Enantiodivergent Radical Alkylation by Synergistic Lewis‐Acid‐Enzyme and Photoredox Catalysis
Abstract
Abstract Artificial metalloenzymes (ArMs) and photoenzymatic catalysis represent two cutting‐edge approaches to creating new enzyme reactivity. However, the potential of merging these two strategies remains underdeveloped for enantiocontrolled biotransformations. Herein, we develop a synergistic metalloenzymatic and photoredox catalysis platform to enable enantiodivergent radical alkylation of 2‐acyl imidazoles. Specifically, cupin proteins are redesigned to function as copper(II)‐based Lewis‐acid‐enzymes (LAses), which, in synergy with tripyridinyl‐ruthenium‐based photoredox catalysis, precisely control the generation, reactivity, and selectivity of abiological radicals, thereby unlocking non‐natural enzyme reactivity. Powered by protein engineering, repurposed photo‐LAses facilitate the green and efficient synthesis of diverse enantioenriched α‐chiral ketones in high enantioselectivity (both enantiomers accessible, up to 97% yield and 98.5:1.5 enantiomeric ratio [er]). Detailed mechanistic studies suggest a radical addition to the metalloenzymatic enolate pathway and explain the switched selectivity from dark to photoconditions.
Article Details
Authors (13)
Jiawei Zhang
Qiaoyu Zhang
State Key Laboratory of Physical Chemistry of Solid Surfaces and Fujian Provincial Key Laboratory of Theoretical and Computational Chemistry, College of Chemistry and Chemical Engineering
Ran Ge
Department of Chemical and Biochemical Engineering, College of Chemistry and Chemical Engineering, Key Laboratory for Synthetic Biotechnology of Xiamen City
Aokun Liu
Bin Chen
Zihan Zhang
Beibei Zhao
Jinhai Yu
State Key Laboratory of Coordination Chemistry, Chemistry and Biomedicine Innovation Center (ChemBIC), Frontier Interdisciplinary Science Research Center, School of Chemistry and Chemical Engineering
Yue Zhao
Lu Yu
Mingfeng Cao
Department of Chemical and Biochemical Engineering, College of Chemistry and Chemical Engineering, Key Laboratory for Synthetic Biotechnology of Xiamen City
Binju Wang
State Key Laboratory of Physical Chemistry of Solid Surfaces and Fujian Provincial Key Laboratory of Theoretical and Computational Chemistry, College of Chemistry and Chemical Engineering
Xiaoqiang Huang