Metal mediated reaction, thiols with

However, the reaction requires only a general acid catalyst rather than the specific acid catalyst H+, and the corresponding reactions of the soft thioether may be better mediated by softer Lewis acids such as Cu+, Ag+, Hg2+, Pd2+, Pt2+ or Au3+. In many cases the aqua-ted metal ion is the most convenient Lewis acid, but in the case of some metals, particularly the second and third row transition metal ions, the aqua ions are not isolable and other complexes (particularly those with chloride ligands) are equally effective. The role of these softer metal ions as Lewis acids is two-fold. Firstly, the sulfur is co-ordinated to the metal, which increases the polarisation of the C-S bond and enhances the electrophilic character of the carbon, and, secondly, the thiol (or thiolate) leaving group is stabilised by co-ordination (Fig. 4-39). 

Important chemical reactions mediated by enz3rmes, which are proteins, are often controlled by the interaction of a nucleophile with an electrophile. Proteins are polymeric structures made of amino acids units (called amino acid residues). Important nucleophilic groups include the hydroxyl (OH) group of the amino acid serine (72), the thiol unit (SH) of cysteine (73 see Chapter 27) and the nitrogen of the imidazole group of histidine (74). Note that the term nucleophilic in this biochemical context does not necessarily indicate reaction at carbon, but rather indicates a two-electron donor. The electron-deficient center (called an electrophilic site or electrophilic group) may be a metal such as Mg, Mn+2, Fe", or an ammonium unit (-NH3+). In some cases, the electron-deficient center is a carbonyl group (C=0) in which the electron donor is indeed a nucleophile because the reaction occurs at the carbonyl carbon. 

Though tremendous success has been achieved with the development of Cu(I)-mediated Huisgen 1,3-dipolar cycloaddition reaction of azides and acetylenes as a robust and ef cient synthetic tool, it has several limitations which inclnde the need for a metal catalyst, an inability to photochemi-cally control the reaction or to conduct the reaction in the absence of solvent. In comparison, the century-old addition of thiols to alkene (the hydrothiolation of a C=C bond), which is currently called thiol-ene coupling (TEC), has many of the attributes of chck chemistry without, however, some of the aforesaid disadvantages of the CuAAC reaction. 

In order for the 2-(trimethylsilyl)ethylthio unit to lose its protecting group upon treatment with the fluoride, the sulfur must be attached to an unsaturated carbon. Hence the fluoride mediated sulfur deprotection is feasible for 2-(trimethyl-silyl)ethylthio substituted (het)arenes, alkenes, alkynes, and acid derivatives such as carboxylic and selenothiophosphinic acid salts. In thiolate form, the substrates have value for the formation of self-assembled monolayers or as metal complexing agents. Simple addition of acid to the thiolate to give a stable thiol characterizes 2-(trimethylsilyl)ethanethiol as a simple M" (HS) equivalent that is only capable of a single substitution reaction. ... 

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