Navigating the Radical Oxo‐Functionalization of Alkenes Toward Ketones

Abstract

Ketones are ubiquitous structural motifs in pharmaceuticals, natural products, agrochemicals, and functional materials, as well as indispensable building blocks in organic synthesis. This outlines the design of efficient carbonyl‐forming strategies a crucial target in methodology development. Alongside classical textbook polar, two electron (2e – ) approaches, the so‐called single‐electron (1e – ) logic has established itself as the contemporary method of choice for direct, de novo construction of structurally complex ketones from simple commodity chemicals, under mild conditions. In this context, radical 1,2‐oxo‐functionalization of alkenes represents a valuable, practical platform to rapidly enhance molecular complexity via one‐pot difunctionalization of “flat” feedstock chemicals, thereby avoiding tedious isolation and purification of intermediates en route to target ketones. This Review surveys recent advances in radical alkene oxo‐functionalization, with a particular emphasis on methodologies enabled by thermal, transition metal‐catalyzed, photochemical, and electrochemical activations. The mechanistic principles governing the finely‐tuned orchestration of sequential vicinal CX (with X = carbon or heteroatom) and CO bond formations—including single‐electron transfer, hydrogen atom transfer, and radical polar crossover—are discussed alongside the diverse carbonyl oxygen atom sources employed, such as tert ‐butyl hydroperoxide (TBHP), dimethyl sulfoxide (DMSO), and molecular oxygen (O 2 ).