Co-ordinated thiolates

Note that these reactions are reversible, and indeed one of the best methods for the preparation of thioether complexes is by alkylation of a co-ordinated thiolate. In general, the dealkylation reactions require forcing conditions, but in some cases they proceed in an... 

One of the simplest and widely used methods of forming C-S bonds involves nucleophilic attack of a thiolate on a suitable C-centred electrophile such as an alkyl halide (Fig. 5-74). Co-ordinated thiolate ligands behave as nucleophiles in exactly the same manner, and the method has been extensively used for the preparation of thioethers and their metal complexes. The method has been particularly commonly utilised in the formation of macrocyclic ligands in templated syntheses (see Chapter 6). 

As mentioned above, reactions of this type have been widely used in the synthesis of macrocyclic ligands. Indeed, some of the earliest examples of templated ligand synthesis involve thiolate alkylations. Many of the most important uses of metal thiolate complexes in these syntheses utilise the reduced nucleophilicity of a co-ordinated thiolate ligand. The lower reactivity results in increased selectivity and more controllable reactions. This is exemplified in the formation of an A -donor ligand by the condensation of biacetyl with the nickel(n) complex of 2-aminoethanethiol (Fig. 5-78). The electrophilic carbonyl reacts specifically with the co-ordinated amine, to give a complex of a new diimine ligand. The beauty of this reaction is that the free ligand cannot be prepared in a metal-free reac-... 

Many exotic electrophiles have been shown to react with co-ordinated thiolate for example new disulfide bonds may be formed by reaction with S2C12. The nickel(n) complex of a very unusual tetrasulfide macrocyclic ligand may be prepared by this method (Fig. 5-83). Notice that this reaction utilises the nickel complex of the N2S2 ligand prepared by a metal-directed reaction in Fig. 5-78. 

Even an olefin may be sufficiently electrophilic to react with co-ordinated thiolate, and some nickel dithiolene complexes have been shown to react smoothly with norbornadiene (Fig. 5-84). Naturally, the dithiolene complexes also react with more conventional electrophiles, such as methyl iodide (Fig. 5-85). 

There is some evidence that the alkylation of co-ordinated thiolate is a reversible process, and there are a number of examples known in which a co-ordinated thioether is de-alkylated to yield a co-ordinated thiolate. In general, these reactions are rather sluggish, but occur in hot dmf solution. Whether the mechanism involves simple thermal dealkylation, or the intermediacy of the dmf as an alkyl group acceptor is not clear. 

As mentioned above, it is not necessary for the metal ion itself to be an oxidising agent, and co-ordinated thiolates also undergo rapid oxidation by dioxygen. Very often, in these cases, only catalytic amounts of metal ion are required for the oxidation of the thiols by dioxygen. Examples are seen in the oxidation of mercaptoacetic acid or cysteine in the presence of metal ions (Fig. 9-12). This reaction has obvious implications for the effects of transition metal ions upon proteins containing cysteine residues. 

The transfer of oxygen atoms to centres other than carbon is also well-known. The commonest examples are concerned with the oxidation of co-ordinated thiolate to sulfe-nate or sulfinate (Fig. 9-38). Simple oxidising agents such as hydrogen peroxide are very effective in reactions of this type. 

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). 

A second more subtle effect may also be operative in the metal ion control of nucleophilic reactions. When amines, thiolates or alkoxides are used as nucleophiles, they are expected to be highly reactive and hence relatively unselective. However, we saw in Chapter 2 that the proximity of the metal cation to the nucleophile reduces the charge density on the donor atom, and is thus expected to reduce the reactivity. We can use the reduced reactivity, and greater selectivity, of such co-ordinated nucleophiles to direct reaction towards the cyclic products. 

Another common type of reaction involving sulfur compounds is the oxidation of thiols or thiolates to disulfides. This process is found to be very sensitive to the presence of metal ions. The metal can act as the primary oxidant, or dioxygen may be involved in a reaction with a co-ordinated thiol (Fig. 9-10). Very often, oxidation reactions involving metal ions and thiols are catalytic in the metal. 

Figure 9-12. Co-ordinated thiols or thiolates are readily oxidised by dioxygen to disulfides. The amino acid cysteine may be oxidised to the corresponding disulfide, cystine, in this way.

Figure 9-38. The successive oxidation of a thiolate co-ordinated to chromium(in) by hydrogen peroxide to give sulfenate or sulfinate complexes.

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