Synthesis of chiral sulfoxides

Chiral sulfoxides are useful intermediates in asymmetric synthesis. A number of methods for their preparation were developed in the last decade. An interesting displacement of dimethylphosphonylmethyl moiety, a carbon leaving group, from sulfur by Grignard reagents was used to obtain enantiomerically purep-tolyl sulfoxides.3 4 Optically pure methyl 4-bromophenyl sulfinate was subjected to a one-pot sequence yielding unsymmetrical dialkyl sulfoxides in 60-97% yield and 98% ee. A simple one-pot synthesis of chiral sulfoxides from norephedrine-derived 

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The Andersen synthesis of chiral sulfoxides has also been extended to diastereomerically or enantiomerically pure arenesulfinamides, which on treatment with methyllithium give optically active methyl aryl sulfoxides (83,85). The use of menthyl sulfinates in the synthesis of sulfoxides has been exploited in the preparation of optically active sulfoxides 47 and 48, which are chiral by virtue of isotopic substitution, H- D (86), and (87), respectively. More recent... 

An alternative stereospecific synthesis of chiral sulfimides reported by Nudelman (137) consists of the reaction of the diastereomeric menthyl p-toluenesulfinimidoates 90 with Gri ard reagents giving the optically active sulfimide 91. This reaction, like the Andersen synthesis of chiral sulfoxides, proceeds with inversion of configura-... 

Wudl and Lee (96,97) reported the first preparation and resolution of the cyclic diastereomeric amidosulfites 58, which have been successfully used in the synthesis of chiral sulfoxides. A mixture of diastereomeric menthyl dimethylamidosulfites (100) was obtained in the reaction of racemic dimethylaminosulfinyl chloride (101) with menthol in the presence of pyridine (149). The degree of asymmetric... 

A similiar approach was performed by van de Velde (1999), using incorporation of vanadate into an acid phosphatase (phytase) to create a semi-synthetic peroxidase similar to the heme-dependent chloroperoxidase. The latter is a useful enzyme for the asymmetric epoxidation of olefins, but less stable due to oxidation of the porphyrin ring and difficult to express outside the native fungal host. The authors exploited the structural similarity of active sites from vanadate-dependent halo-peroxidases and acid phosphatases and have shown the useful application as an enantioselective catalyst for the synthesis of chiral sulfoxides (van de Velde, 1999). 

Synthesis of chiral sulfoxides through 5-membered cyclic sulfites of ethyl lactate 91PS(56)89. 

RECENT ADVANCES IN THE STEREOSELECTIVE SYNTHESIS OF CHIRAL SULFOXIDES... 

Oxidation by chiral oxaziridines. For more than a decade, Davis s group49,71 76 has been working on the stoichiometric asymmetric oxidation of prochiral sulfides. In a series of elegant and important papers, they have demonstrated that their approach is one of the best methods in the synthesis of chiral sulfoxides. This research has yielded four generations of chiral oxaziridines 41- 44 exhibiting different stereoselectivities as a result of their dissimilar active-site structures (Fig. 5). 

This is the second important contribution of Kagan s group in the synthesis of chiral sulfoxides. The method was reported in 1989 for the synthesis of tert-butyl sulfoxides,90 and the full paper on the generalization of the method was published in 1991.86 The approach is based on the synthesis and use of an o.p. cyclic sulfite in the synthesis of various sulfoxides by two successive condensations of two organometallic reagents, RjM and R2M. Thus, the sulfoxides are produced in three separate steps the formation of cyclic sulfite, synthesis of sulfinate esters, and transformation of sulfinates to chiral sulfoxides. 

As part of a program examining the utility of chiral auxiliary rrans-2-phenylcy-clohexanol 60, introduced by Whitesell s group in 1985,96 the same group has investigated the use of this alcohol for the synthesis of chiral sulfoxides. 

Major interest has been expressed in the synthesis of chiral sulfoxides since the early 1980s, when it was discovered that chiral sulfoxides are efficient chiral auxiliaries that are able to bring about important asymmetric transformations [22]. Sulfoxides are also constituents of important drugs (e.g., omeprazole (Losec , Priso-lec )) [23]. There is a plethora of routes of access to enantioenriched sulfoxides, and many involve metal-catalyzed asymmetric oxidations [24]. Examples of ruthenium metal-based syntheses of sulfoxides are scarce, presumably due to the tendency of sulfur atoms to bind irreversibly to a ruthenium center. Schenk et al. reported a dia-stereoselective oxidation of Lewis acidic Ru-coordinated thioethers with dimethyl-dioxirane (DMD) (Scheme 10.16) [25[. Coordination of the prochiral thioether to the metal is followed by diastereoselective oxygen transfer from DMD in high yield. The... 

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