Imine hydrogenation with simple alkaline earth metal catalysts

Abstract

Hydrogenation of unsaturated bonds is dominated by transition metal catalysis. Compared with transition metals, the use of other metals is less explored, especially so for the s-block elements despite their ready availability and low cost. Here, we show that group 2 metal amides (M[N(SiMe3)2]2, M = Mg, Ca, Sr, Ba) unexpectedly catalyse the hydrogenation of aldimines with H2 at 80 °C and a remarkably low H2 pressure of 1–6 bar. Conversion rates increase with metal size: Mg < Ca < Sr < Ba (for Ba, quantitative conversion is reached within 15 min). The key to this catalysis is the unanticipated formation of metal hydride species by deprotonation of H2 (pK a ≈ 49) with a weak base M[N(SiMe3)2]2 (HN(SiMe3)2: pK a ≈ 25.8). Density functional theory calculations suggest that the most favourable pathway indeed involves metal hydride intermediates. The efficient alkaline earth metal-catalysed hydrogenation of imines with molecular hydrogen at remarkably low pressure provides an attractive alternative to transition metal catalysis.

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Fig. 1 |: Calcium-mediated hydrogenation.
Fig. 2: Classification of imine hydrogenation catalysts.
Fig. 3: Electronic and steric effects governing catalytic conversion.
Fig. 4: Selected alkaline earth metal catalysts.
Fig. 5: Energy profiles for catalytic hydrogenation of (E)-PhC(H)=NtBu.
Fig. 6: Stoichiometric imine hydrogenation.

References

  1. 1.

    de Vries, J. G. & Elsevier, C. J. Handbook of Homogeneous Hydrogenation: 3 Volumes (Wiley-VCH, Weinheim, 2007).

  2. 2.

    Albrecht, M., Bedford, R. & Plietker, B. Catalytic and organometallic chemistry of earth-abundant metals. Organometallics 33, 5619–5621 (2014).

    CAS  Article  Google Scholar 

  3. 3.

    Schafer, L. L., Mountford, P. & Piers, W. E. Earth abundant element compounds in homogeneous catalysis. Dalton Trans. 44, 12027–12028 (2015).

    CAS  Article  Google Scholar 

  4. 4.

    Harder, S. From limestone to catalysis: application of calcium compounds as homogeneous catalysts. Chem. Rev. 110, 3852–3876 (2010).

    CAS  Article  Google Scholar 

  5. 5.

    Hill, M. S., Liptrot, D. J. & Weetman, C. Alkaline earths as main group reagents in molecular catalysis. Chem. Soc. Rev. 45, 972–988 (2016).

    CAS  Article  Google Scholar 

  6. 6.

    Berben, L. A. Catalysis by aluminum(III) complexes of non-innocent ligands. Chem. Eur. J. 21, 2734–2742 (2015).

    CAS  Article  Google Scholar 

  7. 7.

    Spielmann, J., Buch, F. & Harder, S. Early main-group metal catalysts for the hydrogenation of alkenes with H2. Angew. Chem. Int. Ed. 47, 9434–9438 (2008).

    CAS  Article  Google Scholar 

  8. 8.

    Greb, L. et al. Metal-free catalytic olefin hydrogenation: low-temperature H2 activation by frustrated Lewis pairs. Angew. Chem. Int. Ed. 51, 10164–10168 (2012).

    CAS  Article  Google Scholar 

  9. 9.

    Stephan, D. W. The broadening reach of frustrated Lewis pair chemistry. Science 354, 1248–1256 (2016).

    CAS  Article  Google Scholar 

  10. 10.

    Stephan, D. W. & Erker, G. Frustrated Lewis pair chemistry: development and perspectives. Angew. Chem. Int. Ed. 54, 6400–6441 (2015).

    CAS  Article  Google Scholar 

  11. 11.

    Stephan, D. W. Frustrated Lewis pairs: from concept to catalysis. Acc. Chem. Res. 48, 306–316 (2015).

    CAS  Article  Google Scholar 

  12. 12.

    Schuhknecht, D., Lhotzky, C., Spaniol, T. P., Maron, L. & Okuda, J. Calcium hydride cation [CaH]+ stabilized by an NNNN-type macrocyclic ligand: a selective catalyst for olefin hydrogenation. Angew. Chem. Int. Ed. 56, 12367–12371 (2017).

