Grignard-type reaction

Organogallium reagents, RsGa, have been added enantioselectively to aldehydes, using TiCl4 as a Lewis acid catalyst, with a chiral salan ligand.258 

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Phenyllithium can be used in Grignard-type reactions involving attachment of phenyl group, eg, in the preparation of analgesics and other chemotherapeutic agents (qv). It also may be used in metal—metal interconversion reactions leading, eg, to phenyl-substituted siUcon and tin organics. 

Organic halides play a fundamental role in organic chemistry. These compounds are important precursors for carbocations, carbanions, radicals, and carbenes and thus serve as an important platform for organic functional group transformations. Many classical reactions involve the reactions of organic halides. Examples of these reactions include the nucleophilic substitution reactions, elimination reactions, Grignard-type reactions, various transition-metal catalyzed coupling reactions, carbene-related cyclopropanations reactions, and radical cyclization reactions. All these reactions can be carried out in aqueous media. 

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. 

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. 

The first reaction of this kind was described in 1965 (example 1, Table IV). More recently Grignard-type reactions with nickel have been carried... 

Diels-Alder adduct from cyclopentadiene, 8 222t Diels-Alder reactions of, 25 488-489 economic aspects of, 25 507-509 electrophilic addition of, 25 490 in ene reactions, 25 490 esterification of, 25 491 free-radical reactions of, 25 491 from butadiene, 4 371 Grignard-type reactions of, 25 491 halogenation of, 15 491—492 health and safety factors related to, 25 510-511... 

Conventionally, organometallic chemistry and transition-metal catalysis are carried out under an inert gas atmosphere and the exclusion of moisture has been essential. In contrast, the catalytic actions of transition metals under ambient conditions of air and water have played a key role in various enzymatic reactions, which is in sharp contrast to most transition-metal-catalyzed reactions commonly used in the laboratory. Quasi-nature catalysis has now been developed using late transition metals in air and water, for instance copper-, palladium- and rhodium-catalyzed C-C bond formation, and ruthenium-catalyzed olefin isomerization, metathesis and C-H activation. Even a Grignard-type reaction could be realized in water using a bimetallic ruthenium-indium catalytic system [67]. 

The 4,4 -dibromobiphenyl was used as the starting material The strategy taken for the synthesis of the organosilica was to carry out Grignard-type reaction to incorporate tetraethyl orthosilicate (TEOS) to 4,4 -dibromobiphei5rl to create 4,4 -Bis(triethoxysilyl)biphenyl. Materials from this procedure had been subjected to polymerization surfactant-mediated polymerization. The product obtained was a white powder aggregate. Shown in Table 47.1 are the formulations used for the samples and the heat treatment. 

Barbier-Grignard-type reactions in water (Li, 1996) between aUyl hahdes and carbonyl compounds can be mediated by metals of tin, zinc, or indium. Usually the generation of the organometalhc reagent takes place in anhydrous organic solvents, but using softer metals allows this reaction to take place in water. 

Acetylenic precursors employed in the syntheses of sugars may be divided into three groups (a) aldehydes (usually in the form of acetals), (b) alkyl alkynyl ethers, and (c) alkynols or alkynediols. Some of them are commercially available (for example, 2-butyne-l,4-diol), and others are prepared by Grignard-type reactions between 1-alkynylmag-nesium halides or lithium alkynes and suitable aldehydes, ketones, or epoxides. In this way, the synthesis of substrates having the desired number of carbon atoms, as well as the necessary functional groups, can be achieved. The next step consists in partial saturation of the triple bond to afford the desired cis- or trans-alkene. ct.s-Alkene systems... 

Application of the alcohol interchange reaction (method 6) is limited by certain phenols and also di and trisubstituted glyoxides (while the reaction of metals with glycols gives only monosubstituted derivatives) [745, 621, 575, 1584,1369]. As redox processes (method 7) can be considered the Grignard-type reactions — the interaction of metal alkyls with carbonyl compounds,... 

Bacteria, antimicrobials against, 12, 456 Baeyer-Villiger oxidation, via tin amides, 9, 370 Barbier-Grignard-type reactions, and sonochemical metal insertions, 1, 315 Barbier-type reactions allenyl and propargyl tins, 9, 358 with allylic tins, 9, 357 with antimony(III) compounds, 9, 426 with bismuth(III) compounds, 9, 433 with cerium reagents, 10, 409 with indium compounds, 9, 685... 

Phenyllithium lO Colorless pyrophoric solid used in Grignard-type reactions to attach a phenyl group... 

Interestingly, better diastereoselectivity is obtained than in the corresponding reactions with trivalent lanthanide alkoxides. The use of optically active (l)-menthoxide afforded moderate enantioselectivities. Further stimulus for Sm(II)-OR -based transformations has come from the initial investigations of Sm(II)-triflate mediated Grignard-type reactions [259],... 

The conventional Grignard reaction (Fig. 2, route I) would generate both a stoichiometric amount of halide waste and a stoichiometric amount of metal waste. It also requires multistep synthesis of the halides. On the other hand, an alternative Grignard-type reaction via catalytic C-H activation in water (Fig. 2, route II) would preclude the use of flammable organic solvents and also avoid the wasteful process of drying them. Obviously, it would provide a cleaner solution for organic synthesis and provide a theoretical 100% atom-efficiency. 

I. Grignard- type reaction via C-H activation in aqueous media... 

The allylation of imines with allylindium reagents in organic solvents gives the corresponding homoallylic amines.251-253 Under solvent-free conditions, the indium-mediated reaction of iV-benzylideneaniline furnishes a mixture of mono-allylated 79 and bis-allylated products 80 (Equation (56)). The bis-allylated product 80 presumably arises via a formation of an iminium salt, which is subsequently attacked by the allylindium nucleophiles. Formation of 80 is entirely suppressed by addition of allyl bromide to indium metal prior to any addition of the imine (Grignard-type reaction).254... 

An indium-mediated ring-expansion reaction of a cyclic thioether derivative 31 in aqueous medium leads to the eight-membered cyclic thioether derivative 32, which isomerizes to the more stable conjugated product 33 in 62% yield (referred to 31) (Scheme 10) <1999SL735>. For a review of such Barbier-Grignard type reactions in water see <1996T5643>. 

Stereoselective catalysis in zeolites is still one of the ultimate goals in zeolite science. Earlier work in this field was summarized recently [4]. More recently, Mahrwald et al. [95] reported that the addition of aluminophosphate molecular sieves in the liquid phase alkylation of a-chiral benzaldehydes by butyllithium results in an increased proportion of the so-called Cram product in the diastereomeric mixture. It is argued that in this Grignard type reaction the adsorption of the reactants on the molecular sieves favors the attack at the sterically less hindered position of the molecule. This shape selectivity effect is even observed when the reactant is adsorbed at the outer crystal surface, as demonstrated for the case of the small-pore AIPO4-I7. 

Li, C.-J. Aqueous Barbier-Grignard type reaction scope, mechanism, and synthetic applications. Tetrahedron 1996, 52, 5643-5668. 

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