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Preparation of chiral-at-metal catalysts and their use in asymmetric photoredox chemistry

Nature Protocols volume 13, pages 605–632 (2018)Cite this article

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Abstract

Asymmetric catalysis is a powerful approach for the synthesis of optically active compounds, and visible light constitutes an abundant source of energy to enable chemical transformations, which are often triggered by photoinduced electron transfer (photoredox chemistry). Recently, bis-cyclometalated iridium(III) and rhodium(III) complexes were introduced as a novel class of catalysts for combining asymmetric catalysis with visible-light-induced photoredox chemistry. These catalysts are attractive because of their unusual feature of chirality originating exclusively from a stereogenic metal center, which offers the prospect of an especially effective asymmetric induction upon direct coordination of the substrate to the metal center. As these chiral catalysts contain only achiral ligands, special strategies are required for their synthesis. In this protocol, we describe strategies for preparing two types of chiral-at-metal catalysts, namely the Λ- and Δ-enantiomers (left- and right-handed propellers, respectively) of the iridium complex IrS and the rhodium complex RhS. Both contain two cyclometalating 5-tert-butyl-2-phenylbenzothiazoles in addition to two acetonitrile ligands and a hexafluorophosphate counterion. The two cyclometalated ligands set the propeller-shaped chiral geometry, but the acetonitriles are labile and can be replaced by substrate molecules. The synthesis protocol consists of three stages: first, preparation of the ligand 5-tert-butyl-2-phenylbenzothiazole; second, preparation of salicylthiazoline (used for iridium) and salicyloxazoline (used for rhodium) chiral auxiliaries; and third, the auxiliary-mediated synthesis of the individual enantiopure Λ- and Δ-configured catalysts. This class of stereogenic-only-at-metal complexes is of substantial value in the field of asymmetric catalysis, offering stereocontrolled radical reactions based on visible-light-activated photoredox chemistry. Representative examples of visible-light-induced asymmetric catalysis are provided.

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Figure 1: Structures of the chiral-at-metal complexes focused on in this protocol.
Figure 2: Selected examples of enantioselective α-alkylations (1,2), a trichloromethylation (3), and an amination (4) catalyzed by chiral-at-metal iridium(III) or rhodium(III) complexes under photoredox conditions.
Figure 3: Selected examples of asymmetric Giese-type reactions catalyzed by the combination of a chiral-at-metal rhodium(III) complex and an additional photoredox catalyst.
Figure 4: Optimized auxiliary-mediated synthesis of enantiomerically pure Λ- and Δ-IrS, and Λ- and Δ-RhS.
Figure 5: Preparation of cyclometalating ligand and chiral auxiliary compounds.
Figure 6: Iridium cyclometalation reaction (Steps 90 and 91).
Figure 7: rac-IrS crystals.
Figure 8: Reaction control and resolution of iridium diastereomers.
Figure 9: TFA-mediated removal of chiral auxiliary ligand from iridium diastereomer.
Figure 10
Figure 11: Separation of chiral auxiliary rhodium complexes Λ-(S)-13 and Δ-(S)-13 by exploiting the different solubility in EtOH.
Figure 12: TFA-mediated removal of chiral auxiliary ligand from rhodium diastereomer.
Figure 13

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References

  1. Walsh, P.J. & Kozlowski, M.C. Fundamentals of Asymmetric Catalysis. University Science Books, 2009.

    Google Scholar 

  2. Fontecave, M., Hamelin, O. & Ménage, S. Chiral-at-metal complexes as asymmetric catalysts. in Topics in Organometallic Chemistry, Vol. 15 (eds. Lemaire, M. & Mangeney, P.) 271–288 (Springer, 2005).

  3. Gong, L., Chen, L.A. & Meggers, E. Asymmetric catalysis mediated by the ligand sphere of octahedral chiral-at-metal complexes. Angew. Chem. Int. Ed. 53, 10868–10874 (2014).

    Article  CAS  Google Scholar 

  4. Cao, Z.-Y., Brittain, W.D., Fossey, J.S. & Zhou, F. Recent advances in the use of chiral metal complexes with achiral ligands for application in asymmetric catalysis. Catal. Sci. Technol. 5, 3441–3451 (2015).

