Dialkylaminoalkylation of β-ketosulfones via ring-opening of 3-sulfonylpyrrolidines

Herein, a three-step method for the simultaneous dialkylaminoethylation and heteromethylation of active methylene β-ketosulfones, promoted by a leaving benzoyl group, is proposed. The primary domino reaction of sarcosine, paraformaldehyde, and β-ketosulfones affords 3-sulfonyl-3-benzoylpyrrolidines in good to high yields. Further treatment with alkyl halides and heating of the quaternary ammonium salt in the presence of a O-, S- or N-nucleophile with cesium carbonate leads to a retro-Claisen reaction, ring-opening and Michael addition. The resulting novel 4-Nu-3-sulfonylbutan-1-amines are isolated in moderate to excellent overall yields. The reduction of the obtained products with LiAlH 4 leads to a substitution of the attached nucleophilic moiety with hydrogen in good yields.