Addition of Cyanide to Aldehydes and Ketones

The conversion of aldehydes (6.53) into the corresponding cyanohydrins (6.54) is an appealing synthetic transformation, since cyanohydrins are readily converted into a number of important functional groups such as a-hydroxy acids (6.55) and P-amino alcohols (6.56). 

The most popular and selective catalysts for the asymmetric transformation of aldehydes into cyanohydrins are oxynitrilase enzymes. However, as the emphasis of this book is on chemically catalysed transformations, a discussion ofbiocatalysed 

The Lewis acid-catalysed addition of trimethylsilyl cyanide to aldehydes has been reported using several different catalysts. Titanium-based Lewis adds have proved to be particularly popular. In a typical reaction, benzaldehyde (6.01) is converted into the cyanohydrin (6.57) usually after removal of the trimethylsilyl group by hydrolysis. A wide variety of ligands have been used for this reaction and 

Some of the highest ees are obtained with ligand (6.61) 8 and (6.62). The former also shows good scope and catalyses the cyanation of aliphatic aldehydes such as isobutyraldehyde with up to 95% ee. Ligand (6.60) is notable for its high catalytic efficiency in this procedure, since only 0.1 mol% is required. 

Aluminium-BINOL-based complexes have also been shown to be highly selective bifunctional asymmetric cyanation catalysts. For example the bisphosphine oxide (6.65) developed by Shibasaki and coworkers catalyses the cyanation of both aromatic and aliphatic aldehydes with ees ranging from 83-98%.  

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Biphasic conditions can also be used to suppress background reaction. HnL-catalysed asymmetric addition of cyanide to aldehydes and ketones provides an important example,... 

The products from addition of cyanide to aldehydes and ketones are often versatile substrates that lend themselves for further transformations to useful compounds. The early use of the dangerous HCN gas for this cyanohydrin formation could be circumvented by using TMSCN instead, as discovered by Evans etaL [43, 44). Loh et al subsequently reported the first adaptation of the TMSCN addition to aldehydes and ketones in water using Inp3 as the Lewis acid catalyst, with success even for trifluoro ethyl hemiacetal, the commercially available form of trifluoroacetaldehyde [45] (Figure 8.22). However, this procedure is not successful for ketones. 

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