1234333-48-2

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• 1234333-39-1 2-(3'-methylbenzyl)indole 

Relevant academic research and scientific papers

Diboron-mediated palladium-catalyzed asymmetric transfer hydrogenation using the proton of alcohols as hydrogen source

The developments of hydrogen sources stand at the forefront of asymmetric reduction. In contrast to the well-studied alcohols as hydrogen sources via β-hydride elimination, the direct utilization of the proton of alcohols as a hydrogen source for activator-mediated asymmetric reduction is rarely explored. Herein we report the proton of alcohols as a hydrogen source in diboron-mediated palladium-catalyzed asymmetric transfer hydrogenation of 1,3-diketones and indoles, providing a series of chiral β-hydroxy ketones and indolines with excellent yields and enantioselectivities. This strategy would be useful for the synthesis of chiral deuterium-labelled compounds due to the ready availability of deuterium-labelled alcohols. Mechanistic investigations and DFT calculations revealed that active chiral Pd-H species was generated from the proton of alcohols by activating of tetrahydroxydiboron, hydrogen transfer was the rate-determining step, and the reaction preferred Pd(0)-catalyzed mechanism. [Figure not available: see fulltext.]

Method for synthesizing chiral indoline through palladium catalyzed asymmetric hydrogenation of indole generated in situ

The invention discloses a method for synthesizing chiral indoline through palladium-catalyzed asymmetric hydrogenation of indole generated in situ. The method is characterized in that an indole compound generated in situ is subjected to asymmetric hydrogenation by using 1-5 mol% of a palladium catalyst and adding 1-2.0 equev acid to obtain a corresponding chiral indoline compound, wherein the enantiomeric excess can reach 96% at most. According to the invention, the method is simple and convenient to operate, practical, easy to implement, high in yield, environmentally friendly, available in catalyst business and mild in reaction condition, and has potential practical application value.

Enantioselective hydrogenation of N-heteroaromatics catalyzed by chiral diphosphine modified binaphthyl palladium nanoparticles

The first application of binaphthyl-stabilized palladium nanoparticles (Bin-PdNPs) with chiral modifiers in asymmetric hydrogenation of N-heteroaromatics is revealed. With an appropriate ratio of R-BINAP/Bin-PdNPs used, the pre-prepared chiral nanocatalyst achieves asymmetric hydrogenations of 2-substituted quinolines with good to excellent yields and moderate enantioselectivities, which showed superior catalytic properties to the R-BINAP/Pd complex. Moreover, this protocol is also applicable to 2-substituted indoles.

Highly Enantioselective Synthesis of Indolines: Asymmetric Hydrogenation at Ambient Temperature and Pressure with Cationic Ruthenium Diamine Catalysts

A highly enantioselective synthesis of indolines by asymmetric hydrogenation of 1H-indoles and 3H-indoles at ambient temperature and pressure, catalyzed by chiral phosphine-free cationic ruthenium complexes, has been developed. Excellent enantio- and diastereoselectivities (up to >99 % ee, >20:1 d.r.) were obtained for a wide range of indole derivatives, including unprotected 2-substituted and 2,3-disubstituted 1H-indoles, as well as 2-alkyl- and 2-aryl-substituted 3H-indoles.

Homogenous Pd-catalyzed asymmetric hydrogenation of unprotected indoles: Scope and mechanistic studies

An efficient palladium-catalyzed asymmetric hydrogenation of a variety of unprotected indoles has been developed that gives up to 98% ee using a strong Br?nsted acid as the activator. This methodology was applied in the facile synthesis of biologically active products containing a chiral indoline skeleton. The mechanism of Pd-catalyzed asymmetric hydrogenation was investigated as well. Isotope-labeling reactions and ESI-HRMS proved that an iminium salt formed by protonation of the C=C bond of indoles was the significant intermediate in this reaction. The important proposed active catalytic Pd-H species was observed with 1H NMR spectroscopy. It was found that proton exchange between the Pd-H active species and solvent trifluoroethanol (TFE) did not occur, although this proton exchange had been previously observed between metal hydrides and alcoholic solvents. Density functional theory calculations were also carried out to give further insight into the mechanism of Pd-catalyzed asymmetric hydrogenation of indoles. This combination of experimental and theoretical studies suggests that Pd-catalyzed hydrogenation goes through a stepwise outer-sphere and ionic hydrogenation mechanism. The activation of hydrogen gas is a heterolytic process assisted by trifluoroacetate of Pd complex via a six-membered-ring transition state. The reaction proceeds well in polar solvent TFE owing to its ability to stabilize the ionic intermediates in the Pd-H generation step. The strong Br?nsted acid activator can remarkably decrease the energy barrier for both Pd-H generation and hydrogenation. The high enantioselectivity arises from a hydrogen-bonding interaction between N-H of the iminium salt and oxygen of the coordinated trifluoroacetate in the eight-membered-ring transition state for hydride transfer, while the active chiral Pd complex is a typical bifunctional catalyst, effecting both the hydrogenation and hydrogen-bonding interaction between the iminium salt and the coordinated trifluoroacetate of Pd complex. Notably, the Pd-catalyzed asymmetric hydrogenation is relatively tolerant to oxygen, acid, and water.

Pd-catalyzed asymmetric hydrogenation of unprotected indoles activated by bronsted acids

The first highly enantioselective hydrogenation of simple indoles was developed with a Brnsted acid as an activator to form the iminium intermediate in situ, which was hydrogenated using Pd(OCOCF3)2/(R)-H8- BINAP catalyst system with up to 96% ee. The present method provides an efficient route to enantioenriched 2-substituted and 2,3-disubstituted indolines.