CROSS-COUPLING MADE EASIER
STEVE RITTER · Chemical & Engineering News · 2009
AN EASIER, greener route to aryl-alkyl crosscoupling reactions—one of the most indispensable types of reactions in organic synthesis—is being reported by Bruce H. Lipshutz and coworkers at the University of California, Santa Barbara ( J. Am. Chem. Soc., DOI: 10.1021/ja906803t). The approach takes advantage of micelles as nanoreactors for the in situ generation of an alkylzinc reagent that sparks a standard palladium-catalyzed Negishi crosscoupling reaction. Using aqueous conditions and generating the organozinc reagent on the fly at room temperature weren’t thought to be possible for this type of cross-coupling before now. The strategy builds on Lipshutz’ efforts to use nanomicelles as a medium for transition-metal-catalyzed reactions. Lipshutz, Arkady Krasovskiy, and Christophe Duplais made a micellar solution by dissolving in water one of Lipshutz’ designer nonionic surfactants—the commercially available polyoxyethanyl α-tocopheryl sebacate. The water-insoluble aryl halide substrate, alkyl halide, and palladium catalyst migrate to the inside of the micelles, where the concentration of the reactants ...