Catalytic reductive aminations using molecular hydrogen for synthesis of different kinds of amines.

Reductive aminations constitute an important class of reactions widely applied in research laboratories and industries for the synthesis of amines as well as pharmaceuticals, agrochemicals and biomolecules. In particular, catalytic reductive aminations using molecular hydrogen are highly valued and essential for the cost-effective and sustainable production of different kinds of amines and their functionalization. These reactions couple easily accessible carbonyl compounds (aldehydes or ketones) with ammonia, amines or nitro compounds in the presence of suitable catalysts and hydrogen that enable the preparation of linear and branched primary, secondary and tertiary amines including N-methylamines and molecules used in life science applications. In general, amines represent valuable fine and bulk chemicals, which serve as key precursors and central intermediates for the synthesis of advanced chemicals, life science molecules, dyes and polymers. Noteworthily, amine functionalities are present in a large number of pharmaceuticals, agrochemicals and biomolecules, and play vital roles in the function of these active compounds. In general, reductive aminations are challenging processes, especially for the syntheses of primary amines, which often are non-selective and suffer from over-alkylation and reduction of carbonyl compounds to the corresponding alcohols. Hence, the development of suitable catalysts to perform these reactions in a highly efficient and selective manner is crucial and continues to be important and attracts scientific interest. In this regard, both homogeneous and heterogeneous catalysts have successfully been developed for these reactions to access various amines. There is a need for a comprehensive review on catalytic reductive aminations to discuss the potential catalysts used and applicability of this methodology in the preparation of different kinds of amines, which are of commercial, industrial and medicinal importance. Consequently, in this review we discuss catalytic reductive aminations using molecular hydrogen and their applications in the synthesis of functionalized and structurally diverse benzylic, heterocyclic and aliphatic primary, secondary and tertiary amines as well as N-methylamines and more complex drug targets. In addition, mechanisms of reductive aminations including selective formation of desired amine products as well as possible side reactions are emphasized. This review aims at the scientific communities working in the fields of organic synthesis, catalysis, and medicinal and biological chemistry.

Reductive amination using cobalt-based nanoparticles for synthesis of amines.

Reductive aminations are an essential class of reactions widely applied for the preparation of different kinds of amines, as well as a number of pharmaceuticals and industrially relevant compounds. In such reactions, carbonyl compounds (aldehydes, ketones) react with ammonia or amines in the presence of a reducing agent and form corresponding amines. Common catalysts used for reductive aminations, especially for the synthesis of primary amines, are based on precious metals or Raney nickel. However, their drawbacks and limited applicability inspired us to look for alternative catalysts. The development of base-metal nanostructured catalysts is highly preferable and is crucial to the advancement of sustainable and cost-effective reductive amination processes. In this protocol, we describe the preparation of carbon-supported cobalt-based nanoparticles as efficient and practical catalysts for synthesis of different kinds of amines by reductive aminations. Template synthesis of a cobalt-triethylenediamine-terephthalic acid metal-organic framework on carbon and subsequent pyrolysis to remove the organic template resulted in the formation of supported single cobalt atoms and nanoparticles. Applying these catalysts, we have synthesized structurally diverse benzylic, aliphatic and heterocyclic primary, secondary and tertiary amines, including pharmaceutically relevant products, starting from inexpensive and easily accessible carbonyl compounds with ammonia, nitro compounds or amines and molecular hydrogen. To prepare this cobalt-based catalyst takes 26 h, and the reported catalytic reductive amination reactions can be carried out within 18-28 h.

Ultra-small cobalt nanoparticles from molecularly-defined Co-salen complexes for catalytic synthesis of amines.

We report the synthesis of in situ generated cobalt nanoparticles from molecularly defined complexes as efficient and selective catalysts for reductive amination reactions. In the presence of ammonia and hydrogen, cobalt-salen complexes such as cobalt(ii)-N,N'-bis(salicylidene)-1,2-phenylenediamine produce ultra-small (2-4 nm) cobalt-nanoparticles embedded in a carbon-nitrogen framework. The resulting materials constitute stable, reusable and magnetically separable catalysts, which enable the synthesis of linear and branched benzylic, heterocyclic and aliphatic primary amines from carbonyl compounds and ammonia. The isolated nanoparticles also represent excellent catalysts for the synthesis of primary, secondary as well as tertiary amines including biologically relevant N-methyl amines.

Cobalt-based nanoparticles prepared from MOF-carbon templates as efficient hydrogenation catalysts.

The development of efficient and selective nanostructured catalysts for industrially relevant hydrogenation reactions continues to be an actual goal of chemical research. In particular, the hydrogenation of nitriles and nitroarenes is of importance for the production of primary amines, which constitute essential feedstocks and key intermediates for advanced chemicals, life science molecules and materials. Herein, we report the preparation of graphene shell encapsulated Co3O4- and Co-nanoparticles supported on carbon by the template synthesis of cobalt-terephthalic acid MOF on carbon and subsequent pyrolysis. The resulting nanoparticles create stable and reusable catalysts for selective hydrogenation of functionalized and structurally diverse aromatic, heterocyclic and aliphatic nitriles, and as well as nitro compounds to primary amines (>65 examples). The synthetic and practical utility of this novel non-noble metal-based hydrogenation protocol is demonstrated by upscaling several reactions to multigram-scale and recycling of the catalyst.

Simple ruthenium-catalyzed reductive amination enables the synthesis of a broad range of primary amines.

The production of primary benzylic and aliphatic amines, which represent essential feedstocks and key intermediates for valuable chemicals, life science molecules and materials, is of central importance. Here, we report the synthesis of this class of amines starting from carbonyl compounds and ammonia by Ru-catalyzed reductive amination using H2. Key to success for this synthesis is the use of a simple RuCl2(PPh3)3 catalyst that empowers the synthesis of >90 various linear and branched benzylic, heterocyclic, and aliphatic amines under industrially viable and scalable conditions. Applying this catalyst, -NH2 moiety has been introduced in functionalized and structurally diverse compounds, steroid derivatives and pharmaceuticals. Noteworthy, the synthetic utility of this Ru-catalyzed amination protocol has been demonstrated by upscaling the reactions up to 10 gram-scale syntheses. Furthermore, in situ NMR studies were performed for the identification of active catalytic species. Based on these studies a mechanism for Ru-catalyzed reductive amination is proposed.