Ruthenium(II)-Catalyzed C?H Activation of Imidamides and Divergent Couplings with Diazo Compounds: Substrate-Controlled Synthesis of Indoles and 3H-Indoles

Article abstract of DOI:10.1002/anie.201606316

Indoles are an important structural motif that is commonly found in biologically active molecules. In this work, conditions for divergent couplings between imidamides and acceptor–acceptor diazo compounds were developed that afforded NH indoles and 3H-ind

Full text of DOI:10.1002/anie.201606316

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International Edition: DOI: 10.1002/anie.201606316
German Edition: DOI: 10.1002/ange.201606316
À
C H Activation
À
Ruthenium(II)-Catalyzed C H Activation of Imidamides and
Divergent Couplings with Diazo Compounds: Substrate-Controlled
Synthesis of Indoles and 3H-Indoles
Yunyun Li, Zisong Qi, He Wang, Xifa Yang, and Xingwei Li*
Abstract: Indoles are an important structural motif that is
commonly found in biologically active molecules. In this work,
conditions for divergent couplings between imidamides and
acceptor–acceptor diazo compounds were developed that
afforded NH indoles and 3H-indoles under ruthenium catal-
ysis. The coupling of a-diazoketoesters afforded NH indoles by
À
cleavage of the C(N2) C(acyl) bond whereas a-diazomalo-
À
nates gave 3H-indoles by C N bond cleavage. This reaction
constitutes the first intermolecular coupling of diazo substrates
À
Scheme 1. Arene C H activation and intermolecular coupling with
diazo compounds.
À
with arenes by ruthenium-catalyzed C H activation.
I
ndoles are ubiquitously found in a diverse array of
biologically active molecules.[1] Thus the synthesis of indoles[2]
has attracted widespread interest. In particular, 3H-indoles
exhibit excellent pharmacological properties, including anti-
bacterial, antifungal, anti-inflammatory, and antiviral activ-
ity.[3] Their significance in pharmacology has called for the
development of more efficient synthetic methods. However,
most of the reported methods require highly functionalized
starting materials and suffer from low atom economy and
harsh reaction conditions.[4] It is thus highly desirable to
develop cost-effective and efficient methods to access indoles
and 3H-indoles.
ner is mostly limited to alkenes, alkynes, aryl/alkyl halides,
isocyanates, allyl sources, and amidating reagents, among
others.[13] Whereas Che, Yu, and co-workers have reported
RuII-catalyzed intramolecular carbenoid insertion reactions
À
into C H bonds that proceeded by an outer-sphere mecha-
nism,[14] to the best of our knowledge, the combination of
II
À
Ru -catalyzed arene C H activation and intermolecular
coupling with diazo compounds has remained underexplored.
We reasoned that the reactivity of a Ru C bond towards an
electrophile might also parallel and even exceed that of the
RhIII counterparts.[13k,l] We now report the facile construction
of 2,3-disubstituted NH indoles and 3H-indoles by RuII-
II
À
À
Over the past decades, transition-metal-catalyzed C H
À
bond activation has emerged as a powerful synthetic strat-
catalyzed C H activation of imidamides and coupling with
egy.[5] Recently, metal-catalyzed carbenoid functionalization
diazo compounds.
À
has been increasingly employed for C C bond formation,
We initiated our studies by screening the reaction
parameters of the coupling of N-phenylacetimidamide (1a)
and ethyl a-diazoacetoacetate (2a; Table 1).[15] Using [Ru(p-
cymene)Cl2]2/AgSbF6 as the catalyst, indole 3aa was isolated
in 64% yield (808C, entry 1). The yield was slightly reduced in
the absence of CsOAc (entry 3). When cobalt(III) catalysts
were employed, the desired reaction did not occur (entries 4
and 5). With AcOH as an additive (2.0 equiv), the yield was
significantly improved to 91% (entry 7) whereas other acid
additives (PivOH and MesCO2H) were less efficient
(entries 8 and 9). Lowering the catalyst loading to 2 mol%
resulted in diminished yield (entry 10). The effect of the
reaction temperature was then explored, and coupling at
408C or higher temperatures gave comparable results
(entries 11 and 12).
With optimized reaction conditions in hand (condi-
tions A), we then explored the scope and generality of this
coupling (Scheme 2). Acetimidamides bearing various elec-
tron-donating, -withdrawing, or halogen substituents at the
para position of the N-aryl ring all reacted smoothly with 2a,
affording various NH indoles in 63–96% yield (3ba–3ia).
