1304141-62-5Relevant articles and documents
Homogenous Pd-catalyzed asymmetric hydrogenation of unprotected indoles: Scope and mechanistic studies
Duan, Ying,Li, Lu,Chen, Mu-Wang,Yu, Chang-Bin,Fan, Hong-Jun,Zhou, Yong-Gui
, p. 7688 - 7700 (2014/06/10)
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.
An enantioselective approach to 2,3-disubstituted indolines through consecutive Bronsted acid/Pd-complex-promoted tandem reactions
Duan, Ying,Chen, Mu-Wang,Ye, Zhi-Shi,Wang, Duo-Sheng,Chen, Qing-An,Zhou, Yong-Gui
supporting information; experimental part, p. 7193 - 7197 (2011/07/30)
In tandem: A divergent and enantioselective approach to 2,3-disubstituted indolines was developed through consecutive Bronsted acid/Pd-complex- promoted tandem reactions from simple 2-substituted indoles and aldehydes in one operation to give up to 98 % ee (see scheme; R1=H, F, or Me; R 2=alkyl; R3=aryl or alkyl). Three Bronsted acid promoted steps and two Pd-catalyzed hydrogenation steps were involved in this process. Copyright
