608525-25-3

Upstream product

• 95279-34-8 2-[2-(3,4-Dimethoxy-phenyl)-ethyl]-quinoline 
• 91-63-4 2-methylquinoline 
• 21852-32-4 4-bromomethyl-1,2-dimethoxybenzene 
• 104967-54-6 2-(3,4-dimethoxy-β-phenethyl)-1,2,3,4-tetrahydroquinoline 

Downstream Products

• 442-33-1 (R)-2-[2-(3,4-dimethoxyphenyl)ethyl]-1-methyl-1,2,3,4-tetrahydroquinoline 

Relevant academic research and scientific papers

Manganese-Catalyzed Asymmetric Hydrogenation of Quinolines Enabled by π–π Interaction**

The non-noble metal-catalyzed asymmetric hydrogenation of N-heteroaromatics, quinolines, is reported. A new chiral pincer manganese catalyst showed outstanding catalytic activity in the asymmetric hydrogenation of quinolines, affording high yields and enantioselectivities (up to 97 % ee). A turnover number of 3840 was reached at a low catalyst loading (S/C=4000), which is competitive with the activity of most effective noble metal catalysts for this reaction. The precise regulation of the enantioselectivity were ensured by a π–π interaction.

Synergistic Chemo/Biocatalytic Synthesis of Alkaloidal Tetrahydroquinolines

The power of complementary chemocatalytic and biocatalytic transformations is demonstrated in the asymmetric synthesis of 2-substituted tetrahydroquinolines. A series of racemic tetrahydroquinolines were synthesized through a convergent one-pot Rh(I)-catalyzed addition/condensation sequence of alkyl vinyl ketones and aminophenylboronic acids. The resulting tetrahydroquinolines were thereafter shown to be substrates for the flavin-dependent enzyme cyclohexylamine oxidase, and preparative-scale deracemizations have been demonstrated on these high-value targets.

Solvent-Regulated Asymmetric Hydrogenation of Quinoline Derivatives in Oligo(Ethylene Glycol)s through Host–Guest Interactions

The asymmetric hydrogenation of quinolines in oligo(ethylene glycol)s (OEGs) and poly(ethylene glycol)s (PEGs) with chiral cationic ruthenium diamine complexes has been investigated. Interestingly, in liquid PEGs or long-chain OEGs, the Ru catalysts lost their reactivity. Upon the addition of a little MeOH, the hydrogenation of quinoline was switched “ON”. Evidence from mass spectrometry and control experiments revealed that encapsulation of the quinolinium salt by PEG or long-chain OEG molecules through supramolecular interactions is possibly the main reason for such a switchable hydrogenation reaction. Moreover, the asymmetric hydrogenation of 2-substituted quinoline derivatives was achieved in triethylene glycol (3-OEG), thereby affording 1,2,3,4-tetrahydroquinolines with excellent reactivities and enantioselectivities (up to 99 % ee). Furthermore, the Ru catalyst could be readily recycled for both pure 3-OEG and biphasic 3-OEG/n-hexane systems without a clear loss of reactivity and enantioselectivity.

Highly enantioselective synthesis of chiral tetrahydroquinolines and tetrahydroisoquinolines by ruthenium-catalyzed asymmetric hydrogenation in ionic liquid

Asymmetric hydrogenation reactions of quinolines and 3,4- dihydroisoquinolines using the chiral cationic ruthenium complex Ru(TsDPEN) [TsDPEN=N-(p-toluenesulfonyl)-1,2-diphenylethylenediamine] as catalyst in neat imidazolium ionic liquids have been investigated. The catalytic performance was influenced by the anion of the ionic liquids for both substrate classes. A range of 2-alkyl-substituted 1,2,3,4-tetrahydroquinolines and 1-alkyl-substituted 1,2,3,4-tetrahydroisoquinolines was obtained in high yields with up to >99% ee. Interestingly, the hydrogenation of quinoline derivatives bearing a carbonyl group was selective for the C-N (quinoline) over the C-O (ketone) bonds, while such a unique chemoselectivity was not observed in methanol. Furthermore, the ruthenium catalysts could be easily recycled at least 5 times in the asymmetric hydrogenation of 3,4-dihydroisoquinoline by solvent extraction. To further facilitate the recovery of catalyst and reduce the use of organic solvent, a thin film of ionic liquid containing Ru(TsDPEN) was supported on silica gels. This supported ionic liquid-phase catalyst was effective in the asymmetric hydrogenation of quinoline, and could be recycled at least 6 times by simple filtration. Copyright

