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).