Determination of the Hammett Acidity of HF/Base Reagents.

Harnessing the acidity of HF/base reagents is of paramount importance to improve the efficiency and selectivity of fluorination reactions. Yet, no general method has been reported to evaluate their acidic properties, and experimental designs are still relying on a trial-and-error approach. We report a new method based on 19F NMR spectroscopy which allows highly sensitive measures and short-time analyses. Advantageously, the basic properties of the indicators can be determined upstream by DFT calculations, affording a simple yet robust semiempirical approach. In particular, the indicators used in this study were rationally designed to fit on the conceptually appealing and commonly used Hammett scale. This method has been applied to commercially available and recently developed HF/base reagents.

Exploring Superacid-Promoted Skeletal Reorganization of Aliphatic Nitrogen-Containing Compounds.

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.

Direct Superacid-Promoted Difluoroethylation of Aromatics.

Under superacid conditions, aromatic amines are directly and regioselectively 1,1-difluoroethylated. Low temperature in situ NMR studies confirmed the presence of benzylic α-fluoronium and α-chloronium ions as key intermediates in the reaction. This method has a wide substrate scope and can be applied to the late-stage functionalization of natural alkaloids and active pharmaceutical ingredients.

Access to Optically Pure Benzosultams by Superelectrophilic Activation.

Through superacid activation, N-(arenesulfonyl)-aminoalcohols derived from readily available ephedrines or amino acids undergo an intramolecular Friedel-Crafts reaction to afford enantiopure benzosultams bearing two adjacent stereocenters in high yields with fully controlled diastereoselectivity. Low-temperature NMR spectroscopy demonstrated the crucial role played by the conformationally restricted chiral dicationic intermediates.