Direct Deoxyarylation of Non-Activated Alcohols

The formation of carbon-carbon bonds constitutes the most critical fundamental reaction in organic synthesis. Although synthetic chemists have achieved significant advancements in the cross-coupling of stable C(sp³) substrates, such as aliphatic carboxylic acids and alkyl halides, cost-effective, accessible, and versatile sources of alkyl groups, specifically alcohols, remain underutilized. The direct deoxygenation of alcohols under mild circumstances presents a significant challenge in organic synthesis, primarily due to the absence of an efficient mechanism for the direct activation of C─O bonds. Consequently, there is an imperative necessity for chemists to devise a multifaceted approach for the cross-coupling of alcohols. This study aims to utilize neutral diphenylboron radicals as hydroxyl activation agents to directly activate the carbon-oxygen bonds of prevalent alcohols, thereby generating alkyl radicals, which are subsequently involved in nickel-catalyzed arylation processes. Both free alcohols and aryl bromides, which are easily accessible compounds, can serve as coupling partners directly without requiring pre-functionalization. The direct arylation process of alcohols exhibits a broad substrate scope, as demonstrated by the subsequent arylation of several structurally intricate natural compounds and pharmaceuticals.