Imperial College London
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Dr James A Bull

Faculty of Natural Sciences, Department of Chemistry

Reader in Synthetic Chemistry
 
 
 
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Contact

 

+44 (0)20 7594 5811j.bull Website

 
 
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Location

 

501bMolecular Sciences Research HubWhite City Campus

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Summary

 

Publications

Citation

BibTex format

@article{Rojas:2022:10.1038/s41557-021-00856-2,
author = {Rojas, J and Croft, R and Sterling, A and Briggs, E and Antermite, D and Schmitt, D and Blagojevic, L and Haycock, P and White, A and Duarte, F and Choi, C and Mousseau, J and Bull, J},
doi = {10.1038/s41557-021-00856-2},
journal = {Nature Chemistry},
pages = {160--169},
title = {Amino-oxetanes as amide isosteres by an alternative defluorosulfonylative coupling of sulfonyl fluorides},
url = {http://dx.doi.org/10.1038/s41557-021-00856-2},
volume = {14},
year = {2022}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Bioisosteres provide valuable design elements for medicinal chemists to adjust the structural and pharmacokinetic characteristics of bioactive compounds towards viable drug candidates. Aryl oxetane amines offer exciting potential as bioisosteres for benzamides, an extremely common pharmacophore, but are rarely examined due to the lack of available synthetic methods. Here, we describe a new class of reactions for sulfonyl fluorides to form aminooxetanes by an alternative pathway to the established SuFEx (sulfonyl-fluoride exchange) click reactivity. A defluorosulfonylation forms planar oxetane carbocations simply on warming. This disconnection, comparable to a typical amidation, will allow the application of vast existing amine libraries. The reaction is tolerant to a wide range of polar functionalities and is suitable for array formats. Ten oxetane analogues of bioactive benzamides and marketed drugs are prepared. Kinetic and computational studies support the formation of an oxetane carbocation as the rate determining step, followed by a chemoselective nucleophile coupling step.
AU  - Rojas,J
AU  - Croft,R
AU  - Sterling,A
AU  - Briggs,E
AU  - Antermite,D
AU  - Schmitt,D
AU  - Blagojevic,L
AU  - Haycock,P
AU  - White,A
AU  - Duarte,F
AU  - Choi,C
AU  - Mousseau,J
AU  - Bull,J
DO  - 10.1038/s41557-021-00856-2
EP  - 169
PY  - 2022///
SN  - 1755-4330
SP  - 160
TI  - Amino-oxetanes as amide isosteres by an alternative defluorosulfonylative coupling of sulfonyl fluorides
T2  - Nature Chemistry
UR  - http://dx.doi.org/10.1038/s41557-021-00856-2
UR  - https://doi.org/10.1038/s41557-021-00856-2
UR  - http://hdl.handle.net/10044/1/92951
VL  - 14
ER  -
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