Substrate-Directed Hydroacylation: Rhodium-Catalyzed Coupling of Vinylphenols and Nonchelating Aldehydes

We report a protocol for the hydroacylation of vinylphenols with aryl, alkenyl, and alkyl aldehydes to form branched products with high selectivity. This cross‐coupling yields α‐aryl ketones that can be cyclized to benzofurans, and it enables access to eupomatenoid natural products in four steps or less from eugenol. Excellent reactivity and high levels of regioselectivity for the formation of the branched products were observed. We propose that aldehyde decarbonylation is avoided by the use of an anionic directing group on the alkene and a diphosphine ligand with a small bite angle. COs with a local branch: A hydroacylation of vinylphenols with aryl, alkenyl, and alkyl aldehydes gave the branched products: α‐aryl ketone precursors to benzofurans. This cross‐coupling enabled access to eupomatenoid natural products in four steps or less from eugenol (see scheme; cod=1,5‐cyclooctadiene). Aldehyde decarbonylation was avoided by use of an anionic directing group on the alkene and a small‐bite‐angle diphosphine ligand.