A Chiral BINOL-Zinc Complex as a Novel Catalyst for the Enantioselective Epoxidation of α,β-Enones

Abstract

First systematic studies on asymmetric epoxidation of electron-deficient α,β-enones with a simple zinc-BINOL catalyst in the presence of tert-butyl hydroperoxide and cumene hydroperoxide are described. The epoxidation proceeds in moderate to excellent yields with complete diastereoselectivity and high enantiomeric excesses by using enantiomerically pure BINOL. ­Different substituent effects are discussed.

enantioselective epoxidation - enones - BINOL - zinc - catalysis

References

For a recent review, see:

1a Porter MJ. Skidmore J. Chem. Commun.  2000,  1215 

1b Nemoto T. Ohshima T. Shibasaki M. J. Synth. Org. Chem. Jpn.  2002,  60:  94 

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2b For a recent review, see: Porter MJ. Roberts SM. Skidmore J. Bioorg. Med. Chem.  1999,  7:  2145 

2c Pu L. Tetrahedron: Asymmetry  1998,  9:  1457 

2d Ebrahim S. Wills M. Tetrahedron: Asymmetry  1997,  8:  3163 

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4 Yu H.-B. Zheng X.-F. Lin Z.-M. Hu Q.-S. Huang W.-S. Pu L. J. Org. Chem.  1999,  64:  8149 

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6

Typical Procedure for the Asymmetric Epoxidation: (R)-BINOL (57 mg, 0.2 mmol) was dissolved in Et₂O (20 mL) in a 50 mL Schlenk flask equipped with a magnetic stirring bar under an inert atmosphere. After cooling to 0 °C with an ice-bath ZnEt₂ (0.33 mL, 0.36 mmol, 1.1 M solution in toluene) was added with stirring. After 15 min the α,β-unsaturated ketone (1 mmol) and the oxidant (0.24 mL, 1.2 mmol, 5-6 M in decane in the case of TBHP; 0.22 mL, 1.2 mmol, 80% solution in cumene in the case of CMHP) were added, and the resulting mixture was allowed to warm to r.t. overnight. The reaction was quenched with aq sat. NaHSO₃ and extracted with EtOAc. The organic layer was washed with aq Na₂CO₃ and brine. The combined organic layers were dried over MgSO₄ and the solvent was evaporated in vacuo. The residue was purified by column chromatography (SiO₂: Macherey-Nagel type 60, 0.063-0.2 mm). CH₂Cl₂ was used as eluent in all cases and remaining starting material and the α,β-epoxy-ketone were isolated in this sequence. As the last fraction (R)-BINOL was recovered almost quantitatively. The ee of the epoxides were determined by HPLC analysis on a stationary phase: Chiracel OD/OD-H column with n-hexane-2-propanol as eluent and 254 nm UV detector. The absolute configuration of the products has been assigned by comparison of optical rotation with literature values and the elution order of the two enantiomers on the HPLC column.

The syntheses of the α,β-unsaturated ketones have been described previously:

7a 1a and 1e: Dimmock JR. Zello GA. Oloo EO. Quail JW. Kraatz H.-B. Perjesi P. Aradi F. Takacs-Novak K. Allen TM. Santos CL. Balzarini J. De Clercq E. Stables JP. J. Med. Chem.  2002,  45:  3103 

7b 1b and 1d (1d was synthesised by an analogous procedure as for the corresponding chloride): Krauss SR. Smith SG. J. Am. Chem. Soc.  1981,  103:  141 

7c

1f, 1g, 1h, and 1i: See ref. [3b]

7d 1k: Wiberg KB. Rowland BI. J. Am. Chem. Soc.  1955,  77:  1159 

The characterisation of the α,β-epoxy ketones and the conditions for the chiral HPLC analysis have been described previously:

8a 2a, 2b, and 2e: Adam W. Rao PB. Degen H.-G. Saha-Möller CR. J. Am. Chem. Soc.  2000,  122:  5654 

8b

2d: Complete characterisation of 2d was accomplished

8c

2f, 2g, 2h, and 2i: See ref. [3b]

8d

2k: See ref. [4]