C-S Bond Formations

A wide variety of catalytic functionalizations of C(sp )-H have already been developed to date and have had a significant impact not only in the field of organic chemistry but also in related fields of chemistry. The methods have been applied to the synthesis of synthetically useful compounds, such as materials, fine chemicals, 

PPhg 20 mol% PivOH 0.2 equiv Na2C03 2 equiv DMSO 3.5 equiv Ar- 

Compared to C—N and C—O bond formation, there are far fewer examples of catalytic C—S bond forming processes. However, reactions have now been developed that exploit the highly nucleophilic character of thiols and related functional groups, and synthetically useful methods have been reported. The use of these reactions in the synthesis of heterocycles is also a burgeoning area. 

One of the first reported C-S organocatalytic bond formations was reported by Pracejus in 1977. In this pioneering work benzylthiol, a-phthalimidomethacrylate, and catalytic amounts of chiral amines reacted to form several cysteine derivatives. With the advent of organocatalysis and iminium catalysis, several sulfa-Michael reactions have been developed. 

Since then, and inspired by this pioneering report, several groups have developed organocatalytic cascade reactions starting with a sulfa-Michael addition [68, 69]. 

---

Oxidative Ring Closure Reactions 4.03.4.1.1 C—N bond formation N—N bond formation C—S bond formation N—S bond formation O—C bond formation O—N bond formation S—S, S—Se and Se—Se bond formation Electrophilic Ring Closures via Acylium Ions and Related Intermediates Ring Closures via Intramolecular Alkylations... 

Two-component methods represent the most widely applied principles in sulfone syntheses, including C—S bond formation between carbon and RSOz species of nucleophilic, radical or electrophilic character as well as oxidations of thioethers or sulfoxides, and cheletropic reactions of sulfur dioxide. Three-component methods use sulfur dioxide as a binding link in order to connect two carbons by a radical or polar route, or use sulfur trioxide as an electrophilic condensation agent to combine two hydrocarbon moieties by a sulfonyl bridge with elimination of water. 

An unusual template reaction leads to the Ni11 complex of a tetrabenzo-N2S2 macrocyclic ligand (676) via C—Cl bond cleavage and C—S bond formation according to Equation (25).1701... 

General procedure for C-S bond formation. A 50 mL of reactor was charged with 232.5 mg (0.25 mm) of POPdl, 1.36 g (12.0 mmol) of 3-chloropyridine, 1.18 g (10.0 mmol) of 1-hexanethiol and 1.92 g (20.0 mmol) of NaO-tBu in 15.0 mL of toluene. The resulting mixture was refluxed for 16 h before the mixture was cooled to room temperature and quenched with 100 mL of H20. The mixture was transferred to a separatory funnel, and extracted with EtOAc (2 X 200 mL). The layers were separated, and organic layer was washed with H20 (100 mL), brine (150 mL), and dried over MgS04, filtered, and the solvents removed from the filtrate by rotary evaporation. The final product was chromatographed on silica gel using ethyl acetate/hexane (5% volume ratio) as eluant. The eluate was concentrated by rotary evaporation to yield 1.90 g (97% yield) of 3-hexylthiopyridine. 

The first gold catalyzed C-S bond formation was demonstrated in a route to the 2,5-dihydrothiophene 16 via cycloisomerization of the allene 17 which occurred with high chirality transfer (d.r. > 95 5) <06AG(E)1897>. 

Pyrimidine thioethers may also be synthesized via direct Pd-catalyzed C—S bond formation between halopyrimidines and thiolate anions. For very unreactive thiol nucleophiles such as 2-thiopyrimidine, both a strong base and a palladium catalyst are essential. Without a palladium catalyst or replacing f-BuONa with K2C03, the reaction failed to furnish the desired pyrimidine thioether [49]. 

According to results from laser flash photolysis, the p-(methoxyphenyl) sulfanyl radical adds exclusively to the central atom in of 2,4-dimethylpenta-2,3-diene (If) with a rate constant of 1.1 x 10s M-1 s-1 (23 1 °C) (Scheme 11.6) [45], A correlation between the measured rate constants for addition of para-substituted arylsulfanyl radicals to allene If was feasible using Brown and Okomoto s o+ constant [46], The p+ value of 1.83, which was obtained from this analysis, was interpreted in terms of a polar transition state for C-S bond formation with the sulfanyl radical being the electrophilic part [45]. This observation is in agreement with an increase in relative rate constant for phenylsulfanyl radical addition to 1-substituted allene in the series of methoxyallene lg, via dimethylallene Id, to phenylsulfanylallene lh, to ester-substituted 1,2-diene li (Table 11.2). 

An interesting C-S bond formation mediated by benzyltriethylammonium tetrathiomolybdate converts -halo acid chlorides into thiolactones [64] (Scheme 4.16). 

Reaction (7.63) shows an example of C—S bond formation [73,74]. In fact, the aryl radical formed by iodine abstraction by (TMS)3Si radical rearranged by substitution to the sulfur atom, with expulsion of the acyl radical and concomitant formation of dihydrobenzothiophene (60). This procedure... 

Thiepane (35) has been synthesized by an intramolecular radical addition of the thiyl radical (equation 59) which was generated by photolysis of a thiol (71TL2025). Similarly, C—S bond formation has been achieved (equation 60) by an intramolecular condensation of 6-mercaptohexanoic acid to give the thiolactone, thiepan-2-one (135) (64MI51700). A Dieckmann-type base-catalyzed cyclization of a diester precursor followed by acid-catalyzed hydrolysis and decarboxylation has been used in the synthesis of thiepan-3-one (41) as indicated in equation (61) (52JA917). 

Oxidative C—S bond formation (I2, Br2 or SOCl2) converts thioanilides PhNHCSR into benzothiazoles (281) (the Jacobson-Hugershoff synthesis). Thus, ArNHCSCH(C02Et)2 with bromine yields the benzothiazole (282) (73ZC176). 

Ethoxycarbonyl groups show efficient regiodirecting powers in sulfonate additions, giving exclusive C—S bond formation at the allyl terminus remote to the carbonyl functionality (equation 284).219 Remote oxygen functionality also directs incoming sulfonate nucleophiles to the distal allyl terminus (equation 285).215... 

The addition of thiophenol to cyclohexenone in the presence of a cinchona quat gave the Michael adduct in 85% yield and 36% op [47f]. Other C-S bond formations are also noted [ I le,26b,47d,47e,81]. 

Keywords penicillamine, acetone, cysteine, cyclization, gas-solid reaction, C-S bond formation, thiazolidine... 

Type of reaction C-S bond formation Reaction condition solvent-free... 

---