Synthetic and Mechanistic Investigations of Ruthenium Catalyzed Coupling Reactions via C−C and C−N Bond Activation

Transition-metal catalyzed C-N and C-C bond activation reactions are synthetically valuable reactions for selective and atom-economical synthesis of complex organic molecules. Catalytic reactions that involve activation of unreactive bonds are important for the stereoselective synthesis of molecular scaffolds from readily available substrates derived from bio-mass feedstock. Despite these advances, designing a broadly applicable catalytic method faces challenges of selectivity and harsh reaction conditions. A five coordinate Ru-H complex was found to be an effective catalyst for promoting the multicomponent deaminative coupling reaction of anilines, aldehydes and tertiary amines to selectively afford 2,3-disubstituted quinoline products. The scope of the reaction was expanded to enamines to generate 2,3,4-trisubstituted quinolines. We devised a stereoselective synthesis of (Z)-acrylic nitriles from the Ru-catalyzed coupling reaction of nitriles with unsaturated carbonyl compounds via C–C bond cleavage. Mechanistic studies revealed that the C-C bond cleavage step is the rate-determining step of the reaction mechanism. A tetranuclear Ru-H complex was found to be an effective catalyst for the hydrodeaminative coupling reaction of nitriles and amides to afford secondary amides. The inverted V-shaped Hammett plot revealed a change in reaction mechanism depending on the electronic environment of the nitrile substrate. We detected a catalytically relevant intermediate by generating a Ru-H species in situ. A tentative mechanism for the coupling reaction was proposed based on the experimental data which involves nucleophilic attack of amide on the nitrile substrate followed by amine hydrogenolysis.