Chemoselective oxidative N-debenzylation of aryl halogenated amines using the Laccase LAC97/TEMPO system

Abstract

The N-debenzylation of aryl-halogenated amines using the Laccase LAC97/TEMPO system is reported, demonstrating selective N-debenzylation with no dehalogenation of the phenyl ring, which is observed with conventional debenzylation methods such as palladium-catalysed hydrogenation. This reaction was performed under ambient conditions in acidic buffer with 5 % DMSO as co-solvent in an open-to-air vessel. The versatility and robustness of the system was demonstrated on substrates harbouring different halogen moieties. The limitations of the Laccase LAC97/TEMPO system were also studied, highlighting the formation of by-products due to overoxidation on selected substrates. A series of substrates with various halogens were studied. High conversion (78–90 %) in 6 h and full conversion was achieved within 24 h using HPLC to monitor the reaction. Overall, this system is presented as a chemoselective N-debenzylation alternative for aryl-halogenated substrates.