Barbier process

Samarium diiodide is a one electron reductant that is capable of reducing both alkyl halides and carbonyl compounds. The rate of the reduction depends on the nature of the substrate and the reaction conditions. The mechanism of the addition of alkyl halides to carbonyls was extensively studied. In case of the samarium Grignard processes, it was concluded that the reaction proceeds through an organosamarium intermediate. However, the mechanism of the samarium Barbier processes is not fully understood and there is no unambiguous evidence in favor of any of the possible pathways. 

A few reactions using zinc as the metal in a Barbier process have been published.267 Methallyl bromide and salicylaldehyde sonicated in THF with zinc yield the expected alcohol, which cyclizes by acidic treatment to a chromene.268... 

The processes used in the manufacture of morphine are believed to be still based on that described by the Scottish chemist Gregory,in 1833, with improvements devised by Anderson. A description has been published by Schwyzer, who also deals with the manufactme of codeine, narcotine, cotarnine, and the commercially important morphine derivatives, diamorphine (diacetylmorphine), and ethylmorphine (morphine ethyl ether). More recently Barbier has given an account of processes, based on long experience in the preparation of alkaloids from opium. Kanewskaja has described a process for morphine, narcotine, codeine, thebaine and papaverine, and the same bases are dealt with by Chemnitius, with the addition of narceine, by Busse and Busse, and by Dott. It is of interest to note that a number of processes for the extraction and separation of opium alkaloids have been protected by patent in Soviet Russia. ... 

This lithium process is the analogue of the magnesium-based Barbier reaction [135],... 

Grigg and coworkers developed bimetallic domino reactions such as the electro-chemically driven Pd/Cr Nozaki-Hiyama-Kishi reaction [69], the Pd/In Barbier-type allylation [70], Heck/Tsuji-Trost reaction/1,3 dipolar cycloaddition [71], the Heck reaction/metathesis [72], and several other processes [73-75]. A first example for an anion capture approach, which was performed on solid phase, is the reaction of 6/1-134 and 6/1-135 in the presence of CO and piperidine to give 6/1-136. Liberation from solid phase was achieved with HF, leading to 6/1-137 (Scheme 6/1.30) [76]. 

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

An electroreductive Barbier-type allyla-tion of imines (434) with allyl bromide (429) also occurs inaTHF-PbBr2/Bu4NBr-(Al/Pt) system to give homoallyl amine (436) (Scheme 151) [533]. The combination of Pb(II)/Pb(0) redox and a sacrificial metal anode in the electrolysis system plays a role as a mediator for both cathodic and anodic electron-transfer processes. The metals used in the anode must have a less positive anodic dissolution potential than the oxidation potentials of the organic materials in order to be present or to be formed in situ. In addition, the metal ion plays the role of a Lewis acid to form the iminium ion (437) by associating with imine (435) (Scheme 151). 

Thus, chloro enamines 113, either under Barbier-type reaction conditions (—40 °C) or in a two-step process (hthiation at —90 °C and Sg reaction at —90 to —40 °C), were lithiated with DTBB (5%) and finally hydrolyzed, after condensation with different electrophiles, giving the expected functionalized enamines 114 (Scheme 44) °. ... 

The Barbier-type reaction shown in Scheme 121 was also applied to the dichlorinated materials 432-434, as well as trichloroaUcanes 435 and even tetrachloromethane 436. In every case, all chlorine atoms were replaced by electrophilic fragments, so the starting material behaved as polylithium synthons. Actually, the whole process takes place probably by successive tandem lithiation-SE reactions until consumption of all chlorine atoms... 

In the case of chlorobenzyl chlorides 504, the same process had to be performed under Barbier-type reaction conditions. These dichlorinated materials 504 were lithiated with DTBB in a catalytic amount (4%) in the presence of different electrophiles to give, after final hydrolysis with water, the corresponding difunctionalized products 505 (Scheme 141) ". ... 

This sacrificial anode process compares favorably with Wakselman s classical Barbier procedure which requires activated zinc powder, and CF3Br under pressure, leading to lower yields with benzaldehyde (52% in DMF)21. These good results compared to those obtained from a mixture of CF3ZnBr and (CF3)2Zn allow one to illustrate the formation of a transient organozinc compound of the type CF3—Zn , which would be the really active species. This prompts the following question does the reduction of Zn2+ in Zn... 

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)... 

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

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