Cobalt-Catalyzed Enantioselective Reductive Amination of Ketones with Hydrazides.

An efficient cobalt-catalyzed asymmetric reductive amination of ketones with hydrazides has been realized, directly producing valuable chiral hydrazines in high yields and enantioselectivities (up to 98% enantiomeric excess).

Cobalt-Catalyzed Efficient Asymmetric Hydrogenation of α-Primary Amino Ketones.

Based on an amino-group-assisted coordination strategy and a proton-shuttle-activated outer-sphere mode, the cobalt-catalyzed asymmetric hydrogenation of α-primary amino ketones has been developed, resulting in the efficient synthesis of chiral vicinal amino alcohols bearing functionalized aryl rings in high yields and enantioselectivities (up to 99% enantiomeric excess (ee)) within 0.5 h.

Cobalt-Catalyzed Efficient Convergent Asymmetric Hydrogenation of E/Z-Enamides.

Using the diphosphine-cobalt-zinc catalytic system, an efficient asymmetric hydrogenation of internal simple enamides has been realized. In particular, the Ph-BPE ligand can achieve convergent asymmetric hydrogenation of E/Z-substrates. High yields and excellent enantioselectivities were obtained for both acyclic and cyclic enamides bearing α-alkyl-ß-aryl, α-aryl-ß-aryl, and α-aryl-ß-alkyl substituents. Hydrogenated products can be applied for the synthesis of useful chiral drugs such as Arfromoterol, Rotigotine, and Norsertraline. In addition, reasonable catalytic mechanism and stereocontrol mode are proposed based on DFT calculations.

Precise Synthesis of Chiral Z-Allylamides by Cobalt-Catalyzed Asymmetric Sequential Hydrogenations.

Asymmetric sequential hydrogenations of conjugated enynes have been developed using a Ph-BPE-CoI catalyst for the precise synthesis of chiral Z-allylamides in high activity (up to 1000 substrate/catalyst (S/C)) and with excellent enantioselectivity (up to >99 % enantiomeric excess (ee)). Mechanism experiments and theoretical calculations support a cationic CoI /CoIII redox catalytic cycle. The catalytic activity difference between cobalt complexes of Ph-BPE and QuinoxP* was explained by the process decomposition of rate-determining step in the second hydrogenation.

Azole-Directed Cobalt-Catalyzed Asymmetric Hydrogenation of Alkenes.

The azole-directed cobalt-catalyzed asymmetric hydrogenation of alkenes has been developed with high efficiency. With this approach, chiral pyrazole compounds were obtained in quantitative yields and excellent enantioselectivities (up to 99 % ee) under mild conditions, and the hydrogenation was conducted on a gram scale with up to 2000 TON. Several useful applications were demonstrated including the convenient introduction of ß-chirality to a drug intermediate containing an azole ring.

Asymmetric hydrogenation for the synthesis of 2-substituted chiral morpholines.

Asymmetric hydrogenation of unsaturated morpholines has been developed by using a bisphosphine-rhodium catalyst bearing a large bite angle. With this approach, a variety of 2-substituted chiral morpholines could be obtained in quantitative yields and with excellent enantioselectivities (up to 99% ee). The hydrogenated products could be transformed into key intermediates for bioactive compounds.

Catalytic Asymmetric Synthesis of the anti-COVID-19 Drug Remdesivir.

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.