Concise Enantioselective Total Synthesis of Daphenylline Enabledby an Intramolecular Oxidative Dearomatization br

Daphenylline is a structurally unique member of the triterpenoidDaphniphyllumnatural alkaloids, which exhibitintriguing biological activities. Six total syntheses have been reported,five of which utilize aromatization approaches. Herein, wereport a concise protecting-group-free total synthesis by means of a novel intramolecular oxidative dearomatization reaction, whichconcurrently generates the critical seven-membered ring and the quaternary-containing vicinal stereocenters. Other notabletransformations include a tandem reductive amination/amidation double cyclization reaction, to assemble the cage-like architecture,and installation of the other two chiral stereocenters via a highly enantioselective rhodium-catalyzed challenging hydrogenation ofthe diene intermediate (90% e.e.) and an unprecedented remote acid-directed Mukaiyama-Michael reaction of the complexbenzofused cyclohexanone (13:1 d.r.)