'Product Blog'

Commercially available, well established ligands for chiral transformations

Chiral transformations are now both ubiquitous and critical for a variety of industries across pharmaceutical and fine chemical industries. Having highly pure versions (both in terms of chemical and isomer purity, ee% etc.) is critical to not just the economics of these processes but also the usability and efficacy of the final desired chiral products. One of the most well-known families of ligands are the Duphos family. Solvay is the global leader of supplying commercial chiral phosphine ligands, such as MeDuphos and derivatives of these products to the market.

(R,R) Methyl DuPhos

CAS 147253-67-6

Strem # 97-0096

MeDuphos is most widely known for its use in chiral hydrogenations.(1-4) This includes hydrogenations of C=N, enamides, olefins, reductive amidations and many more. They cover a broad range of substrates with direct relevance to important target molecules. Notably, MeDuphos can be used in the rhodium catalyzed transformation of achiral precursors required for the synthesis of Pregablin (Lyrica).(5) In this reaction a key step is the asymmetric hydrogenation of the 3-cyano-5-methylhex-3-enoic acid as described below.

The DuPhos family of ligands has also been used in the synthesis of axially chiral molecules.(6) In these cases axial chiral systems can be synthesized from [2+2+2] cycloaddition reactions leading to axially chiral compounds containing C₂ symmetry as depicted below. Of note, in these cases the opposite enantiomers of S,S and R,R did indeed give the opposite isomer as a final product.

The Duphos family of ligands are well established chiral ligands for chiral hydrogenations, but have also been explored in ethylene tri and tetramerization reactions,(7) along with polymerization (8) reactions, although these areas are much less well studied. One key item for success in all these applications is the consistent purity and availability of the chiral bidentate ligand.

Derivatives of MeDuphos, such as EtDuphos and iPrDuphos (multiple enantiomers) can also be produced commercially when required. Furthermore, many other high purity chiral bidentate ligands are available and can be produced by current commercial technologies. These chiral ligands have made important innovations in the last 20 years and continue to develop more today.

CYTOP® phosphines and phosphine oxides, as well as CYPHOS® phosphonium ionic liquids are readily available in high-purity at commercial and lab scales.  Custom packaging and logistics support is available at commercial scale. To learn more about other ligands for catalysis, please refer to the Solvay offering at Strem or the Solvay website.

References:

1.    J. Am. Chem. Soc. 1992, 114, 6266-6267.
2.    J. Am. Chem. Soc. 1998, 120, 657-663.
3.    J. Am. Chem. Soc. 1998, 120, 4345-4353.
4.    Tetrahedron, 1994, 50, 4399-4428.
5.    J. Org. Chem. 2003, 68, 5731-5374.
6.    J. Am. Chem. Soc. 2004, 126, 8382-8383.
7.    Organometallics, 2020, 39, 976-987.
8.    J. Am. Chem. Soc. 1995, 117, 4455-4467.

Featured Product:

97-0096  (-)-1,2-Bis((2R,5R)-2,5-dimethylphospholano)benzene, min.97% (R,R)-Me-DUPHOS (147253-67-6)

Related Products:

CYTOP® Products

Phosphorus Ligands and Compounds Booklet

All products sold in collaboration with Solvay