Fluoroalkyl carbenes: versatile platforms for fluoroalkylated functional molecules

Fluoroalkyl carbenes have emerged as versatile and synthetically powerful reactive intermediates for the construction of structurally diverse fluorinated molecules, driven by their distinctive electronic properties and highly tunable reactivity. In particular, the interplay between the electrophilic carbenic center and the adjacent fluoroalkyl group enables unconventional bond-forming processes, including sequential and dual bond formation at the carbenic carbon, thereby providing unique disconnections for complex molecule construction. This review provides a comprehensive and critical analysis of the development of fluoroalkyl carbene chemistry, encompassing advances in carbene precursor design, generation strategies, and synthetic applications. The discussion is organized according to two interconnected reactivity modes: transformations centered at the carbenic carbon and processes involving cooperative reactivity between carbenic and fluorinated carbon atoms. A particular emphasis is placed on the evaluation of reaction scope and limitations, mechanistic insights, structure-reactivity relationships, stereochemical control, late-stage functionalization, and applications in the synthesis of biologically active complex molecules. Finally, current challenges and future opportunities are identified to guide the continued development of fluoroalkyl carbene chemistry. Reactions involving fluorocarbenes and difluorocarbenes are beyond the scope of this review.