Dehydrogenative Synthesis of Imines from Alcohols and Amines Catalyzed by a Ruthenium N-Heterocyclic Carbene Complex

A new method for the direct synthesis of imines from alcohols and amines is described where hydrogen gas is liberated. The reaction is catalyzed by the ruthenium N-heterocyclic carbene complex [RuCl2(IiPr)(p-cymene)] in the presence of the ligand DABCO and molecular sieves. The imination can be applied to a variety of primary alcohols and amines and can be combined with a subsequent addition reaction. A deuterium labeling experiment indicates that the catalytically active species is a ruthenium dihydride. The reaction is believed to proceed by initial dehydrogenation of the alcohol to the aldehyde, which stays coordinated to ruthenium. Nucleophilic attack of the amine affords the hemiaminal, which is released from ruthenium and converted into the imine. ■ INTRODUCTION The imine is an important functional group in organic chemistry and is often used for the synthesis of amines by various addition reactions. Imines are usually prepared by condensation of an aldehyde or a ketone with a primary amine but can also be formed by oxidation of secondary amines, oxidative condensation of primary amines, and the aza-Wittig reaction. In addition, imines can be prepared by coupling of alcohols and amines in the presence of an oxidant. Recently, new dehydrogenative reactions have been developed for the coupling of alcohols and amines where hydrogen gas is liberated and no stoichiometric additives are necessary. These procedures constitute more environmentally benign methods for oxidative couplings and produce a minimum of waste. Ruthenium pincer complexes have been shown to mediate the coupling to form both amides and imines, depending on the structure of the ligand. An osmium pincer complex has been shown to catalyze the formation of imines, while the heterogeneous catalysts Ag/Al2O3 9 and Pt/ TiO2 10 mediate the formation of amides and imines, respectively. We have shown that ruthenium N-heterocyclic carbene complexes can catalyze the synthesis of amides from primary alcohols and amines with the extrusion of hydrogen gas. Following our initial findings, several ruthenium Nheterocyclic carbene and related complexes have been shown to mediate the amidation. Among these, the reaction is most efficiently performed with ruthenium complex 1 (Figure 1) in the presence of tricyclohexylphosphine (PCy3) and potassium tert-butoxide. During the study of the mechanism of this reaction, we observed that imines in some cases were formed to a significant degree and we speculated whether the conditions could be altered into a dehydrogenative imine synthesis. Herein, we describe a new ruthenium-catalyzed synthesis of imines from primary alcohols and amines where hydrogen gas is liberated