Esters Reformatsky reagents with

The reaction of the Reformatsky reagents with a-chloro ethers gives j8-alkoxycarboxylic acid esters 73, 290, 291, 294, 526). For example,... 

Reactions of Reformatsky reagents with esters or with acid chlorides generally give only low yields of P-keto esters. Hauser reported that ethyl a-bromoisobutyrate could be acylated in reasonable yields with either the acid chlorides or the phenyl esters of aromatic acids, but the reaction fails with acylating... 

The first step is considered to involve the condensation of the Reformatsky reagent with benzonitrile to yield the Zn-salt 5. C-alkylation by bromoacetate, followed by ring closure, is believed to lead to the hitherto elusive key intermediate 6A, a pyrrolinone ester. Condensation with a second molecule of benzonitrile and subsequent cyclization of intermediate 7, which could be isolated and was also mentioned by Famum, finally affords the DPP 2. 

Moreover, Soai et al.53c found that the enantioselective addition of Reformatsky reagents to prochiral ketones proceeds well when N,N-dialkylnorephedine 59 is used as the chiral ligand. When (15, 2R)-59a is used, the //-hydroxyl ester is obtained in 74% ee and 65% yield with ( -configuration predominant. When (lR,25,)-59a is used, the product is obtained in 74% ee and at 47% yield with (R)-configuration prevailing. 

This strategy also provides a convenient method for amination of various ester enolates with DPH Ih (Scheme 14). The amination of lithium eniminate of phenyl acetonitrile, the silyl enolate of ethyl phenylacetate and the Reformatsky reagent derived from ethyl a-bromoacetate with DPH were found to be unsuccessful. A failure of DPH for the amination of sodium enolates of S-diketones and the lithium enolate of 3-methylbutanoic acid was also reported . 

Equations 36-39 suggest that fluorine substituents at the a position of the ester enolate play a role in favouring the formation of /J-arnino esters. This conclusion is supported by the condensation of the Reformatsky reagent deriving from 20 with imines, the only product being the open-chain adduct 63 (equation 40)123. 

Allylic substitution reactions affording y, 5 -unsaturated esters have been also reported for example, Reformatsky reagents react with allylic halides in the presence of 5% Cu(acac)2 in Et20/DMS0 mainly affording Sw2-type products (equation 71)162. 

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... 

The indium-induced Reformatsky reaction with stoichiometric amounts of chiral amino alcohols such as cinnco-nine and cinchonidine gives optically active /3-hydroxy esters with 40%-70% ee (Table 19). In contrast to the smooth reaction with uncomplexed indium-based Reformatsky reagents, ketones do not react with the complexed indium Reformatsky reagents. Other chiral ligands, including (—)-spartein, (—)-norephedrine, (+)-(l-methylpyrrolidin-2-yl)diphenylmethanol, (+)-Dibutyl tartrate and (+)-l,l -bi-2-naphthol, are not effective for this reaction.324... 

Reformatsky reagents react with a-amino ethers to give -amino esters (67). Acetals undergo alkoxymethylation of Reformatsky reagents (98). 

Reformatsky condensation of the reagent with ethyl bromod-ifluoroacetate afforded the 2,2-difluoro ester, which was further elaborated to the 2-deoxy-2-difluoro-L-ribofuranose. From there, various 2 -deoxy-2, 2 -difluoro-L-nucleosides were prepared (eq5). ... 

Access to 2-difluoro-2-deoxy-D-sugars and their derived nucleosides was realized by Reformatsky condensation of the reagent with ethyl bromodifluoroacetate. The resulting difluoro ester was obtained as a 2.5 1 antUsyn mixture. Following separation, the ma-... 

Zinc enolates (Reformatsky reagents), generated finom a-bromo esters and zinc, react with imines derived finom aromatic amines to yield 3-lactams (Scheme 19).>40-142 -phe stereoselectivity of the reaction varies 4 >46 (jjg nature of ester substituents R and R the bulkier the groups, the more trans isomer is produced. 

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