Asymmetric Organocatalytic Oxidative Michael addition–Electrocyclization Cascade towards the Enantioselective Dihydroisoindole-triones

Abstract A novel asymmetric organocatalytic cascade sequence involving an oxidative Michael addition followed by a 6π-electrocyclic ring closure has been developed. A novel camphor sulfonyl-substituted primary amine catalyst efficiently delivers structurally unique chiral dihydroisoindole-1,3-diones (3a–p) in good yields (up to 74%) and excellent enantioselectivities (up to 96%) from a broad range of enones. The incorporation of the 1,3-dione moiety within the dihydroisoindole core provides a valuable handle for further synthetic elaboration. The proposed reaction mechanism is supported by the identification of a key intermediate (4) that forms exergonically (-33.64 kJ/mol) from oxidative Michael reaction, validated through free-energy profiling via DFT calculations at the B3LYP/6-31G(d,p) level. Additionally, non-covalent interaction (NCI) analysis supported the proposed reaction mechanism.