Sharpless reagent

Asymmetric epoxidation of racemic unsaturated fluoro alcohols by the chiral Sharpless reagent can be exploited for kmetic resolution of enantiomers The recovered stereoisomer has 14-98% enantiomeric excess [55] (equation 50)... 

Significant improvements in asymmetric oxidations were made by Modena and, especially, by Kagan, and their coworkers. Both groups used chiral peroxotitanium complexes patterned after the Sharpless reagent as the oxidants. 

The standard Sharpless reagent [Ti(OPr-i)4/(R, R)-diethyl tartrate (DET)/t-BuOOH] oxidizes methyl p-tolyl sulphide into a mixture of racemic sulphoxide and sulphone286. 

The modified Sharpless reagent was also successfully applied288 for the asymmetric oxidation of a series of 1,3-dithiolanes 248 to their S-monooxides 249 (equation 134). It was observed that the optical induction on sulphur (e.e. from 68 to 83%) is not significantly affected by the substituents R1 and R2. Asymmetric oxidation of a few aryl methyl sulphides by organic hydroperoxides in the presence of a catalytic amount of the optically active Schiff base-oxovanadium(IV) complexes gave the corresponding sulphoxides with e.e. lower than 40%289. 

Sesquinorbornatrienes 949 Sharpless asymmetric epoxidation 826 Sharpless reagent 73, 289, 291 Shift reagents, coordination of sulphoxides with 573... 

TABLE 4-1. Asymmetric Epoxidation of Allylic Alcohols by Sharpless Reagents (Method A) and by the Modified Sharpless Reagents (Method B)... 

Conditions Method A Epoxidation using Sharpless reagent method B addition of 0.05-0.1 equivalent of calcium hydride and 0.1-0.15 equivalent of silica gel to the Sharpless reagent, ee = Enantiomeric excess. 

Chiral sulfoxides (12, 92). Chiral sulfoxides are obtained with improved enantioselectivity by substitution of cumene hydroperoxide (CHP, Aldrich) for r-butyl hydroperoxide in the Sharpless reagent.5... 

G. Kinetic Resolution Using a Modified Sharpless Reagent. 120... 

The Sharpless reagent, i.e. Ti(OPr-i)4/TBHP/diethyl tartrate, has been tested in the asymmetric BV oxidation of mono and bicyclic butanones . Conversions are low in all cases and ee values range from moderate to good. The best result has been obtained with the most bulky bicyclic ketone of the series, oxidized to the corresponding lactone with ee values up to 75%, using (+)-diethyl tartrate as ligand (equation 79). The use of a modified Sharpless reagent, based on Ti-TADDOL catalyst , increased the reaction rates, but decreased the enantiomeric excesses . ... 

The enantioselective chemical and enzymatic oxidations of sulfides [86, 94] have also received many interesting developments. High e.e. values have been obtained independently by Kagan [103,104] and Modena [105] via modified Sharpless reagents and by Davis s group [106], which used various chiral oxaziridines. 

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 oxidation of sulfides to sulfoxides by TBHP in the presence of Mo and V catalysts has been extensively studied.230,256 A modified Sharpless reagent,243 i.e. Ti(OPr )4/2 diethyl tartrate/1 H20, was used for the asymmetric oxidation of prochiral sulfides to sulfoxides with enantiomeric excess greater than 90% (equation 82).160,257... 

In the Sharpless epoxidation of divinylmethanols only one of four possible stereoisomers is selectively formed. In this special case the diastereotopic face selectivity of the Sharpless reagent may result in diastereomeric by-products rather than the enantiomeric one, e.g., for the L,-(+)-DIPT-catalyzed epoxidation of (E)-a-(l-propenyl)cyclohexanemethanol to [S(S)-, [R(S)-, [S(R)- and [R(R)-rrans]-a-cyclohexyl-3-methyloxiranemethanol the ratio of rate constants is 971 19 6 4 (see above S.L. Schreiber, 1987). This effect may strongly enhance the e.e. in addition to the kinetic resolution effect mentioned above, which finally reduces further the amount of the enantiomer formed. 

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],... 

Oxidation of 6,ll-diethyl[l,4]dithiino[5,6- ]benzopentathiepin 35 by a Sharpless reagent [Ti(0-i-Pr)4// ,/ -DET/ /-BuOOH] produced optically active 4,9-diethyl[ l,4]-dithiino[5,6-/]bcnzo[ l, 2,3]trithiole-5-oxidc 36 (Scheme 4). The reaction was accompanied by desulfurization and ring contraction of the pentathiepin ring <2003HAC88>. 

Chiral sulfoxides or selenoxides.1 This oxaziridine (1) is generally more effective than the modified Sharpless reagent of Kagan (13, 52) for enantioselective oxidation of alkyl aryl sulfides or selenides to the corresponding sulfoxides or selenoxides. The polar Cl groups of 1 improve both rate and the enantioselectivity. 

Chiral sulfoxides. The Sharpless reagent lor asymmetric epoxidation also effects asymmetric oxidation of prochiral sulfides to sulfoxides. The most satisfactory results are obtained for the stoichiometry Ti(0-(-Pr)4/L DET/H20/(CH,),C00H = 1 2 1 2 for I equiv. of sulfide. In the series of alkyl p-tolyl sulfides, the (R)-sulfoxide is obtained in 41-90% ee the enantioselectivity is highest when the alkyl group is methyl. Methyl phenyl sulfide is oxidized to the (R)-sulfoxide in 81% ee. Even optically active dialkyl sulfoxides can be prepared in 50-71% ee the enantioselectivity is highest for methyl octyl sulfoxide. 

---