Mechanistic interrogation of the asymmetric lithiation-trapping of N-thiopivaloyl azetidine and pyrrolidine

Peter J. Rayner; Joshua C. Smith; Charline Denneval; Peter O'Brien; Paul A. Clarke; Richard A J Horan

doi:10.1039/c5cc08690f

Mechanistic interrogation of the asymmetric lithiation-trapping of N-thiopivaloyl azetidine and pyrrolidine

Peter J. Rayner, Joshua C. Smith, Charline Denneval, Peter O'Brien^*, Paul A. Clarke, Richard A J Horan

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract

A fundamental mechanistic study of the s-BuLi/chiral diamine-mediated lithiation-trapping of N-thiopivaloyl azetidine and pyrrolidine is reported. We show that lithiated thiopivalamides are configurationally unstable at -78 °C. Reaction then proceeds via a dynamic resolution of diastereomeric lithiated intermediates and this accounts for the variable sense and degree of asymmetric induction observed compared to N-Boc heterocycles.

Original language	English
Pages (from-to)	1354-1357
Number of pages	4
Journal	Chemical Communications
Volume	52
Issue number	7
Early online date	27 Nov 2015
DOIs	https://doi.org/10.1039/c5cc08690f
Publication status	Published - 25 Jan 2016

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AU - Rayner, Peter J.

AU - Smith, Joshua C.

AU - Denneval, Charline

AU - O'Brien, Peter

AU - Clarke, Paul A.

AU - Horan, Richard A J

PY - 2016/1/25

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AB - A fundamental mechanistic study of the s-BuLi/chiral diamine-mediated lithiation-trapping of N-thiopivaloyl azetidine and pyrrolidine is reported. We show that lithiated thiopivalamides are configurationally unstable at -78 °C. Reaction then proceeds via a dynamic resolution of diastereomeric lithiated intermediates and this accounts for the variable sense and degree of asymmetric induction observed compared to N-Boc heterocycles.

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U2 - 10.1039/c5cc08690f

DO - 10.1039/c5cc08690f

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EP - 1357

JO - Chemical Communications

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Mechanistic interrogation of the asymmetric lithiation-trapping of N-thiopivaloyl azetidine and pyrrolidine

Abstract

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