Abstract
The first Ru(II)-catalyzed arylation of substrates without a directing group was recently developed. Remarkably, this process only worked in the presence of a benzoate additive, found to be crucial for the oxidative addition step at Ru(II). However, the exact mode of action of the benzoate was unknown. Herein, we disclose a mechanistic study that elucidates the key role of the benzoate salt in the C–H arylation of fluoroarenes with aryl halides. Through a combination of rationally designed stoichiometric experiments and DFT studies, we demonstrate that the aryl–Ru(II) species arising from initial C–H activation of the fluoroarene undergoes cyclometalation with the benzoate to generate an anionic Ru(II) intermediate. The enhanced lability of this intermediate, coupled with the electron-rich anionic Ru(II) metal center renders the oxidative addition of the aryl halide accessible. The role of an additional (NMe4)OC(CF3)3 additive in facilitating the overall arylation process is also shown to be linked to a shift in the C–H pre-equilibrium associated with benzoate cyclometalation.
Highlights
The polyfluorobiphenyl unit is a recurrent building block found as a structural component in drugs,1a−c agrochemicals,1e,f and numerous functional materials1g−m such as organic light-emitting diodes (OLEDs)1j and liquid crystals.1k,i cross-coupling methods can be applied to access these biaryl moieties,[2] C−H arylation strategies have been acknowledged as a more sustainable alternative strategy to selectively form aryl−aryl bonds.[3]
Our experiments demonstrate that aryl− Ru(II) species such as Ru1b, which are inert toward oxidative addition with aryl bromides 2, can undergo cyclometalation with the benzoate salt to form an anionic Ru(II) intermediate that is highly reactive toward oxidative addition and is essential to the reactivity of the system
The specific requirement for a benzoate salt for the reaction to proceed led us to hypothesize that the benzoate may be undergoing ortho-C−H activation as its mode of action
Summary
The polyfluorobiphenyl unit is a recurrent building block found as a structural component in drugs,1a−c agrochemicals,1e,f and numerous functional materials1g−m such as organic light-emitting diodes (OLEDs)1j and liquid crystals.1k,i cross-coupling methods can be applied to access these biaryl moieties,[2] C−H arylation strategies have been acknowledged as a more sustainable alternative strategy to selectively form aryl−aryl bonds.[3]. Our group expanded upon the range of transition metal catalysts able to promote this particular type of coupling.[7] The arylation of fluoroarenes with aryl halides occurred with a Ru(II) catalyst, [Ru(tBuCN)6][BF4]2, aided by (NMe4)OPiv and (NMe4)(4-FC6H4CO2) cocatalysts and (NMe4)OC(CF3)[3] base in t-BuCN (Scheme 1a). This methodology is the first Rucatalyzed C−H arylation process operating without the need for a directing group in the arene. We have recently proposed that the mechanism of the Ru(II)-catalyzed C−H arylation of N-chelating substrates with aryl (pseudo)halides involves a bis-cyclometalated Ru(II) species as the key intermediate required for oxidative addition to occur.[8]
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