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Synthesis of CBD and Its Derivatives Bearing Various C4'-Side Chains with a Late-Stage Diversification Method
Xudong Gong1,2, Changliang Sun3, Melkamu Alemu Abame4
1The Key Laboratory of Plant Resources and Chemistry in Arid Regions and Key Laboratory of Xinjiang Indigenous Medicinal Plants Resource Utilization , Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences , South Beijing Road 40-1 , Urumqi , Xinjiang 830011 , People's Republic of China.
Abstract:
A novel synthetic route for making (-)-CBD and its derivatives bearing various C4'-side chains is developed by a late-stage diversification method. Starting from commercially available phloroglucinol, the key intermediate (-)-CBD-2OPiv-OTf is efficiently and regioselectively prepared and further undergoes Negishi cross-coupling to furnish (-)-CBD. This approach allowed an efficient synthesis of (-)-CBD in a five-step total 52% yield on a 10 g scale. Furthermore, diversification on the C4'-side chain with this method can be realized in a wide range.
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