Dimethylbisdiphenylphosphinoxanthene
[CAS# 161265-03-8]

Identification

• Classification: Organic raw materials >> Organic phosphine compound
• Name: Dimethylbisdiphenylphosphinoxanthene
• Synonyms: 9,9-Dimethyl-4,5-bis(diphenylphosphino)xanthene; Xantphos
• Molecular Formula: C₃₉H₃₂OP₂
• Molecular Weight: 578.63
• CAS Registry Number: 161265-03-8
• EC Number: 605-249-4
• SMILES: CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C

Properties

• Melting point: 226-230 °C

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H315-H319-H335
• Safety Statements: P261-P264-P264+P265-P271-P280-P302+P352-P304+P340-P305+P351+P338-P319-P321-P332+P317-P337+P317-P362+P364-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Eye irritation	Eye Irrit.	2	H319
Specific target organ toxicity - single exposure	STOT SE	3	H335
Skin irritation	Skin Irrit.	2	H315
Acute toxicity	Acute Tox.	4	H302
Acute toxicity	Acute Tox.	4	H332
Skin sensitization	Skin Sens.	1	H317
Eye irritation	Eye Irrit.	2A	H319
Acute toxicity	Acute Tox.	4	H312

Discovery and Applications

Dimethylbisdiphenylphosphinoxanthene is a phosphine ligand that has been widely used in transition metal catalysis, particularly in palladium-catalyzed reactions. As a member of the xanthene-based phosphine ligands, it has garnered significant interest due to its unique combination of electronic and steric properties, which enhance the efficiency, selectivity, and stability of catalysts used in various organic synthesis processes.

The discovery of dimethylbisdiphenylphosphinoxanthene was motivated by the ongoing search for more efficient ligands that could improve the performance of metal catalysts, especially in carbon-carbon and carbon-nitrogen bond-forming reactions. The xanthene backbone in this compound offers rigidity, while the diphenylphosphine groups provide both steric bulk and electronic modulation, making it an effective ligand in catalytic systems.

In the realm of catalysis, dimethylbisdiphenylphosphinoxanthene has proven particularly valuable in palladium-catalyzed cross-coupling reactions, such as the Suzuki-Miyaura and Buchwald-Hartwig amination reactions. These reactions are essential in the synthesis of complex organic molecules, including pharmaceuticals, agrochemicals, and materials science applications. In the Suzuki-Miyaura reaction, which is widely used to form biaryl compounds, dimethylbisdiphenylphosphinoxanthene helps to enhance the reactivity and selectivity of the palladium catalyst. This reaction involves the coupling of aryl halides with organoboron compounds, and the use of this ligand often results in higher yields and greater selectivity, making it ideal for synthesizing intricate organic structures.

Similarly, in the Buchwald-Hartwig amination, which forms carbon-nitrogen bonds, dimethylbisdiphenylphosphinoxanthene plays a critical role. This reaction is pivotal in the production of arylamines, which are important building blocks in the synthesis of many pharmaceuticals and bioactive compounds. The ligand’s ability to stabilize the palladium catalyst under mild conditions allows for efficient catalysis, even with substrates that are typically challenging to activate. As a result, dimethylbisdiphenylphosphinoxanthene has become a go-to ligand for chemists seeking to optimize these types of reactions.

The structural design of dimethylbisdiphenylphosphinoxanthene is central to its effectiveness. The xanthene backbone not only provides a stable framework for the ligand but also influences the electronic properties of the metal center to which it binds. This electronic tuning is crucial for controlling the reactivity of the metal catalyst. Additionally, the diphenylphosphine groups introduce significant steric hindrance around the metal center, which can help to prevent unwanted side reactions by protecting the active site from interacting with undesired molecules. This steric bulk is particularly beneficial in achieving high selectivity in catalytic reactions, where precise control over reaction pathways is required.

Beyond its established applications, dimethylbisdiphenylphosphinoxanthene continues to be a subject of research, with chemists exploring its potential in new catalytic systems. This ongoing research is driven by the need for more efficient, selective, and sustainable catalytic processes, particularly in the pharmaceutical and fine chemical industries. As new reactions are developed and the demand for more complex molecules grows, the role of ligands like dimethylbisdiphenylphosphinoxanthene is expected to expand. Future research may lead to the development of modified ligands based on the xanthene framework, offering even greater control over catalytic processes and enabling the synthesis of more sophisticated molecules.

In conclusion, dimethylbisdiphenylphosphinoxanthene is a versatile and highly effective ligand that has significantly impacted the field of transition metal catalysis. Its ability to enhance the performance of palladium-catalyzed reactions, particularly in the formation of carbon-carbon and carbon-nitrogen bonds, underscores its importance in organic synthesis. As research continues, it is likely that this ligand will play an increasingly prominent role in the development of new catalytic methodologies.

References

Sun, Y., Wang, B., Wang, C. et al. (2024). Cobalt-catalyzed highly α-selective hydrostannylation of terminal alkynes. Science China Chemistry, 67, 3624-3630.
DOI: https://doi.org/10.1007/s11426-024-2362-4

Xing, Y., Yu, R., Jiao, M. et al. (2024). Construction of remote cyano-substituted quaternary carbon centers via nickel-catalyzed migratory hydrocyanation of unconjugated dienes. Science China Chemistry, 67, 3397-3405.
DOI: https://doi.org/10.1007/s11426-024-2182-9

Bastick, K. A. C., Roberts, D. D. and Watson, A. J. B. (2024). The current utility and future potential of multiborylated alkanes. Nature Reviews Chemistry, 8, 741-761.
DOI: https://doi.org/10.1038/s41570-024-00650-x