Molecular biology achieves control over complex reaction networks by means of molecular systems that translate a chemical input (such as ligand binding) into an orthogonal chemical output (such as acylation or phosphorylation). We present an artificial molecular translation device that converts a chemical input - the presence of chloride ions - into an unrelated chemical output: modulation of the reactivity of an imidazole moiety, both as a Brønsted base and as a nucleophile. The modulation of reactivity operates through the allosteric remote control of imidazole tautomer states. The reversible coordination of chloride to a urea binding site triggers a cascade of conformational changes in a chain of ethylene-bridged hydrogen-bonded ureas, switching the chain's global polarity, that in turn modulates the tautomeric equilibrium of a distal imidazole, and hence its reactivity. Switching reactivities of active sites by dynamically controlling their tautomer states is an untapped strategy for building functional molecular devices with allosteric enzyme-like properties.

Two short pentapeptides rich in α-aminoisobutyric acid (Aib) residues have been shown to act as enantioselective organocatalysts for the conjugate addition of nucleophiles to nitroolefins. An L-alanine terminated peptide, (Aib)4(L-Ala)NHtBu, which has neither functionalised sidechains nor a highly designed reactive site, used an exposed N-terminal primary amine and the amide bonds of the backbone to mediate catalysis. Folding of this peptide into a 310 helical structure was observed by crystallography. Folding into a helix relays the conformational preference of the chiral alanine residue at the C-terminus to the primary amine at the N-terminus, 0.9 nm distant. The chiral environment and defined shape produced by the 310 helix brings the amine site into proximity to two exposed amide NHs. Reaction scope studies implied that the amine acts as a Brønsted base and the solvent-exposed NH groups of the helix, shown to weakly bind β-nitrostyrene, are needed to obtain an enantiomeric excess. Replacement of L-alanine with D-phenylalanine gave (Aib)4(D-Phe)NHtBu, a peptide that now catalysed the benchmark reaction with the opposite enantioselectivity. These studies show how achiral residues can play a key role in enantioselective catalysis by peptides through the promotion of folding.

AbstractThe reversible coordination of anions to an N,N’‐disubstituted 3,5‐bis(trifluoromethyl)phenylurea located at a terminus of a linear chain of ethylene‐bridged hydrogen‐bonded ureas triggers a cascade of conformational changes. A series of hydrogen‐bond polarity reversals propagates along the oligomer, leading to a global switch of its hydrogen‐bond directionality. The induced polarity switch, transmitted through four reversible urea groups, results in a change in emission and excitation wavelengths of a fluorophore located at the opposite terminus of the oligomer. The molecule thus behaves as a chemical sensor with a relayed remote spectroscopic response to variations in anion concentration. The polarity switch induced by anion concentration constitutes an artificial communication mechanism for conveying information through oligomeric structures.

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

To investigate how remotely induced changes in ligand folding might affect catalysis by organometallic complexes, dynamic α-amino-iso-butyric acid (Aib) peptide foldamers bearing rhodium(I) N-heterocyclic carbene (NHC) complexes have been synthesized and studied. X-ray crystallography of a foldamer with an N-terminal azide and a C-terminal Rh(NHC)(Cl)(diene) complex showed a racemate with a chiral axis in the Rh(NHC) complex and a distorted 310 helical body. Replacing the azide with either one or two chiral L-α-methylvaline (L-αMeVal) residues gave diastereoisomeric foldamers that each possessed point, helical and axial chirality. NMR spectroscopy revealed an unequal ratio of diastereoisomers for some foldamers, indicating that the chiral conformational preference of the N-terminal residue(s) was relayed down the 1 nm helical body to the axially chiral Rh(NHC) complex. Although the remote chiral residue(s) did not affect the stereoselectivity of hydrosilylation reactions catalysed by these foldamers, these studies suggest a potential pathway towards remote conformational control of organometallic catalysts.

