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

Herein, we present a Cu(ii)-mediated C-C reaction with alpha-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, a Cu(ii)-mediated C-C reaction was developed for the synthesis of cyanomethylated tetrahydroisoquinolines via the coupling of C(sp(3))-Br and C(sp(3))-H bonds. This method offers a versatile approach for the synthesis of various tetrahydroisoquinolines and provides valuable insights for the design of biologically active compounds.