Allylic halides Barbier-type reactions

Reisse used activated zinc for aqueous Barbier-type reactions.66 Submicromic zinc powder produced by pulsed sono-electroreduction is about three times more effective than the commercial variety. The stereochemical course of the allylation and propargylation of several aldehydes with crotyl and propenyl halides using zinc powder as the... 

Scheme 168 Samarium-mediated Barbier-type reaction of carbonyl compounds with allyl halides.

The coupling reaction of a-keto esters with allyl, propargyl, and allenyl halides using indium metal in aqueous solvents affords a-hydroxy-y,<5-unsaturated esters (Equation (28)).197,198 1,3-Dicarbonyl compounds undergo efficient carbonyl allylation reactions in an aqueous medium through a Barbier-type reaction (Equation (29)). The reaction is general and a variety of 1,3-dicarbonyls has been alkylated using allyl bromide or allyl chloride in conjunction with indium.199... 

Another important metal for Barbier-type reaction is samarium. Allyl bromide reacts with a ketone and Sm to give the homoallylic alcohol. Samarium compounds, such as Sml2, can also be used with allylic halides. 

These examples again have some mechanistic implications in that they appear to rule out cyclization via 5n2 displacement of the halide by a samarium ketyl. However, one cannot distinguish between a mechanism based on allylsamarium addition to the carbonyl versus an electron transfer mechanism as outlined for the alkyl hdide substrates above. Both mechanisms allow for isomerization of the double bond (via 1,3-allylic transposition in the case of an allylmetallic, or configurational instability in an allylic radical in a diradical coupling mechanism) and also provide reasonable routes for generation of butadiene. Further mechanistic work is clearly required in order to provide a more detailed understanding of all of these intramolecular Barbier-type reactions. 

The Barbier-type reaction of aldehydes and ketones with allyl halides (485) in the presence of Smh, leading to homoallyl alcohols (486), has received recent interest as a one-step alternative to the Grignard reaction. However, the reactions require the use of stoichiometric amounts of the reducing Sm(III) species. Recently, the electroreductive Barbier-type allylation of carbonyl compounds in an Sml2-mediated reaction has been developed [569]. The electrolysis of (485) is carried out in a DMF-SmCl3-(Mg/Ni) system in an undivided cell to give the adduct (486) in 50 85% yields (Scheme 168) [569]. Electrosynthesis of y-butyrolactones has been achieved by the reductive coupling of ethyl 3-chloropropionate with carbonyl compounds in the presence of a catalytic amoxmt of SmCfi [570]. 

More Barbier-Type Reactions with Allylic Halides... 

Indium mediated Barbier-type cross coupling between carbonyl compounds and allyl halides proceed efficiently under solvent-free conditions. No apparent competing pinacol-coupling or homo-coupling of the allyl halide was observed. The reactions were found to be mediated also by zinc, tin, bismut and copper [45]. 

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... 

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... 

Recently, Sarangi et al. (1995) discovered that the Barbier-type allylation of carbonyl compounds could be mediated by zero-valent copper. In the experimental procedure copper(ll) chloride in its hydrated form was mixed with magnesium powder. This reaction did not proceed with anhydrous CuCU, but addition of water to this anhydrous salt in the presence of magnesium allowed the allylation of aldehydes and ketones with allylic bromides. In the absence of halides, the hydrated reagent (CuCl2 2H20/Mg) turned out to be efficient in the reduction of aldehydes. However, the water of crystallization could not suffice and addition of water promoted the reduction process (Sarangi eta/., 1995). 

Barbier-type additions are attractive methods because the required allylic halide precursors are often commercially available, and are more stable than a preformed organometallic reagent (Equation 5). The required 2-alkoxycarbonyl allylic zinc reagents can be prepared from zinc powder. Lactonization tends to occur under the reaction conditions however, the diastereoselectivity of the reactions tends to be poor with 3-substituted reagents. Zinc-mediated Barbier-type allylations are mild enough for use with functionalized substrates and can utilize both aldehydes and ketones as substrates. 

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