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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

Authors :
Heewon Lee
Nelu Grinberg
Nizar Haddad
Chris H. Senanayake
Nathan K. Yee
Joshua D. Sieber
Dmitry Kurouski
Nitinchandra D. Patel
Keith R. Fandrick
Jinhua J. Song
Bo Qu
Jean-Nicolas Desrosiers
Sonia Rodriguez
Hari P. R. Mangunuru
Source :
Advanced Synthesis & Catalysis. 358:3522-3527
Publication Year :
2016
Publisher :
Wiley, 2016.

Abstract

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.

Details

ISSN :
16154150
Volume :
358
Database :
OpenAIRE
Journal :
Advanced Synthesis & Catalysis
Accession number :
edsair.doi...........d6e810be6ea7dfab71f5da954bd3c84a
Full Text :
https://doi.org/10.1002/adsc.201600889