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Synlett 2008(12): 1797-1800  
DOI: 10.1055/s-2008-1077901
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

SimplePhos as Efficient Ligand for the Copper-Catalyzed Kinetic Resolution of Cyclic Vinyloxiranes with Grignard Reagents

Renaud Millet, Alexandre Alexakis*
Department of Organic Chemistry, University of Geneva, 30 Quai Ernest Ansermet, 1211 Geneva, Switzerland
Fax: +41(22)3793215; e-Mail: alexandre.alexakis@chiorg.unige.ch;
Further Information

Publication History

Received 15 March 2008
Publication Date:
02 July 2008 (online)

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Abstract

Cyclic vinyloxiranes react with Grignard reagents under copper catalysis. Highly efficient kinetic resolution is achieved with the new SimplePhos family of chiral phosphorus ligands. Stereodivergence could be exploited to get either the SN2 or SN2′ product with up to 96% ee.

Key words

epoxides - asymmetric synthesis - Grignard reagents - catalysis - copper

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Typical Procedure In a dried Schlenk tube under N2 atmosphere were placed CuTC (5.7 mg, 0.03 mmol) and (S,S)-L1 (13.5 mg, 0.03 mmol). Then, CH2Cl2 was added (6 mL) and the mixture was stirred at r.t. for 20 min. The tube was cooled down to -78 ˚C and 1,3-cyclohexadiene monoepoxide 1 (100 µL, 1 mmol) was added. c-HexMgCl (250 µL, 2.0 M in Et2O, 0.5 mmol) was added dropwise over a period of 3 min. The reaction was stirred for 3 h and quenched with MeOH and (NH4)2SO4 before being allowed to reach r.t. The aqueous phase was extracted with CH2Cl2 and the organic layer was dried over MgSO4 and the solvent removed on rotary evaporator (55% conversion, 88% ee). The crude product was purified by flash chromatography on SiO2 (pentane then pentane-Et2O, 75:25) yielding 79 mg (44% yield) of a white solid. [α]D ²0
-128.2 (c 0.87, CHCl3, ee = 88%). ¹H NMR (400 MHz, CDCl3): δ = 5.68 (m, 2 H), 4.20 (br, 1 H), 2.09 (m, 1 H), 1.97 (m, 1 H), 1.74-1.60 (m, 6 H), 1.45-1.35 (m, 3 H), 1.22-1.12 (m, 4 H), 1.07-0.97 (m, 2 H). ¹³C NMR (100 MHz, CDCl3): δ = 133.3, 130.1, 67.5, 42.4, 41.1, 32.7, 30.2, 29.7, 26.7, 23.7.