Construction of Morphan Derivatives by Nitroso-Ene Cyclization: Mechanistic Insight and Total Synthesis of
Li Zhai1,2, Xuechao Tian3, Chao Wang1,2
1Key Laboratory of Synthetic Chemistry of Natural Substances, Shanghai Institute of Organic Chemistry (CAS), 345 Lingling Road, Shanghai, 200032, China.
Abstract:
A type II nitroso-ene cyclization was developed for the construction of morphan derivatives with good functional-group tolerance. DFT calculations revealed that the nitroso-ene reaction proceeds in a stepwise manner involving diradical or zwitterionic intermediates. The rate-determining step is C-N bond formation, followed by a rapid hydrogen-transfer step with a chair-conformation transition state. The current approach was also successfully applied in the first total synthesis of (±)-kopsone, a highly strained yet simple morphan-type alkaloid isolated from Kopsia macrophylla.
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