    CAS  Article  Google Scholar 

  13. 13.

    Harder, S. & Brettar, J. Rational design of a well-defined soluble calcium hydride complex. Angew. Chem. Int. Ed. 45, 3474–3478 (2006).

    CAS  Article  Google Scholar 

  14. 14.

    Jochmann, P., Davin, J. P., Spaniol, T. P., Maron, L. & Okuda, J. A cationic calcium hydride cluster stabilized by cyclen-derived macrocyclic N,N,N,N ligands. Angew. Chem. Int. Ed. 51, 4452–4455 (2012).

    CAS  Article  Google Scholar 

  15. 15.

    Leich, V., Spaniol, T. P., Maron, L. & Okuda, J. Molecular calcium hydride: dicalcium trihydride cation stabilized by a neutral NNNN-type macrocyclic ligand. Angew. Chem. Int. Ed. 55, 4794–4797 (2016).

    CAS  Article  Google Scholar 

  16. 16.

    Causero, A. et al. Stabilization of calcium hydride complexes by fine tuning of amidinate ligands. Organometallics 35, 3350–3360 (2016).

    CAS  Article  Google Scholar 

  17. 17.

    Causero, A. et al. β-Diketiminate calcium hydride complexes: the importance of solvent effects. Dalton Trans. 46, 1822–1831 (2017).

    CAS  Article  Google Scholar 

  18. 18.

    Penafiel, J., Maron, L. & Harder, S. Early main group metal catalysis: how important is the metal? Angew. Chem. Int. Ed. 54, 201–206 (2015).

    CAS  Article  Google Scholar 

  19. 19.

    Harder, S., Feil, F. & Knoll, K. Novel calcium half-sandwich complexes for the living and stereoselective polymerization of styrene. Angew. Chem. Int. Ed. 40, 4261–4264 (2001).

    CAS  Article  Google Scholar 

  20. 20.

    Abdur-Rashid, K. et al. An acidity scale for phosphorus-containing compounds including metal hydrides and dihydrogen complexes: toward the unification of acidity scales. J. Am. Chem. Soc. 122, 9155–9171 (2000).

    CAS  Article  Google Scholar 

  21. 21.

    Zeng, G. & Li, S. Mechanistic insight on the hydrogenation of conjugated alkenes with H2 catalyzed by early main-group metal catalysts. Inorg. Chem. 49, 3361–3369 (2010).

    CAS  Article  Google Scholar 

  22. 22.

    Fabrello, A., Bachelier, A., UrrutigoÏty, M. & Kalck, P. Mechanistic analysis of the transition metal-catalyzed hydrogenation of imines and functionalized enamines. Coord. Chem. Rev. 254, 273–287 (2010).

    CAS  Article  Google Scholar 

  23. 23.

    Blaser, H.-U. et al. Selective hydrogenation for fine chemicals: recent trends and new developments. Adv. Synth. Catal. 345, 103–151 (2003).

    CAS  Article  Google Scholar 

  24. 24.

    Wang, C., Villa-Marcos, B. & Xiao, J. Hydrogenation of imino bonds with half-sandwich metal catalysts. Chem. Commun. 47, 9773–9785 (2011).

    CAS  Article  Google Scholar 

  25. 25.

    Willoughby, C. A. & Buchwald, S. L. Catalytic asymmetric hydrogenation of imines with a chiral titanocene catalyst: kinetic and mechanistic investigations. J. Am. Chem. Soc. 116, 11703–11714 (1994).

    CAS  Article  Google Scholar 

  26. 26.

    Obora, Y., Ohta, T., Stern, C. L. & Marks, T. J. Organolanthanide-catalyzed imine hydrogenation. Scope, selectivity, mechanistic observations, and unusual byproducts. J. Am. Chem. Soc. 119, 3745–3755 (1997).

    CAS  Article  Google Scholar 

  27. 27.

    Hatnean, J. A., Thomson, J. W., Chase, P. A. & Stephan, D. W. Imine hydrogenation by alkylaluminum catalysts. Chem. Commun. 50, 301–303 (2014).

