Cyanhydrins, chiral

Acyloxy-l-cyanoalkanes [45, 46], which can be used as precursors for ketones [47], a-hydroxy ketones [48] and 1,4-dicarbonyl compounds [47], are prepared in one pot from the appropriate aldehyde, sodium or potassium cyanide, and the acylating agent under phase-transfer catalytic conditions [47-49]. Attempts to synthesize chiral cyanhydrins using chiral phase-transfer catalysts have been unsuccessful (see Section 12.3). 

Attempts to produce chiral cyanhydrins under phase-transfer catalytic conditions (3.3.9) using ephedrinium or cinchoninium catalysts has been singularly unsuccessful [21,22]. Optical purities varying from 0 to 60% have been recorded [22], but verification of the reproducibility of the higher values is needed. Similarly, nucleophilic attack on a carbonyl group by the trichloromethyl anion under phase-transfer catalytic conditions (see Section 7.4) in the presence of benzylquininium chloride produces a chiral product, but only with an enantiomeric excess of 5.7% [23]. The veracity of this observation has also been questioned [24],... 

F]Fluorobenzaldehydes have also been used as starting materials for the preparation of enantiomers of [6- F]fluoronorepinephrine,a myocardial marker [166]. The key step is the formation of a protected F-cyanhydrine which is reduced into an amino alcohol. Deprotection, purification and resolution on a chiral column provide both enantiomers (Scheme 30). 

Initial preparative work with oxynitrilases in neutral aqueous solution [517, 518] was hampered by the fact that under these reaction conditions the enzymatic addition has to compete with a spontaneous chemical reaction which limits enantioselectivity. Major improvements in optical purity of cyanohydrins were achieved by conducting the addition under acidic conditions to suppress the uncatalyzed side reaction [519], or by switching to a water immiscible organic solvent as the reaction medium [520], preferably diisopropyl ether. For the latter case, the enzymes are readily immobilized by physical adsorption onto cellulose. A continuous process has been developed for chiral cyanohydrin synthesis using an enzyme membrane reactor [61]. Acetone cyanhydrin can replace the highly toxic hydrocyanic acid as the cyanide source [521], Inexpensive defatted almond meal has been found to be a convenient substitute for the purified (R)-oxynitrilase without sacrificing enantioselectivity [522-524], Similarly, lyophilized and powered Sorghum bicolor shoots have been successfully tested as an alternative source for the purified (S)-oxynitrilase [525],... 

Brussee, J., Van der Gen, A. Biocatalysis in the Enantioselective Formation of Chiral Cyanhydrins, Valuable Building Blocks in Organic Synthesis. In Stereoselective Biocatalysis, Patel, R. N. Ed., Dekker New York, 2000, p. 289. 

Less effective, in terms of insecticidal activity, is the asymmetric induction in the course of the addition of optically active (S)-cyanhydrine-isomer 299 to the ketene 388 of fenvaleric acid in the presence of a chiral cyclopeptide (D-Phe-D-Ala) 380 [871], optically active amines or even in the absence of any additional reagent [872]. The yield of the actual insecticidal S-aS-ester (esfenvalerate) is low. However, the overall yield in the interesting S-configurated acid component is essentially quantitative (Reaction scheme 261). 

After repeated cyanhydrin reactions, four tetroses will provide a total of eight pentoses (each tet-rose provides a pair of new diastereomers with one more chiral center), which can then yield sixteen stereoisomeric hexoses. The compounds derived from D-glyceraldehyde are designated as D-aldoses and those from L-glyceraldehyde as L-aldoses. 

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