Organometallics
Article
Lab, Department of Chemistry and Biochemistry, University of
Wisconsin−Milwaukee (Milwaukee, WI, USA). Elemental analyses
were performed at the Midwest Microlab (Indianapolis, IN, USA).
General Procedure for the Catalytic Synthesis of Indole and
Quinoline Products. In a glovebox, complex 2 (13 mg, 0.75 mol %)
and HBF4·OEt2 (12 mg, 7 mol %) were dissolved in 1,4-dioxane (1
mL) in a 25 mL Schlenk tube equipped with a Teflon stopcock and a
magnetic stirring bar. The resulting mixture was stirred for 5 to 10 min
until the solution turned to a pale green color. In an alternative
procedure, complex 1 (17 mg, 3 mol %) and HBF4·OEt2 (12 mg, 7
mol %) were dissolved in 1,4-dioxane (1 mL). An arylamine (1.0
mmol), a diol (1.5 mmol), cyclopentene (204 mg, 3 equiv), and 1,4-
dioxane (2 mL) were added to the reaction tube. After the tube was
sealed, it was brought out of the glovebox and was stirred in an oil bath
set at 110−130 °C (130−150 °C for the quinoline products) for 14 h.
The reaction tube was taken out of the oil bath and was cooled to
room temperature. After the tube was open to air, the solution was
filtered through a short silica gel column by eluting with CH2Cl2 (10
mL), and the filtrate was analyzed by GC-MS. Analytically pure
product was isolated by a simple column chromatography on silica gel
(280−400 mesh, hexanes/EtOAc).
ation of diol to α-hydroxy ketone and the subsequent ortho-
arene C−H activation and annulation processes.
On the basis of these results, we present a plausible
mechanistic hypothesis for the coupling reaction of aniline
with a 1,2-diol (Scheme 1). As observed in the control
Scheme 1. Plausible Mechanistic Pathway for the
Dehydrative Coupling of Aniline with a 1,2-Diol
ASSOCIATED CONTENT
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experiments, we propose the initial dehydrogenation of diol
substrate followed by the dehydrative coupling of aniline with
the resulting α-hydroxy ketone, which would lead to the
formation of an α-hydroxyimine intermediate product 6. The
subsequent ortho-arene C−H metalation followed by the
dehydrative C−O bond cleavage and the reductive annulation
steps would form the indole product 3, in a similar fashion to
the dehydrative C−H insertion reactions of phenols.10 The
requisite ortho-metalation and dehydration steps would be
promoted by an electrophilic Ru-hydroxo species 7. We
recently showed that Ru-hydroxo complexes are a key
intermediate species in ketone hydrogenolysis reaction.15 Late
metal-hydroxo and -phenoxo complexes have also been found
to mediate a number of C−O cleavage reactions.16 In addition,
the formation of N-alkylated product 5 can be readily explained
by invoking a competitive hydrogenolysis pathway especially in
the case for the coupling of an electron-poor aniline with a 1,3-
diol substrate. Our mechanistic hypothesis not only can explain
the observed regioselectivity pattern on the indole product 3
but also is supported by both control experiments as well as the
literature precedents on the alcohol dehydrogenation reac-
tion.14,17
S
* Supporting Information
The Supporting Information is available free of charge on the
Experimental procedures and NMR spectra of organic
AUTHOR INFORMATION
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Corresponding Author
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
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The authors gratefully acknowledge financial support from the
National Science Foundation (CHE-1358439) and National
Institute of Health General Medical Sciences (R15
GM109273).
REFERENCES
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CONCLUSION
(1) Recent reviews on the catalytic C−H coupling methods directed
to the synthesis of nitrogen heterocycles: (a) Yeung, C. S.; Dong, V.
M. Chem. Rev. 2011, 111, 1215−1292. (b) Girard, S. A.; Knauber, T.;
Li, C.-J. Angew. Chem., Int. Ed. 2014, 53, 74−100. (c) Ye, B.; Cramer,
N. Acc. Chem. Res. 2015, 48, 1308−1318.
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In summary, the cationic ruthenium-hydride complex was
found to be an effective catalyst precursor for the dehydrative
coupling of anilines with 1,2- and 1,3-diols to form substituted
indole and quinoline products. The catalytic method employs
readily available arylamine and diol substrates, exhibits high
activity toward substituted anilines, and does not require any
reactive reagents or generate any toxic byproducts.
(2) Selected reviews on the synthesis of indole and related nitrogen
heterocycles: (a) Ranu, B. C. Eur. J. Org. Chem. 2000, 2000, 2347−
2356. (b) Cacchi, S.; Fabrizi, G. Chem. Rev. 2005, 105, 2873−2920.
(c) Kruger, K.; Tillack, A.; Beller, M. Adv. Synth. Catal. 2008, 350,
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2153−2167. (d) Inman, M.; Moody, C. J. Chem. Sci. 2013, 4, 29−41.
(3) (a) Zeni, G.; Larock, R. C. Chem. Rev. 2006, 106, 4644−4680.
(b) Shi, Z.; Zhang, C.; Li, S.; Pan, D.; Ding, S.; Cui, Y.; Jiao, N. Angew.
Chem., Int. Ed. 2009, 48, 4572−4576. (c) Shi, Z.; Glorius, F. Angew.
Chem., Int. Ed. 2012, 51, 9220−9222. (d) Platon, M.; Amardeil, R.;
Djakovitch, L.; Hierso, J.-C. Chem. Soc. Rev. 2012, 41, 3929−3968.
EXPERIMENTAL SECTION
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General Information. All operations were carried out in a
nitrogen-filled glovebox or by using standard high-vacuum and Schlenk
techniques unless otherwise noted. Solvents were freshly distilled over
appropriate drying reagents. All organic substrates were received from
commercial sources and were used without further purification. The
́ ́
(4) (a) Lerchen, A.; Vasquez-Cespedes, S.; Glorius, F. Angew. Chem.,
2
1H, H, 13C, and 31P NMR spectra were recorded on a Varian 300 or
Int. Ed. 2016, 55, 3208−3211. (b) Liang, Y.; Jiao, N. Angew. Chem., Int.
Ed. 2016, 55, 4035−4039. (c) Kong, L.; Yu, S.; Zhou, X.; Li, X. Org.
400 MHz FT-NMR spectrometer. Mass spectra were recorded on an
Agilent 6850 GC-MS spectrometer with an HP-5 (5% phenyl-
methylpolysiloxane) column (30 m, 0.32 mm, 0.25 μm). High-
resolution mass spectra were obtained at the Mass Spectrometry/ICP
́
Lett. 2016, 18, 588−591. (d) Wang, H.; Moselage, M.; Gonzalez, M. J.;
Ackermann, L. ACS Catal. 2016, 6, 2705−2709. (e) Zhang, Z.-Z.; Liu,
B.; Xu, J.-W.; Yan, S.-Y.; Shi, B.-F. Org. Lett. 2016, 18, 1776−1779.
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