Iridium-catalyzed direct asymmetric reductive amination utilizing primary alkyl amines as the N-sources

Direct asymmetric reductive amination is one of the most efficient methods for the construction of chiral amines, in which the scope of the applicable amine coupling partners remains a significant challenge. In this study we describe primary alkyl amines effectively serve as the N-sources in direct...

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Published inNature communications Vol. 13; no. 1; p. 3344
Main Authors Wu, Zitong, Wang, Wenji, Guo, Haodong, Gao, Guorui, Huang, Haizhou, Chang, Mingxin
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 10.06.2022
Nature Publishing Group
Nature Portfolio
Subjects
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140/131
140/58
639/638/403/933
639/638/77/883
Amination
Amines
Asymmetry
Bonding strength
Catalysis
Catalysts
Density functional theory
Enantiomers
Humanities and Social Sciences
Hydrogen bonding
Iridium
Ligands
multidisciplinary
Reaction mechanisms
Science
Science (multidisciplinary)
Substrates
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Summary:Direct asymmetric reductive amination is one of the most efficient methods for the construction of chiral amines, in which the scope of the applicable amine coupling partners remains a significant challenge. In this study we describe primary alkyl amines effectively serve as the N-sources in direct asymmetric reductive amination catalyzed by the iridium precursor and sterically tunable chiral phosphoramidite ligands. The density functional theory studies of the reaction mechanism imply the alkyl amine substrates serve as a ligand of iridium strengthened by a (N)H-O(P) hydrogen-bonding attraction, and the hydride addition occurs via an outer-sphere transition state, in which the Cl-H H-bonding plays an important role. Through this concise procedure, cinacalcet, tecalcet, fendiline and many other related chiral amines have been synthesized in one single step with high yields and excellent enantioselectivity. Direct asymmetric reductive amination is one of the most efficient methods for obtaining chiral amines. Here the authors show how primary alkyl amines can undergo this transformation in the presence of an iridium catalyst with sterically tuneable chiral phosphoramidite ligands, achieving the synthesis of pharmaceutical compounds.
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ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-022-31045-5