Mariusz Zalewski, Sebastian Stecko
The α-amino ketone motif is fundamentally important in both synthetic organic and medicinal chemistry due to its frequent occurrence in biologically active molecules and its versatility as a building block in drug discovery. This significance has spurred the development of numerous innovative synthetic methodologies over recent decades. Advancements in transition-metal catalysis, organocatalysis, and contemporary photochemical approaches, including photoredox and dual metal/photoredox catalysis, have revolutionised the synthesis of complex molecular scaffolds. These modern strategies enable more efficient, selective, and sustainable access to valuable targets. Traditional methods for synthesising bifunctional molecules such as α-amino ketones, including functional group interconversions and C-N bond formation, are increasingly being replaced by direct C-C bond-forming protocols. These new approaches provide improved atom economy, greater functional group tolerance, and broader substrate scope, facilitating the rapid assembly of α-amino ketone frameworks. This review comprehensively compiles and critically evaluates synthetic protocols for α-amino ketones published since 2020, organised by disconnection strategy and transformation type. Special attention is given to pharmaceutical applications and mechanistic details. The review concludes by exploring future directions and the ongoing promise of α-amino ketone chemistry in synthetic methodology and drug discovery.