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The importance and prevalance of O-, N-, and S-atom containing saturated four-membered ring motifs in biologically active molecules and potential therapeutics continues to drive efforts in their efficient synthetic preparation. In this review, general and recent strategies for the synthesis of these heterocycles are presented. Due to the limited potential bond disconnections, retrosynthetic strategies are broadly limited to cyclizations and cycloadditions. Nonetheless, diverse approaches for accessing cyclization precursors have been developed, ranging from nucleophilic substitution to C–H functionalization. Innovative methods for substrate activation have been developed for cycloadditions under photochemical and thermal conditions. Advances in accessing oxetanes, azetidines, and thietanes remain active areas of research with continued breakthroughs anticipated to enable future applications.
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Recent advances in the synthesis and reactivity of azetidines: strain-driven character of the four-membered heterocycle
Azetidines represent one of the most important four-membered heterocycles used in organic synthesis and medicinal chemistry. The reactivity of azetidines is driven by a considerable ring strain, while at the same the ring is significantly more stable than that of related aziridines, which translates into both facile handling and unique reactivity that can be triggered under appropriate reaction conditions. Recently, remarkable advances in the chemistry and reactivity of azetidines have been reported. In this review, we provide an overview of the synthesis, reactivity and application of azetidines that have been published in the last years with a focus on the most recent advances, trends and future directions. The review is organized by the methods of synthesis of azetidines and the reaction type used for functionalization of azetidines. Finally, recent examples of using azetidines as motifs in drug discovery, polymerization and chiral templates are discussed.
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- Award ID(s):
- 1650766
- PAR ID:
- 10224921
- Date Published:
- Journal Name:
- Organic & Biomolecular Chemistry
- Volume:
- 19
- Issue:
- 15
- ISSN:
- 1477-0520
- Page Range / eLocation ID:
- 3274 to 3286
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1039/d1ob00061f
