Olefin Metathesis in Confined Geometries: A Biomimetic Approach toward Selective Macrocyclization.

The synthesis of macrocycles is severely impeded by concomitant oligomer formation. Here, we present a biomimetic approach that utilizes spatial confinement to increase macrocyclization selectivity in the ring-closing metathesis of various dienes at elevated substrate concentration up to 25 mM using an olefin metathesis catalyst selectively immobilized inside ordered mesoporous silicas with defined pore diameters. By this approach, the ratio between macro(mono)cyclization (MMC) product and all undesired oligomerization products (O) resulting from acyclic diene metathesis polymerization was increased from 0.55, corresponding to 35% MMC product obtained with the homogeneous catalyst, up to 1.49, corresponding to 60% MMC product. A correlation between the MMC/O ratio and the substrate-to-pore-size ratio was successfully established. Modification of the inner pore surface with dimethoxydimethylsilane allowed fine-tuning the effective pore size and reversing surface polarity, which resulted in a further increase of the MMC/O ratio up to 2.2, corresponding to >68% MMC product. Molecular-level simulations in model pore geometries help to rationalize the complex interplay between spatial confinement, specific (substrate and product) interaction with the pore surface, and diffusive transport. These effects can be synergistically adjusted for optimum selectivity by suitable surface modification.

Single-Molecule and Ensemble Diffusivities in Individual Nanopores with Spatially Dependent Mobility.

We investigated single-molecule and ensemble diffusivities in a silica nanopore with a chemically modified surface by molecular dynamics simulations. Solutes with graded polarity (nonpolar ethylbenzene and moderately polar benzyl alcohol) were equilibrated with a 40:60 v/v water/acetonitrile solvent in a 10 nm pore, the surface of which was rendered hydrophobic by modification with alkyl chains. Simulations enable detailed sampling of spatially dependent solvent and solute mobilities, which originate from microheterogeneity induced by the surface modification. Acetonitrile is enriched near the ends of the alkyl chains and forms a high-mobility interface region between the (nonpolar) bonded phase at the surface and the (polar) bulk liquid in the center of the pore. Solvent and solute diffusivities calculated from the time average of a single molecule and from the ensemble average over all molecules, respectively, revealed excellent agreement, which implies validity of ergodicity. The molecular-simulation approach to investigate the time average of a single molecule, on the one hand, and the ensemble average over a larger number of molecules, on the other hand, is general and can be adapted for a variety of surfaces, solvents, and solute molecules by using pores with tailored geometries and surface modifications.