    CAS  Article  Google Scholar 

  28. 28.

    Jochmann, P. & Stephan, D. W. H2 cleavage, hydride formation, and catalytic hydrogenation of imines with zinc complexes of C5Me5 and N-heterocyclic carbenes. Angew. Chem. Int. Ed. 52, 9831–9835 (2013).

    CAS  Article  Google Scholar 

  29. 29.

    Jochmann, P. & Stephan, D. W. Zincocene and dizincocene N-heterocyclic carbene complexes and catalytic hydrogenation of imines and ketones. Chem. Eur. J. 20, 8370–8378 (2014).

    CAS  Article  Google Scholar 

  30. 30.

    Rueping, M., Azap, C., Sugiono, E. & Theissmann, T. Brønsted acid catalysis: organocatalytic hydrogenation of imines. Synlett 15, 2367–2369 (2005).

    Article  Google Scholar 

  31. 31.

    Rueping, M., Sugiono, E., Azap, C., Theissmann, T. & Bolte, M. Enantioselective Brønsted acid catalyzed transfer hydrogenation: organocatalytic reduction of imines. Org. Lett. 7, 3781–3783 (2005).

    CAS  Article  Google Scholar 

  32. 32.

    Hoffmann, S., Seayad, A. M. & List, B. A powerful Brønsted acid catalyst for the organocatalytic asymmetric transfer hydrogenation of imines. Angew. Chem. Int. Ed. 44, 7424–7427 (2005).

    CAS  Article  Google Scholar 

  33. 33.

    de Vries, J. G. & Mršić, N. Organocatalytic asymmetric transfer hydrogenation of imines. Catal. Sci. Technol. 1, 727–735 (2011).

    Article  Google Scholar 

  34. 34.

    Zhou, S., Fleischer, S., Junge, K. & Beller, M. Cooperative transition-metal and chiral Brønsted acid catalysis: enantioselective hydrogenation of imines to form amines. Angew. Chem. Int. Ed. 50, 5120–5124 (2011).

    CAS  Article  Google Scholar 

  35. 35.

    Tang, W. et al. Cooperative catalysis: combining an achiral metal catalyst with a chiral Brønsted acid enables highly enantioselective hydrogenation of imines. Chem. Eur. J. 19, 14187–14193 (2013).

    CAS  Article  Google Scholar 

  36. 36.

    Samec, J. S. M. & Bäckvall, J.-E. Ruthenium-catalyzed transfer hydrogenation of imines by propan-2-ol in benzene. Chem. Eur. J. 8, 2955–2961 (2002).

    CAS  Article  Google Scholar 

  37. 37.

    Chase, P. A., Welch, G. C., Jurca, T. & Stephan, D. W. Metal-free catalytic hydrogenation. Angew. Chem. Int. Ed. 46, 8050–8053 (2007).

    CAS  Article  Google Scholar 

  38. 38.

    Chase, P. A., Jurca, T. & Stephan, D. W. Lewis acid-catalyzed hydrogenation: B(C6F5)3-mediated reduction of imines and nitriles with H2. Chem. Commun. 1701–1703 (2008).

  39. 39.

    Paradies, J. Frustrated Lewis pair catalyzed hydrogenations. Synlett 24, 777–780 (2013).

    CAS  Article  Google Scholar 

  40. 40.

    Oestreich, M., Hermeke, J. & Mohr, J. A unified survey of Si–H and H–H bond activation catalysed by electron-deficient boranes. Chem. Soc. Rev. 44, 2202–2220 (2015).

    CAS  Article  Google Scholar 

  41. 41.

    Brady, E. D., Hanusa, T. P., Pink, M. & Young, V. G. Jr The first noncoordinated phosphonium diylide, [Me2P(C13H8)2], and its ylidic and cationic counterparts: synthesis, structural characterization, and interaction with the heavy group 2 metals. Inorg. Chem. 39, 6028–6037 (2000).

    CAS  Article  Google Scholar 

  42. 42.

    Westerhausen, M. Synthesis and spectroscopic properties of bis(trimethylsilyl)amides of the alkaline-earth metals magnesium, calcium, strontium, and barium. Inorg. Chem. 30, 96–101 (1991).

    CAS  Article  Google Scholar 

  43. 43.

