Asymmetric Oxidation Reactions in Organic Synthesis

Asymmetric oxidation reactions occupy a central role in modern organic synthesis, enabling the introduction of oxygen functionality with precise control over stereochemistry. By harnessing chiral catalysts—whether metal complexes, organocatalysts or enzymes—chemists can achieve high enantioselectivity in transformations such as epoxidation, hydroxylation, allylic oxidation and Baeyer–Villiger oxidation. Advances in ligand design, mechanistic understanding and photochemical activation have broadened the scope of accessible substrates, while biocatalysis offers mild conditions and remarkable selectivity through engineered monooxygenases and peroxygenases. These methods underpin the efficient assembly of pharmaceuticals, agrochemicals and complex natural products, reducing waste and improving atom economy. Recent breakthroughs have extended asymmetric oxidation to challenging substrates, including unactivated C–H bonds and heteroatom centres, underscoring the global significance of these processes for sustainable, stereocontrolled synthesis.

Research from Nature Portfolio

Recent studies have demonstrated a photoinduced thia-Baeyer–Villiger-type oxidation of sulfoxides to sulfinic esters using an iron porphyrin catalyst under ultraviolet irradiation in the presence of tert-butyl hydroperoxide. This transformation proceeds with high chemoselectivity, avoiding overoxidation to sulfones, and offers a mild, stepwise approach to functionalise sulphur compounds. Mechanistic investigations combining experimental data and computational analysis have clarified the radical and peroxyl intermediates involved, paving the way for biomimetic routes to important biphenyl derivatives.

Asymmetric Oxidation Reactions in Organic Synthesis publication trend

The graph below shows the total number of articles in asymmetric oxidation reactions in organic synthesis across all publications each year (not limited to Nature Index journals).

Technical terms

Enantioselectivity: preferential formation of one enantiomer over its mirror image in a chemical reaction.

Baeyer–Villiger oxidation: conversion of ketones into esters or lactones through insertion of an oxygen atom adjacent to a carbonyl group.

Kinetic resolution: selective reaction of one enantiomer in a racemic mixture to afford separation of enantiomers based on reaction rates.

Monooxygenase: enzyme that catalyses the incorporation of one oxygen atom from molecular oxygen into organic substrates.

References

1. The Kornblum DeLaMare rearrangement in natural product synthesis: 25 years of innovation. Natural Product Reports (2024).
2. Biocatalytic Conversion of Cyclic Ketones Bearing α‐Quaternary Stereocenters into Lactones in an Enantioselective Radical Approach to Medium‐Sized Carbocycles. Angewandte Chemie International Edition (2018).
3. Post-functionalization of dibenzothiophene to functionalized biphenyls via a photoinduced thia-Baeyer-Villiger oxidation. Nature Communications (2020).
4. Cu( ii )/SPDO complex catalyzed asymmetric Baeyer–Villiger oxidation of 2-arylcyclobutanones and its application for the total synthesis of eupomatilones 5 and 6. Chemical Science (2022).