Chemists have tweaked a century-old, chiral cobalt complex to catalyze reactions via hydrogen bond donors on the ligands, rather than at the central metal.
John A. Gladysz, chemistry professor at Texas A&M University, College Station, and his colleagues think the new class of versatile and low-cost enantioselective catalysts may greatly broaden the options for synthesizing enantiomerically pure pharmaceuticals and agrochemicals.
Hydrogen bond donation catalysis is becoming increasingly popular as a strategy for controlling enantioselectivity. Previous work has focused on organic catalysts containing NH and OH groups that catalyze reactions by stabilizing transition states in specific orientations through hydrogen bonding.
“We have expanded this concept to a new, unexplored corner of the ‘chiral pool’ that has never been used for enantioselective catalysis,” Gladysz tells C&EN.
The group fitted a cobalt(III) Werner complex with 1,2-diphenylethylenediamine ligands, which catalyze reactions via their NH groups. They used the catalyst to perform a carbon-carbon bond-forming reaction, the Michael addition of malonate esters to nitroalkenes, with up to 98% enantioselectivity (ACS Cent. Sci. 2015, DOI: 10.1021/acscentsci.5b00035).
“This is a fundamentally important concept in utilizing … these complexes for asymmetric catalysis—a scaffold that had no prior catalytic applications,” says Thomas J. Colacot, global R&D manager for homogeneous catalysis at Johnson Matthey Catalysis & Chiral Technologies in West Deptford, N.J.
Also, since the complexes have 12 NH bonds to participate in the reaction, as opposed to just two for most current hydrogen bond donors, the group should be able to create new catalysts, Gladysz tells C&EN.
“This novel mode of ligand-centered catalysis … should inspire new catalyst design, as ancillary ligands are traditionally used to modulate reactivity at the metal center,” Colacot says.
Yuri Belokon, professor at the Russian Academy of Sciences’ A. N. Nesmeyanov Institute of Organoelement Compounds in Moscow, agrees. He predicts that within several years many groups will be employing hydrogen-bond-donating chiral cobalt(III) complexes in their reactions.