Electrochemical Iodine-Mediated Oxidation of Enamino-Esters to 2H-Azirine-2-Carboxylates Supported by Design of Experiments.

An electrochemical iodine-mediated transformation of enamino-esters for the synthesis of 2H-azirine-2-carboxylates is presented. In addition, a thermic conversion of azirines to 4-carboxy-oxazoles in quantitative yield without purification was described. Both classes 2H-azirines-2-carboxylates and the 4-carboxy-oxazoles are substructures in natural products and therefore are of considerable interest for synthetic and pharmaceutical chemists. The optimization was not performed in a conventional manner with a one-factor-at-a-time process but with a Design of Experiments (DoE) approach. Beside a broad substrate scope the reaction was also employed to a robustness screen, a sensitivity assessment, and complemented with mechanistic considerations from cyclic voltammetry experiments.

Iodine(III)-Mediated Electrochemical Trifluoroethoxylactonisation: Rational Reaction Optimisation and Prediction of Mediator Activity.

A new electrochemical iodine(III)-mediated cyclisation reaction for the synthesis of 4-(2,2,2-trifluoroethoxy)isochroman-1-ones is presented. Based on this reaction design of experiments and multivariate linear regression analysis were used to demonstrate their first application in an electrochemical reaction. The broad applicability of these reaction conditions could be shown by a range of substrates and an extensive compatibility test.