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.