Nitriles Reformatsky reagent

A tandem one-pot method for the construction of highly substituted pyridine derivatives from nitriles, Reformatsky reagents, and 1,3-enynes was developed by Lee and coworkers in 2011 [64], The reaction sequential consisted of the reaction of nitrile with a Reformatsky reagent and then selective addition of the Blaise reaction intermediate to 1,3-enyne, followed by isomerization, cyclization, and an aromatiza-tion cascade to give the final pyridines in moderate to excellent yields. 

The reaction of a nitrile with a Reformatsky reagent is known as the Blaise reaction and when applied to (9-trimethylsilyl cyanohydrins leads to the formation of tetronic acids with high ee [79]. By working-up the Blaise reaction with ammonium chloride it is possible to isolate... 

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. 

The most successful acylations of Reformatsky reagents have been obtained with nitriles. This reaction, first reported in 1901 by Blaise, was little used until Kagan and Suen reported that slow addition of a benzene solution of a-bromo esters to a refluxing mixture of zinc and the nitrile gave good yields (70-83%) of a,a-disubstituted 3-keto esters. Hannick and Kishl reported that a similar proce-... 

This reaction is believed to proceed by a mechanism analogous to that of the Reformatsky Reaction involving an initial condensation of the nitrile with the Reformatsky reagent the intermediate is finally transformed into 0-keto ester via acidic hydrolysis,as illustrated here. 

The Pd-catalyzed a-allylation of esters was first achieved by the reactions of aUylic carbonates with ketene silyl acetals that can be generated by treating esters with McsSiCl in the presence of a base. The yields of the desired products based on ketene silyl acetals were generally good except in the allylation of lactones (Scheme Selection of solvents is critical since the use of nitriles, such as MeCN and PhCN, leads only to the formation of a,/3-unsaturated esters rather than the a-ally-lated products. Both Reformatsky reagents and lithium enolates of esters have also been successfully a-allylated in the presence of Pd catalysts (Scheme 10). A highly regio- and stereospecific allylation of y-butyrolactone with ( )-2-hexenyl acetate is noteworthy. Since the lithium enolate of esters would react with allylic chlorides even in the absence of a Pd catalyst, however, it is not clear to what extent the reaction is catalyzed by a Pd complex. 

REFORMATSKY BLAISE Zincahyiallon Synthesis of -hydrexyesters from cartxinyl derivatives arxl a-haloesters via a zmc reagent (Reformatsky). Synthesis ol eloesleis from nitriles and a-haloesters via a zinc reagent (QIaise). 

The starting reagent is the Reformatsky-typt. In this case, instead of adding to a carbonyl group, addition is to the nitrile. See Reformatskv Reaction for a discussion of reagent. 

Reformatsky first introduced electron-withdrawing substituents on the a-carbon of an organozinc halide, leading to the more reactive and thermally stable a-(alkoxycarbonyl)alkylzinc halides (123).107 Typically these reagents react with aldehydes or ketones to afford 3-hydroxy esters while nitriles afford 3-keto esters (Blaise reaction),l07b>c but 1,4-conjugate additions to select a,3 unsaturated ketones are precedented (Section 1.2.2.2.2). 

The electrosynthesis of /Miydroxy esters (220), 2,3-epoxy esters (221) and /Miydroxy nitriles (222) was achieved under nickel-catalyzed conditions, obviating Reformatsky reaction 70(equation 112-114). The reaction proceeds in excellent yield when a sacrificial zinc rod is used as the anode. A mechanism has been proposed which involves reduction of a Ni(II) complex to a Ni(0) complex, oxidative addition of the a-chloroester to the Ni(0) complex, and a zinc (II)/Ni(II) exchange, leading to an organozinc reagent, in analogy to the Reformatsky reactions. 

Orsini reported the use of a 10 mol % Sml2-Mg reagent system in the Reformatsky reactions of a-halocarbonyl compounds, nitriles and phospho-nates with ketones, aldehydes and imines.29... 

Nitriles and esters are also unreactive in Smh-promoted Barbier reactions. A very useful procedure for lactone synthesis has been developed making use of this fact. Treatment of 7-bromobutyrates or 8-bro-movalerates with Smh in THF/HMPA in the presence of aldehydes or ketones results in generation of lactones through a Barbier-type process (equations 25 and 26). This nicely complements the -metaUo ester or homoenolate chemistry of organosamarium(III) reagents described above (Section 1.9.2.1), and also the Reformatsky-type chemistry promoted by Sml2 (Section 1.9.2.3.2). Further, it provides perhaps the most convenient route to 7- and 8-carbanionic ester equivalents yet devised. 

Synthesis of p-hydroxyesters from carbonyl derivatives and a-halo esters via a zinc reagent (Reformatsky). Synthesis of p-ketoesters from nitriles and a-halo esters via a zinc reagent (Blaise) (see 1st edition). 

Reformatsky-type reagents The synthesis of P-hydroxy nitriles (9 examples,... 

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