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Updated: Feb 20, 2026

Preparation of Stable Bicyclic Aziridinium Ions and Their Ring-Opening for the Synthesis of Azaheterocycles
Published on: August 22, 2018
HFIP-Promoted Strain-Release-Driven Functionalization of Azabicyclo[1.1.0]butanes with Heterocyclobutane
Pujan Sasmal1, Subhadeep Hazra1, Thakar Neha Rajendra1
1Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Sahibzada Ajit Singh Nagar 160 062, India.
None:
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.
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