Zinc Compounds Reformatsky reagent

The intermediate Reformatsky reagent BrZnC(Br)(COOEt)2 is an a-halogenoorganozinc compound, which can be regarded as a bis-(carbethoxy)carbenoid of zinc. The reaction of alkylidene malonate with polyhaloacetate in the presence of zinc gives cyclopropane derivatives 176). Addition of ethyl bromocyanoacetate to aromatic aldehydes in the... 

Zinc, like magnesium, is a two-electron donor and likes to be oxidized from Zn(0) to Zn(ll). This enolate is often called the Reformatsky reagent after its inventor, which is fine, and often drawn as a C-Zn compound, which is not fine because it isn t one. 

Spectroscopic and crystallographic studies of Reformatsky reagents derived from a-halo esters showed that the enoiate is present in the C-enolate form and in ether solvents they form dimers. Enolates derived from a-halo ketones prefer the O-metal enoiate form. It is assumed, based on theoretical calculation, that the zinc enoiate dimers are dissociated by the action of the carbonyl compound and converted to the corresponding O-zinc enolates. Subsequently, the reaction goes through six-membered chairlike transition state. 

The activated zinc will also react rapidly with a-chloroesters in THF. However, the yields are not as high and generally are in the 70-80% range. The Reformatsky reagent can be prepared separately and then added dropwise to the carbonyl compound at room temperature. In addition, the Reformatsky reagent in THF or diethyl ether can be purchased from Rieke Metals, LLC. The shelf life of the Reformatsky reagent is limited and slowly decomposes over a period of 10-20 days even if it is stored in a refrigerator. The best results are obtained if it is used as soon as possible. 

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. 

The Reformatsky reagents are the compounds of a a-haloester with zinc. Further, with the compounds of /(- or y-haloester with zinc the coupling reactions are able to proceed in the presence of catalysts such as palladium, copper and nickel compounds. These reactions are called the Remote Reformatsky reactions. For example, the reaction with palladium catalyst is shown in eq. (5.24) [42],... 

The Reformatsky reaction, the zinc-mediated reaction of a-halo esters with aldehydes or ketones, may be considered an alternative to the aldol addition. As far as enantioselective versions are concerned, this method was much less developed than the aldol protocols [155]. In an early approach, Guette and coworkers explored the Reformatsky reaction of ethyl bromoacetate in the presence of stoichiometric amounts of sparteine although a high enantiomeric excess was observed with benzaldehyde (94% ee), the method was much less satisfactory for other carbonyl compounds [156]. According to a report of Yamano and coworkers, high enantioselectivity (up to 97% ee) was obtained when the Reformatsky reagent generated from ethyl bromoacetate was allowed... 

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. 

Carbohydrate lactones have been used as the carbonyl reagent in the Reformatsky reaction. Thus, 2,3 5,6-di-O-cyclohexylidene-D-mannono-1,4-lactone [44, obtained by oxidation of the mannofuranose derivative (49)] reacted with ethyl bromoacetate and zinc to give the protected 2-deoxy-3-octulosonic acid ethyl ester (45a) in 69% yield (50). Ketonic hydrolysis with potassium hydroxide in aqueous methanol, followed by acidification and heating, afforded the 1-deoxyheptulose derivative 45b. Similarly, starting from compound 44, the 1-C-substituted allyl and propar-gyl lactols were prepared on reaction with allyl or propaigyl bromides in the presence of zinc (51). 

In the example given in Scheme 3j18 the primary step in the Reformatsky reaction is the addition of the halide reagent and zinc to the protected peptide 12 in THF hydrolysis of the intermediate formed results in the corresponding difluoroalkyl alcohol 13. Since compound... 

---