Palladium catalysts can do it
Direct coupling of aryl halides and alkyllithium compounds by palladium catalysis

Date:
October 9, 2020
Source:
Wiley
Summary:
Palladium catalysts help synthesize key chemicals for many
industries.

However, direct reaction of two basic reagents, aryl halides
and alkyllithium compounds, remains a challenge. Now, a team
of scientists have found that a catalyst containing YPhos-type
ligands can mediate this reaction even at room temperature. This
discovery may contribute to the development of more sustainable
processes in the chemical industry.



FULL STORY ========================================================================== Palladium catalysts help synthesize key chemicals for many
industries. However, direct reaction of two basic reagents, aryl halides
and alkyllithium compounds, remains a challenge. Now, a team of scientists
have found that a catalyst containing YPhos-type ligands can mediate
this reaction even at room temperature. This discovery may contribute to
the development of more sustainable processes in the chemical industry,
the authors write in the journal Angewandte Chemie.


========================================================================== Palladium-catalyzed chemical processes are very useful. Palladium
catalysts help to couple simple carbon-containing compounds to form more complicated chemical structures. However, they have yet failed to couple
two common reagents in chemical synthesis, aryl halides and alkyllithium compounds. Among the aryl halides, aryl chlorides are common synthesis
reagents that react variably during palladium-catalyzed reactions to
produce side products.

For coupling reactions with aryl halides and alkyllithium compounds,
chemists usually take "detours" by adding intermediate synthesis
steps. Unfortunately, every extra synthesis step produces chemical waste
and adds costs.

This problem led Viktoria Daeschlein-Gessner and her team from Ruhr
University Bochum to investigate new palladium catalysts. They thought
that a functional catalyst would ease many chemical syntheses. "The
coupling of aryl chloride and alkyllithium reagents represents one of
the most challenging reactions and - - if being successful -- promises
a broad applicability," the authors explain.

After testing various existing catalysts, the authors identified
a promising candidate. This catalyst was based on a class of
ylide-substituted phosphines called YPhos.

Chemists use YPhos-containing palladium catalysts for difficult coupling reactions. The YPhos ligands combine a negatively charged carbon
center and a positively charged phosphonium group (the ylide) with a phosphine-type ligand - - phosphines are typical ligands in palladium catalysis. This ylide-phosphine ligand setup results in special electronic properties. The scientists observed that the ligand electronics helped
to activate aryl halides, which is a crucial step in the reaction between
aryl halides and alkyllithium compounds.

One of the YPhos class of ligands, a ligand called joYPhos, was shown
to have the most favorable architecture. Its combination of electronic properties and a space-filling architecture suppressed the many side
reactions otherwise occurring in the coupling.

The authors remark that precatalysts containing the YPhos ligands also performed extraordinarily well. Precatalysts have their ligands and a
palladium source prearranged in separate compounds. Like two-component adhesives, they assemble in the reaction mixture to form the effective catalyst. This prearrangement makes their handling user-friendly and the compounds are more stable than the free ligands, according to the authors.

In a scale-up of the reaction, the scientists synthesized a building
block of lesinurad, a drug used for treating gout. They also showed that
the catalyst performed well for many variations of the aryl halide and alkyllithium reagents. These results led to the conclusion that this transformation is generally applicable. This new palladium catalyst may
thus help to avoid costly "detours" in future organic syntheses.


========================================================================== Story Source: Materials provided by Wiley. Note: Content may be edited
for style and length.


========================================================================== Journal Reference:
1. Viktoria H. Gessner, Thorsten Scherpf, Henning Steinert, Angela
Grossjohann, Katharina Dilchert, Jens Tappen, Ilja
Rodstein. Efficient Pd‐Catalyzed Direct Coupling of
Aryl Chlorides with Alkyllithium Reagents. Angewandte Chemie
International Edition, 2020; DOI: 10.1002/ anie.202008866 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/10/201009102741.htm

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