Gif reactions, iron

Using FeS04 (1.67 x 10 M) in conjunction with equimolar amounts of methyl-pyrazine-5-carboxylic acid N-oxide and trifluoroacetic acid, in a water-acetonitrile-benzene (5 5 1 v/v/v) biphasic system, with benzene-H202-FeS04 = 620 60 1, a benzene conversion of 8.6% is achieved (35 °C 4h). Hydrogen peroxide conversion is almost complete (95%) and selectivities to phenol are 97% (based on benzene) and 88% (based on H2O2) [13]. These values are definitely higher than those described in the literature for the classical Fenton system [14], whereas iron complexes with pyridine-2-carboxylic acid derivatives are reported to be completely ineffective in the oxidation of benzene under the well-knovm Gif reaction conditions [15]. 

Towards the end of this section it may be worthwhile to point out some new reactions with high-valent metals and TBHP. The first is a pyridinium dichromate PDC-TBHP system134. Nonsubstituted or alkyl-substituted conjugated dienes, such as 1,3-cyclooctadiene (87) and others (also linear dienes), yield keto allyl peroxides 88 (equation 18), whereas phenyl-substituted dienes such as 1,4-diphenylbutadiene (89) gave diketo compounds, 90 (equation 19). In further research into a GIF-type system135 with iron and TBHP, limonene gave a mixture of products with carvone as the major product. The mechanism is thought to proceed initially by formation of a Fe(V)-carbon... 

Gif catalyst.1 Reaction of iron dust, acetic acid, and pyridine at 30° results in a triiron cluster compound with the empirical formula Fe2FeO(OAc)6Py35. This... 

Interestingly, the presence of hydrogen sulfide, which is much more easily oxidized than the saturated hydrocarbon, did not inhibit the reaction but, in contrast, was an essential additive. Later, it was shown that the same holds true for other easy-to-oxidize compounds such as Ph2S, PPh3 and P(OMe)3. It was assumed that the iron species that attacks the alkane is only activated by contact with it (called the Sleeping Beauty Effect by Barton). This observation is known as the Gif paradox [2]. 

Iron Catalysts Iron-catalyzed C—H oxidation systems such as the Gif [59] and Fenton [60] reactions are well-known examples of C—H functionalization. However, stereospecific sp3 C—H bond oxidation is still a great challenge for the application of iron-catalyzed C—H oxidations. Recently, selective oxidation of non-activated sp3 C—H bonds has been realized (Equation 11.25) [61]. Various complex substrates are converted into the corresponding alcohols with high diastereoselectivity under mild reaction conditions. 

Barton and co-workers have developed a family of systems for oxidation and oxidative functionalization of alkanes under mild conditions exhibiting unusual selectivity (see reviews [50], polemics [50d,e], the first publication [51] and some recent publications[52], as well as the papers of other authors concerning these systems[53]). These oxidations occur in pyridine in the presence of an organic acid and are catalyzed by complexes of transition metals (mainly iron). If dioxygen is used as an oxidizing regent, a reductant must also take part in the reaction. The first such a system was invented in Gif-sur-Yvette [51]. Thus their name Gif systems. The systems with geographically based names are mentioned in Table IX.5. All Gif systems have the same chemical peculiarities ... 

Of the Gif systems developed in Gif-sur-Yvette, Barton et al had already shown that the Gif system, which uses an iron(II) salt in pyridine-acetic acid with zinc dust-oxygen as an oxidant, is the most efficient. In cyclohexane oxidation they obtained mainly cyclohexanone with a turnover number of 121 in 4 h of reaction. On the other hand,... 

In addition, during the course of recent mechanistic studies, new methodology for the functionalization of saturated hydrocarbons based on Gif-type protocol has been invented. These reactions are of interest as mechanistic probes and also from the point of view of synthetic utility. Thus, cycloalkanes are transformed with vaiying efficiency into mono-substituted cycloalkyl derivatives (chlorides, bromides, azides, cyanides, thiocyanates, dicycloalkyl sulfides, or nitroalkanes) by conducting iron or copper catalyzed reactions in the presence of alkali metal salts (scheme). 

The Gif-Orsay II system has been further improved in yields and simplified with respect to the reaction conditions. Cyclododecane, adamantane and cyclooctane are oxidized in 17-30 mmolar amounts and coulombic yields of around 30% with oxygen, pyridine, trifluoroacetic acid and an iron catalyst in an undivided cell. Cyclododecane afforded a 18.9% yield of alcohol and ketone in a ratio of 0.14, adamantane a 14% coulombic yield, cyclooctane and cyclohexane coulombic yields up to 48%. The C /C ratio with adamantane reached values up to 40. With paraquat or 4,4 -bipyridyl as electron transfer reagent and under otherwise the same conditions, a coulombic yield of 49% cyclohexanol and cyclohexanone (1 7.88) was obtained. In this process oxygen is reduced to superoxide, which oxidizes iron(II) to an active iron catalyst that is able to react with the hydrocarbon. 

The available experimental information about the chemistry of the various Gif systems can be explained by the working hypothesis given in Scheme 6 [129,139] (the ligands of iron are omitted for clarity). The main features are as follows. The starting iron species is a p-oxo-iron(III) dimer (14), which is formed via the reaction of... 

Barton et al. used zinc (Zn) as a reductant. They isolated a trinuclear iron complex, Fe"Fe 20(OAc)6(py)i,s, from a reaction system containing iron powder, carboxylic acids, and H2S in aqueous pyridine under 1 atm O2 and found that it oxidized alkanes in the presence of Zn, pyridine, and acetic acid under 1 atm (Gif system). Later, the Gif type oxygenations were performed mostly by using monoiron salts, e.g. FeCl2 4H20 or FeCI,i 6H20. Barton et al reported a number of experiments for application of this system to the more complicated compounds such as steroids " and for clarification of mechanism, specially participation of the radical and nonradical processes. Intermediate formation of Fe -... 

Since the reaction order of alkane hydroxylation in Gif system (secondary > tertiary >primary) differs from the radical reaction (tertiary > secondary> primary), the system is clearly distinguishable from the Fenton reaction of H2O2 with Fe(II). While this system is effective toward the alkane, it is unable to hydroxylate arene. Although the accurate reaction mechanism of the Gif system involving the active site of the iron complex has not been elucidated, it is strongly demonstrated that some kinds of reducing agents are... 

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