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 Academic Article uri icon

abstract

  • © 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.).

published proceedings

  • Advanced Synthesis & Catalysis

author list (cited authors)

  • Haddad, N., Mangunuru, H., Fandrick, K. R., Qu, B. o., Sieber, J. D., Rodriguez, S., ... Senanayake, C. H

citation count

  • 11

complete list of authors

  • Haddad, Nizar||Mangunuru, Hari PR||Fandrick, Keith R||Qu, Bo||Sieber, Joshua D||Rodriguez, Sonia||Desrosiers, Jean-Nicolas||Patel, Nitinchandra D||Lee, Heewon||Kurouski, Dmitry||Grinberg, Nelu||Yee, Nathan K||Song, Jinhua J||Senanayake, Chris H

publication date

  • September 2016

publisher