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Synfacts 2025; 21(01): 11
DOI: 10.1055/a-2467-5646
Synthesis of Heterocycles

Synthesis of Tetrahydroquinolines from Arylaminomenthyl Cyclopropanes

Contributor(s):
Mark A. Reed
,
Meng Zhao (Paraza Pharma)
Devaraj T, Srinivasan K *. Bharathidasan University, Tiruchirappalli, India
Ytterbium Triflate-Catalyzed Intramolecular Arylative Ring Opening of Arylaminomethyl-Substituted Donor−Acceptor Cyclopropanes: Access to Tetrahydroquinolines.

J. Org. Chem. 2024;
89: 13886-13893
DOI: 10.1021/acs.joc.4c00924
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Keywords

tetrahydroquinolines - cyclopropanes - ytterbium triflate catalysis

Significance

Tetrahydroquinoline is a key heterocyclic scaffold found in various natural products, including aspernigerin, dynemicin A, martinelline, and virantmycin. Therefore, numerous strategies have already been explored for their synthesis. In this article, authors presented a novel approach for the synthesis of tetrahydroquinolines using donor–acceptor cyclopropanes (DACs) 3. The synthesis yielded the products 4 as single diastereomers.


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Comment

The starting material 3 was synthesized by reacting cinnamaldehydes with diethyl bromomalonate, followed by reductive amination with N-substituted anilines 2. The catalyst, Yb(OTf)3, was optimized to provide the best product yield for 4a. The reaction scope was explored using DACs with different substituents on aromatic rings (4b−n). Electron-withdrawing (4c,e,l), electron-donating (4b,d,k), and halogen (4f,h,i,m) substituents furnished the desired products in good yields, however, the one with bromo-substituent gave only 30 % yield (4 h). Unfortunately, N-unsubstituted DACs were not successful (4o).


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Publication History

Article published online:
20 December 2024

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