Acetone: acylation cyanohydrin from

In 1992, Oda et al. reported a one-pot synthesis of optically active cyanohydrin acetates from aldehydes, which were converted to the corresponding racemic cyanohydrins through transhydrocyanation with acetone cyanohydrin, catalyzed by a a strongly basic anion-exchange resin [46]. The racemic cyanohydrins were acetylated by a lipase from P. cepacia (Amano) with isopropenyl acetate as the acyl donor. The reversible nature of the base-catalyzed transhydrocyanation enabled continuous racemization of the unreacted cyanohydrins, thereby effecting a total conversion (Figure 4.21). 

Table 11.1-20). A very good illustration for the potential of enantiomer-differentiating acylation catalyzed by lipases is provided by the high-yield synthesis of a series of aromatic cyanohydrin acetates (la-g) from aldehydes, acetone cyanohydrin and vinyl acetate in the presence of Pseudomonas cepacia lipase and a basic anion-exchange resin in diisopropyl ether which proceeds under kinetic resolution coupled with in situ formation and racemization of the cyanohydrin representing a dynamic kinetic resolution. For further examples see Table 11.1-24. 

Cyanohydrins are usually prepared from carbonyl compounds and a cyanide source. Initially performed with volatile and very toxic hydrogen cyanide, the reaction is now carried out with safer cyanide agents, such as acetone cyanohydrin, acyl cyanides, cyanoformates or the most used trimethylsilyl cyanide. In terms of atom economy, this reaction is 100% atom efficient and is widely used despite the toxicity of the reagents. The asymmetric reaction can now be efficiently catalysed by a variety of chiral Lewis acids, and a recent review presents in detail the work realised in this field, with a large description of titanium-based catal)dic systems. 

The kinetic resolution of cyanohydrins via enantioselective acylation may be converted into a dynamic process by making use of the chemical instability of cyanohydrins (Scheme 3.15) [235], Thus, racemic cyanohydrins were generated from an aldehyde and acetone cyanohydrin (as a relatively safe source of hydrogen cyanide) under catalysis by an anion exchange resin. The latter also served as catalytic base for the in-situ racemization. Enantioselective acylation using PSL and tsopropenyl acetate led to the exclusive formation of the corresponding (S)-cyanohydrin acetates in 47-91% optical purity. 

Many other hydroxy compounds bearing a secondaiy hydroxy group can be enan-tioselectively acylated. In the case of a few cyanohydrins, optically active acetates are prepared in a one-pot procedure from the aldehyde and acetone cyanohydrin, followed by a lipase-catalyzed transesterification [196]. Also, 2-hydroxy acids and esters [197-201] can be enzymatically resolved, as shown in Scheme 43. 

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