Ketones cyanation

Peroxomonosulfuric acid oxidi2es cyanide to cyanate, chloride to chlorine, and sulfide to sulfate (60). It readily oxidi2es carboxyflc acids, alcohols, alkenes, ketones, aromatic aldehydes, phenols, and hydroquiaone (61). Peroxomonosulfuric acid hydroly2es rapidly at pH <2 to hydrogen peroxide and sulfuric acid. It is usually made and used ia the form of Caro s acid. 

Ozone can be used to completely oxidize low concentrations of organics in aqueous streams or partially degrade compounds that are refractory or difficult to treat by other methods. Compounds that can be treated with ozone include alkanes, alcohols, ketones, aldehydes, phenols, benzene and its derivatives, and cyanide. Ozone readHy oxidizes cyanide to cyanate, however, further oxidation of the cyanate by ozone proceeds rather slowly and may require other oxidation treatment like alkaline chlorination to complete the degradation process. 

A one-step synthesis o( mtnles from carbonyls by a reductive cyanation with tosylmethyl isocyanide (TosMIC), also synthesis of 1,3-azole or of ketones... 

Cyanation of ketones, nitro compounds, or benzylic compounds... 

The synthetic utility of the carbonylation of zirconacycles was further enhanced by the development of a pair of selective procedures producing either ketones or alcohols [30] and has been extensively applied to the synthesis of cyclic ketones and alcohols, most extensively by Negishi [22—27,29—33,65,87,131—134], as detailed below in Section I.4.3.3.4. The preparation of unsaturated aldehydes by carbonylation with CO is not very satisfactory. The use of isonitriles in place of CO, however, has provided a useful alternative [135], and this has been applied to the synthesis of curacin A [125]. Another interesting variation is the cyanation of alkenes [136]. Further developments and a critical comparison with carbonylation using CO will be necessary before the isonitrile reaction can become widely useful. The relevant results are shown in Scheme 1.35. 

Autoxidation of secondary acetonitriles under phase-transfer catalytic conditions [2] avoids the use of hazardous and/or expensive materials required for the classical conversion of the nitriles into ketones. In the course of C-alkylation of secondary acetonitriles (see Chapter 6), it had been noted that oxidative cleavage of the nitrile group frequently occurred (Scheme 10.7) [3]. In both cases, oxidation of the anionic intermediate presumably proceeds via the peroxy derivative with the extrusion of the cyanate ion [2], Advantage of the direct oxidation reaction has been made in the synthesis of aryl ketones [3], particularly of benzoylheteroarenes. The cyanomethylheteroarenes, obtained by a photochemically induced reaction of halo-heteroarenes with phenylacetonitrile, are oxidized by air under the basic conditions. Oxidative coupling of bromoacetonitriles under basic catalytic conditions has been also observed (see Chapter 6). 

Another reaction type for which EGA catalysis has been thoroughly explored is the reaction between organo-silicon nucleophiles and acetals or unprotected aldehydes and ketones [31-33]. The reaction types are aldol condensation, allyla-tion, cyanation, and hydride reductions depending on which of the nucleophiles (16) to (20) is used. 

The cyanation reactions with (19) (extremely toxic and requires essentially nonacidic reaction conditions) can also he carried out with unprotected aldehydes in good yields but with higher charge consumption (88-97%, 0.15-0.45 F). For ketones, the products are isolated as trimethylsilyl ethers, whereas for aldehydes the sdyl ethers are hydrolyzed to alcohols [33]. 

Cyanation of aldehydes and ketones is an important chemical process for C C bond formation." " Trimethylsilyl cyanide and/or HCN are commonly used as cyanide sources. The intrinsic toxicity and instability of these reagents are problematic in their applications. Acetyl cyanide and cyanoformates were used as cyanide sources in the enantioselective cyanation of aldehydes catalyzed by a chiral Ti complex and Lewis base (Scheme 5.31)." The Lewis base was necessary for the good yields and selectivities of these reactions. The desired products were obtained in the presence of 10mol% triethyl amine and 5mol% chiral titanium catalyst (Figure 5.14). Various aliphatic and aromatic aldehydes could be used in these reactions. 

