Categories: Synthesis of N-Heterocycles >
Synthesis of isoquinolines
Recent Literature

Reaction of N-carbamoyl-functionalized enamine derivatives with benzyne
affords substituted indolines. An orthogonal reactivity is uncovered when
related enamine derivatives are modified as amides, such that isoquinolines are
formed as the product of condensation with benzyne.
C. D. Gilmore, K. M. Allan, B. M. Stoltz, J. Am. Chem. Soc., 2008,
130, 1558-1559.

CuI-catalyzed coupling of 2-halobenzylamines with β-keto esters or 1,3-diketones
in i-PrOH in the presence of of K2CO3 produced
1,2-dihydroisoquinolines as the cyclization products, which underwent smooth
dehydrogenation under air atmosphere to afford substituted isoquinolines.
B. Wang, B. Lu, Y. Jiang, Y. Zhang, D. Ma, Org. Lett.,
2008,
10, 2761-2763.

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.

Ag-catalyzed cyclization of 2-alkynyl benzyl azides offers an efficient method for the synthesis of substituted isoquinolines. The reaction
proceeds smoothly in good yields and tolerates various functional groups.
Y.-N. Niu, Z.-Y. Yan, G.-L. Gao, H.-L. Wang, X.-Z. Shu, K-G. Ji, Y.-M. Liang, J. Org. Chem., 2009,
74, 2893-2896.

The reaction of 2-alkynyl-1-methylene azide aromatics with iodium donors gave
1,3-disubstituted 4-iodoisoquinolines in good yields. Electron-donating and
withdrawing substituents on the aromatic ring were equally tolerated. At the
alkyne terminus, electron-neutral or donating substituents are clearly favored.
A short synthesis of norchelerythrine is described.
D. Fischer, H. Tomeba, N. K. Pahadi, N. T. Patil, Z. Huo, Y. Yamamoto, J. Am. Chem. Soc., 2008,
130, 15720-15725.

Readily available 2-azido-3-arylacrylates react with α-diazocarbonyl compounds
and triphenylphosphine to furnish isoquinolines in good yields. The efficient
and general procedure involves a Wolff rearrangement, an aza-Wittig reaction,
and an electrocyclic ring closure.
Y.-Y. Yang, W.-G. Shou, Z.-B. Chen, D. Hong, Y.-G. Wang, J. Org. Chem., 2008,
73, 3928-3930.

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.
