New System For Aerobic Oxidations

Natural metalloenzymes and their small-organic-molecule cofactors are model cooperative catalytic reaction systems that chemists like to emulate when trying to improve the efficiency of organic syntheses. Shū Kobayashi and coworkers at the University of Tokyo have now demonstrated the first example of a heterogeneous nanocluster catalyst cooperating with an organocatalyst cofactor. The pairing enables amine oxidations to be carried out under mild reaction conditions (J. Am. Chem. Soc., DOI: 10.1021/ja306934b).

Cooperative catalysts are typically homogeneous systems involving a soluble transition-metal complex and a small organic molecule. The two work together to overcome energy barriers along the reaction pathway, enabling high reactivity and enantioselectivity that neither catalyst can accomplish on its own.

Kobayashi’s group previously developed bi­metallic nanoclusters “incarcerated” in a styrene-based co­polymer support material. Although these immobilized metal nanocluster catalysts are highly effective in facilitating some types of aerobic oxidations, they have had limited utility in converting amines to imines because they require high temperatures, Kobayashi says.

The Tokyo researchers have now tested their incarcerated catalysts on the oxidation of amines to imines using platinum-iridium nanoclusters with 4-tert-butylcatechol as the cofactor, a system that mimics the action of amine oxidases. They converted dibenzylamines to the corresponding imines in air at room temperature in up to 90% isolated yield, recycling the nanocluster catalyst five times without loss of activity. In a bonus finding, Kobayashi’s team discovered that the catalyst system can convert secondary amines to imines—natural metalloenzyme-cofactor systems can’t do that.

Mechanistic studies suggest that the catechol and amine form a quinone complex that binds to the nanocluster surface. This bound intermediate then undergoes hydride transfer from the amine to the nanocluster to generate the imine C=N bond.

“Transition-metal-catalyzed oxidations to dehydrogenate aliphatic amines to imines require vigorous reaction conditions,” comments Chul-Ho Jun, a specialist in metal-organic cooperative catalysis at Yonsei University in Seoul, South Korea. The synergistic action of this unique heterogeneous cooperative catalyst lowers the activation energy to overcome that problem, Jun adds.