    Liu, B., Roisnel, T., Carpentier, J.-F. & Sarazin, Y. When bigger is better: intermolecular hydrofunctionalizations of activated alkenes catalyzed by heteroleptic alkaline earth complexes. Angew. Chem. Int. Ed. 51, 4943–4946 (2012).

    CAS  Article  Google Scholar 

  44. 44.

    Reichardt, C. Solvents and Solvent Effects in Organic Chemistry 3rd edn (Wiley-VCH, Weinheim, 2003).

  45. 45.

    Harder, S., Feil, F. & Weeber, A. Structure of a benzylcalcium diastereomer: an initiator for the anionic polymerization of styrene. Organometallics 20, 1044–1046 (2001).

    CAS  Article  Google Scholar 

  46. 46.

    Fraser, R. R., Mansour, T. S. & Savard, S. Acidity measurements on pyridines in tetrahydrofuran using lithiated silylamines. J. Org. Chem. 50, 3232–3234 (1985).

    CAS  Article  Google Scholar 

  47. 47.

    Maitland, B. et al. A simple route to calcium and strontium hydride clusters. Angew. Chem. Int. Ed. 56, 11880–11884 (2017).

    CAS  Article  Google Scholar 

  48. 48.

    Zhao, Y. & Truhlar, D. G. The M06 suite of density functionals for main group thermochemistry, thermochemical kinetics, noncovalent interactions, excited states, and transition elements: two new functionals and systematic testing of four M06-class functionals and 12 other functionals. Theor. Chem. Acc. 120, 215–241 (2008).

    CAS  Article  Google Scholar 

  49. 49.

    Marenich, A. V., Cramer, C. J. & Truhlar, D. G. Universal solvation model based on solute electron density and on a continuum model of the solvent defined by the bulk dielectric constant and atomic surface tensions. J. Phys. Chem. B 113, 6378–6396 (2009).

    CAS  Article  Google Scholar 

  50. 50.

    Berkessel, A., Schubert, T. J. S. & Müller, T. N. Hydrogenation without a transition-metal catalyst: on the mechanism of the base-catalyzed hydrogenation of ketones. J. Am. Chem. Soc. 124, 8693–8698 (2002).

    CAS  Article  Google Scholar 

  51. 51.

    Yamakawa, M., Ito, H. & Noyori, R. The metal-ligand bifunctional catalysis: a theoretical study on the ruthenium(II)-catalyzed hydrogen transfer between alcohols and carbonyl compounds. J. Am. Chem. Soc. 122, 1466–1478 (2000).

    CAS  Article  Google Scholar 

  52. 52.

    Dub, P. A., Henson, N. J., Martin, R. L. & Gordon, J. C. Unravelling the mechanism of the asymmetric hydrogenation of acetophenone by [RuX2(diphosphine)(1,2-diamine)] catalysts. J. Am. Chem. Soc. 136, 3505–3521 (2014).

    CAS  Article  Google Scholar 

  53. 53.

    Kozuch, S. & Shaik, S. How to conceptualize catalytic cycles? The energetic span model. Acc. Chem. Res. 44, 101–110 (2011).

    CAS  Article  Google Scholar 

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Acknowledgements

M.A. thanks the Fund for Scientific Research–Flanders (FWO-12F4416N) for a postdoctoral fellowship and the Free University of Brussels (VUB) for financial support. F.D.P. acknowledges the Research Foundation Flanders (FWO) and Strategic Research Program funding of the VUB. He also acknowledges the Francqui foundation for a position as ‘Francqui research professor’. S.H. acknowledges the Deutsche Forschungsgemeinschaft for financial support (HA 3218/7-1).

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H.B., H.E., C.F. and A.C. are responsible for the experimental work. J.P. and G.B. measured and determined the crystal structures. M.A. and F.D.P. conducted theoretical calculations. S.H. supervised the experimental work and prepared the manuscript with feedback from the other authors.

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Correspondence to Mercedes Alonso or Sjoerd Harder.

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Bauer, H., Alonso, M., Färber, C. et al. Imine hydrogenation with simple alkaline earth metal catalysts. Nat Catal 1, 40–47 (2018). https://doi.org/10.1038/s41929-017-0006-0

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