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Synthesis of bicyclic scaffolds has gained significant attention in drug discovery due to their potential to mimic benzene bioisosteres. Here, we present a mild and scalable Sc(OTf)3‐catalyzed [3+2] cycloaddition of bicyclo[1.1.0]butanes (BCBs) with ynamides, yielding a diverse array of polysubstituted 2‐amino‐bicyclo[2.1.1]hexenes in good to excellent yields. These products offer valuable starting materials for the construction of novel functionalized bicyclo[1.1.0]butanes. Preliminary mechanistic studies indicate that the reaction involves a nucleophilic addition of ynamides to bicyclo[1.1.0]butanes, followed by an intramolecular cyclization of in situ generated enolate and keteniminium ion. We expect that these findings will encourage utilization of complex bioisosteres and foster further investigation into BCB‐based cycloaddition chemistry. [ABSTRACT FROM AUTHOR]