Categories: Synthesis of N-Heterocycles > benzo-fused N-Heterocycles >
Synthesis of 3,4-dihydroisoquinolines
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.
Tf2O promotes a Bischler-Napieralski-type synthesis of 3,4-dihydroisoquinolines from phenylethanols and nitriles via a tandem annulation, in which a phenonium ion as a stable and reactive primary phenylethyl carbocation is formed.
L. Min, W. Yang, Y. Weng, W. Zheng, X. Wang, Y. Hu, Org. Lett., 2019, 21, 2574-2577.
The direct conversion of various amides to isoquinoline and β-carboline derivatives via mild electrophilic amide activation, with trifluoromethanesulfonic anhydride in the presence of 2-chloropyridine followed by cyclodehydration upon warming provides the desired products with short overall reaction times.
M. Movassaghi, M. D. Hill, Org. Lett., 2008, 10, 3485-3488.
Elimination of the amide group as the nitrile via retro-Ritter reaction is avoided in a modified Bischler-Napieralski procedure by its conversion to an N-acyliminium intermediate with oxalyl chloride-FeCl3. Removal of the oxalyl group in refluxing MeOH-sulfuric acid provides 3,4-dihydroisoquinolines in good yields.
R. D. Larsen, R. A. Reamer, E. G. Corley, P. Davis, E. J. J. Grabowski, P. J. Reider, I. Shinkai, J. Org. Chem., 1991, 56, 6034-6038.
α-Azido carbonyl compounds bearing a 2-alkenylaryl moiety at the α-position are promising precursors for synthesis of isoindole and isoquinoline derivatives via 1,3-dipolar cycloaddition of azides onto alkenes and 6π-electrocyclization of N-H imine intermediates, respectively.
B. W.-Q. Hui, S. Chiba, Org. Lett., 2009, 11, 729-732.