'Product Blog'
A Fresh Success for Chiral Hydrogenation
This bidentate phosphine ligand plays an important role in L-Menthol
Despite the importance of asymmetric hydrogenation being recognized in 2001 by the awarding of the Nobel Prize in Chemistry to W.S. Knowles and R. Noyori, very few large scale industrial processes utilize the technology today. An exception that has always been of keen interest to me, based on my love of everything mint flavored, is the manufacture of L-Menthol by BASF.
The process developed by BASF involves the catalytic enantioselective hydrogenation of citral to (+)-(R)-citronellal (1) which can then be further converted to L-Menthol. The catalyst for the chiral hydrogenation is a ruthenium complex of the Chiraphos ligand (( 2R,3R)-(+)-2,3-Bis(diphenylphosphino)butane and marketed by Solvay as RhodaPhos® CP100R) (2). Given the preponderance of mint flavoring in consumer products, at the time the first plant operating this process in Ludwigshafen was commissioned in 2012 the demand for L-Menthol had outstripped the supply available from natural and pre-existing synthetic sources (3). The success of BASF’s Menthol Process was evidenced by the commissioning of a second plant in 2017, located in Kuantan, Malaysia in a joint venture with Petronas (4).
Other Transformations Facilitated by Chiraphos
Chiraphos has also been used in many other enantioselective hydrogenations, for example the asymmetric reduction of coumarin, an important intermediate to the overactive bladder treatment R-tolterodine(5).
The ligand has found utility in other chiral syntheses, for example the iron-catalyzed ortho-alkylation and ortho-arylation of ferrocenes bearing ortho-directing groups (6), the rhodium-catalyzed enantioselective synthesis of acyclic β-diaryl ketones and esters via 1,4-addition of arylboronic acids to β-aryl-α,β-unsaturated ketones or esters (7,8), the enantioselective [3 + 2] annulation of N-heteroarenes with alkynes with a cobalt / Chiraphos catalyst system (9) and the modification of thiostrepton, a complex molecule with potent antibacterial properties, via rhodium-catalyzed conjugate arylation (10).
RhodaPhos® CP100R is a commercial scale, bidentate phosphine ligand.
To learn more about other specialty phosphorus products, please refer to the Solvay offering at Strem or the Solvay website.
References:
- US Patent 7973198.
- Specialty Chemicals Magazine, March 2011, 30-33.
- https://www.basf.com/us/en/media/science-around-us/the-cool-freshness-of-menthol.html
- https://www.basf.com/global/en/media/news-releases/2016/09/p-16-290.html
- J. Org. Chem. 2007, 72, 6056-6059.
- Organometallics 2017, 36, 4979-4989.
- Tetrahedron 2006, 62, 9610-9621.
- Tetrahedron: Asymmetry 2017, 28, 196-202.
- J. Am. Chem. Soc. 2022, 144, 1087-1093.
- J. Am. Chem. Soc. 2017, 139, 15460-15466.
Featured Products:
97-0165 (2R,3R)-(+)-Bis(diphenylphosphino)butane, min.98%,(R,R)-CHIRAPHOS [RHODAPHOS® CP100R] (74839-84-2)
Related Products:
All products sold in collaboration with Solvay
Phosphorus Ligands and Compounds Booklet
