Intramolecular Nickel‐Catalyzed Reductive Coupling: Enantioselective Synthesis of Tetrahydroisoquinolines and Related Heterocycles

Description

Thilo Bender, Markus Leutzsch, Yannik Sell, and Alois Furstner reported in 2026 a nickel-catalyzed coupling that builds ring systems found in many natural products, with control of handedness. The reaction joins two parts within one molecule, closing a ring. For the substrates here, amino-bearing diene esters with a tethered aldehyde, the route had little precedent.

A chiral phosphorus ligand called AntPhos proved the best partner for the nickel catalyst. The products include hydroxylated tetrahydroisoquinolines with an amino alcohol pattern that is hard to make in pure handed form by other routes. One product was quickly carried on to a fluorinated building block and to the core of a family of cell-killing alkaloids. NMR and crystal data pinned down the reactive species. Readers get a new ring-closing tool for complex molecule synthesis.

Catalog record

Source: https://europepmc.org/articles/PMC13676398