Total Synthesis of (±)-Clivonine via Diels-Alder Reactions of 3,5-Dibromo-2-pyrone
Cheng-Dong Wang1, Qinyang Chen1, Seunghoon Shin1
1Center for New Directions in Organic Synthesis, Department of Chemistry, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Korea.
Abstract:
New synthetic routes to (±)-clivonine were devised starting with the Diels-Alder cycloadditions of 3,5-dibromo-2-pyrone with styrene pinacol boronate dienophiles. In the first-generation synthesis, the pivotal perhydroindoline system including the C5-hydroxyl group was constructed via a reaction sequence involving the Eschenmoser-Claisen rearrangement and regio/stereoselective epoxide opening reaction. In the second-generation synthesis, a radical-mediated cyclization approach was employed for the rapid assembly of the pyrrolidine ring. In this route, the C5-hydroxyl group provided by the dienophile in a stereochemically defined form was preserved throughout the synthesis.
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