Synthetic and mechanistic studies on asymmetric cyanohydrin synthesis using a titanium(salen) bimetallic catalyst

Abstract

A bimetallic titanium(salen) complex 1 was found to catalyse the asymmetric addition of ethyl cyanoformate to aldehydes. Best results were obtained using 5 mol% of the catalyst at −40 °C and under these conditions, both aromatic and aliphatic aldehydes were converted into cyanohydrin carbonates with up to 99% enantiomeric excess. The same catalyst could also be used to catalyse the asymmetric addition of potassium cyanide to aldehydes in the presence of propionic anhydride, leading to cyanohydrin esters. Mechanistic studies showed that the enantiomeric excess of the product increased during the early stages of this reaction. However, by adding a ‘sacrificial aldehyde’ this effect could be eliminated. The structure of the catalyst in solution was investigated using variable concentration, variable temperature and variable solvent NMR studies. These experiments showed that the catalyst exists as a mixture of monometallic 4 and bimetallic 1 species, a result which is consistent with previous mechanistic studies on the asymmetric addition of trimethylsilyl cyanide to aldehydes and ketones catalysed by the same catalyst. A mechanistic rationale for all of these observations is reported.