Reduction of Substituted Benzo-Fused Cyclic Sulfonamides with Mg-MeOH: An Experimental and Computational Study

Abstract

A study involving the use of Mg-MeOH for the double reductive cleavage of both N–S and C–S bonds in a series of 11 benzo-fused cyclic sulfonamides is reported. Examples where the sulfonamide nitrogen atom is part of a pyrrolidine ring effectively undergo reduction, as long as a methoxy substituent is not para -positioned in the aromatic ring, relative to the sulfonyl group. In contrast, if the nitrogen atom is contained within an aromatic ring (pyrrole or indole), the presence of a para -methoxy substituent does not prohibit reduction. If deuterated methanol is used, aromatic ortho- deuterium incorporation was observed. To better understand how structure affects reactivity, density functional theory calculations were performed using three functionals. Results using CAM-B3LYP were found to best correlate with experimental observations, and these demonstrate the impact that the different aromatic substitution patterns and types of N-atom have on the lowest unoccupied molecular orbital (LUMO) energies and adiabatic electron affinities.

Deuteration of Arylthianthren-5-ium Salts in CD3OD

“…Deuterated solvents are commercially available, environmental benign, and easy to handle, which have been routinely used in NMR spectroscopy for the structural characterization of organic compounds . The utilization of deuterated solvents as isotope sources in deuterium-labeling reactions has also been studied. , Very recently, Ritter and co-workers reported a Pd-catalyzed homogeneous hydrogenolysis of arylthianthrenium salts with deuterium and tritium gas (Scheme ). In this article, we found that reactions of arylthianthren-5-ium salts with CD 3 OD as both solvent and deuteration reagent could allow a mild synthesis of deuterated products with high selectivity under diverse conditions.…”