Window[1]resorcin[3]arenes: A Novel Macrocycle Able to Self-Assemble to a Catalytically Active Hexameric Cage.

The hexameric resorcin[4]arene capsule has been utilized as one of the most versatile supramolecular capsule catalysts. Enlarging its size would enable expansion of the substrate size scope. However, no larger catalytically active versions have been reported. Herein, we introduce a novel class of macrocycles, named window[1]resorcin[3]arene (wRS), that assemble to a cage-like hexameric host. The new host was studied by NMR, encapsulation experiments, and molecular dynamics simulations. The cage is able to bind tetraalkylammonium ions that are too large for encapsulation inside the hexameric resorcin[4]arene capsule. Most importantly, it retained its catalytic activity, and the accelerated conversion of a large substrate that does not fit the closed hexameric resorcin[4]arene capsule was observed. Thus, it will help to expand the limited substrate size scope of the closed hexameric resorcin[4]arene capsule.

Biomimetic tail-to-head terpene cyclizations using the resorcin[4]arene capsule catalyst.

The tail-to-head terpene (THT) cyclization is a biochemical process that gives rise to many terpene natural product skeletons encountered in nature. Historically, it has been difficult to achieve THT synthetically without using an enzyme. In this protocol, a hexameric resorcin[4]arene capsule acts as an artificial enzyme mimic to carry out biomimetic THT cyclizations and related carbocationic rearrangements. The precursor molecule bears a leaving group (usually an alcohol or acetate group) and undergoes the THT reaction in the presence of the capsule catalyst and HCl as a cocatalyst. Careful control of several parameters (including water content, amount of HCl cocatalyst, temperature and solvent) is crucial to successfully carrying out the reaction. To facilitate the application of this unique capsule-catalysis methodology, we therefore developed a very detailed procedure that includes the preparation and analysis of all reaction components. In this protocol, we describe how to prepare two different terpenes: isolongifolene and presilphiperfolan-1ß-ol. The two procedures differ in the water content required for efficient product formation, and thus exemplify the two common use cases of this methodology. The influence of other crucial reaction parameters and means of precisely controlling them are described. A commercially available substrate, nerol, can be used as simple test substrate to validate the reaction setup. Each synthetic procedure requires 5-7 d, including 1-5 h of hands-on time. The protocol applies to the synthesis of many complex terpene natural products that would otherwise be difficult to access in synthetically useful yields.

Tautomerism and Self-Association in the Solution of New Pinene-Bipyridine and Pinene-Phenanthroline Derivatives.

Two novel pinene-type ligands have been synthesized and their tautomeric and self-associating behavior studied in solution and in the solid state. The first ligand, an acetylated derivative of 5,6-pinene-bipyridine, displays keto-enol tautomerism in solution. This tautomeric equilibrium was studied by NMR and UV-Vis spectroscopy in various solvents, and the results were compared with the ones obtained through DFT calculations. The second ligand was obtained by an unusual oxidation of the phenanthroline unit of a pinene-phenanthroline derivative. This compound exists as a single tautomer in solution and aggregates both in solution (as observed by NMR) and in the solid state through H-bonding as observed by X-ray structure determination and confirmed by DFT studies.