Convergent Synthesis of Enantioenriched ortho-Fused Tricyclic Diketones via Catalytic Asymmetric Intramolecular Vinylogous Aldol Condensation

Herein, we describe a catalytic asymmetric intramolecular vinylogous aldol reaction by taking advantage of dual organocatalysts, which enables convergent synthesis of ortho-fused tricyclic diketones in excellent enantioselectivities and diastereoselectivities. Noteworthy is that the reaction stereoselectively forges three consecutive stereogenic carbon centers including a quaternary one. Density functional theory calculations reveal that the enantioselectivity was facilitated by a transannular hydrogen bonding between the protonated quinuclidine moiety of the chiral aminocatalyst and the diketone fragment of the substrate.

Automated summary

In this study, a catalytic asymmetric intramolecular vinylogous aldol reaction using dual organocatalysts was described, allowing for the convergent synthesis of ortho-fused tricyclic diketones with excellent enantioselectivities and diastereoselectivities. Notably, the reaction selectively generates three consecutive stereogenic carbon centers, including a quaternary one. Density functional theory calculations revealed that the enhanced enantioselectivity was facilitated by a transannular hydrogen bonding between the protonated quinuclidine moiety of the chiral aminocatalyst and the diketone fragment of the substrate.