Highly enantioselective hydrogenation of quinolines using phosphine-free chiral cationic Ruthenium catalysts: Scope, mechanism, and origin of enantioselectivity

Asymmetric hydrogenation of quinolines catalyzed by chiral cationic η6-arene-N-tosylethylenediamine-Ru(II) complexes have been investigated. A wide range of quinoline derivatives, including 2-alkylquinolines, 2-arylquinolines, and 2-functionalized and 2,3-disubstituted quinoline derivatives, were efficiently hydrogenated to give 1,2,3,4-tetrahydroquinolines with up to >99% ee and full conversions. This catalytic protocol is applicable to the gram-scale synthesis of some biologically active tetrahydroquinolines, such as (-)-angustureine, and 6-fluoro-2-methyl-1,2,3,4-tetrahydroquinoline, a key intermediate for the preparation of the antibacterial agent (S)-flumequine. The catalytic pathway of this reaction has been investigated in detail using a combination of stoichiometric reaction, intermediate characterization, and isotope labeling patterns. The evidence obtained from these experiments revealed that quinoline is reduced via an ionic and cascade reaction pathway, including 1,4-hydride addition, isomerization, and 1,2-hydride addition, and hydrogen addition undergoes a stepwise H+/H- transfer process outside the coordination sphere rather than a concerted mechanism. In addition, DFT calculations indicate that the enantioselectivity originates from the CH/π attraction between the η6-arene ligand in the Ru-complex and the fused phenyl ring of dihydroquinoline via a 10-membered ring transition state with the participation of TfO- anion.

Bronsted acid differentiated metal catalysis by kinetic discrimination

A Bronsted acid differentiated metal catalyzed hydrogenation has been developed. A combinatorial variation of chiral triflylamides with achiral metal complexes results in a highly active catalyst for the asymmetric reduction.

Asymmetrie hydrogenation with water/silane as the hydrogen source

"Chamical Equation presentd" Water as a hydride source : A new pathway to form metal-hydride bonds has been developed through the reaction of easily available metal-silyl compounds with water. This method has been successfully applied to asymmetric hydrogenation of heteroaromatic compounds with up to 93 % ee under mild autoclave-free conditions (see scheme).

Asymmetric hydrogenation of quinolines activated by Br?nsted acids

Enantioselective hydrogenation of quinolines and quinoxalines catalyzed by iridium/diphosphine complex with catalytic amount of Br?nsted acid as activator was developed. In the presence of piperidine·TfOH as the activator, full conversions and up to 92% ee were obtained.

Inhibiting deactivation of iridium catalysts with bulky substituents on coordination atoms

Introducing bulky groups on the coordination phosphorus atoms can effectively block the formation of inactive dimer species and improve the activity of the iridium catalysts. Results of ESI-MS analysis gave strong evidence. This strategy was successfully

Thieme chemistry journal awardees - Where are they now? Asymmetric br?nsted acid catalyzed transfer hydrogenations

Asymmetric hydrogenations are of great importance in the synthesis of optically active amines. This account highlights the development of the first metal-free transfer hydrogenation that is both highly enantioselective and inspired by natures dehydrogen?ase. Further focus is given to the extension of this bioinspired process to provide a variety of valuable, biologically active products and natural products under mild reaction conditions. Georg Thieme Verlag Stuttgart - New York.