    Article  CAS  Google Scholar 

  5. Zhang, L. & Meggers, E. Stereogenic-only-at-metal asymmetric catalysts. Chem. Asian J. 12, 2335–2342 (2017).

    Article  CAS  Google Scholar 

  6. Chavarot, M. et al. 'Chiral-at-metal' octahedral ruthenium (II) complexes with achiral ligands: a new type of enantioselective catalyst. Inorg. Chem. 42, 4810–4816 (2003).

    Article  CAS  Google Scholar 

  7. Hartung, J. & Grubbs, R.H. Highly Z-selective and enantioselective ring-opening/cross-metathesis catalyzed by a resolved stereogenic-at-Ru complex. J. Am. Chem. Soc. 135, 10183–10185 (2013).

    Article  CAS  Google Scholar 

  8. Hartung, J., Dornan, P.K. & Grubbs, R.H. Enantioselective olefin metathesis with cyclometalated ruthenium complexes. J. Am. Chem. Soc. 136, 13029–13037 (2014).

    Article  CAS  Google Scholar 

  9. Knof, U. & von Zelewsky, A. Predetermined chirality at metal centers. Angew. Chem. Int. Ed. 38, 302–322 (1999).

    Article  Google Scholar 

  10. Amouri, H. & Gruselle, M. Chirality in transition metal chemistry: molecules. supramolecular assemblies and materials (Wiley, 2008).

  11. Meggers, E. Chiral auxiliaries as emerging tools for the asymmetric synthesis of octahedral metal complexes. Chem. Eur. J. 16, 752–758 (2010).

    Article  CAS  Google Scholar 

  12. Zhang, L. & Meggers, E. Steering asymmetric Lewis acid catalysis exclusively with octahedral metal-centered chirality. Acc. Chem. Res. 50, 320–330 (2017).

    Article  CAS  Google Scholar 

  13. Xu, G.Q. et al. Catalytic enantioselective α-fluorination of 2-acyl imidazoles via iridium complexes. Chem. Asian J. 11, 3355–3358 (2016).

    Article  CAS  Google Scholar 

  14. Gong, J., Li, K., Qurban, S. & Kang, Q. Rhodium(III)/amine synergistically catalyzed enantioselective alkylation of aldehydes with α,β-unsaturated 2-acyl imidazoles. Chin. J. Chem. 34, 1225–1235 (2016).

    Article  CAS  Google Scholar 

  15. Sun, G.-J., Gong, J. & Kang, Q. Chiral rhodium(III) complex-catalyzed cascade Michael-alkylation reactions: enantioselective synthesis of cyclopropanes. J. Org. Chem. 82, 796–803 (2017).

    Article  CAS  Google Scholar 

  16. Deng, T., Thota, G.K., Li, Y. & Kang, Q. Enantioselective conjugate addition of hydroxylamines to α,β-unsaturated 2-acyl imidazoles catalyzed by a chiral-at-metal Rh(III) complex. Org. Chem. Front. 4, 573–577 (2017).

    Article  CAS  Google Scholar 

  17. Li, S.-W., Gong, J. & Kang, Q. Chiral-at-metal Rh(III) complex-catalyzed decarboxylative Michael addition of β-keto acids with α,β-unsaturated 2-acyl imidazoles or pyridine. Org. Lett. 19, 1350–1353 (2017).

    Article  Google Scholar 

  18. Li, K., Wan, Q. & Kang, Q. Chiral-at-metal Rh(III) complex catalyzed asymmetric conjugate addition of unactivated alkenes with α,β-unsaturated 2-acyl imidazoles. Org. Lett. 19, 3299–3302 (2017).

    Article  CAS  Google Scholar 

  19. Lin, S.-X., Sun, G.-J. & Kang, Q. Visible-light-activated rhodium complex in enantioselective conjugate addition of α-amino radicals with Michael acceptors. Chem. Commun. 53, 7665–7668 (2017).

    Article  CAS  Google Scholar 

  20. Flamigni, L., Barbieri, A., Sabatini, C., Ventura, B. & Barigelletti, F. Photochemistry and photophysics of coordination compounds: iridium. Top. Curr. Chem. 281, 143–203 (2007).

    Article  CAS  Google Scholar 

  21. Shaw, M.H., Twilton, J. & MacMillan, D.W. Photoredox catalysis in organic chemistry. J. Org. Chem. 81, 6898–6926 (2016).

