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Self-Amplifying Stereodynamic Catalysts in Enantioselective Catalysis

Final Report Summary - AMPCAT (Self-Amplifying Stereodynamic Catalysts in Enantioselective Catalysis)

Highly promising reactions such as enantioselective autocatalysis (Soai reaction) and chiral catalysts undergoing dynamic interconversions, e.g. BIPHEP ligands, are highly attractive, because in there is the opportunity to design new processes, which can interact with their chemical environment and switch the output in a smart way.
In the present project novel switchable chiral ligands undergoing dynamic interconversions were synthesized and their stereochemical behaviour characterized. These chiral ligands were subjected a high-throughput screening procedure to find catalytic processes and more important the reaction kinetics was studied to get insights into the reaction mechanism. First self-amplifying processes could be identified and investigated. Here the interaction of substrates led to the partial conversion of these stereodynamic ligands into a single form, which was then used in a catalytic reaction to obtain stereoisomers in high enantioselectivities.
To rapidly screen the here investigated reactions high-throughput multiplexing HPLC (ht mpHPLC) was developed, which utilizes bare-codes consisting of binary sequences of the elements 0 and 1 to rapidly inject a sequence of samples into the separation device. Rapid injections are achieved by direct addressing of the hardware of one or more commercial autosampler injection devices using conventional multi-well plates or vial racks. A software algorithm has been developed to encode samples and to generate sequences, which control the hardware. The novel encoding scheme and deconvolution algorithm allows obtaining high-resolution chromatographic data. Exceptional high throughputs can be achieved and about 1000 samples per day analysed with a single instrument, which can be only achieved by 10 conventional instruments.
With this tool in hands we have investigated one of the most intriguing self-amplifying enantioselective reaction, namely the Soai reaction. Comprehensive kinetic data provided detailed insights into this self-amplifying process. The understanding of the reaction mechanism provided a blueprint for highly efficient chemical processes.
Most importantly we have successfully transferred these findings to the development and design of a self-amplifying enantioselective catalyst that is able to detect the handedness of the chirality of the targeted product and can switch its selectivity, so that exclusively the targeted product with the targeted handedness is produced.