Acetimidamides bearing meta halogen substituents also
afforded the corresponding products in good yields with
II
III
III
III
À
especially by Pd -, Rh -, Co -, and Ir -catalyzed C H
activation of arenes in the presence of a directing group (DG;
Scheme 1).[6] In particular, Yu and co-workers disclosed the
III
À
first Rh -catalyzed intermolecular insertion of C(aryl) H
bonds into diazo compounds.[6g] Following this report, the
groups of Glorius,[7] Ackermann,[8] Wang,[9] Chang,[10] and
others[11] have made significant progress in the construction of
heterocycles by such approaches.
On the other hand, ruthenium(II) complexes have been
À
shown to efficiently catalyze arene C H activation with
outstanding cost efficiency.[5c,12] However, the coupling part-
[*] Y. Li, Dr. Z. Qi, Dr. H. Wang, X. Yang, Prof. X. Li
Dalian Institute of Chemical Physics
Chinese Academy of Sciences
Dalian 116023 (China)
E-mail: xwli@dicp.ac.cn
Y. Li, X. Yang
University of Chinese Academy of Sciences
Beijing 100049 (China)
Supporting information for this article can be found under:
http://dx.doi.org/10.1002/anie.201606316.
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Table 1: Optimization studies.[a]
N-Aryl benzimidamides with different substituents on the
À
N-aryl ring were also coupled successfully, and C H activa-
tion occurred exclusively at the N-aryl ring (3ra–3va). The
C substituent of the imidamide was also extended to other
primary, secondary, and tertiary (cyclo)alkyl substituents, and
the corresponding products were obtained in consistently
high yields (3wa–3eaa). The scope of a-diazoketoesters was
examined with 1a, and they were all converted into the
desired products in good yields (3ab–3ad). Furthermore,
symmetric a-diazoacetylacetone delivered indole 3ae in 46%
yield (808C). Decreasing the catalyst loading to 2 mol% was
attempted for several substrates (3aa, 3ea, and 3ra), and the
yields were not significantly affected. In line with previous
reports on the RhIII-catalyzed system,[15] coupling 1a with
different diazo esters 2 f–2i afforded the same product 3aa
[Eq. (1)], and PhC(O)NH2 was detected as a byproduct for
Entry
Catalyst (mol%)
Additive
T [8C]
Yield [%][b]
1
2[c]
3[d]
4
[Ru(p-cymene)Cl2]2 (4)
[Ru(p-cymene)Cl2]2 (4)
[Ru(p-cymene)Cl2]2 (4)
[Cp*CoI2CO] (8)
–
–
–
–
–
–
80
80
80
80
80
80
80
80
80
80
40
30
64
37
55
NR
NR
35
91
65
57
64
95
70
5
[Cp*CoI2]2 (4)
6[e]
7
[Ru(p-cymene)Cl2]2 (4)
[Ru(p-cymene)Cl2]2 (4)
[Ru(p-cymene)Cl2]2 (4)
[Ru(p-cymene)Cl2]2 (4)
[Ru(p-cymene)Cl2]2 (2)
[Ru(p-cymene)Cl2]2 (4)
[Ru(p-cymene)Cl2]2 (4)
AcOH
PivOH
MesCO2H
AcOH
AcOH
AcOH
8
9
10[f]
11
12
[a] 1a (0.2 mmol), 2a (0.3 mmol), catalyst, AgSbF6 (20 mol%), additive
(0.4 mmol), CsOAc (50 mol%), DCE (2 mL), 16 h. [b] Yields of isolated
products. [c] Without AgSbF6. [d] Without CsOAc. [e] In EtOH. [f] AgSbF6
(10 mol%). DCE=1,2-dichloroethane, Mes=2,4,6-trimethylphenyl,
Piv=pivaloyl.
