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- Title
Palladium(II)-catalyzed annulation of N-methoxy amides and arynes: computational mechanistic insights and substituents effects.
- Authors
Alves, Erick H. S.; Oliveira, Daniel A. S.; Braga, Ataualpa A. C.
- Abstract
Context: The combined use of transition metal-catalyzed C–H activation with aryne annulation reactions has emerged as an important strategy in organic synthesis. In this study, the mechanisms of the palladium(II)-catalyzed annulation reaction of N-methoxy amides and arynes were computationally investigated by density functional theory. The role of methoxy amide as a directing group was elucidated through the calculation of three different pathways for the C–H activation step, showing that the pathway where amide nitrogen acts as a directing group is preferable. At the reductive elimination transition state, an unstable seven-membered ring is formed preventing the lactam formation. A substituent effect study based on an NBO analysis, Hammet, and using a More O'Ferall-Jenks plot indicates that the C–H activation step proceeds via an electrophilic concerted metalation-deprotonation (eCMD) mechanism. The results show that electron-withdrawing groups increase the activation barrier and contribute to an early Pd–C bond formation and a late C–H bond breaking when compared with electron-donating substituents. Our computational results are in agreement with the experimental data provided in the literature. Methods: All calculations were performed using Gaussian 16 software. Geometry optimizations, frequency analyses at 393.15 K, and IRC calculations were conducted at the M06L/Def2-SVP level of theory. Corrected electronic energies, NBO charges, and Wiberg bond indexes were computed at the M06L/Def2-TZVP//M06L/Def2-SVP level of theory. Implicit solvent effects were considered in all calculations using the SMD model, with acetonitrile employed as the solvent.
- Subjects
ARYNE; ANNULATION; AMIDES; ORGANIC synthesis; PALLADIUM; DENSITY functional theory; ACETONITRILE
- Publication
Journal of Molecular Modeling, 2024, Vol 30, Issue 5, p1
- ISSN
1610-2940
- Publication type
Article
- DOI
10.1007/s00894-024-05930-3