Sulfuranes, chirality

CSAs may also be valuable in providing proof of chirality as structural support for novel or unknown compounds. Martin and coworkers (95) have demonstrated the chirality of various sulfuranes, such as 53, by observing their nonequivalence in the presence of TFPE and TFAE. 

Tetracoordinate sulfur compounds containing a lone pair of electrons at sulfur possess a more or less distorted trigonal-bipyramidal structure, in common with the vast majority of other pentacoordinated molecules of the main group elements (189,191,199). A common name, sulfurane, is generally accepted for this type of compound. In principle, sulfuranes are chiral. However, both the number of optically active isomers and their optical stability depend on the nature of substituents bonded to the central sulfur atom, the apicophilicity of the substituents, and the energy required for permutational isomerization processes. In this context it is interesting to note that acyclic sulfuranes with four different ligands should exist in 20 isomeric forms. 

The first indication of the chirality of sulfuranes was provided by the X-ray analysis of spirosulfurane 176 (192). This work clearly demonstrated the presence of enantiomeric pairs of 176 in the crystal lattice. In 1975, the optically active chlorosulfurane 177, the first example of an optically active tetracoordinate sulfurane, was synthesized by Martin and Balthazor (194,195) by the route indicated in Scheme 15. Reaction of (-)-(5)-menthyl benzenesulfinate 178 with the protected Grignard reagent 179 gave the corresponding sulfoxide alcohol (-)-(5>180 which was cyclized to the chlorosul-... 

The stereochemistry of chiral sulfuranes is in its infancy, and further studies in this field are both expected and desirable. 

Heteroaromatic sulfoxides and sulfones ligand exchange and coupling in sulfuranes and //Avo-substitutions, 49, 1 Heteroaromatic systems, Claisen rearrangements in, 42, 203 Heteroaromatics, quantitative analysis of steric effects in, 43, 173 Heterocycles aromaticity of, 17, 255 chiral induction using, 45, 1 containing the sulfamide moiety,... 

This molecule has an approximately TBP electronic structure and is chiral. However, potentially it could racemize via a series of Berry pseudorotations. 2 That it does not do so readily, and is therefore the first optically active sulfurane to have been isolated, has been attributed to the fact that all racemization pathways must proceed through a TBP with an apical lone pair.53 As we have seen in the preceding chapter, there is a very strong tendency for the lone pair to seek an equatorial site. The reluctance of the lone pair to occupy an apical site appears to be a sufficient barrier to allow the enantiomers to be isolated. 

The oldest syntheses of chrysanthemates are those starting from 2,5-dimethyl-2,4-hexadiene (238). There have been more papers on the use of rhodium or antimony to catalyze the addition of diazoacetate and chiral copper complexes to create asymmetry during the addition (see Vol. 4, p. 482, Refs. 219-222). The problem with this route is to avoid the use of diazo compounds. An old synthesis of Corey and Jautelat used the ylide addition of a sulfurane to a suitable precursor (in this case a C3 unit was added to methyl 5-methyl-2,4-hexadienoate, 239), and a recent paper gives details about the addition of ethyl dimethylsulfuranylideneacetate to 2,5-dimethyl-4-hexen-3-one (240). This led exclusively to the tran -isomer 241, from which ethyl trans-chrysanthemate (185, R = Et) was made. Other ylide additions are mentioned below. 

There has been no systematic study of chromatographic properties, but the enantiomers of the spiro sulfurane (24) have been separated using liquid chromatography on a commercially available chiral stationary phase <93TA2329>. 

Many spiro-oxysulfuranes have been already reported by Martin and his coworkers. Recently, tetra- and pentacoordinated spiro-sulfuranes have been reported, and their characteristic features with regard to their optical properties, dynamic behavior, and reactivities have attracted attention. It should be noted that these compounds become chiral when they contain at least three different ligands. However, due to the topological properties of such molecules, the spirosystems containing two pairs of equivalent substituents (unlike the acyclic analogs) are chiral, as shown in Fig. 4. 

Efficient synthetic approaches to the optically active spiro-sulfuranes and their oxides have been reported by Martin and Drabowicz [65]. The preparation of optically active spirosulfuranes 45 and 46 was performed by asymmetric dehydration of the corresponding prochiral sulfoxide diols 47, as shown in Scheme 29. The optically active oxides 48 and 49 were prepared by oxidation of 45 and 46 with m-chloroperbenzoic acid (mCPBA). The synthesis of the optically active oxides was conducted by the stereoselective conversion of the chiral sulfuranes using Ru04, according to the procedure reported earlier [66]. 

The first step is acetylation of the sulfoxide oxygen and the release of an acetate ion (7 8 Scheme 20.31. Recent computational studies have shown that the initial acetylation step is rate determining and that the release of the acetate ion proceeds by stabilization of the acetate by coordination with a positively charged sulfur, which yields an achiral sulfurane 11. It is generally accepted that the formation of this sulfurane is responsible for the poor enantioselectivity shown in the reactions of chiral sulfoxides. However, sulftirane formation can be avoided by some additives, for exanple, iV,iV-dimethylacetamide (DMAC), iV-methyl-2-pyrrolidone (NMP), or the acetate trap DCC. ... 

The next step in the sulfurane-mediated mechanism is the elimination of acetic acid, providing a racemic mixture of ylides 12. Alternatively, and avoiding the sulfurane, the chiral ylide 9 is... 

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