Trifunctionalization of Iodoarenes via Sequence-Controlled Double Ortho C─H Acylations by Palladium/Norbornene Catalysis

Abstract

Herein we report a novel palladium/norbornene-catalyzed trifunctionalization reaction of ortho-unsubstituted iodoarenes by incorporating two distinct acyl groups at their ortho C─H positions and replacing the ipso-iodide with an alkenyl or aryl group. Notably, this transformation was enabled by the alkyl/aryl mixed anhydrides, which were utilized as dual acylation reagents by abstracting their central oxygen atom with electrophilic 2-chloro-4,6-dimethoxy-1,3,5-triazine. Mechanistic studies revealed that the alkyl-acyl unit of such an anhydride was employed for the first C─H alkyl-acylation, and in situ released aryl carboxylate anion was then rapidly activated with triazine chloride to provide an aryl–acyl electrophile for the second C─H acylation, thus enabling the trifunctionalization of iodoarenes by termination with an intermolecular Heck or intramolecular arylation reaction. In addition, the synthetic utility of this method is exemplified by the selective manipulation of carbonyl groups of the products.