Palladium-Catalyzed Mono-α-arylation of Acetone at Room Temperature

The first examples of acetone mono‐α‐arylation at room temperature are described, enabled by use of a [Pd(cinnamyl)Cl]2/JosiPhos catalyst system. (Hetero)aryl chloride, bromide, and iodide electrophiles featuring or lacking ortho‐substitution, and comprising a range of functionalities (e.g., alkoxy, cyano, fluoro, trifluoromethyl, or alkenyl) and heteroaryl motifs (e.g., pyrrole, pyridine, isoquinoline, quinoline, quinaldine, (benzo)thiophene, benzothiazole, or benzodioxole) were successfully accommodated. Proof‐of‐principle experiments confirm that other (hetero)aryl methyl ketones can also be employed in such room temperature mono‐α‐arylations. The established substrate scope is the most extensive reported to date for acetone mono‐α‐arylation under any conditions, and more generally represents the first room temperature ketone mono‐α‐arylations employing a structurally diverse set of (hetero)aryl chlorides. Chill out: The first examples of acetone mono‐α‐arylation at room temperature are described. The substrate scope is the most extensive reported to date for acetone mono‐α‐arylation under any conditions, and represents the first room temperature ketone mono‐α‐arylations employing a diverse set of (hetero)aryl chlorides.