Nickel‐Catalyzed Csp²Csp³ Bond Formation by CarbonFluorine Activation

Abstract

We report herein a general catalytic method for Csp(2)-Csp(3) bond formation through C-F activation. The process uses an inexpensive nickel complex with either diorganozinc or alkylzinc halide reagents, including those with β-hydrogen atoms. A variety of fluorine substitution patterns and functional groups can be readily incorporated. Sequential reactions involving different precatalysts and coupling partners permit the synthesis of densely functionalized fluorinated building blocks.

Nickel‐Catalyzed Cross‐Coupling of Organolithium Reagents with (Hetero)Aryl Electrophiles

“…Additionally, nickel has also been found to activate very strong C−F bonds . Thus, the coupling of aromatic fluorides with organometallic compounds has been reported, although activated fluoroarenes or polyfluorinated aromatic substrates are usually employed . Some of these reactions suffer from competing isomerization of the alkyl coupling partners …”

Activation and Formation of Aromatic C–F Bonds

“…The Love group has also recently described an example of nickel-catalyzed Negishi cross-coupling of aryl fluorides with organozinc reagents to afford new C (sp 2 )-C(sp 3 ) bonds [117]. Employing a bench-stable NiCl 2 (PEt 3 ) 2 salt, a variety of polysubstituted fluoroaromatics may be accessed using either alkyl zinc halide reagents including those having β-hydrogen or diorganozinc reagents (Eq.…”

Copper‐Catalyzed Defluorinative Hydroarylation of Alkenes with Polyfluoroarenes

“…[8] Whereas the requirement of prior preparation of stoichiometric quantities of Grignard, organozinc and organolithium reagents along with the generation of metal salts waste in these processes inevitably significantly limits the functional group tolerance and synthetic efficiency. Besides, either directing groups were required to preinstall to facilitate ortho ‐selective C−F bond cleavage [8c–i] or 1,3‐butadiene and pentadiene as only valid alkylating reagents [8k–m] in these cases that could further significantly restrict their widespread synthetic applications. Therefore, the development of a new catalytic, non‐directing method, which has the capacity to circumvent these limitations, would be particularly appealing.…”