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. 2024 Apr;107(4):e202300244.
doi: 10.1002/hlca.202300244. Epub 2024 Feb 9.

Design and Synthesis of Dialkylarylphosphine Urea Ligands and their Application in Palladium-Catalyzed Cross-Coupling Reactions

Lupita S Aguirre  1 , Levi T Litwiller  1 , Alexis N Lugo  1 , Andy A Thomas  1
Affiliations

Design and Synthesis of Dialkylarylphosphine Urea Ligands and their Application in Palladium-Catalyzed Cross-Coupling Reactions

Lupita S Aguirre et al. Helv Chim Acta. 2024 Apr.

Abstract

We describe herein the design and synthesis of a new class of dialkylarylphosphine ligands incorporating a Lewis-basic urea subunit. The ligand synthesis consisted of six linear steps and was enabled by the discovery of a new N-to-N alkyl migration reaction. This new series of dialkylarylphosphine urea ligands were applied in common palladium-catalyzed cross-coupling reactions for the formation of carbon-carbon and carbon-nitrogen bonds in moderate to high yields.

Keywords: N-to-N alkyl migration; dialkylarylphosphine; palladium-catalyzed cross-coupling; urea.

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Conflict of interest statement

Conflict of Interest The authors declare the following competing financial interest(s): The authors declare that they have filed a provisional patent on the design and synthesis of the dialkylarylphosphine urea ligands.

Figures

Figure 1.
Figure 1.
(A) Complex lead compounds synthesized using specialized SPhos ligand (αvβ3 Inhibitor) and XPhos ligand (p38α MAP Kinase Inhibitor); (B) Phosphine ligands possessing primary and/or secondary ligand interactions; (C) This work.
Figure 2.
Figure 2.
Displacement ellipsoid plots of L1 and L2 ligands are plotted at 50% probability. H-atoms and solvents are removed for clarity.
Scheme 1.
Scheme 1.
Synthetic route for the development of dialkylarylphosphine urea ligands L1 and L2.
Scheme 2.
Scheme 2.
Proposed reaction mechanism of the N-to-N alkyl migration leading to the formation of intermediate 4.
See this image and copyright information in PMC

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