Svenja Werkmeister

Hydrogenation of Esters to Alcohols with a Well‐Defined Iron Complex

We present the first base-free Fe-catalyzed ester reduction applying molecular hydrogen. Without any additives, a variety of carboxylic acid esters and lactones were hydrogenated with high efficiency. Computations reveal an outer-sphere mechanism involving simultaneous hydrogen transfer from the iron center and the ligand. This assumption is supported by NMR experiments.

Pincer‐Type Complexes for Catalytic (De)Hydrogenation and Transfer (De)Hydrogenation Reactions: Recent Progress

Pincer complexes are becoming increasingly important for organometallic chemistry and organic synthesis. Since numerous applications for such catalysts have been developed in recent decades, this Minireview covers progress in their use as catalysts for (de)hydrogenation and transfer (de)hydrogenation reactions during the last four years. Aside from noble-metal-based pincer complexes, the corresponding base metal complexes are also highlighted and their applications summarized.

Mild and selective hydrogenation of aromatic and aliphatic (di)nitriles with a well-defined iron pincer complex

The catalytic hydrogenation of carboxylic acid derivatives represents an atom-efficient and clean reduction methodology in organic chemistry. More specifically, the selective hydrogenation of nitriles offers the possibility for a green synthesis of valuable primary amines. So far, this transformation lacks of useful, broadly applicable non-noble metal-based catalyst systems. In the present study, we describe a molecular-defined iron complex, which allows for the hydrogenation of aryl, alkyl, heterocyclic nitriles and dinitriles. By using an iron PNP pincer complex, we achieve very good functional group tolerance. Ester, ether, acetamido as well as amino substituents are not reduced in the presence of nitriles. Moreover, nitriles including an α,β-unsaturated double bond and halogenated derivatives are well tolerated in this reaction. Notably, our complex constitutes the first example of an homogeneous catalyst, which permits the selective hydrogenation of industrially important adipodinitrile to 1,6-hexamethylenediamine.

Cooperative Iron–Brønsted Acid Catalysis: Enantioselective Hydrogenation of Quinoxalines and 2 H-1,4-Benzoxazines

Chiral six-membered nitrogen heterocycles, such as substituted piperazines, morpholines and piperidines, are found in many naturally occurring alkaloids as well as in pharACHTUNGTRENNUNGmaACHTUNGTRENNUNGceuACHTUNGTRENNUNGtiACHTUNGTRENNUNGcals and constitute an integral part of numerous important bioactive compounds. The biological and pharmacological properties of their aryl-fused analogues tetrahydroquinoxaline and dihydro-2 H-benzoxazine have been known for a long time. As early as 1947 various tetrahydroquinoxalines have already been synthesised to explore antimalarial activity, whereas the antituberculouses properties of dihydrobenzoxazines have been shown only ten years later. Since then, interest in tetrahydroquinoxalines and dihydro-2 H-benzoxazines has increased significantly and today optically active 2-substituted 1,2,3,4-tetrahydroquinoxalines and 3-substituted 3,4-dihydro2 H-1,4-benzoxazines constitute interesting building blocks in the drug discovery process and are an important motif of many naturally occurring alkaloids (Figure 1). More specifically, the chiral 1,2,3,4-tetrahydroquinoxaline A is a promising M2 acetylcholine receptor inhibitor, whereas B has been pursued as a potent V2 receptor antagonist. In addition, C is known to represent an active cholesteryl ester transfer protein inhibitor and the chiral 1,4-benzoxazine D is a promising candidate in atherosclerosis treatment. Levofloxacin is a commercialised highly potent antibacterial agent and obscurinervine and its related compounds are examples for naturally accruing alkaloids. With the growing importance of such chiral compounds in the life science industries, the development of efficient enantioselective methodologies continues to be interesting for organic chemistry and catalysis. Clearly, beside different multistep methods to synthesise chiral tetrahydroquinoxalines and dihydro-benzoxazines the most direct and atom-economic approach represents the enantioselective hydrogenation of quinoxalines and benzoxazines. Notably, virtually all of the known catalysts for the latter enantioselective hydro-

Consecutive Intermolecular Reductive Hydroamination: Cooperative Transition-Metal and Chiral Brønsted Acid Catalysis

Enantiomerically pure chiral amines are of increasing importance and commercial value in the fine chemical, pharmaceutical, and agrochemical industries. Here, we describe the straightforward synthesis of chiral amines by combining the atom-economic and environmentally friendly hydroamination of alkynes with an enantioselective hydrogenation of in situ generated imines by using inexpensive hydrogen. By following this novel approach, a wide range of terminal alkynes can be reductively hydroaminated with primary amines including alkyl-, and arylalkynes as well as aryl and heteroaryl amines. Excellent yields and selectivities up to 94 % ee and 96 % isolated yield were obtained.

Development of new hydrogenations of imines and benign reductive hydroaminations: zinc triflate as a catalyst.

The hydrogenation of imines to amines in the presence of catalytic amounts of zinc triflate has been demonstrated for the first time. In addition, an efficient procedure for the reductive hydroamination of alkynes to amines is presented using zinc triflate as a catalyst precursor. In both protocols a variety of different functional groups are tolerated, and the reactions proceed smoothly in high yields.

Selective Ruthenium‐Catalyzed Transfer Hydrogenations of Nitriles to Amines with 2‐Butanol

Transfer your hydrogen: Fast and general transfer hydrogenation of nitriles to form primary amines is possible with a homogeneous Ru/1,4-bis(diphenylphosphino)butane (DPPB) catalyst (see scheme). The use of 2-butanol as the hydrogen-transfer reagent is essential for the selective reduction of aromatic, heteroaromatic, and aliphatic nitriles with this system.

Copper-catalyzed reductive amination of aromatic and aliphatic ketones with anilines using environmental-friendly molecular hydrogen

A convenient and practical copper-catalyzed reductive amination was discovered. In the presence of easily available and inexpensive Cu(OAc)2 various ketones react with anilines and molecular hydrogen to give the desired amines in high yields.

Ruthenium/Imidazolylphosphine Catalysis: Hydrogenation of Aliphatic and Aromatic Nitriles to Form Amines

A convenient and efficient catalyst system for the hydrogenation of aliphatic nitriles towards the corresponding primary amines in high to excellent yields is presented. In addition, aromatic nitriles are reduced smoothly, too. The use of low catalyst loadings and molecular hydrogen make this protocol an attractive methodology.

Towards a zinc-catalyzed asymmetric hydrogenation/transfer hydrogenation of imines.

The first asymmetric hydrogenation/transfer hydrogenation of imines to amines using zinc(II) triflate in combination with chiral ligands is described. The monodentate binaphthophosphepine ligand (3 g) provided the highest enantioselectivities. Using different imines, the corresponding amines were obtained in moderate yields and enantioselectivities.