Novel chemo-enzymatic strategies for asymmetric aldol-type reactions using in situ formed acetaldehyde in deep eutectic solvents

Müller, Christoph R.; Leitner, Walter (Thesis advisor); Spieß, Antje (Thesis advisor)

Aachen (2016)
Dissertation / PhD Thesis

Dissertation, RWTH Aachen, 2016


This Ph.D. thesis deals with the question, if an in situ generation of acetaldehyde is advantageous for chosen catalytic processes. Starting point of this idea is a slow release of highly reactive acetaldehyde by transesterification reactions of vinyl esters with the enzyme CALB. Another approach is the oxidation by alcohol dehydrogenases. As benchmark reaction for detecting acetaldehyde, the cross coupling aldol reaction with p-nitrobenzyaldehyde catalyzed by proline derivatives was chosen. Overall, this system describes a chemo-enzymatic one-pot multi-step reaction. One of the key factors was the use of a new solvent class: A deep eutectic solvent (DES). Under all tested solvents, this solvent class delivered best results. A deep eutectic solvent is a mixture of molten salts which has a lower melting point than those observed for the single components. An important criteria for counting to the class of DES is a melting point of <150 °C. After optimization, the sensitive benchmark reaction gave the desired product in up to 84 % yield and 96 % ee. Further studies focus then on the recyclability of the solvent. It was also possible to demonstrate that the organocatalyst was immobilized in the DES phase. In a first proof of concept, four cycles could be successfully conducted without further addition of catalyst. Even though the system suffers catalyst leaching, this system is superior in certain aspects compared to already established reaction systems (e.g. by reducing the amount of acetaldehyde equivalents to a minimum, substituting hazardous components with harmless ones). In conclusion, this work emphasizes the potential of DES in the area of bio- and organocatalysis as well as the advantage of generating highly reactive reaction partners in situ.