Synthesis and Reactions of Optically Active Cyanohydrins

Franz Effenberger * . Cyanohydrins have always held a place of importance both as technical products and as reagents in organic chemistry. It is surprising. therefore. that optically active cyanohydrins have been extensively investigated and employed for syntheses relatively recently. This can be explained by the fact that only in the past few years have enzymatic methods made chiral cyanohydrins readily available in high optical purity. Chiral cyanohydrins are widespread in nature in the form of the respective glycosides and serve roughly 3000 plants and many insects as antifeedants. For the preparative organic chemist. this class of compounds offers an enormous synthetic potential for making other chiral compounds accessible. In a few instances, the pharmacological principle of a drug also incorporates a chiral cyanohydrin as constitutive structural element. In the development of novel. physiologically active compounds all possible stereoisomers must be synthesized and investigated with respect to their activity range and the pathway of their metabolic transformations and/or degradation. The development of simple synthetic procedures for such compounds, which also entail a high degree of stereoselectivity, therefore has prime importance. To this end chiral cyanohydrins may serve as stereochemically pure starting materials. In the present review, the following topics will be addressed: enantioselective addition of hydrogen cyanide (HCN). catalyzed by the enzymes (R)and (S)-oxynitrilase, to aldehydes and ketones yielding ( R ) and (S) cyanohydrins, respectively; enantioselective addition of HCN to aldehydes catalyzed by cyclic dipeptides; enantioselective esterification of racemic cyanohydrins and enantioselective hydrolysis of cyanohydrin esters catalyzed by lipases and esterases, respectively: transformation of the nitrile group of chiral cyanohydrins to provide optically active z-hydroxycarboxylic acids, aldehydes, and ketones, as well as 2-amino alcohols; sulfonylation of the OH group of chiral cyanohydrins to furnish optically active r-sulfonyloxynitriles which undergo S,2 displacement of the activated OH group yielding r-azido-, r-amino. and a-fluoronitriles with inverted configuration.