Comprehensive Summary TBAJ‐876, developed by TB Alliance, a novel anti‐tuberculosis‐specific drug, has entered Phase II clinical trials. Herein, the first asymmetric synthesis of TBAJ‐876 has been realized using synergistic Li/Li catalysis with excellent yield of 95% and 88 : 12 er (99.6 : 0.4 er, 10 : 1 dr after simple recrystallization). Furthermore, DFT calculations and 7Li‐NMR analysis illustrated the mechanism of the synergistic reaction: a chiral Li‐complex activates the nucleophile to control the stereoselectivity, while the other achiral Li‐complex activates the electrophile to catalyze the carbonyl addition reaction. Additionally, this protocol has been successfully carried out at 5 gram‐scale, showing its industrial potential.

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With his hand holding the sail and his feet on the sailboard, the position of the windsurfer mimics the key strategy of this work: the activation of hydrogenated substrates by chelating coordination with cobalt. The surfer is the cobalt catalyst holding the sail to coordinate parazole, and with his foot on the hydrogenated substrate board to coordinate the vinyl group. Bubbles in the seawater represent the main reagent of the reaction, hydrogen, the dolphin represents the hydrogenated product of this reaction, and the wind represents the bisphosphine ligand that promotes the catalytic activity. Overall, the picture shows that the reaction we developed is powerful like the sport of surfing. More information can be found in the Research Article by Z. Zhang, W. Zhang, and co‐workers (DOI: 10.1002/chem.202201517).

Utilizing a chiral bicyclic imidazole organocatalyst and adopting a continuous injection process, an alternative route has been developed for the efficient synthesis of chiral phthalidyl ester prodrugs via dynamic kinetic resolution of 3hydroxyphthalides through enantioselective acylation (up to 99 % ee). The computational studies suggest a general base catalytic mechanism differing from the widely accepted nucleophilic catalytic mechanism. The structure analysis of the key transition states shows that the CH-p interactions and not the previously considered cation/p-p interactions between the catalyst and substrate is the dominant factor giving rise to the observed stereocontrol. Figure 1. Representative ester-based prodrugs.

TBAJ-587, an analogue of the antituberculosis drug bedaquiline (BDQ), bearing a diarylquinoline skeleton retains the high bacterial potency, is less toxic, and has a better pharmacokinetic profile than the parent molecule, which has entered phase I clinical trials. In contrast to its fascinating bioactivity, however, the highly efficient synthesis of this molecule is still an unsolved challenge. Herein, the first asymmetric synthesis of TBAJ-587 based on a synergistic Li/Li bimetallic system is reported. The product could be obtained in an excellent yield of 90% and an enantiomeric ratio (er) of 80:20. Furthermore, the reaction could be conducted on a 5 g scale, and the product was obtained with 99.9:0.1 er after a simple recrystallization. The realization of this protocol will greatly aid the demand for clinical drug production.