Categories: Synthesis of N-Heterocycles > benzo-fused N-Heterocycles >
Synthesis of azaindoles
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.