Sulfenylation, reviews

Sulfenamides, R2NSR, prepared from an amine and a sulfenyl halide, are readily cleaved by acid hydrolysis and have been used in syntheses of peptides, penicillins, and nucleosides. They are also cleaved by nucleophiles and by Raney nickel desulfurization." The synthesis and application of sulfenamides have been reviewed. ... 

Scheme 2 summarizes the mechanism for the formation of thiosulfonate from sulfinyl radicals it is shown that the sulfinyl radicals combine to give both yic-disulfoxides and O, S-sulfenyl sulfinates, although they may rearrange to thiosulfonates either via a free radical route or via a concerted mechanism. The reader is referred to the recent review of Freeman22, who has collected and discussed the vast amount of information published on yic-disulfoxides and O, S-sulfenyl sulfinates. 

The reactions of thiosulfonates shown in general form in (167), and which constitute the majority of their chemistry, are, of course, substitution reactions at a dico-ordinate, or sulfenyl, sulfur. Substitutions of this type occur widely and with great frequency in the chemistry of all types of sulfenyl compounds. Because of their extreme importance in the chemistry of both thiolsulfonates and other sulfenyl derivatives, it is appropriate that we now review some of the major features regarding their mechanism that have emerged from the study of such reactions with various sulfenyl derivatives. 

The addition of sulfenyl halides to both alkenes and alkynes had been the subject of extensive mechanistic study. The salient results up to about 1969 have been reviewed by Mueller (1969) and Modena and Scorrano (1968). Considerable additional work on various aspects of the detailed mechanisms has been done since that time by Schmid and his co-workers (Schmid and Csizmadia, 1972 Schmid et al., 1972 Schmid and Nowlan, 1976 Schmid et al., 1976b Cerksus et al., 1978). A recent short review by Smit et al. (1979) criticizes some aspects of earlier interpretations of mechanism. 

The sulfenylation of dienes as a distinct class of compounds has not been specifically reviewed, although several examples have been reported in early papers2a,7b. 

Oxathiazoles and dithiazoles with exocyclic conjugation have also been obtained from appropriately substituted sulfenyl chlorides and carboxamides as detailed in Scheme 46. Part of the chlorocarbonylsulfenyl chloride chemistry has been reviewed <70AG(E)54>. 

In order to obtain heterodimers a cysteine residue of one peptide has to be specifically activated for subsequent reaction with the cysteine residue of the second peptide. Thiols are activated by introducing an electron-withdrawing substituent that increases the responsiveness of the sulfur to nucleophilic substitution. This topic has been reviewed 41311 Of the various older methods known in sulfur chemistry for the preparation of unsymmetrical disulfides, i.e. thiosulfates,11321 S-alkylthiosulfonates,11331 5-alkylthiosulfinates,11341 sulfanyl-amines,11351 sulfanylimides,11361 sulfanyl thiocyanates and sulfenyl chlorides,1137,1381 sulfan-... 

Toluenesulfenyl chloride has been prepared by the action of chlorine on a solution of -toluenethiol or />-tolyl disulfide in anhydrous carbon tetrachloride.2,3 Benzenesulfenyl chloride has also been obtained by the interaction of hydrogen chloride and N,N-diethylbenzenesulfenamide 4 and by reaction of benzenethiol with N-chlorosuccinimide.6 A comprehensive review dealing with sulfenyl halides and related compounds is available.6... 

The introduction of a-heteroatom functionalization into an aldehyde or ketone is a very useful class of transformation. Performing it directly and asymmetrically, using organocatalysts, has been reviewed for reactions such as amination, oxygenation, halo- genation, and sulfenylation (44 references).260... 

A very general method for preparing 1,3,4-oxathiazole and 1,2,4- and 1,3,4-dithiazole derivatives from sulfenyl chlorides and amides is shown in Scheme 45, and some of this work has been reviewed (70AG(E)54). As is apparent, the nature of the sulfenyl chloride, and particularly of the amide, strongly influences the course of the reaction. 

