Synlett 2007(3): 0435-0438  
DOI: 10.1055/s-2007-967945
LETTER
© Georg Thieme Verlag Stuttgart · New York

Copper-Catalyzed Kinetic Resolution of 1,3-Cyclohexadiene Monoepoxide 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 24 November 2006
Publication Date:
07 February 2007 (online)

Abstract

Chiral ferrocenyl-based diphosphines lead to kinetic ­resolution of 1,3-cyclohexadiene monoepoxide with moderate to good enantioselectivity (up to 90% ee) and good regioselectivity with various Grignard reagents through an anti-SN2′ pathway.

    References and Notes

  • 1 Modern Organocopper Chemistry   Krause N. Wiley-VCH; Weinheim: 2002. 
  • 2a Badalassi F. Crotti P. Macchia F. Pineschi M. Arnold A. Feringa BL. Tetrahedron Lett.  1998,  39:  7795 
  • 2b For a review see: Pineschi M. New J. Chem.  2004,  28:  657 
  • 3 Equey O. Alexakis A. Tetrahedron: Asymmetry  2004,  15:  1531 
  • 4 Knochel P. Singer RD. Chem. Rev.  1993,  93:  2117 
  • 5a Yorimitsu H. Oshima K. Angew. Chem. Int. Ed.  2005,  44:  4435 
  • 5b Alexakis A. Malan C. Lea L. Tissot-Croset K. Polet D. Falciola C. Chimia  2006,  60:  124 
  • 6 Martin D. Kehrli S. d’Augustin M. Clavier H. Mauduit M. Alexakis A. J. Am. Chem. Soc.  2006,  128:  8416 
  • 7 Okamoto S. Tominaga S. Saimo N. Kase K. Shomoda K. J. Organomet. Chem.  2005,  690:  6001 
  • 8 Feringa BL. Badorrey R. Pena D. Harutyunyan SR. Minnaard AJ. Proc. Natl. Acad. Sci. U.S.A.  2004,  101:  5834 
  • 9 Lopez F. van Zijl AW. Minnaard AJ. Feringa BL. Chem. Commun.  2006,  409 
  • 10 Alexakis A. Benhaim C. Rosset S. Humam M. J. Am. Chem. Soc.  2002,  124:  5262 
  • 11 Marino JP. Floyd DM. Tetrahedron Lett.  1979,  675 
  • 14 Bertozzi F. Crotti P. Macchia F. Pineschi M. Feringa BL. Angew. Chem. Int. Ed.  2001,  40:  930 
12

Et2O is purified by filtration over Al2O3, whereas MTBE has to be distilled over Na/benzophenone.

13

Typical Procedure: In a dried Schlenk tube under N2 atmosphere were placed CuBr (1.4 mg, 0.01 mmol) and (R,S)-L11 (7.0 mg, 0.011 mmol). Et2O was added (6 mL) and the mixture was stirred at r.t. for 20 min. The tube was cooled to -78 °C and 1,3-cyclohexadiene monoepoxide (1; 100 µL, 1 mmol) was added. BuMgCl (250 µL, 2.0 M in Et2O, 0.5 mmol) was added dropwise over a period of 3 min. The reaction was stirred for 1 h and quenched with MeOH and (NH4)2SO4 before being allowed to reach r.t. The aqueous phase was extracted with Et2O and the organic layers were dried over Na2SO4 and the solvent was removed on a rotary evaporator (45% conversion, 90% ee). The crude was poured in Ac2O (1 mL, 10 mmol) in the presence of Et3N (100 µL) and DMAP (a few mg). The mixture was stirred overnight at r.t. The reaction was quenched with MeOH (100 µL) and diluted with Et2O (5 mL). The organic phase was washed with 1 M NaOH (1 mL) and the aqueous phase with Et2O (2 × 1 mL). The organic layer was dried over Na2SO4 and the solvent was removed on a rotary evaporator. The crude residue was purified by flash chromatography on silica gel (cyclohexane-EtOAc 19:1) yielding the pure product (69 mg, 35% yield). 1H NMR (400 MHz, CDCl3): δ = 5.79 (m, 1 H), 5.58 (m, 1 H), 5.28 (m, 1 H), 2.08 (m, 1 H), 2.05 (s, 3 H), 1.87 (m, 1 H), 1.56 (m, 1 H), 1.30 (br, 7 H), 0.89 (t, J = 6.8 Hz, 3 H). 13C NMR (100 MHz, CDCl3): δ = 171, 136.9, 125.9, 77.2, 35.4, 35.1, 29.2, 27.7, 26.5, 22.9, 21.5, 14.0. [α]D 20 -167° (c = 15.2, CHCl3, ee = 90%).