1. Abstract
Iron catalysis is attractive for organic synthesis because it is inexpensive, abundant, and non-toxic compared to other catalysts like Nickel and Palladium. There are many reactions that catalyzed by iron, but the most important reaction is the formation of carbon-carbon bonds. Iron-catalyzed coupling reactions with organometallics, such as Grignard reagents, have shown their great compatibility with various functional groups and it is then not surprising that they have then been frequently applied as a key step in syntheses of natural products and/or compounds of pharmacological interest.
2. Introduction
The chemical industry of the 20th century could not have developed to its present status on the basis of non-catalytic, because some of the reactions need to a high temperature and pressure to occur reaction to proceed at a reasonable rate of production, but the reactors in which such conditions can be safely maintained become progressively more expensive and difficult to make.
For example, the conversion of N_2 and H_2 into ammonia is practically impossible above 600 °C. Nevertheless, higher temperatures are needed to break triple bond in N_2. Without catalysts, many reactions that are common in the chemical industry would not be possible, and many other processes would not be economical.1
Catalysis in chemistry, the modification of the rate of a chemical reaction, usually an acceleration, by addition of a substance called a catalyst is not consumed during the reaction. Actually, we can describe the catalytic system as a cyclic event in which the catalyst participates and is recovered in its original form at the end of the cycle.2 The catalytic cycle starts with the bonding of molecules A and B to the catalyst. A and B then react within this complex to give a product P. In the final step, P separates from the catalyst then, the catalyst begins with a new cycle which is shown in figure 1.

The catalyst displays an alternative path for the reaction, which is obviously more complicated, but energetically much more convenient. Potential energy diagram of a heterogeneous catalytic reaction with gaseous reactants and products and a solid catalyst which is shown in figure 2. Note that the reaction without catalyst has to overcome a substantial energy barrier, while the barriers in the catalytic path are much lower.3

Indeed, more than 90 % of industrial processes use catalysts in one form or the other. Owing to expanding rapidly need of mankind, production in all branch is increasing at a quick rate and catalysis science and technology has a major contribution in this they have an influence on our life in the economy, petroleum, polymer production, food industry and pollution control include catalytic processes.4
Metals especially transition metal in the middle of the periodic table are commonly used catalysts. Iron is a catalyst for some significant industrial chemical reaction and have growing application in organic synthesis and some natural products or pharmacologically because it has advantages which are presents in this article.
3. Historic development of iron catalysis
Historically, an iron catalyst was used for more than a century. In 1910, the Haber-Bosch process is the synthesis of ammonia from nitrogen and hydrogen was patented. It utilizes a heterogeneous iron catalyst, which promotes the kinetically determined cleavage of the triple bond in N_2. The ammonia obtained by this process is the basis for the synthesis of fertilizers.
The Fischer-Tropsch process, which is a transformation of a mixture of CO and
“synthesis gas” to obtain hydrocarbons was developed nearly in 1925, iron catalysis also utilized for the Fischer-Tropsch process.
Homogeneous Reppe chemistry (the hydroformylation of olefins using CO and water to obtain alcohols and aldehydes) was first reported in 1953 to be catalyzed by
(Iron pentacarbonyl).
Since then, homogeneous transition metal catalysis became a major branch of organometallic chemistry. Then, in the early 1970s, the Kumada cross-coupling reaction of Grignard reagents with organic halides is catalyzed by iron salts.
In the late 1970s when the oxygen transfer from an iron porphyrin complex to a substrate was investigated, quickly leading to iron porphyrin catalysts for oxidation reactions.
In the late 1990s, Brookhart and Gibson discovered that bis(imino)pyridyl iron complexes were active catalysts for ethylene polymerization reactions. Finally, growing research activities can be observed in all branches of the field.5
Most of the catalysts are based on precious metals such as palladium, rhodium, ruthenium, iridium, and osmium, which are becoming increasingly expensive because of the dwindling resources. Furthermore, the use of heavy metals as catalysts in the pharmaceutical and agricultural industries has limitations because of toxicity. So there is an urgent need to explore effective and abundant replacements for the rare and toxic metals. Iron is a readily available, inexpensive and environmentally friendly metal, which represents an ideal alternative to the precious metals.6
A comparison between iron salts FeCl2 and some metal salts (NiCl2, CoCl2, PdCl2) is given in Table 1.7

LD50 (mg kg?1) Toxicity Price (€ per g) Metal Salts
450 No significant toxicity reported 14–19 FeCl2

37–46 NiCl2
28–36 CoCl2
58–106 PdCl2

5. Reaction and application of iron catalysis
5.1 C–C Bond-Forming Reactions
Coupling reactions combine small building blocks to obtain larger units is the core challenge in many synthetic transformations. Carbon-carbon bonds through iron catalysis are mainly formed either through Cross-coupling reactions of organometallic reagents (Scheme 1) or through a cross dehydrogenative coupling (CDC, Scheme 2).5

Scheme 2. Dehydrogenative cross-coupling reactions

5.1.1 Cross-coupling reactions of organometallic reagents

Involve the formation of a new carbon-carbon single bond by the coupling of a nucleophilic organometallic reagent (Grignard reagents) with an electrophilic organohalide. Salts of iron(II) and iron(III) are extremely active catalysts for the coupling of a variety of electrophiles catalyzed reactions.

