Reformatsky reactions organozinc compounds

The Reformatsky reaction is a classical reaction in which metallic zinc, an a-haloester, and a carbonyl compound react to give a (i-hydroxyester.162 The zinc and a-haloester react to form an organozinc reagent. Because the carboxylate group can stabilize the carbanionic center, the product is essentially the zinc enolate of the dehalogenated ester.163 The enolate effects nucleophilic attack on the carbonyl group. 

The oldest reaction involving a rearrangement of an organozinc compound is probably the Reformatsky reaction54 55. It took one hundred years until its key step could be classified as a [3,3)-sigmatropic shift ( metallo-Claisen rearrangement) on the basis of computational studies (equation 51)56. 

REFORMATSKY REACTION. Dating back to 1887, this reaction depends on interaction between a carbonyl compound, an a-halo ester, and activated zinc in the presence of anhydrous ether or ether-benzene, followed by hydrolysis. The halogen component for example ethyl bromoacetate, combines with zinc bo form an organozinc bromide that adds to the carbonyl group of the second component to give a complex readily hydrolyzed to carbinol. The reaction... 

In contrast to the polar nature of C-Li and C-MgX bonds, the C-Zn bond is highly covalent and hence less reactive, allowing the preparation of functionalized derivatives. Utilization of organozinc reagents in organic synthesis has mainly centered around the preparation and utilization of functional organozinc compounds in organic syntheses (Reformatsky reaction), cyclopropanation (Simmons-Smith reaction), and transmetalations with transition metals. 

Alternatives which are more useful for /3-hydroxy carbonyl compounds are organometallic reagents. Organozinc reagents (67) react with aldehydes and ketones but not with esters so they can be made from a-halo esters. This, the Reformatsky reaction, has the advantage that the -halo esters are easily made (see Chapter 7). 

CH3CH2CH2CH2COOH.The Reformatsky reaction is one that occurs between an organozinc compound derived from an a-haloester and an aldehyde or ketone to form a B-hydroxyester. By working backwards, we can devise a method of preparing n-valeric acid by using the Reformatsky reaction, n-Valeric... 

Besides the aldol reaction to form y0-hydroxyketone, 1,3-Dipolar Cycloaddition can also form similar molecules. In addition to the Mukaiyama Aldol Reaction, the following are also similar or closely related to the aldol reaction the Claisen-Schmidt Condensation (the aldol reaction between benzaldehyde and an aliphatic aldehyde or ketone in the presence of relatively strong bases to form an o, )0-unsaturated aldehyde or ketone), the Henry Reaction (base-catalyzed addition of nitroalkane to aldehydes or ketones), the Ivanov Reaction (the addition of enediolates or aryl acetic acid to electrophiles, especially carbonyl compounds), the Knoevenagel Reaction (the condensation of aldehydes or ketones with acidic methylene compounds in the presence of amine or ammonia), the Reformatsky Reaction (the condensation of aldehydes or ketones with organozinc derivatives of of-halo-esters), and the Robinson Annulation Reaction (the condensation of ketone cyclohexanone with methyl vinyl ketone or its equivalent to form bicyclic compounds). 

Organozinc Compounds from Organomagnesium Halide (Reformatsky Reaction)... 

It was from Saytzeff s laboratory (Sect. 1.2.5) that Reformatsky [4] first reported the successful synthesis of 3-hydroxyalkanoic acid esters with the aid of an intermediate organozinc compound, thus developing the reaction which still bears his name ... 

The Reformatsky reaction provides a method of converting a-bromoesters via the zinc reagent into j3-hydroxy- or j8-keto-esters. The reactions may be carried out either in situ, where zinc, the bromo ester and the carbonyl compound are all warmed together in a solvent (ether, benzene or 1,2-dimethoxyethane), or in two stages by forming the zinc intermediate first. The actual zinc reagent is probably an enolate rather than an organozinc species ... 

The Reformatsky reaction is one of the representative reactions of zinc being used as a catalysts [12,35-38,41,64—74]. The Reformatsky reaction is that reaction with a-haloesters, carbonyl compounds and zinc that produces )5-hydroxyester as shown in eq. (5.20). The reaction of a-haloesters with zinc yields organozinc compounds (XZnCH2COOR) which are called the Reformatsky reagents. These Reformatsky reagents are the organozinc compounds which are considered to be the intermediates of the Reformatsky reaction. 

Zaitsev reactions also proceed similar to the Reformatsky reactions. Namely, organozinc compounds are synthesized in advance, and subsequently they react with aldehydes or ketones. Therefore, addition to the carbonyl of arylzinc compounds as shown in eq. (5.15) is also known as the Zaitsev reaction. Not only the addition to the carbonyl group of aldehydes or ketones but also the addition to carbon—carbon double bonds are the related reactions of Zaitsev reactions as shown in eq. (5.26) [37]. 

The most frequently used reaction involving zinc is the Reformatsky reaction, which uses zinc, ethyl bromoacetate, and carbonyl compounds to give (3-hydroxyesters. The reaction by which the organozinc intermediate is formed is presumably similar to that in Grignard reagent formation. The adjacent carbonyl... 

Solid zinc activation has been used with success for the formation of stable organozinc compounds from functionalized benzylic bromides [8] and has been applied to the condensation of activated halides with nitriles [9] (Blaise reaction) or carbonyl compounds (10] (Reformatsky reaction). In this case, solid zinc is activated by catalytic generated zinc formed by electroreduction of anhydrous ZnBr2 solution in acetonitrile as solvent. Results and practical approaches have been reported [llj. 

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