Nitrile chemoselectivity

Huonnations with DAST proceed with high chemoselectivity In general, under very mild reaction conditions usually required for the replacement of hydroxyl groups, other functional groups, including phenolic hydroxyl groups [112], remain intact This provides a method for selective conversion of hydroxy esters [95 97] (Table 6), hydroxy ketones [120, 121], hydroxy lactones [722, 123], hydroxy lactams [124] and hydroxy nitriles [725] into fluoro esters, fluoro ketones, fluoro lactones, fluoro lactams, and fluoro nitnles, respectively (equations 60-63)... 

It has been reported that an allylic C-Si bond can be cleaved by tetrabutylammonium fluoride to give an anionic allylic species, which chemoselectively adds to carbonyl compounds (nitriles, esters, and epoxides failed) to form homoallylsilyloxy compounds13. 

The compound NaBH4 in the presence of Me2N=CHCl" Cl" reduces carboxylic acids to primary alcohols chemoselectively in the presence of halide, ester, and nitrile groups Fujisawa, T. Mori, T. Sato, T. Chem. Lett., 1983, 835. 

As shown in Table 6 all the reactions proceed with complete chemoselectivity to the corresponding N,N-disilylamine. The reactions have been performed without solvent facilitating the collection of the products. With catalyst B, using HSiMc3, as hydrosilane reagent, quantitative yields of products have been obtained with ben-zonitrile, as well as with other nitriles, containing... 

The chemoselectivity of Schwartz s reagent (1) toward alkynes, alkenes, nitriles, and carbonyl groups, and thus its general functional group compatibility, can be modulated. However, it is important to keep in mind that the presence of functional groups may have regiochemical consequences on the hydrozirconation reaction. 

Martinkova, L. and Kren, V. (2002) Nitrile- and amide-converting microbial enzymes stereo-, regio- and chemoselectivity. Biocatalysis and Biotransformation, 20,73-93. 

The Chemoselective Conversion of Carbonyl Compounds to Nitriles Ethyl 4-Cyanopentanoate. 

Palladium-catalyzed cyclization of alkenes and alkynes were reported by Balme and co-workers.143 144 Intramolecular carbopalladation occurs to give polycyclic compounds. It has been shown that the nucleophile type has a large influence on the cyclization process. Both 5-exo- and 6-endo-cyclization are observed for substrates with nitrile (116 and 118) and ester (120, 122, and 124) substituents, respectively (Scheme 36). When a mixed nucleophile (CN and C02Me) is used, a mixture of 5-exo and 6-endo products is obtained. The chemoselectivity is controlled by the size of the nucleophile used. The stereochemistry of the initial double bond plays an important role on the stereoselectivity of the cyclization. (Z)-olefins (118 and 120) and (/. )-olefins (116 and 124) afford as- (119 and 121) and trans-cyclization products (117 and 123), respectively. 

Iridium hydride complexes effectively catalyze addition of nitriles or 1,3-dicarbonyl compounds (pronucleophiles) to the C=N triple bonds of nitriles to afford enamines.42S,42Sa Highly chemoselective activation of both the a-C-H bonds and the C=N triple bonds of nitriles has been observed (Equation (72)). To activate simple alkane dinitriles, IrHs(P1Pr3)2 has proved to be more effective (Equation (73)). The reaction likely proceeds through oxidative addition of the a-C-H bonds of pronucleophiles to iridium followed by selective insertion of the CN triple bonds to the Ir-C bond. 

Burk et al. showed the enantioselective hydrogenation of a broad range of N-acylhydrazones 146 to occur readily with [Et-DuPhos Rh(COD)]OTf [14]. The reaction was found to be extremely chemoselective, with little or no reduction of alkenes, alkynes, ketones, aldehydes, esters, nitriles, imines, carbon-halogen, or nitro groups occurring. Excellent enantioselectivities were achieved (88-97% ee) at reasonable rates (TOF up to 500 h ) under very mild conditions (4 bar H2, 20°C). The products from these reactions could be easily converted into chiral amines or a-amino acids by cleavage of the N-N bond with samarium diiodide. 

Martin and Furstner showed that an iron(-II) complex can be used as a precatalyst. This result is very interesting for mechanistic considerations. Unfortunately, this sophisticated complex is not very attractive for large-scale applications. The reaction is remarkably chemoselective, thus the presence of ketone, ester, isocyanide, chloride and nitrile is tolerated (Scheme 41). 

The Ojima group has extended their studies of silylformylation to include more complex substrates, such as alkenyne, dialkyne, alkynyl nitrile, and ethynyl pyrrolidinone. Use of rhodium or rhodium-cobalt metal complexes catalyzes the silylformylation of these substrates with high chemoselectivity, as the other functionalities present are inert to the reaction.122b,c d... 

Rapid reduction of aromatic nitro compounds into amines has been described using sodium hypophosphite and FeSC>4-7H20. The reactions showed best results in terms of yields and purity, when the substrates were pre-absorbed on alumina and irradiated by microwaves under solvent-free conditions. The reaction is chemoselective and does not affect functional groups such as CN, OH, COOH, CONH2 or halogens. In addition, oximes were not reduced under the given reaction conditions, but were dehydrated to the corresponding nitriles instead (Scheme 4.32)57. 

This reaction is chemoselective, because only the aldehyde function is attacked even in the presence of other electrophilic groups such as ketones or nitriles 18... 

The silver acetate-promoted 1,3-dipolar cycloaddition of nitrilimines with 3(/f )-pheny]-4(A )-cinnamoyl-2-azetidinone produced the major adduct, 4-(4,5-dihydro- (g) pyrazol-5-yl)carbonyl-2-azetidinones, with high stereoselectivity.70 The 1,3-dipolar cycloadditions of substituted 2,7-dime(liyl-3-thioxo-3,4,5,6-ici.rahydro-2//- 1,2,41 triazepin-5-one with iV-aryl-C-ethoxycarbonylnitrilimines are highly chemoselective, where the sulfur atom of the dipolarophile interacts with the carbon atom of the dipole.71 The enantioselective 1,3-dipolar cycloaddition of nitrile imines with electron deficient acceptors produces dihydropyrazoles in the presence of 10 mol% of chiral Lewis acid catalyst.72... 

Using catalyst 9, Michael reaction of nitriles can be also performed highly efficiently under neutral conditions. Addition of ethyl 2-cyanopropanoate (12) to 2-propanal proceeds chemoselectively to give the adduct 13 without contamina-... 

Addition of nitriles to acetylenic compounds proceeds with chemoselectivity in contrast with the corresponding base-promoted reactions, where the products derived from acetylides are contaminants. The RuH2(PPh3)4-catalyzed reaction of ethyl 2-cyanopropionate (12) with methyl propiolate (14) at room temperature gave 15 in 90 % yield. 

An important feature of the present reaction is the chemoselective addition of activated nitriles to the CN triple bonds of nitriles in the presence of carbonyl groups, because of the strong coordination ability of nitriles toward metals. The iridium-catalyzed addition of ethyl cyanoacetate to 4-acetylbenzonitrile (30) gives ethyl (Z)-3-(4-acetylphenyl)-3-amino-2-cyano-2-propenoate (31, 59%) chemoselec-tively, while the same reaction promoted by a conventional base such as AcONH4 and NaOH gives ethyl 2-cyano-3-(4-cyanophenyl)-2-butenoate (32) ( Z= 55 45) [20]. 

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