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The mechanisms of N‐heterocyclic carbene (NHC)‐catalyzed dearomatization reaction of alkyl pyridinium have been intensively studied using the density functional theory (DFT) method. The chemoselectivity and stereoselectivity were both analyzed based on the established mechanisms. The computational results showed that the chemoselective C4‐addition occurred before the C2‐addition, which is mainly because the C4 atom was more reactive according to the local reactivity analysis. The stereoselectivity was also investigated, and the C−C bond formation step was identified as the stereoselectivity‐determining step. The C−H⋅⋅⋅F and O−H⋅⋅⋅N interactions are identified as the main factors that govern the stereoselectivity by NCI analysis, and the preferred product was the RS‐configuration. This theoretical investigation would provide a case for understanding and predicting the selectivity of the organocatalytic dearomatization reactions of alkyl pyridinium. [ABSTRACT FROM AUTHOR]

The development of enantiodivergent catalysis for the preparation of both enantiomers of a chiral compound is of importance in pharmaceutical and bioorganic chemistry. With the design of a class of reactive and stereoselective organocatalysts, acyclic chiral secondary amines, a method for achieving the enantiodivergence is developed simply by changing the secondary N-i-Bu- to N-Me-group within the catalyst architecture while maintaining the same absolute configuration of the catalysts, which modulates the catalyst conformation. This catalyst-controlled enantiodivergent method not only enables challenging asymmetric transformations to occur in an enantiodivergent manner but also features a high level of stereocontrol and broad scope that is demonstrated in eight different reactions (90 examples), all delivering both enantiomers of a range of structurally diverse products including hitherto less accessible, yet important, compounds in good yields with high stereoselectivities. Enantiodivergent methods, which to access both enantiomers of the same compound, are of importance in drug synthesis. Here, the authors show that by simply changing a NiBu- to a NMe-group in readily available amine organocatalysts, high stereocontrol and broad scope are achieved in eight asymmetric reactions. [ABSTRACT FROM AUTHOR]

The discovery of proper ligands to simultaneously modulate the reactivity and effectively control the stereoselectivity is a central topic in the field of enantioselective C−H activation. Herein, we reported the synthesis of axially chiral biaryls by Pd‐catalyzed atroposelective C−H olefination. A novel chiral spiro phosphoric acid, STRIP, was identified as a superior ligand for this transformation. A broad range of axially chiral quinoline derivatives were synthesized in good yields with excellent enantioselectivities (up to 98 % ee). Density functional theory was used to gain a theoretical understanding of the enantioselectivities in this reaction. [ABSTRACT FROM AUTHOR]

Selectivity control is a challenging and important subject in semihydrogenation of alkynes. Here, a combined theoretical and experimental study was performed to reveal the origin of the chemo- and stereoselectivity in cobalt-catalyzed stereodivergent semihydrogenation of alkynes. Three NNP and PNP type pincer ligands were considered in calculation. The computational results show that over-reduction of the alkene is forbidden in this catalytic system because the alkylcobalt(I) intermediate formed by alkene insertion prefers to undergo β -H elimination rather than protonation of the Co C bond. Distortion–interaction analysis along the reaction coordinate suggests that the higher distortion energy during methanol-mediated protonation of the alkylcobalt(I) species suppresses formation of the side product, thereby determined the chemoselectivity. Mechanistic investigation reveals that the active cobalt(I) hydride species formed by pre-catalyst [ C ] has strong catalytic activity for alkene isomerization. Subsequent control experiments combined with free energy comparison confirms this conclusion and reveals that fast deactivation of catalyst and the weaker reactivity of the cis-alkene intermediate in the presence of the alkyne substrate prevents Z / E alkene isomerization using pre-catalyst [ C ]. This results in the divergent stereoselectivity in the presence of different cobalt pincer complexes. [ABSTRACT FROM AUTHOR]

TheCo2(CO)8-mediated intramolecular Pauson–Khandreaction is an efficient approach to the trans-decalinsubunit with a defined C1 quaternary chiral center. The newly developeddensity functional theory method M11-L was employed to study the mechanism,reactivity, and stereoselectivity for this reaction. The rate- andstereoselectivity-determining step is the intramolecular alkene insertioninto the carbon–cobalt bond. Insertion of the alkene by the re- and si-face was studied to explainthe stereoselectivity. The effects of varying the substituent on theacetylene and the C3 chirality were investigated experimentally andtheoretically. [ABSTRACT FROM AUTHOR]