YPhos ligands for palladium-catalyzed coupling reactions
Highly electron-rich ylide substituted phosphines enabling unprecedented efficiency and versatility
When combined with a suitable palladium precursor, the YPhos family of ligands offers several significant advantages:
- Facile coupling of aryl halides, particularly aryl chlorides, which are typically challenging substrates for cross-coupling reactions1-4.
- Mild reaction conditions are appropriate, which can result in improved selectivity as fewer side reactions are observed.
High activity in C-N and C-C cross-coupling reactions1-8. - It allows for the coupling of organolithium, magnesium, and zinc reagents, broadening the range of possible reactions and substrates that can be used5,6,8.
These advantages make YPhos ligands particularly useful for palladium-catalyzed coupling reactions, Additionally, they are suitable for a variety of applications, including the Buchwald-Hartwig amination and a-arylation of aliphatic cyclic ketones1-4,7.
joYPhos
Tricyclohexyl((dicyclohexylphosphanyl)(phenyl)methylene)phosphane
CAS Number: 2271302-85-1
Chemical formula: C37H60P2
Empirical formula: PCy3C(Ph)PCy2
trYPhos
Tricyclohexyl(1-(di-tert-butylphosphanyl)ethylidene)phosphane
CAS Number: 2271302-83-9
Chemical formula: C28H54P2
Empirical formula: PCy3C(Me)PtBu2
keYPhos
Tricyclohexyl(1-(dicyclohexylphosphanyl)ethylidene)phosphane
CAS Number: 14185-94-5
Chemical formula: C32H58P2
Empirical formula: PCy3C(Me)PCy2
piperYPhos
Tris(1-piperidyl)((dicyclohexylphosphanyl)(2-tolyl)methylene)phosphane
Chemical formula: C35H59N3P2
Empirical formula: PPip3C(o-Tol)PCy2
pinkYPHos
Tricyclohexyl((dicyclohexylphosphanyl)(2-tolyl)methylene)phosphane
CAS Number: 2495200-15-0
CAS Number 2: 2495200-11-6
Chemical formula: C38H62P2
Empirical formula: PCy3C(o-Tol)PCy2
Umicore CX512
Chlorophenylallyl(tricyclohexyl((dicyclohexylphosphanyl)(phenyl)methylene)phosphine)palladium(II)
CAS Number: 2412537-46-1
Chemical formula: C46H69ClP2Pd
Empirical formula: Pd(joYPhos)(cinnamyl)Cl
1. Weber, P.; Scherpf, T.; Rodstein, I.; Lichte, D.; Scharf, L. T.; Gooßen, L. J.; Gessner, V. H. A highly active Ylide‐Functionalized phosphine for Palladium‐Catalyzed aminations of aryl chlorides. Angewandte Chemie International Edition 2019, 58 (10), 3203–3207. https://doi.org/10.1002/anie.201810696.
2. Tappen, J.; Rodstein, I.; McGuire, K.; Großjohann, A.; Löffler, J.; Scherpf, T.; Gessner, V. H. Palladium Complexes based on Ylide‐Functionalized Phosphines (YPHOS): broadly applicable High‐Performance precatalysts for the amination of aryl halides at room temperature. Chemistry - a European Journal 2020, 26 (19), 4281–4288. https://doi.org/10.1002/chem.201905535.
3. Rodstein, I.; Prendes, D. S.; Wickert, L.; Paaßen, M.; Gessner, V. H. Selective Pd-Catalyzed Monoarylation of Small Primary Alkyl Amines through Backbone-Modification in Ylide-Functionalized Phosphines (YPhos). The Journal of Organic Chemistry 2020, 85 (22), 14674–14683. https://doi.org/10.1021/acs.joc.0c01771.
4. Neigenfind, P.; Knyszek, D.; Handelmann, J.; Gessner, V. H. Synthesis of sterically encumbered di- and triarylamines by palladium-catalysed C–N coupling reactions under mild reaction conditions. Catalysis Science & Technology 2022, 12 (11), 3447–3453. https://doi.org/10.1039/d1cy02352g.
5. Scherpf, T.; Steinert, H.; Großjohann, A.; Dilchert, K.; Tappen, J.; Rodstein, I.; Gessner, V. H. Efficient Pd‐Catalyzed Direct Coupling of Aryl Chlorides with Alkyllithium Reagents. Angewandte Chemie International Edition 2020, 59 (46), 20596–20603. https://doi.org/10.1002/anie.202008866.
6. Hu, Z.; Wei, X.; Handelmann, J.; Seitz, A.; Rodstein, I.; Gessner, V. H.; Gooßen, L. J. Coupling of Reformatsky Reagents with Aryl Chlorides Enabled by Ylide‐Functionalized Phosphine Ligands. Angewandte Chemie International Edition 2021, 60 (12), 6778–6783. https://doi.org/10.1002/anie.202016048.
