NEWS OF THE WEEK
SHINING LIGHT ON NICKEL CATALYSIS ORGANIC SYNTHESIS: Light-activated
iridium catalyst enhances nickel’s ability to form C–O bonds
C
HEMISTS REPORT A SIMPLE, low-tempera-
ture method for synthesizing aryl ethers, an important class of compounds used in fragrances, cosmetics, and pharmaceuticals. The key to the method is using light to push a nickel catalyst to perform a type of reaction it generally struggles to do. This general photocatalytic strategy could be used to expand the types of possible reactions other metal catalysts can handle, the researchers say. Palladium and copper catalysts can form C–O bonds to create aryl ethers, but these reactions typically require high temperatures and strong bases, which can adversely affect sensitive substituents. Ni in low oxidation states can catalyze such reactions too, but only in rare cases. Ni in higher oxidation states, Ni(III) or Ni(IV), can catalyze a wider range of C–O bond forming reactions, but chemists have to use either noncatalytic reagents, which can be costly and reduce synthetic efficiency, or strong bases to get the metal into those states. David W. C. MacMillan of Princeton University and coworkers have now used light and a separate catalytic cycle to oxidize Ni(II) to Ni(III), allowing the metal to catalyze C–O bond formation between aryl bromides and alcohols at room temperature. Alkoxide and aryl groups from the reagents first coordinate with Ni(II). Visible light then activates an iridium(III) photocatalyst so it can oxidize the Ni(II)
complex to the Ni(III) state. This allows Ni to perform a reductive elimination to form the aryl ether. Finally, the Ir and Ni catalysts react together to return to their starting oxidation states, readying them for another catalytic cycle. The reaction has broad substrate scope, coupling a variety of arene and heteroarene bromides with diverse primary and secondary alcohols to form a wide range of aryl ether products (Nature 2015, DOI: 10.1038/ nature14875). R OH “We get a Ni(II) Alcohol alkoxide to move to Ni catalyst and Visible a very high-energy Br Ir photocatalyst light Ni(III) species at room temperature, R´ which allows it to Aryl bromide readily participate R, R´= various groups in reductive elimination, a reaction it is famous for not being able to do with alcohols,” MacMillan says. “This metallo-photoredox concept might be used to switch on mechanisms or reactions that were previously impossible for all sorts of cheap and broadly available metal catalysts.” For many years, chemists have been thinking about how to perform catalytic versions of reductive eliminations with Ni complexes, “and MacMillan and coworkers now have elegantly shown how to do so with a photoredox system,” comments John F. Hartwig of the University of California, Berkeley, a specialist in transition metal-catalyzed reactions. “This is a very important paper,” says C–O bond formation expert Stephen L. Buchwald of MIT. The corresponding Pd- and Cu-catalyzed methods “have significant limitations,” and “the development of basic methods that can facilitate reductive elimination is potentially a game changer for many related reactions.”—
R
O R´ Aryl ether
STU BORMAN
APRECIA PHARMACEUTICALS
PHARMACEUTICALS U.S. Food & Drug Administration approves first 3-D printed drug The first 3-D printed drug, designed for zures, on the market by early 2016. people with epilepsy and who have a Aprecia describes Spritam as “a hard time swallowing pills, got a green porous formulation that rapidly disinlight from the tegrates.” The U.S. Food & Drug company’s manuAdministration. facturing process Manufacturer arranges up to Aprecia Phar1,000 mg of levetimaceuticals racetam in a single says it hopes to dose. have Spritam, Patients can its 3-D printed take a tablet with version of lea sip of liquid, vetiracetam, a making the pill widely prescribed easier to ingest, drug for the Spritam is an anti-seizure drug manufactured the company says. via commercial-scale 3-D printing. treatment of seiThis is important
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AUGUST 17, 2015
for children, the elderly, and others who may have a hard time swallowing pills, the company says. “Spritam is designed to fill a need for patients who struggle with their current medication experience,” said Don Wetherhold, chief executive officer of Aprecia. Spritam is the first 3-D printed drug that has gained FDA approval, an agency spokeswoman says. The printing technique that Aprecia used to create Spritam originated from Massachusetts Institute of Technology. There is growing interest in printing biological specimens, and 3-D printing is already used to manufacture some medical devices.—JESSICA MORRISON