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

Ethylene-bridged oligoureas are dynamic foldamers in which the polarity of a coherent chain of intramolecular hydrogen bonds may be controlled by intra- or intermolecular interactions with hydrogen-bond donors or acceptors. In this paper, we describe the way that supramolecular interactions between ethylene-bridged oligoureas bearing a 3,5-bis(trifluoromethyl)phenylurea (BTMP) terminus leads to higher-order structures both in the crystalline state and in solution. The oligoureas self-assemble by head-to-tail hydrogen bonding interactions to form either supramolecular 'nanorings' with cyclic hydrogen bond chain directionality, or supramolecular helical chains of hydrogen bonds. The self-assembly process features a cascade of cooperative positive allostery, in which each intermolecular hydrogen bond formation at the BTMP terminus switches the native hydrogen bond chain directionality of monomers, favouring further assembly. Monomers with a benzyl urea terminus self-assemble into nanorings, whereas monomers with a N-ethyl urea terminus form helical chains. In the crystal state, parallel helices have identical handedness and polarity, whereas antiparallel helices have opposite handedness. The overall dipole moment of crystals is zero due to the antiparallel arrangements of local dipoles in the crystal packing. Supramolecular interactions in solution were also examined by VT and DOSY NMR spectroscopy, up to the point of crystal formation. The size of higher aggregates in dichloromethane was estimated by their hydrodynamic radius. The relative orientation of the monomers within the aggregates, determined by 2D ROESY NMR, was the same as in the crystals, where syn-orientations lead to the formation of rings and anti-orientations result in chains. Overall, the switch of hydrogen bond polarity propagates intermolecularly in crystal and solution states, constituting an example of intermolecular communication within supramolecular polymers.

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

Communication of information through the global switching of conformation in synthetic molecules has hitherto entailed the inversion of chirality. Here, we report a class of oligomer through which information may be communicated through a global reversal of polarity. Ethylene-bridged oligoureas are constitutionally symmetrical, conformationally flexible molecules organized by a single chain of hydrogen bonds running the full length of the oligomer. NMR reveals that this hydrogen-bonded chain may undergo a coherent reversal of directionality. The directional uniformity of the hydrogen-bond chain allows it to act as a channel for the spatial communication of information on a molecular scale. A binding site at the terminus of an oligomer detects local information about changes in pH or anion concentration and transmits that information—in the form of a directionality switch in the hydrogen-bond chain—to a remote polarity-sensitive fluorophore. This propagation of polarity-encoded information provides a new mechanism for molecular communication.

Because of its low-lying sigma* orbitals, the C-S bond can interact with electron donors. In this short review, our goal is to focus on intramolecular interactions between bivalent sulfur and basic nitrogen atoms. In particular, we will consider the synthesis of selected heterobiaryls for which 1,4 NS inter-ring interactions can be identified from X-ray diffraction data. Finally, we will briefly touch on the use of such conformational preferences in various applications. 1 Introduction 2 Cross-Coupling with C-C Bond Formation 3 Cross-Coupling with C-N Bond Formation 4 Nucleophilic Addition to Azine Followed by Oxidation 5 Multicomponent Reactions 6 Heterobiaryl Formation by Azine Building 7 Heterobiaryl Formation by Building of the Sulfur-Containing Heterocycle 8 Cycloaddition Reactions 9 Other Syntheses 10 Conclusion

Organic Compounds David Tilly,† Floris Chevallier,† Florence Mongin,*,† and Philippe C. Gros*,‡,§ †Equipe Chimie et Photonique Molećulaires, Institut des Sciences Chimiques de Rennes, UMR 6226 CNRS-Universite ́ de Rennes 1, Bat̂iment 10A, Case 1003, Campus de Beaulieu, Avenue du Geńeŕal Leclerc, 35042 Rennes Ced́ex, France ‡HECRIN, Universite ́ de Lorraine, SRSMC UMR 7565, Boulevard des Aiguillettes, 54506 Vandoeuvre-les̀-Nancy, France HECRIN, CNRS, SRSMC UMR 7565, Boulevard des Aiguillettes, 54506 Vandoeuvre-les̀-Nancy, France

This review provides a perspective on C–H bond functionalization mediated by cobalt complexes used in either stoichiometric or catalytic amounts, without the contribution of any other transition metal, for organic synthesis applications.