7. Hu, X.-Q.; Lichte, D.; Rodstein, I.; Weber, P.; Seitz, A.-K.; Scherpf, T.; Gessner, V. H.; Gooßen, L. J. Ylide-Functionalized Phosphine (YPhos)–Palladium Catalysts: Selective Monoarylation of Alkyl Ketones with Aryl Chlorides. Organic Letters 2019, 21 (18), 7558–7562. https://doi.org/10.1021/acs.orglett.9b02830.
8. Daeschlein-Gessner, V.; Rodstein, I.; Scherpf, T.; Doppiu, A. ORGANOMETALLIC COMPOUNDS, PRODUCTION AND USE THEREOF. WO2023198596A1, October 19, 2023.
9. Su, Y.; Zhao, Y.; Zhang, H.; Luo, Y.; Xu, X. Rare-Earth Aryloxide/Ylide-Functionalized phosphine frustrated Lewis pairs for the polymerization of 4-Vinylpyridine and its derivatives. Macromolecules 2021, 54 (17), 7724–7731. https://doi.org/10.1021/acs.macromol.1c01339.
10. Rodstein, I.; Kelling, L.; Löffler, J.; Scherpf, T.; Sarbajna, A.; Andrada, D. M.; Gessner, V. H. Formation of exceptional monomeric YPhos–PdCl2 complexes with high activities in coupling reactions. Chemical Science 2022, 13 (45), 13552–13562. https://doi.org/10.1039/d2sc04523k.
J. Löffler, N. Kaiser, D. Knyszek, K.-S. Feichtner, M. Jörges, F. Krischer, V. H. Gessner*
P,N-coordinating Ylide-Functionalized Phosphines (NYPhos): A Ligand Platform for the selective Monoarylation of small Nucleophiles
Angew. Chem. Int. Ed. 2024, 63, e202408947. https://doi.org/10.1002/anie.202408947
D. Knyszek, V. H. Gessner*
Ylide-Substituted Phosphines in Palladium-Catalyzed Coupling Reactions
Aldrichimica Acta 2024, 57, 17 – 28.
S. Manna, F. Papp, Y. Hisata, J. Löffler, M. Rybka, V. H. Gessner,* Y. Hoshimoto,* L. J. Goossen*
Palladium-Catalyzed γ-Arylation of Acylketene Synthons with Aryl Chlorides Enabled by Ylide-Functionalized Phosphines (YPhos) Adv. Synth. Catal. 2024, https://doi.org/10.1002/adsc.202301474.
A. Burhenn, R. Bavaro, V.H. Gessner
Pd-catalysed hydrodehalogenation of aryl chlorides: a mild method for deuteration and detoxification
Catal. Sci. Technol., 2023, 13, 3545-3550. doi: 10.1039/D3CY00432E
I. Rodstein, A. Doppiu, V.H. Gessner*
Ylide-Functionalized Phosphine (YPhos) Platinum Complexes: Synthesis and Application in Hydrosilylations at Mild Conditions
Organometallics 2023, 42, 1021-1029. doi: 10.1021/acs.organomet.3c00156
F. Papp, D. Sowa Prendes, S. Manna, A-K. Seitz, S. Kostiukovska, J. Löffler, V.H. Gessner*, L.J. Gooßen*
Palladium-Catalyzed Arylation of Hydantoins with Aryl Chlorides Enabled by Ylide-Functionalized Phosphines (YPhos)
ACS Catal. 2023, 13, 6846-6850. doi: 10.1021/acscatal.3c01403
J. Löffler, S.M.P. Vanden Broeck, C.S.J. Cazin, S.P. Nolan, V.H. Gessner
Correlation of Experimental and Calculated Reaction Enthalpies with Ligand Donor Strengths
Chem. Eur. J. 2023, e202300151. doi: 10.1002/chem.202300151
I. Rodstein, V.H. Gessner*
Carbanion-functionalized phosphines: New design elements for catalyst development
Adv. Catal. 2023, 72, 1-56. https://doi.org/10.1016/bs.acat.2023.07.002
J.F. Goebel, J. Löffler, Z. Zeng, J. Handelmann, A. Hermann, I. Rodstein, T. Gensch, V.H. Gessner, L.J. Gooßen
Computer-Driven Development of Ylide Functionalized Phosphinesfor Palladium-Catalyzed Hiyama Couplings
Angew. Chem. Int. Ed. 2023, e202216160. doi: 10.1002/anie.202216160
X.-J. Wei, B. Xue, J. Handelmann, Z. Hu, H. Darmandeh, V.H. Gessner*, L.J. Gooßen*
Ylide-Functionalized Diisopropyl Phosphine (prYPhos): A Ligand for Selective Suzuki-Miyaura Couplings of Aryl Chlorides
Adv. Synth.Catal.2022, 364, 3336-3341. doi: 10.1002/adsc.202200321
S. Lapointe, A. Sarbajna, and V.H. Gessner*
Ylide-Substituted Phosphines: A Platform of Strong Donor Ligands for Gold Catalysis and Palladium-Catalyzed Coupling Reactions. Acc. Chem. Res. 2022, 55, 5, 770–782. doi: 10.1021/acs.accounts.1c00797