posted on 2023-04-11, 10:29authored byMartin
J. Power, David T. J. Morris, Iñigo J. Vitorica-Yrezabal, David A. Leigh
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 pKaH+ values as high as
32.2 in acetonitrile, which is up to 13 pKaH+ units greater than the pKaH+ 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.