A combinatorial approach to the identification of self-assembled ligands for rhodium-catalysed asymmetric hydrogenation

Abstract

An effective and efficient means to catalyst discovery is the high-throughput screening of catalyst libraries. However, the current status of this approach suffers from a number of limitations, namely access to structurally diverse and meaningful ligand libraries and the enormous effort required for massive parallel screening of the resulting catalysts. We report an integrated solution to these drawbacks, which combines a diversity-oriented ligand synthesis, a catalyst-generation process driven by self-assembly and, finally, a combinatorial iterative library deconvolution strategy to identify the optimal catalyst. As a test case, rhodium-catalysed asymmetric hydrogenation was studied and, from a library of 120 self-assembling catalysts, highly enantioselective catalysts for the asymmetric hydrogenation of different olefinic substrates were identified within 17 experiments. Comparison of the results of the iterative library deconvolution strategy with those of the classic parallel-screening process confirmed the validity of this approach.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Figure 1: Self-assembly of bidentate ligands by DNA-inspired complementary hydrogen bonding.
Figure 2: Combinatorial approach to the identification of the most active and selective ligand combination(s).
Figure 3: Parallel screening of a library of 120 self-assembled catalysts – the classic approach.

References

  1. 1

    Zhang, W., Chi, Y. & Zhang, Z. Developing chiral ligands for asymmetric hydrogenation. Acc. Chem. Res. 40, 1278–1290 (2007).

    CAS  Article  Google Scholar 

  2. 2

    Tang, W. & Zhang, X. New chiral phosphorus ligands for enantioselective hydrogenation. Chem. Rev. 103, 3029–3070 (2003).

    CAS  Article  Google Scholar 

  3. 3

    Blaser U. & Schmidt, E. Asymmetric Catalysis on Industrial Scale: Challenges, Approaches and Solutions (Wiley, 2003).

    Google Scholar 

  4. 4

    Gennari, C. & Piarulli, U. Combinatorial libraries of chiral ligands for enantioselective catalysis. Chem. Rev. 103, 3071–3100 (2003).

    CAS  Article  Google Scholar 

  5. 5

    Jaekel, C. & Paciello, R. High-throughput and parallel screening methods in asymmetric hydrogenation. Chem. Rev. 106, 2912–2942 (2006).

    CAS  Article  Google Scholar 

  6. 6

    Knowles, W. S. Asymmetric hydrogenation. Acc. Chem. Res. 16, 106–112 (1983).

    CAS  Article  Google Scholar 

  7. 7

    Mori, S., Vreven, T. & Morokuma, K. Transition states of binap-rhodium(I)-catalyzed asymmetric hydrogenation: theoretical studies on the origin of the enantioselectivity. Chem. Asian J. 1, 391–403 (2006).

    CAS  Article  Google Scholar 

  8. 8

    Reetz, M. T., Sell, T., Meiswinkel, A. & Mehler, G. A new principle in combinatorial asymmetric transition-metal catalysis: mixtures of chiral monodentate P ligands Angew. Chem. Int. Ed. 42, 790–793 (2003).

    CAS  Article  Google Scholar 

  9. 9

    Reetz, M. T. & Mehler, G. Mixtures of chiral and achiral monodentate ligands in asymmetric Rh-catalyzed olefin hydrogenation: reversal of enantioselectivity. Tetrahedron Lett. 44, 4593–4596 (2003).

    CAS  Article  Google Scholar 

  10. 10

    Reetz, M. T. & Li, X. Combinatorial approach to the asymmetric hydrogenation of β-acylamino acrylates: use of mixtures of chiral monodentate P-ligands. Tetrahedron 60, 9709–9714 (2004).

    CAS  Article  Google Scholar 

  11. 11

    Reetz, M. T. & Li, X. The influence of mixtures of monodentate achiral ligands on the regioselectivity of transition-metal-catalyzed hydroformylation. Angew. Chem. Int. Ed. 44, 2959–2962 (2005).

    CAS  Article  Google Scholar 

  12. 12

    Pena, D. et al. Improving conversion and enantioselectivity in hydrogenation by combining different monodentate phosphoramidites; a new combinatorial approach in asymmetric catalysis. Org. Biomol. Chem. 1, 1087–1089 (2003).

