Computational and Experimental Studies of Phthaloyl Peroxide-Mediated Hydroxylation of Arenes Yield a More Reactive Derivative, 4,5-Dichlorophthaloyl Peroxide

• Published in: Journal of organic chemistry Vol. 80; no. 16; pp. 8084 - 8095
• Main Authors: Camelio, Andrew M, Liang, Yong, Eliasen, Anders M, Johnson, Trevor C, Yuan, Changxia, Schuppe, Alex W, Houk, K. N, Siegel, Dionicio
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 21.08.2015; Amer Chemical Soc
• Subjects: Benzene Derivatives - chemistry; Chemistry; Chemistry, Organic; Hydroxylation; Molecular Structure; Peroxides - chemical synthesis; Peroxides - chemistry; Phthalic Acids - chemical synthesis; Phthalic Acids - chemistry; Physical Sciences; Quantum Theory; Science & Technology; AROMATIC OXYGENATION; ACID; CUPRIC CHLORIDE; HYDROCARBONS; DIISOPROPYL PEROXYDICARBONATE; CYCLIC DIACYL PEROXIDES; HYDROGEN-PEROXIDE; OXYFUNCTIONALIZATION; ALKYLBENZENES; FRIEDEL-CRAFTS OXYGENATION
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/acs.joc.5b01079

The oxidation of arenes by the reagent phthaloyl peroxide provides a new method for the synthesis of phenols. A new, more reactive arene oxidizing reagent, 4,5-dichlorophthaloyl peroxide, computationally predicted and experimentally determined to possess enhanced reactivity, has expanded the scope of the reaction while maintaining a high level of tolerance for diverse functional groups. The reaction proceeds through a novel “reverse-rebound” mechanism with diradical intermediates. Mechanistic insight was achieved through isolation and characterization of minor byproducts, determination of linear free energy correlations, and computational analysis of substituent effects of arenes, each of which provided additional support for the reaction proceeding through the diradical pathway.