Synthesis of Quinolines via a Metal-Catalyzed Dehydrogenative N-Heterocyclization

Abstract

Efficient ruthenium-, rhodium-, palladium-, copper- and iridium-catalysed methodologies have been recently developed for the synthesis of quinolines by the reaction of 2-aminobenzyl alcohols with carbonyl compounds (aldehydes and ketones) or the related alcohols. The reaction is assumed to proceed via a sequence involving initial metal-catalysed oxidation of 2-aminobenzyl alcohols to the related 2-aminobenzaldehydes, followed by cross aldol reaction with a carbonyl compound under basic conditions to afford α,β-unsaturated carbonyl compounds. These aldehydes or ketones can be also generated in situ via dehydrogenation of the related primary and secondary alcohols. In the final step cyclodehydration of the α,β-unsaturated carbonyl compound intermediates gives quinolines. Good yields of quinolines were also obtained by reacting 2-nitrobenzyl alcohols and secondary alcohols in the presence of a ruthenium catalyst. Finally, aniline derivatives afforded also a useful access to quinolines by the reaction with 1,3-propanediol or 3-amino-1-propanol, or in a three-component reaction with benzyl alcohol and aliphatic alcohols.

Keywords: Alcohols; aldehydes; dehydrogenation; ketones; metal complexes; quinolones.