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

Lan-Feng Dong , Victoria J.A. Jameson , David Tilly , Lubomir Prochazka , Jakub Rohlena , Karel Valis , Jaroslav Truksa , Renata Zobalova , Elahe Mahdavian , Katarina Kluckova , Marina Stantic , Jan Stursa , Ruth Freeman , Paul K. Witting , Erik Norberg , Jacob Goodwin , Brian A. Salvatore , Jana Novotna , Jaroslav Turanek , Miroslav Ledvina , Pavel Hozak , Boris Zhivotovsky , Mark J. Coster , Stephen J. Ralph , Robin A.J. Smith , Jiri Neuzil a,e,n

With the aim of synthesizing biaryl compounds, several aromatic iodides were prepared by the deprotonative metalation of methoxybenzenes, 3-substituted naphthalenes, isoquinoline, and methoxypyridines by using a mixed lithium/zinc-TMP (TMP=2,2,6,6-tetramethylpiperidino) base and subsequent iodolysis. The halides thus obtained, as well as commercial compounds, were cross-coupled under palladium catalysis (e.g., Suzuki coupling with 2,4-dimethoxy-5-pyrimidylboronic acid) to afford various representative biaryl compounds. Deprotometalation of the latter compounds was performed by using the lithium/zinc-TMP base and evaluated by subsequent iodolysis. The outcome of these reactions has been discussed in light of the CH acidities of these substrates, as determined in THF solution by using the DFT B3LYP method. Except for in the presence of decidedly lower pKa values, the regioselectivities of the deprotometalation reactions tend to be governed by nearby coordinating atoms rather than by site acidities. In particular, azine and diazine nitrogen atoms have been shown to be efficient in inducing the reactions with the lithium/zinc-TMP base at adjacent sites (e.g., by using 1-(2-methoxyphenyl)isoquinoline, 4-(2,5-dimethoxyphenyl)-3-methoxypyridine, or 5-(2,5-dimethoxyphenyl)-2,4-dimethoxypyrimidine as the substrate), a behavior that has already been observed upon treatment with lithium amides under kinetic conditions. Finally, the iodinated biaryl derivatives were involved in palladium-catalyzed reactions.

The deprotonating ability of mixed lithium-zinc or lithium-magnesium-zinc combinations containing amido and alkyl ligands in tetrahydrofuran were compared using anisole as substrate and iodine to quantitatively trap the formed arylmetal species. The results showed that the deprotonating ability is hampered if a Grignard reagent is employed to introduce the alkyl ligand, and is reduced when 2,2,6,6-tetramethylpiperidino ligands are replaced by less hindered/basic chiral amido or alkyls. Concerning the interception of the generated lithium-zinc aryl species by aldehydes, the presence of amido ligands leads to side reactions/lower yields, and no clear improvement was observed if lithium-magnesium-zinc aryl species are used. Racemic mixtures to very low enantioselectivities were noted when chiral amido ligands were incorporated in the composition of the bases.Still with enantioselective aryl transfer to aldehyde as purpose, the deprotonating ability of mixed lithium-cobalt combinations containing amido and alkyl ligands were compared using anisole as substrate and anisaldehyde to trap the formed arylmetal species. As before, the deprotonating ability is reduced when 2,2,6,6-tetramethylpiperidino ligands are replaced by less hindered/basic alkyls or chiral amido. The trapping step using aldehydes being in this case more efficient, even in the presence of amido ligands, the alcohols were obtained in higher yields. With recourse to a lower interception temperature, and using only bis[(R)-1-phenylethyl]amino as ligands, 32 and 22% yield, and 69 and 65% ee were obtained using, respectively, anisaldehyde and 3,4,5-trimethoxybenzaldehyde to intercept the metalated anisole. (C) 2012 Elsevier Ltd. All rights reserved.

Directed remote aromatic metalations are useful synthetic transformations allowing for rapid regioselective access to elaborate highly substituted carbocyclic aromatic and heteroaromatic systems. This review unravels the tangle of data reported on directed remote aromatic metalations. Through a careful analysis of critically selected examples, advanced rationalizations of remote metalation regioselectivities are presented. These extend beyond the complex-induced proximity effect (CIPE). Mechanisms, driving forces, and parameters influencing remote metalations are discussed. An understanding of these metalation mechanisms enables more accurate predictability of justification of regiochemical outcomes of these useful synthetic transformations.