A Mild and Base-Free Protocol for the Ruthenium- Catalyzed Hydrogenation of Aliphatic and Aromatic Nitriles with Tridentate Phosphine Ligands Rosa Adam, Charles Beromeo Bheeter, Ralf Jackstell, and Matthias Beller* [a] Introduction Amines are present in natural compounds such as nucleotides, neurotransmitters, and amino acids, which play an important role in biological processes. Moreover, a large number of in- dustrially relevant dyes, solvents, additives, anti-foam agents, detergents, agrochemicals, and drugs contain amines in their structure. [1] In particular, primary amines are of interest as they are essential intermediates that can easily be modified by follow-up reactions to obtain secondary and tertiary amines, [2] for example, through reductive amination [3] or N-alkylation with alcohols [4] or carboxylic acids. [5] Among the available methodologies for the synthesis of primary amines, [6] nitrile re- duction constitutes a clean and atom economical approach. [7] On a laboratory scale, nitriles are commonly reduced with stoi- chiometric amounts of metal hydrides such as LiAlH 4 or NaBH 4 , generating metal salts as waste. [8] Thus, hydrogenation of ni- triles constitutes a more environmentally benign and clean methodology to obtain primary amines. In industry, heteroge- neous catalysts, usually Raney$-Ni and -Co, are the selected ones for performing such reactions. [9] However, these catalysts do not tolerate some functional groups and/or need additives, such as ammonia, to avoid the formation of side products. After pioneering work in the 1980s [10] based in the use of Ru or Rh hydride complexes, recently several catalyst systems for nitriles hydrogenation based on Ru, [11] Ir, [12] Re, [13] and Mo [14] have been described. Remarkably, also non-noble metal sys- tems have been successfully applied to this reaction. For exam- ple, two Fe pincer complexes [15] developed by our group and Milstein’s group and a Co pincer complex [16] published by Mil- stein and co-workers are the most representative examples. Despite all these advances, nitrile hydrogenation is still an interesting reaction in terms of selectivity. As shown in Scheme 1, initially the nitrile is hydrogenated to the primary imine, which leads either the desired primary amine (pathway A), or to the secondary amine or imine (pathway B). To avoid the formation of the latter products, derived from pathway B, several strategies can be applied, the addition of a base to shift the equilibrium to the primary imine being the most fre- quent. Furthermore, it has been showed that in some cases a basic additive not only has a positive effect on the selectivity, but also on the performance of the catalyst. [11g] Hence, the de- velopment of more active catalytic systems that can perform nitrile hydrogenation selectively without the need for any addi- tive is highly desirable. Currently, only a few Ru systems [11a,b,d,e] as well as a Fe–PNP complex [15a] are known to perform nitrile hydrogenation in the absence of base. Recently, our group has reported the synthesis of novel tri- dentate phosphine ligands that are inspired by the so-called triphos ligand (Figure 1). [17] Catalytic applications of these systems included the produc- tion of g-valerolactone from biomass derivatives, such as methyl levulinate and levulinic acid. [18] Based on our previous experience in nitrile hydrogenation using the combination of [Ru(cod)(methylallyl) 2 ] (cod = cyclooctadiene) and monoden- tate or bidentate P- or PN- ligands in the presence of a basic additive, we decided to explore this reaction using the new tri- dentate ligands. A novel protocol for the general hydrogenation of nitriles in the absence of basic additives is described. The system is based on the combination of [Ru(cod)(methylallyl) 2 ] (cod = cy- clooctadiene) and L2. A variety of aromatic and aliphatic ni- triles is hydrogenated under mild conditions (50 8C and 15 bar H 2 ) with this system. Kinetic studies revealed higher activity in the case of aromatic nitriles compared with aliphatic ones. Scheme 1. Catalytic hydrogenation of nitriles to primary amines (A) and pos- sible side reaction (B). [a] Dr. R. Adam, Dr. C. B. Bheeter, Dr. R. Jackstell, Prof. M. Beller Leibniz-Institut für Katalyse e.V. Albert-Einstein-Str. 29a, 18059 Rostock (Germany) E-mail : matthias.beller@catalysis.de Supporting Information and the ORCID identification number(s) for the author(s) of this article can be found under http://dx.doi.org/10.1002/ cctc.201501367. ChemCatChem 2016, 8, 1329 – 1334 # 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim 1329 Full Papers DOI: 10.1002/cctc.201501367