The Directing Group: A Tool for Efficient and Selective C–F Bond Activation

Abstract

C−F bond activation is currently considered to be "a hot topic" in many different but interconnected fields of research, due to its inherent inertness and unique properties. While considerable progress has been made in this particular field of research, activating strong bonds, such as the C−F bond, continues to be a challenge. Because polyfluorinated compounds are commercially available, the functionalization of C−F bonds has been extensively studied for preparing partially fluorinated compounds, some of which are biologically active and are used as functionalized materials. However, chemo-and regioselective methods are still required to prepare useful partially fluorinated compounds. In addition, a new strategy for the activation of a C−F bond in less reactive monofluorinated compounds remains a need. Directed strategies have been extensively used in C−H bond activation chemistry to achieve high efficiency as well as a high regioselectivity. On the other hand, a directed strategy that is applicable to the activation of various unreactive bonds, such as C−O, C−N, C−F, and others is still needed, compared with directed C−H bond activation. In this Review, we focus on the directed strategy for the activation of inert C−F bonds.

Transition-Metal-Free, Site-Selective C–F Arylation of Polyfluoroarenes via Electrophotocatalysis

“…Due to the synthetic simplicity and efficiency, direct activation and functionalization of C–F bonds of commercially available fluorinated molecules is a promising strategy to prepare desired organofluorines. Over the past decades, developing green and general synthetic methods for organofluorines, especially polyfluorobiaryls, has made important progress . And most successes thus far have relied on transition metal catalysis, , i .…”

Selective Nickel-Catalyzed Hydrodefluorination of Amides Using Sodium Borohydride

“…In this study, we applied a nickel catalyst system to hydrodefluorination that is both site-selective and proceeds under mild reaction conditions using relatively benign reagents. Based on our previous studies on C–F activations using nickel(0), − , we demonstrate the use of sodium borohydride as the source of hydrogen, enabling ortho-selective defunctionalization. This is applicable to highly fluorinated substrates, enabling the synthesis of new fluorinated or deuterated substitution patterns in substrates along with tolerance for a wide variety of functional groups on both sides of the amide.…”

Nickel‐Catalyzed Carboxylation of Aryl C−F Bonds with CO2

“…To the best of our knowledge, there is no report about direct aryl C−F bond carboxylation with CO 2 . We envisioned the possibility of direct carboxylation of aryl C−F bond enabled by chelation assistance to realize chemodivergent C−F activation over C−H activation [19] . If success, the development of highly selective C−F bond carboxylation with CO 2 is meaningful for sustainable chemistry, because both CO 2 and hydrofluorocarbon (HFC) are recognized to be greenhouse gases [20] .…”

“…We envisioned the possibility of direct carboxylation of aryl CÀ F bond enabled by chelation assistance to realize chemodivergent CÀ F activation over CÀ H activation. [19] If success, the development of highly selective CÀ F bond carboxylation with CO 2 is meaningful for sustainable chemistry, because both CO 2 and hydrofluorocarbon (HFC) are recognized to be greenhouse gases. [20] Besides, this approach will also provide us an opportunity to synthesize partially fluorinated carboxylation compounds, which are otherwise difficult to be prepared.…”