Delft University of Technology Efficient and Practical Transfer Hydrogenation of Ketones Catalyzed by a Simple Bidentate Mn−NHC Complex

Catalytic reductions of carbonyl-containing compounds are highly important for the safe, sustainable, and economical production of alcohols. Herein, we report on the efficient transfer hydrogenation of ketones catalyzed by a highly potent Mn(I)-NHC complex. Mn-NHC 1 is practical at metal concentrations as low as 75 ppm, thus approaching loadings more conventionally reserved for noble metal based systems. With these low Mn concentrations, catalyst deactivation is found to be highly temperature dependent and becomes especially prominent at increased reaction temperature. Ultimately, understanding of deactivation pathways could help close the activity/stability-gap with Ru and Ir catalysts towards the practical implementation of sustainable earth-abundant Mn-complexes. The reduction of ketones to their corresponding alcohols is an important transformation for the production of pharmaceuticals, flavors, flagrances, and agrochemicals. Catalytic transfer hydrogenation (TH) protocols offer an attractive and sustainable alternative to well-known stoichiometric approaches.[1] Recently the development of non-noble metal catalysts based on abundant 3d transition metals such as Fe, Co, and Mn has received significant attention.[2] This has led to an impressive expansion of the field and the discovery of novel reactivity patterns of 3d metals versus their noble metal analogues. Remarkably, of the Mn-catalysts currently discussed in the open literature[3], several of the most active systems do not rely on phosphine ligands, but instead are based on simple bidentate Ndonors (Scheme 1, A C).[3b, 3h, 3i, 4] Sortais and co-workers reported on the use of 2-picolylamine as a ligand for Mn, while also disclosing a series of in-situ systems bearing bidentate diamines as ligands.[3b, 3h] Additionally, the group of Khusnutdinova very recently disclosed a Mn-bipyridine-derived complex which showed good activity for the TH of ketones, aldehydes, and imines at 0.3 mol% Mn (3000 ppm Mn; 330 TON).[3i] However, several challenges remain to be addressed before earth-abundant catalytic systems can be practically utilized in (industrial) organic synthesis. For example, compared to noble metals, reported metal loadings for 3d transition metals (TM) remain up to four orders of magnitude higher at several thousands of ppm (i.e., 0.1 – 1.0 mol%).[1, 5] Although catalyst consumption typically is not a large concern for academic researchers, it likely presents a critical hurdle for any commercial application. Moreover, in order to reduce operational cost it is desirable to replace highly complex, synthetically challenging, and expensive phosphines for simpler and more scalable alternatives. N-Heterocyclic carbenes (NHCs) in principle meet the main requirements to replace phosphine donors. The steric and electronic properties of NHCs are highly tunable, their synthesis is well established, scalable, and can conveniently be performed in air.[6] Introduction of NHC to noble metals has been very successful, resulting in highly active and (enantio-) selective hydrogenation catalysts for a variety of chemistries.[7] Following these works, several groups have reported the synthesis of Mn(I)-NHCs[8] and their applications in reduction catalysis (Scheme 1, D & E).[3c, 9] Taking notice of the recent developments in the field of Mn(I)-NHC catalysis, we hypothesized that the combination of a bidentate ligand bearing a strongly donating NHC group and an amine donor function could lead to a highly active and stable catalytic system. At the same time such a complex would maintain attractive ligand simplicity. Based on prior work with NHCs in our group[7d, 7e], we sought to synthesize and test two simple bidentate Mn-NHC complexes 1 and 2 (Scheme 1).