Racemic sulfoxide

Numerous reactions of racemic sulfoxides with chiral reagents have been accomplished2,12. These examples of kinetic resolution usually lead to sulfoxides of low enantiomeric purity, but there are some exceptions. 

Preparation of the appropriate optically active sulfmate ester is initially required for reaction with a Grignard or other organometallic reagent. If the method is to produce homochiral sulfoxides, the precursor sulfmate ester must be optically pure. An exception to this statement occurs if the reaction yields a partially racemic sulfoxide which can be recrystallized to complete optical purity. 

In principle, it should be possible to selectively reduce one of the enantiomers in a racemic sulfoxide mixture that is, an asymmetric kinetic resolution via reduction should... 

Sharpless and Klunder22 are developing a new procedure for conversion of sulfonyl chlorides directly into menthyl sulflnate esters using trimethyl phosphite as a reducing agent (equation 2). This method, starting with sulfonyl chlorides rather than with the much less available sulfinyl chlorides, should allow access to an even wider range of sulfinate esters and, ultimately, to various chiral, non-racemic sulfoxides. 

Parallel to the modification of the catalytic performance in Baeyer-Villiger oxidations, random mutagenesis was successfully applied to improve the stereoselectivity of CHMOAcineto hi cascs of essentially racemic sulfoxide formation. In addition, enantiodivergent clones with >98% ee for both antipodal products were identified (Table 9.5) [205]. However, improvement in stereoselectivity of mutant enzymes was often accompanied by increased formation of sulfone. This effect can also be utilized to resolve racemic sulfoxides. 

Ohta and coworkers used a bacterium, Corynebacterium equi IFO 3730, rather than a fungus, to oxidize eight alkyl phenyl and p-tolyl sulfides to their respective sulfoxides (119, 120) of configuration R. Virtually all of the sulfur compounds were accounted for as the sum of uncreacted sulfide, sulfoxide and sulfone. The enantiomeric purities of the sulfoxides obtained were quite good and are shown below in parentheses. The formation of the allyl sulfoxides in high optical purity is noteworthy. The authors believe that the sulfoxides were formed by enantioselective oxidation of the sulfides rather than by enantioselective oxidation of racemic sulfoxides, since the yield of sulfoxides was greater than 50% in five of the ten oxidations reported (see also Reference 34). 

This chapter, however, does not deal with above-mentioned reactions of sulfoxides. Rather it is limited to asymmetric synthesis using a-sulfinyl carbanions and -unsaturated sulfoxides, specifically in which the stereogenic sulfoxide sulfur atom is enantiomerically pure. Therefore reactions of racemic sulfoxides are for the most part excluded from this review. For more general discussions, the reader is referred to other chapters in this volume and to other reviews on the chemistry of sulfoxides. Especially useful are the reviews by Johnson and Sharp and by Mislow in the late 1960s and by Oae and by Nudelman as well as a book by Block . A review by Cinquini, Cozzi and Montanari" through mid-1983 summarizes the chemistry and stereochemistry of optically active sulfoxides. This chapter emphasizes results reported from 1984 through mid-1986. 

With this encouraging result from the model system, a gram quantity of the racemic sulfoxide 40 was prepared by oxidation of benzoxathiin 16 with mCPBA and a small amount of chiral sulfoxide (A)-40 with 94% ee was isolated by subsequent chiral HPLC separation (Scheme 5.12). When chiral sulfoxide (S)-40 was treated with borane-dimethylsulfide, a clean reduction of the olefin and the sulfoxide was observed. More surprisingly, only the desired cis-diaryl dihydrobenzoxathiin 12 was observed in high yield and unchanged 94% ee. No trans-isomer or 16 was observed. With this proof of concept in hand, an efficient... 

In addition, a recent report details a very efficient nonenzymatic method for the asymmetric oxidation of sulfides this employs an organo-vanadium species featuring the imine (38) (Scheme 25)[111]. A second, complementary strategy for the preparation of optically active sulfoxides involves the enantioselective oxidation of racemic sulfoxides. ... 

The mixture was cooled to 22 °C, then titanium(IV) isopropoxide (0.09 mL) and hydroperoxide (228 mg) were added. Stirring was maintained for 10 minutes and racemic sulfoxide (110 mg solved in 1.5 mL of anhydrous dichloromethane) added to the mixture. 

Table 8.2 Kinetic resolution of racemic sulfoxides (R-SO-Me) with 1.

This LSR-CSA technique (discussed in detail in ref. 76) has also been appUed to a series of sulfoxides. Nitroarylsulfoxides are also capable of a strong three-point interaction with fluoroalcohols 1, an ability that is responsible for a considerable difference in stability between the solvates. Mixtures of Id and 2,4-dinitrophenyl methyl sulfoxide are red, and the intensity of this color is inversely proportional to temperature, consistent with formation of tt-tt complexes. Crystallization of the racemic sulfoxide from carbon tetrachloride solutions of (/ )- d leaves mother liquor enriched in the (i )-sulfoxide enantiomer, that predicted by the usual solvation model (41), to form the more stable solvate. With this compound it is also apparent that the (/ , iS )-solvate may differ considerably from the predicted conformation, by population of 42. This additional interaction. 

Since in principle the reactions of enantiomeric sulfoxides with a chiral reagent are expected to proceed at unequal rates, a possibility exists for obtaining chiral sulfoxides, especially when the reacting racemic sulfoxide is used in excess in relation to the chiral reagent. A typical example of such a kinetic resolution of a racemic sulfoxide is its reaction with a deficiency of chiral peracid, affording a mixture of optically active sulfoxide and achiral sulfone (62,63). However,... 

Optically active sulfoxides can also be obtained when a racemic sulfoxide is reduced with an insufficient amount of a chiral reagent. Balenovic and Bregant (65) found that L-cysteine reacted with racemic sulfoxides to produce a mixture of sulfide, L-cystine, and nonreduced optically active starting sulfoxide. Mikoikjczyk and Para... 

Recently, Juge and Kagan (68) reported that a more efficient kinetic resolution of racemic sulfoxides takes place in the Pummerer-type reaction with optically active a-phenylbutyric acid chloride 38 in the presence of N,A-dimethylaniline. In contrast to the asym-... 

A special mention in the field of enantioselective HPLC separations must be made of chiro-optical detection systems, such as circular dichroism (CD) and optical rotation (OR), which can be also used to circumvent the low UV detectability of chromophore-lacking samples [40, 61]. While sensitivity of chiro-optical detection is not always sufficient to perform enantiomeric trace analysis, the stereochemical information contained in the bisignate spectropolarimetric response is useful in establishing elution order for those compounds not available as single enantiomers of known configuration. An example of application of different online detection systems (UV and CD at 254 nm) in the enantioselective separation of a racemic sulfoxide on a commercially available TAG CSP is reported in Figure 2.12, under NP conditions. 

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