Benzylic halides Barbier reaction

The mechanisms of reactions of benzylmagnesium halides can be either homolytic or concerted. As with allylic Grignard reagents, also reversible addition reactions with benzylic Grignard reagents and carbonyl compounds have been reported. In general, yields of normal alcohols are low, and such alcohols are obtained in much better yields by use of dibenzylcadmium [66] or benzyllithium [67]. However, in 1980, it was demonstrated that, by far, the best and quickest results for the synthesis of these normal addition reaction products are obtained by applying benzylic halides in the one-step Li-Barbier reaction under ultrasonic irradiation [68,69]. 

The general scheme for the one-step Barbier addition reaction of alkenyl and benzylic halides with aliphatic or aromatic aldehydes is shown in Eq. (1). 

Barbier coupling reaction Metal-mediated addition of alkyl, allyl or benzyl halides to carbonyl compounds. 38... 

Barbier reaction. A catalytic amount of AgN03 is important in the Zn-mediated reaction of benzylic halides with ArCHO in buffer solutions (pH 12) as less bibenzyls are formed. 

In general, in the reaction of benzyl halide with lithium, the yield of benzyl-lithium is low since the Wurts coupling reaction proceeds. How ever, with the addition of ketones to this reaction system and ultrasound irradiation, Barbier reaction then proceeds. It is believed that this reaction yields benzyllithium as an intermediate and the benzyllithium reacts with ketone [23]. 

Benzyl halides and allyl (propargyl) halides are structurally similar but have drastically different chemical reactivities in the aqueous Barbier-Grignard-type reactions. Although tribenzyl and dibenzyltin derivatives have been prepared in aqueous conditions since the 1960s, they do not add onto carbonyls, most likely because it is not possible to form a six-membered cyclic transition state with the carbonyl group in a two-componenf fashion. Still, zinc-mediated benzylation of carbonyl compounds in aqueous media was reported by Bieber et al. recently. The benzylation of 4-nitrobenzaldehyde could be controlled chemoselectively by using various phase transfer catalysts and metal reductants in water (Eq. 4.41). 2... 

The reaction could be extended to the alkylation of immonium cations generated from secondary amines and aldehydes. The allylation of 1-(aminoalkyl)benzotriazoles proceeded smoothly only in the presence of water. More interestingly, alkylation agents used include benzyl and methyl halides hitherto unknown for an aqueous Barbier reaction (Katritzky et al., 1992). 

Indium-mediated Barbier-type coupling between carbonyl compounds and allyl halides has been revealed to proceed effectively in diverse reaction media. Even under solvent-free conditions, allylation works well, although no reaction is observed with benzyl bromide and a-halo carbonyl compounds.59 Various aldehydes react with allyl bromide mediated by indium in liquid carbon dioxide to give homoallylic alcohols (Scheme 1). In contrast to the corresponding neat allylation, the liquid C02-mediated reaction can allylate solid aldehydes successfully.60 Indium-mediated allylations of carbonyl compounds with allyl bromide proceed in room temperature ionic liquids. In [bmim][BF4] and [bmim][PF6] (bmin l-butyl-3-methylimidazolium), the desired homoallylic alcohols are formed with good levels of conversion.61 Homoallyllic alcohols are also prepared by the reaction of resin-bound aldehydes (Equation (l)).62... 

Kagan also showed that allylic, benzylic and propargylic halides undergo efficient reaction with ketones (Scheme 5.65).98 Importantly, in the absence of ketone, these alkyl halides react rapidly with Sml2 to yield Wurtz homocoupled products, hence the use of Barbier conditions is crucial. 

A general method makes use of Barbier conditions combined with ultrasonication. The organic halide, RX, bis(tributyltin) oxide, and magnesium powder are caused to react in THF, in the presence of 1,2-dibromoethane, in an ultrasonic cleaning bath at about 35 °C for one hour.16 The presence of a surface-active compound in the bath assists cavitation. The reactions proceed in good yield with alkyl, vinyl, allyl, benzyl, aryl, and heteroaryl halides (usually bromides). 

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