Taming diamines and acyl chlorides by carbon dioxide in selective mono-acylation reactions

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Diamides are ubiquitous in chemical structures of organic molecules with a variety of applications. Most of these diamides are accessed via acylation of diamines with corresponding acyl donors, using a protecting group, or with excess amounts of diamines to prevent unwanted diacylation reactions. Here we report a practical and atom-economical method to access monoamide and unsymmetric diamides with diamines and stoichiometric amounts of acyl chlorides - the most accessible and highly reactive acyl donor. The reactivity of diamines can be controlled by CO2 as a green, temporary and traceless protecting group for monoacylation reactions, achieving high atom efficienty and low environmental factor. We demonstrated the utility of the method with a broad substrate scope and a large scale reaction, and performed control experiments to elucidate the origin of the high selectivity obtained with CO2. We showed that ambient CO2 from thin air affected the selectivity of monoacylation of diamines, implying the pervasive influence of atmospheric CO2 in organic synthesis.

Original languageEnglish
JournalGreen Chemistry
Issue number4
Pages (from-to)1332–1338
Number of pages7
Publication statusPublished - 2023

Bibliographical note

Funding Information:
The generous support of the Department of Chemistry, University of Copenhagen, from the Novo Nordisk Fonden (NNF20OC0064347) is gratefully acknowledged. The authors appreciate Yang Yang for preliminary experimental contributions and Maria Teresa Oliveira for proofreading.

Publisher Copyright:
© 2023 The Royal Society of Chemistry.

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