Synthesis of functionalized spirocyclic oxetanes through Paternò–Büchi reactions of cyclic ketones and maleic acid derivatives

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Abstract

A telescoped three-step sequence to functionalised spirocyclic oxetanes is reported, involving Paternò–Büchi reactions between maleic acid derivatives and cyclic ketones.

Abstract

A telescoped three-step sequence to functionalised spirocyclic oxetanes is reported, involving Paternò–Büchi reactions between maleic acid derivatives and cyclic ketones. p-Xylene suppresses the competing alkene dimerization that has plagued previous work, allowing access to 35 novel spirocyclic oxetanes that cannot be prepared using existing methodologies, and which represent versatile intermediates for further elaboration.

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Most cited references 28

Record: found
Abstract: not found
Article: not found

Four-membered ring-containing spirocycles: synthetic strategies and opportunities.

Erick M. Carreira, Thomas Fessard (2014)

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Record: found
Abstract: found
Article: not found

Oxetanes in drug discovery: structural and synthetic insights.

Georg Wuitschik, Erick M Carreira, Björn Wagner … (2010)

An oxetane can trigger profound changes in aqueous solubility, lipophilicity, metabolic stability, and conformational preference when replacing commonly employed functionalities such as gem-dimethyl or carbonyl groups. The magnitude of these changes depends on the structural context. Thus, by substitution of a gem-dimethyl group with an oxetane, aqueous solubility may increase by a factor of 4 to more than 4000 while reducing the rate of metabolic degradation in most cases. The incorporation of an oxetane into an aliphatic chain can cause conformational changes favoring synclinal rather than antiplanar arrangements of the chain. Additionally spirocyclic oxetanes (e.g., 2-oxa-6-aza-spiro[3.3]heptane) bear remarkable analogies to commonly used fragments in drug discovery, such as morpholine, and are even able to supplant the latter in its solubilizing ability. A rich chemistry of oxetan-3-one and derived Michael acceptors provide venues for the preparation of a broad variety of novel oxetanes not previously documented, thus providing the foundation for their broad use in chemistry and drug discovery.

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Record: found
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Article: not found

Put a ring on it: application of small aliphatic rings in medicinal chemistry

Matthias R Bauer, Paolo Di Fruscia, Simon Lucas … (2021)

Aliphatic small rings including cyclopropanes, cyclobutanes, oxetanes, azetidines and bicyclo[1.1.1]pentanes have been increasingly exploited in medicinal chemistry. This review summarises judicious successful application and reported limitations of these ring systems. Aliphatic three- and four-membered rings including cyclopropanes, cyclobutanes, oxetanes, azetidines and bicyclo[1.1.1]pentanes have been increasingly exploited in medicinal chemistry for their beneficial physicochemical properties and applications as functional group bioisosteres. This review provides a historical perspective and comparative up to date overview of commonly applied small rings, exemplifying key principles with recent literature examples. In addition to describing the merits and advantages of each ring system, potential hazards and liabilities are also illustrated and explained, including any significant chemical or metabolic stability and toxicity risks.

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Author and article information

Contributors

Weronika Z. Michalska: (View ORCID Profile)

Nathan R. Halcovitch: (View ORCID Profile)

Susannah C. Coote: (View ORCID Profile)

Journal

Journal ID (publisher-id): CHCOFS

Title: Chemical Communications

Abbreviated Title: Chem. Commun.

Publisher: Royal Society of Chemistry (RSC)

ISSN (Print): 1359-7345

ISSN (Electronic): 1364-548X

Publication date Created: January 17 2023

Publication date (Electronic): 2023

Volume: 59

Issue: 6

Pages: 784-787

Affiliations

[1 ]Department of Chemistry, Lancaster University, Bailrigg, LA1 4YB, UK

Article

DOI: 10.1039/D2CC06459F

SO-VID: a976a1eb-2a89-4fbc-8b2d-986f1d947d7a

License:

http://creativecommons.org/licenses/by/3.0/

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