Cooperative Conformational Regulation in N-Heterocyclic Fluorohydrins

Alpesh Ramanlal Patel; Fei Liu

doi:10.1071/CH14256

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Cooperative Conformational Regulation in N-Heterocyclic Fluorohydrins

Alpesh Ramanlal Patel ^A and Fei Liu ^A ^B

+ Author Affiliations

- Author Affiliations

^A Department of Chemistry and Biomolecular Sciences, Macquarie University, Sydney, NSW 2109, Australia.

^B Corresponding author. Email: fei.liu@mq.edu.au

Australian Journal of Chemistry 68(1) 50-56 https://doi.org/10.1071/CH14256
Submitted: 24 April 2014 Accepted: 16 May 2014 Published: 18 July 2014

Abstract

Seven-membered N-heterocycles are flexible ring structures, and their conformational control is important to their bioactivity. Our prior work shows that stereoselective monofluorination, if installed diastereoselectively, can bias a seven-membered, substituted azepane ring to one major conformation. However, multiple fluorination may not provide as much conformational bias due to conflicting effects. Here we show in our model azepane system that fluorohydrins can confer strong conformational bias if the relative configuration of the fluorine and hydroxy substitutent is appropriate to enable cooperative conformational control.

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[22] Consistent with earlier observations (Ref. [14c]), none of the fluorohydrin azepane ¹H NMR spectra revealed new conformational equilibria at different temperatures suggesting low barriers for the conformational interchange.

Cooperative Conformational Regulation in N-Heterocyclic Fluorohydrins

Abstract

References

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