Oxidative Addition as the Selectivity-Determining Step in Gold(I)-Catalyzed Cross-Dehydrogenative Coupling of Arenes

The cross-dehydrogenative heterocoupling (hetero-CDC) of electron-poor and electron-rich arenes, catalyzed by an Au(I) complex and promoted by Ag(I) and a hypervalent iodine(III) oxidant such as PBX, delivers heterobiaryl products. Despite considerable advances, the mechanistic origins of chemoselectivity in this reaction─namely, why heterocoupling is favored over homocoupling─are not yet completely clarified. In this study, we address this gap using density functional theory (DFT). The reaction is generally understood to proceed through four key steps: (1) first C-H activation, (2) oxidation of the resulting Au(I)-aryl species by PBX, (3) second C-H activation, and (4) C-C reductive elimination. Our results reveal that the Au(I) oxidation step, long assumed to be mechanistically irrelevant, in fact plays a decisive role in establishing the observed chemoselectivity. We found that the first C-H activation of the electron-poor arene is only mildly endergonic, whereas that of the electron-rich arene is highly endergonic. This leads to a much lower overall Au(I) oxidation barrier for the former, causing the system to selectively activate the electron-poor arene first. Our calculations further show that oxidation of Au(I) by PBX proceeds through a mechanism that we term the double hypervalent-twist-assisted oxidative addition (DHTA-OA).