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The activation of inactive C-H bond has always attracted intensive attention due to its potential utilisation in the organic synthesis; also it can help us in introducing interesting methodologies for various organic, organometallic and inorganic syntheses. The synthesis of various natural and unnatural products have always been a matter of conjecture which can be prominently achieved through C-H bond is a strenuous job due to their almost similar electronegativity of both Carbon and Hydrogen atom, thereby motivating the use of catalysts in the process to control the rate of read.
Hence, the challenging concept of C-H bond activation was thought to be over coined by the use of transition metals as catalysts due to their partially filled d-orbitals which enable them to act as excellent catalysts. Moreover, the uses of group 8 transition metals were considered more favourable, since they have high electron transfer capability and greater co-ordination ability to the heteroatom. The high catalytic ability of transition metals increased their significance to the next level, likely Palladium, Ruthenium, Rhodium, Iridium, Gold Platinum , but due to their greater toxicity and appreciable expenses alternative techniques need to be explored.
This led to the emergence of cheaper, less toxic and environment friendly Iron and Copper to the field. Experimentations illustrated that iron has the most strongly bound nucleus among the elements created by supernova nucleosynthesis ; its most abundant isotope has 26 protons and 30 neutrons. The electronic configuration accounts to 1s2, 2s2, 2p6, 3s2, 3p6, 4s2, 3d6 enabling to acquire a variety of spin states, thus making it more chemically reactive.
It’s use as a catalyst is motivated by its law biological toxicity , high chemical reactivity as well low costs. Apart from this iron has a characteristic property and plays an important role, as catalyst to promote many bio activities, iron due to its abundance is cheaper and nowadays widely utilised for reactions in labs . It is therefore revealed that the C-H bond activation in totally based upon steric bulk, electronic influence of ligands and also on the acidity of the C-H bond to be cleaved . The C-H activation reactions often resembles the coupling reactions in some cases as they occur via organometallic complex formed by the co-ordination of hydrocarboyl group in the inner sphere of transition metal. Experimental observations suggest that iron-catalysed reactions occur via following steps:- I. Insertion of the hydrocarboyl group in the inert sphere of metal atom forming a C-M complex by the reductive elimination to form the highly polar C-X (X=N,O etc.) bond in the synthesis chemistry II. Basically the ligand (generally N, O etc.) extracts the H (hydrogen) of C-H (either by oxidation or reduction) followed by the rebound process. Furthermore, it can also promote activation by the radical pathway .making C-H bond activation a multistep process has been emphasised because of the inertness of the C-H bonds . Many reviews has been published on iron-catalysed reaction like Bolm and Co-workers has summarised the achievements in Iron catalysed reaction in organic synthesis in year 2004, Chang-Liang Sun, Bi-Jie Li and Zhang- Jie Shi published their review on the advance discussion of C-H transformation by iron- catalyst. In contrast to it, the reactivity of organno iron intermediates was however an issue, reactions involving iron as a catalyst took place even or below room temperature and so gave a boost to explore and bring out efficient techniques and developed a thirst to employ efficient ligands to control their reactivity. Recent literatures compile the C-C and C-Heteroatom bond formations from iron catalysed reactions due to its unique and novel reactivity towards it. Scope of Oxidation of C-H bonds The oxidation of c-h bonds is a recurrent process in nature, thought to carried out by SET (single electron transition) process, where SET reaction may be defined as the one that are initiated by the transfer of a single electron from the nucleophile to the substrate leading to the production of a radical intermediate. These c-h bond oxidation reactions have vast biological application as well as where the aim of enzymes containing transition metals exhibit high catalytic properties. Mostly iron and copper can be used to carry out these transformations as the reactions involving iron and copper occur even at room temperature. Apart from this iron catalysed reactions also find synthetic applications which can be concluded as gif chemistry and Fenton’s chemistry. The oxidation reactions catalysed by iron which recently focused on sulphide oxidations and epoxidations underwent a considerable breakthrough in a long time as per the reports of Bolm and coworkers in 2007, who discovered an alternative oxidation of benzyl compounds to the carbonyl derivatives ( the most significant group in organic chemistry) aqueous solution as the oxidant. Certain scrutinizations declared that when benzyl derivatives are subjected to these optimized conditions, the carbonyl derivatives were obtained in high yields. As the treatment of 4-methylanisole and diphenylmethanol resulted in the formation of 4-methoxybenzophenone in high yields. However a sudden twist revealed as the oxidation of triphenylmethane resulted in the tert-butyl triphenylmethylperoxide instead of alcohol. Moreover, the reports of Beller and coworkers in 2010 on the oxidation of sp2c-h bonds of phenols and arenes illustrated the applications of the three component catalyst system. FeCl3.6H2O, pyridine-2,6dicarboxylic acid and various benzylamines were casted off to exidise TMP(trimethylphenol) with a non-toxic and eco-friendly oxidant namely hydrogen peroxide. Furthermore it was observed that the oxidation of TMP and 2-methylnapthalene occurred to about 77% and 55% yield was isolated. Moreover the product results from their oxidation was menadione(vitamins K3 , menaphthone) which served as a forerunner of vitamin K hence the reaction was considered of importance to industries. IRON CATALYSED C-H FUNCTIONALISATION PROCESS
A vast variety of compounds of iron form an important part of biological systems and are important part to the control certain metabolic processes namely eutochrone . Moreover, the recent advancements in the field of iron catalysed reactions as earlier, the C-H bond oxidation reactions occurred via formation of organometallic complexes leading to various endeared waste as in cross-coupling reactions but now it has been significantly recognised that the iron-catalysed C-H bond oxidation occur via two distinct manifolds. The first one involves activayion of outer sphere, basically induced by ligands directly to the metal atom. The second one however operates by the inner sphere, via formation of an organometallic intermediate. Furthermore, these C-H functionalisations involves the iron with high oxidation stateand hence require oxo and imido ligand the reactions were suspected to operate through radial pathways involving the abstraction of hydrogen following by the insertion of C-H bonds with iron-oxo or iron-imido as the key intermediates.
