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Updated: May 30, 2025

A Microwave-Assisted Direct Heteroarylation of Ketones Using Transition Metal Catalysis
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Squaramide-Catalyzed Asymmetric Mannich/Hemiketalization Retro-Henry Cascade Reaction of o-Hydroxy-α-Aminosulfones
Rong-Rong Zhu1, Xi-Qiang Hou1, Da-Ming Du1
1Key Laboratory of Medicinal Molecule Science & Pharmaceutical Engineering, School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing 100081, China.
Abstract:
A concise and efficient asymmetric Mannich/hemiketalization/retro-Henry cascade reaction between o-hydroxy-α-aminosulfones and α-nitroketones was developed by utilizing a cinchona-derived bifunctional squaramide catalyst. This methodology provided access to β-nitro-substituted amino compounds with up to 95% yield and >99% ee. The practicality was demonstrated by scale-up and diverse derivatizations, including the synthesis of imidazolidinone and amino acid analogs. This is the first report of α-nitroketones in such a cascade reaction, offering a valuable approach for the synthesis of chiral β-nitro amino compounds.
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