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These are preliminary reports that have not been peer-reviewed.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
3 files
0/0

Monophosphine Ligands Promote Pd-Catalyzed C–S Cross-Coupling Reactions at Room Temperature with Soluble Bases

preprint
submitted on 18.04.2019 and posted on 19.04.2019 by Jessica Xu, Richard Liu, Charles Yeung, Stephen L. Buchwald

The Pd-catalyzed cross-coupling of thiols with aromatic electrophiles is a reliable method for the synthesis of aryl thioethers, which are important compounds for pharmaceutical and agricultural applications. Since thiols and thiolates strongly bind late transition metals, previous research has focused on catalysts supported by chelating, bisphosphine ligands, which were considered less likely to be displaced during the course of the reaction. We show that by using monophosphine ligands instead, more effective catalysis can be achieved. Notably, compared to previous methods, this increased reactivity allows for the use of much lower reaction temperature, soluble bases, and base-sensitive substrates. In contrast to conventional wisdom, our mechanistic data suggest that the extent of displacement of phosphine ligands by thiols is, firstly, not correlated with the ligand bulk or thiol nucleophilicity, and secondly, not predictive of the effectiveness of a given ligand in combination with palladium.

Funding

Metal-Catalyzed Methods for Organic Synthesis

National Institute of General Medical Sciences

Find out more...

History

Email Address of Submitting Author

ryl@mit.edu

Institution

Massachusetts Institute of Technology

Country

USA

ORCID For Submitting Author

0000-0003-0951-6487

Declaration of Conflict of Interest

No conflicts of interest to declare.

Exports