Catalytic Chemo- and Regioselective Radical Carbocyanation of 2-Azadienes for the Synthesis of alpha-Amino Nitriles

By:Duan, Shengzu; Du, Ya; Wang, Lingling; Tian, Xun; Zi, Yujin; Zhang, Hongbin; Walsh, Patrick J*; Yang, Xiaodong*

Angewandte Chemie International Edition

DOI：10.1002/anie.202300605

Published：2023-May-02

Abstract

alpha-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 alpha- and beta-functionalized alpha-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 alpha-amino nitriles by using redox-active esters (RAEs) and trimethylsilyl cyanide. This cascade process employs a broad scope of RAEs and provides the corresponding alpha-amino nitrile building blocks in 50-95% yields (51 examples, regioselectivity >95:5). The products were transformed into prized alpha-amino nitriles and alpha-amino acids. Mechanistic studies suggest a radical cascade coupling process.

全文链接：https://onlinelibrary.wiley.com/doi/10.1002/anie.202300605