Copper(II)/TBHP-mediated oxidation of isoindolinones and other substrates—effect of air and oxygen

Abstract

When employed in conjunction with tert-butyl hydroperoxide (TBHP), iron(III) and copper(II)-catalyzed oxidation systems have proven to be effective in transforming isoindolinones to the corresponding phthalimides. Considering both metal-mediated processes, one of the issues that still requires attention is the extended reaction times required for isoindolinones to give modest to good yields of imide in the presence of sensitive functionality. As an extension of our previously reported Cu(II)/TBHP protocol, a plausible avenue to enhance the copper-catalyzed process was to conduct the Cu(II)/TBHP-mediated oxidations in the presence of molecular oxygen or air. Consequently, improvement in reaction time and/or isolated yield with selected substrates was observed with Cu(II)/TBHP and oxygen at atmospheric pressure, while at the same time side reactions leading to unwanted by-products from over-oxidation were not evident. The Cu(II)/TBHP system was also applied to selected non-nitrogenous benzylic substrates to examine the broader utility of the oxidation conditions.