Synthetic Utility. The broad generality of this nucleophilic azetidinyation protocol encouraged us to explore the late-stage installation of the azetidine ring into more complex molecules (Figure ). Eight approved drugs featuring diverse types of nucleophiles, such as aniline, aliphatic amine, tetrazole, sulfonamide, carboxylic alcohol, and phenol, were successfully coupled with ATA 5 in moderate to good yields, demonstrating broad generality and exceptional chemoselectivity (72-79). Furthermore, our protocol can simplify the synthesis of known compounds (Figure ). For instance, acid 83, an advanced intermediate for the LPA1-receptor antagonist 84, was previously synthesized in six steps (process route) or seven steps (medicinal route). By directly coupling 2-methyl-furan 81 with ATA 80, followed by selective furan oxidative cleavage, acid 83 can now be efficiently prepared in just two steps (Figure ). Additionally, ether 87, previously synthesized in five steps, can now be produced by directly coupling ATA 85 with alcohol 86 (Figure ). Interestingly, we observed the formation of product 88, likely via carbocation rearrangement. Moreover, compound 38 was prepared in one step with an 88% yield using our protocol, representing a significant improvement over its Tsprotected analogue, which previously required six steps to synthesize (Figure ). In addition to compound 84, another bioactive compound, 93, an agent for treating CNS conditions, can be formally synthesized using our protocol (Figure ). The direct coupling of ATA 89 and imine 90, followed by deprotection under acidic conditions, allows for the easy preparation of free amine 92, a key intermediate toward bioactive compound 93. Lastly, we demonstrated the utility of our protocol by synthesizing azetidine analogues for drug molecules, showcasing its potential applicability in drug discovery campaigns (Figure ). As noted at the outset, azetidines can serve as bioisosteric replacements for piperidines. Therefore, we directly targeted two piperidinecontaining drug molecules, Pethidine 97 and Lomotil 100. Using the selective furan oxidative cleavage strategy, we synthesized Boc-protected azetidine carboxylic acid 94 on a gram scale. Notably, both acid 94 and its Cbzprotected analogue 95 hold high commercial value (ca. 1300$/g). Subsequently, acid 94 was condensed with ethanol, followed by Boc group deprotection using TFA, resulting in the formation of free azetidine. This crude free azetidine underwent reductive amination with paraformaldehyde to deliver compound 96, an analogue of the drug Pethidine 97. Additionally, the free azetidine participated in an SN2 reaction with alkyl bromide 98, leading to the formation of compound 99, an azetidine analogue for the drug Lomotil 100.