Reengineered BI‐DIME Ligand Core Based on Computer Modeling to Increase Selectivity in Asymmetric Suzuki–Miyaura Coupling for the Challenging Axially Chiral HIV Integrase Inhibitor

Abstract

AbstractThrough a computer‐guided approach, new series of monophosphine ligands were designed and developed for asymmetric Suzuki–Miyaura couplings of challenging heterocyclic substrates. Computer modeling pointed to a tunable, yet unexplored quadrant in BI‐DIME, leading to the discovery of the 3′,5′‐dimethyl‐substituted ligand which improved the atropisomeric selectivity of the Suzuki–Miyaura reaction from the previously reported 5:1 dr to 15:1 dr for the synthesis of a challenging HIV integrase intermediate, and up to 24:1 dr with various other quinoline substrates.magnified image