Optically active sulfoxides preparation methods

Table 11 Result of one-pot preparation method of optically active sulfoxides (64a-d) by a combination of oxidation of sulfide and enantiomeric ...

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. ... 

OpticaUy active iV-tosylsulfoximides produced in the copper-catalyzed reaction of chiral sulfoxides with tosyl azide may be hydrolyzed with strong acid (H2SO4) to optically active free sulfoximides. However, this procedure often fails and/or results in decomposition. It is interesting to note in this connection that a simple one-step method for the preparation of optically active unsubstituted sulfoximides has been reported recently by Johnson and co-workers (180). It involves the reaction between optically active sulfoxides and 0-mesi-tylsulfonylhydroxylamine and results in sulfoximides 60 of high optical purity. As expected, this imidation process occurs with retention of configuration at sulfur. 

The most important and w idely used approach to sulfoxides of high optical purity is based on the reaction of diastereomerically pure menthyl arenesulfinates with Grignard reagents. ( + )-(A)-l-Ethylsulfinyl-4-methylbenzene, prepared from (- j-menthyl (S)-4-mcthylbenzene-sulfmate and ethylmagnesium bromide, was the first optically active sulfoxide obtained by this method 13. 

Optically active sulfoxides are readily obtained from menthyl sulfinate by a Grignaid reaction. This reaction was originally proposed by Gilman and applied to optically active products by Andersen - this is a pure 5n2 reaction at sulfur with displacement of the menthoxy group by the Grignard. A great variety of sulfoxides have been prepared by this method " " other organometallics have also been used. A few examples are shown in Scheme 40. 

Several approaches have been described for the preparation of optically active sulfoxides [5-7]. The three main routes to obtain these compounds are as follows (i) the asymmetric sulfoxidation of prochiral sulfides, (ii) nucleophilic substitution using a chiral sulfur precursor, and (iii) the kinetic resolution of racemic sulfoxides. The first of tiiese methods involves the use of various oxidants and catalysts and has been the most extensively employed. There are many examples in the scientific literature and reviews are available on this approach. In recent years, much attention has been focused on the synthesis of organic sulfoxides by emplo5dng conditions compatible with the green chemistry procedures [8-10]. For this reason, mild oxidants such as molecular oxygen or hydrogen peroxide are considered in combination with novel catalysts in order to develop a mild and environmentally friendly process. 

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. 

An interesting example of a chemical method for determining the absolute configuration of diastereomeiic a-phenylethyl p-tolyl sulfoxides 195 based on the stereospecific sulfinate-sulfoxide conversion has been reported by Nishio and Nishihata (206). In this work optically active a-phenylethyl p-tolyl sulfoxides 195 and the corresponding sulfones 196 were prepared in two different ways and their specific rotations compared (see Scheme 18). Thus, oxidation of (-H5c) Phenylethyl p-tolyl sulfide 197 with hydrogen peroxide... 

Formation of a-Sulfinyl carbanions has been widely investigated17. Several bases were found to be suitable for the generation of these species, e.g., methyllithium and lithium diisopropyl-amide. Butyllithium and rm-butyllithium, however, must be used with caution since they can cause cleavage of the carbon sulfur bond, resulting in an exchange of the ligand at sulfur by a nucleophilic displacement28-29. This method has been used for the preparation of optically active alkyl methyl sulfoxides 28. 

The one-pot method is also applicable to the preparation of optically active epoxides and sulfoxides.25... 

Many organosulfur compounds can be resolved into optically active forms (enantiomers) owing to the presence of a chiral (asymmetric) sulfur atom 5 important examples include sulfoxides and sulfonium salts. Chiral sulfoxides containing amino or carboxylic acid groups have been resolved by formation of the diastereoisomeric salts with d-camphor-10-sulfonic acid or d-brucine. The salts can then be separated by fractional crystallisation and the free optically isomeric sulfoxides liberated by acid hydrolysis. However, a more convenient synthetic procedure for the preparation of chiral sulfoxides of high optical purity is Andersen s method (see p. 30). 

