A hydrogen-bond stabilized cavitand receptor for coronene that has an unprecedented conformational flexibility and adapts to the guest's shape.

The synthesis of optically and diastereomerically pure P-stereogenic phosphine-imidazole ligands is reported. The new ligands contain either a benzoimidazole or a 4-phenylimidazole as a N-donor fragment. The ligands have been coordinated to iridium and the structure of the corresponding cationic COD complexes has been determined by X-ray analysis. The combination of the chiral phosphorus atom and the imidazole substituents generate a strong chiral environment around the metal 2 center. Preliminary hydrogenation reactions with a model cyclic -enamide are also reported. RESULTS AND DISCUSSIONLigand Synthesis. Phosphino imidazole ligands have been synthetized according to the retrosynthetic analysis shown in Scheme 1. Condensation of valine with orthophenylenendiamine and 2-bromoacetophenone should provide the corresponding chiral protected benzo-and 4-phenylimidazole amines. N-Alkylation and Boc deprotection would provide the corresponding primary amines. These will be coupled with either enantiomer of the optically pure tert-butylmethylphosphinous acid borane in a SN2 reaction at the stereogenic P-center (SN2@P) to afford the desired ligands. Scheme 1: Retrosynthetic plan for the synthesis of phosphino imidazole ligands. The synthesis of free (R)-2-methyl-1-(1-methylbenzoimidazol-2-yl)propan-1-amine 4 was conducted as shown in Scheme 2. Condensation of N-Boc valine with orthophenylenendiamine was carried out through a two-step procedure as described in the literature. 15 Isobutyl chlorocarbonate-mediated amide coupling and cyclization with AcOH at 65 ºC provided the desired N-Boc protected benzoimidazole 2 in 54% yield. Next, N-methylation of the benzoimidazole heterocycle was carried selectively with MeI and NaOH pellets in acetonitrile. This cleanly afforded 3 in 90% yield. Finally, Boc deprotection was performed in MeOH/HCl(aq) which afforded the desired benzoimidazole amine 4 in excellent yield and purity.

The conformational equilibria and guest exchange process of a resorcin[4]arene derived self‐folding cavitand receptor have been characterized in detail by molecular dynamics simulations (MD) and 1H EXSY NMR experiments. A multi‐timescale strategy for exploring the fluxional behaviour of this system has been constructed, exploiting conventional MD and accelerated MD (aMD) techniques. The use of aMD allows the reconstruction of the folding/unfolding process of the receptor by sampling high‐energy barrier processes unattainable by conventional MD simulations. We obtained MD trajectories sampling events occurring at different timescales from ns to s: 1) rearrangement of the directional hydrogen bond seam stabilizing the receptor, 2) folding/unfolding of the structure transiting partially open intermediates, and 3) guest departure from different folding stages. Most remarkably, reweighing of the biased aMD simulations provided kinetic barriers that are in very good agreement with those determined experimentally by 1H NMR. These results constitute the first comprehensive characterization of the complex dynamic features of cavitand receptors. Our approach emerges as a valuable rational design tool for synthetic host‐guest systems

We report a chiral deep cavitand receptor based on calix[5]arene stabilized by a cooperative network of hydrogen bonds and having a highly flexible structure. The cavitand displays enantioselective molecular recognition with a series of chiral quaternary ammonium salts, providing unprecedented stability ratios between the corresponding diastereomeric host–guest complexes. Molecular dynamics simulations corroborate the higher flexibility of the new host and the emergence of superior induced-fit behavior with regards to resorcin[4]arene derived self-folding cavitands.

We report a chiral deep cavitand receptor based on calix[5]arene stabilized by a cooperative network of hydrogen bonds and having a highly flexible structure. The dynamic features of the host have been studied by 1H NMR spectroscopy, revealing a bowl inversion motion that is slow in the NMR time scale. The cavitand displays enantioselective molecular recognition with a series of chiral quaternary ammonium salts, providing unprecedented stability ratios between the corresponding diasteromeric host-guest complexes. Molecular dynamics simulations corroborate the higher flexibility of the new host and the emergence of superior induced fit behavior with regards to resorcin[4]arene derived self-folding cavitands.