Morpholine Amides: Classical but Underexplored Acylating Intermediates in Organic Synthesis

Morpholine amides are classical yet underexplored acylating agents in organic synthesis. Compared to the 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 advances in the use of morpholine amides for the synthesis of ketones, aldehydes, and acylsilanes via selective mono-addition of organometallic or hydride reagents. Their application in key steps of complex molecules including natural product synthesis, Vilsmeier-Haack reactions, and polymer recycling processes is 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. 1 Introduction 2 Ketone Formation from Morpholine Amides and Organometallic Reagents 3 Ketone Formation in Complex Molecular Synthesis 4 Ketone Formation from Morpholine Amides via Vilsmeire-Haac Reaction 5 Aldehyde Formation from Morpholine Amides and Hydride Reducing Agents 6 Acylsilane Formation from Morpholine Amides and a Silyllithium Reagent 7 Selective and Divergent Transformations of Morpholine