Nucleophilic addition of cyanide

Predict the product formed by nucleophilic addition of cyanide ion (CN ) to the carbonyl group of acetone, followed by protonalion to give an alcohol ... 

The displacement of CN by RS in surprising since C-labelled cyanide ion does not exchange with unlabelled ferricyanide . Wiberg et have shown that no exchange occurs under the conditions of the oxidation and that the effect of added cyanide is to be attributed to nucleophilic addition of cyanide to the thiol, viz. 

Vedejs developed an enantiocontrolled synthesis of aziridinomitosenes involving internal alkylation of the oxazole 132 to produce an oxazolium salt 133 followed by nucleophilic addition of cyanide providing the adduct 134 <00JA5401>. Electrocyclic ring opening of 134 to the azomethine ylide 135 with internal [2+3] trapping produces the tetracyclic product 137 via the pyrroline 136. 

The asymmetric reactions discussed in this chapter may be divided into three different types of reaction, as (1) hydrometallation of olefins followed by the C—C bond formation, (2) two C C bond formations on a formally divalent carbon atom, and (3) nucleophilic addition of cyanide or isocyanide anion to a carbonyl or its analogs (Scheme 4.1). For reaction type 1, here described are hydrocarbonyla-tion represented by hydroformylation and hydrocyanation. As for type 2, Pauson-Khand reaction and olefin/CO copolymerization are mentioned. Several nucleophilic additions to aldehydes and imines (or iminiums) are described as type 3. 

The Lewis acid-catalyzed three-component reaction of dihydropyridines, aldehydes, and />-substituted anilines efficiently yields highly substituted tetrahydroquinolines in a stereoselective manner, through a mechanism believed to be imine formation followed by formal [4-1-2] cycloaddition (Scheme 41). The 1,4-dihydropyridine starting materials were also prepared in situ by the nucleophilic addition of cyanide to pyridinium salts, creating in effect a one-pot four-component reaction <20030L717>. 

Intermolecular addition of carbon nucleophiles to the ri2-pyrrolium complexes has shown limited success because of the decreased reactivity of the iminium moiety coupled with the acidity (pKa 18-20) of the ammine ligands on the osmium, the latter of which prohibits the use of robust nucleophiles. Addition of cyanide ion to the l-methyl-2//-pyr-rolium complex 32 occurs to give the 2-cyano-substituted 3-pyrroline complex 75 as one diastereomer (Figure 15). In contrast, the 1-methyl-3//-pyrrolium species 28, which possesses an acidic C-3-proton in an anti orientation, results in a significant (-30%) amount of deprotonation in addition to the 2-pyrroline complex 78 under the same reaction conditions. Uncharacteristically, 78 is isolated as a 3 2 ratio of isomers, presumably via epimerization at C-2.17 Other potential nucleophiles such as the conjugate base of malononitrile, potassium acetoacetate, and the silyl ketene acetal 2-methoxy-l-methyl-2-(trimethylsiloxy)-l-propene either do not react or result in deprotonation under ambient conditions. 

The reaction has two steps nucleophilic addition of cyanide, followed by protonation of the anion. In fact, this is a general feature of all nucleophilic additions to carbonyl groups. 

To start this chapter, here are four reactions of the same ketone. For each product, the principal absorptions in the IR spectrum are listed. The pair of reactions on the left should come as no surprise to you nucleophilic addition of cyanide or a Grignard reagent to the ketone produces a product with no C—O peak near 1700 cm-1, but instead an O-H peak at 3600 cnrT1. The 2250 cm-1 peak is C=N C=C is at 1650 cm-1. 

The nucleophilic addition of cyanide ions to the electrochemically generated iminium cation is a synthetically very useful reaction and has been studied for a variety of symmetric and unsymmetric ions (Table 10) [266]. 

When cyclopropylideneamines 4 are formed under basic conditions by 1,3-dehydrochlorination of a-chloro ketimines 1 in the presence of cyanide ion, the stable hydrogen cyanide adducts 3 can be isolated. This cyclization to yield cyclopropanes only applies to tertiary a-chloro ketimines 1, which with cyanide also give rise to the formation of a a-cyanoaziridine 2, the latter being formed by nucleophilic addition of cyanide across the imino double bond followed by intramolecular nucleophilic substitution. ... 

Danion, D., and Carrie, R., Nucleophilic addition of cyanide ion to a-cyanovinylphosphonic esters. Synthesis and physicochemical properties of 1,2-dicyanoethylphosphonic esters. Bull. Soc. Chim. Pr., 1538, 1974. 

Each elementary step is reversible. At fist glance, this type of reaction should afford a complex reaction mixture of product, all possible intermediates, and starting materials. However, if the desired adduct is thermodynamically more stable than any other intermediates, the reaction can still be high yielding and become synthetically useful. The Strecker reaction is a typical example. Although the condensation of an aldehyde, an amine leading to iminium intermediate and subsequent nucleophilic addition of cyanide are in principle reversible under aqueous acidic conditions. The a-aminonitrile can be obtained in high yield under appropriate conditions. 

The Pachter modification of the Timmis synthesis is performed in the presence of cyanide ion,129 products other than those expected being obtained. For example, the condensation of phenylacetonitrile with 5-nitroso-2-phenylpyrimidine-4,6-diamine in the presence of cyanide ion gives, not 7-methyl-2,6-diphenylpteridin-4-amine but 2,6-diphenylpteridine-4,7-diamine (5).121 The mechanism of the reaction is still uncertain, but it may involve nucleophilic addition of cyanide ion to the Schiff base formed by condensation between the nitroso group and the active methylene, cyclization to yield a dihydropteridine, and subsequent elimination. 

Most of the elementary reactions in the classic MCRs are equilibrium processes. Therefore, thermodynamic factors can significantly impact the reaction pathways in addition to the reaction kinetics. A classic example is the Strecker synthesis of a-amino nitrile 9 from aldehydes, amines, and cyanide (Scheme 15.5). The key step in this reaction is the nucleophilic addition of cyanide to the in situ formed iminium. However, condensation of a carbonyl compound with an amine leading to iminium is an equilibrium process, especially under aqueous conditions. Therefore, the desired addition reaction is in competition with direct addition of cyanide to the aldehyde, leading to cyanohydrin 10. However, since the formation of both 9 and 10 were reversible, only the more stable adduct 9 was produced at the expense of cyanohydrin 10 under thermodynamically controlled conditions. 

Cyano-3,3-dimethylazetidines (164) have been prepared by a novel procedure which involves nucleophilic addition of cyanide to... 

Imine formation proceeds by nucleophilic addition-elimination of NH3 to the ketone carbonyl group, with loss of water. Imines, like ketones, are polarised by the electronegativity difference between carbon and nitrogen. Nucleophilic addition of cyanide occurs to give an amino nitrile intermediate. 

Nucleophilic addition of cyanide ion to the carbonyl carbon gives a tetrahedral carbonyl addition compound. 

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