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

Abstract

Herein, we present a Cu(II)-mediated C–C reaction with α-haloacetonitrile derivatives and aryl tetrahydroisoquinolines via a coupling of C(sp³)–Br and C(sp³)–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.