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.