Sharpless reagent, water-modified

The Orsay group found serendipitously that methyl p-tolyl sulfide was oxidized to methyl p-toly 1 sulfoxide with high enantiomeric purity (80-90% ee) when the Sharpless reagent was modified by addition of 1 mole equiv. of water [16,17]. The story of this discovery was described in a review [19], Sharpless conditions gave racemic sulfoxide and sulfone. Careful optimization of the stoichiometry of the titanium complex in the oxidation of p-tolyl sulfide led to the selection of Ti(0iPr)4/(7 ,7 )-DET/H20 (1 2 1) combination as the standard system [ 17]. In the beginning of their investigations, the standard conditions implied a stoichiometric amount of the chiral titanium complex with respect to the prochiral sulfide [16,17,20-23]. Later, proper conditions were found, which decreased the amount of the titanium complex without too much alteration of the enantioselectivity [24,25],... 

Chiral sulfoxides (12, 92). Kagan et al.3 have reviewed the asymmetric oxidation of sulfides by a water-modified Sharpless reagent. Optical yields are generally highest in the oxidation of aryl methyl sulfides (—75-90%). 

The original Sharpless reagent, a mixture of tetraisopropyl orthotitan-ate, (i ,/ )-diethyl tartrate, and tert-butyl hydroperoxide in the ratio 1 1 2 in dry dichloromethane or 1,2-dichloroethane [1025, is modified by adding 1 mol of water 224, 1029]. Such a reagent gives higher enantiomeric excesses. Of many sulfide oxidations that have been carried out, the conversion of methyl p-tolyl sulfide into the sulfoxide is shown in equation 565. 

A modified Sharpless reagent has been developed by Kagan [503, 814], Modena [502, 814] and their coworkers. This new catalyst is formed by mixing water, Ti(0/-Pr)4, and diethyltartrate in a ratio of 1/1/2. The modified catalyst promotes enantioselecfrve oxidation of arylalkylsulfides by fert-BuOOH, and chiral sulfoxides are produced with excellent enantiomeric excesses (> 90%). Lower selectivities are observed from dialkylsulfides. From (R,R) or (5 S)-diethyl tartrate, either sulfoxide enantiomer can be obtained. The use of cumene hydroperoxide as the oxidant may improve the enantioselectivity. Uemura and coworkers obtained similar results by replacing the tartrates in these complexes with binaph-thols [815],... 

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