NEWS OF THE WEEK
JUST A PINCH SYNTHESIS: Highly enantioselective transformations proceed with tiny amounts of organocatalyst
S P E E D Y A new organocatalyst (above arrow) permits a range of enantioenriched, derivatized cyclic compounds to be produced from simple organic starting materials.
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NUSUALLY SMALL AMOUNTS of a new organo catalyst can accelerate highly enantioselective reactions of broad scope, a new study shows. Organocatalysts (organic compounds that catalyze organic reactions without the use of metals) are be coming increasingly popular. That's because they are readily available and inexpensive, sometimes permit new types of reactions to be carried out, and don't con taminate products with metals as do traditional metal lic catalysts. Organocatalysts typically must be used in large amounts, however, and the reactions they drive often are limited in scope. Assistant professor of chemistry Jeffrey W. Bode and coworkers at the University of California, Santa Barbara, now report an unusual case in which an or ganocatalyst can be used in small quantities to acceler ate reactions of broad synthetic scope, yielding a wide range of derivatized products (J. Am. Chem. Soc, DOI: io.i02i/jao6638or). Bode's group has been developing new organocatalytic reactions promoted by N-heterocyclic carbenes (NHCs). Earlier, the researchers described highly enan tioselective NHC-catalyzed reactions of enals and α,βunsaturated imines (J. Am. Chem. Soc. 2006,128,8418). In their new report, they have considerably expanded the scope of this transformation. The newly reported re actions, called oxodiene Diels-Alder reactions, produce a range of products with less than 1 mol % of a chiral NHC organocatalyst and feature outstanding enantioselectivities (usually greater than 99% enantiomeric excesses) and short reaction times. According to Bode, the need for large amounts of organocatalysts, usually 5-20 mol %, has been a long standing limitation and source of criticism of the or-
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ganocatalysis field. "We believe our work is one of the first broad demonstrations that enantioselec tive organocatalysis can proceed with the low cata lyst loadings often enjoyed by transition-metalcatalyzed processes," he says. Chemistry professor Li Deng of Brandeis Uni versity says that with catalyst loadings as low as 0.5 mol %, the Bode group's reactions "transform simple starting materials directly into complex, stereochemistry-rich lactone rings with very high enantioselectivity and diastereoselectivity. The combination of exceptional catalyst efficiency with a remarkable value-added asymmetric transformation makes this reaction an outstanding accomplishment." The new catalyst "might be useful for the life-sci ence industry for the synthesis of biologically active compounds under easy and simple reaction condi tions," says chemistry professor Karl Anker J0rgensen of Denmark's Aarhus University. Organic chemistry professor Garsten Bolm of RWTH Aachen University, Aachen, Germany, says that the new findings are "most remarkable." Efficient asymmetric catalysis requires both high enantioselectivity and low catalyst loading, Bolm notes, and the new technique is unusual in satisfying both requirements. "This discovery gives hope that even more complex chiral organocata lysts will soon find application in multistep enantiose lective total synthesis," he says.—STU BORMAN
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Undergrads Gerson J. Uc {back, from left) and JiYoungYoon, Bode, andgrad students (front, from left) Justin R. Struble and Ming He helped develop the new organocatalyzed oxodiene DieL·Alder reactions.
DRUG RESEARCH Bayer to consolidate in U.S., cutting 600 jobs Bayer will close two major U.S. research labs and eliminate about 600 positions, mostly in pharmaceutical R&D, as it ad vances its integration of the drugmaker Schering AG. Bayer says it has worked out a struc ture for the new Bayer Schering Pharma R&D organization. Under this structure, research conducted at numerous sites worldwide will be consolidated into three major R&D centers, in Berlin and Wuppertal, Germany, and Berkeley, Calif.
The Berlin site will focus on diagnostic imaging, oncology, and gynecology/andrology. Wuppertal will be the base for cardiology research. Berkeley will contin ue its focus on protein-based drugs and become an anchor for work in immunol ogy, inflammation, and hematology. Bayer's U.S. research site in West Haven, Conn., will close, as will the Rich mond, Calif., labs of Schering's Berlex subsidiary. The firm expects to complete the consolidation by mid-2007.
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NOVEMBER 13. 2006
The restructuring around large R&D sites focused on specific therapeutic ar eas is reminiscent of the measures Pfizer took in 2003 in the wake of its acquisi tion of Pharmacia. That program affected more than 2,000 people in R&D. Bayer says it will also restructure in Germany, where both Bayer and Schering are based, and in other countries. "It is not yet possible to issue concrete statements on headcounts and schedules," it says of these measures.-MICHAEL MCCOY
