Recent advances in oxidative allylic C-H functionalization via group IX-metal catalysis.

Allylic substitution, pioneered by the work of Tsuji and Trost, has been an invaluable tool in the synthesis of complex molecules for decades. An attractive alternative to allylic substitution is the direct functionalization of allylic C-H bonds of unactivated alkenes, thereby avoiding the need for prefunctionalization. Significant early advances in allylic C-H functionalization were made using palladium catalysis. However, Pd-catalyzed reactions are generally limited to the functionalization of terminal olefins with stabilized nucleophiles. Insights from Li, Cossy, and Tanaka demonstrated the utility of RhCpx catalysts for allylic functionalization. Since these initial reports, a number of key intermolecular Co-, Rh-, and Ir-catalyzed allylic C-H functionalization reactions have been reported, offering significant complementarity to the Pd-catalyzed reactions. Herein, we report a summary of recent advances in intermolecular allylic C-H functionalization via group IX-metal π-allyl complexes. Mechanism-driven development of new catalysts is highlighted, and the potential for future developments is discussed.

Analysis of MEMO1 Binding Specificity for ErbB2 Using Fluorescence Polarization and Molecular Dynamics Simulations.

ErbB2 signaling pathways are linked to breast cancer formation, growth, and aggression; therefore, understanding the behavior of proteins associated with these pathways as well as regulatory factors that influence ErbB2 function is essential. MEMO1 is a redox active protein that is shown to associate with phosphorylated ErbB2 and mediate cell motility. We have developed a fluorescence polarization assay to probe the interaction between MEMO1 and an ErbB2-derived peptide containing a phosphorylated tyrosine residue. This interaction is shown to be pH-dependent and stronger with longer peptides as would be expected for protein-protein interactions. We have quantitatively mapped the binding interface of MEMO1 to the peptide using the fluorescence polarization assay and molecular dynamics simulations. We have confirmed that phosphorylation of the peptide is essential for binding and through mutagenesis have identified residues that contribute to favorable interactions. Our results highlight the importance of the protein-protein interactions of MEMO1 that complement the oxidase activity. In the future, these studies will provide a method for screening for selective modulators of MEMO1, which will allow for additional biological investigations.