Hybrid Organometallic and Enzymatic Tandem Catalysis for Oxyfunctionalisation Reactions

Domestici, C.; Wu, Y.; Hilberath, T.; Alcalde, Miguel; Hollmann, F.; Macchioni, Alceo

doi:10.1002/cctc.202201623

Hybrid Organometallic and Enzymatic Tandem Catalysis for Oxyfunctionalisation Reactions

Title

Hybrid Organometallic and Enzymatic Tandem Catalysis for Oxyfunctionalisation Reactions

Author

Domestici, C. (University of Perugia)
Wu, Y. (TU Delft BT/Biocatalysis)
Hilberath, T. (TU Delft BT/Biocatalysis)
Alcalde, Miguel (IATA-CSIC)
Hollmann, F. (TU Delft BT/Biocatalysis)
Macchioni, Alceo (University of Perugia)

Date

2023

Abstract

Unspecific peroxygenases (UPOs) are promising biocatalysts for oxyfunctionalisation reactions, owing to their simplicity of handling, stability and robustness. A limitation of using UPOs on a large scale is their deactivation in the presence of even rather modest concentrations of H₂O₂, requiring a constant and controlled supply of low amount of H₂O₂. Herein, we report an organometallic complex [Cp*Ir(pica)NO₃] {pica=picolinamidate=κ²-pyridine-2-carboxamide ion (−1)} 1 capable of efficiently regenerating FMNH₂ from FMN (TOF=350 h⁻¹, 298 K), driven by NaHCOO; FMNH₂, in turn, spontaneously reacts with O₂ leading to H₂O₂. After having studied the compatibility of 1 with the UPO from Agrocybe aegerita (rAaeUPO PaDa-I) and individuated the best experimental conditions, we applied such a hybrid catalytic tandem in some hydroxylation, epoxidation and sulfoxidation reactions. Best performances were obtained by using a 1/rAaeUPO molar ratio of 50. TONs for the biocatalyst of up to 18933 were obtained for the transformation of ethylbenzene derivatives into (R)-1-phenylethanols (ee>99 %). 1/rAaeUPO was found to oxidise also cis-methyl styrene (TON=13488), leading exclusively (1R,2S)-cis-methyl styrene oxide (ee>99 %), cyclohexane (TON=1634) and thioanisole (TON=1369).