HFIP-Promoted Strain-Release-Driven Functionalization of Azabicyclo[1.1.0]butanes with Heterocyclobutane Trichloroacetimidates
Pujan Sasmal, Subhadeep Hazra, Thakar Neha Rajendra, Jaideep Saha, Rahul Jain, Ravi Kumar
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.
Topics & Concepts
ChemistryGlycosylationSurface modificationCombinatorial chemistryNanotechnologyGroup (periodic table)Reaction conditionsProtocol (science)StereochemistryPosttranslational modificationCatalysisMolecular conformationSynthesis and Catalytic ReactionsCarbohydrate Chemistry and SynthesisRadical Photochemical Reactions