Catalytic Chemo‐ and Regioselective Radical Carbocyanation of 2‐Azadienes for the Synthesis of α‐Amino Nitriles. Issue 19 (31st March 2023)

• Record Type: Journal Article
• Authors: Duan, Shengzu; Du, Ya; Wang, Lingling; Tian, Xun; Zi, Yujin; Zhang, Hongbin; Walsh, Patrick J.; Yang, Xiaodong
• Is Part Of: Angewandte Chemie international edition. Volume 62:Issue 19(2023)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2023-03-31
• Subjects: α-Amino Nitriles -- Carbocyanation -- Copper -- Photocatalysis -- Radicals; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.202300605
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: α‐Amino nitriles are versatile structural motifs in a variety of biologically active compounds and pharmaceuticals and they serve as valuable building blocks in synthesis. The preparation of α‐ and β‐functionalized α‐amino nitriles from readily available scaffolds, however, remains challenging. Herein is reported a novel dual catalytic photoredox/copper‐catalyzed chemo‐ and regioselective radical carbocyanation of 2‐azadienes to access functionalized α‐amino nitriles by using redox‐active esters (RAEs) and trimethylsilyl cyanide. This cascade process employs a broad scope of RAEs and provides the corresponding α‐amino nitrile building blocks in 50–95 % yields (51 examples, regioselectivity >95 : 5). The products were transformed into prized α‐amino nitriles and α‐amino acids. Mechanistic studies suggest a radical cascade coupling process. Abstract : A mild and broadly applicable method for the construction of complex α‐ and β‐functionalized α‐amino nitrile derivatives through a novel cascade strategy is presented. Alkyl radicals are generated by the photo‐mediated reductive decarboxylation of redox‐active esters, captured by 2‐azadienes to provide 2‐azallyl radicals and cyanized by a copper catalyst.