Mechanism of the Barbier Reaction

At the beginning of the 1990s, regarding the different views on the mechanism of the Grignard reagent formation reaction, the question was in short formulated as follows [65]  

Does Grignard reagent formation proceed entirely via free radicals, or are other intermediates such as radical anions involved  

The D Model (see also a later publication by Garst et al. [66]) allows all radicals to leave the surface and diffuse freely in solution all times . 

On the basis of further studies of reactions of bromocyclopropanes [65,67] Walborsky et al. came to the conclusion [65] that the mechanism 

Conclusion. There is a general agreement on the existence of radicals on the metal surface in the Grignard reagent formation reaction. A large part of the halide is converted to a radical anion followed by heterolytic cleavage of the carbon-halogen bond. 

---

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. 

It should be mentioned here however that products of this type are seldom reported and therefore seem not to be formed in considerable quantities. The reaction of the halide with the metal and consecutive reaction of the intermediate organometallic species (see Sect. 4.4 for a discussion of the mechanism of the Barbier reaction) with the carbonyl compound seems to be fast enough to prevent this ether formation. 

Studies on the stereochemistry of these intramolecular Barbier reactions in which mono- and tetra-substituted cyclohexanones and several other cycloal-kanones were involved revealed a preference for the cis ring closure. Some preliminary conclusions were drawn regarding the mechanism of the Barbier reaction (see also Sect. 4.4). 

With the simultaneous presence of three reactants, i.e. the organo halide, substrate and metal, the mechanism of the Barbier reaction could be said to be even more difficult to elucidate, since interaction with the metal could take place consecutively with each reagent or with both at the same time. 

And very recently, systematic research on the mechanism of the Barbier reaction has also been published. 

In view of the elucidation of the mechanism of the Barbier reaction it is to be hoped that also coadsorption on the metal surface of carbonyl compounds together with organo halides will be studied. 

Studies with Bulky Reagents 1977-1988. New contributions to the elucidation of the mechanism of the Barbier reaction soon followed the previous ones. Molle, Bauer and Dubois and coworkers discovered [47] that when the reaction mixture of 1-bromoadamantane (IV) (Ad-Br) and magnesium was not stirred the desired Grignard reagent could be obtained in yields varying from 25% to 60% depending on the solvent used (lowest in THF, highest in diethyl ether and in din-butyl ether). 

Effects of the Activation of the Metals. In the last decade several reports on the mechanism of the Barbier reaction have appeared in which not magnesium but lithium and zinc were the metals applied. 

Semiempirical MO Calculations. A more detailed picture of the radical ion mechanism of the Barbier reaction was given by Luche and co-workers [93] using semiempirical MO calculations. A theoretical support was provided for the observed configuration inversion at the halide carbon center as found in the reaction of S( + ) 2-halooctane mentioned above. 

---