Subsequent contributions to the field, highlighted the application of iron complexes in promoting stoichiometric activation of C-H bonds. For instance, Klein and his co-workers suggested the stoichiometric ortho selective metallations or ketimines by iron complexes having low valency and also defined a complex [Fe(FMe)3]4.
The use of low valent complexes lead to the evolution of oxidation states from Fe(II)/Fe(III)/Fe(I), thereby giving detailed mechanistics which was considered out of reach.
High bond dissociation energy (BDE), lack of the active HOMOor LUMO to interact with transition metal catalytic centers, as well as difficulty to control the selectivity of C-H transformations are the challenges faced in the activation of inert C-H bonds of alkyl groups. In comparison to sp C-H and sp2 C-H bond, much less research has been devoted to the activation of more ”inert” sp3 C-H bonds of alkyl groups because the activation energy, highly selective functionalization of sp3 C-H bonds is much more difficult than both due to the lack of the assistance of p-groups, which could efficiently interactwith transition metal centers.
To overcome the challenges faced in sp3 C-H activation, the broadly used directing group-oriented strategy in sp2 C-H activation is also preferred to promote both reactivity and selectivity of sp3 C-H activation. In the recent studies, the activation of the sp3 C-H bonds is also possible and resembled to that of sp2 C-H and sp C-H.
The Bolm and the co-workers demonstrated iron(III) chloride modulated oxidation of the benzylic compounds which occurred under mild and convenient reaction conditions . It was however found that the solvents in the reaction acted as the coordination agents,there was no requirement of any ligand and slow addition of reagent was however required.Furthermore the reaction resulted in the formation of ketone giving a yield of Ketone in 91%. In the presence of FeCl3.6H2O and 3equivalents of TBHP.
The direct alpha C(sp3)-H functionalisation forming a C(sp3)-C(sp3) bond was investigated by Zhang FeCl3 was selected as the general catalyst was economical and was easily accessible. The FeCl3 and Fe(acac)3 catalyst were less effective and the substrate based distereoselectivity was thus discovered .The distereo control repented upon the relative bulk of the R2 and R3 groups of alkenes as illustrated:
During this research, an iron-catalyzedarylation of the ?-methyl position of a 2,2-disubstitute propionamide bearing an 8-aminoquinolinyl group (NH-Q) as the amide moiety in thepresence of an organic oxidant under mild thermal conditions. Becauseof the sensitivity of the reaction towards the choice of the ligand and also it showscomplete preference toward C-H bond activation on the methylgroup over the benzyl group, the reaction has less of the radical character previously observedin iron catalysis and more organometallic character.
So we conclude that the reaction conditions forreplacing a C(sp3)-H bond with a new C-aryl bond at the ?-position of a 2,2-disubstituted carboxamide, where thequinolineamide group acts as a uniquely effective directing groupfor iron has been found during research. The overwhelmingly higher reactivity of a methyl group over a benzylic group excludes a radical mechanism, and the highsensitivity of the yield to the structure of the substrate and theligand suggests involvement of organoiron intermediates in some crucial steps.
These are some examples which prove that sp3 C-H bond activation is also possible under iron catalyst. Recent studies make changes and add their efforts towards the sp3 C-H bond activation in which they also get success. They not only make Sp3 C-H activation possible with palladium but also with iron catalyst which being very helpful not only being cheap than it whether its use is eco-friendly, it will help in green chemistry. So we can say that recent studies are the proofs of the possibility of sp3 C-H bond activation not only with palladium but also with iron and nickel. These indirect methods has revolutionized the organic synthesis.
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