Protocol for efficient dearomatization of N-heteroaromatics with halogen(I) complex catalyst.

In this protocol, we describe the application of a halogen(I) complex as a highly active non-metallic complex catalyst. Specifically, we present a detailed guide to synthesize the halogen(I) complex catalyst and utilize it as an anion-binding catalyst for the Mukaiyama-Mannich-type reaction of N-heteroaromatics such as pyridines. By utilizing a simple catalyst preparation approach and relatively low catalyst loading, the steps outlined in this protocol contribute to the rapid development of useful substances such as pharmaceuticals and functional materials. For complete details on the use and execution of this protocol, please refer to Oishi et al. (2022).1.

Three-center-four-electron halogen bond enables non-metallic complex catalysis for Mukaiyama-Mannich-type reaction.

The three-center-four-electron halogen bond (3c4e X-bond) presents a fundamental design concept for catalysis. By integrating halogen(I) (X+: I+ or Br+), the bis-pyridyl ligand NN, and a non-nucleophilic counteranion Y, we developed non-metallic complex catalysts, [N···X···N]Ys, that exhibited outstanding activity and facilitated the Mukaiyama-Mannich-type reaction of N-heteroaromatics with parts-per-million-level catalyst loading. The high activity of [N···X···N]SbF6 was clearly demonstrated. NMR titration experiments, CSI-MS, computations, and UV-vis spectroscopic studies suggest that the robust catalytic activity of [N···X···N]Y can be attributed to the unique ability of the 3c4e X-bond for binding chloride: i) the covalent nature transforms the [N···X···N]+ complexation to sp2 CH as a hydrogen-bonding donor site, and ii) the noncovalent property allows for the dissociation of [N···X···N]+ for the formation of [Cl···X···Cl]-. This study introduces the application of 3c4e X-bonds in catalysis via halogen(I) complexes.