The asymmetric oxidation reaction of prochiral poly(ester 0-sulfide)s to optically active poly(ester 0-sulfoxide)s can be accomplished with almost theoretical chemoselactivity and moderate to high enantioselectivity degrees. While the asymmetric oxidation of prochiral sulfides should not be a preparative method for chiral sulfoxides, we expect that the structure of the parent polymers might be specifically designed for the preparation of chiral thermotropic poly(ester 0-sulfoxi-de)s. 

The methods available for the preparation of optically active a,P-unsaturated sulfoxides are discussed, including the asymmetric synthesis of dienyl sulfoxides, as most of the subsequent work discussed in this chapter is concerned with the use of the sulfoxide group as a stereocontrolling element in synthesis. 

The issue of the variable ( ) (Z) ratios synthesized using this method has recently been addressed by Mikolajczyk and coworkers [18], who have reported a new one-pot ( )-stereoselective synthesis of both racemic and optically active (x,P-unsaturated sulfoxides. In this procedure, ( )-a,P-unsaturated sulfoxides were prepared by the reaction of lithium dimethyldiphenylphosphonium diylide (10) with sulfinates such as (11), followed by treatment of the a-sulfinylmethyldiphenylphosphonium ylide (12), formed with benzaldehyde to give the ( )-styryl sulfoxide (13) in 70% yield (Scheme 5.4). 

P-Alkylation. The Michael-Arbuzov reaction of chloromethyl p-tolyl sulfide with trimethyl Phosphite or triethyl phosphite yields dimethyl- or diethylphosphonylmethyl p-tolyl sulfides, which are important intermediates for the synthesis of vinyl sulfides and sulfoxides, as well as for optically active derivatives of dimethylphosphonylmethyl p-tolyl sulfoxide (eq 7). This method of preparation of the chiral p-tolylthio monosulfoxide is complementary to the reaction using dimethylphosphonyl-methyllithium and (—)-(5)-menthyl p-toluenesulfinate in which the (+)-(7 isomer is obtained in high 3ueld and high optical purity (eq 8). The lithio dimethylphosphonylmethyl p-tolyl sulfoxide reacts with aldehydes and ketones to give the corresponding vinyl sulfoxides, which can be converted into optically active allylic alcohols (eq 9). ... 

Cyclic (hetero- and carbocyclic) vinyl sulfoxides have been prepared by a tandem Michael addition/Homer olefination reaction of a-phosphorylvinyl sulfoxides and carbonyl compounds bearing a nucleophilic center. Using optically active a-phosphorylvinyl sulfoxides a series of enantiomeric cyclic vinyl sulfoxides in which the chiral sulfinyl group is bonded to a chromene, pyrrazolyne, quinoline or cyclopen-tene ring, has been obtained. The H-W-E reaction of aldehydes with sulfinimine-derived 3-oxo pyrrolidine phosphonates (228) represents a new method for the asymmetric synthesis of ring-functionalized cw-2,5-disubstituted 3-oxo pyrrolidines (229) (Scheme 90). ... 

One of the key pioneers in this area was Solladie, who thoroughly investigated the reactions of chiral sulfoxide carbanions [21], Their diastereoselec-tive additions to ketones and aldehydes are illustrative of the method (Scheme 13.16) [67]. Addition of 104 to cyclohexyl methyl ketone (105) thus furnished adduct 106. The sulfoxide, having fulfilled its role as an auxiliary, is subsequently subjected to reductive cleavage to afford hydroxy ester 107. After transesterification, alcohol 108 was produced in 95 % ee. Despite the numerous years that have transpired since these results were first published, such optically active tertiary alcohols remain otherwise difficult to prepare, a feature that attests to the potential value of chiral sulfoxide anions in asymmetric synthesis. 

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