A relay strategy involving electrochemically driven selenylation cyclization and Cu(II) catalyzed cycloaddition-isomerization processes for the synthesis of polysubstituted isoquinolines

Abstract

Isoquinoline and isoquinoline N-oxide are core skeletons of numerous biologically active molecules and extensively utilized in organic synthesis. The development of efficient synthetic methods for these valuable building blocks has attracted significant interest within chemical community. In this study, we have developed a relay process which encompasses the electrochemically driven selenylation cyclization reaction of 2-alkynylbenzaldoximes with diselenides and the Cu(II) catalyzed cycloaddition-isomerization reaction of 4-selenylisoquinoline-N-oxides with bicyclobutane derivatives, thereby enabling the synthesis of isoquinolines bearing selenyl, cyclobutanol, and other groups. This protocol is characterized by mild reaction conditions, remarkable stereospecificity, a broad substrate scope, and excellent functional group tolerance. Furthermore, the high efficiency of this reaction in substrates bearing biologically relevant moieties and the successful scale-up experiment readily demonstrate its application potential.