(SP-4-3)-[dicyclohexyl[3,6-dimethoxy-2',4',6'-tris(1-methylethyl)[1,1'-biphenyl]-2-yl]phosphine-κP](methanesulfonato-κO)[2'-(methylamino-κN)[1,1'-biphenyl]-2-yl-κC]-Palladium
[CAS# 1599466-83-7]

Identification

• Classification: Organic raw materials >> Aryl compounds >> Biphenyl compounds
• Name: (SP-4-3)-[dicyclohexyl[3,6-dimethoxy-2',4',6'-tris(1-methylethyl)[1,1'-biphenyl]-2-yl]phosphine-κP](methanesulfonato-κO)[2'-(methylamino-κN)[1,1'-biphenyl]-2-yl-κC]-Palladium
• Synonyms: BrettPhos Pd G4
• Molecular Formula: C₄₉H₆₈NO₅PPdS
• Molecular Weight: 920.53
• CAS Registry Number: 1599466-83-7
• EC Number: 813-487-7
• SMILES: CC(C)C1=CC(C(C)C)=CC(C(C)C)=C1C2=C(P(C3CCCCC3)C4CCCCC4)C(OC)=CC=C2OC.CNC5=C(C6=C([Pd]OS(C)(=O)=O)C=CC=C6)C=CC=C5

Safety Data

• Hazard Symbols: GHS07 Warning
• Hazard Statements: H302-H315-H319-H335
• Precautionary Statements: P261-P280-P301+P312-P302+P352-P305+P351+P338

Hazard Classification

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

Discovory and Applicatios

BrettPhos Pd G4 is a fourth-generation palladium precatalyst designed for cross-coupling reactions, offering excellent reactivity and stability. It is part of a family of precatalysts that combine palladium with the BrettPhos ligand, a biaryl phosphine known for its unique electronic and steric properties. The development of BrettPhos Pd G4 has significantly enhanced the efficiency of Suzuki-Miyaura, Buchwald-Hartwig amination, and related coupling reactions.

The discovery of BrettPhos Pd G4 can be traced back to efforts by the Buchwald group in the early 2010s. Researchers sought to address challenges in achieving high yields and selectivity for difficult cross-coupling substrates, such as sterically hindered or electronically deactivated aryl halides. By incorporating the BrettPhos ligand into a well-defined palladium precatalyst structure, they were able to create a more robust system that allowed for easier handling and higher reaction efficiency. The precatalyst format also provided a stable source of active palladium, which could be conveniently activated under mild conditions.

The synthesis of BrettPhos Pd G4 involves combining a palladium source with the BrettPhos ligand, followed by coordination with appropriate stabilizing ligands and solvents. This results in a preformed palladium(II) complex that readily generates the active species upon exposure to reaction conditions. The G4 designation signifies improvements over earlier generations, including greater solubility, longer shelf life, and enhanced activity for challenging substrates.

BrettPhos Pd G4 has found widespread application in the pharmaceutical and agrochemical industries. It is particularly effective in the Buchwald-Hartwig amination, where it facilitates the formation of C-N bonds between aryl halides and amines. This reaction is pivotal in the synthesis of many drug molecules, including those containing complex heterocyclic frameworks. The precatalyst is also highly effective in Suzuki-Miyaura coupling, enabling the formation of biaryl structures that are key intermediates in the production of active pharmaceutical ingredients and advanced materials.

A key advantage of BrettPhos Pd G4 is its ability to operate at low palladium loadings while maintaining high efficiency. This minimizes the need for costly metal removal processes and reduces environmental impact. The precatalyst's robustness allows it to tolerate a wide range of functional groups, broadening its utility in complex molecule synthesis.

The development of BrettPhos Pd G4 represents a significant advance in the field of cross-coupling catalysis. Its combination of ease of use, stability, and high reactivity has made it a valuable tool for both academic researchers and industrial chemists. Continued exploration of similar precatalyst systems is expected to further expand the scope and efficiency of transition metal-catalyzed reactions.