BY ATTACHING a monodentate aryloxide group to a molybdenum core, chemists have created a new class of chiral catalysts for alkene metathesis reactions (Nature, DOI: 10.1038/nature07594). According to the researchers, the new catalysts will expand the scope of the popular reaction, in which two carbon-carbon double bonds react to form two new carbon-carbon double bonds. Chemists can use the transformation in certain molecules that had previously proved impervious to olefin metathesis.
"The existing catalysts have brought us very far, but the list of olefin metathesis reactions that we cannot carry out today is far longer than those that we can," says Boston College chemistry professor Amir H. Hoveyda, who spearheaded the work with Nobel Laureate Richard R. Schrock of MIT. For example, Hoveyda explains, olefin metathesis can be difficult to use on compounds that contain sterically hindered alkenes and certain functional groups, such as amines and carbonyls.
The researchers demonstrate the versatility of their new catalysts en route to the natural product quebrachamine. While other catalysts give measly or nonexistent yields, the new catalyst drives the reaction to 84% yield with 96% enantiomeric excess, even though the intermediate that undergoes metathesis contains an olefin that's difficult to access sterically and a basic nitrogen. That nitrogen would quickly deactivate most catalysts.
In the new catalysts, an enantiomerically pure, monodentate aryloxide ligand is linked to a stereogenic molybdenum center. Although catalyst makers typically favor rigid molecules, Hoveyda credits the catalysts' activity to their fluxionality—their ability to isomerize at the metal center, which is something they must do twice in the course of each catalytic cycle. Hoveyda also points out that the catalysts are both active and long-lived. "The trick is to make a catalyst that is both fast and stable," he says, "like a Ferrari that never breaks down."
The research is "a beautiful piece of work," says Benjamin G. Davis, a chemistry professor at the University of Oxford. "Stereoselective olefin metathesis is something that, although investigated before, has not quite borne the fruit that one might have expected until now," he notes. "The strategic reevaluation here comes together fantastically to expand both utility and scope, as well as delivering enhanced selectivity in ring-closing olefin metathesis."