The combination of peptide molecular recognition and residue-selective dirhodium catalysis allows modification of aromatic side chains that is selective for coil structures. A rate enhancement of >10(3) relative to nonselective dirhodium modification was observed. The increased reactivity of this approach creates the first selective chemical modification of the phenylalanine residue.

Coiled-coil assembly of substrate peptides with dirhodium metallopeptide catalysts enables side-chain modification on the basis of molecular shape. A wide range of amino acids are effectively modified, including the first examples of carboxamide (glutamine and asparagine) modification. The method is used to achieve covalent modification of the c-Fos bZip domain at different residues, depending on the metallopeptide structure. By combining promiscuous catalytic reactivity with specific molecular recognition, this work establishes a general strategy for protein modification on the basis of molecular shape. A broad range of peptide-protein interactions are potentially amenable to this approach.

The reaction of a palladiumII-hydride species with molecular oxygen to form palladiumII-hydroperoxide has been proposed as a key step in Pd-catalyzed aerobic oxidation reactions. We recently reported one of the first experimental precedents for such a step (Angew. Chem., Int. Ed. 2006, 45, 2904-2907). DFT calculations have been used to probe the mechanism for this reaction, which consists of formal insertion of O2 into the palladium-hydride bond of trans-(NHC)2Pd(H)OAc (NHC = N-heterocyclic carbene). Four different pathways were considered: (1) hydrogen atom abstraction (HAA) of the Pd-H bond by molecular oxygen, (2) reductive elimination of HX followed by oxygenation of Pd0 and protonolysis of the (eta2-peroxo)-PdII species, (3) oxygenation of palladiumII-hydride with subsequent reductive elimination of the O-H bond from an eta2-peroxo-PdIV center, and (4) formation of a cis-superoxide adduct of the palladium-hydride species followed by O-H bond formation via hydrogen atom migration. The calculations reveal that pathways 1 and 2 are preferred energetically, and both pathways exhibit very similar kinetic barriers. This result suggests that more than one pathway is possible for catalyst reoxidation in Pd-catalyzed aerobic oxidation reactions.

A functionalized [9]cycloparaphenylene ([9]CPP) bearing three evenly spaced 5,8-dimethoxynaphth-1,4-diyl units and two macrocyclic [6]CPP precursors have been synthesized. The Diels-Alder reaction between (E,E)-1,4-bis(4-bromophenyl)-1,3-butadiene and 1,4-benzoquinone followed by methylation produces cis-5,8-bis(4-bromophenyl)-5,8-dihydro-1,4-dimethoxynaphthalene as the key intermediate for the construction of the hooplike structures. The nickel-mediated homocoupling reactions followed by aromatization led to the functionalized [9]CPP.

Nickel salts catalyze fast cysteine arylation with 2-nitroarylboronic acids. The process uses cheap, readily-available reagents and allows introduction of diverse chemical handles.

Regioselective copper-catalyzed boracarboxylation of vinyl arenes with bis(pinacolato)diboron and carbon dioxide has been achieved. New boron-functionalized α-aryl carboxylic acids, including nonsteroidal anti-inflammatory drugs (NSAIDs), are obtained in moderate to excellent yields. The synthetic utility of the transformation was shown through subsequent derivatization of the carbon-boron bond yielding formal hydroxy- and fluorocarboxylation products as well as anionic difluoroboralactones.

No abstract

A new method for chemical protein modification is presented utilizing a dirhodium metallopeptide catalyst. The combination of peptide-based molecular recognition and a dirhodium catalyst with broad side-chain scope enables site-specific protein functionalization. The scope and utility of dirhodium-catalyzed biomolecule modification is expanded to allow reaction at physiological pH and in biologically relevant buffer solutions. Specific protein modification is possible directly in E. coli lysate, demonstrating the remarkable activity and specificity of the designed metallopeptide catalyst. Furthermore, a new biotin-diazo conjugate 1b is presented that allows affinity tagging of target proteins.