Asymmetric Intramolecular Dearomatization of Nonactivated Arenes with Ynamides for Rapid Assembly of Fused Ring System under Silver Catalysis

Arene dearomatization is a straightforward method for converting an aromatic feedstock into functionalized carbocycles. Enantioselective dearomatizations of chemically inert arenes, however, are quite limited and underexplored relative to those of phenols and indoles. We developed a method for diazo-free generation of silver-carbene species from an ynamide and applied it to the dearomatization of nonactivated arenes. Transiently generated norcaradiene could be trapped by intermolecular [4 + 2] cycloaddition, synthesizing polycycles with five consecutive stereogenic centers. This protocol constitutes the first highly enantioselective reaction based on the diazo-free generation of silver-carbene species. Mechanistic investigations revealed a dearomatization followed by two different classes of pericyclic reactions, as well as the origin of the chemo- and enantioselectivity.

Automated summary

This study developed a new method for achieving highly enantioselective dearomatization of chemically inert arenes, leading to the synthesis of polycycles with multiple stereogenic centers. Mechanistic investigations revealed the origin of chemo- and enantioselectivity in the reaction process.