Carbothiolations

A number of sulfur-centered radical scavengers have been employed for Meerwein type carbothiolation reactions [109, 110]. The most prominent of those are certainly xanthates [111-113] and thiocyanates, among which the latter have received special attention recently. As shown in Scheme 21, thiocyanates are well-suited for the functionalization of activated and non-activated alkenes [114, 115]. Remarkably, the reaction of 56 with 2-methallyl chloride to give 57 is not significantly impeded by the possible (3-fragmentation of a chlorine radical, which would lead to allylation products [116]. With an activated and a non-activated alkene present in a substrate... 

Scheme 21 Carbothiolation of non-activated and activated alkenes with thiocyanates [92, 114, 115]...

In order to avoid even the minimal systemic side effects seen with currently available corticosteroids, scientists at Glaxo synthesized a series of androstane 17/ -car-boxylates and carbothiolates. It was found that halomethyl carbothiolates showed the highest topical activity as assessed by the inhibition of croton oil-induced ear inflammation in mice. The highest activity was found in the fluoromethyl car-bo thiolate-17-propionate (fluticasone propionate) synthesized from flumethasone [49-51],... 

The reaction of 1-amino-l-deoxy-D-fructose with ethyl thiolacetoacetate under the same conditions gives a mixture of ethyl 2-methyl-4-(D-ara6ino-tetrahydroxybutyl)pyrrole-3-carbothiolate (18), a lactone [tentatively considered to be the 7-lactone (27) of 2-methyl-4-(D-aroWno-tetrahydroxy-butyl)pyrrole-3-carboxylic acid (19)], and a small proportion of a com-... 

Ethyl 2-methyl-4-(D-ara6mo-tetrahydroxybutyl)pyrrole-3-carbothiolate (18) yields a tetra-O-acetyl derivative, and, on oxidation with periodic acid, affords ethyl 4-formyl-2-methylpyrrole-3-carbothiolate (22). Lactone (27) gives a tri-O-acetyl derivative and, on alkaline hydrolysis, consumes one equivalent of base and furnishes 2-methyl-4-(D-arofemo-tetrahydroxy-butyl)pyrrole-3-carboxylic acid (19) in almost quantitative yield. This acid can, in turn, be transformed into a tetra-O-acetyl derivative, and, when oxidized with sodium metaperiodate, it gives 4-formyl-2-methyl-pyrrole-3-carboxylic acid (23). Attempts to determine the size of the lactone ring in compound (27) by oxidation with sodium metaperiodate were unsuccessful three moles of metaperiodate were consumed per mole, as if, during the oxidation, hydrolysis of the lactone had occurred. 

Decarbonylation of Thiol Esters to Sulfides and Carbothiolation of Alkynes Catalyzed by Pd... 

They also extend their reaction to the carboselenation of alkynes with selenol esters under similar conditions employed for the carbothiolation (Eq. 33) [66]. 

Carbothiolation affords an opportunity to install C-C and C-S bonds in a single reaction, thereby rapidly generating molecular complexity. This process is... 

Nakamura and coworkers reported an intramolecular carbothiolation of allq nes catalysed by gold(i) chloride at room temperature. The protocol allowed for the synthesis of 2,3-disubstituted benzothiophenes in short reaction times, with excellent yields when 2 mol% of the catalyst was used (Scheme 16.62). 

Cycloisomerization of a-thioallenes to 2,5-dihydrothiophenes [222] and intramolecular carbothiolation of alkynes to 2,3-disubstituted benzothiophenes [223] have been successfully achieved by using a catalytic amount of AuCl. 

Brpnsted acids have shown good-to-excellent levels of selectivity in C S bond formations. This chapter aims to review the stereoselectivity aspect of C—S bond formations that use commodity chemicals such as alkynes, alkenes, and alkanes. The stereoselective functionalization of alkynes is reviewed in section 1 using hydrothiolation, bisthiolation, and carbothiolation that necessitate transition metal and Brpnsted acid catalysis. The next section covers sulfethera-tion and conjugate addition reactions, where electron-rich and electron-poor alkenes are exploited under Lewis acid and Brpnsted acid catalysis. The last section is centered on the use of alkanes in the stereoselective 5-alkylation catalyzed by transition metal and organocatalysis. 

The introduction of sulfur moieties to unsaturated hydrocarbon compounds is an important synthetic strategy in the preparation of bioactive compounds. In particular, the use of alkynes enables the facile synthesis of alkenyl sulfides that are stereochemically as well as regiochemically defined structures. Given the important role of catalysts in the stereospecific addition of sulfur-containing reagents to alkynes, the following four sections are devoted to hydrothiolation, bisthiolation, carbothiolation, and related reactions. 

Carbothiolation of alkynes allows for a simultaneous construction of C(sp )-C and C(sp )-S bonds into unsaturated hydrocarbon compounds. The nature of resulting C(sp )—C bonds can be varied depending on the source of reagents that need to be activated by transition metals. 

In 2011, Matsubara et al. developed the Ni-catalyzed decarbonylative carbothiolation of alkynes 87 using thio-phthahc anhydride 88 in which the selective formation of sulfur heterocyclic compounds was accomplished under three different catalyst conditions using different phosphine hgands (Scheme 46.12). ... 

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