Diving into the Shielding Surfaces: Construction of Atropisomeric Axes via Multicomponent Reactions

Abstract

The CH⋅⋅⋅π interaction, characterized by a CH group acting as a hydrogen bond donor and π electrons serving as the acceptor, shares structural similarities with hydrogen bond and plays a significant role in a multitude of molecular systems. However, due to the weak and variable nature of these interactions, they remain poorly understood. Recently, we reported the design of high rotational barrier atropisomeric systems incorporating CH⋅⋅⋅π and π⋅⋅⋅π interactions. Building on these insights, we explored the Groebke-Blackburn-Bienaymé three-component reaction (GBB-3CR) to access additional atropisomeric systems. We hypothesized that the GBB-derived scaffold could serve as a modular platform, facilitating the strategic incorporation of CH⋅⋅⋅π and π⋅⋅⋅π interactions to enhance structural diversity and functionality. Using 2-aminopyridine, polyaromatic aldehydes and ortho-substituted phenyl isocyanides, we systematically explored the substrate scope. We investigated the impact of different shelves and arms, emphasizing the effect of aromatic ring topology and number on molecular conformations and ring currents. To analyze experimental NMR signals of methyl groups, we calculated the chemical shifts and estimated the ring current contributions. The through-space NMR shielding calculations and isochemical shielding surface (ICSS) visualizations provided insights into the electronic environments within the scaffold, advancing our understanding of CH⋅⋅⋅π interactions and their potential applications.