Ruthenium‐Catalyzed Butadiene‐Mediated Crotylation and Oxazaborolidine‐Catalyzed Vinylogous Mukaiyama Aldol Reaction for The Synthesis of C1–C19 and C23–C35 of Neaumycin B

Neaumycin B is a femtomolar inhibitor of U87 human glioblastoma. Using a newly developed anti‐diastereoselective ruthenium‐catalyzed butadiene‐mediated crotylation of primary alcohol proelectrophiles via hydrogen auto‐transfer, as well as a novel variant of the catalytic asymmetric vinylogous Mukaiyama aldol (VMA) reaction applicable to linear aliphatic aldehydes and terminally methylated dienyl ketene acetals, preparation of the key C1–C19 and C23–C35 substructures of neaumycin B is achieved in 12 and 7 steps (LLS), respectively. Newly developed ruthenium‐catalyzed anti‐selective butadiene crotylations and a novel variant of the vinylogous Mukaiyama aldol (VMA) reaction unlock key substructures of neaumycin B, a femtomolar inhibitor of U87 human glioblastoma.