Ruthenium-catalysed C-alkylation of 1,3-dicarbonyl compounds with primary alcohols and synthesis of 3-keto-quinolines

Abstract

The mono-alkylation of 1,3-diketones using alcohols is possible in the presence of catalytic amounts of Ru(CO)(PPh₃)₃HCl and 10% mol of the Hantzsch ester. The borrowing hydrogen process between the catalyst and the dihydropyridine/pyridine couple prevents the common double alkylation of the Knoevenagel adduct without the need of stoichiometric reducing agents or sacrificial nucleophiles. The reaction was applied to the synthesis of a lactone intermediate for the preparation of the anti-obesity drug orlistat. Moreover, under the same Ru catalysis, a Friedländer reaction occurred with o-amino benzyl alcohols giving access to different 3-keto-substituted quinolines.