Design of 3D-printed heterogeneous reactor systems to overcome incompatibility hurdles when combining metal and enzyme catalysis in a one-pot process

N. Salitra, J. Gurauskis, H. Gröger, “Design of 3D-printed heterogeneous reactor systems to overcome incompatibility hurdles when combining metal and enzyme catalysis in a one-pot process, Angew. Chem. Int. Ed. (2024), DOI: 10.1002/anie.202316760.

Merging chemo- and biocatalysis in one-pot processes in water has emerged towards a valuable synthetic concept over the last 15 years, which makes an efficient and at the same time sustainable synthesis of a broad range of chiral compounds for in particular pharmaceuticals synthesis possible. Key advantages are the complete avoidance of intermediates, resulting in a decreased or full prevention of organic solvent utilization and consequently in much less amount of waste. Furthermore, unit operation numbers and steps are much more simplified, which also leads to improved economics. While in pioneer work the direct compatibility of chemo- and biocatalysts in water was demonstrated for various examples, within the last decade a major focus was on finding solutions also for such combinations, which lack a compatibility of chemo- and biocatalysts. Among developed solutions, various breakthrough achievements trace back to a concept of nature, namely compartmentalization. Impressive achievements in this field were made via micellar catalysis, developed by the Lipshutz group and jointly further developed with Gallou and his Novartis team. Besides this nano-compartmentalization, membrane-based separation was a further developed tool as exemplified by our group for a combination of a Wacker-oxidation and subsequent biotransformations (reduction, transamination and reductive amination) of the in situ-formed ketones, thus leading to chiral alcohol and amines with high enantioselectivity. In further work by various other groups, the suitability of this PDMS-thimble systems for lab scale applications under combination of a broad range of chemocatalytic and biocatalytic transformations was shown. However, such PDMS-thimbles face a challenge for scale-up and recycling (which is simply illustrated by the fact that by scaling up a process the surface-to-volume ratio becomes more unfavorable, which then hampers this solution based on such a 2D-membrane). Accordingly, we became interested in further compartmentalization strategies, which at the same time gives a perspective for a technical solution in the future. In this contribution, we report on the 3D-printing of heterogeneous catalysts, which can be tailor-made for each reactor system also on scale, thus enabling a combination with non-compatible enzymes in one-pot processes as well as a highly simple recovery and recycling.

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