C( sp 3 )?C( sp 3 ) Bond Formation via Electrochemical Alkoxylation and Subsequent Lewis Acid Promoted Reactions

A two-step transition metal-free methodology for the C(sp3)?C(sp3) functionalisation of saturated N-heterocyclic systems is disclosed. First, aminal derivatives are generated through anodic oxidation readily accessible carboxylic acids. Then, in presence BF3 ? OEt2, iminium ions unmasked and rapidly alkylated by organozinc reagents under flow conditions. Secondary, tertiary quaternary carbon centers have been successfully assembled using this methodology. Such an approach especially relevant to drug discovery since it increases C(sp3)-functionalities within a molecular framework. As proof concept, our was applied derivatization peptides API.