Direct Asymmetric Ruthenium-Catalyzed Reductive Amination of Alkyl–Aryl Ketones with Ammonia and Hydrogen

Abstract

The asymmetric ruthenium-catalyzed reductive amination employing ammonia and hydrogen to primary amines is described. Here we demonstrate the capability of our catalyst to perform a chemo- and enantioselective process while using simple ammonia gas as a reagent, one of the most attractive and industrially relevant nitrogen sources. The presence of a catalytic amount of ammonium iodide was essential for obtaining good yields and enantioselectivities. The mechanism of this reaction was investigated by DFT and we found a viable pathway that also explains the trend and magnitude of enantioselectivity through the halide series in good agreement with the experimental data. The in-depth investigation of substrate conformers during the reaction turned out to be crucial in obtaining an accurate prediction of the enantioselectivity. Furthermore, we report the crystallographic data of the chiral [Ru(I)H(CO)((S,S)-f-binaphane)(PPh)] complex, which we identified as the most efficient catalyst in our investigation.

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

“…Among different kinds of amines, primary benzylic and aliphatic amines constitute valuable fine and bulk chemicals, that serve as versatile feedstocks and key intermediates for advanced chemicals, life science molecules and polymers 1 – 34 . Regarding their synthesis, catalytic reductive amination of carbonyl compounds (aldehydes and ketones) with ammonia in presence of molecular hydrogen represents a waste-free process to access various linear and branched benzylic and aliphatic amines 17 – 27 . In addition, catalytic amination of alcohols with ammonia also constitutes a sustainable methodology to produce primary amines 35 – 38 .…”

“…Apart from transition metal-catalyzed aminations, the Leuckart-Wallach reaction 39 – 41 and reduction of oxime ethers with borane 42 – 44 have also been applied. Noteworthy, selective introduction of primary amine moieties in functionalized compounds by utilizing ammonia constitutes a benign and economic methodology 17 – 27 . Ammonia, which is produced in >175 million tons per year scale, is considered to be an abundant and green chemical used enormously for the large scale production of urea and other fertilizers as well as various basic chemicals 45 – 50 .…”

“…Reductive amination for the preparation of primary amines, especially in industry, is mainly carried out using heterogeneous catalysts 17 – 23 . Compared to heterogeneous catalysts, homogeneous catalysis for amination of structurally diverse molecules is less studied and remains challenging 24 – 27 . Transition metal-catalyzed reactions involving ammonia are often difficult to perform or do not even occur.…”

Easily Synthesized Ru Catalyst Efficiently Converts Carbonyl Compounds and Ammonia into Primary Amines

“…[3d,8] To enhance the efficiency, some special reagents like ammonium acetate and ammonium formate were used as an ammonia surrogate, but it generally requires excessive amounts. [9] So far, the highly efficient and sustainable reductive amination of simple carbonyl compounds with ammonia using molecular H 2 , albeit less progressive, has been accessed with well-defined Rh, [10] Ru [11][12][13] and Co [14] complexes (Scheme 1). For instance, the pioneering work by Beller [10] in 2002 reported [{Rh (cod)Cl} 2 ]-catalyzed reductive amination of aldehydes in the presence of water-soluble phosphine Tppts (I).…”

“…[11] The same group also demonstrated this Ru-protocol can be launched in the asymmetric reductive amination of alkyl-aryl ketones using (S,S)-f-binaphane (III) as the chiral ligand. [12] Besides, a simple RuCl 2 (PPh 3 ) 3 catalyst (IV) was documented by Beller and Jagadeesh enabling the synthesis of a broad range of primary amines. [13] Very recently, they reported a combination of Co(BF 4 ) 2 and tridentate phosphine (V) for the reductive amination of varied aldehydes and ketones.…”