Recent Advances in Homogeneous Catalysts for the Asymmetric Hydrogenation of Heteroarenes

Abstract

The asymmetric hydrogenation of heteroarenes has recently emerged as an effective strategy for the direct access to enantioenriched, saturated heterocycles. Although several homogeneous catalyst systems have been extensively developed for the hydrogenation of heteroarenes with high levels of chemo-and stereoselectivity, the development of mild conditions that allow for efficient and stereoselective hydrogenation of a broad range of substrates remains a challenge. This Perspective highlights recent advances in homogeneous catalysis of heteroarene hydrogenation as inspiration for the further development of asymmetric hydrogenation catalysts, and addresses underdeveloped areas and limitations of the current technology.

Unveiling a key catalytic pocket for the ruthenium NHC-catalysed asymmetric heteroarene hydrogenation

“…Enantioselective hydrogenation is arguably the most straightforward method for the conversion of aromatic to enantioenriched saturated heterocycles, thereby having high potential to promote a much needed expansion of the accessible chemical space. 1 Although an increased interest in the area of enantioselective heteroarene hydrogenation has emerged in academia and industry in recent years, 2 concurrently ensuring catalytic activity and selectivity still remains a particularly challenging task. As a consequence, asymmetric (hetero)arene hydrogenation continues to be considerably less explored compared to the hydrogenation of ketones, imines/enamines, and olefins.…”

Recent developments in enantio- and diastereoselective hydrogenation of N-heteroaromatic compounds

“…This can have a detrimental effect on the resulting enantioselectivities; (2) the poisoning effects of nitrogen or sulphur atoms acting on the chiral catalysts, and (3) the lack of secondary coordinating sites in simple aromatic compounds leading to low selectivities. 5,6,10,15 Efficient strategies have been developed to achieve successful EH of N-heteroaromatic compounds through substrate activation, catalyst activation, and relay activation. 6 Substrate activation consists of the introduction of a second coordinating group to alleviate the effect of aromaticity and/or assist in coordination with the catalyst.…”

Organocatalysis: A Tool of Choice for the Enantioselective Nucleophilic Dearomatization of Electron-Deficient Six-Membered Ring Azaarenium Salts

“…Dearomatization is very appealing since it produces 3D scaffolds from readily available aromatic precursors. Whereas enantioselective hydride addition requires the use of pre-functionalized azaarenes (introduction of Nu prior to the addition of the hydride) and leads to tetrahydro products (and therefore will not be discussed herein) [7][8][9], nucleophilic dearomatization (Nu = H) offers the advantage of introducing chemical diversity Taking into account the above-mentioned challenges, enantioselective nucleophilic dearomatization of azaarenium salts has attracted a great deal of attention mostly by using metal catalysts with chiral ligands [11][12][13][14][15][16][17][18][19][20]. Nevertheless, in the last fifteen years and due to the advent of organocatalysis [21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36], which was recently highlighted through the Taking into account the above-mentioned challenges, enantioselective nucleophilic dearomatization of azaarenium salts has attracted a great deal of attention mostly by using metal catalysts with chiral ligands [11][12][13][14][15][16][17][18][19][20].…”