Carbocation Mechanism Revelation of Molecular Iodine-Mediated Dehydrogenative Aromatization of Substituted Cyclic Ketones to Phenols

• Published in: Journal of organic chemistry 2024-03, Vol.89 (5), p.3226-3237
• Main Authors: Jin, Yangxin, Petrovic, Predrag V., Huang, Shuquan, Banerjee, Shibdas, Nandy, Abhijit, Anastas, Paul T., Lam, Jason Chun-Ho
• Format: Article
• Language: English
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/acs.joc.3c02691

Dehydrogenative aromatization (DA) of cyclic ketones is central to the development of functionalized aromatic precursors and hydrogen transfer–related technologies. Traditional DA strategies require precious metals with oxidants and are typically performed at high temperatures (100–150 °C) to overcome the high energy barrier of aliphatic C–H bond activation. Recently, a mild alternative approach based on I2 has been proposed to realize DA on substituted unsaturated cyclic ketones under ambient conditions. However, depending on the solvent, the product selectivity may vary between phenol ether and phenol, and the reaction mechanisms remain unclear. Herein, based on time-resolved proton nuclear magnetic resonance, DFT calculation, and mass spectrometric analyses, we established a unified mechanism to account for the product distribution. Through substrate scope and desorption electrospray ionization–mass spectrometry, we discovered the formation of a carbocation, which has been overlooked in previous studies. An expanded substrate scope study coupled with spectroscopic observation provided strong evidence to elucidate the formation mechanism and the location of the carbocation. With a renewed understanding of the mechanism, we achieved a phenolic product yield of 17–96% while controlling the selectivity. Moreover, some reactants could undergo DA in H2O, achieving 95–96% yield at below water-boiling temperature.