Dimethyl 2-(4-ethylcyclohex-2-enyl)malonate (5b): ¹H NMR (400 MHz, CDCl3): δ = 0.89 (t, J = 7 Hz, 3 H), 1.20-1.35 (m, 4 H), 1.82-1.95 (m, 3 H), 2.86 (br s, 1 H), 3.24 (d, J = 9 Hz, 1 H), 3.75 (s, 6 H), 5.46 (m, 1 H), 5.64-5.66 (m, 1 H). ¹³C NMR (100 MHz, CDCl3): δ = 169.2, 169.1, 134.5, 127.1, 57.1, 52.6, 37.2, 36.4, 29.0, 28.3, 26.9, 11.4.