Asymmetric transfer hydrogenation (ATH) has developed rapidly since the pioneering report of Nobel Laureate Noyori in the 1990s. Its reaction condition is mild and it utilizes formic acid or isopropanol as the source of hydrogen thus avoiding the hazardous hydrogen gas and specialized equipment. It has been widely used in industrial production. However, the highly regioselective ATH of unsymmetrical 1,2-diketones has been a difficulty, which only has been tried to overcome by Ikariya's group in 2000.

In a study published in Journal of the American Chemical Society, the research group led by Prof. FANG Xinqiang from Fujian Institute of Research on the Structure of Matter of the Chinese Academy of Sciences proposed the group addition-kinetic resolution strategy to systematically solve the problems in asymmetric synthesis, and pioneered in the establishment and development of the research field of 1,2-diketone chemistry. 

The researchers first combined the group addition-kinetic resolution strategy with 1,2-dikeones chemistry, and achieved the ATH-dynamic kinetic resolution of racemic β-substituted 1,2-diketones with high regio- and stereoselectivity by using chiral transition metal complex. They then completed the reaction within 3-5 minutes and did not need to carry it out under anhydrous and oxygen-free conditions. The enantiomeric excess values of the reaction products are all above 90%, and the yield and diastereomeric ratio values are also very high. 

The protocol tolerates a series of aryl and vinyl groups at the β-positions, and both the aryl- and alkyl-substituted ketones are suitable substrates. 1,2-Diols with three stereogenic centers could also be obtained with excellent enantiomeric excess by applying higher temperature and prolonged reaction time. All the products are highly valuable synthons for further transformations including drug molecule synthesis. 

Density Functional Theory (DFT) calculations showed that the ATH of the (S)-1h has the lowest energy barrier for the reduction of the distal carbonyl group, while the energy barrier for the reduction of the same carbonyl group of the (R)-1h is 3.3 kcal/mol higher. At the same time, the energy barriers for the reduction of proximal carbonyls are also high, which well explains the reasons for the high regio- and stereoselectivity of the reaction. 

This study not only proposes a new application of group addition-kinetic resolution strategy in the field of asymmetric synthesis, but also enriches the study of 1,2-diketone chemistry.