An efficient copper-catalyzed domino halogen exchange-cyanation procedure for aryl bromides was developed utilizing 10 mol % CuI, 20 mol % KI, 1.0 equiv of the inexpensive N,N'-dimethylethylenediamine as ligand, and 1.2 equiv of NaCN in toluene at 110 degrees C. The new method represents a significant improvement over the traditional Rosenmund-von Braun reaction: the reaction conditions are much milder, and the use of stoichiometric amounts of copper(I) cyanide and polar solvents is avoided; therefore the isolation and purification of the aromatic nitrile products is greatly simplified. In addition, the new method exhibits excellent functional group compatibility comparable to that of the analogous Pd-catalyzed cyanation methodology.

Nitriles Nitriles Q 0520Copper-Catalyzed Domino Halide Exchange-Cyanation of Aryl Bromides. -This offers a mild, simple, and improved method for the synthesis of aromatic nitriles. -(ZANON, J.; KLAPARS, A.; BUCHWALD*, S. L.; J.

Liraglutide is a new generation lipopeptide drug used for the treatment of type II diabetes. In this work, we describe new approaches for its preparation fully by chemical methods. The key step of these strategies is the synthesis in solution of the Lys/γ-Glu building block, Fmoc-Lys-(Pal-γ-Glu-OtBu)-OH, in which Lys and Glu residues are linked through their side chains and γ-Glu is N(α) -palmitoylated. This dipeptide derivative is then inserted into the peptide sequence on solid phase. As liraglutide is obtained with great purity and high yield, our approach can be particularly attractive for an industrial production. We also report here the results of a circular dichroism conformational analysis in a membrane mimetic environment that offers new insights into the mechanism of action of liraglutide. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.

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The reaction of the new ligand [2,6-(CH2C5H4)2C5H3N]2-Na+ 2 (LNa2) with ZrCl4 in THF affords in good yield the trigonal-bipyramidal complex LZrCl2, where the two chlorine atoms are not equivalent. When LZrCl2 and RMgCl (R = CH3, n-butyl, CH2Si(CH3)3) are reacted in 1:1 and 1:2 molar ratios, the corresponding complexes LZr(Cl)R and LZrR2 can be isolated in good yields. Differently from the Cp2Zr(n-Bu)2, which has never been isolated due to β-H elimination, the analogous LZr(n-Bu)2 is thermally stable and its X-ray crystal structure has been solved, confirming its trigonal-bipyramidal geometry with the alkyl groups occupying an equatorial and an axial position. An NMR study (1H, 13C, HMQC, NOE) allowed the complete structural characterization of the complexes in solution.