Enantioselective Total Synthesis of (−)-Artatrovirenol A
Rémi Lavernhe, Patrick Domke, Qian Wang, Jieping Zhu
Abstract
We report herein an enantioselective total synthesis of (−)-artatrovirenol A, a structurally unprecedented cage-like sesquiterpenoid. The synthesis features the following key steps: (a) cationic chiral oxazaborolidinium-catalyzed Diels–Alder reaction between isoprene and ethyl ( E )-5-(( tert -butyldimethylsilyl)oxy)-4-oxopent-2-enoate for the rapid synthesis of an enantioenriched 10-carbon bicyclic lactone; (b) union of two enantioenriched fragments by a diastereoselective Mukaiyama–Michael addition for the convergent assembly of an intermediate with all 15 carbons of the natural product; (c) intramolecular de Mayo [2 + 2] cycloaddition/retro-aldol sequence transforming a bicyclic compound to a tetracyclic one with concomitant generation of a five- and a seven-membered ring; (d) Lewis acid-triggered intramolecular ring opening of epoxide generating the norbornane substructure; and (e) Chugaev elimination converting the norbornane to the more strained norbornene.