Synthesis of oxetane and azetidine ethers as ester isosteres by Brønsted acid catalysed alkylation of alcohols with 3-aryl-oxetanols and 3-aryl-azetidinols
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Author(s)
Type
Journal Article
Abstract
Oxetanes and azetidines continue to draw significant interest in medicinal chemistry, as small, polar and non-planar motifs. Oxetanes also represent interesting surrogates for carbonyl-containing functional groups. Here we report a synthesis of 3,3- disubstituted oxetane- and azetidine-ethers, with comparisons made to the ester functional group. The tertiary benzylic alcohols of the 4-membered rings are selectively activated using Brønsted acid catalysis and reacted with simple alcohols to form the ethers and maintain the oxetane ring intact. This approach avoids the use of strong bases and halide alkylating agents and allows alcohol libraries to be leveraged. Oxetane ethers demonstrate excellent chemical stability across a range of conditions and an improved stability vis-à-vis analogous esters under basic and reducing conditions.
Date Issued
2023-07-21
Date Acceptance
2023-06-15
Citation
Organic and Biomolecular Chemistry, 2023, 21 (27), pp.5553-5559
ISSN
1477-0520
Publisher
Royal Society of Chemistry
Start Page
5553
End Page
5559
Journal / Book Title
Organic and Biomolecular Chemistry
Volume
21
Issue
27
Copyright Statement
This journal is © The Royal Society of Chemistry 2023. This article is licensed under a Creative Commons Attribution 3.0 Unported Licence.
License URL
Identifier
https://pubs.rsc.org/en/content/articlelanding/2023/ob/d3ob00731f
Publication Status
Published
Date Publish Online
2023-06-15