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
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© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim Through 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. (Figure presented.).
author list (cited authors)
Haddad, N., Mangunuru, H., Fandrick, K. R., Qu, B. o., Sieber, J. D., Rodriguez, S., ... Senanayake, C. H.