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Solid-phase Synthesis of [4.4] Spirocyclic Oximes
Published on: February 6, 2019
Enantioselective [4 + 1] Annulation Reactions of α-Substituted Ammonium Ylides To Construct Spirocyclic Oxindoles
Peng-Fei Zheng1, Qin Ouyang1, Sheng-Li Niu1
1†College of Pharmacy, Third Military Medical University, Chongqing 400038, China.
Abstract:
Ammonium ylides have a long history in organic synthesis, but their application in asymmetric catalysis is still underdeveloped in regard to both substrate scope and reaction pathways compared with phosphorus and sulfur ylides. Here a previously unreported asymmetric [4 + 1] annulation reaction of 3-bromooxindoles and electron-deficient 1-azadienes has been developed through ammonium ylide catalysis of a newly designed 2'-methyl α-isocupreine (α-MeIC), efficiently delivering spirocyclic oxindole compounds incorporating a dihydropyrrole motif in excellent enantioselectivity (up to 99% ee). To the best of our knowledge, this work represents the first example of asymmetric catalysis of ammonium ylides bearing α-substitutions, and the catalytic [4 + 1] annulation pathway of ammonium ylides is also unprecedented. Moreover, (1)H NMR, mass spectroscopy, and computational calculation studies were conducted, and the catalytic cycle and a tentative explanation of the enantioselective mechanism have been successfully elucidated.
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