Synthesis the C1–C15 Fragment of Incednine

Abstract We report on our progress towards the synthesis of the exotic, delicate, and tense polyketidic macrolactam of incednine. This work constitutes a significant advancement towards the total synthesis of a family of molecules of biological and medicinal interest. Some of the key features of this synthesis required evolutions from the initially designed strategy, leading to the use of a Horner–Wadsworth–Emmons olefination to build the C2–C9 tetraene. For this purpose, a polyfunctionalized phosphonate was used that was obtained through an unprecedented Pd-catalyzed cross-coupling involving the zinc salt of diethyl methylphosphonate. The resulting desired C1–C15 fragment displays a carboxylic acid ester at C1 and a vinyl iodide at C15, both functions being ready for subsequent amide coupling with the C16–C23 fragment and final Suzuki cyclization, respectively.