Cu(ii)-catalyzed cross coupling cyanomethylation of tetrahydroisoquinolines with a-bromoalkylnitrile

Herein, we present a Cu(ii)-mediated C-C reaction with a-haloacetonitrile derivatives and aryl tetrahydroisoquinolines via a coupling of C(sp(3))-Br and C(sp(3))-H bonds, yielding cyanomethylated tetrahydroisoquinolines. The reaction led to the synthesis of a broad variety of tetrahydroisoquinolines, such as electron donating and electron withdrawing and hetero ring groups substituted tetrahydroisoquinolines. This methodology provides cyanomethylated products (with excellent yields (47%-89%)) and valuable insights for the design of versatile biologically active products.

Automated summary

In this study, we report a Cu(ii)-mediated reaction that couples a-haloacetonitrile derivatives and aryl tetrahydroisoquinolines via C(sp(3))-Br and C(sp(3))-H bond activation, resulting in the formation of cyanomethylated tetrahydroisoquinolines. This methodology provides a diverse range of tetrahydroisoquinoline products, including those substituted with electron donating and electron withdrawing groups, as well as heterocyclic ring substituents. The high yields (47%-89%) and valuable insights obtained from this reaction offer significant potential for the design of versatile biologically active products.