Exploring Regioselective Bond Cleavage and Cross‐Coupling Reactions using a Low‐Valent Nickel Complex

Recently, esters have received much attention as transmetalation partners for cross‐coupling reactions. Herein, we report a systematic study of the reactivity of a series of esters and thioesters with [{(dtbpe)Ni}₂(μ‐η²:η²‐C₆H₆)] (dtbpe=1,2‐bis(di‐tert‐butyl)phosphinoethane), which is a source of (dtbpe)nickel(0). Trifluoromethylthioesters were found to form η²‐carbonyl complexes. In contrast, acetylthioesters underwent rapid C_acyl?S bond cleavage followed by decarbonylation to generate methylnickel complexes. This decarbonylation could be pushed backwards by the addition of CO, allowing for regeneration of the thioester. Most of the thioester complexes were found to undergo stoichiometric cross‐coupling with phenylboronic acid to yield sulfides. While ethyl trifluoroacetate was also found to form an η²‐carbonyl complex, phenyl esters were found to predominantly undergo C_aryl?O bond cleavage to yield arylnickel complexes. These could also undergo transmetalation to yield biaryls. Attempts to render the reactions catalytic were hindered by ligand scrambling to yield nickel bis(acetate) complexes, the formation of which was supported by independent syntheses. Finally, 2‐naphthyl acetate was also found to undergo clean C_aryl?O bond cleavage, and although stoichiometric cross‐coupling with phenylboronic acid proceeded with good yield, catalytic turnover has so far proven elusive.     

Modified Guanines as Constituents of Smart Ligands for Nucleic Acid Quadruplexes

Repetitive guanine‐rich nucleic acid sequences play a crucial role in maintaining genome stability and the cell life cycle and represent potential targets for regulatory drugs. Recently, it has been demonstrated that guanine‐based ligands with a porphyrin core can be used as markers of G‐quadruplex assemblies in cell tissues. Herein, model systems of guanine‐based ligands are explored by DFT methods. The energies of formation of modified guanine tetrads and those of modified tetrads stacked on the top of natural guanine tetrads have been calculated. The interaction energy has been decomposed into contributions from hydrogen bonding, stacking, and ion coordination and a twist–rise potential energy scan has been performed to find the individual local minima. Energy decomposition analysis reveals the impact of various substituents (F, Cl, Br, I, Me, NMe₂) on individual energy terms. In addition, cooperative reinforcement in forming the modified and stacked tetrads, as well as the frontier orbitals participating in the hydrogen‐bonding framework involving the HOMO–LUMO gap between the occupied σ_HOMO on the proton‐accepting C=O and =N? groups and unoccupied σ_LUMO on the N?H groups, has been studied. The investigated systems are demonstrated to have a potential in ligand development, mainly due to stacking enhancement compared with natural guanine, which is used as a reference.     

Influence of Equilibration Time in Solution on the Inclusion/Exclusion Topology Ratio of Host–Guest Complexes Probed by Ion Mobility and Collision‐Induced Dissociation

Host–guest complexes are formed by the creation of multiple noncovalent bonds between a large molecule (the host) and smaller molecule(s) or ion(s) (the guest(s)). Ion‐mobility separation coupled with mass spectrometry nowadays represents an ideal tool to assess whether the host–guest complexes, when transferred to the gas phase upon electrospray ionization, possess an exclusion or inclusion nature. Nevertheless, the influence of the solution conditions on the nature of the observed gas‐phase ions is often not considered. In the specific case of inclusion complexes, kinetic considerations must be taken into account beside thermodynamics; the guest ingression within the host cavity can be characterized by slow kinetics, which makes the complexation reaction kinetically driven on the timescale of the experiment. This is particularly the case for the cucurbituril family of macrocyclic host molecules. Herein, we selected para‐phenylenediamine and cucurbit[6]uril as a model system to demonstrate, by means of ion mobility and collision‐induced dissociation measurements, that the inclusion/exclusion topology ratio varies as a function of the equilibration time in solution prior to the electrospray process.     

Product Control using Substrate Design: Ruthenium‐Catalysed Oxidative C−H Olefinations of Cyclic Weinreb Amides

A new class of Weinreb amides has been developed as directing groups for the ruthenium‐catalysed regioselective oxidative C?H olefination. The new Weinreb amides successfully inhibit the N?O bond reductive cleavage usually associated with the cationic ruthenium system, thereby keeping intact the synthetic utility of Weinreb amides. Mechanistic studies reveal interesting aspects of the directing group capabilities of Weinreb amides when compared to simple amides of similar structures.