Chemistry - A European Journal
10.1002/chem.202001140
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macrocyclization efficiency factor (Emac) of 7.3, which is among
the highest of which we are aware for a non-templated and
bimolecular amide macrocyclization.28 While simple structures,
these products have been shown to have utility as monomers for
ring-opening polymerization and supramolecular guest binding.29
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In addition to secondary amides, the reactivity of 7’ provides
an added element of control and addressability to these systems,
where the addition of nucleophiles can be exploited to access
substituted macrocycles in a modular fashion. As an illustration,
the addition of a pyridine-tethered alcohol to 7’ can be used to
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generates now amide cages (10b). The latter incorporates three
arms are derived from different units that are each accessible.
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In conclusion, we have described a straightforward approach to
the dynamic formation of amides. The reaction exploits reagents
that are accessible (imines/acid chlorides), occurs at ambient
temperature, and the equilibrium can be readily tuned by
substrate, solvent, temperature or anion. Coupling this with
hydrolysis has opened a route to generate robust secondary
amide products, with structures ranging from amide-macrocycles
to polymers. Considering the utility of amides as products, the
ability to access these structures in a controlled fashion via
dynamic covalent chemistry and from available substrates could
prove relevant in a range of applications. Moreover, this platform
should prove equally adaptable to more classical
supramolecular structural influences, including the use of anions
to template formation of cationic N-acyl iminium salts. Efforts
directed towards these latter goals are currently underway.
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We thank NSERC and FRQNT Centre for Green Chemistry and
Catalysis for support of this research.
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Keywords: dynamic covalent chemistry • amide synthesis •
macrocycles • iminium salts
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