Three-component reactions enable easy difluorinated-compound synthesis. Advances from 2014–2024 have been categorized as (a) radical, (b) difluorocarbene, (c) nucleophilic or electrophilic fluorine routes.
A visible-light-mediated selective difluoroalkylation of α-trifluoromethyl alkenes with difluoroalkylating reagents was developed. This protocol allowed the formation of gem-difluoroalkene difluoroacetates and trifluoromethylated difluoroacetamides.
A Cu-catalyzed cascade difluoroalkylation/5-endo cyclization/β-fluorine cleavage of ynones is reported, delivering α-monofluoroalkenyl cyclopentanones with high efficiency and stereoselectivity.
This review focuses on the progress in catalytic asymmetric difluoroalkylation to construction of difluoroalkylated stereogenic centers. Synthetic methods, active intermediates involved and asymmetric strategies applied were summarized.
A transition metal and external fluorine anion-free method has been developed for the efficient trifluoromethylation of sulfoxonium ylides with BrCF2CO2Et to afford α-trifluoromethyl ketones.