Mechanistic approaches to asymmetric synthesis of aziridines from guanidinium ylides and aryl aldehydes |
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Authors: | Toyokazu Haga Tsutomu Ishikawa |
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Institution: | a Graduate School of Pharmaceutical Sciences, Chiba University, 1-33 Yayoi, Inage, Chiba 263-8522, Japan b Production Department, Technology Group, Eisai Co., Ltd., 22-Sunayama, Hasaki-machi, Kashima-gun, Ibaraki 314-0255, Japan |
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Abstract: | To approach more realistic mechanisms for asymmetric aziridine synthesis from guanidinium ylides and aryl aldehydes, reactions were systematically carried out by using a variety of p-substituted benzaldehydes under modified conditions. Two kinds of reaction mechanisms controlled by the nature of the p-substituents of aryl aldehydes is proposed for the two-steps aziridine synthesis composed of a C-C bond formation by nucleophilic addition of guanidinium ylides to aryl aldehydes (step 1) and the fragmentation of intermediate adducts to aziridine products by intramolecular nucleophilic substitution (step 2). A SNi-like mechanism via cationic-like transition state is proposed for step 2 in the asymmetric synthesis using EDG-substituted benzaldehydes, whereas with EWG-substituted benzaldehydes, a SN2-like mechanism is proposed. Hammett analysis, based on the diastereomeric ratio in the aziridine products, is consistent with the proposed rate-determining steps in these two mechanisms. A second Hammett analysis, based on the enantiomeric ratio of the aziridine products, clearly reveals the difference in the susceptibilities to the electronic substituents effect between step 1 and step 2. |
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Keywords: | Asymmetric synthesis Aziridine Guanidinium ylide Mechanism Hammett analysis |
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