Enantioselective Transfer Hydrogenation Research Articles

Organocatalytic Enantioselective Transfer Hydrogenation of β‐Amino Nitroolefins

AbstractThe asymmetric organocatalytic transfer hydrogenation of β‐acylamino and β‐tert‐butyloxycarbonylamino nitroolefins has been successfully realised in excellent enantioselectivities and yields (up to >99% ee, 97% yield) with a simple thiourea catalyst and a Hantzsch ester as hydrogen source, giving a direct access to enantiomerically pure β‐amino nitroalkanes.magnified image

ChemInform Abstract: Chiral Phosphoric Acid Catalyzed Asymmetric Transfer Hydrogenation of Quinolines in a Sustainable Solvent.

AbstractThe use of diethyl carbonate as a sustainable solvent for enantioselective transfer hydrogenation of 2‐substituted quinolines (I) using a phosphoric acid catalyst and Hantzsch ester as a hydrogen source is reported.

Highly Enantioselective Transfer Hydrogenation of Polar Double Bonds by Macrocyclic Iron(II)/(NH)2P2 Catalysts

We describe herein a new protocol for the synthesis of 2,2′-((1S,1′S)-ethane-1,2-diylbis(phenylphosphanediyl))dibenzaldehyde ((SP,SP)-5), which is the key intermediate in the synthesis of macrocyclic iron(II)/(NH)2P2 catalysts for the highly enantioselective transfer hydrogenation of polar double bonds. The dialdehyde (SP,SP)-5 was obtained as a single diastereoisomer and enantiomer from an optically pure H-phosphinate in 33% yield over five steps. It was further converted to afford multigram quantities of the macrocyclic iron(II)/(NH)2P2 complexes, which were tested in the asymmetric transfer hydrogenation of aryl alkyl ketones and imines in 2-propanol on a 100 mmol scale. Ten substrates, including challenging ones such as tert-butyl phenyl ketone and industrially relevant molecules such as 3,5-bis(trifluoromethyl)acetophenone, were reduced in high yield (89.0–99.7%), excellent enantioselectivity (95.8–99.4% ee), and with low catalyst loadings (S/C up to 10 000/1).

Enantioselective transfer hydrogenation, a key step for the synthesis of 3-aminotetrahydroquinolines

An enantioselective transfer hydrogenation has been successfully achieved to furnish 3-aminotetrahydroquinolines. The reaction was conducted in the presence of Hantzsch dihydropyridine and a catalytic amount of chiral phosphoric acid under mild conditions.

Asymmetric transfer hydrogenation of seven membered tricyclic ketones: N-substituted dibenzo[b,e]azepine-6,11-dione driven by nonclassical CH/O interactions

Enantioselective transfer hydrogenation of dibenzo-fused-azepine-diones: N-substituted dibenzo[b,e]azepin-6-11-dione was achieved by ruthenium catalysis in the presence of formic acid/triethylamine as a mild hydrogen source.

ChemInform Abstract: Phosphothreonine as a Catalytic Residue in Peptide‐Mediated Asymmetric Transfer Hydrogenations of 8‐Aminoquinolines.

Phosphothreonine (pThr) was found to constitute a new class of chiral phosphoric acid (CPA) catalyst upon insertion into peptides. To demonstrate the potential of these phosphopeptides as asymmetric catalysts, enantioselective transfer hydrogenations of a previously underexplored substrate class for CPA-catalyzed reductions were carried out. pThr-containing peptides lead to the observation of enantioselectivities of up to 94:6 e.r. with 2-substituted quinolines containing C8-amino functionality. NMR studies indicate that hydrogen-bonding interactions promote strong complexation between substrates and a rigid β-turn catalyst.

In situ generation of dihydropyridine for the enantioselective transfer hydrogenation of 1,4-benzoxazines

A new strategy for the enantioselective transfer hydrogenation of benzoxazines involving an in situ generation of Hantzsch ester has been developed. Dihydroadducts were isolated in good yields (75–99%) and enantioselectivities (89–96% ee).

