Josiphos ligands

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General scheme for a Josiphos ligand JosiphosNew.svg
General scheme for a Josiphos ligand

A Josiphos ligand is a family of chiral diphosphine ligands that are used for asymmetric catalysis. [2] [3] They feature a 1,2-disubstituted ferrocene backbone.

Contents

History

X-ray crystallographic structure of [(josiphos)Ir(cod)] . Color code: violet = P, blue = Fe, Ir. CSD CIF ASERAR.png
X-ray crystallographic structure of [(josiphos)Ir(cod)] . Color code: violet = P, blue = Fe, Ir.

Modern enantioselective synthesis typically applies a well-chosen homogeneous catalyst for key steps. The ligands on these catalysts confer chirality. The Josiphos family of privileged ligands provides especially high yields in enantioselective synthesis. [4] [5]

In the early 1990s, Antonio Togni began studying at the Ciba (now Novartis) Central Research Laboratories [6] previously-known [7] ferrocenyl ligands for a Au(I)-catalyzed aldol reaction. [6] Togni's team began considering diphosphine ligands, and technician Josi Puleo prepared the first ligands with secondary phosphines. The team applied Puleo's products in an Ru-catalyzed enamide hydrogenation synthesis; in a dramatic success, the reaction had e.e. >99% and a turnover frequency (TOF) 0.3 s−1. [6] [7] The same ligand proved useful in production of (S)-metolachlor, active ingredient in the most common herbicide in the United States. Synthesis requires enantioselective hydrogenation of an imine; after introduction of the catalyst, the reaction proceeds with 100% conversion, turnover number (TON) >7mil, and turnover frequency >0.5 ms−1. This process is the largest-scale application of enantioselective hydrogenation, producing over 10 kilotons/year of the desired product with 79% e.e. [2] [1]

Josiphos ligands also serve in non-enantioselective reactions: a Pd-catalyzed reaction of aryl chlorides and aryl vinyl tosylates with TON of 20,000 or higher, [8] catalytic carbonylation, [9] or Grignard and Negishi couplings [10] [11] A variety of Josiphos ligands are commercially available under licence from Solvias. The (R-S) and its enantiomer provide higher yields and enantioselectivities than the diastereomer (R,R). [1]

The consensus for the naming is abbreviating the individual ligand as (R)-(S)-R2PF-PR'2. The substituent on the Cp is written in front of the F and the R on the chiral center after the F. [2]

Reactions using Josiphos ligands

Some reactions that are accomplished using M-Josiphos complexes as catalyst are listed below. Other reactions where Josiphos ligands can be used are: hydrogenation of C=N, C=C and C=O bonds, catalyzed allylic substitution, hydrocarboxylation, Michael addition, allylic alkylation, Heck-type reactions, oxabicycle ring-opening, and allylamine isomerization.[ citation needed ]

Hydroboration of styrene
HB of styrene.png
Conducted at -78 °C, the above reaction has e.e.'s up to 92% and TOF of 5-10 h−1. [12] Hayashi's Rh-binap complex gives better yield. [13]
Hydroformylation of Styrene
Hydroformylation of styrene.png
This reaction scheme yields of up to 78% ee of the (R) product, but low TON and TOF of 10-210 and 1-14h−1 (respectively). [2] [14]
Reductive amination
Amination of s metolachlor.png
Above is the preparation of (S)-metolachlor. Good yields and a 100% conversion crucially require AcOH solvent. [13]
Hydrogenation of exocyclic methyl imine
Exocyclic imine hydrogenation.png
This key step to synthesize a HIV integrase inhibitor, Crixivan, is one of the few known homogeneous heteroarene hydrogenation reactions. Bulky R groups increase the catalyst's performance, with 97% e.e. and TON and TOF of 1k and 8 min−1, respectively. [15] [16]
Asymmetric synthesis of chromanoylpyridine derivatives
HIV rxn.png
This reaction, for an intermediate in synthesis of an antihypertensive and anti-alopecic chromanoylpyridine derivative, exhibits high enantioselectivity, but low activity. [17]

Modified Josiphos ligands

The ferrocene scaffold has proved to be versatile. [18] [19] [20]

Many variations of Josiphos ligands have been reported. One family is prepared from Ugi's amine.

Josiphos synth scheme.png

An important improvement on initial syntheses has been using N(CH3)2 as a leaving group over acetate, although an acetic acid solvent gives better yields. [6]

Further reading

Clevenger, Andrew L.; Stolley, Ryan M.; Aderibigbe, Justis; Louie, Janis (2020). "Trends in the Usage of Bidentate Phosphines as Ligands in Nickel Catalysis". Chemical Reviews. 120 (13): 6124–6196. doi:10.1021/acs.chemrev.9b00682. PMID   32491839.

