Cu-Catalyzed Aerobic Oxidative Cyclizations of 3-N-Hydroxyamino-1,2-propadienes with Alcohols, Thiols, and Amines To Form alpha-O-, S-, and N-Substituted 4-Methylquinoline Derivatives

摘要

A one-pot, two-step synthesis of -O-, S-, and N-substituted 4-methylquinoline derivatives through Cu-catalyzed aerobic oxidations of N-hydroxyaminoallenes with alcohols, thiols, and amines is described. This reaction sequence involves an initial oxidation of N-hydroxyaminoallenes with NuH (Nu=OH, OR, NHR, and SR) to form 3-substituted 2-en-1-ones, followed by BrOnsted acid catalyzed intramolecular cyclizations of the resulting products. Our mechanistic analysis suggests that the reactions proceed through a radical-type mechanism rather than a typical nitrone-intermediate route. The utility of this new Cu-catalyzed reaction is shown by its applicability to the synthesis of several 2-amino-4-methylquinoline derivatives, which are known to be key precursors to several bioactive molecules.