Approaches Towards a Total Synthesis of Daphenylline

Abstract

The following work describes the synthesis of advanced intermediates enroute to daphenylline. Construction of the ABCE tetracyclic skeleton of daphenylline was accomplished in thirteen steps with seven percent overall yield from commercially available (S)-carvone through [3,3]-allyl cyanate-to-isocyanate rearrangement, intramolecular Heck Reaction, and Intermolecular Diels-Alder/benzannulation strategies. Efforts towards the synthesis of daphenylline’s D ring are discussed. A terse introduction to the scientific literature of daphniphyllum alkaloids and a comprehensive overview of selected approaches and all previous syntheses of daphenylline is given. Experimental procedures and spectroscopic data are provided for all new compounds.