Sulfur nucleophiles substitution reactions

An a-halosulfone 1 reacts with a base by deprotonation at the a -position to give a carbanionic species 3. An intramolecular nucleophilic substitution reaction, with the halogen substituent taking the part of the leaving group, then leads to formation of an intermediate episulfone 4 and the halide anion. This mechanism is supported by the fact that the episulfone 4 could be isolated. Subsequent extrusion of sulfur dioxide from 4 yields the alkene 2 ... 

Only relatively few nucleophilic substitution reactions at sulfur proceed with retention. Oae found that (R)-(+)-methyl p-tolyl sulfoxide exchanged 180 with dimethyl sulfoxide at 150 °C much faster than it racemized thus, the exchange took place with retention. A cyclic intermediate, 136, was proposed to account for this behavior12,147. The same sulfoxide was found to react with N, JV -ditosylsulfurdiimide, 137, with either retention or inversion depending on the reaction conditions. Christensen148 observed retention in benzene whereas Cram and coworkers149 found that inversion took place in pyridine. A four-membered ring intermediate, 138, was postulated to account for the retention, whereas a... 

Whereas the reactions of sulfones with nucleophiles via pathways A and B of equation 1 are most frequently observed, the nucleophilic substitution reaction by pathway D has been observed only in the cases where the leaving carbanion can be stabilized, or in the highly strained molecules. Chou and Chang3 has found recently that an organolithium reagent attacks the sulfur atom of the strained four-membered sulfone in 34. When this sulfone is treated with 1 equivalent methyllithium, followed by workup with water or Mel, 38 or 39 are formed in high yield. 

Sulfoximines bearing a chiral sulfur atom have recently emerged as valuable ligands for metal-catalysed asymmetric synthesis.In particular, C2-symmetric bis(sulfoximines), such as those depicted in Scheme 1.51, were applied to the test reaction, achieving enantioselectivities of up to 93% ee. The most selective ligand (R = c-Pent, R = Ph) of the series was also applied to the nucleophilic substitution reaction of l,3-diphenyl-2-propenyl acetate with substituted malonates, such as acetamido-derived diethylmalonate, which provided the corresponding product in 89% yield and 98% ee. 

Biirgi studied also a series of five coordinated cadmium complexes, 38, that contain three equatorial sulfur ligands, but in which the fourth and fifth, axial ligands, X and Y, are sometimes iodine, sometimes sulfur, and sometimes oxygen (84). The structural correlations have a clear interpretation in terms of the ligand exchange reaction and are reminiscent of the kind of process that is believed to occur in S 2-type nucleophilic substitution reactions ... 

However, the major factor stimulating the rapid development of static and dynamic sulfur stereochemistry was the interest in the mechanism and steric course of nucleophilic substitution reactions at chiral sulfur. Very recently, chiral organic sulfur compounds have attracted much attention as useful and efficient reagents in asymmetric synthesis. 

Johnson demonstrated that the conversion of (+)-(5 -164 into (-)-(/ )-163 takes place with retention of configuration, whereas the nucleophilic substitution reactions occurred with inversion of configuration at sulfur. The only drawback to this study involved the... 

This section surveys the most important reactions of chiral organo-sulfur compounds. Some of these were touched on in the previous sections. For the sake of convenience, a variety of reactions occurring at the chiral sulfur center are divided into three main types of reactions racemization, nucleophilic substitution reactions, and electrophilic reactions. 

The most frequently encountered reactions in organic sulfur chemistry are nucleophilic displacement reactions. The mechanism and steric course of reactions have been the main points of interest of research groups all over the world, in particular, Andersen, Cram, Johnson, and Mislow in the United States Kobayashi and Oae in Japan Kjaer in Denmark and Fava and Montanari in Italy. The results of these investigators have been discussed exhaustively in many reviews on sulfur stereochemistry. In a recent report on nucleophilic substitution at tricoordinate sulfur, the literature was covered by Tillett (10) to the end of 1975. Therefore only some representative examples of nucleophilic substitution reactions at chiral sulfur are discussed here. However, recent results obtained in the authors laboratory are included. 

The addition-elimination mechanism also provides a reasonable explanation for nucleophilic substitution reactions at sulfur that occur with retention of configuration. It is assumed that nucleophilic attack occurs at sulfur in an apical position opposite a substituent... 

Historically, the thermal transesterification of (-)-ethyl p-toluene-sulfinate 224 with n-butanol affording (+)-n-butyl p-toluenesulfinate 225 described by Phillips in 1925 (100) is the first nucleophilic substitution reaction at chiral sulfur involving a Walden-type inversion. The evidence for inversion of configuration in this reaction was based on the assumption that both (-)-esters 224 and 225 obtained from the kinetic resolution have the same configuration. 