the reaction of 2g by GC-MS, indicating the rather rare
À
À
cleavage of the C C and C P bonds in the diazo com-
pound.[15,16]
To better define the scope of the diazo substrate,
a-diazodiethylmalonate was employed. To our delight,
3H-indole 5b was isolated in 50% yield under conditions A
(Scheme 3). Switching to [Ru(p-cymene)(MeCN)3](SbF6)2 as
the catalyst further increased the yield to 75%. Under these
conditions (conditions B), we next investigated the generality
of this coupling. A variety of a-diazomalonates, including an
unsymmetric one, reacted with 1a in moderate to good yields
(5a–5 f, 30–75%). The scope of the imidamide was then
examined. Mono- and disubstituted imidamides as well as
other C-alkyl imidamides were viable substrates for this
transformation, furnishing the desired products 5g–5l in
moderate to high yields. In line with their efficient couplings
with a-diazoacetoacetates, N-aryl benzimidamides also
Scheme 2. Synthesis of N-unprotected indoles. Reaction conditions:
1 (0.2 mmol), 2 (0.3 mmol), [Ru(p-cymene)Cl2]2 (4 mol%), AgSbF6
(20 mol%), CsOAc (50 mol%), AcOH (0.4 mmol), DCE (2 mL), 408C,
16 h. Yields of isolated products after column chromatography are
given. [a] [Ru(p-cymene)Cl2]2 (2 mol%). [b] 808C.
substituent-dependent site selectivity. The coupling occurred
at the less hindered position for Cl and Br substituents (3ja
À
and 3ka), whereas C H functionalization occurred at the
more hindered site for the meta-fluoro substrate (3l).
Furthermore, ortho-Me- and F-substituted and disubstituted
acetimidamides were also viable substrates (3ma–3qa).
Scheme 3. Synthesis of 3H-indoles (see the Supporting Information for
details). [a] [Ru(p-cymene)(MeCN)3](SbF6)2 (4 mol%), 608C.
2
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reacted with a-diazodiethylmalonate with high chemoselec-
tivity; various electron-donating and -withdrawing groups
were tolerated (5m–5t), and reducing the catalyst loading was
also possible in some cases. A meta-fluoro-substituted imida-
mide also reacted with a-diazomalonate, but the reaction
stopped at the alkylation stage [Eq. (2)]. Acetanilide 6 was
Scheme 5. Mechanistic studies.
isolated in high yield after in situ hydrolysis of the imidamide
moiety. The formation of product 6 indicates that the
annulation reactions in Scheme 2 and Scheme 3 likely pro-
À
coupling partner (Scheme 5a), suggesting reversible C H
À
À
ceed by C H activation and carbene insertion.
activation. To further probe the C H activation process, the
To demonstrate the synthetic utility of this transforma-
tion, a gram-scale synthesis of product 3aa was carried out
with reduced catalyst loading, and 3aa was isolated in
moderate yield (Scheme 4a). Derivatizations of 3H-indole
kinetic isotope effect was determined by intermolecular
competition experiments using an equimolar mixture of 1a
À
and [D5]-1a. The small value of kH/kD = 1.6 suggests that C H
bond cleavage is likely not involved in the turnover-limiting
step (Scheme 5b). Moreover, a competition experiment was
conducted with an equimolar amount of 1b and 1e, which
differ in their electronic properties; 3ba and 3ea were
afforded in a ratio of 1:5.5, showing that the electron-poor
À
arene reacted faster (Scheme 5c). This suggests that the C H
activation process might follow a concerted metalation
deprotonation (CMD) mechanism.
On the basis of these observations and previous reports,[15]
a plausible catalytic cycle is shown in Scheme 6. Cyclometa-
lation of the imidamide affords a metallacyclic intermediate
A by CMD. Subsequent coordination of diazo compound 2 or
4 to intermediate A is followed by denitrogenation to
generate ruthenium carbene species B. The ruthenium–aryl
bond in this intermediate will then undergo migratory
insertion into the carbene unit to furnish seven-membered
ruthenacyclic intermediate C. Intermediate D was then
À
=
formed by Ru C(alkyl) migratory insertion into the C N
bond. For diazoketoester substrates, product 3 is eventually
released from D by protonolysis and intramolecular nucleo-
philic addition and subsequent elimination of one molecule of
Scheme 4. Gram-scale synthesis of 3aa and synthetic utility of 3H-
indoles. m-CPBA=meta-chloroperbenzoic acid, Tf=trifluoromethane-
sulfonyl, TMS=trimethylsilyl.
5n were performed to further showcase the synthetic utility of
=
these compounds. Reduction of the C N bond of 5n with
NaBH4/I2 afforded indoline 7 in 98% yield (Scheme 4b).[17]
Further treatment of 7 with m-CPBA afforded 3H-indole
N-oxide 8 in 97% yield.[18] Synthetic applications of N-oxide 8
À
in C H amidation and olefination have been reported by
Zhou and co-workers (Scheme 4c).[11d] When treated with
(trimethylsilyl)methyl triflate and dimethyl butynedioate, 5n
underwent a dipolar addition[17] followed by elimination and
ring scission to afford pyrrole 11 in moderate yield
(Scheme 4d).
