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IOC PAS scientists unlock a new application of anomeric amides.

Amides are ubiquitous functional motifs present in a range of important molecules such as proteins or synthetic polymers. However, the application of amides as reagents in organic synthesis presents a major challenge due to their exceptional stability.

In a recent paper published in Angewandte Chemie, the team from IOC PAS explores the reactivity of a unique class of amides called “anomeric amides”. These reagents were previously recognized as potent nitrenium ion [N + ] surrogates, allowing for direct access to reactive intermediates from nucleophiles (e.g. amines). In this work the scientists present evidence that this reactivity can be expanded on reactions with nitrogen-based heterocycles, adding another facet to the unique chemistry of anomeric amides.

Building on their findings, the team reports a mild, scalable, and highly chemoselective method for the fragmentation of isoxazolones to alkynes. Since isoxazolones can be readily accessed from β-ketoesters, this transformation constitutes nonorthodox functional group interconversion (alkyne from 1,3-dicarbonyl). The reaction can be used to access a variety of underexplored building blocks with potential applications in medicinal chemistry (e.g. piperidine derivatives with propargylic all-carbon quaternary centers, drug conjugates).

Link to article: https://onlinelibrary.wiley.com/doi/10.1002/anie.202518256

The open access preprint version of the article is available on ChemRxiv: https://chemrxiv.org/engage/chemrxiv/article-details/689b640ea94eede154753ed2.

This work was funded by the National Science Centre (grant SONATA no. 2022/47/D/ST4/00332).