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. 2017 Oct 11;2(10):6598-6604.
doi: 10.1021/acsomega.7b01213. eCollection 2017 Oct 31.

Synthesis of Succinimide Derivatives by NHC-Catalyzed Stetter Reaction of Aromatic Aldehydes with N-Substituted Itaconimides

Milind M Ahire  1   2 , Santosh B Mhaske  1   2
Affiliations

Synthesis of Succinimide Derivatives by NHC-Catalyzed Stetter Reaction of Aromatic Aldehydes with N-Substituted Itaconimides

Milind M Ahire et al. ACS Omega. .

Abstract

An N-heterocyclic carbene-catalyzed intermolecular Stetter reaction of aromatic aldehydes with N-substituted itaconimides has been developed. A delicate balance between the Stetter reaction and the competing isomerization of the itaconimide double bond has been achieved in this operationally simple reaction to afford valuable new succinimide derivatives containing 1,4 and 1,5 dicarbonyl scaffolds in good to excellent yields. The reaction tolerates variable substituents on both aldehydes and N-substituted itaconimides.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
Prior and this work on Michael addition with N-substituted itaconimides.
Scheme 1
Scheme 1. N-Aryl Itaconimides from Aromatic Amines and Itaconic Anhydride,
Reaction conditions: (i) amine (1 equiv, 1 g scale), anhydride (1.1 equiv), 1,4-dioxane (0.1 M), 25 °C, 30 min; (ii) APS (2 equiv), DMSO (2 equiv), 100 °C. Isolated yields.
Scheme 2
Scheme 2. Variation in the Itaconimide N-Substituents,
Reaction conditions: 5 (1.0 equiv, 0.35 mmol), 4a–k (1.5 equiv, 0.52 mmol), pre-NHC catalyst A (15 mol %), K2CO3 (50 mol%), THF (2 mL), under argon atmosphere. Isolated yields. Reaction at 5.00 mmol scale.
Scheme 3
Scheme 3. Variation in the Aldehyde Substrate,
Reaction conditions: 5a–h (1.0 equiv, 50 mg), 4a (1.5 equiv), pre-NHC catalyst A (15 mol %), K2CO3 (50 mol%), THF (2 mL), under argon atmosphere. Isolated yields, N.D. = not detected.
See this image and copyright information in PMC

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