References

  1. 1 2 3 4 Blaser, Hans Ulrich; Pugin, Benoît; Spindler, Felix (2021). "Having Fun (And Commercial Success) with Josiphos and Related Chiral Ferrocene Based Ligands". Helvetica Chimica Acta. 104. doi:10.1002/hlca.202000192. S2CID   229427019.
  2. 1 2 3 4 Blaser, Hans-Ulrich; Brieden, Walter; Pugin, Benoit; Spindler, Felix; Studer, Martin; Togni, Antonio (2002). "Solvias Josiphos Ligands: From Discovery to Technical Applications" . Topics in Catalysis. 19 (1): 3–16. doi:10.1023/A:1013832630565.
  3. ↑ Blaser, Hans-Ulrich; Pugin, Benoît; Spindler, Felix; Mejía, Esteban; Togni, Antonio (2011-04-06). Zhou, Qi-Lin (ed.). Josiphos Ligands: From Discovery to Technical Applications (1 ed.). Wiley. pp. 93–136. doi:10.1002/9783527635207.ch3. ISBN   978-3-527-32704-1.
  4. ↑ Spessard, Gary O.; Miessler, Gary L. (2010). Organometallic chemistry (2 ed.). New York: Oxford University Press. pp. 378–379. ISBN   978-0-19-533099-1.
  5. ↑ Elschenbroich, Christopher (2006). Organometallics: Third Edition. pp.518-519
  6. 1 2 3 4 Togni, Antonio (1996-03-27). "Developing New Chiral Ferrocenyl Ligands for Asymmetric Catalysis: A Personal Account". CHIMIA. 50 (3): 86. doi: 10.2533/chimia.1996.86 . ISSN   2673-2424.
  7. 1 2 Ito, Yoshihiko.; Sawamura, Masaya.; Hayashi, Tamio. (October 1986). "Catalytic asymmetric aldol reaction: reaction of aldehydes with isocyanoacetate catalyzed by a chiral ferrocenylphosphine-gold(I) complex" . Journal of the American Chemical Society. 108 (20): 6405–6406. doi:10.1021/ja00280a056. ISSN   0002-7863.
  8. ↑ Littke, Adam F.; Fu, Gregory C. (2002-11-15). "Palladium-Catalyzed Coupling Reactions of Aryl Chlorides" . Angewandte Chemie International Edition. 41 (22): 4176–4211. doi:10.1002/1521-3773(20021115)41:22<4176::AID-ANIE4176>3.0.CO;2-U. PMID   12434342.
  9. ↑ Cai, Chaoxian; Rivera, Nelo R.; Balsells, Jaume; Sidler, Rick R.; McWilliams, J. Christopher; Shultz, C. Scott; Sun, Yongkui (2006-10-01). "An Efficient Catalyst for Pd-Catalyzed Carbonylation of Aryl Arenesulfonates" . Organic Letters. 8 (22): 5161–5164. doi:10.1021/ol062208g. ISSN   1523-7060. PMID   17048868.
  10. ↑ Limmert, Michael E.; Roy, Amy H.; Hartwig, John F. (2005-11-01). "Kumada Coupling of Aryl and Vinyl Tosylates under Mild Conditions" . The Journal of Organic Chemistry. 70 (23): 9364–9370. doi:10.1021/jo051394l. ISSN   0022-3263. PMID   16268609.
  11. ↑ Vo, Giang D.; Hartwig, John F. (2009-08-12). "Palladium-Catalyzed Coupling of Ammonia with Aryl Chlorides, Bromides, Iodides, and Sulfonates: A General Method for the Preparation of Primary Arylamines". Journal of the American Chemical Society. 131 (31): 11049–11061. doi:10.1021/ja903049z. ISSN   0002-7863. PMC   2823124 . PMID   19591470.
  12. ↑ T. Hayashi, Comprehensive Asymmetric Catalyst, eds. E.N. Jacobsen, A. Pfaltz and H. Yamamoto, 1999 pp. 247
  13. 1 2 Blaser, Hans-Ulrich; Buser, Hans-Peter; Jalett, Hans-Peter; Pugin, Benoit; Spindler, Felix (1999-12-31). "Iridium Ferrocenyl Diphosphine Catalyzed Enantioselective Reductive Alkylation of a Hindered Aniline" . Synlett. 1999 (Sup. 1): 867–868. doi:10.1055/s-1999-3106. ISSN   0936-5214. S2CID   99845649.
  14. ↑ Godard, Cyril; Ruiz, Aurora; Claver, Carmen (August 2006). "Systematic Study of the Asymmetric Methoxycarbonylation of Styrene Catalyzed by Palladium Systems Containing Chiral Ferrocenyl Diphosphine Ligands" . Helvetica Chimica Acta. 89 (8): 1610–1622. doi:10.1002/hlca.200690161. ISSN   0018-019X.
  15. ↑ R.Fuchs, EP 803502(1996) assigned to Lonza A.G
  16. ↑ Studer, Martin; Wedemeyer-Exl, Christina; Spindler, Felix; Blaser, Hans-Ulrich (2000-12-13). "Enantioselective Homogeneous Hydrogenation of Monosubstituted Pyridines and Furans" . Monatshefte fuer Chemie/Chemical Monthly. 131 (12): 1335–1343. doi:10.1007/s007060070013.
  17. ↑ E. Broger, Y. Crameri and P. Jones, WO 99/01 453. (1997), assigned to Hoffman-La Roche
  18. ↑ Colacot, Thomas J. (2003). "A Concise Update on the Applications of Chiral Ferrocenyl Phosphines in Homogeneous Catalysis Leading to Organic Synthesis". Chemical Reviews. 103 (8): 3101–3118. doi:10.1021/cr000427o. PMID   12914493.
  19. ↑ Blaser, Hans-Ulrich; Malan, Christophe; Pugin, Benoît; Spindler, Felix; Steiner, Heinz; Studer, Martin (January 2003). "Selective Hydrogenation for Fine Chemicals: Recent Trends and New Developments" . Advanced Synthesis & Catalysis. 345 (1–2): 103–151. doi:10.1002/adsc.200390000. ISSN   1615-4150.
  20. ↑ Chen, W. and Blaser, H.U 2008 in Phosphorus Ligands in Asymmetric Catalysis: Synthesis and Applications. (e.d. A. Borner) pp. 359-393
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