HFIP-Promoted Strain-Release-Driven Functionalization of Azabicyclo[1.1.0]butanes with Heterocyclobutane Trichloroacetimidates
Abstract
We report the activation of oxetanyl, azetidinyl, and thietanyl trichloroacetimidates with 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP), which rapidly couple with azabicyclo[1.1.0]butanes (ABB), following the Schmidt glycosylation strategy. The developed protocol is operationally simple, enabling easy access to a library of medicinally relevant 3,3-functionalized oxetanes, azetidines, and thietanes with N1/C3-functionalized ABB. The practicality of the strategy was demonstrated with more than 50 examples, including gram-scale synthesis. Control experiments revealed that both the trichloroacetimidate group and HFIP were essential for the reaction's success.
Fields of Study & Subjects
Synthesis and Catalytic Reactions
Carbohydrate Chemistry and Synthesis
Radical Photochemical Reactions
Publication details
- Journal / source
- Organic Letters
- Publisher
- American Chemical Society (ACS)
- Volume
- 28
- Issue
- 9
- Pages
- 3026–3032
- Publication date
- 19 February 2026
- Language
- EN