    Article  CAS  Google Scholar 

  22. Kärkäs, M.D., Porco Jr, J.A. & Stephenson, C.R. Photochemical approaches to complex chemotypes: applications in natural product synthesis. Chem. Rev. 116, 9683–9747 (2016).

    Article  Google Scholar 

  23. Ravelli, D., Protti, S. & Fagnoni, M. Carbon–carbon bond forming reactions via photogenerated intermediates. Chem. Rev. 116, 9850–9913 (2016).

    Article  CAS  Google Scholar 

  24. Skubi, K.L., Blum, T.R. & Yoon, T.P. Dual catalysis strategies in photochemical synthesis. Chem. Rev. 116, 10035–10074 (2016).

    Article  CAS  Google Scholar 

  25. Hopkinson, M.N., Sahoo, B., Li, J.L. & Glorius, F. Dual catalysis sees the light: combining photoredox with organo-, acid, and transition-metal catalysis. Chem. Eur. J. 20, 3874–3886 (2014).

    Article  CAS  Google Scholar 

  26. Wang, C. & Lu, Z. Catalytic enantioselective organic transformations via visible light photocatalysis. Org. Chem. Front. 2, 179–190 (2015).

    Article  CAS  Google Scholar 

  27. Meggers, E. Asymmetric catalysis activated by visible light. Chem. Commun. 51, 3290–3301 (2015).

    Article  CAS  Google Scholar 

  28. Brimioulle, R., Lenhart, D., Maturi, M.M. & Bach, T. Enantioselective catalysis of photochemical reactions. Angew. Chem. Int. Ed. 54, 3872–3890 (2015).

    Article  CAS  Google Scholar 

  29. Huo, H. et al. Asymmetric photoredox transition-metal catalysis activated by visible light. Nature 515, 100–103 (2014).

    Article  CAS  Google Scholar 

  30. Huo, H., Wang, C., Harms, K. & Meggers, E. Enantioselective, catalytic trichloromethylation through visible-light-activated photoredox catalysis with a chiral iridium complex. J. Am. Chem. Soc. 137, 9551–9554 (2015).

    Article  CAS  Google Scholar 

  31. Ohkubo, K., Hamada, T., Inaoka, T. & Ishida, H. Photoinduced enantioselective and catalytic reduction of tris(acetylacetonato)cobalt with a chiral ruthenium photosensitizer. Inorg. Chem. 28, 2021–2022 (1989).

    Article  CAS  Google Scholar 

  32. Ohkubo, K., Hamada, T. & Ishida, H. Novel enantioselective photocatalysis by chiral, helical ruthenium(II) complexes. J. Chem. Soc., Chem. Commun. 1423–1425 (1993).

  33. Hamada, T. et al. A novel photocatalytic asymmetric synthesis of (R)-(+)-1,1′-bi-2-naphthol derivatives by oxidative coupling of 3-substituted-2-naphthol with Δ-[Ru(menbpy)3]2+[menbpy = 4,4′-di(1R,2S,5R)-(-)-menthoxycarbonyl-2,2′-bipyridine], which posseses molecular helicity. J. Chem. Soc., Chem. Commun. 909–911 (1993).

  34. Fu, C., Wenzel, M., Treutlein, E., Harms, K. & Meggers, E. Proline as chiral auxiliary for the economical asymmetric synthesis of ruthenium(II) polypyridyl complexes. Inorg. Chem. 51, 10004–10011 (2012).

    Article  CAS  Google Scholar 

  35. Shen, X., Harms, K., Marsch, M. & Meggers, E. A rhodium catalyst superior to iridium congeners for enantioselective radical amination activated by visible light. Chem. Eur. J. 22, 9102–9105 (2016).

    Article  CAS  Google Scholar 

  36. Studer, A. & Curran, D.P. Catalysis of radical reactions: a radical chemistry perspective. Angew. Chem. Int. Ed. 55, 58–102 (2016).

    Article  CAS  Google Scholar 

  37. Huo, H., Harms, K. & Meggers, E. Catalytic, enantioselective addition of alkyl radicals to alkenes via visible-light-activated photoredox catalysis with a chiral rhodium complex. J. Am. Chem. Soc. 138, 6936–6939 (2016).

    Article  CAS  Google Scholar 

  38. Zimmerman, J. & Sibi, M. Enantioselective radical reactions. Top. Curr. Chem. 263, 107–162 (2006).

    Article  CAS  Google Scholar 

  39. Sorin, G. et al. Oxidation of alkyl trifluoroborates: an opportunity for tin-free radical chemistry. Angew. Chem. Int. Ed. 49, 8721–8723 (2010).

