A Combined Experimental and Density Functional Theory Study on the Pd‐Mediated Cycloisomerization of o‐Alkynylnitrobenzenes – Synthesis of Isatogens and Their Evaluation as Modulators of ROS‐Mediated Cell Death

Highly selective cycloisomerization of o ‐alkynylnitrobenzenes, leading to isatogens, has been achieved by employment of a Pd II complex. This reaction is very general and functional‐group‐tolerant. The possible mechanism of this reaction was investigated with the help of DFT calculations. Three possible pathways – namely, the addition of the nitro group either in (i) 5‐ exo ‐dig or (ii) 6‐ endo ‐dig mode and (iii) halopalladation – and subsequent intramolecular events have been considered and studied in detail. These investigations revealed that pathway (i) is the favored route to isatogen formation. A preliminary screening of the available isatogens reveals the 2‐alkylisatogens to be novel ROS scavengers capable of inhibiting cellular necroptosis.