This Review summarizes the advances in the construction of all-carbon quaternary stereocenters via catalytic enantioselective desymmetrization of prochiral and meso-compounds, highlights the power and potential of this strategy in the total synthesis of natural products and biologically active compounds, and outlines the synthetic opportunities still available.

Phosphoranes 2 are identified as a class of effective Lewis bases to activate chiral (salen)AlCl complex 1 to enhance its electrophilicity. Accordingly, a three-component catalyst system consisting of complex 1, phosphorane 2e, and Ph3PO is developed as a powerful tool for asymmetric ketone cyanosilylation. In particular, an unprecedented highly enantioselective cyanosilylation of linear aliphatic ketones is achieved. A tandem Wittig-cyanosilylation sequence starting from phosphorane 2a and enals 10 is further achieved, which internally utilizes the Ph3PO byproduct and remaining phosphorane 2a as cocatalysts for cyanosilylation of α,β,γ,δ-unsaturated enones, providing atom-efficient access to valuable chiral conjugated dienes and enynes. The high efficiency of the cyanosilylation originates from orthogonal activation of both (salen)AlCl complex 1 and cyanotrimethylsilane by the phosphorane and Ph3PO, respectively. This mechanistic insight is supported by NMR, MS, and ReactIR analyses and DFT calculations. Furthermore, the formation of charged complexes through the activation of chiral complex 1 by phosphorane 2a is confirmed by electrical conductivity experiments.

A rare example of a one-pot process that involves asymmetric triple relay catalysis is reported. The key step is an asymmetric [1,5] electrocyclic reaction of functionalized ketimines. The substrates for this process were obtained in situ in a two-step process that involved the hydrogenation of nitroarenes with a Pd/C catalyst to yield aryl amines and their subsequent coupling with isatin derivatives in a Brønsted acid catalyzed ketimine formation reaction. The electrocyclization was catalyzed by a bifunctional chiral Brønsted base/hydrogen bond donor catalyst. The one-pot process gave the desired products in good yields and with excellent enantioselectivity.

A novel palladium-catalyzed norbornene-mediated three-component reaction for the construction of ortho-alkenyl aromatic tertiary amines has been achieved, which represents a useful extension of the Catellani-type tandem ortho-selective CH amination transformations.

All in a sequence: An organocatalyzed Morita-Baylis-Hillman (MBH)/bromination/[3+2] annulation sequence for highly stereoselective syntheses of bis(spirooxindole)s featuring adjacent spiro-stereocenters is described. The key step is an unprecedented catalytic asymmetric [3+2] annulation of isatin-derived MBH adducts, containing a tetrasubstituted alkene moiety, with isatins.

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Myeloperoxidase (MPO)-dependent hypochlorous acid (HOCl) generation plays crucial roles in diabetic vascular complications. As a natural polyphenol, quercetin has antioxidant properties in various diabetic models. Herein, we investigated the therapeutic mechanism for quercetin on MPO-mediated HOCl generation and endothelial dysfunction in diabetic vasculature. In vitro, the presence of MPO could amplify high glucose-induced endothelial dysfunction which was significantly inhibited by the NADPH oxidase inhibitor, HOCl or H2O2 scavengers, revealing the contribution of MPO/H2O2/HOCl to vascular endothelial injury. Furthermore, quercetin effectively inhibited MPO/high glucose-mediated HOCl generation and cytotoxicity to vascular endothelial cells. The inhibitive effect on MPO activity was related to the fact that quercetin reduced high glucose-induced H2O2 generation in endothelial cells and directly acted as a competitive substrate for MPO, thus limiting MPO/H2O2-dependent HOCl production. Moreover, quercetin could attenuate HOCl-caused endothelial dysfunction in endothelial cells and isolated aortas. In vivo, dietary quercetin significantly inhibited aortic endothelial dysfunction in diabetic mice, while this compound simultaneously suppressed vascular MPO expression and activity. Therefore, it was demonstrated herein that quercetin inhibited endothelial injury in diabetic vasculature via suppression of MPO/high glucose-dependent HOCl formation.

We report a novel bifunctional cyanating reagent, Me2(CH2Cl)SiCN, which paves the way to a one-pot sequential synthesis of tertiary alcohols featuring a chloromethyl ketone moiety via enantioselective ketone cyanosilylation. This method contributes to gram-scale enantioselective total synthesis of the aggregation pheromone of the Colorado potato beetle, (S)-CPB.