    Article  CAS  Google Scholar 

  40. Yasu, Y., Koike, T. & Akita, M. Visible light-induced selective generation of radicals from organoborates by photoredox catalysis. Adv. Synth. Catal. 354, 3414–3420 (2012).

    Article  CAS  Google Scholar 

  41. Tellis, J.C., Primer, D.N. & Molander, G.A. Single-electron transmetalation in organoboron cross-coupling by photoredox/nickel dual catalysis. Science 345, 433–436 (2014).

    Article  CAS  Google Scholar 

  42. Wang, C., Harms, K. & Meggers, E. Catalytic asymmetric Csp3H functionalization under photoredox conditions by radical translocation and stereocontrolled alkene addition. Angew. Chem. Int. Ed. 55, 13495–13498 (2016).

    Article  CAS  Google Scholar 

  43. Zhang, J., Li, Y., Zhang, F., Hu, C. & Chen, Y. Generation of alkoxyl radicals by photoredox catalysis enables selective C(sp3)H functionalization under mild reaction conditions. Angew. Chem. Int. Ed. 55, 1872–1875 (2016).

    Article  CAS  Google Scholar 

  44. Tian, C., Gong, L. & Meggers, E. Chiral-at-metal iridium complex for efficient enantioselective transfer hydrogenation of ketones. Chem. Commun. 52, 4207–4210 (2016).

    Article  CAS  Google Scholar 

  45. Luo, S. et al. Enantioselective alkynylation of aromatic aldehydes catalyzed by a sterically highly demanding chiral-at-rhodium Lewis acid. J. Org. Chem. 82, 8995–9005 (2017).

    Article  CAS  Google Scholar 

  46. Gong, L., Wenzel, M. & Meggers, E. Chiral-auxiliary-mediated asymmetric synthesis of ruthenium polypyridyl complexes. Acc. Chem. Res. 46, 2635–2644 (2013).

    Article  CAS  Google Scholar 

  47. Marchi, E. et al. Easy separation of Δ and Λ isomers of highly luminescent [IrIII]-cyclometalated complexes based on chiral phenol-oxazoline ancillary ligands. Chem. Eur. J. 18, 8765–8773 (2012).

    Article  CAS  Google Scholar 

  48. Chepelin, O. et al. Luminescent, enantiopure, phenylatopyridine iridium-based coordination capsules. J. Am. Chem. Soc. 134, 19334–19337 (2012).

    Article  CAS  Google Scholar 

  49. Chen, L.-A. et al. Asymmetric catalysis with an inert chiral-at-metal iridium complex. J. Am. Chem. Soc. 135, 10598–10601 (2013).

    Article  CAS  Google Scholar 

  50. Helms, M., Lin, Z., Gong, L., Harms, K. & Meggers, E. Method for the preparation of nonracemic biscyclometalated iridium (III) complexes. Eur. J. Inorg. Chem. 2013, 4164–4172 (2013).

    Article  CAS  Google Scholar 

  51. Davies, D.L., Singh, K., Singh, S. & Villa-Marcos, B. Preparation of single enantiomers of chiral at metal bis-cyclometallated iridium complexes. Chem. Commun. 49, 6546–6548 (2013).

    Article  CAS  Google Scholar 

  52. Ma, J. et al. Metal-templated chiral Brønsted base organocatalysis. Nat. Commun. 5, 5531 (2014).

    Article  Google Scholar 

  53. Liu, J., Gong, L. & Meggers, E. Asymmetric Friedel–Crafts alkylation of indoles with 2-nitro-3-arylacrylates catalyzed by a metal-templated hydrogen bonding catalyst. Tetrahedron Lett. 56, 4653–4656 (2015).

    Article  CAS  Google Scholar 

  54. Helms, M., Wang, C., Orth, B., Harms, K. & Meggers, E. Proline and α-methylproline as chiral auxiliaries for the synthesis of enantiopure bis-cyclometalated iridium (III) complexes. Eur. J. Inorg. Chem. 2016, 2896–2901 (2016).

    Article  CAS  Google Scholar 

  55. Song, L., Gong, L. & Meggers, E. Asymmetric dual catalysis via fragmentation of a single rhodium precursor complex. Chem. Commun. 52, 7699–7702 (2016).

