Enzymatic and Bio-Inspired Enantioselective Oxidation of Non-Activated C(sp ³)-H Bonds

The enantioselective oxidation of C-H bonds relies on two different approaches: the use of enzymes or bio-inspired transition metal catalysts. Both are powerful tools, as they transform ubiquitous C(sp ³)-H bonds into valuable oxygenated building blocks. However, the reaction remains a challenge in synthetic chemistry, continuously demanding efficient catalytic systems to improve substrate scopes. Optimization of site- and enantioselectivities in bio-catalytic systems is underpinned by protein engineering, while ligand design and medium effects play crucial roles in bio-inspired synthetic complexes. In this Short Review, recent advances in the field are described, focusing on reactions that target strong, non-activated C-H bonds. 1 Introduction 1.1 Enantioselective Catalytic C-H Oxidation in Nature and Bio-Inspired Systems 1.2 Biological C-H Oxidation Mechanism and Challenges for the Implementation of Chirality with Synthetic Catalysts 1.3 Bio-Catalytic C-H Oxidation Systems: From Microorganism to Engineered Enzymes 1.4 Mimicking Nature: The Bio-Inspired C-H Oxidation Approach 1.5 Origin of Enantioselectivity 2 Enantioselective C-H Oxidation of Non-Activated C-H Bonds 2.1 Hydroxylation at Non-Activated C-H Bonds by Bio-Catalytic Systems 2.2 Enantioselective C-H Lactonization with Enzymatic Systems 2.3 Oxidation at Non-Activated C-H Bonds by Synthetic Catalysts 2.4 Enantioselective Lactonization with Small-Molecule Catalysts 3 Conclusions.