A new cost-effective Ru-chloramphenicol base derivative catalyst for the asymmetric transfer hydrogenation/dynamic kinetic resolution of N-Boc α-amino-β-ketoesters and its application to the synthesis of the chiral core of vancomycin

Herein we describe the application of Ru-chloramphenicol base complexes catalyzed highly diastereo- and enantioselective transfer hydrogenation of N-Boc α-amino-β-ketoesters for the asymmetric synthesis of anti-N-Boc-β-hydroxy-α-amino esters.

Catalytic enantioselective OFF ↔ ON activation processes initiated by hydrogen transfer: concepts and challenges.

Hydrogen transfer initiated processes are eco-compatible transformations allowing the reversible OFF ↔ ON activation of otherwise unreactive substrates. The minimization of stoichiometric waste as well as the unique activation modes provided by these transformations make them key players for a greener future for organic synthesis. Long limited to catalytic reactions that form racemic products, considerable progress on the development of strategies for controlling diastereo- and enantioselectivity has been made in the last decade. The aim of this review is to present the different strategies that enable enantioselective transformations of this type and to highlight how they can be used to construct key synthetic building blocks in fewer operations with less waste generation.

The application of novel boron complexes in asymmetric transfer hydrogenation of aromatic ketones

Asymmetric transfer hydrogenation using iso-PrOH as a hydrogen source offers an attractive route for reducing simple unsymmetrical functionalized ketones to chiral alcohols. The combined use of organometallic and coordination chemistry has produced a number of new and powerful synthetic methods for important classes of compounds in general and for optically active substances in particular. For this aim, the (S,Z)-1-((1-hydroxy butane-2-yl imino)methyl)naphthalene-2-ol chiral ligand was chosen to obtain boron complexes. Boronic derivative compounds such as phenylboronic acid, 6-methoxynaphthalen-2-ylboronic acid, 4-methyl-3-nitrophenylboronic acid and 1,4-phenylenediboronic acid were applied to obtain complexation with chiral based ligands. The structures of these ligands and their complexes have been elucidated by a combination of multinuclear NMR spectroscopy, LC–MS/MS, TGA/DTA, UV–Vis., elemental analysis, XRD, SEM, and FTIR. These boron complexes have also been tested as catalysts in the enantioselective transfer hydrogenation of acetophenone derivatives to afford the corresponding product, (S)-1-phenylethanol with high conversions (up to 99%) and modest enantioselectivities (up to 70% ee). The substituents on the backbone of the ligands had a significant effect on both the activity and % ee.

Phosphothreonine as a catalytic residue in peptide-mediated asymmetric transfer hydrogenations of 8-aminoquinolines.

Phosphothreonine (pThr) was found to constitute a new class of chiral phosphoric acid (CPA) catalyst upon insertion into peptides. To demonstrate the potential of these phosphopeptides as asymmetric catalysts, enantioselective transfer hydrogenations of a previously underexplored substrate class for CPA-catalyzed reductions were carried out. pThr-containing peptides lead to the observation of enantioselectivities of up to 94:6 e.r. with 2-substituted quinolines containing C8-amino functionality. NMR studies indicate that hydrogen-bonding interactions promote strong complexation between substrates and a rigid β-turn catalyst.

Phosphothreonine as a Catalytic Residue in Peptide‐Mediated Asymmetric Transfer Hydrogenations of 8‐Aminoquinolines

AbstractPhosphothreonine (pThr) was found to constitute a new class of chiral phosphoric acid (CPA) catalyst upon insertion into peptides. To demonstrate the potential of these phosphopeptides as asymmetric catalysts, enantioselective transfer hydrogenations of a previously underexplored substrate class for CPA‐catalyzed reductions were carried out. pThr‐containing peptides lead to the observation of enantioselectivities of up to 94:6 e.r. with 2‐substituted quinolines containing C8‐amino functionality. NMR studies indicate that hydrogen‐bonding interactions promote strong complexation between substrates and a rigid β‐turn catalyst.

