Historically, the metal catalyzed hydrogenation of unsaturated bonds is a first milestone in catalysis. Dating back as far as 1874, von Wilde reported the first acetylene-to-ethane conversion using platinum. This rapidly developing field of hydrogenation catalysis soon led to Sabatier’s 1912 Nobel Prize in chemistry. Although old hat, today hydrogenation catalysis is still thriving. The increasing relevance of molecular hydrogen, which should be regarded one of the cleanest reducing agents, warrants further continuity for hydrogenation as a highly important industrial key transformation.

While most catalysts are derived from platinum group metals, we have been pioneering catalysis with early main group metals, especially Ca and the heavier group 2 metals. There are clear advantages. Ca is a lot cheaper than Pt but this argument is easily overthrown by the extremely low catalyst loadings for Pt which often cannot be matched by Ca. It is more important that Ca is everywhere. The lack of monopolies avoids speculation, guaranteeing long-term price stability. In addition, compared to the more precious d-block metals like Pt, Ca is biocompatible and there is no need to remove toxic catalyst residues.

As Ca does not have partially filled d-orbitals at its disposal, substrate activation is purely based on its Lewis acidic nature. Although Ca-alkene bonding is very weak and C=C bond lengthening is hardly noticeable, Ca-catalyzed alkene hydrogenation is feasible under mild conditions (20-60 °C, 20 bar) using a highly reactive dibenzylcalcium catalyst.¹ The substrates were initially restricted to conjugated double bonds, which are also prone to give polymer side products. The results are certainly not at par with the state-of-the-art in hydrogenation catalysis but this first demonstration of transition metal-free hydrogenation broke the dogma that alkene activation by d → p* backdonation is an absolute requirement. 

The mechanism is straightforward. It does not involve any redox chemistry but is governed by simple dipolar addition and deprotonation/protonation steps. I still remember the day that one of my coworkers, Christian Färber, proposed to extend this research to the much more important imine-to-amine reduction. My immediate reaction was that this would never work! Although it could follow a similar mechanism, the problem is immediately evident: catalyst formation and the last step can be seen as the deprotonation of H₂ (with a pK_a value close to 50) by a Ca amide intermediate (the pK_a of amines is circa 35). It should be running backwards! But if it would work, simple alkaline earth metal amides like AeN’’₂ (N’’ = N(SiMe₃)₂, Ae = Ca, Sr, Ba) could be used as the catalyst. These widely used precursors in Ae metal chemistry, are easily prepared from the cheap commercial amine HN(SiMe₃)₂. Although fully unexpected, a variety of aldimines could indeed be reduced to amines at 80 °C and at surprisingly low H₂ pressures down to 1 bar.² It was suspected that this transformation may not involve a highly reactive metal hydride catalyst, however, a comprehensive DFT study by our cooperation partners Mercedes Alonso and Frank de Proft was crucial in showing that a metal hydride mechanism is the most likely route.

One can only speculate about the nature of the catalyst. Based on simple thermodynamics the deprotonation of H₂ (pK_a = 49) by CaN’’₂ (pK_a of N’’H = 25.8) should not work, but it does! Saturating a CaN’’₂ solution in C₆D₆ with H₂ gave immediate formation of N’’H. The reason why this acid-base reaction proceeds can be summarized in one word: aggregation. The clustering of N’’CaH and CaH₂ to larger Ca hydride clusters delivers the energy needed for contrathermodynamic H₂ deprotonation. Indeed, by addition of a neutral tridentate ligand, such self-assembled Ca hydride clusters could be isolated in circa 80% yield.³

The advantage of these simple AeN’’₂ catalysts is that the most reactive of them all, BaN’’₂, is quite stable and can be obtained in large quantities in a convenient one-step synthesis. Switching back to alkene hydrogenation, the Ba amide catalyst was found to have enormous advantages.⁴ Its high activity broadened the substrate scope to unactivated (isolated) alkenes like 1-hexene. More important, activated substrates like styrene did not show any sign of polymerization. DFT calculations by our collaborator Mercedes Alonso indicate that this is due to fast trapping of the highly reactive intermediate by reaction with the acidic amine N’’H, thus preventing alkene polymerization. The latest developments show that these simple amide catalysts AeN’’₂ are also active in dehydrogenation catalysis which paved the way for Ae-catalyzed transfer hydrogenation.⁵

The unexpected observation that simple AeN’’₂ complexes can be used as catalysts in imine hydrogenation has been followed by further breakthroughs in alkene hydrogenation. Especially the heavier Ba catalyst is expected to show hitherto unseen reactivity. We foresee many more surprises of these forgotten elements!

For more details, you can read more about our work in Nature Catalysis: https://www.nature.com/articles/s41929-017-0006-0

The authors: Sjoerd Harder (left) and Christian Färber (right)

References

1. 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).
2. Bauer, H., Alonso, M., Färber, C., Elsen, H., Pahl, J., Causero, A., Ballmann, G., De Proft, F. & Harder, S., Imine hydrogenation with simple alkaline earth metal catalysts. Nature Catalysis 1, 40-47 (2018).
3. Maitland, B., Wiesinger, M., Langer, J., Ballmann, G., Pahl, J., Elsen, H., Färber, C. & Harder, S., A simple route to calcium and strontium hydride clusters. Angew. Chem. Int. Ed. 56, 11880-11884 (2017).
4. Bauer, H., Alonso, M., Fischer, C., Rösch, B., Elsen, H. & Harder, S., Simple Alkaline-Earth Metal Catalysts for Effective Alkene Hydrogenation. Angew. Chem. Int. Ed. 57, 15177-15182, (2018).
5. Bauer, H., Thum, K., Alonso, M., Fischer, C. & Harder, S., Alkene Transfer Hydrogenation with Alkaline-Earth Metal Catalysts. Angew. Chem. Int. Ed. 58, 4248-4253 (2019).