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Construction of Morphan Derivatives by Nitroso–Ene Cyclization: Mechanistic Insight and Total Synthesis of (±)‐Kopsone
Author(s) -
Zhai Li,
Tian Xuechao,
Wang Chao,
Cui Qi,
Li Wenhua,
Huang ShaHua,
Yu ZhiXiang,
Hong Ran
Publication year - 2017
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201706018
Subject(s) - ene reaction , chemistry , diradical , nitroso , total synthesis , nitroso compounds , functional group , stereochemistry , computational chemistry , medicinal chemistry , organic chemistry , physics , nuclear physics , singlet state , excited state , polymer
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.