ROBOCAT builds on previous achievements of the laboratory in the development of novel catalytic systems covalently immobilized onto polymers and magnetic nanoparticles, which maintain or even improve the catalytic activity of the homogeneous, referable ligands. We now aim at developing flow processes operable for long periods of time without appreciable decrease in the productivities (TOFs) of the immobilized catalysts. This will allow intensification of different enantioselective processes, improving their sustainability profile (avoidance
of catalyst separation steps, high catalyst recyclability, use of green reaction conditions). Our studies will be mostly oriented to the use of chiral organocatalysts immobilized onto solid supports (polystyrene, silica, and magnetic nanoparticles), but attention will also be paid to metal-catalyzed reactions involving immobilized tris(triazolyl)methyl [TTM] ligands and to novel photocatalytic processes based on cheap, non-toxic Bi2O3. ROBOCAT will be divided into six work packages: a) Novel immobilization strategies leading to more robust
heterogenized catalysts: Immobilized systems avoiding labile benzylic positions should be less prone to cleavage and have a longer useful life. Arene linkers (copolymerization), non-labile triazole linkers (CuAAC), alkylbenzene likers (Friedel-Crafts type), or simple alkyl linkers (cross-methatesis plus hydrogenation) will be explored; b) Understanding and preventing the deactivation of immobilized catalysts: Spectroscopic (NMR) and computational tools will be used to study the interaction between immobilized catalysts and reactants in the most common topologies [concentrated in reduced regions of space (dendron type) or uniformly distributed]; we will also submit selected organocatalytic species to harsh conditions to ascertain the main deactivation routes; c) Immobilized organocatalytic systems that avoid labile reaction intermediates: Enamine intermediates can suffer irreversible degradation under a variety of reaction conditions. Immobilized catalytic systems acting through non-covalent intermediates avoid this known deactivation pathway, thus being “robust-by-design” (e.g. Brønsted acids or H-bonding organocatalytic species); d) Metal complexes of immobilized TTM ligands that do not leach: We recently discovered that cationic Cu complexes of TTM ligands are suitable catalysts for carbene transfer reactions in flow; we
plan to explore the use of similar complexes for a whole range of transformations in batch and flow; e) Photocatalytic processes in flow involving Bi2O3: We recently reported on the use of Bi2O3 as a visible-light photocatalyst. We now plan to integrate this cheap and nontoxic material in photocatalytic flow processes; f) Intensification of processes based on immobilized catalytic species: Work in this area will hopefully contribute to the batch-to-flow transition in catalytic asymmetric synthesis. We aim at developing continuous flow versions of important catalytic enantioselective processes using supported catalysts. Attention will be paid to technological aspects of the flow catalytic process (development of functional microfluidic chips, in-line analysis tools, or design of a configurable reactor for multistep catalytic enantioselective synthesis in flow), and to the construction of the corresponding prototypes. High throughput experimentation methods will be used in ROBOCAT to speed-up discovery and optimization.
Ministerio de Ciencia e Innovación