Total Synthesis of Lavendamycin by a [2+2+2] Cycloaddition

The total synthesis of the bacterial‐derived, pentacyclic, antitumor antibiotic lavendamycin has been achieved through a highly convergent strategy. The key step of this synthesis is a ruthenium‐catalyzed [2+2+2] cycloaddition of an electron‐deficient nitrile to an alkynyl‐ynamide to prepare the carboline scaffold. The elaborate cycloaddition substrate is obtained in few steps by an N‐ethynylation using alkynyliodonium salt chemistry and two palladium‐catalyzed cross‐coupling reactions. An efficient synthesis of a halogenated quinoline‐5,8‐dione building block starting from hydroquinone is presented.