The Barbier Reaction

Name of the One-step Procedure. Early publications in this new field of organic chemistry reveal a bitter rivalry over priority and eponimy between the stu-dent/assistant Grignard (Nobel-prize winner 1912) and the teacher/head-of-the-department Barbier. Several modern historians have come to the conclusion [29] that the most reasonable name for this step-wise procedure would have been Barbier-Grignard reaction. 

The names, given to the one-step procedure, as first published by Barbier, vary from country to country and from individual to individual. 

The most systematic name would be the one in which the procedure is made clear to the reader such as one-pot reaction (e.g. in [30] and [31]) or one-flask reaction, in situ reaction [32], one-step reaction [33], etc. and such names are often encountered. However more often names such as modified) Wagner-Saytzejf reaction, Saytzeff reaction, Barbier-Grignard reaction [29], [34], [35] and [36], batch-method [36], Dreyfuss-Barbier reaction [37], Jaworsky reaction [38], Grignard-type reaction [39], [40], etc. are used. 

Probably because of unfamiliarity with his early work the name Frankland reaction has not been used although, as has been made clear earlier, many good reasons exist for such a claim. 

More recently [41-43] the name Barbier reaction has also been linked up to one-step processes in which metals, different from magnesium, are applied (see chap 3). In this monograph preference is given to names for such processes in which the applied metal is recognizable hence names such as Li-Barbier or Zn-Barbier etc. reactions will be used. 

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More impressive is the striking improvement which sonication afforded to the Barbier reaction [Eq. (39)] (214). This one-step coupling of organic... 

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. 

Although organomagnesium compounds are among the earliest reported organometallic compounds they were regarded as curiosities until 1900. At that time Victor Grignard, then a graduate student, worked in the laboratory of Professor Barbier at the University of Lyon in France. His task was to optimize conditions for what is now known as the Barbier reaction (equation 1). ... 

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)... 

Barhier cyclization The Barbier reaction has been used for cyclopentenone annclation.5 Thus a-allylcycloalkanones are converted into the iodo ketones 1, which on treatment in THF with magnesium activated by HgCl2 are converted into bicycloalkanols (2) in moderate to good yield. Formation of cw-fused products is greatly favored. The reaction gives poor yields when extended to annelation of six-und scvcn-mcmbcred rings. 

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. 

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 ... 

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... 

In contrast, the Barbier reactions of 2-acetamido-2-deoxy sugars with ketones showed a preference for the formation of 1,2-m-C-glycoside products (Scheme 7.39). This was attributed to the complexation of the C2-acetamido group to the glycosyl samarium, thereby reducing the configurational lability of the organometallic species.78,80,81... 

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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