What is the mechanism of asymmetric cyanohydrin and amino nitrile synthesis?

In order to be able to improve on any system (be it a car engine, a computer programme or a chemical reaction), it is essential to have a detailed knowledge of how the system works. It is then possible to construct a model of the system which allows the effect of changes to the system to be quantitatively predicted. This is the process we intend to carry out for a very important class of chemical reactions.The single most important reactions in organic chemistry are those which create a new carbon-carbon bond. An ongoing challenge for chemists is to develop new 'green' methods for the synthesis of these bonds which use catalysts to ensure that the bond is formed under very mild reaction conditions and which produce just the desired product with no waste. This task is complicated by the fact that most complex organic molecules can occur in two different forms (called enantiomers) which are related to one another in the same way as a left and right hand. The two enantiomers of a compound generally have different biological properties, so it is essential that any potential pharmaceutical or agrochemical intermediate be prepared as just one of the two possible enantiomers - unfortunately, this is a difficult task since under 'normal' reaction conditions, chemical reactions will always produce a 1:1 mixture of the two enantiomers. However, by use of a catalyst which itself exists as just one enantiomer (a chiral catalyst), it is possible to catalyse the formation of just one of the two enantiomers of a product.Two of the oldest carbon-carbon bond forming reactions are the additions of cyanide to aldehydes and imines. Over the last ten years we have developed novel chiral catalysts for these reactions and these are now used commercially. However, we still lack a detailed understanding of exactly how the catalysts work and this is preventing the further improvement of the catalysts. Our catalysts are already amongst the best in the world, but if the UK chemicals and pharmaceuticals industries are to stay competitive in an increasingly cut-throat international market place, it is essential that they be improved still further. In particular, for the addition of cyanide to imines it is essential that the substrate to catalyst ratio be improved and that the ratio of the two enantiomeric products produced be improved. Therefore, the aim of this project is to study the mechanism of these reactions in great detail, especially by measuring the rate of reaction under various reaction conditions. The resulting information will then be used to design new catalysts with even better catalytic activity, thus ensuring that the UK retains its world leading position in this area of chemistry.