Synthesis of tetrahydroquinolines
A chiral phosphoric acid as the sole catalyst enables an enantioselective synthesis of tetrahydroquinolines from 2-aminochalcones via chiral phosphoric acid-catalyzed dehydrative cyclization, followed by chiral phosphoric acid-catalyzed asymmetric reduction with Hantzsch ester. Various 2-aminochalcones could be applicable to this protocol, and the desired tetrahydroquinolines were obtained in excellent yields and with excellent enantioselectivities.
D. Y. Park, S. Y. Lee, J. Jeon, C.-H. Cheon, J. Org. Chem., 2018, 83, 12486-12495.
A highly efficient gold-catalyzed tandem hydroamination/asymmetric transfer hydrogenation provides tetrahydroquinolines in excellent yields and enantioselectivities in the presence of a chiral phosphate. In this reaction, the gold catalyst acts as a π-Lewis acid in the hydroamination step and as an effective chiral Lewis acid in the asymmetric hydrogen-transfer.
Y.-L. Du, Y. Hu, Y.-F. Zhu, X.-F. Tu, Z.-Y. Han, L.-Z. Gong, J. Org. Chem., 2015, 80, 4754-4759.
Consecutive hydroamination/asymmetric transfer hydrogenation under relay catalysis of an achiral gold complex/chiral Brønsted acid binary system allows a direct transformation of 2-(2-propynyl)aniline derivatives into tetrahydroquinolines with high enantiomeric purity.
Z.-Y. Han, H. Xiao, X.-H. Chen, L.-Z. Gong, J. Am. Chem. Soc., 2009, 131, 9182-9183.
An environmentally friendly iridium-catalyzed direct cyclization of N-methylanilines with 1,3-propanediol provides tetrahydroquinolines with water as the sole by-product. Under similar reaction conditions, direct cyclization of anilines with 1,3-propanediol produced tetrahydrobenzoquinolizines.
M. Minakawa, K. Watanabe, S. Toyoda, Y. Uozumi, Synlett, 2018, 29, 2385-2389.
A ligand- and base-free silver-catalyzed reduction of quinolines provides a facile, environmentally friendly, and practical access to various 1,2,3,4-tetrahydroquinoline derivatives at room temperature. Mechanistic studies revealed that the effective reducing species was Ag-H.
Y. Wang, B. Dong, Z. Wang, X. Cong, X. Bi, Org. Lett., 2019, 21, 3631-3634.
The use of unsupported nanoporous gold (AuNPore) as a catalyst and organosilane with water as a hydrogen source enables a highly efficient and regioselective hydrogenation of quinoline derivatives to 1,2,3,4-tetrahydroquinolines. The AuNPore catalyst can be readily recovered and reused without any loss of catalytic activity.
M. Yan, T. Jin, Q. Chen, H. E. Ho, T. Fujita, L.-Y. Chen, M. Bao, M.-W. Chen, N. Asao, Y. Yamamoto, Org. Lett., 2013, 15, 1484-1487.
B(C6F5) enables a metal-free hydrogenative reduction of substituted N-heteroaromatics using hydrosilanes as reducing agents. The optimized conditions were successfully applied to quinolines, quinoxalines, and quinoline N-oxides. The initial step in the catalytic cycle involves 1,4-addition of the hydrosilane to the quinoline to give a 1,4-dihydroquinoline followed by (transfer) hydrogenation to deliver the tetrahydroquinoline.
N. Gandhamsetty, S. Park, S. Chang, Synlett, 2017, 28, 2396-2400.
Upon activation with trifluoromethanesulfonyl anhydride, secondary N-arylamides undergo smooth intermolecular dehydrative [4 + 2] aza-annulation with alkenes under mild conditions to give 3,4-dihydroquinolines, amenable to further functionalization. The use of NaBH4 or DDQ in a subsequent step enables the synthesis of tetrahydroquinolines or quinolines, respectively.
Y.-H. Huang, S.-R. Wang, D.-P. Wu, P.-Q. Huang, Org. Lett., 2019, 21, 1681-1685.
A three-component Povarov reaction of aldehydes, anilines, and benzyl N-vinylcarbamate in the presence of 0.1 equiv of a chiral phosphoric acid afforded cis-2,4-disubstituted tetrahydroquinolines in good yields and excellent enantiomeric excesses. This three-component reaction enables a very short synthesis of torcetrapib.
H. Liu, G. Dagousset, G. Masson, P. Retailleau, J. Zhu, J. Am. Chem. Soc., 2008, 131, 4598-4599.
A chiral BINOL-derived phosphoric acid diester catalyzed an inverse electron-demand aza Diels-Alder reaction of aldimine with enol ethers to give tetrahydroquinoline derivatives with excellent enantioselectivity.
T. Akiyama, H. Morita, K. Fuchibe, J. Am. Chem. Soc., 2006, 128, 13070-13071.