Grignard/Barbier conditions

Perfluorovinyl organotin compounds can be prepared from perfluorovinyl Grignard reagents and organotin halides [76] (equation 11) Yields are slightly improved under Barbier conditions [76]... 

Grignard reagents usually give poorer yields than do the alkali metal reagents, but some reactions give good yields under Barbier conditions with ultrasonic assistance (Equation (56)).7... 

A number of methods were developed for the electrophilic amination of Grignard reagents306,30 3 to prepare primary amines. One of the recent examples uses l,3-dioxolan-2-one O-sulfonyloxime.307 The reaction gives imine, which affords primary amine after hydrolysis (Scheme 106). By using acetone 0-(mesitylsulfonyl)-oxime the amination can be performed under Barbier conditions from aryl bromide and magnesium.308... 

Kagan later found that THP was a better solvent than THF for the generation and reaction of allylic and benzylic samariums.107 When THP is used, the allylation of aryl ketones (which are prone to pinacol coupling) is possible, provided that Grignard conditions are employed and ketones that are prone to enolisation are efficiently allylated under Barbier conditions (Scheme 5.66).107... 

Organophosphorus compounds find wide use in the chemical industry as catalysts, intermediates, complexes, and end-use products. Arylphosphines and phosphine oxides are often produced by the reaction of a preformed Grignard reagent with a halophosphine or phosphine oxide. Yields are reduced by the production of unwanted side-reaction products such as biaryls. These unwanted products are reduced when the reaction is conducted under Barbier conditions. When alkyl and aryl halides are reacted with magnesium metal, a trihalophosphine or phosphine oxide, a metal halide or amine catalyst, in THE benzene mixtures, at reflux, good yields of phosphines or phosphine oxides are obtained [74]. For example, triphenylphosphine can be prepared in a 97.2% yield from the reaction of bromobenzene, trichlorophosphine, magnesium metal, aluminum chloride, and sodium chloride in THF-benzene at 70 80 C. 

The reaction of crotyl chloride with TMSCI under Barbier conditions yields the same ratio of products as the reaction of the preformed crotyl Grignard reagent with TMSCI in ether [Eq. (64) 130]. 

Silatranes are unstable in the presence of Grignard reagents, but under Barbier conditions, chloromethylsilatranes react with silyl halides to form silylmethylsilatranes in good yield (54 78%) [Eq. (71) 139]. 

It is facile to prepare dibenzyl derivatives, such as 78, when the corresponding Grignard reagents are stable. However, when they are not, because of the occurrence of an intensive polycondensation of the dihalide in spite of high dilution conditions, Barbier conditions prove to be very efficient (Scheme 3.7.12). The simultaneous reaction of l,4-bis(chloromethyl)benzene or 4,4 -bis(chloromethyl)biphenyl with tricyclohexyltin chloride and magnesium allows the preparation of -substituted dibenzyl derivatives 81 and 84, with one or two phenyl rings. 

The first enantiospecific total synthesis of (+)-ajmaline [(+)-17] was developed by Cook et al. 161). D-(+)-Tiyptophan methyl ester (126) was converted enantiospecifically, via intermediate 127, to the optically active )-N -benayltetracyclic ketone (-) 107, which was then transformed into the ot,P-unsaturated aldehyde (-)-128. When compound (-)-128 was stirred with 3-bromo-4-hq>tene in die Barbier Grignard process conditions the 1,4-addition products 129a,b... 

Keywords Alkyl/aryl/heteroarylAinyl/allyl bromides, magnesium (Mg), tetrahydrofuran (THF), pinacolborane, room temperature, Grignard cOTiditions/Barbier conditions, pinacolboronic esters... 

Clary, J. W., Rettemnaier, T. J., Snelling, R., Bryks, W., Banwell, J., Wipke, W. T., and Singaram, B. (2011). Hydride as a leaving group in the reaction of pinacolborane with halides under ambient Grignard and Barbier conditions, one-pot s5Tithesis of alkyl, aryl, heteroaryl, vinyl, and aUyl pinacol-boronic esters. J. Org. Chem., 76, 9602-9610. 

In 1991, Whitesides etal. reported the first application of aqueous medium Barbier-Grignard reaction to carbohydrate synthesis through the use of tin in an aqueous/organic solvent mixture (Eq. 8.48).106 These adducts were converted to higher carbon aldoses by ozonolysis of the deprotected polyols followed by suitable derivatization. The reaction showed a higher diastereoselectivity when there was a hydroxyl group present at C-2. However, no reaction was observed under the reaction conditions when there was an /V-acctyl group present at the C-2 position. 

In 1991, Li and Chan reported the use of indium to mediate Barbier-Grignard-type reactions in water (Eq. 8.49).108 When the allylation was mediated by indium in water, the reaction went smoothly at room temperature without any promoter, whereas the use of zinc and tin usually requires acid catalysis, heat, or sonication. The mildness of the reaction conditions makes it possible to use the indium method to allylate a methyl ketone in the presence of an acid-sensitive acetal functional group (Eq. 8.50). Furthermore, the coupling of ethyl 2-(bromomethyl)acrylate with carbonyl compounds proceeds equally well under the same reaction conditions, giving ready access to various hydroxyl acids including, for example, sialic acids. 

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). ... 

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. 

---