Barbier-reaction

Barbier reactions have been widely developed to add allyl bromide to carbonyl compounds (aldehydes or ketones) 

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 

In many cases, activation of the zinc dust is necessary to reach complete conversion or to accelerate the reaction. This activation can be achieved by treatment of zinc dust with an acid chloride267 but can be achieved also with liquid ammonia268 or by sonoelectrochemical methods.259,269,269a Activation can be achieved by adding metallic salts such as AICI3, CeCb, PbBr2, or Cul to the reaction mixture.2536,257,270 Sonication proved also to enhance the reactivity of Barbier-type reaction in aqueous media (Equation (157)).2S3 255 2S6 270 270a 271 

Barbier reactions can be highly regioselective depending on the conditions of allylation, they could proceed via Sg2 - or SEZ-pathway.256 270 272 Good diastereoselectivity can also be obtained by using a chiral electrophile (Equations (158)-( 160)).258 273-275 

Madsen and Hyldtoft proposed a novel zinc-mediated domino reaction to give functionalized dienes.267 Using a Barbier reaction, different approaches of interesting compounds have been reported vitamin D3 analogs, 1 bicy- 

The Barbier reaction is an organic reaction between an alkyl halide and a caiboityl group as an electrophihc substrate in the presence of magnesium, aluminium, zinc, indium, tin or its salts. The reaction product is a primary, secondary or tertiary alcohol. Cf. Grignard reactioa 

Name Reactions A Collection of Detailed Mechanisms and Synthetic Applications, DOI 10.1007/978-3-319-03979-4 10, Springer International Publishing Switzerland 2014 

Example 5, The following whole sequence of 5 steps can also be carried out in 

Moyano, A. Pericas, M. A. Riera, A. Luche, J.-L. Tetrahedron Lett. 1990,31,7619-7622. (Theoretical study). 

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The mechanism for the transformation of 5 to 4 was not addressed. However, it seems plausible that samarium diiodide accomplishes a reduction of the carbon-chlorine bond to give a transient, resonance-stabilized carbon radical which then adds to a Smni-activated ketone carbonyl or combines with a ketyl radical. Although some intramolecular samarium(n)-promoted Barbier reactions do appear to proceed through the intermediacy of an organo-samarium intermediate (i.e. a Smm carbanion),10 ibis probable that a -elimination pathway would lead to a rapid destruction of intermediate 5 if such a species were formed in this reaction. Nevertheless, the facile transformation of intermediate 5 to 4, attended by the formation of the strained four-membered ring of paeoniflorigenin, constitutes a very elegant example of an intramolecular samarium-mediated Barbier reaction. 

Similar reactions were also carried out with 3-bromopropene, l-bromo-2-butene, 3-bromocy-clohcxcnc. and 3-bromocyclooctene in refluxing ethanol as solvent24 . Zinc-mediated Barbier reactions can be accomplished with high yields in a mixture of saturated aqueous NH4C1/THF (5 1), at room temperature or below using a 1.2 to 2-fold excess of the halide over the carbonyl compound25. 

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

Mistryukov, E. A. et al., Mendeleev Comm., 1993, (6) 242 Adding formamide to a reaction mixture of allylzinc bromide and a ketone as a proton source for a Barbier reaction in ether or tetrahydrofuran gave uncontrollable explosion-like reaction. The reaction proceeded smoothly when starting from zinc dust and allyl bromide, with both formamide and the ketone in situ. 

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) ... 

As with other haloaromatic systems, Barbier reactions are also suitable for heterocyclic systems. For example, the lithio derivatives formed in situ from iodide 187 upon sonication reacted immediately with electrophiles such as benzaldehyde, hexanal and diphenyl disulfide, to give good yields of 188 <00T3709>. Similar chemistry was also successful with pyrazines, pyrimidines, and pyridazines. 

In a similar manner, starting from 2-methylchloride-naphtho[l,8-de][l,2,3]triazine and magnesium, via a novel sonication-promoted Barbier reaction, an a-aminomethyl carbanion equivalent is generated which reacts in situ with a variety of carbonyl compounds. Subsequent catalytic hydrogenolysis of the triazine moiety yields the corresponding amines <00TL4685>. Sterically controlled regiospecific cyclization of aldose-5-ethyl-l,2,4-... 

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). 

Li, et al. reported ethyl-bridged PMOs with Pd(ll) complexed to 3-aminopropyl-Itrimethoxysilane grafted onto the mesoporous walls to be an efficient catalysts for Barbier reaction of benzaldehyde and allyl bromide (Figure 16) [74]. Use of water as the reaction medium combined with the presence of ethyl moiety in the framework (which increased hydrophobicity of the pores) enhanced diffusion of the organic substrates. As can be seen in Table 3 the PMO material showed superior catalytic efficiency compared to grafted SBA-15 and MCM-41 materials with values comparable to homogeneous trials. 

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]...

Baeyer-Villiger reaction, 9, 3 43, 3 Bamford-Stevens reaction, 23, 3 Barbier Reaction, 58, 2 Bart reaction, 2, 10 Barton fragmentation reaction, 48, 2 Bechamp reaction, 2, 10 Beckmann rearrangement, 11, 1 35, 1 Benzils, reduction of, 4, 5 Benzoin condensation, 4, 5 Benzoquinones ... 

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... 

For a review of diiodosamarium chemistry (including Barbier Reactions) see ... 

Barbier reaction Samarium(II) iodide, 270 Benzoannelation Chromium carbene complexes, 82 Dicarbonylcyclopentadienylcobalt, 96 Ethyl (Z)-3-bromoacryIate, 130 Grignard reagents, 138 Methyl acrylate, 183 Methyllithium, 188 Ruthenium(III) chloride, 268 Benzoin condensation Benzyltriethylammonium chloride, 239 3-EthyIbenzothiazolium bromide, 130 Benzoylation (see also Acylation) Cadmium, 60 Dibutyltin oxide, 95 Birch reduction Birch reduction, 32... 

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