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

Abstract

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.

Gold‐Catalyzed Cross‐Coupling Reactions: An Overview of Design Strategies, Mechanistic Studies, and Applications

“…Possible mechanisms for the heterocoupling of terminal alkynes and alkynyl hypervalent iodiner eagents triggered by Au-TA/AgOTs catalysts and phene ligands. [214] Similart ot he findings by Zhu et al, [102] the Ag I catalyst activatest he CÀHb ond of the cyclopropane, whereas the Au catalyst activates the alkyne coupling partner (Scheme 31). OxidativeAu-catalyzed1,2-difunctionalization of ethyleneand proposed mechanisms.…”

“…During the synergistic homogeneousA u/Pd-catalyzed cross-coupling reactions, the Au complex acts initially as ac onventional pphilic Lewis acid catalyst and then undergoes af acile Au/Pd transmetalation. [102] DFT calculations and experimental studies indicated that Ag I activates the CÀHb ond of electron-poor arenes, whereas the Au III intermediate activates the CÀHb ond [200] of the electron-richa rene coupling partner. In 2015, Larrosa and co-workers developed Au I /Au III -catalyzed synthesis of unsymmetrical biarylst hrough a cross-dehydrogenative coupling assisted by Ag additives.…”

“…[102] Scheme31. These reagents have also helped to disregard the earlier assumption that Au catalysis is inefficient for promoting CÀCc ross-coupling reactions.…”

“…[53][54][55][56] Compared with the advances in heterogeneous goldc atalysis, the field of homogeneous gold catalysis startedt og row only in the first decade of the 21st century.O ver the past two decades, homogeneousg old catalysis has emerged as an eminent synthetic methodology.T he progress in the syntheses and applications of Au catalysts, related reaction mechanisms, and the future prospects of traditional Au I -catalyzed reactions have been reviewed by the groups of Hashmi, [57][58][59][60][61][62] Fürstner, [63,64] To ste, [65] Echavarren, [66][67][68] and others. [92,93,102,[94][95][96][97][98][99][100][101] Some reactions are best catalyzed when multiple Au centers are available to activate the reactants and/or intermediates. Being ah eavy atom with a5 d 10 6s 1 electronic configuration, the relativistic effects strongly affect the dynamics of the valence electrons of Au.…”

Advances and Prospects in Gold‐Catalyzed C−H Activation

“…Zhu et al . designed an operationally simple and highly selective Au/Ag bimetallic‐catalyzed cross‐dehydrogenative biaryl coupling between pyrazoles 140 and fluoroarenes 141 (Scheme ) . From the theoretical calculations they proposed that silver acetate is the actual catalyst for C−H activation of electron‐poor arenes, rather than the previously reported gold(I)‐catalyzed process.…”