Carbon—sulfur bond forming reactions formation

Recently, interest in copper-catalyzed carbon-heteroatom bond-forming reactions has shifted to the use of boronic acids as reactive coupling partners [133], One example of carbon-sulfur bond formation is displayed in Scheme 6.65. Lengar and Kappe have reported that, in contrast to the palladium(0)/copper(l)-mediated process described in Scheme 6.55, which leads to carbon-carbon bond formation, reaction of the same starting materials in the presence of 1 equivalent of copper(II) acetate and 2 equivalents of phenanthroline ligand furnishes the corresponding carbon-sulfur cross-coupled product [113]. Whereas the reaction at room temperature needed 4 days to reach completion, microwave irradiation at 85 °C for 45 min in 1,2-dichloroethane provided a 72% isolated yield of the product. 

Novel Palladium Chloride-Based Catalysts for Carbon-Carbon / Carbon-Heteroatom Bond Formations. The past decade has witnessed the development of novel palladacycles as a new class of catalysts for carbon-carbon/carbon-heteroatom bond-forming reactions. Several types of palladacycles (derived from PdCl2) have appeared in the literature. These include PC type, PCP pincer type, phosphite palladacycles, NC type, NCN pincer type, and sulfur containing palladacycles. Heterogeneous palladacycles have also been reported in the literature. These palladacycles are obtained via direct metallation from appropriate ligands with either PdCl2 or Na2PdCl4. Typical examples are shown in Scheme 1. 

The formation of an alkanethiol by reaction of an alkyl halide or alkyl /Moluenesulfonatc with thiourea occurs with inversion of configuration in the step in which the carbon-sulfur bond is formed. Thus, the formation of (R)-2-butanethiol requires (.S Kvcc-butyl /Moluenesulfonatc, which then reacts with thiourea by an SN2 pathway. The /Moluenesulfonatc is formed from the corresponding alcohol by a reaction that does not involve any of the bonds to the stereogenic center. Therefore, begin with (.S )-2-bulanol. 

Although sulfur forms a variety of structures differing in the number of ligands and valency, the overwhelming majority of stereoselective C-S bond forming reactions are limited to those which afford chiral carbon compounds with the sulfenyl, sulfinyl and sulfonyl moieties bonded to the stereogenic carbon atom. In accord with this, discussion of stereoselective C—S bond formation will be divided into three corresponding subsections. Procedures with stereoselective C—S bond formation where the sulfur is in a less common form are also presented. 

Cheletropic Cycloadditions. If an atom can both donate an electron pair and accept an electron pair to move to a higher covalency, it can act as a dienophile to a diene. Such is the case with the sulfur atom in sulfur dioxide and with phosphoms in tricovalent halides. This type of cycloaddition is called cheletropic, and results in the formation of 5-membered rings. The reaction of butadiene with SO2 is particularly important it is conducted on a commercial scale to produce the cyclic sulfone 5.18 (called sulfolene). Its hydrogenation product 5.19 (sulfolane) is widely used as a nonaqueous highly polar solvent. Substituted dienes also participate in the cycloaddition. Here, the sulfur can donate its electron pair while accepting an electron pair to form a new carbon-sulfur bond. 

Kaupp et al. employed ball-milling technique to transform thioureas 79 by reaction with phenacyl bromide to 2-amino-4-phenyl-thiazole-hydrobromides 80 in quantitative yields from stoichiometric mixtures of the reagents at room temperature (Scheme 4.21) [14]. In soUd-state conditions, base catalyst was not needed. The water formed in the reaction does not hydrolyze phenacyl bromide under applied mild conditions and was removed by heating at 80°C in vacuo. When the same reaction was performed in a melt at 110°C, partial hydrolysis occurred, which diminishes yield, while yields obtained in solntion were lower (80-90%). This Hantzsch thiazole synthesis starts with nucleophilic snbstitution on snlfur and formation of the carbon-sulfur bond (S-alkylation), followed by further reaction cascade which results in heterocychc ring. 

