Categories: Synthesis of N-Heterocycles > benzo-fused N-Heterocycles >
Synthesis of azaindoles
Recent Literature
An efficient protecting-group-free two-step route to a broad range of aza- and
diazaindoles was established, starting from chloroamino-N-heterocycles.
The method involves an optimized Suzuki-Miyaura coupling with
(2-ethoxyvinyl)borolane followed by acetic acid-catalyzed cyclization.
D. K. Whelligan, D. W. Thomson, D. Taylor, S. Hoelder, J. Org. Chem., 2010,
75, 11-15.
An effective reductive alkylation of electron-deficient o-chloroarylamines
was developed. The derived N-alkylated o-chloroarylamines were
elaborated to N-alkylazaindoles and N-alkylindoles via a novel
one-pot process comprising copper-free Sonogashira alkynylation and a
base-mediated indolization reaction.
M. McLaughlin, M. Palucki, I. W. Davies, Org. Lett.,
2006, 8, 3307-3310.
A practical and straightforward preparation of various novel 2-substituted
7-azaindole derivatives from 2-amino-3-iodopyridine by a two-step procedure is
described that gives the desired compounds in good overall yields.
M. C. de Mattos, S. Alatorre-Santamaría, V. Gotor-Fernández, V. Gotor, Synthesis, 2007,
2149-2152.
Silver-catalyzed on-water intramolecular cyclization of acetylenic free amines
affords 7-azaindoles or indoles in very good yields. Neither strong base/acid
catalysts nor N-substituted substrates are required. Hydrogen bonds between
water and the substrates play an important role in improving chemical reactivity
and regioselectivity.
H. Sun, L. Xiao, W. Li, Q. Xie, L. Shao, Synthesis, 2017,
49, 4845-4852.
Site-selective Pd-catalyzed Sonogashira reactions of 3,4-dibromopyridine with
alkynes, followed by Pd-catalyzed tandem C-N couplings and cyclizations with
amines provide 6-azaindoles in very good yield. On the other hand, a 5-azaindole
is obtained by a site-selective Pd-catalyzed C-N coupling reaction of
3,4-dibromopyridine with 4-toluidine, followed by C-C coupling and cyclization
with phenylacetylene.
N. T. Son, T. A. N. Tien, M. B. Ponce, P. Ehlers, N. T. Thuan, T. T. Dang, P.
Langer, Synlett, 2020,
31,
1308-1312.
A new, mild, and efficient method for the synthesis of polyfunctionalized
indoles by direct reaction of substituted 2-chloroanilines with cyclic or
acyclic ketones was developed. This procedure is simple to carry out and
broadly applicable.
M. Nazare, C. Schneider, A. Lindenschmidt, D. W. Will, Angew. Chem. Int. Ed.,
2004, 43, 4526-4528.
A robust and flexible synthesis of 1,3- and 1,3,6-substituted 7-azaindoles
is presented starting from nicotinic acid derivatives or
2,6-dichloropyridine, respectively. Microwave heating dramatically
accelerates the penultimate reaction step, an
epoxide-opening-cyclization-dehydration sequence.
H. Schirok, J. Org. Chem., 2006, 71, 5538-5545.
An imino-Stetter reaction of 2-aminoazacinnamic acid derivatives and aryl
aldehydes provides 2-aryl-substituted azaindole-3-acetic acid derivatives in
good yields. A condensation of 2-aminoazacinnamic acid derivatives with
aldehydes is followed by treatment with cyanide to yield the desired
2-aryl-substituted azaindole-3-acetic acid derivatives.
T. Kim, J. H. Park, C. Jeong, E. Park, J. M. Kim, Y.-J. Kim, J.-N. Heo, C.-H.
Cheon, Synthesis, 2024,
56, 860-870.