Thiols substitution reactions

These reactions which lead to homocysteine formation in some creatures and its utilization in others are undoubtedly representative of a general thiol group transfer mechanism. The initial condensation of the donor thiol, most commonly cysteine, with some suitably reactive receptor generates a thioether. The differences in the requirement for O-acylation when starting from serine and homoserine may refiect two completely different mechanisms for this thiol substitution reaction. In the case of serine, the removal of the hydroxyl as hydroxide and the stabilization of an electrophilic centre on the side-chain carbon can be achieved through the pyridoxal phosphate-amino acid adduct. A similar example is in the carbon-carbon condensation between serine and imidazole in tryptophan... 

Thiol Substitution Reactions. Vital to the usefulness of 2-(trimethylsilyl)ethanethiol is that it behaves as a typical thiol. Base mediated reactions that proceed as expected include alkylation and nucleophilic ring openings. Moreover, addition-eliminations on unsaturated systems, Michael additions, and c -additions to triple bonds (eq 2) are all routine. To access 2-(trimethylsilyl)ethyl thioethers, a useful procedure is hydrolysis of 2-(trimethylsilyl)ethyl thiolacetate and alkylation of the thiolate in a single pot. ... 

These effects can be attributed mainly to the inductive nature of the chlorine atoms, which reduces the electron density at position 4 and increases polarization of the 3,4-double bond. The dual reactivity of the chloropteridines has been further confirmed by the preparation of new adducts and substitution products. The addition reaction competes successfully, in a preparative sense, with the substitution reaction, if the latter is slowed down by a low temperature and a non-polar solvent. Compounds (12) and (13) react with dry ammonia in benzene at 5 °C to yield the 3,4-adducts (IS), which were shown by IR spectroscopy to contain little or none of the corresponding substitution product. The adducts decompose slowly in air and almost instantaneously in water or ethanol to give the original chloropteridine and ammonia. Certain other amines behave similarly, forming adducts which can be stored for a few days at -20 °C. Treatment of (12) and (13) in acetone with hydrogen sulfide or toluene-a-thiol gives adducts of the same type. 

If vinylogous imidazole-A-carboxylates (route A) are treated with nucleophiles such as alkoxides or amines, the corresponding vinylogous carbonic esters or amides are obtained. While reaction of the vinylogous imidazole-TV-carboxylate with a thiol (route A) yields the addition product only, that of the corresponding imidazolium compound (route B) leads to the carbonic thioester in a substitution reaction [3]... 

Furthermore, a neighboring group participation of a phenylthio function is observed in the Lewis acid-catalyzed nucleophilic substitution reaction of various P-nitrosulfides. Because the P-nitrosulfides are readily available, by the Michael addition of thiols to nitroalkenes (see Michael addition Chapter 4), this reaction is very useful. The P-nitrosulfides are prepared stereoselectively, and the reaction proceeds in a stereo-specific way (retention of configuration) as shown in Eqs. 31-34.35... 

Reaction of (34) with the bidentate sulfur ligand isotrithionedithiol (H2dmit, (278)) produced a dianionic complex. The reaction of (278) in which the thiol groups were deprotected in situ prior to the substitution reaction with [TcNClJ in acetonitrile gave a 45% yield of [TcN(dmit)2] ... 

When 2-phenyltetrahydrothiophene (361) was treated with lithium and a catalytic amount of DTBB (5%) in THF at —78 °C, the corresponding intermediate 362 was generated which, by further electrophilic substitution reaction at the same temperature and final hydrolysis, gave the expected functionalized thiols 363 (Scheme 105) . 

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],... 

The principal disadvantage of the intramolecular cyclization approach using Michael addition of a cysteine-based thiol to dehydroalanine is its nonstereoselectivity. Similarly, even when using 3-bromoalanine derivatives in a halide-based substitution reaction with cysteine-... 

In a recent report, 19- or 20-residue thiolated oligonucleotides were used in an exchange reaction with glutathione monolayer-protected gold clusters. After thiol substitution, the resulting DNA-nanoparticle conjugates can be separated by gel electrophoresis on the basis of the number of bound oligonucleotides and assembled with one another by DNA-DNA hybridization [151]. 

---