IRON-CATALYSED CROSS-COUPLING

Iron-Catalysed Cross-coupling: noble job for a cheap metal

Iron-Catalysed Cross-Coupling: Noble Job for a Cheap Metal

Introduction

The palladium and nickel are the best metals which can use as catalysts, but for many reasons especially that related to the environment, another metal has been required to replace palladium and nickel, Iron was the best choice, due to its characteristics and the efficiency in cross-coupling reactions. Moreover, it is much cheaper than palladium and it can be a good substitute of it. Making many industries and laboratories has worked to improve this area (Czaplik, 2009, 610). Over the past decade, metal-catalysed cross-coupling reactions have been taken the widest scope in organic and organ metallic chemistry (Czaplik, 2009, 610).

Background

It is found that Fe(acac)3 can be used as a catalysts in cross-coupling reactions of Grignard reagents with many kinds of functional groups such as electron-deficient aryl chlorides and tosylates, aryl triflates, alkenyl chlorides carboxylic acid chloride, and propargyl epoxides (Seidel, 2004, 395).

Some ligands are hydrophilic and sensitive of oxygen (Furstner, 2002, 1385). Furstner et al searched and investigated the uses of iron salts, and tried to find a new strategy to make it more attractive and efficient to be the substitute of the very expensive palladium and nickel catalysts. They found the iron salts perform the reaction at room temperature or even below it. Not only but also one of the most significant advantages is iron salt enable for activation of aryl chlorides, triflates, and tosylates under “ligand free” condition.

However, industries also seriously require cheap ligands and solvents to use it in small amount with iron-catalysed for large scale application.4 This subject was studied by Cahiez et al, FeCl3 was used as a catalyst of cross-coupling reaction between primary and secondary alkyl bromide and aromatic Grignard reagents by Hayashi and Nagano and Bedford et al. [FeCl(salen)] complex also can be used as a catalyst (the group of Bedford worked in it) (Cahiez, 2007, 436). The disadvantages of that are the yields do not exceed 80%, also a very large amount of Grignard reagent have to add in once. In addition, the reaction happens in diethyl ether under reflux. Also, these methods are not suitable for large-scale applications (Cahiez, 2007, 436).

Most of cross-coupling reactions catalysts depend on metals, because the metals can be compatible with most functional group, the best and most famous metals are used as catalysts by industries and an academic laboratories are nickel and palladium by even though also they take long time to be ready, in addition the palladium cost high and toxicity of nickel salts (Seidel, 2004, 395).

The first iron-catalysed cross-coupling reaction between alkenyl Grignard reagents and n- or s-alkyl was described by Gerard Cahiez et al (Cahiez, 2007, 436). There are many advantages of iron-catalysed cross-coupling, fast reactions under low temperature and ligands free conditions using a cheap, nontoxic and environmentally (Seidel, 2004, 395). Gunter et al proofs these pros by the scalable synthesis of the potent immunosuppressive agent FTY720 (Seidel, 2004, ...