Considering the wide array of nucleophiles available in pharmaceutical chemistry, this direct electrophilic azetidinylation method has the potential to open new frontiers in the azetidine chemical space. Reaction Development. We initiated our research by designing electrophilic azetidinylation reagents (Figure ). Inspired by the Schmidt glycosylation reaction, we speculated that ATAs could generate carbocation intermediates upon activation. These tertiary carbocations may be further stabilized by the nitrogen atom within the azetidine ring through a field effect. In addition, the selection of protecting groups could be crucial as they will influence the stabilizing ability of the nitrogen atom. With these considerations in mind, we embarked on the synthesis of ATA reagents. In search of the synthetic methods, we found the isolated one example documented in patent EP4082611A1 (Figure ). According to this patent, Boc-protected azetidine-3-one 1 reacted with 1.5 equivalents of Phenylmagnesium bromide, affording 3-Ph azetidinol 2 in 92% yield. The purified compound 2 then underwent an efficient addition reaction with Cl3CCN in the presence of 1.2 equivalents of DBU, furnishing pure ATA reagent 3 in quantitative yield. Alternatively, we adopted a two-step, one-purification protocol following our previous synthesis of oxetanyl trichloroacetimidate (OTA) reagents (Figure ). Instead of using PhMgBr, we utilized the in situ generated PhLi reagent to react with inexpensive azetidine-3-one bearing different protecting groups (local price, <1 $/g). Additionally, we found that a catalytic amount of DBU was sufficient for the addition of the crude azetidinol to Cl3CCN. This approach allows for the practical preparation of pure ATA reagents in moderate to good yields. These reagents were non-hygroscopic and exhibited long-term bench-top stability at room temperature (see Figures in Supporting Information for details).