Sulfides acetoxylation

Table 7. Anodic methoxylation and acetoxylation of fluoroaikyl phenyi sulfides...

Since these methoxylated and acetoxylated sulfides have an acetal structure, it is expected that Lewis acid catalyzed demethoxylation should generate a carbocation intermediate which is stabilized by the neighboring sulfur atom. In fact, nucleophilic substitution with arenes has been successfully achieved as shown in Scheme 6.7 [43], This procedure is useful for the preparation of trifluoroethyl aromatics. As already mentioned, generation of carbocations bearing an a-trifluoromethyl group is difficult due to the strong electron-withdrawing effect. Therefore, this carbon-carbon bond formation reaction is remarkable from both mechanistic and synthetic aspects. 

The last reaction in Scheme 13 becomes possible when the sulfide has a CH2 or CH fragment, adjacent to the sulfur atom whose protons are getting more acid when the molecule is oxidized. Electron-withdrawing groups (EWGs) increase the ease of deprotonation of this site even more. Thus, a-MeO-, a-AcO-, and a-F-sulfides were prepared (Eq. 9) [67-70]. When the nucleophihc attack is sterically hindered or a-protons are absent, products acetoxylated in the phenyl ring are... 

Asymmetric epoxidation of 10a under standard conditions yields the crystalline epoxy alcohol 2a in 95% ee (91% chemical yield). Treatment of 9a with thioanisol in 0.5N NaOH, in rerf-butyl alcohol solution, gives -after protection of the hydroxyl groups as benzyl ethers- the sulfide a (60% overall yield) through an epoxide ringopening process involving a Payne rearrangement. Since the sulfide could not be hydrolysed to the aldehyde 7a without epimerisation at the a-position, it was acetoxylated in 71% yield under the conditions shown in the synthetic sequence (8a... 

Table 1 Acetoxylation of Sulfides from Sulfoxides via the Pumtnerer Rearrangement... 

N03)j, a newcomer to the arena of oxidants, is useful for the acetoxylation of aromatic side chains in benzylic positions [415, 416] and for the oxidation of methylene or methyl groups that are adjacent to aromatic rings to carbonyl groups [238, 415, 417]. The reagent also oxidizes alcohols to aldehydes [418, 419, 420, 421] and phenols to quinones [422, 423], cleaves vicinal diols to ketones and a-hydroxy ketones to acids [424, 425], and converts diaryl sulfides into sulfoxides [426]. A specialty of ammonium cerium nitrate is the oxidative recovery of carbonyl compounds from their oximes and semicarbazones [422, 427] and of carboxylic acids from their hydrazides [428] under mild conditions. 

Electrochemical a-acetoxylation of octyl phenyl sulfide, methyl octyl sulfide, and several a-sulfanylated esters and ketones was achieved in HOAc-NaOAc solutions at Pt electrodes using high concentrations of the sulfur compounds [103]. Phenylthio derivatives produce a single a-acetoxy compound, whereas with the methylthio compounds two regioisomers are formed [Eqs. (55)-(56)]. 

Anodic a-methoxylation of phenyl 2,2,2-trifluoroethyl sulfide was carried out using various solid-supported bases as shown in Equation 12.6. Polystyrene and silica -gel are suitable as the solid support for an organic base such as piperidine. It is noteworthy that anodic methoxylation was successfully carried out even after 10 recycles of the solid-supported base. The method has also been successfully applied to electrochemical acetoxylation in acetic add/acetonitrile. 

Anodic substitution reactions of organic nitrogen and sulfur compounds are well-known and they have been used as key reactions for organic synthesis. Recently, Fuchigami and his co-workers have found that aryl 2,2,2-trifluoroethyl sulfides, which are readily derived from inexpensive trifluoroethanol, undergo efficient anodic methoxylation and acetoxylation reactions. In addition, these workers have successfully achieved introduction of oxygen nucleophiles to the position a to the CFj group as shown in Scheme 14. - In contrast, anodic... 

Table 9. Anodic Methoxylation and Acetoxylation of Fluoroalkyl Phenyl Sulfides...

Trifluoroacetaldehyde is difficult to prepare from trifluoroethanol. a-Methoxylated and a-acetoxylated 2,2,2-trifluoroethyl sulfides are trifluoroacetaldehyde equivalents, which are useful building blocks for synthesis of various trifluoromethylated compounds. The a-ace-toxy sulfide 10 is easily converted into trifluoroacetaldehyde phenyl-hydrazone (Eq. 44). The a-methoxy sulfide 9 is also readily transformed into biologically interesting a-monofluoroalkanoic acids (Eq. 45). 

As mentioned above, Fuchigami and his co-workers found that a trifluoromethyl group markedly promotes anodic methoxylation and acetoxylation of 2,2,2-trifluoroethyl sulfides (Scheme 14 and Eq. 96). Based on this finding, this group has explored the anodic substitution reactions of trifluoroethyl sulfides with fluoride ions. ° Anodic... 

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