Direct Access to alpha-Acyloxyketones via Self-Oxidative Coupling of alpha-Arylbromo ketones

Abstract

α-Acyloxy carbonyl compounds and their derivatives are important and useful synthetic intermediates. This class of compound is commonly found in a large number of pharmaceuticals, biologically active natural products, and living organisms. Due to its growing medicinal importance, over the last several years, tremendous efforts have been made to develop novel synthetic methodologies for the synthesis of α-acyloxyketone. There have been efforts in developing newer methodologies to α-acyloxyketones in the literature. Some of the traditional methods rely on α-halocarbonyl compounds and carboxylic acid in presence of transition-metal catalysts/reagents or hypervalent iodine mediated oxidative coupling of carbonyl compounds with carboxylic acids (or their surrogates). Interestingly, the synthesis of α-acyloxyketones via self intermolecular oxidative coupling of aryl ketones has been rarely been explored in the literature. Herein, to the best of our knowledge for the first time, we present the self-intermolecular oxidative coupling of α-bromoketones using KMnO4 and N,N-diisopropylethylamine (DIPEA) to synthesize α- acyloxyketones at room temperature. Under the optimum reaction conditions, various α-bromoketones afforded the corresponding α-acyloxyketones in moderate to good yields. We have performed a series of controlled experiments and extensive literature research to partially probe the mechanism of the transformation. The protocol proved to be practical and user-friendly and is devoid of expensive reagents, temperature, or any pressure. We have also characterized and analyzed the products using spectroscopic techniques such as NMR, HRMS, single-crystal XRD analysis.