Towards Reaction Control: An Expeditious Access to Racemic 5-Substituted Tetramates and 5-Substituted Tetramic Acids from Malimides

A versatile and divergent two-step transformation of malimides to racemic tetramates and tetramic acids is described. The method consists of Grignard reagent addition with malimides to give hemiaminals and concentrated HCl-promoted chemoselective transformations of the latter. When running the reaction in CH₂Cl₂ and in the presence of 2.5 molar equiv. of conc. HCl, 5-alkyltetramates were formed, while in neat conc. HCl, 5-alkyltetramic acids were obtained. Using this method, a variety of title compounds were prepared in good to excellent yields (82%–99%, and 76%/85%). The work also constitutes a formal racemic total synthesis of reutericyclin. On the basis of the experimental evidences and of a deuterium labeling experiment, a plausible reaction mechanism was proposed. This work thus demonstrated two new types of step economical and chemodivergent transformations starting from malic acid.