Iron catalysis alkylation

Scheme 28 Domino iron catalysis for cross-coupling of alkyl and aryl halides [90]...

Iron catalysis in oxidation reactions with peroxides, both hydrogen peroxide and alkyl hydroperoxides, is frequently regarded as just a Haber-Weiss-type system where hydroxyl... 

Recently, Fu and coworkers have shown that secondary alkyl halides do not react under palladium catalysis since the oxidative addition is too slow. They have demonstrated that this lack of reactivity is mainly due to steric effects. Under iron catalysis, the coupling reaction is clearly less sensitive to such steric influences since cyclic and acyclic secondary alkyl bromides were used successfully. Such a difference could be explained by the mechanism proposed by Cahiez and coworkers (Figure 2). Contrary to Pd°, which reacts with alkyl halides according to a concerted oxidative addition mechanism, the iron-catalyzed reaction could involve a two-step monoelectronic transfer. 

Even alkyl Grignard reagents can be coupled with alkyl halides 1 using iron catalysis with the xantphos ligand 11 (entry 16) [56]. The yields are acceptable for primary alkyl bromides. Secondary alkyl halides reacted only in low yield. 

Given the observation of catalysis of alkene epoxidation by iron N-alkyl porphyrins, it is likely that these complexes may yield synthetically useful catalysts (32, 65). The possibility of chiral induction by using either a chiral N-alkyl group (66) or a chiral macrocycle such as N-Me etioporphyrin (67) is an area that should prove fruitful in the near future. 

The substituent R may be alkyl, cydoalkyt. or benzyl. Catalysts are selected from transition metals which can form carbonyl complexes. Ruthenium and especially cobalt form active catalysts, although other metals like Rh. Pd. Ft. Os, Ir, Cr, Mn, Fe, and Nt have also been examined. If metals like ruthenium or iron catalysis are used, carbon dioxide is formed instead of water as the by-product. 

Cross-coupling between alkyl halides and alkenyl Grignard reagents has also been succeeded using iron catalysis. Catalytically active systems are tris(acetylacetonato)iron with TMEDA and hexamethylenetetramine (HMTAy or iron(IIl) chloride as a precatalyst in combination with TMEDA as a ligand (Scheme 4—233). ... 

Iron catalysis has even been reported to allow sp -sp Kumada-type crosscoupling of primary and secondary alkyl halides and alkyl Grignard reagents (Scheme 4-234). Iron(II) acetate in combination with Xantphos as ligand displays the most efficient catalytic system for this transformation. However, the yields hardly exceed a moderate level. ... 

Easy-to-handle arylboronic compounds can also be reacted in a Suzuki-Miyaura-like fashion with nonactivated alkyl halides using iron catalysis (Scheme 4-239). Two novel iron complexes with sterically hindered diphosphane ligands have been developed for this transformation. Additionally, a magnesium cocatalyst is required. For the mechanism, action of the redox couple Fe(III)/Fe(II) is discussed. This requires the intermediate formation of an alkyl radical species as displayed in Scheme 4-238. " ... 

The reduction ofsec-, and /-butyl bromide, of tnins-1,2-dibromocyclohexane and other vicinal dibromides by low oxidation state iron porphyrins has been used as a mechanistic probe for investigating specific details of electron transfer I .v. 5n2 mechanisms, redox catalysis v.v chemical catalysis and inner sphere v.v outer sphere electron transfer processes7 The reaction of reduced iron porphyrins with alkyl-containing supporting electrolytes used in electrochemistry has also been observed, in which the electrolyte (tetraalkyl ammonium ions) can act as the source of the R group in electrogenerated Fe(Por)R. ... 

A mechanistic study of acetophenone keto-enol tautomerism has been reported, and intramolecular and external factors determining the enol-enol equilibria in the cw-enol forms of 1,3-dicarbonyl compounds have been analysed. The effects of substituents, solvents, concentration, and temperature on the tautomerization of ethyl 3-oxobutyrate and its 2-alkyl derivatives have been studied, and the keto-enol tautomerism of mono-substituted phenylpyruvic acids has been investigated. Equilibrium constants have been measured for the keto-enol tautomers of 2-, 3- and 4-phenylacetylpyridines in aqueous solution. A procedure has been developed for the acylation of phosphoryl- and thiophosphoryl-acetonitriles under phase-transfer catalysis conditions, and the keto-enol tautomerism of the resulting phosphoryl(thiophosphoryl)-substituted acylacetonitriles has been studied. The equilibrium (388) (389) has been catalysed by acid, base and by iron(III). Whereas... 

In relation to enzymic cytochrome P-450 oxidations, catalysis by iron porphyrins has inspired many recent studies.659 663 The use of C6F5IO as oxidant and Fe(TDCPP)Cl as catalyst has resulted in a major improvement in both the yields and the turnover numbers of the epoxidation of alkenes. 59 The Michaelis-Menten kinetic rate, the higher reactivity of alkyl-substituted alkenes compared to that of aryl-substituted alkenes, and the strong inhibition by norbornene in competitive epoxidations suggested that the mechanism shown in Scheme 13 is heterolytic and presumably involves the reversible formation of a four-mernbered Fev-oxametallacyclobutane intermediate.660 Picket-fence porphyrin (TPiVPP)FeCl-imidazole, 02 and [H2+colloidal Pt supported on polyvinylpyrrolidone)] act as an artificial P-450 system in the epoxidation of alkenes.663... 

Although mechanistically different, a successful kinetic resolution of cyclic allyl ethers has recently been achieved by zirconium catalysis [2201. Other metals such as cobalt [221], ruthenium [222], and iron [2231 have been shown to catalyze allylic alkylation reactions via metal-allyl complexes. However, their catalytic systems have not been thoroughly investigated, and the corresponding asymmetric catalytic processes have not been forthcoming. Nevertheless, increasing interest in the use of alternative metals for asymmetric alkylation will undoubtedly promote further research in this area. 

The first step of peroxidase catalysis involves binding of the peroxide, usually H2C>2, to the heme iron atom to produce a ferric hydroperoxide intermediate [Fe(IE)-OOH]. Kinetic data identify an intermediate prior to Compound I whose formation can be saturated at higher peroxide concentrations. This elusive intermediate, labeled Compound 0, was first observed by Back and Van Wart in the reaction of HRP with H2O2 [14]. They reported that it had absorption maxima at 330 and 410 nm and assigned these spectral properties to the ferric hydroperoxide species [Fe(III)-OOH]. They subsequently detected transient intermediates with similar spectra in the reactions of HRP with alkyl and acyl peroxides [15]. However, other studies questioned whether the species with a split Soret absorption detected by Back and Van Wart was actually the ferric hydroperoxide [16-18], Computational prediction of the spectrum expected for Compound 0 supported the structure proposed by Baek and Van Wart for their intermediate, whereas intermediates observed by others with a conventional, unsplit Soret band may be complexes of ferric HRP with undeprotonated H2O2, that is [Fe(III)-HOOH] [19]. Furthermore, computational analysis of the peroxidase catalytic sequence suggests that the formation of Compound 0 is preceded by formation of an intermediate in which the undeprotonated peroxide is coordinated to the heme iron [20], Indeed, formation of the [Fe(III)-HOOH] complex may be required to make the peroxide sufficiently acidic to be deprotonated by the distal histidine residue in the peroxidase active site [21],... 

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