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Updated: Jul 16, 2025

Preparation of Contiguous Bisaziridines for Regioselective Ring-Opening Reactions
Published on: July 28, 2022
Computational Study Focusing on a Comprehensive Conformational Analysis of Transition States for Aza-Spiro Ring
Keisuke Fukaya1, Takaaki Sato2, Noritaka Chida2
1Biotechnology Research Center and Department of Biotechnology, Toyama Prefectural University, 5180 Kurokawa, Imizu 939-0398, Toyama, Japan.
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An accurate understanding of conformations in transition states is a critical piece in the theoretical analysis of complex molecular reactions. In this study, we investigated conformationally diverse transition states during intramolecular aza-spiro ring formation with an allylsilane moiety and N-alkoxy iminium ion, a key reaction in the synthesis of fasicularin by Sato and Chida et al., and identified the origins of stereoselectivity of the cyclization. A large number of conformational isomers with forming C-C bonds were comprehensively analyzed using Cremer-Pople puckering parameters. It was found that the conformations of the transition states had different puckering preferences depending on the reactant's double-bond geometry and the product's stereochemical configuration. Furthermore, an asymmetric aza-spiro cyclization with a tolyl group as a chiral auxiliary was investigated, showing that conformational anchoring by both a CH-O hydrogen bond and the CH-π interaction was critical for the asymmetric induction.
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