Ketones cyanohydrin ethers

Cya.nideExcha.nge, Acetone cyanohydrin and methyl isobutyl ketone cyanohydrin [4131 -68-4] dissolved in an organic solvent, such as diethyl ether or methyl isobutyl ketone, undergo cyanide exchange with aqueous cyanide ion to yield a significant cyanide carbon isotope separation. The two-phase system yields cyanohydrin enriched in carbon-13 and aqueous cyanide depleted in carbon-13. Fquilibrium is obtained in seconds. 

Silylated cyanohydrins have also been prepared via silylation of cyanohydrins themselves and by the addition of hydrogen cyanide to silyl enol ethers. Silylated cyanohydrins have proved to be quite useful in a variety of synthetic transformations, including the regiospecific protection of p-quinones, as intermediates in an efficient synthesis of a-aminomethyl alcohols, and for the preparation of ketone cyanohydrins themselves.The silylated cyanohydrins of heteroaromatic aldehydes have found extensive use as... 

A similar method was used for the synthesis of a cyclic cyanohydrin ether 75. The cyclization took place by the intramolecular displacement of the polymer-supported cyanohydrin 74 by treatment with lithium hexa-methyldisilazide (Scheme 21). Target 75 was obtained in 46% yield. While the yield is moderate, a pure product was obtained after a simple workup procedure. The cyanohydrin ether 75 can be readily converted to a cyclic ketone.46... 

The condensation of cyanohydrin ethers with aldehydes or ketones provides a-hydroxy ketones. 0-Benzoyl-protected cyanohydrins react with aldehydes to give a-hydroxy ketones via intramolecular deprotective benzoylation analogous to TMS-protect cyanohydrins (Scheme 10). ... 

Allylic ethers of cyanohydrins are easily prepared through phase transfer allylation. Deprotonation of these ethers with LDA in THF at -78 °C effects 2,3-rearrangement to transient p. y-unsaturated ketone cyanohydrins, which are transformed during work-up to the ketones (Table 16). In an extension of this work, the mixed acetal cyanohydrin ethers (187), prepared by mild acid treatment of the cyanohydrins with 2-methoxy-1,3-butadiene or 1-f-butoxyallene, rearranged to the keto enol ethers (189 equation 40). Hydrolysis of the enol ethers (189) leads to 1,4-dicarbonyl compounds, which can be cyclized to cyclopentenones. 

Heteroatom-stabilized Carbanions. Heteroatom-stabilized and allylic carbanions serve as homoenolate anions and acyl anion equivalents, e.g. a-anions of protected cyanohydrins of aldehydes and Q ,/3-unsaturated aldehydes are intermediates in general syntheses of ketones and Q ,/3-unsaturated ketones (eq 36). Allylic anions of cyanohydrin ethers may be a-alkylated (eq 37) or, if warmed to —25°C, may undergo 1,3-silyl migration to cyanoenolates which may be trapped with TMSCl. Metalated Q -aminonitriles of aldehydes are used for the synthesis of ketones and enamines (eq 38). Similarly, allylic anions from 2-morpholino-3-alkenenitriles undergo predominantly a-C-alkyl-ation to give, after hydrolysis, a,/3-unsaturated ketones (eq 39). ... 

The mono-silyl ether (49) was also produced on attempted formation of the trimethylsilyl cyanohydrin ether of the 37-ketone function of pristinamycin 11, using trimethylsilyl cyanide/zinc iodide according to the procedure of D. Evans and co-workers [116]. 

This form of protection is advantageous for aldehydes, because the trimethylsilyl cyanohydrin ethers of aldehydes present a reactive hydrogen atom on the a carbon. This hydrogen can be replaced with lithium, after which the compound may be converted to a ketone by reaction with an alkyl halide, or it may be converted to an a-hydroxyketone by reaction with another aldehyde or ketone (Scheme 4.4) ... 

Methyl benzyl ketone cyanohydrin and ethyl mercaptan in anhydrous benzene or benzene-ether ice-cooled, satd. with HCl, kept 15 days in a refrigerator, the resulting crude thioimidoester hydrochloride treated with water, and steam-distilled product. Y 80.2%. F. e. s. W.E. Elias, Can. J. Chem. 48, 3662 (1970). 

Conversion of aldehydes to ketones via cyanohydrin derivatives (ethers) by alkylation or Michael addition also used with sdyl ethers, dialtylamlnonitnies (see also Stetter reaction). 

The in situ cyanosilylation of p-an1saldehyde is only one example of the reaction which can be applied to aldehydes and ketones in general. - The simplicity of this one-pot procedure coupled with the use of inexpensive reagents are important advantages over previous methods. The silylated cyanohydrins shown in the Table were prepared under conditions similar to those described here. Enolizable ketones and aldehydes have a tendency to produce silyl enol ethers as by-products in addition to the desired cyanohydrins. The... 

Steroidal 17-cyanohydrins are relatively stable towards chromium trioxide in acetic acid (thus permitting oxidation of a 3-hydroxyl group ) and towards ethyl orthoformate in ethanolic hydrogen chloride (thus permitting enol ether formation of a 3-keto-A system ). Sodium and K-propanol reduction produces the 17j -hydroxy steroid, presumably by formation of the 17-ketone prior to reduction. ... 

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... 

As summarized in Scheme 6.7, several a-acetal ketones were converted to the corresponding cyanohydrin TMS-ethers with 90-98% ee at catalyst loadings of 2-20 mol%. 

Aldehydes, ketones, and acetals react with allyltrimethylsilane in the presence of a catalytic amount of BiX3 (X = C1, Br, OTf) to give homoallyl alcohols or homoallyl alkyl ethers (Equation (52)).91-93 The BiX3-catalyzed allylation of aldehydes and sequential intramolecular etherification of the resulting homoallylic silyl ethers are involved in the stereoselective synthesis of polysubstituted tetrahydropyrans (Equation (53)).94,95 Similarly, these Lewis acids catalyze the cyanation of aldehydes and ketones with cyanotrimethylsilane. When a chiral bismuth(m) catalyst is used in the cyanation, cyanohydrines are obtained in up to 72% ee (Equation (54)). a-Aminonitriles are prepared directly from aldehydes, amines, and cyanotrimethysilane by the BiCl3-catalyzed Strecker-type reaction. 

Synthesis of ketones. Stork and Maldonado have disclosed a new synthesis of ketones from aldehydes RCHO- RCOR. The aldehyde is first converted into the cyanohydrin and then the hydroxyl group is protected by reaction with ethyl vinyl ether to give (1). This is then converted into the anion by reaction with lithium diiso-propylamide under carefully controlled conditions. The base is generated from butyl-lithium and diisopropylamine in THF and then (1) in hexamethylphosphorie triamide... 

TrialkylsUyl cyanides, which also possess sp C—Si bonds, react with carbonyls. Znh, " AlCb, TMSOTf, LnCb (Ln = La, Ce, Sm), etc., are employed as the promoter, and cyanohydrin silyl ethers are obtained in high yields even from hindered ketones (equation 12). The products are converted to various synthetically important intermediates such as cyanohydrins, a,p-unsaturated nitriles or amino alcohols. 

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