To gain insight into the mechanism of this cyclization
process, a series of experiments were performed. H/D
exchange of 1a at the ortho’ position (the 7-position of the
indole) was observed (with 22% D) in the presence of the
Scheme 6. Proposed reaction mechanism.
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À
[5] For selected reviews on transition-metal-catalyzed C H bond
activation, see: a) G. Song, X. Li, Acc. Chem. Res. 2015, 48, 1007;
b) Z. Chen, B. Wang, J. Zhang, W. Yu, Z. Liu, Y. Zhang, Org.
Chem. Front. 2015, 2, 1107; c) L. Ackermann, Acc. Chem. Res.
2014, 47, 281; d) N. Kuhl, M. N. Hopkinson, J. Wencel-Delord, F.
Glorius, Angew. Chem. Int. Ed. 2012, 51, 10236; Angew. Chem.
2012, 124, 10382; e) K. M. Engle, T.-S. Mei, M. Wasa, J.-Q. Yu,
Acc. Chem. Res. 2012, 45, 788; f) S. R. Neufeldt, M. S. Sanford,
Acc. Chem. Res. 2012, 45, 936; g) S. H. Cho, J. Y. Kim, J. Kwak, S.
Chang, Chem. Soc. Rev. 2011, 40, 5068; h) L. McMurray, F.
OꢂHara, M. J. Gaunt, Chem. Soc. Rev. 2011, 40, 1885; i) C. S.
Yeung, V. M. Dong, Chem. Rev. 2011, 111, 1215.
amide, together with regeneration of the active ruthenium(II)
catalyst. In contrast, for diazomalonates, intermediate D
undergoes elimination of ammonia with assistance of RuII or
acetic acid, furnishing 3H-indole 5 as the final product. This
change in selectivity is likely caused by the reduced electro-
philicity of the ester carbonyl group.
In summary, we have developed the first ruthenium(II)-
catalyzed intermolecular coupling between aryl imidamides
À
and diazo compounds by C H activation, which enabled the
synthesis two classes of indole derivatives by [4+1] annulation
under mild conditions. The coupling of a-diazoketoesters
[6] a) P. Bai, X.-F. Huang, G.-D. Xu, Z.-Z. Huang, Org. Lett. 2016,
18, 3058; b) H. Wang, L. Li, S. Yu, Y. Li, X. Li, Org. Lett. 2016,
18, 2914; c) J. H. Kim, S. Greßies, F. Glorius, Angew. Chem. Int.
Ed. 2016, 55, 5577; Angew. Chem. 2016, 128, 5667; d) R. S.
Phatake, P. Patel, C. V. Ramana, Org. Lett. 2016, 18, 292; e) D.
Zhao, J. H. Kim, L. Stegemann, C. A. Strassert, F. Glorius,
Angew. Chem. Int. Ed. 2015, 54, 4508; Angew. Chem. 2015, 127,
4591; f) Y. Xia, Z. Liu, S. Feng, Y. Zhang, J. Wang, J. Org. Chem.
2015, 80, 223; g) W.-W. Chan, S.-F. Lo, Z. Zhou, W.-Y. Yu, J. Am.
Chem. Soc. 2012, 134, 13565; for a review on metal-catalyzed
functionalizations of diazo compounds, see: h) Q. Xiao, Y.
Zhang, J. Wang, Acc. Chem. Res. 2013, 46, 236.
[7] a) J. H. Kim, T. Gensch, D. Zhao, L. Stegemann, C. A. Strassert,
F. Glorius, Angew. Chem. Int. Ed. 2015, 54, 10975; Angew. Chem.
2015, 127, 11126; b) Z. Shi, D. C. Koester, M. Boultadakis-
Arapinis, F. Glorius, J. Am. Chem. Soc. 2013, 135, 12204.
[8] J. Li, M. Tang, L. Zang, X. Zhang, Z. Zhang, L. Ackermann, Org.
Lett. 2016, 18, 2742.
À
afforded NH indoles by cleavage of the C(N2) C(acyl) bond
whereas a-diazomalonates gave 3,3-disubstituted 3H-indoles
À
by C N bond cleavage. These efficient synthetic methods may
find application in the synthesis of bioactive compounds.
