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.
Key words
total synthesis - natural products - palladium - enantioselectivity - olefination
reaction
