Reformatsky reagents derivatives

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. 

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. 

According to Gaudemar and Curd, dimethoxymethane is an especially useful solvent for two-stage reactions and they report yields of 70-80% for the Reformatsky reagents derived from a variety of a-bromo esters (equation 2) however, the procedure was unsatisfactory with ethyl a-bromopropionate, methyl a-bromophenylacetate and phenyl a-bromoisobutyrate. The zinc enolates were generally used shortly after preparation and no data on their stability in this solvent were reported. 

The homo-Reformatsky reagent derived from the benzyl ester of N-Boc protected P-iodoalanine (Ch. 5, p. 204) reacts under sonication with various electrophiles. With acyl chlorides in the presence of a palladium catalyst, protected y-keto a-amino acids are obtained without racemization (Fig. 28).i An experiment is described in Chapter 9 (p. 348). 

The reactions of ketenes or ketene equivalents with imines, discussed above, all involve the imine acting as nucleophile. Azetidin-2-ones can also be produced by nucleophilic attack of enolate anions derived from the acetic acid derivative on the electrophilic carbon of the imine followed by cyclization. The reaction of Reformatsky reagents, for example... 

Improvement to the Reformatsky reactions was achieved (53) by the use of a highly activated zinc - silver couple dispersed on the surface of graphite. T reatment of protected aldono-1,4-lactones 10b or 25b and 1,5-lactones 51a or 51b with a Reformatsky reagent prepared from a-haloesters or alkyl 2-(bromomethyl)acrylates resulted in the formation of the corresponding 3-or 4-glyculofuranos (or pyranos)onates 49a,b-50a,b, or 52a,b, respectively, under mild conditions (— 40 ° to 00) and in very good yields. Ethyl 2-deoxy-2-fluoro (and 2-bromo)-a-D-wa o-3,6-furanos-3-octulosonate derivatives were also obtained. 

The te.te-difluoro Reformatsky reagent has been applied extensively to preparation of compounds containing the —CF2C(0)— group and its derivatives since this functionality often confers enhanced biological activity. Typical examples include the preparation of... 

En route to 1 -/J-methyl carbapenem antibiotics, the reaction of 31 with Reformatsky reagents 78 has been explored it likely involves preliminary formation of the intermediate 79, which then undergoes nucleophilic addition to give 2-(4-oxoazetidin-2-yl)-propanoic acid derivatives 80 (equation 48). 

The a,a-difluoro Reformatsky reagent has been applied extensively to the preparation of compounds containing the -CF2C(0)- group and its derivatives,2 since this functionality often confers enhanced biological activity. Typical examples include the preparation of selectively fluorinated thromboxane A2 analogues24 and the preparation of a difluoro-y-lactone intermediate which was subsequently converted to l-(2-deoxy-2,2-difluororibofuranosyl) pyrimidine nucleosides (Equation 4.10).25... 

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... 

Interesting results are provided by reactions performed with the chiral organometal reagent deriving from the a-bromo ester 301 and zinc (Reformatsky reaction) (Fig. 116), which produces the diastereomeric hydroxy-aminocsters 303 from the achiral (3-ami-nopropiophenones 302. 

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. 

Addition of the Reformatsky reagent to the A -20-keto-steroid (255) afforded the pentacyclic derivatives (256) and (257), which could be converted into various 16a-substituted 20-keto-pregnanes/ The 16/S-dimethylaminopregnane (259) has been obtained by cleavage of ring E of the pentacyclic steroid (258) (see... 

Reformatsky reagent which then adds to carbonyl derivatives according to Scheme 20. These authors also observed conjugate addition of the homoenolate anion to a,)5-unsaturated ketones in the presence of copper ion as shown ... 

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