Squaramide-Catalyzed Asymmetric Mannich/Hemiketalization Retro-Henry Cascade Reaction of <i>o</i>-Hydroxy-α-Aminosulfones with α-Nitroketones

A concise and efficient asymmetric Mannich/hemiketalization/retro-Henry cascade reaction between <i>o</i>-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.