C&EN: TODAY'S HEADLINES - CATALYSIS BY HYDROGEN BONDING

MAUREEN ROUHI

Catalysis by simple organic compounds is of enormous interest to chemists hoping to avoid contamination of asymmetric reaction products by the usual metal-based catalysts. Now, chemists at the University of Chicago have demonstrated that hydrogen bonding like that used by enzymes can bring about highly enantioselective organic catalysis.

Viresh H. Rawal and coworkers find that cycloadditions of a diene and various aldehydes catalyzed by a chiral alcohol bearing naphthyl groups proceed by a hydrogen-bonding mechanism. The adduct is formed in greater than 98% enantiomeric excess and is further converted to a dihydropyrone [Nature, 424, 146 (2003)].

The chemistry is "conceptually novel," says David W. C. Macmillan, a chemistry professor at California Institute of Technology. "Hydrogen-bonded activation of substrates by simple and environmentally benign organic molecules is an important advance in asymmetric catalysis," he adds.

In organic catalysis, the catalyst usually forms a covalent bond with the substrate, a chiral intermediate is formed, and a chiral product is liberated. In the Chicago group's chemistry, substrate and catalyst interact through a hydrogen bond. Rawal believes that hydrogen bonding draws the substrate to the catalyst and that the interaction between the substrate's carbonyl group and the alcohol's naphthalenes is stabilized by stacking.

Many enzymatic reactions rely on hydrogen bonding to help organize the structure of the enzyme and to activate the substrate, Rawal says, and using hydrogen bonding to catalyze nonenzymatic asymmetric reactions is not unprecedented. However, previous work on cycloadditions achieved only modest selectivities, he adds.