Diastereodivergent Synthesis of trans ‐ and cis ‐Cyclobutane‐Based γ ‐Aminobutyric Acid Derivatives via Cu( OTf ) 2 ‐Catalyzed Strain‐Release Reactions of Bicyclo[1.1.0]butanes

Comprehensive Summary Herein, we report the synthesis of multifunctionalized trans ‐ and cis ‐cyclobutane‐based γ ‐aminobutyric acid derivatives via diastereodivergent Cu(OTf) 2 ‐catalyzed strain‐release reactions of bicyclo[1.1.0]butanes with amines. This protocol enables precise control of product configuration via ligand selection, providing a powerful tool for modulating the stereochemistry of the resulting compounds. In addition, the synthesized cyclobutane‐based γ ‐aminobutyric acid derivatives significantly expand substituent diversity, thereby greatly enhancing molecular complexity. The method proceeds under mild conditions and exhibits excellent tolerance toward a broad range of functional groups, making it a versatile platform for the development of novel drug candidates.