Enantioselective α-Oxytosylation of Ketones Catalysed by Iodoarenes

Abstract

The α-oxytosylation of ketones catalysed by enantioenriched iodoarenes using mCPBA as stoichiometric oxidant is reported to give useful synthetic intermediates in good yield and modest enantioselectivity. We believe this to be the first report of an enantioselective catalytic reaction involving hypervalent iodine ­reagents which should open up a new field for enantioselective ­organocatalysis of oxidation reactions.

Key words

hypervalent iodine reagents - organocatalysis - oxidation - stereoselective synthesis

References and Notes

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7

Commerical mCPBA obtained as a 70-77% mixture with H₂O and mCBA is used in the reaction without any attempts at purification or drying. We find that this performs as well as mCPBA that has been dried before use, obviating the need for the dangerous drying process.

9

After seeing results of Y. Kita (Dohi, T.; Maruyama, A.; Minamitsuji, Y.; Takenaga, N.; Kita, Y. Chem. Commun. 2007, DOI: 10.1039/b616510a, in press) in which 2,2,2-trifluoroethanol can be used as solvent to increase the rate of oxidation of 4-iodotoluene by mCPBA, we applied to the iodobenzene-catalysed oxytosylation of propiophenone but this gave no increase in reaction rate.

12

Representative Experimental Procedure
A solution of propiophenone (1, 67 mg, 0.5 mmol) in MeCN (1 mL) was added to a solution of iodoarene 5 (15 mg, 0.05 mmol) TsOH·H₂O (285 mg, 1.5 mmol) and mCPBA (366 mg, 77% wet with H₂O, 1.5 mmol) in MeCN (2 mL) at r.t. The resulting solution was stirred at r.t. for 60 h then quenched by addition of sat. aq Na₂S₂O₃ (5 mL) and sat. aq Na₂CO₃ (5 mL). The mixture was extracted with EtOAc (3 × 5 mL), the combined organic layers were washed with brine (10 mL), dried over Na₂SO₄, filtered and concentrated under reduced pressure. The residue was purified by flash column chromatography (SiO₂, 80:20 hexane-EtOAc) to yield tosylate 3 (119 mg, 0.39 mmol, 78%) as a white powder. The ee was determined by HPLC on the crude and purified products: Chiracel OB-H column, 40:60 hexane-2-PrOH, 0.5 mL·min^-1, 40 °C, t _R = 18.1 min (R), 21.6 min (S).