Scheme 3. First Fe-catalysed cross-coupling with a Grignard by Tammura and Kochi (1971)

This is proposed mechanism for iron catalyzed cross-coupling of alkenyl halides and methyl Grignard reagents, the cycle starts with attacking Me which is carries a negative charge the Fe(III), the oxidation state change it to (I), then formation intermediate compound to form a new bond with C-C and give E-but-2-ene, after that iron bromide reacts with methyl Grignard reagent to start a new cycle. 8

Scheme 4. Proposed mechanism for iron-catalyzed cross-coupling reaction.

With alkenyl halides

For example, iron-catalyzed coupling reaction of an homoallylic Grignard reagent (1 )with a (Z)-bromoalkene (2) and led to a key diene (3) of defined Z,E configuration (70% yield), which after dihydroxylation will lead to cis or trans solamins, which use for Sickle cell anemia and Arthritic pains.7

Scheme 6. Fe-catalysed cross-coupling of homoallylic magnesium bromide with a (Z)-bromoolefin for the synthesis of solamin.

With aryl halides

For example synthesis of FTY720 (Fingolimod) which is an immunosuppressive agent.7 OTf triflate.

Scheme 7. Fe-catalyzed coupling of octyl magnesium bromide with an aryl triflate.

With acyl chlorides

Alkyl Grignard with an acyl chloride for the synthesis of latrunculin B, It is under investigation for the treatment of cancer. 9

Scheme 8. Fe-catalyzed cross-coupling between MeMgBr and functionalized
enantiopure acyl chloride.

Dehydrogenative cross-coupling reactions

Formation of the C-C bond by the removal of hydrogen atoms from two carbon atoms of two different compound by iron compounds.10

Scheme 9. The representative example of the iron-catalyzed dehydrogenative cross-coupling reaction.
5.1.3 Lewis acid catalysis
Iron salts are one of the first Lewis acids used in the Friedel- Crafts reaction (electrophilic aromatic substitution). The Friedel-Crafts alkylation is an organic reaction used to conversion an aryl compound and an alkyl halide to a substituted aromatic compound using a catalyst FelCl3. The reaction starts with the Lewis acid removes the halide from the alkyl halide to form an electrophilic alkyl cation and a tetra substituted iron anion. The aromatic compound after that attacks the alkyl cation electrophilic aromatic substitution to give a cationic product with loss of aromaticity. Deprotonation with the iron anion results in the final aromatic product and restoration of the Lewis acid catalyst.12

Bach used FeCl3 in an intermolecular Friedel-Crafts reaction between a phenol derivative (1) and a functionalized benzyl alcohol (2) in the total synthesis of (?)-podophyllotoxin, which is a medical cream that is used to treat genital warts. 7

Scheme 11. Fe-catalyzed Friedel Crafts reaction to synthesis (-)Podophyllotoxin.

Oxidation Reactions

Iron-catalyzed oxidation of hydrocarbons or other functional groups is an important objective. The research in the field led to a number of iron-based catalytic systems that can oxidize a number of organic substrates, for example, convert alkene to an epoxy compound by used oxygen, peroxides, or other oxidizing agents.5

Scheme 12. Example of an iron-catalyzed oxidation reaction
Reduction Reactions

Significant progress has also been made in the iron-catalyzed hydrogenation and transfer hydrogenation of alkenes, alkynes, and carbonyl groups. Casey reported the iron hydride complex to be an efficient catalyst in the hydrogenation of carbonyl compounds to obtain the corresponding alcohols with a high yield.5 ??? ??????????

Scheme 13. Hydrogenation of carbonyl compounds by iron hydride.
5.4 Polymerization Reactions
Polymerization reactions have great economic significance, as polymerization products find widespread applications as plastics and rubbers.
For example, the polymerization of 1,3?dienes by Iminopyridine?based FeCl2 catalysts and provide stereoselective access to elastomers such as polyisoprenes.11

6. Impurities in Iron Metal
Iron is often contaminated with trace amounts of copper or other metal. For certain reactions, the presence of copper is essential in order for the iron catalyst to expose its activity, highly (>99.99%) pure FeCl3 did show significantly decreases catalytic activity, whereas FeCl3 with > 98% purity or highly pure FeCl3 treated with
showed high activity. Chemical species like cu that improve catalytic activity are called co-catalysts or promoters in cooperative catalysis.5


7. Conclusions
There are a lot of reactions that catalyzed by iron, but the most important reaction is the cross-coupling reaction between Grignard reagents and numerous electrophiles to from a new C-C bond. The synthetic chemist, iron salts are often intimately connected to the centenarian Friedel–Crafts reaction, an electrophilic aromatic substitution promoted by metal salts, often including FeX_3 (X = Br, Cl).
Nowadays Iron-catalyzed reactions are key tools in the total synthesis of natural products and pharmacologically important chemical entities for example cis and trans solamins and Fingolimod(FTY720) also it uses in industry chemistry like preparation of elastomers, because iron is inexpensive, abundant, and non-toxic.