Total syntheses of (+)-dalesconols A and B enabled by triple-relayed remote chirality transfer

Dalesconols A and B, featuring unique and highly congested polycyclic carbon frameworks and notable biological activities, have attracted sustained attention. However, their structural complexity constitutes a significant challenge for total synthesis. Herein, we present the asymmetric total syntheses of (+)-dalesconols A and B via a remote chirality transfer strategy. Central to this approach is the implementation of our palladium/norbornene-catalyzed trifunctionalization method, which enables one-step construction of the chiral polycyclic core skeleton via a triple relay of point-to-axial, axial-to-axial, and axial-to-point chirality transfer. Combined with intramolecular Michael addition, C−H oxidation/retro-Michael elimination, and global demethylation, this triple-relayed remote chirality transfer strategy allows concise and modular access to (+)-dalesconols A and B. Natural products with densely fused polycyclic frameworks, such as dalesconols A and B, pose longstanding challenges for asymmetric synthesis due to their intricate stereochemistry. Here, the authors report concise, enantioselective total syntheses via a triple-relayed remote chirality transfer strategy using palladium/norbornene catalysis.