Organic Letters
Letter
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and 6p (60%) were prepared. All possess a N-4-chlorophenyl
group and different substituents at C2: phenyl, 4-CN-phenyl, 4-
OMe-phenyl, and 3,5-di-OMe-phenyl, respectively (Scheme 3).
The highest yield was obtained for 6o, and indeed, when a
chlorine atom is present at the N-aryl moiety along with an EWG
at the phenylacetylene moiety, higher conversions were
observed.
To expand the applicability of the approach, alkyl substituents
at C2 were tested. Azaindoles 6q (54%) and 6r (45%) were
prepared highlighting the versatility of the method.
In summary, we have developed the first one-pot reaction to
access all four 1,2-diaryl azaindoles isomers from available amino-
o-bromopyridines. This approach, involving N-arylation/Sono-
gashira/cyclization reaction, proved to be versatile and
compatible with both an EWG and EDG at both the
phenylacetylene and aryl iodide. Moreover, difficulties associated
with the challenging N-arylation of 2-aryl azaindoles were
overcome. Furthermore, the approach proved to be compatible
with C-2 alkyl substituents.
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ASSOCIATED CONTENT
* Supporting Information
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́
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2013, 69, 4767−4834.
The Supporting Information is available free of charge on the
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Experimental details, compound characterization data for
all isolated compounds, and NMR spectra (PDF)
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AUTHOR INFORMATION
(17) Pham, N. N.; Dang, T. T.; Ngo, N. T.; Villinger, A.; Ehlers, P.;
Langer, P. Org. Biomol. Chem. 2015, 13, 6047−6058.
(18) Cullen, M. H. S.; Geng, B.; Foley, M.; Bastos, C. M.; Munoz, B.;
Haeberlein, M. Proteasome activity enhancing compounds
WO2015073528, 2015.
■
Corresponding Author
ORCID
(19) Qian, G.; Hong, X.; Liu, B.; Mao, H.; Xu, B. Org. Lett. 2014, 16,
Author Contributions
5294−5297.
(20) Pires, M. J. D.; Poeira, D. L.; Purificaca̧ o, S. I.; Marques, M. M. B.
̃
‡M.J.D.P. and S.I.P. have contributed equally.
Org. Lett. 2016, 18, 3250−3253.
(21) Carvalho, L. C. R.; Pires, M. J. D.; Fernandes, E.; Marques, M. M.
B. RSC Adv. 2013, 3, 25711−25715.
Notes
The authors declare no competing financial interest.
(22) Carvalho, L. C. R.; Ribeiro, D.; Seixas, R. S. G. R.; Silva, A. M. S.;
Nave, M.; Martins, A. C.; Erhardt, S.; Fernandes, E.; Cabrita, E. J.;
Marques, M. M. B. RSC Adv. 2015, 5, 49098−49109.
(23) Marelli, E.; Corpet, M.; Minenkov, Y.; Neyyappadath, R. M.;
Bismuto, A.; Buccolini, G.; Curcio, M.; Cavallo, L.; Nolan, S. P. ACS
Catal. 2016, 6, 2930−2938.
ACKNOWLEDGMENTS
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We thank to the FC&T for fellowship SFRH/BD/89518/2012.
This work was supported by the Associated Laboratory for
Sustainable Chemistry-Clean Processes and Technologies-
LAQV which is financed by national funds from FCT/MEC
(UID/QUI/50006/2013) and cofinanced by the ERDF under
the PT2020 Partnership Agreement (POCI-01-0145-FEDER-
007265). The NMR spectrometers are part of The National
NMR Facility, supported by FC&T (RECI/BBB-BQB/0230/
2012).
(24) Pires, M. J. D.; Poeira, D. L.; Marques, M. M. B. Eur. J. Org. Chem.
2015, 7197−7234.
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