    CAS  Article  Google Scholar 

  13. 13

    Pena, D., Minnaard, A. J., de Vries, J. G. & Feringa, B. L. Highly enantioselective rhodium-catalyzed hydrogenation of β-dehydroamino acid derivatives using monodentate phosphoramidites. J. Am. Chem. Soc. 124, 14552–14553 (2002).

    CAS  Article  Google Scholar 

  14. 14

    Duursma, A. et al. First examples of improved catalytic asymmetric C–C bond formation using the monodentate ligand combination approach. Org. Lett. 5, 3111–3113 (2003).

    CAS  Article  Google Scholar 

  15. 15

    Monti, C., Gennari, C. & Piarulli, U. Rh-catalysed asymmetric hydrogenations with a dynamic library of chiral tropos phosphorus-ligands. Tetrahedron Lett. 45, 6859–6862 (2004).

    CAS  Article  Google Scholar 

  16. 16

    Monti, C., Gennari, C. & Piarulli, U. Enantioselective conjugate addition of phenylboronic acid to enones catalysed by a chiral tropos/atropos rhodium complex at the coalescence temperature. Chem. Commun. 5281–5283 (2005).

  17. 17

    Dahmen S. & Braese S. Combinatorial methods for the discovery and optimisation of homogeneous catalysts. Synthesis 10, 1431–1449 (2001).

    Google Scholar 

  18. 18

    Reetz, M. T. Combinatorial transition-metal catalysis: mixing monodentate ligands to control enantio-, diastereo-, and regioselectivity. Angew. Chem. Int. Ed. 47, 2556–2588 (2008).

    CAS  Article  Google Scholar 

  19. 19

    Breit, B. & Seiche, W. Self-assembly of bidentate ligands for combinatorial homogeneous catalysis based on an A–T base-pair model. J. Am. Chem. Soc. 125, 6608–6609 (2003).

    CAS  Article  Google Scholar 

  20. 20

    Breit, B. & Seiche, W. Self-assembly of bidentate ligands for combinatorial homogeneous catalysis based on an A–T base-pair model. Angew. Chem. Int. Ed. 44, 1640–1643 (2005).

    CAS  Article  Google Scholar 

  21. 21

    Seiche, W., Schuschkowski, A. & Breit, B. Room temperature/ambient pressure regioselective hydroformylation of terminal alkenes. Adv. Synth. Catal. 347, 1488–1494 (2005).

    CAS  Article  Google Scholar 

  22. 22

    Breit, B. & Seiche, W. Self-assembly of bidentate ligands for combinatorial homogeneous catalysis. Pure Appl. Chem. 78, 249–256 (2006).

    CAS  Article  Google Scholar 

  23. 23

    Chevallier, F. & Breit, B. Self-assembled bidentate ligands for Ru-catalyzed anti-Markovnikov hydration of terminal alkynes. Angew. Chem. Int. Ed. 45, 1599–1602 (2006).

    CAS  Article  Google Scholar 

  24. 24

    Birkholz, M.-N. et al. Enantioselective Pd-catalyzed allylic amination with self-assembling and non-assembling monodentate phosphine ligands. Tetrahedron: Asymmetry 18, 2055–2060 (2007).

    CAS  Article  Google Scholar 

  25. 25

    Weis, M., Waloch, C., Seiche, W. & Breit, B. Self-assembly of bidentate ligands for combinatorial homogeneous catalysis: asymmetric rhodium-catalyzed hydrogenation. J. Am. Chem. Soc. 128, 4188–4189 (2006).

    CAS  Article  Google Scholar 

  26. 26

    Smejkal, T. & Breit, B. Self-assembled bidentate ligands for ruthenium-catalyzed hydration of nitriles. Organometallics 26, 2461–2464 (2007).

    CAS  Article  Google Scholar 

  27. 27

    Wieland, J., Waloch, C., Keller, M. & Breit, B. Self-assembly of bidentate ligands for combinatorial homogeneous catalysis: methanol-stable platforms analogous to the adenine thymine base pair. Angew. Chem. Int. Ed. 46, 3037–3039 (2007).

