Combinatorial search for novel transformations catalyzed by transition metal complexes carrying fluoroalkylphosphines as ligands
Analytical Chemistry
Final Report Abstract
After initial experiments on the project, we have decided to change the goal of the project to development of a system that allows automated analysis of multicomponent high throughput search for new reactions. This decision was made based on high potential of such a methodology to perform a quick and thorough evaluation of big amounts of experimental data and eliminate the laborious and error-prone manual analysis. The new goal of the project was reached by development of a method based on the combination of chemistry and information technology that we coined Flash Deconvolution. By this approach, chemically inert and electronically innocent substituents enable identification of the reactants that form an unknown product by comparing the molecular masses of the products formed from multiple sets of reactants containing the same functional groups but different substituents. This Flash Deconvolution strategy enables about 75,000 possible reactions to be run, assayed, and products identified within a few days with only a sealed 96-well plate and access to MS Excel. Our method identified six established reactions, used as positive controls, within more than 800 (if only two and three component reactions are considered) possible combinations of reactants with 96 different combinations of metal and ligand, corresponding to more than 75,000 possible reactions. This automated method also identified two previously unknown processes from GC/MS traces with multiple low-intensity and overlapping peaks. The methods and programs developed in this project will be used as a basis for further research. In our current investigations, we focused on reactions occurring between components containing two or three of the designed substituents. Our approach, however, is not limited to reactions between components containing the designed substituents. One can search for products resulting from additional components in the mixture. For example, products formed in a system containing an untagged reagent, such as CO, CO2, a source of fluorine or a source of a fluoroalkyl group, could be identified by selecting for products in each of the three sets with added masses corresponding to that of the additional reagent. Studies targeting such reactions are currently ongoing in the host institution.
