Experimental and computational journey on transition-metal-catalyzed CH functionalization with fluorinated π-systems

Abstract

Transition-metal-catalyzed direct CH functionalization utilizing unsaturated hydrocarbons have been established as a robust strategy to increase molecular complexity without the need of substrate prefunctionalization. Especially, the CH functionalization mode involving several innovative fluorinated π-systems, including difluorinated alkynes, cyclopropenes as well as allenes, has been intensively investigated in recent years, which not only enriches the new connotation of this hot topic but also opens up a new field of vision on how to promote organic integration of transition-metal-catalyzed CH functionalization with fluorine chemistry, even with pharmaceutical science. Induced by their inherently distinctive fluorine effects, these fluorine-functionalized π-compounds have efficiently expanded the scope of the CH functionalization reactions by introducing enhanced chemoselectivity, regioselectivity and stereoselectivity, which greatly enriches the connotation of CH activation chemistry, and ultimately, promoting the development of organic chemistry. In this review, we provide a comprehensive summary of the latest progress in transition-metal-catalyzed CH functionalization with recently developed fluorinated π-systems since 2017, with particular focus on a rational analysis on reaction development and the elucidation of their mechanisms revealed by integrating computational investigation with experimental data. Finally, several challenges and future perspectives on this topic are also discussed. We believe that this review can offer a profound insight into the synergistic combination of experimental and theoretical studies for the future design of unexplored CH functionalization reaction modes driven by diverse CH activation substrates and fluorinated π-partners. This, in turn, is expected to spur the discovery and development of innovative reaction paradigms in this field of transition-metal-catalyzed CH activation/functionalization.