American Chemical Society
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Dynamic Biphasic Counterion Exchange in a Configurationally Stable Aziridinium Ion:  Efficient Synthesis and Isolation of a Koga C2-Symmetric Tetraamine Base

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journal contribution
posted on 2007-03-16, 00:00 authored by Matthew J. Frizzle, Sebastien Caille, Teresa L. Marshall, Kenneth McRae, Kelly Nadeau, Gary Guo, Steven Wu, Michael J. Martinelli, George A. Moniz
An efficient synthetic process for chiral tetraamine base (R,R)-5 is reported that leverages mechanistic understanding to enable control over key transformations. Specifically, a configurationally stable and observable aziridinium ion intermediate was found to undergo counterion exchange impacting the feasibility of the process. Mechanistic investigations revealed that both counterion exchange and trapping of the aziridinium ion were biphasic events and that the former could be suppressed at lower temperatures, facilitating the reaction on both small and large scales. The mechanistic insights gained have led to the development of an efficient one-pot process that enables preparation of multiple kilograms of (R,R)-5 as a crystalline solid without chromatography in excellent chemical and chiral purity.