Given that alcohol is the most frequent functional group found in bioactive natural products and marketed drugs, and is versatile synthetic intermediate with a middle level of carbon oxidation state with massive synthetic applications, accessing alcohol-containing architectures via difunctionalization of alkenyl alcohols is highly fascinating.

In addition to well-known challenges for dicarbofunctionalization of unactivated alkenes, the main obstacles to develop difunctionalization reactions with the alcohol as the native directing group are their low binding affinity for transition metals, and their conformational flexibility relative to more commonly used native functional group, such as acid and amide.

In a study published in Chem Catalysis, Prof. WANG Peng and colleagues at Shanghai Institute of Organic Chemistry of the Chinese Academy of Sciences reported a Ni(II)-catalyzed 1,2-arylalkylation and 1,2-alkenylalkylation of alkenyl alcohols in a regioselective manner with an alcohol group as the native directing group.

Researchers demonstrated a Ni-catalyzed 1,2-hydroxylarylation of homoallyl alcohols enabled by a bulky β-diketone ligand. They found that bulky β-diketone ligand (Amacac) plays a crucial role in enhancing the reactivity and suppressing many competitive processes. 

The obtained complex of Ni₂(Amacac)₄(EtOH)₂ showed high catalytic reactivity (88% nuclear magnetic resonance yield), which indicates that the β-diketone coordinated nickel complex is probably the active catalyst precursor. 

“This bulky β-diketone ligand could act as either an LL type or LX type of ligand, depending on the chemical environment of Ni center. This offers a means to fine-tune the Lewis acidity of catalyst, enhancing the reactivity of the catalyst in several elementary steps,” explained Prof. WANG.

This protocol accommodates a wide range of substrates with excellent functional group tolerance, paving the way for the efficient preparation of alcohol-containing synthetic intermediates and bioactive compounds.