Metal Barbier reaction

An example of a 4-lithio species that has been prepared is the 2-methylthio derivative 325 that has been prepared from the iodo compound 324 by both conventional halogen-metal exchange reaction with butyllithium <2001TL311, 2001TL8697, 2005JOC6204> and under Barbier conditions with sonication <2000T3709>. 

The Barbier reaction is the reaction between a halogenated derivative and a ketone or an aldehyde in the presence of a metal. As an organometallic intermediate species is often postulated, this reaction is usually conducted after careful exclusion of water. Yet it has been shown that this reaction takes place not only in presence of some water, but even in water itself. 

Commercial ordinary zinc is generally poorly reactive due to the inertness of the oxide passivation layer, its compactness, and adherence to the underlying metal.11 The Barbier reaction (and others) requires activation which can be accomplished by several methods. 

Cementation consists in the formation of a surface alloy with a less reactive metal. For zinc, alloying can be effected with mercury (amalgamation), copper, silver, nickel.12 The reactivity of a cemented metal can be explained considering that the supporting metal plays only the role of an electron reservoir, the true chemistry is effected by the superficial additional metal. Zinc can also be activated by washing with aqueous ammonium chloride,13 or by reacting the powder with trimethyl-chlorosilane.14 In this latter case, Barbier reactions were effected even at 0°C in short times. The activation mechanism was not determined. 

In conclusion, it can be stated that the Barbier reaction was an important discovery for organic synthesis. Besides the historical and theoretical interests, we can see that the applications in various domains of synthesis are numerous, due to the experimental simplicity and the good to excellent results, frequently equal or better than more complicated conventional techniques. These qualities appear in the examples discussed above and zinc is the metal of choice for many applications. The discovery of the aqueous reactions should lead to more and more applications, especially as a result of the care being paid to environmental questions by chemists. 

Barbier reaction reaction of an organic halide with a substrate and metal... 

Mg Si bonds have long been inferred in reactions that generate hexaorganodisilanes from halo(triorgano)silanes and either a Grignard reagent or Mg metal ( Silico-Barbier reaction). Similarly, the electrochemical reduction of chloro(triorgano)silanes with sacrificial Mg electrodes yields... 

The samarium(ll)-mediated Barbier reaction has been used as an alternative to the deprotonation chemistry to generate 2-alkyl-metallated oxazoles (Scheme 43). This reaction is very useful for the coupling of 2-iodomethyl oxazoles and aliphatic aldehydes. However, reactions with aromatic aldehydes gave mainly pinacol coupling products <20050L4099>. 

There are very few studies of the Barbier reaction mechanism with magnesium as the metallic source. However, with the discovery that the reaction will often proceed to a greater extent with other metals such as lithium, some good mechanistic studies have been conducted. The focus of most of these studies has been the reaction of an alkyl or aryl halide with a ketone. The conclusions drawn from these studies are considered to be valid for magnesium as well, and they will be referenced in this section. 

Although the mechanism of the Barbier reaction is not completely resolved, the best evidence now indicates that radical anion or radical species, or both, are involved. These radical moieties most likely are formed by SET reactions on the metal surface and may involve the electrophile as well as the halide. The body of evidence indicates that a short-lived R MgX species is not formed in most Barbier reactions. 

In their studies on the use of silyl-substituted ligands as thermal and oxidative stabilizers of transition metals, Pannell and collaborators [79] show that tram- -trimethylsilyl-3- / -allyl(trimethyl)tin can be prepared in an approximate 50% yield by the Barbier reaction of a trialkyl or triarylmetal chloride with magnesium metal and l-trimethylsilyl-3-chloroprop-l-ene. With nickel(II) chloride, magnesium, a trace of mercuric(ll) chloride, and 2-trimethylsilyl-3-chloroprop-l-ene, the thermally and oxidatively stable bis( / -2-trimethylsilylallyl)nickel derivative is prepared in 36% yield. The unsubstituted derivative is thermally unstable and ignites in air. 

Functionally substituted benzylic, allylic, and vinylic compounds containing alkoxides, esters, ethers, nitriles, or amides can be reacted with halosilanes under Barbier conditions using HMPT to yield C- and O-silylated products, 1,2- or 1,4-addition products, as well as reductive dimers. Radical and anionic intermediates are postulated, based on SET reactions from the metal, and multiple silated species can be obtained. The use of the TMSCl-Mg-HMPT system has been extensively investigated by Galas group [85] at the University of Bordeaux, and their work has greatly advanced the science of the Barbier reaction with silanes. 

The Barbier reaction with other metals can occupy an entire volume on its own and, hence, will not be reviewed in this work. The interested reader should refer to the references cited at the beginning of this text and those noted in the following for additional information. 

In the last 10 years, the Barbier reaction method has been utilized more with other metals than with magnesium. The number of papers published on the lithium-Barbier reaction is three to four times that of magnesium [149-157]. Reactions can be carried out at lower temperatures than possible with Mg-Barbier reactions and yields are often very high with fewer by-products. Other metals of note are samarium, in the form of its diiodide [158-165], and zine [166-169], the metal of choice for the pre-Barbier one-step reaction, and the classic Reformatsky reaction. In situ reactions have been reported for A1 [170], Ce [171], Cd [172,173], Ga [174], Hg [175], In [176], Mn [177], Pb [178-180], Sb [181-183], Sn [184,185], and Ti [186]. An excellent paper by Li reviews the Barbier reactions of many metals in aqueous media [187]. 

Dichloromethylphosphonate carbanions are generally prepared in situ from dialkyl trichlorometh-ylphosphonates by a halogen-metal exchange reaction under Barbier conditions, by electrophilic chlorination of a chloromethylphosphonate carbanion, or by a double electrophilic chlorination of methylphosphonate with phenylsulfonyl chloride (2 eq) in the presence of n-BuLi (3 eq). ... 

The Barbier reaction, described in 1898 [94], consists of a one-pot coupling reaction between an alkyl halide onto a carbonyl compound in the presence of a metal. This reaction which was formerly conducted in an organic solvent with careful exclusion of water is now performed in water in high yields onto a wide variety of substrates. The first aqueous allylation, albeit in low yields, was performed as long as twenty years ago, using zinc in refluxing ethanol containing 5% water [95]. 

The indium-mediated Barbier reaction has certainly become one of the most popular reactions for creating a carbon-carbon bond under aqueous conditions and has led to spectacular developments in recent years. Compared to other metals, indium is resistant to oxidation, hydrolysis, and has a very low first ionization potential (5.79 eV, in contrast to the second one which is quite normal) which confers on it a remarkable reactivity in Barbier-type reactions. In 1991, Li and co-workers reported the first allylation of aldehydes and ketones mediated by indium in water without any additives or special activation [133]. In particular, the use of indium allowed reactions with acid-sensitive compounds [134] or the preparation of complex carbohydrates such as deaminated... 

Barbier et al. during the hydrogenation of benzene (a typical metal-catalyzed reaction) over Pt/Al202 at 358 K. The poisoning by ammonia is a sensitive reaction, since the remaining activity is more important when the metallic particles are larger. 

Note that there are several modern versions of the Barbier reaction that use transition metals or their derivatives.Examples include indium metal, samarium iodide, and lead. An example using lead reacted benzaldehyde with allyl bromide in the presence of lead metal to give a 99% yield of 45.56 A retro-Barbier fragmentation has also been reported in which an alcohol was treated with 10 equivalents of bromine and 15 equivalents of potassium carbonate in chloroform to give a bromo ketone.5 ... 

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