Intramolecular Pd(0)-Catalyzed Reactions of (2-Iodoanilino)- aldehydes: A Joint Experimental?Computational Study

摘要

An extensive joint experimental−computationalndensity functional theory (DFT) study has been carried out tongain insight into the factors that control the chemoselectivity (i.e.,nacylation vs α-arylation reaction) of palladium-catalyzed cyclizationsnof (2-iodoanilino)-aldehydes. To this end, the nature of thentethers joining the aniline nitrogen and the aldehyde moiety,ndifferent palladium precatalysts and reaction conditions (base and temperature), as well as different additives (mono- andnbidendate ligands) has been explored. The adequate selection of these variables allows for the control of the selectivity of thenprocess. Thus, (2-iodoanilino)-aldehydes generally lead to the formation of nucleophilic addition derived products whennCs2CO3/Et3N is used as base. In contrast, the use of stronger bases like KtOBu (in the presence of PhOH) mainly forms α-narylation reaction products. The different reaction pathways leading to the experimentally observed reaction products have beennstudied by means of computational tools.