Categories: Synthesis of N-Heterocycles > benzo-fused N-Heterocycles >
Synthesis of tetrahydroisoquinolines
An intramolecular Friedel-Crafts cyclization of an in situ generated tosylate intermediate enables an efficient construction of 3-substituted 1,2,3,4-tetrahydroisoquinolines from N,N-dibenzyl-α-aminols.
S. Chandrasekhar, P. K. Mohanty, K. Harikishan, P. K. Sasmal, Org. Lett., 1999, 1, 877-879.
Arene/Ru/TsDPEN complexes bearing a heterocyclic group catalyze the asymmetric transfer hydrogenation (ATH) of 1-aryl dihydroisoquinolines (DHIQs) to provide tetrahydroisoquinolines of high enantiomeric excess.
J. Barrios-Rivera, Y. Xu, Martin Wills, Org. Lett., 2020, 22, 6283-6287.
Irradiation of blue light enables a low cost and heavy-metal-free decarboxylative alkylation of benzylic C(sp3)-H bonds of N-aryl tetrahydroisoquinolines under mild conditions.
L. Ren, H. Cong, Org. Lett., 2018, 20, 3225-3228.
An efficient CuCl2-catalyzed coupling of nonfunctionalized tetrahydroisoquinolines with organozinc reagents under aerobic conditions proceeds in high yields under mild reaction conditions and is broadly applicable to a wide range of substrates. The reaction involves an iminium ion intermediate that is formed via a SET process.
T. Wang, M. Schrempp, A. Berndhäuser, O. Schiemann, D. Menche, Org. Lett., 2015, 17, 3982-3985.
An oxidative C1 arylation of tetrahydroisoquinolines with aryl Grignard reagents is mediated by diethyl azodicarboxylate (DEAD). This C-H activation under metal-free conditions delivers target compounds, including some naturally occurring alkaloids, in good yields.
K. N. Singh, S. V. Kessar, P. Singh, P. Singh, M. Kaur, A. Batra, Synthesis, 2014, 46, 2644-2650.
Microwave-assisted Bischler-Napieralski or Pictet-Spengler reactions allowed the production of substituted isoquinoline libraries. The generated dihydroisoquinolines and tetrahydroisoquinolines could be oxidized to their corresponding isoquinoline analogues. A more practical and efficient route to C1- and C4-substituted isoquinolines involves the preparation and activation of isoquinolin-1(2H)-ones.
E. Awuah, A. Capretta, J. Org. Chem., 2010, 75, 5627-5634.
An electron donor-acceptor complex-initiated α-cyanation of tertiary amines proceeds smoothly without the presence of photocatalysts and transition metal catalysts to provide various α-amino nitriles under mild conditions.
Q. Xia, Y. Li, L. Cheng, X. Liang, C. Cao, P. Dai, H. Deng, W. Zhang, Q. Wang, Org. Lett., 2020, 22, 9638-9643.