Acknowledgements
Financial support from the NSFC (21525208, 21272231, and
21472186) is gratefully acknowledged. This work was also
supported by the fund for new technology of methanol
conversion from the Dalian Institute of Chemical Physics and
by the Strategic Priority Research Program of the Chinese
Academy of Sciences (XDB17020300).
À
Keywords: C H activation · diazo compounds · indoles ·
[9] a) K. Yu, Y. Liang, B. Li, B. Wang, Adv. Synth. Catal. 2016, 358,
661; b) L. Shi, K. Yu, B. Wang, Chem. Commun. 2015, 51, 17277;
c) Y. Liang, K. Yu, B. Li, S. Xu, H. Song, B. Wang, Chem.
Commun. 2014, 50, 6130.
ruthenium · transition-metal catalysis
[10] R. B. Dateer, S. Chang, Org. Lett. 2016, 18, 68.
[11] a) Y. Li, F. Wang, S. Yu, X. Li, Adv. Synth. Catal. 2016, 358, 880;
b) X. Li, M. Sun, Q. Jin, K. Liu, P. N. Liu, J. Org. Chem. 2016, 81,
3901; c) J.-Q. Wu, Z. Yang, S.-S. Zhang, C.-Y. Jiang, Q. Li, Z.-S.
Huang, H. Wang, ACS Catal. 2015, 5, 6453; d) Y. Yang, X. Wang,
Y. Li, B. Zhou, Angew. Chem. Int. Ed. 2015, 54, 15400; Angew.
Chem. 2015, 127, 15620; e) T. K. Hyster, K. E. Ruhl, T. Rovis, J.
Am. Chem. Soc. 2013, 135, 5364; f) S. Cui, Y. Zhang, D. Wang, Q.
Wu, Chem. Sci. 2013, 4, 3912.
[12] a) T. Gensch, M. N. Hopkinson, F. Glorius, J. Wencel-Delord,
Chem. Soc. Rev. 2016, 45, 2900; b) S. De Sarkar, W. Liu, S. I.
Kozhushkov, L. Ackermann, Adv. Synth. Catal. 2014, 356, 1461;
c) P. B. Arockiam, C. Bruneau, P. H. Dixneuf, Chem. Rev. 2012,
112, 5879.
[13] a) N. Y. Phani Kumar, A. Bechtoldt, K. Raghuvanshi, L. Acker-
mann, Angew. Chem. Int. Ed. 2016, 55, 6929; Angew. Chem.
2016, 128, 7043; b) Y.-Q. Zhu, L. Dong, J. Org. Chem. 2015, 80,
9973; c) J. Li, S. Warratz, D. Zell, S. D. Sarkar, E. E. Ishikawa, L.
Ackermann, J. Am. Chem. Soc. 2015, 137, 13894; d) J. Hubrich,
T. Himmler, L. Rodefeld, L. Ackermann, ACS Catal. 2015, 5,
4089; e) H. Cheng, W. Dong, C. A. Dannenberg, S. Dong, Q.
Guo, C. Bolm, ACS Catal. 2015, 5, 2770; f) Q.-Z. Zheng, Y.-F.
Liang, C. Qin, N. Jiao, Chem. Commun. 2013, 49, 5654; g) Y.
Aihara, N. Chatani, Chem. Sci. 2013, 4, 664; h) K. Raghuvanshi,
D. Zell, K. Rauch, L. Ackermann, ACS Catal. 2016, 6, 3172; i) R.
Manikandan, P. Madasamy, M. Jeganmohan, Chem. Eur. J. 2015,
21, 13934; j) K. Muralirajan, K. Parthasarathy, C.-H. Cheng, Org.
Lett. 2012, 14, 4262; k) J. Wu, W. Xu, Z. Yu, J. Wang, J. Am.
Chem. Soc. 2015, 137, 9489; l) P. Zhao, X. Li, Org. Lett. 2013, 14,
5506.
[1] a) T. Eicher, S. Hauptmann, A. Speicher, The Chemistry of
Heterocycles: Structure, Reactions, Syntheses, and Applications,
2nd ed., Wiley-VCH, Weinheim, 2003; b) M. Somei, F. Yamada,
Nat. Prod. Rep. 2004, 21, 278; c) A. J. Kochanowska-Karamyan,
M. T. Hamann, Chem. Rev. 2010, 110, 4489.
[2] For selected reviews on indole synthesis, see: a) S. Cacchi, G.
Fabrizi, Chem. Rev. 2005, 105, 2873; b) G. R. Humphrey, J. T.