In addition to metal catalysts, organocatalysts could also be used in asymmetric cyanation reactions. Chiral Lewis bases, modified cinchona alkaloids, catalyzed asymmetric cyanation of ketones by using ethyl cyanoformate as the cyanide source (Scheme 5.34)." Similar to metal-catalyzed reactions, ethyl cyanoformate was first activated by chiral Lewis bases to form active nucleophiles. Various acyclic and cyclic dialkyl ketones were transformed into the desired products. Because of using... 

Scheme 5.34. Chiral base-catalyzed asymmetric cyanation of ketones.

Furthermore, Rueping and coworkers applied their reaction conditions to the cyanation of ketimines [54]. The use of A-benzylated imines derived from aryl-methyl ketones generally gave comparable yields, but lower enantioselectivities. However, this method furnished Strecker products bearing a quaternary stereogenic center, which are valuable intermediates for the preparation of optically active a,a-disubstituted a-amino acids. 

The double process of cyanation/transcyanation of co-bromoaldehydes and racemic cyanohydrins as a source of HCN is a really interesting process (Scheme 10.25). Thus, using this reaction it is possible to obtain optically active (S)-ketone- and (R)-aldehyde-cyanohydrins in one pot [55], The reaction is carried out in diisopropyl ether using a crude extract of almond containing (R)-oxynitrilase as biocatalyst. The optically active (a-bromocyanohydrins prepared by this method is used as starting materials for the synthesis of valuable compounds such as... 

Aldehydes or Ketones with Other Functional Groups Aldehydes, Ketones with Other Functional Groups Kepone Chlordecone Aliphatic Flydrocarbons Aliphatic Nitriles and Cyanates Acetonitrile Acrylonitrile Aliphatic Nitriles Aliphatic Nitrosamines Aliphatic Nitrosamines A-Nitrosodimethylamine (NDMA)... 

Other examples of electrophilic toxic chemicals are aldehydes and ketones, especially unsaturated ones, acyl halides and cyanates. 

Reductive cyanation (5, 684 6, 600).1 The original conditions for conversion of ketones into nitriles give low yields when applied to aldehydes. Satisfactory results are obtained, however, if the initial reaction with TosMIC is conducted at 50° in DME before addition of methanol and reflux. Yields of 50-70% are then possible. 

The most common synthetic methods involving formation of three or more bonds and leading to polyheteroatom systems are of the [2 + 2+2] type. Condensations employing a wide range of different two-atom fragments have been reported, and examples involving the use of sulfur trioxide, nitriles, ketones, isocyanates, ketenes, thioketenes and cyanates as the two-atom components are known. Of these, the reactions of sulfur trioxide and isocyanates are probably the more important, and a few illustrative examples are given here. 

Keywords Cyanation, a-Cyanohydrin, a-Aminonitrile, Cyanide, HCN, TMSCN, Lewis acid, Metal-free, Organocatalyst, C=0 bond, C=N bond, Strecker, Reissert, Aldehydes, Ketones, Imines, Aldimines, Ketoimines... 

Cyanation of carbonyl compounds has one of the richest histories of any transformation in the field of asymmetric catalysis, and intensive research efforts have continued unabated since the editorial deadline for the first edition of Comprehensive Asymmetric Catalysis in 1998. This chapter will summarize all efforts in this area from 1998 to date, highlighting the most important catalytic systems from a synthetic and/or mechanistic standpoint. Significant advances in both the cyanation of aldehydes (formation of secondary cyanohydrins Section 28.2.1) and the cyanation of ketones (formation of tertiary cyanohydrins Section 28.2.2) will be addressed [1,2]. 

Relatively few of the enzymatic methods applicable to the preparation of secondary cyanohydrins have been adapted successfully to the synthesis of optically pure tertiary cyanohydrins [1,3,4]. Similarly, progress in asymmetric hydro-cyanation of ketones with synthetic catalysts lagged far behind advances in aldehyde cyanation. This situation has changed fairly dramatically over the past... 

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