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

2025/09/07 by Ling Chen, Jun‐Cheng Jin, Qi‐Guo Zheng +2
Biochemistry, Genetics and Molecular Biology · Chemistry · #Asymmetric Synthesis and Catalysis #Chemical Synthesis and Analysis #Synthetic Organic Chemistry Methods

paper · doi:10.1002/cjoc.70261

openalex publication_date 2025/09/07 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/30

Abstract

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.

Related

• Dancing on Ropes ‐ Enantioselective Functionalization of Preformed <scp>Four‐Membered</scp> Carbocycles
• Diastereoselective Synthesis of <i>N</i>‐Heterocycle Substituted Cyclobutanes <i>via</i> Michael Addition onto Cyclobutenes
• Cycloaddition and Annulation Reactions with Donor‐Acceptor Cyclobutanes
• Electrophilic Bicyclobutane Synthons
• Catalytic &amp; Enantioselective Ring Opening of Azabicyclo[1.1.0]Butyl Carbinols <i>via</i> <i>N</i> ‐Allylation of Strained Tertiary Amines