Accessing remote sulfonylated 8-aminoimidazo[1,2-a]pyridine derivatives: copper(II)-catalyzed synthesis, DFT calculations and docking studies.

An efficient base-free approach for the remote C5-H sulfonylation of 8-aminoimidazo[1,2-a]pyridine (8-AIP) derivatives with sulfonyl chloride has been described under CuII-catalysis without an external oxidant. This strategy shows high conversion efficiency, a broad substrate scope, and good tolerance towards different functional groups. Furthermore, mechanistic investigations suggest that a single-electron-transfer process is involved in this C-S cross-coupling reaction. Considering that imidazopyridine derivatives and their analogues are known to be pharmacological agents for treating cancers through inhibition of the tankyrase-2 (TNKS-2) enzyme, docking studies were performed to understand the binding potential of our compounds to this protein, and the results revealed that several compounds had higher predicted binding energies than the crystal-bound ligand. Accordingly, our findings offer plausible mechanistic insights into the radical aromatic substitution of remote C-H bonds and open new avenues for the rational design of novel, drug-like molecules as potent TNKS-2 inhibitors.