Total Synthesis of Daphenylline via Diels-Alder Cycloaddition and Rhodium-Catalyzed C-H Alkynylation.

Daphenylline, a structurally intricate alkaloid, poses a formidable synthetic challenge due to its highly fused hexacyclic [6.6.5.7.6.5] framework and multiple stereocenters. Herein, we report an efficient total synthesis of daphenylline in 12 steps from known starting materials, featuring a key intramolecular Diels-Alder reaction, oxidative aromatization, Rh-catalyzed C-H alkynylation, and aldol condensation. Our approach leverages a carbonyl-directed C-H functionalization strategy to achieve regioselective alkynylation within a complex pentacyclic framework without the need for strongly coordinating directing groups.