1918
N. Batail et al. / Tetrahedron Letters 52 (2011) 1916–1918
Table 2
Larock heteroannulation for 2,3-diphenylindoles via ligand free Pd/C catalysed coupling of diphenylacetylene with 2-bromoanilinesa
Ph
Ph
Pd/C (2 mol%)
Br
Na2CO3 (3 equiv.)
+
Ph
R1
R1
DMF, 140 °C
N
NH2
H
Ph
Entry
1
Aniline
T (d)
3
Conv.b (%)
Product
Yieldc (%)
Ph
Br
100
100
70
70
Ph
NH2
N
H
Ph
Me
Cl
Me
Cl
Br
2
3
3
6
71
55
Ph
N
NH2
H
Ph
Br
Ph
N
H
NH2
Ph
Br
Ph
4
10
50
—
N
H
NH2
Br
Br
a
b
c
Reaction conditions: 1 mmol 2-bromoaniline, 3 mmol alkyne, 2 mol % Pd/C, 3 equiv Na2CO3, 2 mL DMF, 140 °C.
Determined by GC with an internal standard (biphenyl, Drel
= 5%).
Isolated yield after flash chromatography on silica.
2. Bandini, M.; Eichholzer, A. Angew. Chem., Int. Ed. 2009, 48, 9608–9644.
3. Gribble, G. W. J. Chem. Soc., Perkin Trans. 1 2000, 1045–1075.
4. Humphrey, G. R.; Kuethe, J. T. Chem. Rev. 2006, 106, 2875–2911.
5. Cacchi, S.; Fabrizi, G. Chem. Rev. 2005, 105, 2873–2920.
the use of highly desactivated 2,6-bromoaniline that resulted in a
very low reaction rate as after 10 d only 50% of the starting aniline
was converted.
6. Ackermann, L.; Kaspar, L. T.; Gschrei, S. J. Chem. Commun. 2004, 2824–2825.
7. Ibarguren, O.; Zakri, C.; Fouquet, E.; Felpin, F. X. Tetrahedron Lett. 2009, 50,
5071–5074.
8. Joucla, L.; Djakovitch, L. Adv. Synth. Catal. 2009, 351, 673–714.
9. Joucla, L.; Batail, N.; Djakovitch, L. Adv. Synth. Catal. 2010, 352, 2929–2936.
10. Larock, R. C.; Yum, E. K. J. Am. Chem. Soc. 1991, 113, 6689–6690.
11. Larock, R. C.; Yum, E. K.; Refvik, M. D. J. Org. Chem. 1998, 63, 7652–7662.
12. Batail, N.; Bendjeriou, A.; Lomberget, T.; Barret, R.; Dufaud, V.; Djakovitch, L.
Adv. Synth. Catal. 2009, 351, 2055–2062.
In summary, we developed for the first time a regioselective in-
dole synthesis from 2-bromanilines and internal alkynes catalysed
by commercially available Pd/C catalyst without adding any ligand
or salt. The new protocol led to useful and high isolated yields (55–
95%) whatever the alkynes or bromoanilines engaged. We believe
that this highly practical procedure is very competitive with re-
spect to existing ones, particularly in the chemical industries
where economical considerations are concerned.
13. Batail, N.; Bendjeriou, A.; Djakovitch, L.; Dufaud, V. Appl. Catal., A: Gen. 2010,
388, 179–187.
14. Shen, M.; Li, G.; Lu, B. Z.; Hossain, A.; Roschangar, F.; Farina, V.; Senanayake, C.
H. Org. Lett. 2004, 6, 4129–4132.
Acknowledgement
15. Cui, X.; Li, J.; Fu, Y.; Liu, L.; Guo, Q.-X. Tetrahedron Lett. 2008, 49, 3458–3462.
16. Pd/C (10 wt % on dry basis) was purchased from Aldrich Chemical (E101 NE/W)
and is characterised by a low degree of reduction (XPS analyses) and high
water content (52%). Typical experimental procedure for the larock
heteroannulation: aryl bromide (1 mmol), alkyne (3 mmol), Na2CO3
(3 mmol), Pd/C (2 mo l%) and DMF (2 mL) were introduced in a sealed tube.
The reactor was placed under stirring in a preheated oil bath at 120 °C or
140 °C after being flushed by argon. The reaction completion was monitored by
GC. After cooling to room temperature, the reaction mixture was filtered
through a celite pad, which was washed with EtOAc (100 mL). The resulting
organic layer was then washed with Na2CO3 (2 ꢀ 40 mL) and brine (40 mL).
The organic layer was dried over Na2SO4 and the solvent was removed under
reduced pressure. If necessary (for the silylated compounds), the crude product
could be fully deprotected by treatment with HCl 1 M before being purified by
flash chromatography on silica.
The authors gratefully acknowledge the Région Rhône-Alpes,
Programme CIBLE-2007 (Contract number 07 016376 01/02/03)
for the financial support.
Supplementary data
Supplementary data (general information, typical experimental
procedure for the Larock heteroannulation, physical properties of
isolated compounds, copy of 1H and 13C NMR spectra and copy of
MS spectra are available) associated with this article can be found,
17. Maassarani, F.; Pfeffer, M.; Le Borgne, G. Organometallics 1987, 6, 2029–2043.
References and notes
1. De Sa Alves, F. R.; Barreiro, E. J.; Manssour Fraga, C. A. Mini-Rev. Med. Chem.
2009, 9, 782–793.