Ruthenium-catalysed synthesis of 2- and 3-substituted quinolines from anilines and 1,3-diols?

Organic & Biomolecular Chemistry Pub Date: 2010-11-22 DOI: 10.1039/C0OB00676A

Abstract

A straightforward synthesis of substituted quinolines is described by cyclocondensation of anilines with 1,3-diols. The reaction proceeds in mesitylene solution with catalytic amounts of RuCl3·xH2O, PBu3 and MgBr2·OEt2. The transformation does not require any stoichiometric additives and only produces water and dihydrogen as byproducts. Anilines containing methyl, methoxy and chloro substituents as well as naphthylamines were shown to participate in the heterocyclisation. In the 1,3-diol a substituent was allowed in the 1- or the 2-position giving rise to 2- and 3-substituted quinolines, respectively. The best results were obtained with 2-alkyl substituted 1,3-diols to afford 3-alkylquinolines. The mechanism is believed to involve dehydrogenation of the 1,3-diol to the 3-hydroxyaldehyde which eliminates water to the corresponding α,β-unsaturated aldehyde. The latter then reacts with anilines in a similar fashion as observed in the Doebner–von Miller quinoline synthesis.

Graphical abstract: Ruthenium-catalysed synthesis of 2- and 3-substituted quinolines from anilines and 1,3-diols
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