Asymmetric Total Synthesis of Biphenylquinolizidine Alkaloids 4″‑O‑Demethyllythridine and 14-epi-4″‑O‑Demethyllythridine

The first asymmetric total synthesis of new biphenylquinolizidine alkaloids 4″-O-demethyllythridine and 14-epi-4″-O-demethyllythridine isolated from Heimia salicifolia was accomplished. The key steps in the synthesis were a copper­(I)-catalyzed asymmetric intramolecular aza-Michael reaction to build a chiral 4-arylquinolizidine unit and an intramolecular Suzuki–Miyaura cross-coupling reaction to construct a macrolactone ring comprising a biphenyl moiety.