Construction of Morphan Derivatives by Nitroso–Ene Cyclization: Mechanistic Insight and Total Synthesis of (±)‐Kopsone. Issue 38 (9th August 2017)

• Record Type: Journal Article
• Authors: Zhai, Li; Tian, Xuechao; Wang, Chao; Cui, Qi; Li, Wenhua; Huang, Sha‐Hua; Yu, Zhi‐Xiang; Hong, Ran
• Is Part Of: Angewandte Chemie international edition. Volume 56:Issue 38(2017)
• Page Start: 11599
• Page End: 11603
• Publication Date: 2017-08-09
• Subjects: alkaloids -- cyclization -- diradicals -- morphan core -- nitroso–ene reactions; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201706018
• Languages: English
• ISSNs: 1433-7851

Abstract

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. Abstract : ENErgize morphan synthesis ! A type II nitroso–ene cyclization complementary to the known type I transformation was developed for the construction of morphan derivatives with good tolerance of a variety of functional groups. DFT calculations provided insight into the reaction mechanism. This method was successfully applied to the total synthesis and structural verification of (±)‐kopsone, a unique natural monoterpenoid.