As the last point in Sect. IV, we discuss briefly the reactions of chiral sulfur compounds with electrophilic reagents. In contrast to nucleophilic substitution reactions, the number of known electrophilic reactions at sulfur is very small and practically limited to chiral tricoordinate sulfur compounds that on reacting with electrophilic reagents produce more stable tetracoordinate derivatives. It is generally assumed that the electrophilic attack is directed on the lone electron pair on sulfur and that the reaction is accompanied by retention of configuration. As typical examples of electrophilic reactions at tricoordinate sulfur, we mention oxidation, imination, alkylation, and halogenation. All these reactions were touched on in the section dealing with the synthesis of chiral tetracoordinate sulfur compounds. 

A double nucleophilic substitution reaction on 1,6-dibromohexane with sodium sulfide has been found to give an acceptable yield (59%) of the thiepane (35 equation 62) (81SC409). The reversible 1,6-addition of sulfur dioxide to ds-hexatriene (equation 63) provides a convenient synthetic route to the 2,7-dihydrothiepin 1,1-dioxide (116) (67JA1281). 

Nucleophilic addition of sulfur ylides to C=0 double bonds is an important means of synthesis of epoxides [198], Because optically active epoxides are widely applied as versatile intermediates in the preparation of, e.g., pharmaceuticals, the asymmetric design of this sulfur ylide-based reaction has attracted much interest [199, 200, 212, 213], One aspect of this asymmetric organocatalytic process which has been realized by several groups is shown in Scheme 6.87A. In the first step a chiral sulfur ylide of type 204 is formed in a nucleophilic substitution reaction starting from a halogenated alkane, a base, and a chiral sulfide of type 203 as organocata-... 

The principal focus of our examination of the experimental data in Tables IV through IX will be the dependence of the quantity log(ks/kH2o)r on the structures of both the sulfur nucleophile and the haloaliphatic substrate. Log(ks/kH2o)r (referred to here as the "substrate selectivity" for reaction r) is a measure of the selectivity of a particular substrate between each of the sulfur nucleophiles and H2O with respect to halogen displacement via substitution (if r SN) or dehydrohalogenation (if r E). The use of log(ks/kjj2o)r f°r this purpose serves two functions It "normalizes" sulfur nucleophile reactivity data to a common point of reference, and it gives an indication of the importance of each sulfur nucleophile in reactions with the substrate of interest, relative to the most abundant nucleophile in natural waters, H2O. 

Since sulfonation of pyridine iV-oxide is about as difficult as is that of pyridine itself and takes place at the 3-position,17 it has been assumed18 that, in fuming sulfuric acid, pyridine iV-oxide reacts only in the salt form (3), when the prediction is that substitution at C-3 would take place. It is, however, difficult to account for the fact that bromination, even at 110° in the presence of iron powder, does not occur.17 Bromination in chloroform solution in the presence of acetic anhydride and sodium acetate (when the O-acetate is the the probable substrate) take place readily, however, to give 3,5-dibromopyridine JV-oxide.19 The predicted order of nucleophilic reactivity, on the basis of both atom localization energies and ground-state v-electron density calculations, is 4 > 2 > 3. The same order is predicted for the nucleophilic substitution reactions of the salts of pyridine JV-oxide. In actual practice, iV-alkoxypyridinium derivatives undergo nucleophilic attack preferentially at C-2.20-23 The reaction of some pyridine iV-oxides with phosphorus pentachloride may involve the formation... 

Sulfonic acids, like sulfuric acid, are much stronger acids than carboxylic acids. However, their chemical behavior resembles that of carboxylic acids in many other respects. Sulfonic acids form the same type of derivatives, sulfonyl chlorides, esters, amides, and so on, as do carboxylic acids. These derivatives are intercon-verted by nucleophilic substitution reactions that resemble those of carboxylic acid derivatives. 

So far little information is available on electrophilic substitution reactions these are mainly expected to occur in the azine ring when activated by electron-releasing substituents. Nucleophilic substitution reactions, however, occur readily in either ring. The N—S bond may be cleaved by nucleophilic attack at sulfur and this may be the preferential reaction path in some cases. The N—S bond may also be cleaved as a result of proton abstraction from the azole ring. 

Thus, the kinetic results show that selenophene undergoes both electrophilic and nucleophilic substitution reactions somewhat more readily than does thiophene. Hence, the reactivity of the heterocycle increases when sulfur is replaced by selenium a possible explanation might be that the selenium atom is larger and more polarizable, and therefore more willing both to release its p electrons and to accept electrons into its free d orbitals. 

According to kinetic measurements (21), this reaction proceeds as a nucleophilic substitution reaction with sulfur acting as EPD and apparently involves an electron shift from the more negative to the more positive part of the hypochlorite ion. Formation of a coordinate bond between sulfur and oxygen has been demonstrated using relabeled 0C1-. 

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