Electroreductive deconstruction and oxygenation of cyclic amines

Abstract

Here, we introduce a greener, atom-economical, and sustainable electroreductive deconstructive functionalization approach (E-Factor = 0.9) for transforming cyclic amines into δ-substituted amides via C-N bond cleavage, and further extended towards the synthesis of δ-ketoamides through the trapping of environmentally benign oxygen molecules without using any sacrificial hydrogen donor, oxidant/reductant, or catalyst. Several structurally modified cyclic amines, ranging from strained to unstrained ring systems, were employed to synthesize corresponding structural moieties that are difficult to construct through traditional methods. Late-stage derivatization of proline incorporating natural and medicinally active compounds has also been performed. Moreover, we conducted electrochemical scaffold hopping of a bridged bicyclic amine to generate γ-lactone. Remarkably, our strategy proved scalable, and further derivatization of our product has been carried out to demonstrate its synthetic utility. A detailed mechanistic study has been performed to understand the reaction pathway.