Organocatalytic aromatization-promoted umpolung reaction of imines

Chen, Ye-Hui1; Duan, Meng2; Lin, Si-Li1; Liu, Yu-Wei1; Cheng, Jun Kee1; Xiang, Shao-Hua1; Yu, Peiyuan1; Houk, Kendall N.2; Tan, Bin1

2023-12-01

10.1038/s41557-023-01384-x

NATURE CHEMISTRY   影响因子和分区

1755-4330

1755-4349

["The umpolung functionalization of imines bears vast synthetic potential, but polarity inversion is less efficient compared with the carbonyl counterparts. Strong nucleophiles are often required to react with the N-electrophiles without catalytic and stereochemical control. Here we show an effective strategy to realize umpolung of imines promoted by organocatalytic aromatization. The attachment of strongly electron-withdrawing groups to imines could enhance the umpolung reactivity by both electronegativity and aromatic character, enabling the direct amination of (hetero)arenes with good efficiencies and stereoselectivities. Additionally, the application of chiral Bronsted acid catalyst furnishes (hetero)aryl C-N atropisomers or enantioenriched aliphatic amines via dearomative amination from N-electrophilic aromatic precursors. Control experiments and density functional theory calculations suggest an ionic mechanism for the umpolung reaction of imines. This disconnection expands the options to forge C-N bonds stereoselectively on (hetero)arenes, which represents an important synthetic pursuit, especially in medicinal chemistry.","The umpolung functionalization of imines bears vast synthetic potential, but polarity inversion is less efficient compared with the carbonyl counterparts. Now, an alternative strategy exploiting chiral phosphoric acid catalytic aromatization has been developed, affording structures possessing a central chirality or a stereogenic C-N axis with high efficiency and enantiocontrol."]

SCI

英语

NI论文

第一 ; 通讯

National Science Foundation (NSF)["21825105","22231004","22271135"] ; National Natural Science Foundation of China["2022YFA1503703","2021YFF0701604"] ; National Key R&D Program of China[OCI-1053575] ; National Science Foundation[2019BT02Y335] ; Guangdong Innovative Program["KQTD20210811090112004","JCYJ20210324120205016","JCYJ20210324105005015"]

Chemistry

Chemistry, Multidisciplinary

WOS:001115920700001

NATURE PORTFOLIO

Web of Science

1.Southern Univ Sci & Technol, Shenzhen Grubbs Inst, Dept Chem, Shenzhen 518055, Peoples R China
2.Univ Calif Los Angeles, Dept Chem & Biochem, Los Angeles, CA 90095 USA

Chen, Ye-Hui,Duan, Meng,Lin, Si-Li,et al. Organocatalytic aromatization-promoted umpolung reaction of imines[J]. NATURE CHEMISTRY,2023.

Chen, Ye-Hui.,Duan, Meng.,Lin, Si-Li.,Liu, Yu-Wei.,Cheng, Jun Kee.,...&Tan, Bin.(2023).Organocatalytic aromatization-promoted umpolung reaction of imines.NATURE CHEMISTRY.

Chen, Ye-Hui,et al."Organocatalytic aromatization-promoted umpolung reaction of imines".NATURE CHEMISTRY (2023).