Thiolate substitution reactions

Fig. 5.9. Thiolate substitution reaction in [Fc4S4SR4] species [Que Jr. L, Anglin JR, Bobrik MA, Davison A, Holm RH (1974) J. Am. Chem. Soc. 96 6042]...

Iron-proteins can themselves participate in thiolate substitution reactions. There are indeed two types of this kind of process, namely active center core extrusion and protein reconstitution. Both are related to displacement of the Fe-S core between the protein and an appropriate organic thiol ... 

In a one-pot synthesis of thioethers, starting from potassium 0-alkyl dithiocarbonate [36], the base hydrolyses of the intermediate dialkyl ester, and subsequent nucleophilic substitution reaction by the released thiolate anion upon the unhydrolysed 0,5-dialkyl ester produces the symmetrical thioether. Yields from the O-methyl ester tend to be poor, but are improved if cyclohexane is used as the solvent in the hydrolysis step (Table 4.13). In the alternative route from the 5,5-dialkyl dithiocarbonates, hydrolysis of the ester in the presence of an alkylating agent leads to the unsymmetrical thioether [39] (Table 4.14). The slow release of the thiolate anions in both reactions makes the procedure socially more acceptable and obviates losses by oxidation. 

The best enantioselectivity (35% ee) was observed in the reaction of l-(l-naphthyl)-2-propyn-l-ol with acetone in the presence of a complex bearing a 1-naphthylethylthio-lato moiety as a chiral ligand. Although the enantioselectivity is not yet satisfactory, this was the first example of an enantioselective propargylic substitution reaction catalyzed by transition metal complexes [27]. It is noteworthy that the chiral thiolate-bridged ligands work to control the chiral environment around the diruthenium site. 

Scheme 7.19 The first example of enantioselective propargylic substitution reactions catalyzed by chiral thiolate-bridged diruthenium complexes.

Scheme 7.21 Enantioselective propargylic substitution reactions of various propargylic alcohols catalyzed by a chiral thiolate-bridged diruthenium complex.

Thiodisaccharides in the GlcNAc series were recently synthesized. The substitution reaction of the triflate at C-4 of 2-acetamido- and 2-azido-o- galacto-sides (34 d) and (34 e) in DMF with thiolate nucleophiles (8i) or (8j) and (30b) afforded the expected disaccharides (aroimd 50 and 68%), from which the deprotected (41) and (42) were obtained [39a, 32] (Scheme 13). The coupling of the triflate (34 f) with the thiol (8j) in DMF in the presence of cysteamine gave a 63% yield of the expected thiocfrsaccharide which was converted into (41) in high yield [39b],... 

Analogous substitution reactions take place with alkane- and arene-thiolate anions <73JCS(P1)16S9), and pyridine-2- and -4-thiones are usually prepared by use of sodium or potassium hydrogen sulfide or thiourea (74JCS(P1)2300). 

Although 3-chloro- and 3-bromo-hexahydroazocin-2(l//)-one (12) and (13) undergo substitution reactions when treated with thiolate ions to give (14), only elimination products are formed from other anions subsequently the anions sometimes add to the a,(3-unsaturated intermediate (15) to give 4-substituted derivatives such as (16) (81AJC569). 

Aryl- and heteroaryl halides can undergo thermal or transition metal catalyzed substitution reactions with amines. These reactions proceed on insoluble supports under conditions similar to those used in solution. Not only halides, but also thiolates [76], nitro groups [76], sulfinates [77,78], and alcoholates [79] can serve as leaving groups for aromatic nucleophilic substitution. 

Earlier investigations pointing to ET mechanisms in reactions of nucleophiles should be consulted in this context. The studies of Meyers and coworkers7 9 on radical anion-radical pair (RARP) transitions in halogenations with perhaloalkanes and nucleophilic (ionic) vs electron-transfer substitution reactions of trityl chloride with thiolates and other anions, and the studies of Chanon and coworkers10,99b which utilized radical-clock traps in efforts to monitor the intermediacy of free radicals in the ET pathways suggested by Meyers and colleagues. 

Thiolate ions have been reported to undergo reactions with aliphatic a-halonitro compounds5114,115 to yield the substitution products a-nitrosulphides or disulphides by oxidative dimerization. The substitution reaction is favoured by weakly nucleophilic thiolate ions and proceeds by an S l mechanism. On the other hand, strongly nucleophilic thiolate ions favour the redox reaction by an ionic abstraction (X-philic) mechanism. 

Many halogenated hydrocarbons are substrates for GSH-transferase-catalyzed nucleophilic substitution reactions that produce S-substituted glutathione (GSH) derivatives. These are normal SN2 displacements of halide with thiolate anion that occur with inver-... 

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