Rh(i)-catalyzed stereoselective desymmetrization of prochiral cyclohexadienones via highly exo-selective Huisgen-type [3+2] cycloaddition

A Rh(i)-catalyzed highly stereoselective desymmetrization of 2-alkynylbenzaldehyde-tethered cyclohexadienones triggered by intramolecular Huisgen-type [3 + 2] cycloaddition has been developed. This method enables convergent construction of complex epoxy-bridged polycyclic ring systems with five contiguous stereocenters with excellent exo-selectivity and broad substrate scope. The highly atom-economical process involves 6-endo-dig cyclization of carbonyl oxygen onto an activated alkyne resulting in a highly reactive metal-benzopyrylium intermediate, which readily undergoes intramolecular [3 + 2] annulation/hydration. Asymmetric induction is also achieved for the first time in Rh(i)-catalyzed 1,3-dipolar cycloaddition using an easily accessible chiral diene as the ligand.

Automated summary

A highly stereoselective desymmetrization reaction of 2-alkynylbenzaldehyde-tethered cyclohexadienones catalyzed by Rh(i) has been developed for the convergent construction of complex epoxy-bridged polycyclic ring systems. The process involves intramolecular Huisgen-type [3+2] cycloaddition, leading to the formation of five contiguous stereocenters with excellent exo-selectivity. Asymmetric induction is achieved for the first time in Rh(i)-catalyzed 1,3-dipolar cycloaddition using a readily accessible chiral diene as the ligand.