And the Barbier reaction

Sml2, which can be prepared conveniently from samarium powder and 1,2-diiodoethane in THF, finds application as a versatile one-electron reducing agent in organic synthesis. Two typical synthetic procedures mediated by Sml2 are the pinacol coupling of aldehydes and the Barbier reaction, as shown in the following schemes ... 

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. 

The phenomena observed in the above-mentioned reaction present the first example of the trapping of the radical from the alkyl halide other than by the same alkyl radical or by MgX-. Thus an independent proof for the occurrence of alkyl radicals during the Grignard and the Barbier reaction has been obtained. 

The other reactions are the addition reaction of carbonyl groups [16,19], the addition reaction of carbon—nitrogen unsaturated bond, intramolecular rearrangements (3.19) [16] and the Barbier reaction of sonochemistry, etc. Here, 1 will describe only the Barbier reactions of sonochemistry. Recently, an ultrasonic technique has been used for dispersion, emulsification, deaeration, and washing. In 1986, this ultrasonic technique had also started to be used for organosynthetic reactions, and it was noted that the organosynthetic method simply shows short reaction time and high yields [22]. It is considered that the improvements in the reaction rate with ultrasound is caused by cavitation phenomena. 

The report by Luche and coworkers that ultrasonic waves from a common ultrasonic laboratory cleaner aid the formation of organolithium and Grignard reagents and also improve the Barbier reaction spurred much of the current interest in the synthetic applications of ultrasound(lO) ... 

Blomberg, G. The Barbier Reaction and Related One-step Processes Springer Berlin, 1998. 

An extension of the Barbier reaction to carboxylates salts [90] affords a simple access to furanyl ketones [91]. By sonication of a mixture of a lithium carboxylate, an alkyl chloride and lithium in THE at room temperature, the intermediate organolithium reagent forms rapidly, then generates the 2-furanyl lithium which adds to the carboxylate group in high yields. The method constitutes an example of a reaction cascade , in which several intermediates are generated sequentially (Scheme 3.13). 

Table 3. Catalysis results for the Barbier reaction of benzaldehyde and allyl bromide in presence of homogeneous palladium catalyst (entry 1) and those prepared by complexing palladium to amine functionalized mesoporous silica (entry 2-4) [74]...

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. 

The reaction with alkyl- and aryllithium reagents has also been carried out without preliminary formation of RLi a mixture of RX and the carbonyl compound was added to a suspension of lithium pieces in THF.364 Yields were generally satisfactory. The magnesium analog of this process is called the Barbier reaction,365 Lithium dimethylcopper Me2CuLi... 

C. Blomberg, The Barbier Reaction and Related One-Step Processes, (Reactivity and Structure. Concepts in Organic Chemistry, Vol 31), Springer Verlag, Berlin-New York (1993)... 

The oxidative insertion of zinc into a-halo carbonyl compounds and the subsequent reaction of the zinc enolates formed with various electrophiles can either be carried out in a one-pot Barbier-type fashion or in two consecutive steps.1-3 Zinc enolates exhibit a reasonably high stability over a wide temperature range (from -78°C to above 80°C for short periods of time) compared to other metal enolates. Although it has been reported that solutions of BrZnCH2COOtBu can be stored for several days without loss in activity,5 it is generally advisable to use freshly prepared reagents in order to avoid... 

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. 

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. 

Blomberg, C. The Barbier reaction and related one-step processes. Springer-Ver-lag Berlin, 1993. 

Especially noteworthy in the Barbier reaction is the tolerance of water. Many reactions could be performed in a mixture of an organic solvent and water (THF/NH4CI), or in a pure aqueous media (water, aqueous ammonium... 

Inanaga showed that the presence of HMPA also accelerates the Barbier addition of alkyl halides to ketones and significantly improves the yield of the adducts.14 He also found that HMPA was a useful additive in the Sml2-mediated synthesis of lactones from bromo esters and ketones (Scheme 2.5). Since Inanaga s pioneering work, the Barbier reaction employing Sml2 HMPA... 

The classical (Grignard-like) mechanism for Barbier reactions involves the primary formation of an Sm-alkyl species via halogen abstraction and subsequent reduction of the alkyl radical formed after the first electron transfer. Be that as it may, the Barbier reaction can be used to construct complex polycyclic target molecules, e.g. the synthesis of tetraquinanes from diquinane precursors by two independent intramolecular cyclization steps (Scheme 24) [83]. 

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