Construction of Morphan Derivatives by Nitroso–Ene Cyclization: Mechanistic Insight and Total Synthesis of (±)‐Kopsone

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.