Radical anions Barbier reaction

The mechanism of the intramolecular samarium-initiated Barbier reaction is still a matter of debate [80-82], One of several mechanistic possibilities is primary reductive generation of the ketyl radical anion which can subsequently initiate a second... 

The mechanism of the Barbier reaction is believed to proceed initially through the same radical anion species postulated for the Grignard reaction. The resulting... 

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. 

The general reaction of ketones with halides under Barbier conditions is analogous to that of aldehydes. Usually, the reaction products are alcohols. The major by-products are diols resulting from the coupling of ketyl radical anions [Eq. (5)]. 

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. 

Since the observation that allylation of carbonyl compounds could be mediated by tin in aqueous medium [77], there has been an intensive development of the Barbier-type allylation reaction in water. Three metals were particularly investigated zinc, tin, and indium. In the aqueous zinc-promoted allylation, allylzinc species are considered unlikely. The initiation of the reaction could be attributed to the formation of an allylic radical anion on the metal surface this radical surface could then react with the carbonyl compound to give an alkoxide radical, which could add an electron and form the alcohols [82]. Allyl bromide or even chloride reacts with aldehydes and ketones in the presence of commercial zinc powder in a mixture of tetrahydrofuran and saturated ammonium chloride aqueous solution (Eq. 7) [83]. 

We remarked that the first step of the radical-anion chain mechanism (Fig. 4) can be considered as a reduction of the halide by the nucleophile. Consequently, we tried to use well known reductants such as zinc. However, no reaction occurred when the halide is placed in the presence of zinc in various solvents. By analogy with the thiophenoxide condensation, we attempted the transformation in DMF under slight pressure. Consumption of the reagents was only observed when electrophilic substrates, such as carbonyl compounds, are present since the beginning of the reaction. These Barbier like condensations started more easily in pyridine than in DMF (ref. 19). Moderate yields were obtained with aldehydes as substrates (Fig. 6). 

The condensation between xanthen-9-one and an organometallic derived from tropylium bromide is not feasible due to the antiaromatic character of the anion. The problem was solved by an "umpolung" Barbier condensation (Eq. 7).82 The LiDBB radical anion, from lithium and DBB, releases its electron in a two-step reaction to reduce the carbonyl group to the dianion, making the process catalytic in DBB. Without sonication, the process is too slow to be useful. 

These experiments conclude that the Barbier reaction is a one-step Grignard reaction when alkyl chlorides are used. On the other hand, when the starting material is a bromide, radical anions as the actual reactive species should be considered, and the Barbier reaction has no obvious parenthood with a Grignard reaction. Applications of this finding are discussed later. 

Although the mechanistic details of the Li-Barbier reaction will be discussed in Sect. 4.4.2, it should be mentioned here that a mechanism in which an intermediately formed radical anion (or ketyl) reacts with the organic halide to give an alkoxide radical as given in the following equations ... 

With saturated carbonyl compounds participating in Barbier reactions the initial step should be the formation of the halide radical anion (Path A). 

As C—M bonds of most post-transition metals have a strong covalent character and because many reactions can occur also via radical and radical anion processes on metal surfaces, it is not surprising that many other metals have been foimd to mediate the Barbier-Grignard-type reactions in water. 

In organic solvents, it was demonstrated that the Barbier reaction did not necessarily involve the formation of an organometallic species. In some cases there is a radical pathway in which the anion radical resulting from single electron transfer from the metal to the halogenated compound is trapped by the ketone or the ketyl radical on the surface of the metal (Molle and Baner, 1982). 

Initial formation of a radical anion of the type [RX] seems highly probable as in the Barbier reaction. The radical ion absorbed on the metal surface, more or less readily cleaved in a radical, is trapped by the a,P-unsaturated carbonyl compound, affording an a-keto radical, which is further rapidly... 

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