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

Abstract

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.

Selective Transformations of Triglycerides into Fatty Amines, Amides, and Nitriles by using Heterogeneous Catalysis

“…It is noteworthy that the thus‐obtained fatty amines are an important class of chemicals for the industrial production of surfactants, germicides, and softeners. Although the reductive amination of relatively reactive carbonyl compounds such as ketones and aldehydes into amines has been studied extensively, reports on the reductive amination of carboxylic acids and esters including triglycerides remain relatively rare . Our heterogeneous catalytic system using NH 3 as a nitrogen source and H 2 does not require any additives and could thus serve as an effective method for the direct transformation of triglycerides into fatty amines.…”

Direct Catalytic Conversion of Furfural to Furan‐derived Amines in the Presence of Ru‐based Catalyst

“…Amines represent a privileged class of compounds that have garnered broad interest from the chemical industry owing to their nucleophilic properties, conferring them high reactivity . In particular, primary amines constitute valuable fine and bulk chemicals, which serve as versatile feedstocks and key intermediates for the synthesis of advanced chemicals, life science molecules, and polymers . For example, furfurylamines from biomass‐derived furfural can be used in diverse applications, including the preparation of polymers, biologically active compounds, and as intermediates for the synthesis of pharmaceuticals such as antiseptic agents, antihypertensives, and diuretics …”

“…Reductive amination of aldehydes or ketones for preparing primary amines is performed at industrial level by using heterogeneous catalysts based on supported Cu, Ni, Pt, Ru, Rh, or Pd, owing to their easy separation and recyclability and lack of use of toxic reagents and/or stoichiometric reductants . In particular, reductive amination using NH 3 and H 2 has been explored in the field of organic chemistry, giving access to a variety of amines . However, reductive amination reactions can suffer from overalkylation and the reduction of the aldehydes/ketones to alcohols, decreasing the selectivity to primary amines .…”

Electrocatalytic Water Splitting and CO2 Reduction: Sustainable Solutions via Single‐Atom Catalysts Supported on 2D Materials

“…The C vacancies on the graphene or N‐doped graphene (NGN) offer chemical bonding to SACs for stable combination with each other. The electronic structure of SACs, which are bonded with N‐doped graphene, gets significantly changed due to the difference of elemental electronegativity, leading to the electron transfer from C atom to N atom in N‐doped graphene, thus making the positively charged C atom active for the absorption and activation of target molecules …”