Template-Directed Synthesis of Multiply Mechanically Interlocked Molecules Under Thermodynamic Control

• Published in: Chemistry : a European journal 2005-08, Vol.11 (16), p.4655-4666
• Main Authors: Aricó, Fabio, Chang, Theresa, Cantrill, Stuart J., Khan, Saeed I., Stoddart, J. Fraser
• Format: Article
• Language: English
• Subjects: dynamic covalent chemistry; imine formation; molecular recognition; noncovalent interactions; reductive amination
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.200500148

The template‐directed construction of crown‐ether‐like macrocycles around secondary dialkylammonium ions (R2NH2+) has been utilized for the expedient (one‐pot) and high‐yielding synthesis of a diverse range of mechanically interlocked molecules. The clipping together of appropriately designed dialdehyde and diamine compounds around R2NH2+‐containing dumbbell‐shaped components proceeds through the formation, under thermodynamic control, of imine bonds. The reversible nature of this particular reaction confers the benefits of “error‐checking” and “proof‐reading”, which one usually associates with supramolecular chemistry and strict self‐assembly processes, upon these wholly molecular systems. Furthermore, these dynamic covalent syntheses exploit the efficient templating effects that the R2NH2+ ions exert on the macrocyclization of the matched dialdehyde and diamine fragments, resulting not only in rapid rates of reaction, but also affording near‐quantitative conversion of starting materials into the desired interlocked products. Once assembled, these “dynamic” interlocked compounds can be “fixed” upon reduction of the reversible imine bonds (by using BH3⋅THF) to give kinetically stable species, a procedure that can be performed in the same reaction vessel as the inital thermodynamically controlled assembly. Isolation and purification of the mechanically interlocked products formed by using this protocol is relatively facile, as no column chromatography is required. Herein, we present the synthesis and characterization of 1) a [2]rotaxane, 2) a [3]rotaxane, 3) a branched [4]rotaxane, 4) a bis [2]rotaxane, and 5) a novel cyclic [4]rotaxane, demonstrating, in incrementally more complex systems, the efficacy of this one‐pot strategy for the construction of interlocked molecules. You can have your cake and eat it! When it comes to making mechanical bonds rapidly and efficiently, the combination of supramolecular assistance—that relies on hydrogen bonding for the most part—to dynamic covalent synthesis involving activated imine bond formation takes a bit of beating. An example of the types of molecules that can result is shown here.