Sulfur nucleophiles, reaction with arene oxides

The intracellular nucleophile glutathione (GSH y-Glu-Cys-Gly) acts as a protective mechanism against electrophilic insults and may be present at concentrations of up to 10 mM [26]. The reaction of glutathione with a non-polar compound bearing an electrophilic carbon, nitrogen or sulfur atom may be mediated enzymatically by glutathione-S-transferase (GST), with typical substrates being species such as arene oxides, quinones and a,P-unsaturated carbonyl compounds. 

The yellow CpFe1 (//6-arene) salts (most commonly BF4 or PF6 ) are usually stable up to at least 200 °C, are stable in concentrated sulfuric acid, and are very resistant towards oxidation (until recently, it was believed that they could not be oxidized [23] vide infra). They are not easy to reduce either [23] (vide infra). The chloride salts [CpFe+( f -arene) Cl- are water-soluble they are formed upon hydrolysis following ligand-exchange reactions between ferrocene and the arene in the presence of aluminum chloride [21]. Such aqueous solutions may sometimes be directly used for nucleophilic reactions [22] (vide infra). The BF4- salts are also sometimes quite soluble in water, but the PF6- salts are much less so. Electrophilic reactions that are readily undergone by the free arenes, such as Friedel-Crafts reactions, are no longer possible on the CpFe+( /6-arene) complexes [19, 23]. On the other hand, a range of nucleophilic reactions that are impossible or very difficult to carry out with free arenes become possible under ambient or mild conditions with the CpFe+()/6-arene) complexes (Scheme 2) [16-20]. 

Is usually mixed with the arene oxide In a polar solvent such as acetone, dioxane, acetonitrile, DMSO or methanol but the reaction may also be run In aqueous buffer solutions. Even though the addition of base Increases the nucleophilicity of the sulfur, the pH should not be Increased too much since that will lead to more complex reaction product mixtures (167). A PTC mediated reaction with tetrabutylammonlum blsulfate has been suggested for the synthesis of N-acetyl-cystelne conjugates of epoxides (167). The recent synthesis of some premercapturlc acid type conjugates from epoxides Is summerlzed In Table VII. 

Alternatively, the arene can be left complexed so that the chemistry of the Ti -arene complex can be exploited (see Section 10.3). " The Dotz reaction between the cyclohexenyl carbene 8.52 and the benzylic alkyne 8.53 in the presence of a silylating agent gave the ti -complex 8.54 (Scheme 8.18). Treatment of this complex with LDA resulted in formation of the anion a- to sulfur 8.55 that cyclized by nucleophilic attack onto the chromium-complexed aromatic ring. Oxidative work-up then gave the tetracycle 8.57. 

---