Chirality of the sulfur atom

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. 

Also, on chelation to a benzimidazole the heterocyclic system is not planar as shown by the crystal data of 4-phenoxy-l/4,2,4,6-thiatriazino[4,3-sulfur atom lies visibly out of the best plane of the ring system. Even in solution thiatriazinobenzim-idazoles exhibit nonplanarity, as shown by the H NMR of jV-tosyl-4-(2,2,2-trichloroethoxy)-l/4,2,4,6-thiatriazino 4,3-<7]benzimidazol-2-amine (see Section 2.1.1.1.2., compound 3d). The CH, moiety of the 2,2,2-trichloroethoxy group in the 4-position gives an AB quartet defining the chirality of the sulfur atom.54... 

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 addition to chemical correlations discussed above, several physical methods are now available for the determination of the relative and absolute configurations of chiral sulfur compounds. Among these, NMR, infrared (IR), optical rotatory dispersion (ORD), circular dichroism (CD), and X-ray analysis are the most important. Sections III-B-1 to III-B-5 outline applications of these techniques for establishing the chirality around the sulfur atom. 

The addition criterion may similarly be applied to recognize diastereotopic faces. Methyl a-phenethyl ketone, 58 in Fig. 19 has a chiral center addition clearly gives rise to diastereomers (59a, 59b) the faces of the carbonyl carbon are diastereotopic and the C = 0 group is prochiral. This case is of importance in conjunction with Cram s rule 10). Compounds 60, 62 and 64 also display diastereotopic faces even though the products 61, 63 and 65 are not chiral 60, 62 and 64 have prostereogenic rather than prochiral faces. The C=0 group in 60 is propseudoasymmetric, since C(3) in 61 is a pseudoasymmetric center. a-Phenethyl methyl sulfide (66) displays diastereotopic sides of a molecular plane not due to a double bond 5,24> and may alternatively be considered a case of diastereotopic phantom ligands (unshared pairs on sulfur). This case does involve chirality and the sulfur atom is prochiral. 

Providing the two groups attached to sulfur are different, a sulfoxide is chiral at the sulfur atom. There are two important ways of making sulfoxides as single enantiomers, both asymmetric versions of reactions otherwise used to make racemic sulfoxides oxidation and nucleophilic substitution at sulfur. 

Lithiated chiral dihydro-1,4-dithiins (152) have been recently utilized in the addition to prochiral aldehydes in the presence of Ti(OPi )4 (Scheme 23). Under such conditions (Z)-allylic alcohols have been obtained in good yields and with satisfactory enantioselectivity (ee >40%), after removal of the chiral sulfur-containing moiety of the addition product. The reaction is likely to proceed via the formation of a cyclic five-membered transition state (153) involving titanium, oxygen and one of the sulfur atoms. When Ti(OPi )4 is replaced by TiCLt, the addition becomes slower than the uncatalyzed reaction itself. 

Chirally modified thiocuprates are used mostly in the catalytic process. The success is probably due to the high affinity of the sulfur atom to copper and the great stability of the sulfur-copper bond. 

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