Kuethe, Chem. Rev. 2006, 106, 2875; c) L. Ackermann, Synlett
2007, 507; d) K. Krꢀger nꢁe Alex, A. Tillack, M. Beller, Adv.
Synth. Catal. 2008, 350, 2153; e) M. Shiri, Chem. Rev. 2012, 112,
3508; f) M. Inman, C. J. Moody, Chem. Sci. 2013, 4, 29.
[3] a) M. Jesus, P. Elias, A. M. Lucas, M. S. Joel, K. G. Neil, J. Am.
Chem. Soc. 2016, 138, 1162; b) M. J. James, P. OꢂBrien, R. J. K.
Taylor, W. P. Unsworth, Chem. Eur. J. 2016, 22, 2856; c) Y.
Shiono, K. Akiyama, H. Hayashi, Biosci. Biotechnol. Biochem.
2000, 64, 1519; d) X.-H. Cai, Q.-G. Tan, Y.-P. Liu, T. Feng, Z.-Z.
Du, W.-Q. Li, X.-D. Luo, Org. Lett. 2008, 10, 577; e) K.-H. Lim,
O. Hiraku, K. Komiyama, T. Koyano, M. Hayashi, T.-S. Kam, J.
Nat. Prod. 2007, 70, 1302.
[4] For selected reports on indole synthesis, see: a) B. Z. Lu, H.-X.
Wei, Y. Zhang, W. Zhao, M. Dufour, G. Li, V. Farina, C. H.
Senanayake, J. Org. Chem. 2013, 78, 4558; b) J. Jadhav, V.
Gaikwad, R. Kurane, R. Salunkhe, G. Rashinkar, Synlett 2012,
2511; c) G. Li, X. Huang, L. Zhang, Angew. Chem. Int. Ed. 2008,
47, 346; Angew. Chem. 2008, 120, 352; d) B. M. Trost, A.
McClory, Angew. Chem. Int. Ed. 2007, 46, 2074; Angew. Chem.
2007, 119, 2120; e) F. Liu, D. Ma, J. Org. Chem. 2007, 72, 4844;
f) A. Fayol, Y.-Q. Fang, M. Lautens, Org. Lett. 2006, 8, 4203;
g) M. S. Islam, C. Brennan, Q. Wang, M. M. Hossain, J. Org.
Chem. 2006, 71, 4675.
[14] a) V. K.-Y. Lo, Z. Guo, M. K.-W. Choi, W.-Y. Yu, J.-S. Huang, C.-
M. Che, J. Am. Chem. Soc. 2012, 134, 7588; b) W.-H. Cheung, S.-
L. Zheng, W.-Y. Yu, G.-C. Zhou, C.-M. Che, Org. Lett. 2003, 5,
4
www.angewandte.org
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2535; c) M. K.-W. Choi, W.-Y. Yu, C.-M. Che, Org. Lett. 2005, 7,
[18] R. M. Letcher, D. W. M. Sin, K.-K. Cheung, J. Chem. Soc. Perkin
1081.
Trans. 1 1993, 939.
[15] Z. Qi, S. Yu, X. Li, Org. Lett. 2016, 18, 700.
[16] a) W.-S. Yong, S. Park, H. Yun, P. H. Lee, Adv. Synth. Catal.
2016, 358, 1958; b) F. Ye, C. Wang, Y. Zhang, J. Wang, Angew.
Chem. Int. Ed. 2014, 53, 11625; Angew. Chem. 2014, 126, 11809.
[17] Z. He, H. Li, Z. Li, J. Org. Chem. 2010, 75, 4636.
Received: June 29, 2016
Revised: July 29, 2016
Published online: && &&, &&&&
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Communications
À
C H Activation
Y. Li, Z. Qi, H. Wang, X. Yang,
X. Li*
&&&& — &&&&
À
Ruthenium(II)-Catalyzed C H Activation
of Imidamides and Divergent Couplings
with Diazo Compounds: Substrate-
Controlled Synthesis of Indoles and 3H-
Indoles
Which way to go: NH indoles and 3H-
indoles were synthesized by ruthenium-
The coupling of a-diazoketoesters
afforded NH indoles by cleavage of the
À
À
(II)-catalyzed C H activation of imida-
C(N2) C(acyl) bond whereas a-di-
=
mides and intermolecular coupling with
diazo compounds under mild conditions.
azomalonates gave 3H-indoles by C N
bond cleavage.
6
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