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Comprehensive Summary: Herein, we report an iridium‐catalyzed asymmetric hydrogenation of hydantoin and thiazolidinedione derived exocyclic alkenes using our developed BiphPHOX as a ligand. The transformation shows good functional group tolerance, and gives the hydrogenated products with excellent yields (up to 99%) and enantioselectivities (up to 98% ee). A gram‐scale reaction was also carried out, and provided the hydrogenated product in excellent yield with no erosion in enantioselectivity. Finally, the transformation of the hydrogenated product provided an efficient approach for the synthesis of the intermediate of a HIV protease inhibitor. [ABSTRACT FROM AUTHOR]

The catalytic asymmetric synthesis of the anti‐COVID‐19 drug Remdesivir has been realized by the coupling of the P‐racemic phosphoryl chloride with protected nucleoside GS441524. The chiral bicyclic imidazole catalyst used is crucial for the dynamic kinetic asymmetric transformation (DyKAT) to proceed smoothly with high reactivity and excellent stereoselectivity (96 % conv. 22:1 SP:RP). Mechanistic studies showed that this DyKAT is a first‐order visual kinetic reaction dependent on the catalyst concentration. The unique chiral bicyclic imidazole skeleton and carbamate substituent of the catalyst are both required for the racemization process, involving the phosphoryl chloride, and subsequent stereodiscriminating step. A 10 gram scale reaction was also conducted with comparably excellent results, showing its potential for industrial application. [ABSTRACT FROM AUTHOR]

In this report, the desymmetrization of cyclic enones under relay Heck conditions with an array of aryl boronic acids, alkenyl triflates and indole derivatives is described. This method grants facile access to diverse γ‐functionalized cyclopentenones and δ‐functionalized cycloheptenones. Using this approach, a formal synthesis of (S)‐baclofen was completed in high yield and excellent enantioselectivity. [ABSTRACT FROM AUTHOR]

A palladium‐catalyzed enantioselective redox‐relay Heck reaction of 2‐indole triflates and disubstituted alkenes is reported. This process combines readily available indole triflates with a variety of alkenes to afford a range of indole derivatives bearing a stereocenter adjacent to C2. Enantioselectivity is achieved through use of a simple pyridine‐oxazoline ligand. Tuning the electronics of the indole, through judicious choice of N‐protecting group, is required to ensure selective β‐hydride elimination away from the indole core. Utility of this method is highlighted in a modular formal synthesis of an S1P1 agonist precursor developed by Merck. A palladium‐catalyzed enantioselective redox‐relay Heck reaction of 2‐indole triflates and disubstituted alkenes is reported. This process combines readily available indole triflates with a variety of alkenes to afford a range of indole derivatives bearing a stereocenter adjacent to C2. Enantioselectivity is achieved through use of a simple pyridine‐oxazoline ligand. [ABSTRACT FROM AUTHOR]

Frontispiz: Catalytic Asymmetric Synthesis of the anti-COVID-19 Drug Remdesivir Keywords: asymmetric catalysis; drug design; organocatalysis; phosphoramidates; synthetic methods EN asymmetric catalysis drug design organocatalysis phosphoramidates synthetic methods 1 1 1 11/11/20 20201116 NES 201116 B Asymmetrische Synthese b Die erste katalytische asymmetrische Synthese von Remdesivir durch die Kupplung von P-racemischem Phosphorylchlorid mit dem geschützten Nukleosid GS441524 wird von W. Zhang et al. in der Zuschrift auf S. 21000 vorgestellt. Asymmetric catalysis, drug design, organocatalysis, phosphoramidates, synthetic methods. [Extracted from the article]