Several medio are available for the intnxluction of sulfenyl groups a to carbonyl derivatives and these have been reviewed. - The most versatile procedure involves reaction of the enolate with an appropriate thiol derivative, but the preferred m od is largely dependent on the nature of the substrate employed (see below). In most instances, sulfur has been introduced in the divalent state and subsequently oxidized, although the oxidative step has been avoided by the direct introduction of sulfur at the S oxidation level. The oxidation of sulfides to sulfoxides is a trivial procedure that can be effected by a variety of reagents. Sodium metaperiodate, m-chloroperbenzoic acid and hydrogen peroxide are the most common oxidants, but r-butyl hydroperoxide, r-butyl hypochlorite, N-chlorobenzotriazole,... 

For a more comprehensive account of the methods available for the sulfenylation of carbonyl compounds the review by Trost is recommended. ... 

A large class of compounds derived from sulfur dichlorides are the sulfenyl chlorides, RSCI. They are most commonly obtained by chlorination of a disulfide (RSSR) using CI2 or SO2CI2. They have a large organic chemistry that has been reviewed selected reactions are illustrated in Figure 40. 

The chemistry of the l,3-dithiole-2,4,5-trithione oligomer system 374 derived from monomers 375 and 376 (Scheme 49) has been the subject of a review <2006CHE423>. This system easily depolymerized (heat or UV irradiation at 253 nm) and was effective in Diels-Alder-type cycloadditions. Reactions with unsaturated compounds constituted an efficient method for synthesis of functionalized l,3-dithiole-2-thiones containing substituted 1,4-dithiin rings and are examples of reactivity of thione or sulfenyl substituents (stmctures 374-376) attached to the 1,3-dithiole ring carbon atom. 

Electrophilic addition of sulfenyl compounds at carbon-carbon double bonds, extensively studied and reviewed TOd numerous synthetic applications owing to the regio- and stereoselectivity of the addition . The most common types of agents for the electrophilic addition of sulfur to double and triple bonds are sulfenyl halides (RSX,... 

REVIEWS - Useful reviews have appeared entitled "As5nranetric Syntheses" "New applications of Malononltrlle in Organic Synthesis," s "Intramolecular Ene Reaction in Organic Synthesis," and "a-Sulfenylated Carbonyl Compounds in Organic Synthesis." Additional articles summarize stereospecific olefin syntheses, heterocyclic syntheses by benzyne cycllza-tlons, and ring transformations of pyrimidines. ... 

Photolytic cleavage reactions (e.g., of c-nitrobenzyl, phenacyl, and nitrophenyl-sulfenyl derivatives) take place in high yield on irradiation of the protected compound for a few hours at 254-350 nm. For example, the c-nitrobenzyl group, used to protect alcohols, amines, and carboxylic acids,has been removed by irradiation. Protective groups that have been removed by photolysis are described at the appropriate places in this book in addition, the reader may wish to consult five review articles." - ... 

All of the synthetic routes reviewed so far have primarily involved the use of sulfur as a nucleophile. Sulfur can also act as an electrophile in the formation of precursors of the benzothiazine ring system. Reaction of sulfenyl chloride with ketones gives / -keto sulfides. The acetophenone adduct 90 has been cyclized with stannous chloride and hydrogen chloride in acetic acid to give 3-phenyl-6-chloro-2H-1,4-benzothiazine (91).135... 

Little preparative importance attaches to conversion of organic sulfides into chloro compounds The fission of compounds R-S-R by chlorine, bromine, cyanogen bromide, and methyl iodide, with replacement of C-S by C-halogen bonds has been reviewed by Tarbell and Harnish.1287 The action of 1 mole of bromine on thioacetals in an anhydrous medium (ether) at room temperature affords bromo hemiacetals (a-bromo sulfides) and a sulfenyl bromide, and bromo sugars analogously from ethyl thioglycosides. 

In the absence of other substrates, the corresponding alcohol, aldehyde/ ketone, sulfide (alkyl -I- sulfenyl), and alkyl dimer are isolated [51], The details of all of the studies conducted with this method are beyond the scope of this review, but a brief overview is appropriate. 

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