Reformatsky reagent aldehydes

Specific enol equivalents will be needed for both synthons (61) and (66), Since (61) is to give a double bond but (66) is to give an alcohol, the logical choices are a Wittig reagent - actually (67) - for (61) and a Reformatsky reagent for (66). The ester to aldehyde conversion (65 63) Is easiest by over-reduction and re-... 

Bieber reported that the reaction of bromoacetates is greatly enhanced by catalytic amounts of benzoyl peroxide or peracids and gives satisfactory yields with aromatic aldehydes. A radical chain mechanism, initiated by electron abstraction from the organometallic Reformatsky reagent, is proposed (Scheme 8.27).233 However, an alternative process of reacting aldehydes with 2,3-dichloro-l-propene and indium in water followed by ozonolysis provided the Reformatsky product in practical yields.234 An electrochemical Reformatsky reaction in an aqueous medium and in the absence of metal mediator has also been reported.235... 

The Reformatsky reagent from 2a shows only slight diastereoselectivity in reactions with aldehydes but reactions with 2b give 2,3-vyn-aldols as the major prod-... 

An isoborneol with a cA-a-amino group gives ees of up to 93% in addition of Reformatsky reagents to aldehydes 271 ... 

The first enantioselective one-pot, three-component imino Reformatsky reactions q have been reviewed 98 (—)-A, A-Dimethylami noisoborneol has been found to be an excellent ligand for the enantioselective addition of Reformatsky reagents to aromatic and aliphatic aldehydes 99 Enantioselectivities up to 93% ee have been obtained with sulfur-containing aldehydes. 

The Reformatsky reagents, i.e. zinc enolates of esters, undergo Ni catalysed cross-coupling with aryl halides.53 The Ni catalysed reaction of arylzincs with a-bromoacetates also permits a-arylation of esters54 (Scheme 11.13). However, a-alkenylation of enolates of ketones, aldehydes, and esters has been less satisfactory. Its further development is clearly desirable. Alternatively, a-alkenylation of a-iodoenones in conjunction with conjugate reduction discussed earlier should be considered. 

The insight that zinc ester enolates can be prepared prior to the addition of the electrophile has largely expanded the scope of the Reformatsky reaction.1-3 Substrates such as azomethines that quaternize in the presence of a-halo-esters do react without incident under these two-step conditions.23 The same holds true for acyl halides which readily decompose on exposure to zinc dust, but react properly with preformed zinc ester enolates in the presence of catalytic amounts of Pd(0) complexes.24 Alkylations of Reformatsky reagents are usually difficult to achieve and proceed only with the most reactive agents such as methyl iodide or benzyl halides.25 However, zinc ester enolates can be cross-coupled with aryl- and alkenyl halides or -triflates, respectively, in the presence of transition metal catalysts in a Negishi-type reaction.26 Table 14.2 compiles a few selected examples of Reformatsky reactions with electrophiles other than aldehydes or ketones.27... 

An indium Reformatsky reagent has been prepared from 2-(chlorodifluoroacetyl)furan, which couples with aldehydes (Equation (84)).334 A similar Reformatsky-type reaction between some /3-aminovinyl chlorodifluoromethyl... 

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... 

The Reformatsky reagent from diethyl bromomalonate reacts with a variety of aldehydes. The resulting alcoholates react with acetyl chloride to give the corresponding acetates 174). 

There is a competition between alkoxymethylation and acylation in this reaction. Alkoxymethylation by cleavage of acetals is also applicable to alcoholates obtained by condensing Reformatsky reagents with aldehydes and ketones (98, 174a). 

Enantioselective Addition of Cyanomethylzinc Bromide, Reformatsky Reagent, and Alkynylzinc Reagents to Aldehydes. The enantioselective additions of cyanomethylzinc... 

Enantioselective addition of a Reformatsky reagent to aldehydes and ketones in the presence of DBNE or N,N-diallylnorephedrine (3) affords the corresponding p-hydroxy esters in up to 75% ee (eq 12). 

Aminoalkylation of aldehydes. After imination of aldehydes under catalysis of LiCIO the addition of proper carbon nucleophiles (e.g., Reformatsky reagents) completes the functional chain extension process. 

To avoid side products derived from further addition of the Reformatsky reagent to the newly formed resin-bound ester, careful optimization of the reaction conditions was undertaken. The best yields, without detectable amounts of side products, were obtained by using 10 equiv. of the Reformatsky reagent. For each supported amino acid (except, of course, for glycine), a pair of diastereoisomers was formed, the ratio of which was found to be strongly dependent on the nature of the aldehyde employed. 

The Reformatsky reaction is the reaction of an a-halo ester with an aldehyde or ketone in the presence of zinc metal as shown in Scheme 1. The usual product of the reaction is a -hydroxy ester, which may be dehydrated in subsequent steps to give an unsaturated ester. A zinc ester enolate (1), the so-called Reformatsky reagent, is an intermediate in the reaction and the sequence is thus classified as an aldol condensation. Compared to the usual base-promoted aldol procedures, the distinguishing features of the Reformatsky reaction are the use of a metal-halogen redox reaction rather than an acid-base reaction to form the enolate, and the fact that the counterion of the enolate is zinc. 

This chapter summarizes studies on the nature of the Reformatsky reagent as well as other, related, zinc enolates and outlines the synthetic aspects of the reaction with aldehydes and ketones. In addition, reactions of the Reformatsky reagent with imines and nitriles (the Blaise reaction) are described. 

In addition to aldehydes and ketones, organic compounds which are known to react with Reformatsky reagents include esters,nitriles, acid chlorides, organic halides,epoxides, nitrones, azirenes" and imines. This section describes the selectivity reported for Reformatsky reactions with functionally substituted aldehydes or ketones. 

TABLE 1.69. 2-(2-HYDROXYETHYL)-4-OXAZOLECARBOXYLIC ACID ETHYL ESTERS FROM 2-(BROMOMETHYL)-4-OXAZOLECARBOXYLIC ACID ETHYL ESTER REFORMATSKY REAGENT AND ALDEHYDES OR KETONES-... 

The Reformatsky reagent from ethyl difluorobromoacetate is prepared with zinc under sonication (Ch. 5, p. 232). Its relative stability allows its condensation with aldehydes to be effected under sonication in a separate step (Eq. 14). This procedure gives cleaner products than with the traditional one-step process.ios... 

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