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DOI: 10.1055/a-2675-3988
Morpholine Amides: Classical but Underexplored Acylating Intermediates in Organic Synthesis
This work was supported by the Japan Science and Technology Agency (JST PRESTO, Grant No. JPMJPR2372)
Abstract
Morpholine amides are classical yet underexplored acylating agents in organic synthesis. Compared to other amides, such as Weinreb amides, morpholine amides offer distinct advantages such as high water solubility, economic accessibility, and operational stability. This review highlights recent advancements in the use of morpholine amides for the synthesis of ketones, aldehydes, and acylsilanes via selective mono-addition of organometallic or hydride reagents. Their applications in key steps of complex molecule synthesis, including natural product synthesis, Vilsmeier–Haack reactions, and polymer recycling processes, are also discussed. Particular attention is paid to the unique reactivity and chemoselectivity of morpholine amides that distinguish them from other amide derivatives, offering practical and scalable strategies in modern synthetic chemistry.
Keywords
Morpholine amide - Acylating agent - Mono-addition - Ketone synthesis - Weinreb alternative - Divergent building block - Hydride reductionPublication History
Received: 24 June 2025
Accepted after revision: 28 July 2025
Accepted Manuscript online:
03 August 2025
Article published online:
28 August 2025
© 2025. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).
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