news of the week AU GUST 17, 20 0 9 EDITED BY KIMBERLY R. TWAMBLY & ALICIA J. CHAMBERS
FLEXIBLE FLUORINATION
Furthermore, the reaction employs simple, nucleophilic fluorine sources such as cesium fluoride. Some other fluorinations employ electrophilic fluorine sources, which tend to be expensive and unstable, Buchwald explains. “For 18F radiochemists, this is a ORGANOMETALLIC CHEMISTRY: Pdbreakthrough conceptual advance as nucleophilic 18F catalyzed reaction adds fluorine fluoride is widely available and is the preferred reagent to a wide variety of substrates to produce 18F radiotracers,” says Véronique Gouverneur of the University of Oxford, who also develops new tactics for making radiotracers. ITH THE HELP OF a bulky ligand, chemists Key to the new have devised a versatile new reaction for method is a pair of OSO2CF3 F Pd catalyst installing fluorine atoms on aromatic rings. bulky, electron-rich + CsF The advance could have a big impact on the synthesis phosphine-containof pharmaceuticals, agrochemicals, and radiolabeled ing ligands developed R R agents for medical imaging applications. by the Buchwald R = various groups Fluorine atoms abound in drugs because they can group. These lifavorably alter compounds’ metabolic stability or gands are thought FACILE FLUORIDES The new reaction works other properties in the body. But getting fluorine into to promote efficient on a wide range of aryl triflates. a molecule easily, selectively, and safely is often still a carbon-fluorine bond challenge. formation from a Now, chemistry professor Stephen L. Buchwald, Pd(II) center. Pioneering work by Vladimir V. Grushin postdoctoral associate Donald A. Watson, and colof DuPont has demonstrated that such bond formaleagues at Massachusetts Institute of Technology tions are notoriously difficult, Buchwald says. Other groups have tried to use phosphine ligands to promote the reaction without much success or have opted to form C–F bonds via a Pd(IV) center instead. This work surmounts the challenges and is “a beautiful testament to how ancillary ligands can be exploited to modify the ‘typical’ reactivity of metal complexes,” says organometallic chemist Melanie S. Sanford of the University of Michigan, Ann Arbor. The new reactions must be set up in a glove box because they are sensitive to water. By exploring other ways to dry the fluorine source, the group hopes to move past that limitation, says Watson, who is now an assisORCHESTRATOR tant professor of chemistry at the University The bulkiness of the phosphine ligand in Buchwald’s Pd of Delaware. It’s not yet clear whether water catalysts is evident in this X-ray structure. sensitivity is related to the catalytic reaction. If that turns out to be the case, it may be poshave developed a palladium-catalyzed reaction that sible to design ligands that fix the problem, he says. The replaces a triflate group on an aromatic ring with a team has submitted a patent application for the reacfluorine atom (Science, DOI: 10.1126/science.1178239). tion, he adds. The reaction works with catalytic amounts of Pd “Over the past several years, the Buchwald group has and does not require directing groups. Other metalredefined what is possible in cross-coupling chemistry mediated routes to aryl fluorides possess just one of by developing new classes of ligands for palladium cathose attributes—Buchwald’s is the first to feature talysis, and this new carbon-fluorine bond formation both. The procedure works on a range of triflate is a dramatic example,” says organic chemist Eric N. substrates, including highly functionalized triflates Jacobsen of Harvard University. “This work is certain derived from the natural product quinine and the dye to find immediate application in pharmaceutical refluorescein. search,” he adds.—CARMEN DRAHL
COURT ESY OF DONALD A. WATSON
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AUGUST 17, 2009
