Simple Tandem Olefin Isomerization/Intramolecular Hydroamination of Alkenyl Amines with Various Allylic Tethers
Young Ho Kim, Dong Bin Kim and So Won Youn*
*Center for New Directions in Organic Synthesis, Department of Chemistry and Research Institute for Natural Sciences, Hanyang University, Seoul 04763, Korea,
Email: sowony73hanyang.ac.kr
Y. H. Kim, D. B. Kim, S. W. Youn, J. Org. Chem., 2022, 87, 11919-11924.
DOI: 10.1021/acs.joc.2c01640
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Abstract
An operationally simple and efficient AgOTf-promoted tandem olefin isomerization/intramolecular hydroamination of 1,1-disubstituted alkenyl amines provides diverse 2-alkyl-substituted 1,3-X,N-heterocycles in very good yields through chemo- and regioselective C(sp3)-N bond formation with high atom economy. The reaction offers high functional group tolerance and broad substrate scope.
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proposed mechanism
Details
The document discusses a study on a simple and efficient AgOTf-promoted tandem olefin isomerization/intramolecular hydroamination of 1,1-disubstituted alkenyl amines. This one-pot process is a facile route for synthesizing diverse 2-alkyl-substituted 1,3-X,N-heterocycles through chemo- and regioselective C(sp3)−N bond formation with atom economy. The method uses a readily available catalyst under aerobic conditions, yielding good to excellent chemical results with high functional group tolerance and broad substrate scope. The study highlights the advantages of using simple catalytic systems and the absence of additional strong acids. Optimization studies showed AgOTf as the most effective catalyst, providing high yields and efficiency. The substrate scope was explored, revealing that various functional groups and tethers (X = O, NR″, S) were well tolerated, producing diverse heterocycles. Mechanistic studies suggested the involvement of TfOH generated in situ from AgOTf, with a proposed mechanism involving olefin isomerization followed by intramolecular hydroamination. The method demonstrates significant synthetic potential, offering a practical and efficient approach to constructing heterocycles found in bioactive natural products, pharmaceuticals, and functional molecules.
General Procedure for AgOTf-Promoted Tandem Olefin Isomerization/Hydroamination
Substrate (0.189 - 3.171 mmol, 1 equiv) and AgOTf (2 - 20 mol%) were dissolved in ClCH2CH2Cl (1.9~31.7 ml, 0.1 M). The resulting mixture was stirred at 80 - 120 °C for the reported time under aerobic conditions (in a closed vial with a screw cap). After the reaction was completed, the reaction mixture was concentrated in vacuo. The residue was purified by column chromatography on silica gel (EtOAc : n-Hexane = 1:3, 1:5, 1:6, 1:8, or 1:10) to give the corresponding product. All reactions were carried out 2-3 times repetitively and the average values of yields are given.
Key Words
benzo-fused N-heterocycles, benzo-fused S-heterocycles, oxazolidines, benzoxazolines
ID: J42-Y2022