Ylide-functionalized Phosphines (YPhos)

Coupling Reactions Under Mild Conditions

Professor Viktoria Gessner and coworkers from the Ruhr-University Bochum have developed a class of ylide-substituted phosphines (YPhos) which contain a bulky ylide-substituent directly bound at the phosphorus atom.^[1] These ligands are especially electron-rich and thus allow for palladium catalyzed coupling reactions at remarkably mild reaction conditions. They enable the conversion of often challenging aryl chlorides in good yield with short reaction times. For example, keyPhos (No. 913294) and joYPhos (No. 912042) perform excellently in the Buchwald-Hartwig aminations at room temperature. JoYPhos also readily converts aryl halides (including chlorides) with organolithium, Grignard and zinc reagents. The strongest donor trYPhos (No. 913030) is best suited for challenging alpha-arylations.

Key Advantages of YPhos Ligands

• Facile coupling of aryl halides, especially aryl chlorides
• Mild reaction conditions
• High activity in C-N and C-C cross coupling reactions
• Coupling of organolithium, magnesium and zinc reagents

Representative Applications of YPhos Ligands

keYPhos with a methyl group in the ylide-backbone is a valuable ligand for the palladium catalyzed coupling of aryl chlorides with primary and secondary alkyl and aryl amines at room temperature. The ligand performs well with common palladium sources such as Pd₂(dba)₃, Pd(OAc)₂, [Pd(allyl)Cl]₂ or [Pd(cinamyl)Cl]₂.^[2,3]

JoYPhos featuring a phenyl group at the ylide substituent is also an excellent ligand for Buchwald-Hartwig aminations^[4,5] as well as for C-C coupling reactions. It allows the previously unprecedented direct coupling of alkyllithium reagents with aryl chloride.^[6]

In this series, trYPhos is the most electron-rich YPhos ligand and was found to be active for alpha-arylation of aliphatic cyclic ketones.^[7]  

References

1. Scherpf T, Schwarz C, Scharf LT, Zur J, Helbig A, Gessner VH. 2018. Ylide-Functionalized Phosphines: Strong Donor Ligands for Homogeneous Catalysis. Angew. Chem. Int. Ed.. 57(39):12859-12864. https://doi.org/10.1002/anie.201805372

2. Weber P, Scherpf T, Rodstein I, Lichte D, Scharf LT, Gooßen LJ, Gessner VH. 2019. A Highly Active Ylide-Functionalized Phosphine for Palladium-Catalyzed Aminations of Aryl Chlorides. Angew. Chem. Int. Ed.. 58(10):3203-3207. https://doi.org/10.1002/anie.201810696

3. Scharf LT, Rodstein I, Schmidt M, Scherpf T, Gessner VH. 2020. Unraveling the High Activity of Ylide-Functionalized Phosphines in Palladium-Catalyzed Amination Reactions: A Comparative Study with ^CyJohnPhos and PtBu₃. ACS Catal.. 10(2):999-1009. https://doi.org/10.1021/acscatal.9b04666

4. Tappen J, Rodstein I, McGuire K, Großjohann A, Löffler J, Scherpf T, Gessner VH. 2020. Palladium Complexes Based on Ylide-Functionalized Phosphines (YPhos): Broadly Applicable High-Performance Precatalysts for the Amination of Aryl Halides at Room Temperature. Chem. Eur. J.. 26(19):4281-4288. https://doi.org/10.1002/chem.201905535

5. Rodstein I, Prendes DS, Wickert L, Paaßen M, Gessner VH. 2020. Selective Pd-Catalyzed Monoarylation of Small Primary Alkyl Amines through Backbone-Modification in Ylide-Functionalized Phosphines (YPhos). J. Org. Chem.. 85(22):14674-14683. https://doi.org/10.1021/acs.joc.0c01771

6. Scherpf T, Steinert H, Großjohann A, Dilchert K, Tappen J, Rodstein I, Gessner VH. 2020. Efficient Pd-Catalyzed Direct Coupling of Aryl Chlorides with Alkyllithium Reagents. Angew. Chem. Int. Ed.. 59(46):20596-20603. https://doi.org/10.1002/anie.202008866

7. Hu X, Lichte D, Rodstein I, Weber P, Seitz A, Scherpf T, Gessner VH, Gooßen LJ. 2019. Ylide-Functionalized Phosphine (YPhos)-Palladium Catalysts: Selective Monoarylation of Alkyl Ketones with Aryl Chlorides. Org. Lett.. 21(18):7558-7562. https://doi.org/10.1021/acs.orglett.9b02830