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Iterative Arylation of Itaconimides with Diazonium Salts through Electrophilic Palladium Catalysis: Divergent β‑H-Elimination Pathways in Repetitive Matsuda–Heck Reactions

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journal contribution
posted on 16.04.2019, 00:00 by Nastja Riemer, Michael Shipman, Pablo Wessig, Bernd Schmidt
N-Arylitaconimides, accessible from maleic anhydride, anilines, and paraformaldehyde, react with arene diazonium salts in Pd-catalyzed Matsuda–Heck arylation to the pharmacologically relevant E-configured 3-arylmethylidene pyrrolidine-2,5-diones (also known as arylmethylidene succinimides) through exo-selective β-H-elimination. The coupling proceeds at ambient temperature with the simple and easy-to-handle precatalyst Pd-II–acetate under ligand- and base-free conditions. Notable features are high isolated yields, regio- and stereoselectivities, and short reaction times. In a comparative investigation, aryl iodides, bromides, and triflates were shown to be inferior coupling reagents in this reaction. The 3-arylmethylidene pyrrolidine-2,5-diones undergo second Matsuda–Heck coupling, which proceeds via endo-selective β-H-elimination to give diarylmethyl-substituted maleimides as coupling products. These products can also be accessed in one flask by sequential addition of different arene diazonium salts to the starting itaconimide. The potential of 3-arylmethylidene succinimides as photoswitches was tested. Upon irradiation of the E-isomer at 300 nm, partial isomerization to the Z-isomer (E/Z = 65:35 in the photostationary state) was observed. The isomerization was found to be nearly completely reversible by irradiating the mixture at 400 nm.