Palladium‐Catalyzed Aminocarbonylation of Aryl Halides with N,N‐Dialkylformamide Acetals

Abstract

AbstractWe developed a protocol for the palladium‐catalyzed aminocarbonylation of aryl halides using less‐toxic formamide acetals as bench‐stable aminocarbonyl sources under neutral conditions. Various aryl (including heteroaryl) halides reacted with N,N‐dialkylformamide acetals in the presence of a catalytic amount of tris(dibenzylideneacetone)dipalladium(0)‐chloroform adduct and xantphos to give the corresponding aromatic carboxamides at 90–140 °C without any activating agents or bases in up to quantitative chemical yield. This protocol was applied to aryl bromides, aryl iodides, and trifluoromethanesulfonic acid, as well as to relatively less‐reactive aryl chlorides. A wide range of functionalities on the aromatic ring of the substrates were tolerated under the aminocarbonylation conditions. The catalytic aminocarbonylation was used to prepare the insect repellent N,N‐diethyl‐3‐methylbenzamide as well as a synthetic intermediate of the dihydrofolate reductase inhibitor triazinate.