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Development of Molecular-defined Non-noble Metal Complexes and Nano-structured Materials for Sustainable Redox Reactions Development of Molecular-defined Non-noble Metal Complexes and Nano-structured

Periodic Reporting for period 3 - NoNaCat (Development of Molecular-defined Non-noble Metal Complexes and Nano-structured Materials for Sustainable Redox ReactionsDevelopment of Molecular-defined Non-noble Metal Complexes and Nano-structured)

Reporting period: 2018-12-01 to 2020-05-31

The general goal of this project is to develop novel innovative base metal catalysts for green and sustainable transformations. Catalysis is a key technology for the European chemical industry as well as life science industries.
Due to the inherent advantages of earth abundant metals there is an increasing interest in doing catalysis in the presence of such bio-relevant systems. In this respect, catalysis with non-noble metal complexes offers a highly attractive replacement. Hence, this area is increasingly attractive for homogeneous and heterogeneous catalysis. Within the ERC project NoNaCat novel molecularly-defined catalysts and nano-structured materials are prepared and explored for sustainable redox reactions. In the first year several interesting results have been achieved:
1. In our initial work, we demonstrated the first example of homogeneous non-noble metal-catalyzed transfer hydrogenations of N-heteroarenes. More specifically, we showed that the combination of simple cobalt salts with tris-2-(diphenylphosphino)-phenyl)phosphine L1 is able to selectively reduce quinolines in the presence of other sensitive functional groups, under mild conditions (Scheme1). Advantageously, these reductions can be performed without any external pressure simply using formic acid as a hydrogen source.

To be provided on demand = Scheme 1. Yield of product 2a in the transfer hydrogenation of quinoline (1a) using different reducing agents.

2. Most recently, we described the first heterogeneous single atom catalysts (SACs), which are conveniently prepared by decorating alumina nanorods with platinum atoms. The resulting stable material efficiently catalyzes hydrosilylation of industrially relevant olefins with high TON (≈105) (Scheme 2). In general, such catalytic hydrosilylations represents a straightforward and atom-efficient methodology for the creation of C−Si bonds. While the application of homogeneous platinum complexes prevails in industry and academia, the new heterogeneous catalysts constitute state-of-the-art systems. A variety of substrates was selectively hydrosilylated including compounds with sensitive reducible and other functional groups (N, B, F, Cl). Notably, the single atom based catalyst shows significantly higher activity compared to related Pt nanoparticles.

To be provided on demand = Scheme 2. Pt-SAC show similar performance to best homogeneous Pt catalysts.

3. The first general and efficient non-noble metal-catalyzed reductive C2-alkoxylation of cyclic imides (phthalimides and succinimides) was achieved (Scheme 3). Crucial for the success was the use of a [Co(BF4)2·6H2O/Triphos] system. Using this catalyst, the hydrogenation of the aromatic ring of the parent phthalimide is avoided and only one of the carbonyl groups was selectively functionalized. The resulting products, N- and aryl-ring substituted 3-alkoxy-2,3-dihydro-1H-isoindolin-1-one and N-substituted 3-alkoxy-pyrrolidin-2-one derivatives were prepared under mild conditions in good to excellent isolated yields. Intramolecular reductive couplings can also be performed affording tricyclic compounds in one-step process. The new protocol opens the way to the development of different base-metal processes for the straightforward synthesis of functionalized N-heterocyclic compounds with pharmaceutical and biological interest.

To be provided on demand = Scheme 3. Selective Co-catalyzed reduction of phthalimides and succinimides.

4. In a microreview, we highlighted the importance of base-metal catalysis, especially with non-noble-metal pincer-type catalysts, which is increasingly used in organic synthesis and thus becoming more and more important for organometallic chemistry.

5. Hydrodehalogenation is a straightforward approach for detoxifications of harmful anthropogenic organohalide-based pollutants, as well as removal of halide protecting groups used in multistep syntheses. A novel sustainable catalytic material was prepared from biowaste (chitosan) in combination with an earth-abundant cobalt salt. This heterogeneous catalyst was fully characterized by transmission electron microscope, X-ray diffraction, and X-ray photoelectron spectroscopy measurements, and successfully applied to hydrodehalogenation of alkyl and (hetero)aryl halides with broad scope (>40 examples) and excellent chemoselectivity using molecular hydrogen as a reductant. The general usefulness of this method was demonstrated by successful detoxification of non-degradable pesticides and fire retardants. Moreover, the potential of the catalyst as a deprotection tool is demonstrated in a multistep synthesis of (±)-peronatin B (alkaloid).

