March 3, 2026

N -Alkylsulfonamide Nucleophilicity: Experimental and Computational Assessment of Nitrogen Nucleophilicity of ( S )-2-(Iodomethyl)-1-tosylpyrrolidine

Key Points

N-alkylsulfonamides exhibit sufficient nucleophilicity, allowing for reactions with electrophilic centers.
In experiments, the nitrogen nucleophilicity of (S)-2-(iodomethyl)-1-tosylpyrrolidine was confirmed and measured.
Utilizing DFT calculation, the study supports the observed nucleophilicity with computational evidence.
The work highlights a contrast with the nucleophilic behaviors of amides, particularly in iodoamidation reactions.

Abstract

Sulfonamides are generally considered to be non-nucleophilic due to the presence of a sulfonyl group. We show that N-alkylsulfonamides are sufficiently basic/nucleophilic to be protonated and react with electrophilic centers. Contrasts with N- and O-reactivities of amides are made for intramolecular iodoamidations of alkenes. The nucleophilicity of nitrogen of (S)-2-(iodomethyl)-1-tosylpyrrolidine was confirmed experimentally and by DFT calculation.

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Cite This Study

Escudero et al. (Wed,) studied this question.

synapsesocial.com/papers/69a75bb6c6e9836116a23890 https://doi.org/https://doi.org/10.1021/acs.orglett.5c05226

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