Formal total synthesis of (+)-lysergic acid via zinc(II)-mediated regioselective ring-opening reduction of 2-alkynyl-3-indolyloxirane

摘要

Asymmetric formal synthesis of (+)-lysergic acid was achieved with a reductive ring-opening reaction of chiral 2-alkynyl-3-indolyloxirane with NaBH_3CN as the key step. With Zn(OTf)_2 as an additive, the ring-opening reaction proceeded regioselectively at the 3-position to give the corresponding propargyl alcohol, which was a precursor of the allenic amide for palladium-catalyzed domino cyclization to construct the ergot alkaloid core structure.