The broad class of products described as sulfonates results from reactions that create a carbon-sulfur bond and utilizes sulfur VI reagent SO3 and its derivatives and adducts such as sulfuric acid. A smaller number of sulfonate products are prepared using sulfur IV reagent SOj as well as its derivatives and adducts such as sodium bisulfite. The preparation of sulfate esters involves the creation of carbon-oxygen-sulfur bonds, and can utilize SO3, sulfuric acid, or chlorosul-fonic acid to form alcohol sulfates that are labile and susceptible to hydrolysis in the presence of water as well as elimination reactions at elevated temperatures, and must be handled under milder conditions than sulfonates during formation and neutralization. Numerous older reviews and recent publications exist covering sulfonation and sulfation processes to produce surfactant products. " ... 

Synthesis of Sulfur Amino Acids. Of the many oxidation states of sulfur, only sulfite has been shown to be utilized by cell-free systems in the net synthesis of compounds with carbon-sulfur bonds, although mutant studies have indicated that more reduced forms can be incorporated. The formation of cysteinesulfinic acid from sulfite has been demonstrated in extracts of acetone-dried rabbit kidney it is possible that this reaction participates in the principal mechanism of sulfur incorporation. In many organisms that require preformed sulfur amino acids, cysteine may be formed from methionine. Only the sulfur of methionine is transferred to cysteine the carbon skeleton of cysteine is derived exclusively from serine. Transsulfuration appears to require the formation of homocysteine from methionine. Homocysteine and serine condense to form a thioether, cystathionine (V). Pyridoxal phosphate has been... 

Scheme 10 shows a proposed scheme of the overall reaction catalyzed by IPNS [161]. Mechanistic studies have been performed using kinetic isotope effects [166-168] and substrate analogues [153, 169-178] by Baldwin et al. Based on these reactivities, it has been proposed that an enzyme-bound P-lactam intermediate attached to the iron(IV) (ferryl) center is formed and that the complex reacts to complete carbon-sulfur bond formation by a free-radical mechanism. Each ring closure inhibits a marked primary kinetic isotope effect and monocyclic products without thiazolidine ring closure are formed by using ACV analogues. It was shown that the C-S bond formation proceeds with complete retention of stereochemistry [179] and that an epoxide is formed from... 

Beyond C-C bond forming reactions, decarboxylative couplings have recently found application in regiospecific formations of carbon-halogen [82, 83], carbon-sulfur [84, 85], carbon-phosphorus [86, 87], carbon-nitrogen [88], and carbon-oxygen bonds [89]. 

Because of the carbon-sulfur bond, oligomerization to polysulfides, which is common with hydrosulfides, is not favored, and the reaction will usually terminate with the formation of the disulfide, RSSR. Some of the disulfides are stripped out in the spent regenerator air. The bulk of the remaining disulfides can normally be decanted from the solution surface, since they are very sparingly soluble in aqueous solutions. If they ate not removed, a large proportion of the disulfide impurities formed in the process are adsorbed on the sulfur surface and leave the system in the filtercake. Because this disulfide component also contains unconverted mercaptans, the sulfur produced may have a distinct unpleasant mercaptan odor. 

Due to sluggish reactivity of aryl and vinyl halides in nucleophiUc substitution reactions, the formation of sulfur-carbon(sp ) bonds is typically carried out using transition metal catalysis [22-27]. While the field is dominated by the use of palladium, copper, and nickel catalysts, considerable advances have been made using more abundant metal catalysts such as iron. Additionally, a number of transition metal-fiee approaches have been developed for the formation of sulfur-carbon(sp ) bonds. The following sections will highlight representative examples of C—S bond forming reactions. 

In this chapter, we provide a short review of the use of sulfones in carbon-carbon, bond-forming reactions. We shall present also less classic reactions of sulfur dioxide and their applications in the development of new reaction cascades that permit diastereoselective C—C bond formation. Applications of the latter to the efficient synthesis of... 

In this behavior, sulfur resembles iodine, which reacts in an analogous way to form polyiodides. Sulfur will also remove hydrogen from saturated hydrocarbons to produce H2S with the formation of carbon-carbon double bonds. Sulfur dissolves in hot concentrated nitric acid as a result of being oxidized as shown in this reaction ... 

---