Palladium‐catalyzed cyclization of 2‐alkynyl‐N‐ethanoyl anilines to indoles: synthesis, structural, spectroscopic, and mechanistic study. (4th August 2015)

• Record Type: Journal Article
• Authors: Hoque, Mohammad Mazharol; Halim, Mohammad A.; Sarwar, Mohammed G.; Khan, Md. Wahab
• Is Part Of: Journal of physical organic chemistry. Volume 28:Number 12(2015:Dec.)
• Page Start: 732
• Page End: 742
• Publication Date: 2015-08-04
• Subjects: cross‐coupling -- density functional theory (DFT) -- indole derivatives -- palladium catalysis -- time‐dependent density functional theory (TD‐DFT) -- transition states; Chemistry, Physical organic -- Periodicals; 547.1
• DOI: 10.1002/poc.3477
• Languages: English
• ISSNs: 0894-3230

Abstract

Abstract : This study reports a facial regio‐selective synthesis of 2‐alkyl‐ N ‐ethanoyl indoles from substituted‐ N ‐ethanoyl anilines employing palladium (II) chloride, which acts as acyclization catalyst. The mechanistic trait of palladium‐basedcyclization is also explored by employing density functional theory. In a two‐step mechanism, the palladium, which attaches to the ethylene carbons, promotes the proton transfer andcyclization . The gas‐phase barrier height of the first transition state is 37 kcal/mol, indicating the rate‐determining step of this reaction. Incorporating acetonitrile through the solvation model on density solvation model reduces the barrier height to 31 kcal/mol. In the presence of solvent, the electron‐releasing (–CH3 ) group has a greater influence on the reduction of the barrier height compared with the electron‐withdrawing group (–Cl). These results further confirm that solvent plays an important role on palladium‐catalyzed proton transfer andcyclization . For unveiling structural, spectroscopic, and photophysical properties, experimental and computational studies are also performed. Thermodynamic analysis discloses that these reactions are exothermic. The highest occupied molecular orbitallowest unoccupied molecular orbital gap (4.9–5.0 eV) confirms that these compounds are more chemically reactive than indole. The calculated UV–Vis spectra by time‐dependent density functional theory exhibit strong peaks at 290, 246, and 232 nm, in good agreement with the experimental results. Moreover, experimental and computed 1 H and 13 C NMR chemical shifts of the indole derivatives are well correlated. Copyright © 2015 John Wiley & Sons, Ltd. Abstract : A facial route has been adopted to synthesize 2‐alkyl‐ N ‐ethanoyl indoles, which are more chemically reactive than indole. Solvent and electron‐releasing group play important roles on lowering the barrier height of the rate‐determining step of the palladium‐catalyzed cyclization reaction. Moreover, details structural, spectroscopic, and photophysical properties of these compounds are explored by density functional (DFT) and time‐dependent density functional theories (TD‐DFT).