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WingPhos: A Unique and Versatile Chiral Bisphosphorus Ligand for Asymmetric Catalysis
Enhance your asymmetric catalysis and synthesis toolbox
Today’s blog was written by Prof. Wenjun Tang, from the Shanghai Institute of Organic Chemistry, CAS.
Prof. Tang is the inventor of a class of phosphine ligands with the 2,3-dihydrobenzo[d][1,3]oxaphosphole motif. One such ligand belonging to this class is the WingPhos ligand, which has seen widespread use in recent years for a variety of asymmetric transformations.
For a more comprehensive biographical sketch and more information on Prof. Tang’s chemistry, please read The Strem Chemiker Vol. XXXI No. 1 or watch our webinar on this topic.
Prof. Wenjun Tang
WingPhos: A Unique and Versatile Chiral
Bisphosphorus Ligand for Asymmetric Catalysis
Among thousands of chiral bisphosphorus ligands developed so far, there are some unique ones that differentiate themselves from others. WingPhos belongs to the category which is unique not only in its structure but also its applications in asymmetric catalysis. It is thus a strongly recommended addition to the toolbox of every researcher in the field of asymmetric catalysis and synthesis. Structurally, WingPhos is designed to have deep chiral pockets by attaching two anthracenyl groups to its core. They resemble two wings surrounding the nearby metal center (Figure 1), which is the origin of the ligand name. The metal center is located deep inside of the pocket so that good interactions between the substrate and the anthracenyl groups are expected. The unique structure of WingPhos has enabled its outstanding applications in asymmetric catalysis.
Figure 1. The structure of M(Rh)-WingPhos
The followings are some transformations powered by WingPhos:
1. Asymmetric hydrogenation[1]
WingPhos has shown high efficiency in rhodium-catalyzed asymmetric hydrogenation of (E)-β-aryl-N-acetyl enamides, cyclic β-arylenamides, and heterocyclic β-arylenamides. A series of chiral β-arylisopropylamines, 2-aminotetralines, and 3-aminochromans are synthesized in excellent ee’s at high substrate to catalyst ratios (showing up to 10,000 TON).
2. Addition of arylboroxines to simple aryl ketones [2]
Highly enantioselective additions of arylboroxines to simple aryl ketones have been achieved for the first time with a Rh-WingPhos catalyst, providing a range of chiral diaryl alkyl carbinols in excellent ee’s and yields.
3. Addition of arylboroxines to N-unprotected ketimines [3]
Highly enantioselective rhodium-catalyzed addition of arylboroxines to N-unprotected ketimines are realized by employing WingPhos as the chiral ligand, providing facile and practical access to a range of chiral α-trifluoromethyl-α,α-diaryl amines in excellent ee‘s and yields with the Rh loading as low as 1 mol %.
4. Asymmetric macrocyclization[4]
A highly enantioselective macrocyclization between benzyl chloride and a carbene has been realized only with a Pd-WingPhos catalyst by Professor Zhenhua Gu at University of Science and Technology of China, leading to the cyclization product in 93% ee.
5. Tandem allylic substitution[5]
A general and enantioselective palladium-catalyzed tandem allylic substitution of butenylene dicarbonate powered by Wingphos has been developed, forming a series of chiral substituted heterocycles including tetrahydroquinoxalines, piperazines, dihydro-2H-benzo[b][1,4]-oxazine, and morpholines in excellent ee’s and yields.
6. Asymmetric Hydroesterification[6]
An efficient asymmetric hydroesterfication of diarylmethyl carbinols is developed for the first time with a Pd-WingPhos catalyst, resulting in a series of chiral 4-aryl-3,4-dihydrocoumarins in excellent enantioselectivities and good yields.
In summary, WingPhos with its unique structural feature has shown its special effectiveness in various asymmetric catalytic reactions including asymmetric hydrogenation, asymmetric nucleophilic addition, asymmetric macrocyclization, asymmetric tandem allylic substitution, and asymmetric hydroesterification. It is expected that more efficient and powerful asymmetric catalytic reactions will be developed employing WingPhos as the chiral ligand.
References:
1. Angew. Chem. Int. Ed. 2013, 52, 4235-4238.
2. Angew. Chem. Int. Ed. 2016, 55, 4527-4531.
3. Angew. Chem. Int. Ed. 2019, 58, 16119-16123.
4. Chin. J. Chem. 2020, 38, 1081-1085.
5. Org. Lett. 2020, 22, 4483-4488.
6. Angew. Chem. Int. Ed. doi: 10.1002/anie.202015450.
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96-3810 AntPhos and WingPhos Kit
Related Products and Resources:
Phosphorus Ligands and Compounds Booklet
The Strem Chemiker - Vol. XXXI No. 1
