Nitriles carbonyl derivatives

One development involves the use of vitamin B 2 to cataly2e chemical, in addition to biochemical processes. Vitamin B 2 derivatives and B 2 model compounds (41,42) cataly2e the electrochemical reduction of alkyl haUdes and formation of C—C bonds (43,44), as well as the 2inc—acetic acid-promoted reduction of nitriles (45), alpha, beta-unsaturated nitriles (46), alpha, beta-unsaturated carbonyl derivatives and esters (47,48), and olefins (49). It is assumed that these reactions proceed through intermediates containing a Co—C bond which is then reductively cleaved. 

In all cases, the generation of a true nitrile imine was confirmed by the formation of the expected cycloadducts (e.g., 139) with the expected regioselectivity. However, in several cases, carbonyl derivatives (e.g., 137) were also formed in relatively low yield. These compounds were not formed when triethylamine was used as the base. From these data, it was suggested that the dehydrochlorination is a two-step process, involving first silver-ion promoted dehalogenation to give the carbocation... 

The employment of activated cyanomethylene compounds (e.g., malononitrile) for condensation with -amino carbonyl derivatives (e.g., the protected aminoacetaldehyde 184) provides 2-aminopyrroles 185 (Scheme 101) <2004OL2857>. In a comparable fashion, the condensation of -mercapto carbonyl compounds with malononitrile derivatives provides 2-aminothiophenes (Scheme 102) <1979LA328>. Similarly, 2-aminofuran-3-nitriles can be obtained by base-catalyzed condensation of -hydroxy ketones with malononitrile < 1966GB 1002>. 

The general representation of the classic Wittig reaction is presented in equation (21). The ( )- and (Z)-selectivity may be controlled by the choice of the type of ylide (95), the carbonyl derivative (94), the solvent and the counterion for ylide formation. As a general rule, the use of a nonstabilized ylide (95 X and Y are H or alkyl substituents and is phenyl) and salt-free conditions in a nonprotic, polar solvent favors the formation of the (Z)-alkene isomer (96) in reactions with an aldehyde. A stabilized ylide with strongly conjugating substituents such as an ester, nitrile or sulfone forms predominantly the (f -alkene. 

Other sp -type, nitrogen-containing carbonyl derivatives (6), such as a-amino alcohols, " a-amino ethers" e.g. oxazolidines ), a-amino sulfides e.g. thiazolidines ) and a-amino nitriles, are efficient sources for iminium ions (Scheme 3). 

Formation of 2-aminothiophenes by condensation of a-mercaptoaldehydes or ketones with an activated nitrile or by condensation of carbonyl derivatives with activated nitriles and sulfur. Also formation of 2-aminofurans or 2-aminopyrroles from a-hydroxy- or a-aminoketones (see 1 st edition). 

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). 

Similar reactivity was observed for the reaction of 347 with nitrile activated substrates. Treatment of 438 with 347 generated the a-NHR substituted carbonyl derivative 439 (eq. 92).107... 

Catalytic hydrogenation is commonly used for the reduction of alkenes, alkynes, aromatic hydrocarbons, and aromatic heterocycles, carbonyl derivatives, nitriles, and nitro compounds. The reaction with alkenes proceeds on the surface of a heterogeneous metal catalyst, via cleavage of diatomic hydrogen and adsorption... 

The protonated form of Fp can add to conjugated carbonyl derivatives such as acrylonitrile596 and also with conjugated dienes.597 Both S03598 and carbon monoxide can be inserted into the Fe—C bond of FpR.598 Protonolysis provides a synthetic route to substituted nitriles or alkenes. In each case the Fp unit can also be removed photochemically, thermally, or by treatment with triphenylphosphine. Hydride extraction to give an alkene or a diene is also known.599... 

B.iv. Nitrile Enolates. Nitrile enolates are formed by reaction of a nitrile with LDA or another suitable base. Both alkylation 30 and condensation reactions with aldehydes 3 or ketones are known. 32 in addition to alkyl halides and carbonyl derivatives, condensation can occur with another nitrile. The base-catalyzed condensation of two nitriles to give a cyano-ketone, via an intermediate cyano enolate, is known as the Thorpe reaction. 33.109e Reaction of butanenitrile with sodium ethoxide gave a nitrile enolate, which reacted with a second molecule of butanenitrile at the electrophilic cyano carbon to give 206. Hydrolysis gave an intermediate imine-nitrile (207), which is in equilibrium with the enamine form (208, sec. 9.6.A). Hydrolysis led to the final product of the Thorpe reaction, an a-cyano ketone, 209. 33 Mixed condensations are possible when LDA and kinetic conditions are used to generate the a-lithionitrile (a mixed Thorpe reaction). When pentanenitrile was treated with LDA and condensed with benzonitrile, 2-cyano-l-phenyl-1-pentanone was the isolated product after acid hydrolysis. Nitrile enolates can also be alkylated with a variety of alkyl halides. 34... 

Palladium-catalyzed a-Arylation of Carbonyl Compounds and Nitriles. A variety of bases have been used in the palladium-catalyzed a-arylation of carbonyl derivatives. The pKa of the carbonyl moiety determines the choice of the base. For instance, a-arylation with ester derivatives requires the use of strong bases such as NaHMDS. The best yields for the arylation of t-butyl acetate were reported with LHMDS, whereas the arylation of f-butyl propionate occurred in higher yields in the presence of NaHMDS (eq 12). ... 

Some variations of Pd-catalyzed conjugate substitution of a,/S-unsaturated carbonyl derivatives are known. They involve the use of acetals, nitriles, sulfones, sulfoxides, and so on in place of carbonyl compounds. The current scope of these variations is still very limited. Some representative examples are shown in Scheme 10. 

Nitrile enolates can also react with carbonyl derivatives such as oxalate, which serves as a carboxyl surrogate. Reaction of 2-phenylacetonitrile and diethyl oxalate, in the presence of sodium amide, gave 4.99. " Catalytic hydrogenation of the cyano group and hydrolysis led to ethyl 2-phenyl-3-aminopropanoate, 4.100. In this case also, the nitrile moiety was an amine surrogate. Other a-aryl acetonitrile derivatives... 

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