2-(Dicyclohexylphosphino)-2',4',6'-triisopropylbiphenyl
[CAS# 564483-18-7]

Identification

• Classification: Chemical reagent >> Organic reagent >> Phosphine ligand
• Name: 2-(Dicyclohexylphosphino)-2',4',6'-triisopropylbiphenyl
• Synonyms: X-Phos
• Molecular Formula: C₃₃H₄₉P
• Molecular Weight: 476.72
• CAS Registry Number: 564483-18-7
• EC Number: 611-387-6
• SMILES: CC(C)C1=CC(=C(C(=C1)C(C)C)C2=CC=CC=C2P(C3CCCCC3)C4CCCCC4)C(C)C

Properties

• Melting point: 187-190 °C

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H302-H315-H319-H335-H413
• Safety Statements: P261-P264-P264+P265-P270-P271-P273-P280-P301+P317-P302+P352-P304+P340-P305+P351+P338-P319-P321-P330-P332+P317-P337+P317-P362+P364-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Skin irritation	Skin Irrit.	2	H315
Specific target organ toxicity - single exposure	STOT SE	3	H335
Eye irritation	Eye Irrit.	2	H319
Acute toxicity	Acute Tox.	4	H302
Chronic hazardous to the aquatic environment	Aquatic Chronic	4	H413
Eye irritation	Eye Irrit.	2A	H319
Chronic hazardous to the aquatic environment	Aquatic Chronic	3	H412

Discovery and Applications

2-(Dicyclohexylphosphino)-2',4',6'-triisopropylbiphenyl, commonly abbreviated as XPhos, is a key ligand in organometallic chemistry. Discovered in the late 1990s by researchers at the Massachusetts Institute of Technology (MIT), XPhos arose from the pursuit of ligands that enhance the catalytic activity of palladium-catalyzed cross-coupling reactions. The structure features a bulky biphenyl backbone with dicyclohexylphosphino and triisopropyl groups, which give it unique stereo- and electronic properties.

XPhos is widely used in palladium-catalyzed cross-coupling reactions such as Suzuki-Miyaura, Heck, and Buchwald-Hartwig amination reactions. Its bulky structure provides high reactivity and selectivity, making it ideal for the synthesis of complex molecules. XPhos facilitates the coupling of aryl halides with a variety of nucleophiles, greatly expanding the toolbox for building carbon-carbon and carbon-nitrogen bonds.

In the pharmaceutical industry, XPhos catalyzes the synthesis of active pharmaceutical ingredients (APIs). Its efficiency in forming complex molecular structures helps simplify the synthesis of drug candidates, thereby facilitating the development of new drugs.

XPhos also plays a role in materials science, particularly in the synthesis of organic electronic materials. It is used to make polymers and small molecules with desired electronic properties, which is essential for the development of advanced materials for organic light-emitting diodes (OLEDs) and organic photovoltaics.

The ligand supports the principles of green chemistry, enabling more efficient reactions through lower catalyst loadings and milder conditions. This reduces waste and energy consumption, contributing to more sustainable chemical processes.

XPhos has been used in asymmetric catalysis, allowing the synthesis of chiral molecules with high enantioselectivity. This application is essential for the production of chiral pharmaceuticals and agrochemicals.

References

2023. Miniaturization of popular reactions from the medicinal chemists’ toolbox for ultrahigh-throughput experimentation. Nature Synthesis, 2(10).
DOI: 10.1038/s44160-023-00351-1

2020. Recent Applications of Continuous Flow in Homogeneous Palladium Catalysis. Synthesis, 52(15).
DOI: 10.1055/s-0040-1707212

2003. Insights into the Origin of High Activity and Stability of Catalysts Derived from Bulky, Electron-Rich Monophosphinobiaryl Ligands in the Pd-Catalyzed C-N Bond Formation. Journal of the American Chemical Society, 125(45).
DOI: 10.1021/ja037932y