Cooperative Au/Ag Dual-Catalyzed Cross-Dehydrogenative Biaryl Coupling: Reaction Development and Mechanistic Insight

An
operationally simple and highly selective Au/Ag bimetallic-catalyzed
cross-dehydrogenative biaryl coupling between pyrazoles and fluoroarenes
has been developed. With this reaction, a wide range of biheteroaryl
products can be obtained in moderate to good yields with excellent
functional group compatibility. The exact role of silver salts, previously
overlooked in most gold-catalyzed transformations, has been carefully
investigated in this biaryl coupling. Insightful experimental and
theoretical studies indicate that silver acetate is the actual catalyst
for C–H activation of electron-poor arenes, rather than the
previously reported gold­(I)-catalyzed process. An unprecedented Au/Ag
dual catalysis is proposed, in which silver­(I) is responsible for
the activation of electron-poor fluoroarenes via a concerted metalation–deprotonation
pathway, and gold­(III) is responsible for the activation of electron-rich
pyrazoles via an electrophilic aromatic substitution process. Kinetic
studies reveal that ArFnAu­(III)-mediated C–H activation
of pyrazoles is most likely the rate-limiting step.