C–F bond functionalizations via fluorinated carbenes

Abstract

Fluorinated carbenes play an important role in the synthesis of fluorine-containing molecules in organic synthesis. When carbon centered carbenes are installed with fluorides, this might influence the carbene reactivities due to the high electronegativity, low polarizability and small atomic radius of fluorine. A carbene center directly installing a fluorine will stabilize the reactive center thermodynamically, while fluorides next to the carbene carbon center will kinetically stabilize the carbene through inhibiting the 1,2-fluorine shift. On the other hand, late-stage modifications of fluorinated molecules have become one of the most challenging tasks because of the notorious inertness of the C–F bond and the potential for over-defluorination. In order to evaluate the diversities and bioactivities of fluorinated compounds, fluorinated carbenes have been recognized not only as a powerful tool for installing fluorinated groups into organic skeletons, but also potentially for simultaneous C–F bond functionalization. This feature article systematically summarizes the developments of alpha- and beta-fluorinated carbene transformations, and their consequent C–F functionalization in a cascade platform to construct a variety of high-value functionalized and complex molecules.