Asymmetric addition of cyanide to aldehydes and imines

Abstract

Cyanohydrins are a group of compounds that are widely used in industry as common building blocks for asymmetric synthesis. In this thesis, novel methods of synthesizing chiral cyanohydrins are investigated using complexes of transition metals complexed to salen ligands. To start the project, alternative sources of cyanide were investigated. Unfortunately, this investigation could not uncover a new cyanide source that was more effective than trimethylsilyl cyanide as a substrate for titanium(salen) based catalysts. However, this research has led to the finding that KCN / 18-Crown-6 can be used as a co-catalyst in the addition of ethyl cyanoformate to various aldehydes. This has led to a huge reduction in the amount of catalyst that is required to achieve the same enantiomeric excess. In addition, the diastereoselective synthesis of cyanohydrin derivatives using chiral cyanoformates was made possible for the first time. Some of the cyanohydrins synthesized by the new ethyl cyanoformate route were taken a step further, and their use as chiral building blocks was also studied. By using a palladium based catalyst, α,β,-unsaturated cyanohydrins were converted into amides via a two-step reaction. Research into the Strecker reaction was also carried out using vanadium(V)(salen) complexes as catalysts. In this field, the use of phenols as co-catalysts was discovered, and this has led to a world leading enantiomeric excess.