Thermal Nickel-Catalyzed Carbon–Oxygen Cross-Coupling of (Hetero)aryl Halides with Alcohols Enabled by the Use of a Silane Reductant Approach

Herein, we disclose a highly efficient thermal Ni-catalyzed C–O cross-coupling of aryl halides with primary and secondary alcohols, without the need for photo- or electrocatalysis. The protocol is simple and has a wide substrate scope, particularly for challenging electron-rich aryl halides. Additionally, this methodology has been successfully applied to the late-stage functionalization of drugs and natural products, as well as the synthesis of pharmaceuticals such as pramoxine and the delamanid key intermediate. Preliminary mechanistic studies suggest the in situ generation of active Ni(I) species from inexpensive NiBr2-bipyridine and PhSiH3.