Compact Rotaxane Superbases

Challenges for the development of efficacious new superbases include their ease of synthesis, chemical stability, and high basicity, while minimizing nucleophilicity is important for reducing unwanted side reactions. Here, we introduce a new family of organic superbases, compact amine-crown ether rotaxanes, which show desirable characteristics in all these respects. Metal-free active template synthesis provides access to a range of rotaxanes with as little as three atoms between the stoppering groups, locking the location of a small crown ether (21C7 and 24C8 derivatives) over the amine group of the axle. The forced proximity of the interlocked protophilic components results in pK_aH⁺ values as high as 32.2 in acetonitrile, which is up to 13 pK_aH⁺ units greater than the pK_aH⁺ values of the non-interlocked components, and brings the free base rotaxanes into the basicity realm of phosphazene superbases. The rotaxane superbases are generally chemically stable and, in a model reaction for superbases, eliminate HBr from a primary alkyl bromide with complete selectivity for deprotonation over alkylation. Their modest size, ease of synthesis, high basicity, low nucleophilicity, and, in the best cases, rapid substrate deprotonation kinetics and excellent hydrolytic stability make compact amine-crown ether rotaxane superbases intriguing candidates for potential applications in synthesis and supramolecular and materials chemistry.