Electroreductive deconstruction and oxygenation of cyclic amines

Abstract

Here, we introduce a greener and sustainable electroreductive deconstructive functionalization approach (E-factor = 1.2) for transforming cyclic amines into δ-substituted amides via C–N bond cleavage, and further extended it towards the synthesis of δ-ketoamides through trapping with environmentally benign oxygen molecules without using any external sacrificial hydrogen donor or oxidant/reductant. Several structurally modified cyclic amines, ranging from strained to unstrained ring systems, were employed to synthesize the 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 a γ-lactone. Remarkably, our strategy proved scalable, and further derivatization of our products was carried out to demonstrate their synthetic utility. A detailed mechanistic study was performed to understand the reaction pathway.