Centre for Synthesis and Chemical Biology, School of Chemistry, University College Dublin, Dublin D04 N2E5, Ireland.
J Org Chem. 2022 Sep 16;87(18):12087-12095. doi: 10.1021/acs.joc.2c01169. Epub 2022 Sep 1.
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 -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 -methoxy substituent does not prohibit reduction. If deuterated methanol is used, aromatic 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.
一项涉及使用 Mg-MeOH 对一系列 11 个苯并稠合环状磺酰胺的 N-S 和 C-S 键进行双重还原裂解的研究被报道。只要磺酰胺氮原子不在相对于磺酰基的芳环的 - 位上，作为吡咯烷环的一部分的磺酰胺氮原子就可以有效地进行还原。相比之下，如果氮原子包含在芳环（吡咯或吲哚）中，则 - 甲氧基取代基的存在并不阻止还原。如果使用氘化甲醇，则观察到芳族氘的掺入。为了更好地了解结构如何影响反应性，使用三种函数进行了密度泛函理论计算。结果表明，使用 CAM-B3LYP 的结果与实验观察结果相关性最好，并且这些结果表明不同的芳族取代模式和 N 原子类型对最低未占据分子轨道（LUMO）能量和绝热电子亲合能的影响。
