Cyanation of aliphatic aldehydes

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. 

Optically active cyanohydrins can be easily transformed to P-hydroxy amines, a-hydroxy and a-amino carboxylic acids, which represent versatile intermediates for the synthesis of biologically important compounds, including insecticides and medicines [189, 190]. Asymmetric cyanation of carbonyl compounds catalyzed by chiral metal complexes, particularly titanium compounds, has provided one of the most convenient protocols to the access of these type of compounds. The first example of catalytic asymmetric cyanation of aliphatic aldehydes was realized in Reetz s group using BINOL-Ti complex as the catalyst to give the cyanohydrins in up to 82% ee [104] (Scheme 14.85). 

In 2002, a C2-symmetrical bicyclic guanidine 12 (Scheme 30.2) was successfully used to for the cyanation of aliphatic aldehydes 11 to give (R)-cyanohydrins 13 in quantitative yields and reasonable enantioselectivities (60-70% ee) [10]. The use of ketones resulted in lower enantioselectivities. 

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