    Article  CAS  Google Scholar 

  56. Yao, S.-Y., Ou, Y.-L. & Ye, B.-H. Asymmetric synthesis of enantiomerically pure mono-and binuclear bis (cyclometalated) iridium (III) complexes. Inorg. Chem. 55, 6018–6026 (2016).

    Article  CAS  Google Scholar 

  57. Xu, W. et al. Metal-templated design: enantioselective hydrogen-bond-driven catalysis requiring only parts-per-million catalyst loading. J. Am. Chem. Soc. 138, 8774–8780 (2016).

    Article  CAS  Google Scholar 

  58. Ma, J., Shen, X., Harms, K. & Meggers, E. Expanding the family of bis-cyclometalated chiral-at-metal rhodium(III) catalysts with a benzothiazole derivative. Dalton Trans. 45, 8320–8323 (2016).

    Article  CAS  Google Scholar 

  59. Nonoyama, M. Benzo[h]quinolin-10-yl-N iridium (III) complexes. Bull. Chem. Soc. Jpn. 47, 767–768 (1974).

    Article  CAS  Google Scholar 

  60. Lo, K.K.-W., Li, C.-K., Lau, K.-W. & Zhu, N. Luminescent cyclometallated rhodium(III) bis(pyridylbenzaldehyde) complexes with long-lived excited states. Dalton Trans. 4682–4689 (2003).

  61. Nguyen, T.B., Ermolenko, L., Retailleau, P. & Al-Mourabit, A. Elemental sulfur disproportionation in the redox condensation reaction between o-halonitrobenzenes and benzylamines. Angew. Chem. Int. Ed. 53, 13808–13812 (2014).

    Article  CAS  Google Scholar 

  62. Beaumont, S., Ilardi, E.A., Monroe, L.R. & Zakarian, A. Valence tautomerism in titanium enolates: catalytic radical haloalkylation and application in the total synthesis of neodysidenin. J. Am. Chem. Soc. 132, 1482–1483 (2010).

    Article  CAS  Google Scholar 

  63. Sibi, M.P., Ji, J., Wu, J.H., Gürtler, S. & Porter, N.A. Chiral Lewis acid catalysis in radical reactions: enantioselective conjugate radical additions. J. Am. Chem. Soc. 118, 9200–9201 (1996).

    Article  CAS  Google Scholar 

  64. Gong, L., Mulcahy, S.P., Harms, K. & Meggers, E. Chiral-auxiliary-mediated asymmetric synthesis of tris-heteroleptic ruthenium polypyridyl complexes. J. Am. Chem. Soc. 131, 9602–9603 (2009).

    Article  CAS  Google Scholar 

  65. Wegner, H.A. et al. Oligoindenopyrenes: a new class of polycyclic aromatics. J. Org. Chem. 71, 9080–9087 (2006).

    Article  CAS  Google Scholar 

  66. Kelly, C.B. et al. Preparation of visible-light-activated metal complexes and their use in photoredox/nickel dual catalysis. Nat. Protoc. 12, 472–492 (2017).

    Article  CAS  Google Scholar 

  67. Ham, W.T., Mueller, H.A. & Sliney, D.H. Retinal sensitivity to damage from short wavelength light. Nature 260, 153–155 (1976).

    Article  Google Scholar 

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Acknowledgements

Funding from the Deutsche Forschungsgemeinschaft (ME 1805/13-1) is gratefully acknowledged. We are grateful for careful revisions of Boxes 1 and 2 by H. Huo.

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  1. Jiajia Ma and Xiao Zhang: These authors contributed equally to this work.

Authors and Affiliations

  1. Fachbereich Chemie, Philipps-Universität Marburg, Marburg, Germany

    Jiajia Ma, Xiao Zhang, Xiaoqiang Huang, Shipeng Luo & Eric Meggers

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Contributions

E.M. coordinated the project. J.M., X.Z., X.H., and S.L. performed the syntheses. E.M., J.M., and X.Z. wrote the manuscript. J.M. and X.Z. contributed equally to this work.

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Correspondence to Eric Meggers.

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Ma, J., Zhang, X., Huang, X. et al. Preparation of chiral-at-metal catalysts and their use in asymmetric photoredox chemistry. Nat Protoc 13, 605–632 (2018). https://doi.org/10.1038/nprot.2017.138

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