Synthesis of tetrahydroisoquinolines
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 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.