Synthesis of N‐Arylated Lactam‐Type Iminosugars by Cascade Radical Cleavage of α‐Amino Carbonyl Compound and Intramolecular Amidation

A simple and efficient one-pot protocol has been developed for the synthesis of diverse N-arylated lactam-type iminosugars or 4-aminobutanamide derivatives through cascade radical cleavage of α-amino carbonyl compounds and intra-/intermolecular amidation reactions.

A metal-free method is developed for the synthesis of N-arylated lactam-type iminosugars using hydrogen peroxide (35% in water) as an oxidant. The reaction of various α-amino carbonyl compounds is performed in methanol, and the active methylene adjacent to the carbonyl group is rapidly removed to form a carboxylic acid as the key intermediate through a cascade radical cleavage reaction. Following an intramolecular amidation reaction, a series of N-arylated lactam-type iminosugars are prepared in satisfactory yields, providing an alternative protocol for the synthesis of such bioactive iminosugars. Additionally, several 4-aminobutanamide derivatives are obtained by intermolecular amidation of the carboxylic acid intermediate.

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