Solvent-Controlled, Chemodivergent Oxidative Anionic Fries Rearrangement of O-Aryl Carbamates Under Aerobic Conditions

Abstract

We disclose herein a mild and efficient organolithium-mediated protocol which enables the chemodivergent transformation of ortho-cresol derived O-aryl carbamates into diverse molecular structures by simply changing the nature of the reaction medium, working under air and at room temperature. The use of the biobased 2-MeTHF as solvent allows for the chemoselective preparation of α-hydroxy arylacetamides in a single synthetic operation with a remarkable functional group tolerance. Our strategy, which exploits the presence of molecular oxygen arising from the use of bench-type aerobic conditions, relies on a one-pot anionic homo-Fries rearrangement/amide enolate autoxidation sequence with two consecutive C-C/C-O bond formation events occurring at the same carbon atom. Furthermore, we also describe the successful use of a protic and bioinspired Deep Eutectic Solvents (DES) as an effective tool to tune the chemoselectivity of the proposed transformation. The fast internal protonolysis of the anion solution operated by the protic reaction medium results in an an interrupted metalation/rearrangement sequence, enabling the chemoselective preparation of arylacetamides under bench-type aerobic conditions owing to an efficient suppression of the oxidation step.