Mechanistic Study of Photochemical Aminocarbonylation of Alkyl Iodides Catalyzed by a Palladium Catalyst Using
Erik N A Sundén1,2, Staffan Karlsson1, Okky Dwichandra Putra3
1Early Chemical Development, Pharmaceutical Sciences, R&D, AstraZeneca, Gothenburg SE-43183, Sweden.
Abstract:
Aminocarbonylations are versatile reactions amenable to applications in convergent synthesis and isotope labeling. Herein, a mechanistic study of a previously reported visible-light-promoted aminocarbonylation of unactivated alkyl iodides is presented. This study combines in situ spectroscopy, computational chemistry, and organic chemistry techniques. A T1 excited-state promoted ligand dissociation in concert with an atom transfer radical addition was uncovered as a likely first step in the mechanism, instead of the usual three-center oxidative addition. Improvement in the reaction yield was achieved by optimizing the reaction based on mechanistic insights. This took the form of promoting a computationally uncovered cationic carbonylation pathway with the use of bidentate ligands.
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