Imine Hydrogenation

Abstract

Recent Advances in the Asymmetric Hydrogenation of IminesChiral aromatic amines are extremely interesting products because of their applications in the pharmaceutical, agrochemical and fi ne chemical industries. The enantioselective hydrogenation of C = N double bonds using chiral transition metal complexes as catalysts is one of the most useful methods for preparing optically active amines [1] . This reaction has drawbacks, however: coordination can take place through both the nitrogen donor atom and the double bond, and the substrate and catalyst intermediates are unstable under catalytic conditions. The C = N substrates, for instance, are often sensitive to hydrolysis. Homogeneous catalysts can complex with both the imine and the amine product or can be deactivated by the formation of trimers or oligomers. In consequence, catalytic activity is often low. Furthermore, in the case of the acyclic imines one of the major problems for achieving high enantiomeric excess is the equilibrium between the E and Z isomer of the imine, which makes it diffi cult for the catalyst to convert all stereoisomers in selective manner. Many ruthenium -, rhodium -and iridium -based catalytic systems are excellent in hydrogenating functionalized olefi ns and ketones but are much less effi cient with imine substrates.In spite of these problems, an Ir -catalyzed imine hydrogenation is the key step in the largest scale enantioselective catalytic process used in industry, which is also one of the fastest homogeneous catalytic systems: the industrial production of the chiral herbicide ( S ) -metolachlor [ N -(1 ′ -methyl -2 ′ -methoxyethyl) -N -chloroacetyl -2 -ethyl -6 -methylaniline] in amounts greater than 10 000 tonnes per annum at about 80% ee [2] . The catalyst is a combination of [Ir(COD)Cl] 2 ( COD = 1,5 -cyclooctadiene ), the chiral ferrocenyl diphosphine Xyliphos, tetrabutylammonium iodide ( TBAI ) and sulfuric acid. 2 -Methyl -6 -ethylphenyl -1 ′ -methyl -2 ′ -methoxyethylimine ( MEA(monoethanolamine) -imine ) is hydrogenated under 80 bar (8 MPa) hydrogen pressure at 323 K and at a substrate/catalyst ratio exceeding 10 6 to yield MEA -amine in 79% ee and with an initial turnover frequency that is said to exceed 1.8 × 10 6 h − 1 (Scheme 10.1 ). This process has been extensively studied and

Asymmetric Synthesis of Indolines by Catalytic Enantioselective Reduction of 3H-Indoles

“…Imine reduction continues to be a topic of ongoing interest with considerable efforts devoted to the asymmetric reduction of both cyclic and acyclic imines . While many highly enantioselective hydrogenations of various imines and N-heteroaromatic compounds are known, only a few asymmetric reductions of trisubstituted indoles are available.…”

“…Imine reduction continues to be a topic of ongoing interest with considerable efforts devoted to the asymmetric reduction of both cyclic and acyclic imines . While many highly enantioselective hydrogenations of various imines and N-heteroaromatic compounds are known, only a few asymmetric reductions of trisubstituted indoles are available. Current methods include transition metal catalyzed high-pressure hydrogenation using iridium and ruthenium complexes with a variety of chiral diphosphine, diamine, and phosphoramidite ligands .…”

Asymmetric Reduction of tert-Butanesulfinyl Ketimines by N-Heterocyclic Carbene Boranes

“…However, chiral α-branched amines, which often can be obtained by reduction of ketimines, are more valuable in organic synthesis, as they could be used as resolving agents and a key chiral source of important natural products and biologically active compounds. Normally, the involved reduction process has been reported using hydrogenation, , metallic hydrides, hydrosilylation, transfer hydrogenation, etc. However, to the best of our knowledge, there are no reports related to the reduction of less active ketimines using NHC-BH 3 .…”

Designing New Magnesium Pincer Complexes for Catalytic Hydrogenation of Imines and N-Heteroarenes: H2 and N–H Activation by Metal–Ligand Cooperation as Key Steps

“…Catalytic hydrogenation of unsaturated molecules by H 2 is one of the most practical transformations in laboratory and industry . Classic catalysts mainly rely on late transition metals due to their efficiency in the cleavage of H 2 . , Due to the toxic and costly characteristics, it is increasingly interesting to use cheaper and more environmentally benign catalysts, such as the first-row transition metal compounds and frustrated Lewis pairs (FLPs). − However, as another large group of elements in the periodic table, the main-group metals have received much less attention in catalytic hydrogenation due to their lack of partially filled d orbitals and the instability of many main-group metal compounds, which largely impeded their application in bond activation. − In the 1960s, simple metal hydrides and inorganic bases were known as catalysts for the hydrogenation of benzophenone, alkenes, and alkynes, but harsh conditions were required . In 2008, Harder and co-workers reported a β-diketiminate calcium hydride complex and K, Ca, and Sr benzyl catalysts, providing relatively mild conditions for the catalytic hydrogenation of conjugated alkenes (Figure a) .…”