    Article  Google Scholar 

  28. 28

    de Greef, M. & Breit, B. Self-assembled bidentate ligands for the nickel-catalyzed hydrocyanation of alkenes. Angew. Chem. Int. Ed. 48, 551–554 (2009).

    CAS  Article  Google Scholar 

  29. 29

    Slagt, V. F., van Leeuwen, P. W. N. M. & Reek, J. N. H. Multicomponent porphyrin assemblies as functional bidentate phosphite ligands for regioselective rhodium-catalyzed hydroformylation. Angew. Chem. Int. Ed. 42, 5619–5623 (2003).

    CAS  Article  Google Scholar 

  30. 30

    Slagt, V. F., Roeder, M., Kamer, P. C. J., van Leeuwen P. W. N. M. & Reek, J. N. H. Supraphos: a supramolecular strategy to prepare bidentate ligands. J. Am. Chem. Soc. 126, 4056–4057 (2004).

    CAS  Article  Google Scholar 

  31. 31

    Reek, J. N. H. et al. Supraphos: a supramolecular strategy to prepare bidentate ligands. J. Organomet. Chem. 690, 4505–4516 (2005).

    CAS  Article  Google Scholar 

  32. 32

    Jiang, X.-B. et al. Screening of a supramolecular catalyst library in the search for selective catalysts for the asymmetric hydrogenation of a difficult enamide substrate. Angew. Chem. Int. Ed. 45, 1223–1227 (2006).

    CAS  Article  Google Scholar 

  33. 33

    Takacs, J. M., Reddy, D. S., Moteki, S. A., Wu, D. & Palencia, H. Asymmetric catalysis using self-assembled chiral bidentate P,P-ligands. J. Am. Chem. Soc. 126, 4494–4495 (2004).

    CAS  Article  Google Scholar 

  34. 34

    Duckmanton, P. A., Blake, A. J. & Love, J. B. Palladium and rhodium ureaphosphine complexes: exploring structural and catalytic consequences of anion binding. Inorg. Chem. 44, 7708–7710 (2005).

    CAS  Article  Google Scholar 

  35. 35

    Shi, L. et al. Engineering a polymeric chiral catalyst by using hydrogen bonding and coordination interactions Angew. Chem. Int. Ed. 45, 4108–4112 (2006).

    CAS  Article  Google Scholar 

  36. 36

    Breuil, P.-R. R., Patureau, F. W. & Reek, J. N. H. Singly hydrogen bonded supramolecular ligands for highly selective rhodium-catalyzed hydrogenation reactions. Angew. Chem. Int. Ed. 48, 2196–2199 (2009).

    Article  Google Scholar 

  37. 37

    Bougioukou, D. J. R., Kille, S. Taglieber, A. & Reetz M. T. Directed evolution of an enantioselective enoate-reductase: testing the utility of iterative saturation mutagenesis. Adv. Synth. Catal. 351, 3287–3305 (2009).

    CAS  Article  Google Scholar 

  38. 38

    Polizzi K. M. et al. Simulation modeling of pooling for combinatorial protein engineering. J. Biomol. Screening 10, 865–864 (2005).

    Article  Google Scholar 

Download references

Acknowledgements

This work was funded by the German Research Foundation (International Research Training Group IRTG 1038, ‘Catalysts and Catalytic Reactions for Organic Synthesis’), the Alfried Krupp Award for young university teachers of the Krupp foundation (to B.B.) and BASF SE. We thank A. Lutterer, S. Ikkes, H. Ziegler and G. Leonhard-Lutterbeck for technical assistance.

Author information

Affiliations

Authors

Contributions

J.W. and B.B. conceived and designed the experiments. J.W. performed the experiments. J.W. and B.B. co-wrote the paper.

Corresponding author

Correspondence to Bernhard Breit.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Wieland, J., Breit, B. A combinatorial approach to the identification of self-assembled ligands for rhodium-catalysed asymmetric hydrogenation. Nature Chem 2, 832–837 (2010). https://doi.org/10.1038/nchem.800

Download citation

Further reading