(R)-(+)-2-[2-(Diphenylphosphino)phenyl]-4-isopropyl-2-oxazoline
[CAS# 164858-78-0]

Identification

• Classification: Chemical reagent >> Organic reagent >> Phosphine ligand
• Name: (R)-(+)-2-[2-(Diphenylphosphino)phenyl]-4-isopropyl-2-oxazoline
• Synonyms: (4R)-(+)-4,5-Dihydro-2-(2'-(diphenylphosphino)phenyl)-4-isopropyloxazole
• Molecular Formula: C₂₄H₂₄NOP
• Molecular Weight: 373.43
• CAS Registry Number: 164858-78-0
• EC Number: 690-702-9
• SMILES: CC(C)[C@@H]1COC(=N1)C2=CC=CC=C2P(C3=CC=CC=C3)C4=CC=CC=C4

Properties

• Melting point: 85-90 °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

Discovery and Applications

(R)-(+)-2-[2-(Diphenylphosphino)phenyl]-4-isopropyl-2-oxazoline is a chiral ligand widely used in asymmetric catalysis, valued for its effectiveness in promoting enantioselective reactions. This compound combines the oxazoline ring with a diphenylphosphino group, creating a ligand with unique steric and electronic properties. The chiral oxazoline ring, along with the bulky isopropyl substituent, forms a three-dimensional environment that is crucial for achieving high enantioselectivity in catalytic processes.

The development of this ligand emerged from the need to design efficient chiral ligands for asymmetric synthesis. Researchers aimed to enhance the selectivity of catalytic reactions, particularly in the synthesis of enantiomerically pure compounds, which are essential in pharmaceuticals and fine chemicals. The oxazoline ring was chosen for its ability to form stable complexes with transition metals and to impart chirality, while the diphenylphosphino group stabilizes the metal center and enhances the ligand's effectiveness in catalysis.

One of the primary applications of (R)-(+)-2-[2-(Diphenylphosphino)phenyl]-4-isopropyl-2-oxazoline is in asymmetric hydrogenation. This reaction is critical for producing chiral molecules, such as pharmaceuticals and fine chemicals, with high enantiomeric purity. When used in combination with metals like rhodium or ruthenium, the ligand facilitates the hydrogenation of unsaturated compounds, including alkenes and ketones, with remarkable enantioselectivity. This application underscores the ligand's importance in synthesizing complex chiral molecules.

Another significant application is in asymmetric allylic substitution reactions. These reactions involve replacing an allylic group in a substrate with a nucleophile, resulting in the formation of a new chiral center. The (R)-(+)-2-[2-(Diphenylphosphino)phenyl]-4-isopropyl-2-oxazoline ligand has proven effective in promoting these reactions, yielding products with high enantiomeric excess. This ability to create chiral centers makes the ligand valuable for constructing intricate chiral molecules used as intermediates in the synthesis of natural products and pharmaceuticals.

In addition to asymmetric hydrogenation and allylic substitution, (R)-(+)-2-[2-(Diphenylphosphino)phenyl]-4-isopropyl-2-oxazoline has been applied in other catalytic processes, such as asymmetric cycloaddition and cross-coupling reactions. The ligand's ability to form stable, chiral metal complexes allows it to be versatile in a range of transformations. Its effectiveness in these applications highlights its role in the advancement of synthetic chemistry.

The discovery and application of (R)-(+)-2-[2-(Diphenylphosphino)phenyl]-4-isopropyl-2-oxazoline represent a significant advancement in asymmetric catalysis. The ligand's unique structural features and its success in promoting enantioselective reactions make it a valuable tool in both research and industrial applications. As the demand for chiral molecules continues to rise, ligands like this will remain crucial in developing new, efficient catalytic processes.

References

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DOI: 10.1055/s-0033-1341274

2012. Towards a Zinc-Catalyzed Asymmetric Hydrogenation/Transfer Hydrogenation of Imines. Chemistry - An Asian Journal, 7(8), 1785-1790.
DOI: 10.1002/asia.201200309

2006. Synthesis of P-Stereogenic Phosphines. Synfacts, 2006(6), 0597.
DOI: 10.1055/s-2006-941821