Final Report Summary - BIO PRE-ORGANOCATS (Biomimetic Multibinding Pre-Organocatalysts)
The idea of this project was highly original and ambitious. In order to achieve the final scientific objectives, it was necessary to find a delicate reactivity balance between at least four different chemical entities in the same pot. During two years, different pre-organocatalysts have been synthesized and studied, but none of them has shown an advantageous reactivity compared to the standard aminocatalysts. Nevertheless, the study of the equilibria reactions of some of the reversible reactions of these substances has given key information to develop two new major advances using aminocatalysts.
As usual in long term projects, the deviations of the main project occurred due to unexpected results. As a result of the mechanistic studies performed during this project, two main advances have been possible. The first one is the efficient chiral recognition of lactols and the second one, the discovery of a new really useful parameter to track the rate of the reactions.
The new method for the chiral recognition of lactols is based on the knowledge derived from some of the studies performed during this project. In addition, this knowledge is of vital importance to understand the selectivity of all the aminocatalytic reactions where the distribution of downstream intermediates determines their selectivity. The new method allows the efficient differentiation of enantiomers of lactols in solution, which was impossible until now. This differentiation has already been used as the core of a new technology to separate gram quantities of important chiral lactols, that before could only be accessed from inefficient and expensive synthesis.
During this project, we have also performed numerous studies on the effect of acids and bases on the equilibria involved in the addition of nucleophiles to conjugated aldehydes. We have discovered how sensitive all this equilibria are to the acidity of the media, but how difficult it is to control this parameter, especially when low concentrations of catalyst are used. A new parameter to correlate the rate of iminium activated aminocatalytic reactions has been developed. This new method is highly original and its use has allowed the reduction of the catalyst loading required to complete the reaction in a reasonable amount of time from typically 10-20 mol% to 0.1 mol%.
In addition, in the context of this project, a new simple graphical kinetic analysis has been developed to determine the order of a reaction in catalyst. This new method has already been published in Angewandte Chemie International Edition and it will certainly be useful for many other researchers working in the catalysis area.
The fellow has started his independent research career. He has got independent funding from other research funding agencies and industrial partners. He has participated actively in the teaching of the Chemistry Department at Imperial College London. It has been especially significant the creation of a new course of “Kinetics in Catalysis”, essential to tackle mechanistic studies successfully.
As usual in long term projects, the deviations of the main project occurred due to unexpected results. As a result of the mechanistic studies performed during this project, two main advances have been possible. The first one is the efficient chiral recognition of lactols and the second one, the discovery of a new really useful parameter to track the rate of the reactions.
The new method for the chiral recognition of lactols is based on the knowledge derived from some of the studies performed during this project. In addition, this knowledge is of vital importance to understand the selectivity of all the aminocatalytic reactions where the distribution of downstream intermediates determines their selectivity. The new method allows the efficient differentiation of enantiomers of lactols in solution, which was impossible until now. This differentiation has already been used as the core of a new technology to separate gram quantities of important chiral lactols, that before could only be accessed from inefficient and expensive synthesis.
During this project, we have also performed numerous studies on the effect of acids and bases on the equilibria involved in the addition of nucleophiles to conjugated aldehydes. We have discovered how sensitive all this equilibria are to the acidity of the media, but how difficult it is to control this parameter, especially when low concentrations of catalyst are used. A new parameter to correlate the rate of iminium activated aminocatalytic reactions has been developed. This new method is highly original and its use has allowed the reduction of the catalyst loading required to complete the reaction in a reasonable amount of time from typically 10-20 mol% to 0.1 mol%.
In addition, in the context of this project, a new simple graphical kinetic analysis has been developed to determine the order of a reaction in catalyst. This new method has already been published in Angewandte Chemie International Edition and it will certainly be useful for many other researchers working in the catalysis area.
The fellow has started his independent research career. He has got independent funding from other research funding agencies and industrial partners. He has participated actively in the teaching of the Chemistry Department at Imperial College London. It has been especially significant the creation of a new course of “Kinetics in Catalysis”, essential to tackle mechanistic studies successfully.