ChemInform Abstract: Highly Enantioselective Transfer Hydrogenation of Ketones with Chiral (NH)2P2 Macrocyclic Iron(II) Complexes.

AbstractSeveral iron complexes are presented with the pictured compound FEC being one of the most promising catalysts for the title reaction.

Asymmetric Synthesis of α-Amino Ketones by Brønsted Acid Catalysis.

The highly efficient, regioselective, and enantioselective transfer hydrogenation of α-keto ketimines and reductive amination of diketones by Brønsted acid catalysis is described. A series of chiral α-amino ketones is prepared in high yields (up to >99%), excellent regioselectivities (up to >99:1), and enantioselectivities (up to 98% ee). This method has broad substrate scope.

ChemInform Abstract: Catalytic Highly Enantioselective Transfer Hydrogenation of β‐Trifluoromethyl Nitroalkenes (I). An Easy and General Entry to Optically Active β‐Trifluoromethyl Amines.

ChemInform Abstract: Catalytic Highly Enantioselective Transfer Hydrogenation of β‐Trifluoromethyl Nitroalkenes (I). An Easy and General Entry to Optically Active β‐Trifluoromethyl Amines.

ChemInform Abstract: Isonitrile Iron(II) Complexes with Chiral N2P2 Macrocycles in the Enantioselective Transfer Hydrogenation of Ketones.

Bis(isonitrile) iron(II) complexes bearing a C2-symmetric N2P2 macrocyclic ligand, which are easily prepared from the corresponding bis(acetonitrile) analogue, catalyze the asymmetric transfer hydrogenation (ATH) of a broad scope of ketones in excellent yields (up to 98%) and with high enantioselectivity (up to 91% ee).

Highly Enantioselective Transfer Hydrogenation of Ketones with Chiral (NH)2P2 Macrocyclic Iron(II) Complexes

AbstractBis(isonitrile) iron(II) complexes bearing a C2‐symmetric diamino (NH)2P2 macrocyclic ligand efficiently catalyze the hydrogenation of polar bonds of a broad scope of substrates (ketones, enones, and imines) in high yield (up to 99.5 %), excellent enantioselectivity (up to 99 % ee), and with low catalyst loading (generally 0.1 mol %). The catalyst can be easily tuned by modifying the substituents of the isonitrile ligand.

Highly enantioselective transfer hydrogenation of ketones with chiral (NH)2 P2 macrocyclic iron(II) complexes.

Bis(isonitrile) iron(II) complexes bearing a C2 -symmetric diamino (NH)2 P2 macrocyclic ligand efficiently catalyze the hydrogenation of polar bonds of a broad scope of substrates (ketones, enones, and imines) in high yield (up to 99.5 %), excellent enantioselectivity (up to 99 % ee), and with low catalyst loading (generally 0.1 mol %). The catalyst can be easily tuned by modifying the substituents of the isonitrile ligand.

ChemInform Abstract: Asymmetric Transfer Hydrogenation of Ketimines by Indoline as Recyclable Hydrogen Donor.

The chiral phosphoric acid catalyzed enantioselective transfer hydrogenation of various ketimines was achieved by the use of 2-aryl indoline as the hydrogen donor. Corresponding chiral amines were obtained in good chemical yields with excellent enantioselectivities.

Catalytic highly enantioselective transfer hydrogenation of β-trifluoromethyl nitroalkenes. An easy and general entry to optically active β-trifluoromethyl amines.

In the presence of a thiourea catalyst, β-CF3 nitroalkenes react with Hantzsch esters in a highly enantioselective fashion, giving a broad range of β-CF3 amine precursors with a tertiary stereocentre at the β-position. This reaction represents the first general catalytic enantioselective approach to this important class of β-CF3 amines.