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.