Chiral sulfoxides chirality

Some chiral versions of 1.3-dipolar cycloadditions with nitrones, utilizing chiral sulfoxides, chiral nitrones, and sulfones substituted with a chiral group, are known. 

Synthesis of Chiral Sulfoxides. Chiral sulfoxides have been used extensively in asymmetric synthesis. An extremely... 

The large sulfur atom is a preferred reaction site in synthetic intermediates to introduce chirality into a carbon compound. Thermal equilibrations of chiral sulfoxides are slow, and parbanions with lithium or sodium as counterions on a chiral carbon atom adjacent to a sulfoxide group maintain their chirality. The benzylic proton of chiral sulfoxides is removed stereoselectively by strong bases. The largest groups prefer the anti conformation, e.g. phenyl and oxygen in the first example, phenyl and rert-butyl in the second. Deprotonation occurs at the methylene group on the least hindered site adjacent to the unshared electron pair of the sulfur atom (R.R. Fraser, 1972 F. Montanari, 1975). 

In cyclic sulfoxides Che diastereomeric product ratio is even higher, and the chirality of the sulfur atom has been efficiently transferred to the carbon atom in synthesis. 

Tricoordmate sulfur compounds are chiral when sulfur bears three different sub stituents The rate of pyramidal inversion at sulfur is rather slow The most common compounds m which sulfur is a chirality center are sulfoxides such as... 

Phenyl vinyl sulfoxide is chiral Phenyl vinyl sulfone is achiral... 

Chiral Center. The chiral center, which is the chiral element most commonly met, is exemplified by an asymmetric carbon with a tetrahedral arrangement of ligands about the carbon. The ligands comprise four different atoms or groups. One ligand may be a lone pair of electrons another, a phantom atom of atomic number zero. This situation is encountered in sulfoxides or with a nitrogen atom. Lactic acid is an example of a molecule with an asymmetric (chiral) carbon. (See Fig. 1.13b.)... 

There are a number of important kinds of stereogenic centers besides asymmetric carbon atoms. One example is furnished by sulfoxides with nonidentical substituents on sulfur. Sulfoxides are pyramidal and maintain dieir configuration at room temperature. Unsymmetrical sulfoxides are therefore chiral and exist as enantiomers. Sulfonium salts with three nonidentical ligands are also chiral as a result of their pyramidal shape. Some examples of chiral derivatives of sulfur are given in Scheme 2.1. 

Chiral chemical reagents can react with prochiral centers in achiral substances to give partially or completely enantiomerically pure product. An example of such processes is the preparation of enantiomerically enriched sulfoxides from achiral sulfides with the use of chiral oxidant. The reagent must preferential react with one of the two prochiral faces of the sulfide, that is, the enantiotopic electron pairs. 

An achiral reagent cannot distinguish between these two faces. In a complex with a chiral reagent, however, the two (phantom ligand) electron pairs are in different (enantiotopic) environments. The two complexes are therefore diastereomeric and are formed and react at different rates. Two reaction systems that have been used successfully for enantioselective formation of sulfoxides are illustrated below. In the first example, the Ti(0-i-Pr)4-f-BuOOH-diethyl tartrate reagent is chiral by virtue of the presence of the chiral tartrate ester in the reactive complex. With simple aryl methyl sulfides, up to 90% enantiomeric purity of the product is obtained. 

Verify, by making molecular models, that the bonds to sulfur are arranged in a trigonal pyramidal geometry in sulfoxides and in a tetrahedral geometry in sulfones. Is phenyl vinyl sulfoxide chiral What about phenyl vinyl sulfone ... 

Sharpless and Masumune have applied the AE reaction on chiral allylic alcohols to prepare all 8 of the L-hexoses. ° AE reaction on allylic alcohol 52 provides the epoxy alcohol 53 in 92% yield and in >95% ee. Base catalyze Payne rearrangement followed by ring opening with phenyl thiolate provides diol 54. Protection of the diol is followed by oxidation of the sulfide to the sulfoxide via m-CPBA, Pummerer rearrangement to give the gm-acetoxy sulfide intermediate and finally reduction using Dibal to yield the desired aldehyde 56. Homer-Emmons olefination followed by reduction sets up the second substrate for the AE reaction. The AE reaction on optically active 57 is reagent... 

