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

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 S_N2 or S_N2′ product with up to 96% ee.

epoxides - asymmetric synthesis - Grignard reagents - catalysis - copper

References and Notes

1 Modern Organocopper Chemistry   Krause N. Wiley-VCH; Weinheim: 2002. 

2 Vedjes E. Jure M. Angew. Chem. Int. Ed.  2005,  44:  3974 ; and references cited therein

3a Badalassi F. Crotti P. Macchia F. Pineschi M. Arnold A. Feringa BL. Tetrahedron Lett.  1998,  39:  7795 

3b For a review, see: Pineschi M. New J. Chem.  2004,  28:  657 ; and references cited therein

4 Equey O. Alexakis A. Tetrahedron: Asymmetry  2004,  15:  1531 

5 Millet R. Alexakis A. Synlett  2007,  435 

6 Palais L. Mikhel IS. Bournaud C. Micouin L. Falciola CA. Vuagnoux-d’Augustin M. Rosset S. Bernardinelli G. Alexakis A. Angew. Chem. Int. Ed.  2007,  46:  7462 

7a Yorimitsu H. Oshima K. Angew. Chem. Int. Ed.  2005,  44:  4435 

7b Alexakis A. Malan C. Lea L. Tissot-Croset K. Polet D. Falciola C. Chimia  2006,  60:  124 

7c Tissot-Croset K. Polet D. Alexakis A. Angew. Chem. Int. Ed.  2004,  43:  2426 

7d Alexakis A. Croset K. Org. Lett.  2002,  4:  4147 

7e For a very recent review, see: Falciola CA. Alexakis A. Eur. J. Org. Chem.  2008, DOI: 10.1002/ejoc.200800025

8 Alexakis A. Benhaim C. Rosset S. Humam M. J. Am. Chem. Soc.  2002,  124:  5262 

9 Marino JP. Floyd DM. Tetrahedron Lett.  1979,  25:  675 

10 Bertozzi F. Crotti P. Macchia F. Pineschi M. Feringa BL. Angew. Chem. Int. Ed.  2001,  40:  930 

11

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.