Barbier allylation

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... 

Scheme 2.2.5.17 Synthesis of disaccharide analogues with variable configuration and tether length from generic dialdehyde precursors by Barbier allylation and tandem a.co-aldolization.

Electron-rich phenols react with isoprene in ionic liquids and with added Sc(OTf)3 to give 2,2-dimethylchromans <07SL3050>. Ionic liquids also promote the one-pot synthesis of 4-arylchromans from benzaldehydes, phenols and allyl bromide which involves sequential Barbier allylation, Friedel-Crafts alkylation and an intramolecular hydroalkoxylation <07SL1357>. 

Auge, J., Lubin-Germain, N., Marque, S., Seghrouchni, L. Indium-catalyzed Barbier allylation reaction. J. Organomet. Chem. 2003, 679, 79-83. 

The achiral allylation of aldehydes has also been achieved in recyclable ionic liquids" and in water." Greener still is the corresponding Barbier allylation" of aldehydes and ketones with allylic bromides in water mediated by tin metal. The atom efficiency of this reaction is actually less than the corresponding tetraallyltin allylation of (say) benzaldehyde (65% and 83%, respectively) because of the loss of the heavy bromine atom, but this neglects the synthesis of tetraallyltin, which is prepared from allyl bromide or chloride. A particularly intriguing recent advance with this thoroughly studied reaction is the use of nano-tin " (Scheme 5.8.17). 

Alcohol 51 on oxidation with 2-iodylbenzoic acid (IBX) followed by Barbier allylation and silylation gave diene 52. Deprotection of para-methoxybenzyl (PMB) group in 52 furnished the alcohol 53. Similarly, the known allyhc alcohol 54 was reacted with MOM Cl (methyl chloromethyl ether) to afford ether 55, which on desi-lylation and oxidation with TEMPO/BIAB (2,2,6,6-tetramethylpiperidinyloxy)/(bis-acetoxyiodobenzene) gave the acid 56 (Scheme 6.11). 

Preite MD, Perez-Carvajal A. Granular indium barbier allylation of carbonyl compounds a more economical protocol. Synlett 2006 3337-3339. 

The Barbier-type modification17, in which the allyl Grignard reagent is produced in the presence of a carbonyl compound, seems not to be suitable for enolizable aldehydes. Some... 

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... 

The aqueous Barbier-Grignard-type reaction has also been used in the synthesis of natural products. Chan and Li used the zinc mediated allylation as a key step in a total synthesis of (+)-muscarine (Scheme 8.5).72 The strategy was based on the observation that the diastereoselectivity of the allylation reaction in water can be reversed through the protection of the a-hydroxyl group. 

Diastereoselective allylation under aqueous Barbier conditions of a-amino aldehydes with the chiral building block (Ss)-3-chloro-2-(p-tolylsulfinyl)-l-propene to give enantiomerically pure sulfinyl amino alcohols in good yields and with high diastereoselectivity was reported (Eq. 8.34).73... 

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. 

C-branched sugars or C-oligosaccharides are obtainable through indium-promoted Barbier-type allylations in aqueous media.151 Indium-mediated allylation of a-chlorocarbonyl compounds with various allyl bromides in aqueous media gave the corresponding homoallylic chlorohydrins, which could be transformed into the corresponding epoxides in the presence of a base (Eq. 8.62).152... 

Mg. Li and co-worker first reported magnesium-mediated Barbier-Grignard allylation of benzaldehyde in water (Eq. 8.73).172 Recently, a study was completed in which some water-tolerant allylating agents were prepared in situ from allylmagnesium chloride and various metallic salts reacted with aldehydes in THF-FLO to afford the desired homoallylic alcohols.173... 

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. 

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]. 

Anwar U, Grigg R, Rasparini M, Savic V, Sridharan V (2000) Palladium catalysed cyclisation-Barbier-type allylation cascades Chem Commun 933-934... 

Cleghorn LAT, Cooper IR, Grigg R, MacLachlan WS, Sridharan V (2003b) Additive effects in palladium-indium mediated Barbier type allylations. Tetrahedron Lett 44 7969-7973... 

Figure 2 Plausible mechanism of Barbier-type allylation and alkylation with Sm and iodine (cat.).

For the purpose of carrying out carbonyl addition reactions, allylstannanes can be prepared in situ from metallic tin and an allyl halide (Barbier conditions),259 for example, Equation (93).260... 

Scheme 150 Barbier-type allylation of carbonyl compounds with electrogenerated lead(0).

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