Chiral acetylenic sulfoxides and related compounds in synthesis of heterocycles 97MI39. 

New reactions utilizing features of sulfur atom in chiral sulfoxides, derivatives of heterocycles 99YZ126. 

Remote asymmetric induction using chiral sulfoxides, derivatives of furan, thiophene, and pyrrole 98YGK798. 

A chiral sulfoxide can be used as a leaving group for the asymmetric inducdon via addidon-eliminadonprocess. 5-Lactam enolates are converted into the corresponding nitroalkenes subsdnited with lactams fEq. 4.101. ... 

To control the stereochemistry of 1,3-dipolar cycloaddidon reacdons, chiral auxiliaries are introduced into either the dipole-part or dipolarophile A recent monograph covers this topic extensively ° therefore, only typical examples are presented here. Alkenes employed in asymmetric 1,3-cycloaddidon can be divided into three main groups (1) chiral allyhc alcohols, f2 chiral amines, and Hi chiral vinyl sulfoxides or vinylphosphine oxides. 

Besides simple alkyl-substituted sulfoxides, (a-chloroalkyl)sulfoxides have been used as reagents for diastereoselective addition reactions. Thus, a synthesis of enantiomerically pure 2-hydroxy carboxylates is based on the addition of (-)-l-[(l-chlorobutyl)sulfinyl]-4-methyl-benzene (10) to aldehydes433. The sulfoxide, optically pure with respect to the sulfoxide chirality but a mixture of diastereomers with respect to the a-sulfinyl carbon, can be readily deprotonated at — 55 °C. Subsequent addition to aldehydes afforded a mixture of the diastereomers 11A and 11B. Although the diastereoselectivity of the addition reaction is very low, the diastereomers are easily separated by flash chromatography. Thermal elimination of the sulfinyl group in refluxing xylene cleanly afforded the vinyl chlorides 12 A/12B in high chemical yield as a mixture of E- and Z-isomers. After ozonolysis in ethanol, followed by reductive workup, enantiomerically pure ethyl a-hydroxycarboxylates were obtained. 

High diastereoselectivity at the sulfinyl group bearing carbon and low diastereoselectivity at the prostereogenic carbonyl group resulted on addition of a chiral sulfoxide carbanion to an... 

However, it can be expected that anions of allyl sulfoxides maintain, at low temperature, the chiral integrity of the sulfoxide group and that reactions with electrophiles could have regio-and stereochemical implications. 

The big difference between the extent of asymmetric induction on the addition to a prostereogenic carbonyl group of simple carbanions a to a chiral sulfoxide on the one hand and enolates of sulfinyl esters on the other, can be attributed to the capacity of the ester function to chelate magnesium in the transition states and intermediates. The results already described for the addition of chiral thioacetal monosulfoxide to aldehydes (see Section 1.3.6.5.) underscore the importance of other functions, e.g., sulfide, for the extent of asymmetric induction. 

G. H. Posner, Addition of Organometallic Reagents to Chiral Vinyl Sulfoxides in Asymmetric Synthesis. J. D. Morrison, Ed. Vol. 2, p. 225, Academic, New York 1983. 

Mainly sulfoxide groups are introduced as chiral auxiliaries for the modification of a,/J-unsat-urated enones (see Section D.1.5.3.5.). Chiral imine derivatives have also been used (see Section D.1.5.3.1.). Various chiral alcohols, and in particular 8-phenylmenthol, have been successfully used as auxiliaries, mainly in two-fold Michael additions to a,/ -unsaturatcd esters. 

In this chapter the addition of carbon nucleophiles to simple a,j8-unsaturated sulfoxides, a-sulfinyl-a,/ -unsaturated ketones and a-sulfmyl-a,/ -unsaturated lactones will be discussed separately, in most cases the asymmetric induction arises from the chirality at sulfur. 

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