Cu-Catalyzed Tandem Oxidation-Intramolecular Cannizzaro Reaction of Biorenewables and Bioactive Molecules

A tandem Cu-catalyzed oxidation-intramolecular Cannizzaro reaction leading to bioactive alpha-hydroxyesters from alpha-hydroxyketones is reported. The process uses oxygen as a sole oxidant to achieve the formation of glyoxals, which are efficiently converted in situ to important alpha-hydroxyesters. The mechanistic insights are provided by isotopic labeling and supported by DFT calculations. The transformation proved a robust synthetic tool to achieve the synthesis of human metabolites and hydroxyl esters of various biologically active steroid derivatives. A Cu-catalyzed tandem oxidation-intramolecular Cannizzaro reaction that converts alpha-hydroxyketones into valuable alpha-hydroxyesters under mild conditions is reported. The substrate scope encompasses biorenewable synthons and complex structures, such as steroids. We provided mechanistic insights using isotope labeling and rationalization by computational means. image