The research team led by Professor Liu Weiping and Associate Professor Ji Bolin from the College of Chemistry and Chemical Engineering at Donghua University has recently achieved an important breakthrough in the field of earth-abundant metal-catalyzed borrowing hydrogen reactions. The team successfully realized the asymmetric borrowing hydrogen amination of secondary alcohols using an iron catalyst, offering a new strategy for the efficient synthesis of chiral amine compounds. The research, entitled “Iron-Catalyzed Enantioconvergent Amination of Alcohols,” was published in Journal of the American Chemical Society (JACS).
Chiral amines play a vital role in pharmaceuticals, agrochemicals, and natural products, with approximately 40–45% of small-molecule drugs and fine chemicals containing chiral amine structural units. Therefore, developing green, economical, and efficient methods to synthesize chiral amines from widely available raw materials has become a key research focus. Alcohols, as simple, accessible, and environmentally friendly feedstocks, are attractive substrates in borrowing hydrogen amination reactions due to their advantages in step economy, redox neutrality, and the elimination of intermediate purification. However, despite progress in the field, enantioconvergent amination of secondary alcoholsvia borrowing hydrogen remains rare and highly challenging.
The research team utilized a synergistic iron/chiral phosphoric acid catalytic system to achieve enantioconvergent borrowing hydrogen amination of secondary alcohols, successfully synthesizing a series of chiral amine products. This method demonstrates a broad substrate scope, excellent functional group tolerance, compatible with halides, cyano, ester, free amino groups, alkenes, and even polypeptides. Computational studies further revealed that the chiral phosphoric acid catalyst forms hydrogen bonds with the imine intermediate, generating a highly organized chiral pocket that governs the enantioselective outcome of the reaction.
The team has long focused on earth-abundant metal-catalyzed borrowing hydrogen reactions. In their prior research, they developed a series of manganese-catalyzed borrowing hydrogen transformations, enabling atom- and step-economical functionalization 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.
Contributors and Funding
Sun Fan (Ph.D. candidate, Donghua University, 2021) and Yao Boxuan (graduate student, Shantou University) are the co-first authors.
Wang Siyi (graduate student, Donghua University, 2022) contributed as co-author.
Professor Liu Weiping and Associate Professor Ji Bolin (Donghua University), together with Lecturer Ni Shaofei(Shantou University), are the co-corresponding authors, with Donghua University listed as the first corresponding institution.
This research was supported by the General Program of the National Natural Science Foundation of China.
Full Article: https://pubs.acs.org/doi/10.1021/jacs.5c07101
