Total synthesis of the antimalarial naphthylisoquinoline alkaloid 5- epi-4′- O-demethylancistrobertsonine C by asymmetric Suzuki cross-coupling

The first total synthesis of the antimalarial naphthylisoquinoline alkaloid 5- epi-4′- O-demethylancistrobertsonine C ( 1a) and its—as yet unnatural—atropo-diastereomer, 1b, is described. The key step of the synthesis is the construction of the rotationally hindered and thus stereogenic biaryl axis, which was built up by a Suzuki reaction. The use of chiral ligands in the palladium-catalyzed cross-coupling permitted to increase the low internal asymmetric induction up to a diastereomeric ratio of 74:26. The assignment of the axial configurations of the atropo-diastereomers was achieved by 2D NMR experiments and corroborated by quantum chemical CD calculations. [Display omitted]