Asymmetric Photoinduced Excited-State Nazarov Reaction

We report herein the first asymmetric photoinduced excited-state Nazarov reaction of non-aromatic dicyclic divinyl ketones by using hydrogen-bonding catalysis. The enantioselectivity of photoinduced electrocyclization is highly dependent on the structural features of the substrate and its interaction with chiral catalysts. For the simple dicyclic divinyl ketone substrates, there is no discernible selectivity of the hydrogen bond coordination between the thiourea and carbonyl groups of the substrates in the ground state. However, we found that the direction of the electrocyclization was well controlled in each coordination model and the N,N′-dimethylamine motif acts as a base in the regioselective deprotonation process, which leads to the formation of two stereoisomers with high enantioselectivity. Photolysis of dicyclic divinyl ketones bearing a 1,3-dioxolane motif in the presence of bifunctional hybrid peptide-thiourea chiral catalysts gave the tricyclic cis-hydrofluorenones with good enantioselectivity. Mechanistic and DFT studies suggested that the amide and thiourea groups in the bifunctional chiral catalysts play a key role as H-bond donors, which coordinate with both the carbonyl group and the 1,3-dioxolane motif to provide a more favorable chiral species, and control the direction of the electrocyclization. Due to the presence of the rigid 1,3-dioxolane ring, the deprotonation/protonation process occurs regiospecifically with high driving force. This photo-electrocyclization is mild (room temperature and neutral solution), which results a broad reaction scope and functional group tolerance and demonstrates its synthetic potential in organic synthesis.