Design of 3D-Printed Heterogeneous Reactor Systems To Overcome Incompatibility Hurdles when Combining Metal and Enzyme Catalysis in a One-Pot Process.

Combining chemo- and biocatalysis enables the design of novel economic and sustainable one-pot processes for the preparation of industrial chemicals, preferably proceeding in water. While a range of proofs-of-concept for the compatibility of such catalysts from these two different "worlds of catalysis" have recently been demonstrated, merging noncompatible chemo- and biocatalysts for joint applications within one reactor remained a challenge. A conceptual solution is compartmentalization of the catalytic moieties by heterogenization of critical catalyst components, thus "shielding" them from the complementary noncompatible catalyst, substrate or reagent. Exemplified for a one-pot process consisting of a metal-catalyzed Wacker oxidation and enzymatic reduction as noncompatible individual reactions steps, we demonstrate that making use of 3D printing of heterogeneous materials containing Cu as a critical metal component can overcome such incompatibility hurdles. The application of a 3D-printed Cu-ceramic device as metal catalyst component allows an efficient combination with the enzyme and the desired two-step transformation of styrene into the chiral alcohol product with high overall conversion and excellent enantioselectivity. This compartmentalization concept based on 3D printing of heterogenized metal catalysts represents a scalable methodology and opens up numerous perspectives to be used as a general tool also for other related chemoenzymatic research challenges.