Enantioselective sulfoxidation Orsay system

The Orsay system. A good example of serendipity is the discovery by Kagan and co-workers46 at Orsay that 1 mol of water was necessary to produce the active catalyst able to oxidize prochiral sulfides to sulfoxides with high ee. Optimization of the stoichiometry of the titanium complex permitted the determination of the combination Ti(0-i-Pr)4/(/ ,/ )-DET/H20 (1/ 2/ 1) at -20 °C in CH2C12 as the optimal conditions to achieve high enantioselectivity. Table 6 shows some representative results obtained for the oxidation of several thioethers with tert-butyl hydroperoxide (TBHP) under these conditions.50,51... 

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],... 

The Orsay group discovered that addition of 4 mol equiv. of isopropanol to the Padua complex (Ti(0-i-Pr)4/(i ,7 )-DET = 1 4) gave a complex that can be used in catalytic quantities (10 mol % with respect to sulfide) in the sulfoxidations with cumene hydroperoxide [39,40], With this catalyst system, which needs the presence of 4A molecular sieves, enantioselectivities in the range of 90% ee have been achieved for the preparation of various aryl methyl sulfoxides. Even benzyl methyl sulfoxide was obtained with 90% ee. 

A recent systematic study of the role played by titanium alkoxide, 2-propanol, and molecular sieves (MS) has permitted the development of an efficient catalytic system furnishing chiral sulfoxides with high ee.54 This catalyst has a new composition Ti(0-i-Pr)4/(/ ,/ )-DET/i-PrOH (1 / 4 / 4), in the presence of 4A MS, which is a combination of the Modena47 and Sharpless systems. Using this new system, the Orsay group achieved the highest enantioselectivity in catalytic asymmetric oxidation of sulfides by a nonenzymatic method (Table 8). 

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