6. As mentioned above, the development of catalytically active materials from biowaste represents an important aspect of sustainable chemical research. Hence, additional heterogeneous materials were synthesized from inexpensive biomass based on chitosan and abundant Co(OAc)2 via complexation followed by pyrolysis at various temperatures. These materials were applied for the catalytic hydrogenation of nitroarenes using molecular hydrogen. A variety of diversely functionalized nitroarenes including pharmaceutically active compounds were selectively converted to aromatic amines in high yield and selectivity with excellent functional group tolerance (Scheme 4). As an example, this green protocol has also been implemented for the synthesis of biologically important TRPC3 inhibitor.

To be provided on demand = Scheme 4. Hydrogenation of nitroarene-based pharmaceutical drugs.

7. According to the original project proposal novel nitrogen modified cobalt catalysts supported on carbon were prepared by pyrolysis of a mixture generated from cobalt(II) acetate in aqueous solution of melamine or waste melamine resins, which are widely used as industrial polymers. As planned the obtained nanostructured materials catalyze the transfer hydrogenation of N-heteroarenes with formic acid in the absence of base. The optimal Co/Melamine-2@C-700 catalyst exhibited high activity and selectivity for the dehydrogenation of formic acid into molecular hydrogen and carbon dioxide and allowed for the reduction of diverse N-heteroarenes including substrates featuring sensitive functional groups.

8. Looking for further applications of cobalt-based homogenous catalysts we studied the direct CH-alkylation of indoles using carboxylic acids for the first time. As a successful catalytic system the combination of Co(acac)3 and 1,1,1-tris(diphenylphosphinomethyl)-ethane (Triphos) in the presence of Al(OTf)3 as co-catalyst was developed. This system is able to perform the reductive alkylation of 2-methyl-1H-indole with a wide range of carboxylic acids. The utility of the protocol was further demonstrated through the C3 alkylation of several substituted indole derivatives using acetic, phenylacetic or diphenylacetic acids. In addition, a careful selection of the reaction conditions allowed to perform the selective C3 alkenylation of some indole derivatives. Moreover, the alkenylation of C2 position of 3-methyl-1H-indole was also possible. Control experiments indicate that the aldehyde, in situ formed from the carboxylic acid hydrogenation, plays a central role in the overall process. It should be noted that this new protocol enables the direct functionalization of indoles with readily available and stable carboxylic acids using a non-precious metal based catalyst and hydrogen as reductant (Scheme 5).


To be provided on demand = Scheme 5. The first direct CH-alkylation of indoles using carboxylic acids and hydrogen in the presence of a non-noble metal based catalytic system.

9. As an exciting extension of our original proposal we wwere able to synthesize new chiral manganese PNP pincer complexes. An example is shown in Figure 1. Asymmetric hydrogenation of several prochiral ketones with molecular hydrogen in the presence of this complex proceeds under remarkably mild conditions (40 °C, 4 h, 30 bar H2). Besides high catalytic activity for aromatic substrates, aliphatic ketones are hydrogenated with remarkable selectivities (er up to 92:8). DFT calculations support an outer sphere hydrogenation mechanism as well as the experimentally determined stereochemistry.

To be provided on demand = Figure 1. Molecular structure of a chiral manganese pincer complex.

10. Finally, we developed a convenient and practical preparation of novel graphitic shell encapsulated cobalt nanoparticles by template synthesis of cobalt-diamine-dicarboxylic acid metal organic frameworks on carbon and subsequent pyrolysis under inert atmosphere (Figure 2). The resulting nanoscale cobalt particles create a stable and reusable catalysts, which enable the selective reductive aminations for a general synthesis of all kinds of interesting amines including primary, secondary, tertiary and N-methylamines (>140 examples!). Starting from inexpensive and easily accessible carbonyl compounds (aldehydes, ketones), ammonia, or nitro compounds and molecular hydrogen under industrially viable and scalable conditions, this cost-effective reductive amination methodology allows for the synthesis of various life science molecules, chiral amines, amino acids, and actual drug molecules (Scheme 6).

To be provided on demand = Figure 2. Preparation of encapsulated cobalt nanoparticles supported on carbon using MOFs precursors.
Within the first year new nano-structured materials as well as molecularly-defined complexes have been synthesized and characterized.
Several of these materials and complexes showed improved performance for catalytic reductions of nitriles and carboxylic acid derivatives compared to previously known materials. In addition, state-of-the-art catalysts for reductive aminations have been developed, which show unprecedented substrate scope.