Next, we turned our attention to optimize the electrophilic azetidinylation reaction. There was a single precedent reported in the above-mentioned patent EP4082611A1, using 4-Ph-phenol as the nucleophile to couple with ATA 3 in the presence of 10 mol% BF3·OEt2 at -78 °C. Instead, we chose amines, the most commonly encountered nucleophiles in pharmaceutical chemistry, as our model nucleophiles. For aniline 6, we found that the choice of protecting groups had a moderate impact on the reaction yields (Table , entries 1-3). Interestingly, while the Cbz group was reported to have an unexpected stabilizing effect, it afforded the lowest yield in our experiments compared to Boc and Ph2CH protecting groups. Changing the trichloroacetimidate to Nphenyltrifluoroacetimidate led to a significant decrease in yield (Table , entry 4). Cu(OTf)2 proved to be the most efficient catalyst for this transformation, outperforming other Lewis acids and Brønsted acids that we screened (Table , entries 5-6). In the absence of Cu(OTf)2, only trace amounts of product were observed, with ATA 5 almost fully recovered (Table , entry 7). The reaction could also be conducted under air, leading to only a slight decrease in yield (Table , entry 8). However, the omission of 4Å molecular sieves had a deleterious effect, resulting in an increased formation of byproduct 9, probably via the hydration of the carbocation intermediate (Table , entry 9).