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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
Author(s) -
Ramana Chepuri V.,
Patel Pitambar,
Vanka Kumar,
Miao Benchun,
Degterev Alexei
Publication year - 2010
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201000769
Subject(s) - cycloisomerization , chemistry , necroptosis , density functional theory , intramolecular force , nitro , functional group , stereochemistry , combinatorial chemistry , programmed cell death , computational chemistry , catalysis , biochemistry , organic chemistry , apoptosis , alkyl , polymer
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.