Exploring Superacid‐Promoted Skeletal Reorganization of Aliphatic Nitrogen‐Containing Compounds

• Published in: Angewandte Chemie Vol. 136; no. 1
• Main Authors: Artault, Maxime, Cantin, Thomas, Longuet, Mélissa, Vitse, Kassandra, Mbengo, Christ Daniel Matatu, Guégan, Frédéric, Michelet, Bastien, Martin‐Mingot, Agnès, Thibaudeau, Sébastien
• Format: Journal Article
• Language: English
• Published: Weinheim Wiley Subscription Services, Inc 02.01.2024
• Subjects: Aliphatic compounds; Chemistry; Fluorine; Heterocycles; Labeling; Nitrogen; NMR; Nuclear magnetic resonance; Polycations; Protonation; Rearrangement; Substrates; Superacid
• ISSN: 0044-8249; 1521-3757
• DOI: 10.1002/ange.202316458

Here we report a method to reorganize the core structure of aliphatic unsaturated nitrogen‐containing substrates exploiting polyprotonation in superacid solutions. The superelectrophilic activation of N‐isopropyl systems allows for the selective formal Csp3−H activation/cyclization or homologation / functionalization of nitrogen‐containing substrates. This study also reveals that this skeletal reorganization can be controlled through protonation interplay. The mechanism of this process involves an original sequence of C−N bond cleavage, isopropyl cation generation and subsequent C−N bond and C−C bond formation. This was demonstrated through in situ NMR analysis and labelling experiments, also confirmed by DFT calculations. The rearrangement of isopropyl‐containing nitrogen‐containing compounds allows the skeletal reorganization to cyclic and elongated functionalized systems. An unprecedented tandem C−N bond cleavage / C−C and C−N bond formation through the generation of a dication is shown.