Total Synthesis of\nthe Phenylnaphthacenoid Type II\nPolyketide Antibiotic Formicamycin H via Regioselective Ruthenium-Catalyzed\nHydrogen Auto-Transfer [4 + 2] Cycloaddition

The first total synthesis of the pentacyclic phenylnaphthacenoid\ntype II polyketide antibiotic formicamycin H is described. A key feature\nof the synthesis involves the convergent, regioselective assembly\nof the tetracyclic core via ruthenium-catalyzed α-ketol-benzocyclobutenone\n[4 + 2] cycloaddition. Double dehydration of the diol-containing cycloadduct\nprovides an achiral enone, which upon asymmetric nucleophilic epoxidation\nand further manipulations delivers the penultimate tetracyclic trichloride\nin enantiomerically enriched form. Subsequent chemo- and atroposelective\nSuzuki cross-coupling of the tetracyclic trichloride introduces the\nE-ring to complete the total synthesis. Single-crystal X-ray diffraction\nanalyses of two model compounds suggest that the initially assigned\nstereochemistry of the axially chiral C6–C7 linkage may require\nrevision.