Pd-Ag Catalyzed Aza-Piancatelli Reaction: From Synthesis to Mechanistic Investigations
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Authors
Khandelwal, Megha
Issue Date
2024
Type
Dissertation
Language
en_US
Keywords
Alternative Title
Abstract
This work demonstrates a cocatalytic approach using Pd(OAc)2 and AgSbF6 at room temperature for synthesizing trans-substituted cyclopentenones derivatives utilizing the Piancatelli reaction. The methodology resulted in a broad substrate scope across ortho-substituted anilines but shows limited reactivity with para-substituted anilines at room temperature. Oxygen nucleophiles were found to be unsuccessful. At elevated temperature of 80°C, para-substituted anilines showed improved reactivity with silver catalyst alone being sufficient for the transformation. The possibility of dual mechanistic pathways was explored, one requiring both palladium and silver at room temperature and another involving only silver at an elevated temperature of 80°C. Particularly for the electron-rich substrates at high-temperature conditions the formation of Friedel-Crafts product as a byproduct is observed. The third chapter examines the nature of catalysts used in the current work. As no single definitive experiment could conclusively differentiate between homogeneous or heterogeneous catalysis, multiple tests were conducted to investigate the nature of catalysis in a Pd-Ag co-catalyzed system and suggested the possibility of a homogeneous catalytic system. To further reveal insights into the mechanism of the reaction, two analytical methods ReactIR and GCMS reaction monitoring were explored in chapter 4. While the ReactIR studies proved unsuccessful due to metallic deposition on the probe and baseline drift in spectra, further GCMS based investigations revealed the presence of an N-substituted intermediate. At elevated temperature, a faster reaction rate was observed compared to room temperature. The Hammett plot analyses resulted in a non-linear relationship at room temperature. Although at an elevated temperature, more linear trends were observed, revealing further clues into the intricate mechanism of the proposed reaction. This research provides insights into transition metal-catalyzed heterocycle synthesis and opens new directions for methodology development.