Recently, the team of Weiping Liu/Berlin Ji from the College of Chemistry and Chemical Engineering has made new progress in the field of catalytic hydrogen borrowing reaction using abundant metal. The team realized the asymmetric hydrogen-borrowing amination reaction of secondary alcohols using abundant metal iron catalysts, which provides a new idea for the synthesis of chiral amine compounds. The work was recently published in the international journal Journal of the American Chemical Society under the title ‘Iron-Catalyzed Enantioconvergent Amination of Alcohols’.
Chiral amines are important components in drugs, pesticides and natural products, and about 40-45% of small molecule drugs and fine chemicals contain chiral amine fragments. Therefore, much attention has been paid to how to synthesize chiral amines from cheap and easily available bulk chemicals in a green and efficient manner. Alcohols, as a simple, easy-to-obtain, environmentally friendly, green and sustainable raw material, have attracted much attention because of the advantages of ‘hydrogen borrowing’ amination of alcohols, such as economical steps, redox neutrality, and no need for intermediate isolation and purification. Although the transition metal-catalyzed ‘hydrogen borrowing’ amination of alcohols has made significant progress, the enantioselective amination of secondary alcohols to synthesize chiral amine compounds using this strategy has rarely been reported and is still very challenging.
The team has synthesized a series of chiral amines through enantioselective amination of secondary alcohols using an iron/chiral phosphoric acid co-catalytic system and a ‘hydrogen borrowing’ reaction strategy. The method is characterized by a wide range of substrates and good functional group compatibility, which are compatible with halogen-containing, cyano-containing, ester-containing, free amino-containing, olefin-containing and peptide-containing compounds. Computational results show that the chiral phosphoric acid interacts with the imine intermediate via hydrogen bonding to form an intermediate, creating a chiral pocket environment that controls the enantioselectivity of the reaction. The team has been working for a long time on the study of hydrogen borrowing reactions catalyzed by abundant metals. In previous work, a series of manganese-catalyzed ‘hydrogen borrowing’ reactions were developed to achieve atomic step economy and redox-neutral accretion of multiple examples of simple alcohols (J. Am. Chem. Soc., 2023, 145, 47,25545-25552, Angew. Chem. Int. Ed. 2023, 62, e202215882, Angew. Chem. Int. Ed. 2023, 62, e202303433, Nat. Commun., 2024, 15, 6798).
Fan Sun, a straight PhD student of the College of Chemistry and Chemical Engineering, class of 2021, and Boxuan Yao, a graduate student of Shantou University, are the co-first authors of the paper, and SiYi Wang, a graduate student of the College of Chemistry and Chemical Engineering, class of 2022, is the co-first author of the paper. Researcher Liu Weiping, Associate Professor Ji Berlin, and Lecturer Ni Shaofei of Shantou University were the co-corresponding authors of the paper, and Donghua University was the first corresponding organization. This research work was supported by the National Natural Science Foundation of China under the top-level program.
Link to original article：https://pubs.acs.org/doi/10.1021/jacs.5c07101
