Preparation of N- and C-Functionally-Substituted Glutarimides: A Review

Abstract

Six-membered heterocyclic systems such as glutarimides are widely used in medicinal chemistry. The glutarimide skeleton is found in many commercially available pharmaceuticals due to a wide range of bioactivity. The preparation of C,N-highly functionalized glutarimides is an important topic in modern organic synthesis, since it reveals the ability to build a more complex system and thus expands the range of various drugs. This review describes approaches to the synthesis of N- and C-functionally-substituted glutarimides presented in the literature from 2005 to 2022. Options for the enantioselective synthesis of spiroglutarimides, the use of organocatalysis in the synthesis of glutarimides, and optimization of the synthesis of already known pharmaceuticals are described.

1 Introduction

2 Michael Addition

2.1 Preparation of Glutarimides from Substituted Acrylamides and 1,3-Bielectrophiles

2.2 Preparation of Glutarimides by the Reaction of Acetamide and α,β-Unsaturated Carbonyl Compounds

2.2.1 Preparation of Glutarimides by the Reaction of Acetamide Derivatives and Acrolein Derivatives

2.2.2 Preparation of Spiroglutarimides by the Reaction of Acetamide Derivatives and Bromacrolein Derivatives

2.2.3 Preparation of Spiroglutarimides by the Reaction of Acetamide Derivatives and Acryloyl Cyanide Derivatives

2.2.4 Preparation of Substituted Glutarimides Using Ytterbium Salts

2.3 Michael Addition/Intramolecular Transacylation

2.4 Preparation of Glutarimides from Baylis–Hillman Adducts

3 Multicomponent Reactions

4 Conclusion

Key words

glutarimides - Michael addition - multicomponent reactions - enantioselectivity - organocatalysis

Publication History

Received: 15 February 2023

Accepted after revision: 29 March 2023

Article published online:
10 May 2023

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