Hybrid Chemo-Enzymatic Heterogeneous Catalyst for Green and Enantioselective Hydroxylation.

The implementation of green chemistry principles in catalysis is essential for sustainable production of specialty chemicals, where selectivity and efficiency are paramount. Unspecific peroxygenases (UPOs) have emerged as promising biocatalysts for enantioselective C-H oxyfunctionalization reactions, using hydrogen peroxide (H2O2) as the sole oxidant. However, the instability of UPOs toward H2O2 and the nonsustainable production of this reagent remain key challenges. Herein, we report the design of a hybrid chemo-enzymatic heterogeneous catalyst integrating an Au-Pd-based material with the PaDa-I UPO mutant, using an "enzyme-in-a-cage" immobilization strategy. This bifunctional system enables controlled in situ H2O2 generation directly from H2 and O2, coupled with the enantioselective hydroxylation of ethylbenzene in a single reactor. The catalyst exhibits high activity, excellent enantioselectivity (ee = 97.7%), and stability without enzyme leaching. This approach offers a robust and sustainable platform for one-pot chemo-enzymatic cascade reactions in chemical synthesis.