Barbier-type allylation reaction

Iminium ions, generated in aqueous solution from secondary amines and formaldehyde, undergo a Barbier-type allylation mediated by tin, aluminum, and zinc. The reaction is catalyzed by copper and produces tertiary homoallylamines in up to 85% yield.67 The imines generated in situ from 2-pyridinecarboxaldehyde/2-quinolinecarboxaldehyde and aryl amines undergo indium-mediated Barbier allylation in aqueous media to provide homoallylic amines.68 Crotyl and cinnamyl bromides... 

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]. 

An interesting aspect of the Bi-mediated Barbier-type allylation is that the reaction can be conducted in aqueous media. When the reaction is carried out using metallic bismuth powder in water, addition of an equimolar amount of potassium fluoride improves the yield of homoallyl alcohol (Equation (40)).74 The reaction is also compatible with hydroxyl and carboxyl groups of the carbonyl substrates. When succinaldehydic acid, 4-oxopentanoic acid,... 

Lubineau reported a series of research works on the preparation of C-branched monosaccharides and C-disaccharides under indium promoted Barbier-type allylation in aqueous media [49]. In the case of substrate 97, the reaction, which took place in H20/Et0H (1 2) at 50 °C, gave unique stereoisomer 98 with complete regio- and diastereoselectivity. From... 

Legros, J., Meyer, F., Coliboeuf, M., Crousse, B., Bonnet-Delpon, D., Begue, J.-P. Stereoselective Barbier-Type Allylation Reaction of Trifluoromethyl Aldimines. J. Org. Chem. 2003, 68, 6444-6446. 

This indium-mediated palladium-catalyzed Barbier-type allylation of aldehydes is expanded to cascade reactions with allenes, which give three-component coupling products (Tab. 8.12 and 8.13) [89]. 

Since the observation that allylation of carbonyl compounds could be mediated by tin in aqueous medium [77], there has been an intensive development of the Barbier-type allylation reaction in water. Three metals were particularly investigated zinc, tin, and indium. In the aqueous zinc-promoted allylation, allylzinc species are considered unlikely. The initiation of the reaction could be attributed to the formation of an allylic radical anion on the metal surface this radical surface could then react with the carbonyl compound to give an alkoxide radical, which could add an electron and form the alcohols [82]. Allyl bromide or even chloride reacts with aldehydes and ketones in the presence of commercial zinc powder in a mixture of tetrahydrofuran and saturated ammonium chloride aqueous solution (Eq. 7) [83]. 

Cooper et al. reported that the cascade reaction of the palladium-catalyzed cyclization and the Barbier-type allylation of the 1,3-diene-aryl iodide 514, the aldehydes 515, and indium gave the heterocycles 516 in good yields (Scheme 154).220b The reaction proceeds through oxidative addition of a C—I bond of 514 to Pd(0) and subsequent insertion of a double bond of 517 to give the jr-allylpalladium intermediate 518. Transmetalation of the jr-allylpalladium 518 with indium leads to the allylindium complex 519, and the following reaction with the aldehydes 515 gives 516. 

Homoallylic alcohols were directly prepared from aromatic acetals and dioxolanes (> 80%) using a Barbier-type allylation, Zn/allyl bromide/NH4Cl, in the presence of j3-CD in water at 50 °C (Figure 4.8). The synthesis of enantiomerically enriched homoallylic alcohols is an important goal in organic synthesis. An enantioselective metal-mediated allylation of substitnted benzaldehydes with jS-CD was achieved. The reaction proceeds in short reaction times (Ih) at room temperatnre. The homoallylic alcohols are obtained in moderate yields with up to 93% enantioexcess. 

Table 2.49 Synthesis of Homoallyl Alcohols by Barbier-Type Allylation Reaction ...

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]. 

The electroreductive Barbier-type allylation was applied recently to imines [126] in the following overall reaction ... 

Barbier-type allylation of aldehydes and ketones with allyl bromides and metallic lead in an aqueous reaction medium has been developed to give the corresponding homoallylic alcohol (Scheme 22.3a). Although the process is very effective for aromatic aldehydes, including ot,p-unsaturated ones, it is less good for aliphatic aldehydes and ketones. For crolyl substrates, some syn- [erythro-) selectivity was observed (Scheme 22.3b). 

Loh et al. reported that indium(O) mediated Barbier-type allylation was facilitated effectively in the presence of La(OTf)3 [24]. Lanthanide Lewis acid can be viewed as an ideal activator because Barbier-type reaction usually requires aqueous reaction media. With a wide variety of aldehydes, allylation of allyl bromide (5) proceeded to give y-adduct exclusively in good to excellent yield and diastereoselectivity under sonication (Table 13.10). Hammond et al utilized Barbier-type allylation for the synthesis of p,P-difluorohomopropargyl alcohols [25]. Eu(OTf)3 was found out to be the best catalyst to facilitate the reaction between difluoropropargyl bromide and aldehydes in aqueous THF under sonication (Table 13.11). With 5mol% of catalyst, the corresponding homopropargyl alcohols were obtained in moderate... 

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. 

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... 

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