EDA Complex-Driven Desaturation of Heterocyclic Carbonyl Compounds Enabled by HFIP

Abstract

Recently, electron donor–acceptor (EDA) complex-mediated organic synthetic strategies have emerged as powerful tools for diverse bond-forming transformations; however, their efficiency often diminishes when ionic reactants are involved. This limitation arises from the requirement of polar solvents such as DMSO or DMF to solubilize ionic species for the formation of effective EDA complex. Consequently, these solvents engage in competing EDA complex formation or disrupt ionization equilibria. In parallel, there is a pressing necessity of modern and efficient strategy to achieve dehydrogenation reactions, which are in general limited by the drawbacks of traditional approaches. To address both, herein, we disclose an innovative desaturation strategy based on the formation of an EDA complex between a dihydrogenated organic substrate and an N-methoxy pyridinium salt. In our study, solubility issues, which are associated with the pyridinium salt, are effectively addressed by using hexafluoroisopropanol (HFIP). Beyond enhancing solubility, HFIP also functions as a transient H-shuttle, significantly reducing the activation energy for this transformation. This cooperative interplay between HFIP and the pyridinium salt enables the efficient and selective desaturation of a broad range of heterocyclic carbonyl compounds—including quinolinones, coumarins, and flavones—which are valuable scaffolds in pharmaceutical and agrochemical research. At the end, detailed mechanistic studies with the aid of experiments as well as DFT studies clearly disclose the mechanism as well as the important role of HFIP in this reaction.