Pronounced Steric Effects of Substituents in the Nazarov Cyclization of Aryl Dienyl Ketones


  • A.P.M., A.S.L., and R.S. are grateful to UC Berkeley, the National Science Foundation (CAREER: CHE-0643264), GlaxoSmithKline, and Boehringer Ingelheim for generous financial support, and to Dr. Kathleen Durkin (NSF CHE-0233882) for help with molecular modeling, and Eric Bunnelle and Dr. William Bunnelle for helpful discussions. R.L.D. and D.J.T. gratefully acknowledge support from UC Davis and the National Science Foundation (CAREER: CHE-0449845 and computer time from the Pittsburgh Supercomputer Center).


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1,3-'s a crowd: The facility of the AlCl3-catalyzed Nazarov cyclization of electron-rich aryl dienones was found to be dependent upon the substitution of the diene portion (see scheme). For α,γ-substituted systems, pronounced 1,3-allylic strain in the reactant is alleviated in the transition state for electrocyclization, leading to enhanced reactivity. DFT calculations support this analysis and have proven to be predictive of reactivity.