Fluorinated organic compounds, owing to their unique physicochemical properties, have found extensive applications in pivotal fields including pharmaceuticals, agrochemicals, and materials science. Notably, enantiomerically pure α-carbonyl monofluorinated compounds containing chiral centers have garnered considerable attention in drug discovery in recent years, owing to their crucial role in regulating biological activity and modulating molecular configuration. This review systematically summarizes the major synthetic strategies for constructing such structures over the past decade, which are categorized into three aspects: (1) achievement of asymmetric fluorination through C—F bond formation; (2) asymmetric formation of C—C bonds utilizing fluorinated nucleophilic or electrophilic building blocks; (3) emerging radical and synergistic catalysis modes. By critically analyzing the electronic and steric effects of fluorine atoms on reactivity and stereoselectivity, we assess the substrate scope and inherent limitations of existing methodologies, aiming to provide rational design principles for the future synthesis of monofluorinated chiral centers.

Key words: α-fluoroketone, chiral center, asymmetric fluorination, fluorine-containing building