Experimental and Computational Studies towards Chemoselective C−F over C−Cl Functionalisation: Reversible Oxidative Addition is the Key

Abstract

Catalytic cross‐coupling is a valuable tool for forming new carbon‐carbon and carbon‐heteroatom bonds, allowing access to a variety of structurally diverse compounds. However, for this methodology to reach its full potential, precise control over all competing cross‐coupling sites in poly‐functionalised building blocks is required. Carbon‐fluorine bonds are one of the most stable bonds in organic chemistry, with oxidative addition at C−F being much more difficult than at other C‐halide bonds. As such, the development of methods to chemoselectively functionalise the C−F position in poly‐halogenated arenes would be very challenging if selectivity was to be induced at the oxidative addition step. However, metal‐halide complexes exhibit different trends in reactivity to the parent haloarenes, with metal‐fluoride complexes known to be very reactive towards transmetalation. In this current work we sought to exploit the divergent reactivity of Ni−Cl and Ni−F intermediates to develop a chemoselective C−F functionalisation protocol, where selectivity is controlled by the transmetalation step. Our experimental studies highlight that such an approach is feasible, with a number of nickel catalysts shown to facilitate Hiyama cross‐coupling of 1‐fluoronapthalene under base free conditions, while no cross‐coupling with 1‐chloronapthalene occurred. Computational and experimental studies revealed the importance of reversible C−Cl oxidative addition for the development of selective C−F functionalisation, with ligand effects on the potential for reversibility also presented.

Structure–Reactivity Relationships of Buchwald-Type Phosphines in Nickel-Catalyzed Cross-Couplings

“…Few computational studies have included Buchwald phosphines in their analyses, and the focus was not on the ligand class specifically. 27,28 Nicasio and coworkers have structurally characterized dialkylterphenyl phosphines on Ni; these ligands share certain attributes with Buchwald-type ligands. 29−31 However, to the best of our knowledge, only one example exists in the literature of a structurally characterized Ni complex bound by a Buchwald phosphine: an off-cycle, cyclometalated adduct of BrettPhos formed during the cross-coupling of styrenyl epoxides.…”

“…While these examples illustrate that Buchwald ligands are capable of imparting desirable reactivity in Ni-catalyzed methodologies, little is known about their SRRs in Ni catalysis or how their unique structure and binding modes interface with Ni more generally. Few computational studies have included Buchwald phosphines in their analyses, and the focus was not on the ligand class specifically. , Nicasio and coworkers have structurally characterized dialkylterphenyl phosphines on Ni; these ligands share certain attributes with Buchwald-type ligands. − However, to the best of our knowledge, only one example exists in the literature of a structurally characterized Ni complex bound by a Buchwald phosphine: an off-cycle, cyclometalated adduct of BrettPhos formed during the cross-coupling of styrenyl epoxides . Given the scarcity of relevant studies, insights into the SRRs and mechanism of Buchwald and CataCXium P phosphines in Ni catalysis, along with access to well-defined Ni complexes bearing these ligands, would be of great value both in the discovery of new methodologies and in the further understanding/optimization of existing ones.…”

Structure-Reactivity Relationships of Buchwald-Type Phosphines in Nickel-Catalyzed Cross-Couplings

“…A handful of computational studies have included Buchwald phosphines in their analyses, but the focus was not on the ligand class specifically. 26,27 Nicasio and coworkers have structurally characterized dialkylterphenyl phosphines on Ni; these ligands share certain attributes with Buchwald-type ligands. [28][29][30] However, to the best of our knowledge, only one example exists in the literature of a structurally-characterized Ni complex bound by a Buchwald phosphine: an off-cycle, cyclometalated adduct of BrettPhos formed during the cross-coupling of styrenyl epoxides.…”

Magnetically Recoverable Nanoparticulate Catalysts for Cross-Coupling Reactions: The Dendritic Support Influences the Catalytic Performance

“…Among the recently developed heterogeneous catalysts for cross-coupling reactions there are various supported catalysts, including palladium loaded mesoporous silica [19][20][21][22][23], metal and graphene oxides [24][25][26], zeolites [27][28][29], and organic supports, such as polymers and dendrimers [30][31][32][33][34][35]. Dendrimers are one of the most versatile macromolecular platforms for the stabilization of catalytically active metal complexes or nanoparticles (NPs) because of their hyperbranched architecture [36].…”