ChemRxiv
These are preliminary reports that have not been peer-reviewed. They should not be regarded as conclusive, guide clinical practice/health-related behavior, or be reported in news media as established information. For more information, please see our FAQs.
1/1
0/0

Phosphino-Triazole Ligands for Palladium-Catalysed Cross-Coupling

preprint
submitted on 17.07.2018 and posted on 17.07.2018 by Yiming Zhao, Huy van Nguyen, Louise Male, Philip Craven, Benjamin R. Buckley, John Fossey
Twelve 1,5-disubtituted and fourteen 5-substituted 1,2,3-triazole derivatives bearing diaryl or dialkyl phosphines at the 5-position were synthesised and used as ligands for palladium-catalysed Suzuki-Miyaura cross-coupling reactions. Bulky substrates were tested, and lead-like product formation was demonstrated. The online tool SambVca 2.0 was used to assess steric parameters of ligands and preliminary buried volume determination using XRD obtained data in a small number of cases proved to be informative. Two modelling approaches were compared for the determination of
the buried volume of ligands where XRD data was not available. An approach with imposed steric restrictions was found to be superior in leading to buried volume determinations that closely correlate with observed reaction conversions. The online tool LLAMA was used to determine lead-likeness of potential Suzuki-Miyaura cross-coupling products, from which ten of the most lead-like were successfully synthesised. Thus, confirming these readily accessible triazole-containing phosphines as highly suitable ligands for reaction screening and optimisation in drug discovery campaigns.

Funding

EPSRC (EP/J003220/1), Research Councils UK, Royal Society Industrial Fellowship, Royal Society Research Grant, Wellcome Trust ISSF Award

History

Email Address of Submitting Author

j.s.fossey@bham.ac.uk

Email Address(es) for Other Author(s)

YXZ311@student.bham.ac.uk V.Nguyen@bham.ac.uk P.Craven@bham.ac.uk l.male@bham.ac.uk b.r.buckley@lboro.ac.uk

Institution

University of Birmingham

Country

United Kingdom

ORCID For Submitting Author

0000-0002-2626-5117

Declaration of Conflict of Interest

no conflict of interest

Exports