Syntheses of Combretastatins D‑1, D‑2, and D‑4 via Ring Contraction by Flash Vacuum Pyrolysis

We report the syntheses of combretastatins D-2 and D-4 as well as a formal synthesis of combretastatin D-1 by a conceptually new route harnessing a ring-contracting flash vacuum pyrolytic extrusion of sulfur dioxide from the respective 16-membered sulfone precursors. Via flash vacuum pyrolysis, even metaparacyclophanes as small and strained as the hitherto unknown oxa[1.5]­metaparacyclophane could be prepared as a side product en route to combretastatin D-2 by synchronous extrusion of SO2 and CO2.