Regioselective Ortho‐Arylation of Polyhalo‐Substituted (Hetero)Aryl Tosylates Using an Integrated Continuous Flow/Batch Protocol

Abstract The regioselective ortho arylation of polyhalo‐substituted (hetero)aryl tosylates has been investigated employing an integrated continuous flow/batch protocol. The regioselective ortho metalation of (hetero)aryl tosylates using n ‐BuLi and ZnCl 2 was effectively achieved using continuous flow chemistry in a short residence time of 10.92 s, without removal of the tosyloxy group. The Pd‐catalyzed Negishi coupling reactions of various (hetero)aryl iodides with the resulting arylzinc species proceeded readily at room temperature in 31% to 98% yields. Finally, the method was applied to the synthesis of perampanel in four linear steps, with an overall yield of 43%. magnified image