(2R)-1-[(1R)-1-(Dicyclohexylphosphino)ethyl]-2-(diphenylphosphino)ferrocene
[CAS# 155806-35-2]

Identification

• Classification: Chemical reagent >> Organic reagent >> Phosphorous compound
• Name: (2R)-1-[(1R)-1-(Dicyclohexylphosphino)ethyl]-2-(diphenylphosphino)ferrocene
• Synonyms: (2Sp)-1-[(1R)-1-(Dicyclohexylphosphino)ethyl]-2-(diphenylphosphino)ferrocene
• Molecular Formula: C₃₆H₄₄FeP₂
• Molecular Weight: 594.53
• CAS Registry Number: 155806-35-2
• EC Number: 811-418-5
• SMILES: C[C@H]([C]1[CH][CH][CH][C]1P(c2ccccc2)c3ccccc3)P(C4CCCCC4)C5CCCCC5.[CH]1[CH][CH][CH][CH]1.[Fe]

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H315-H319-H335
• Safety Statements: P261-P305+P351+P338

Discovery and Applications

(2R)-1-[(1R)-1-(Dicyclohexylphosphino)ethyl]-2-(diphenylphosphino)ferrocene, commonly known as a Josiphos ligand, is an important class of chiral diphosphine ligands in asymmetric catalysis. The discovery of this ligand family dates back to the work of researchers at Solvias AG, notably under the leadership of Henri Brunner and Manfred Reetz in the 1990s. The development of Josiphos ligands was aimed at providing highly effective ligands that could address stereoselectivity challenges in various catalytic reactions. Structurally, this ligand combines a ferrocene backbone with two distinct phosphine groups: a dicyclohexylphosphino moiety and a diphenylphosphino moiety, offering a unique blend of steric and electronic properties.

The synthesis of (2R)-1-[(1R)-1-(Dicyclohexylphosphino)ethyl]-2-(diphenylphosphino)ferrocene involves the modification of a ferrocene derivative. Starting from ferrocene, the preparation typically proceeds through lithiation and substitution steps to introduce the chiral phosphino substituents. The stereochemical integrity is controlled through the use of chiral auxiliaries or enantioselective synthetic methods. The resulting ligand is air-stable and can be stored for extended periods without degradation, making it highly practical for laboratory and industrial use.

This ligand has found widespread application in asymmetric hydrogenation, hydroboration, and carbon-carbon coupling reactions. The combination of rigid ferrocene structure and the steric bulk of the dicyclohexylphosphino group provides exceptional selectivity and reactivity in catalytic systems. One of its most notable uses is in the rhodium-catalyzed asymmetric hydrogenation of olefins, where it consistently delivers high enantioselectivity. This has been particularly valuable in the synthesis of chiral pharmaceutical intermediates, such as those used in the production of active ingredients for antihypertensive and anticancer drugs. Additionally, the ligand's effectiveness in hydroboration reactions has enabled the efficient synthesis of chiral alcohols, which are critical building blocks in fine chemicals and agrochemicals.

Research continues to explore the potential of Josiphos ligands in new catalytic processes. Their modular nature allows for structural modifications, leading to the development of tailored ligands for specific reactions. The versatility and effectiveness of (2R)-1-[(1R)-1-(Dicyclohexylphosphino)ethyl]-2-(diphenylphosphino)ferrocene underscore its significance in modern asymmetric synthesis, contributing to advances in both academic research and industrial applications.

References

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