Divergent Reactivity of Rhodium(I) Carbenes Derived from Indole Annulations

Article abstract of DOI:10.1002/anie.201505329

Rhodium(I) carbenes were generated from propargylic alcohol derivatives as the result of a dehydrative indole annulation. Depending on the choice of the electron-withdrawing group on the aniline nitrogen nucleophile, either a cyclopropanation product or dimerization product was obtained chemoselectively. Intramolecular hydroamidation occurred for the same type of propargylic alcohol derivatives when other transition-metal catalysts were employed.

Full text of DOI:10.1002/anie.201505329

Angewandte
Chemie
International Edition: DOI: 10.1002/anie.201505329
German Edition: DOI: 10.1002/ange.201505329
Heterocycles
Divergent Reactivity of Rhodium(I) Carbenes Derived from Indole
Annulations
Xiaoxun Li, Hui Li, Wangze Song, Po-Sen Tseng, Lingyan Liu,* Ilia A. Guzei, and
Weiping Tang*
Abstract: Rhodium(I) carbenes were generated from pro-
pargylic alcohol derivatives as the result of a dehydrative
indole annulation. Depending on the choice of the electron-
withdrawing group on the aniline nitrogen nucleophile, either
a cyclopropanation product or dimerization product was
obtained chemoselectively. Intramolecular hydroamidation
occurred for the same type of propargylic alcohol derivatives
when other transition-metal catalysts were employed.
Scheme 1. Divergent reactivity of rhodium(I)-carbenes derived from
indole annulation. Boc=tert-butoxycarbonyl, Ts =4-toluenesulfonyl.
M
etal carbenes are versatile intermediates for a variety of
reactions.[1] They are generally derived from diazo com-
pounds or related derivatives.[2] Fischer carbenes serve as the
primary precursors of rhodium(I) carbenes,[3] with a few
exceptions.[4] We[5] and others[6] discovered that rhodium(I)
carbenes could be derived from 1,2-acyloxy migration of
propargylic esters for cycloadditions.[7] Recently, we also
found that 3-hydroxy-1,4-enynes could serve as rhodium(I)
carbene precursors and as five-carbon components in [5+1]
cycloaddition reactions.[8] In an effort to develop general
carbene precursors for indole synthesis, we found that indole
annulation of the propargylic alcohol 1 could produce the
rhodium(I) carbene 2, which either underwent chemoselec-
tive cyclopropanation or dimerization to form the products 3a
and 3b, respectively, depending on the choice of the E group
(Scheme 1). Although a related calcium-catalyzed tandem
indole annulation and cyclopropanation involving multiple
cationic species was developed by Niggemann and co-work-
ers, only intramolecular cyclcopropanation was reported by
tethering the alkene to the propargylic alcohol.[9]
Scheme 2. Metal-catalyst-mediated hydroamidation.
co-workers extensively for various gold- and silver-catalyzed
tandem indole annulations and nucleophilic additions
(Scheme 2).[12] We found that other catalysts, such as plati-
num-, palladium-, and copper-based complexes could also
mediate this process.[13] Clearly, the rhodium(I) catalyst is
unique in promoting the formation of the carbene 2, instead
of the hydroamidation product 4, and subsequent divergent
transformations.
Diazomethanes without an adjacent electron-withdrawing
group are generally not very stable and those with an
electron-rich aryl substituent are particularly difficult to
prepare.[14] Indeed, we were not able to prepare the indolyl-
substituted diazomethane precursor for the carbene 2 using
known methods,[14] and thus tried to explore alternative
cyclopropanation methods.[15] A tandem indole annulation of
1 followed by cyclopropanation allows the construction of
both indole and cyclopropane, two of the most important
rings in organic chemistry.[10,16]
Indole is one of the most abundant bioactive heterocycles
in natural products and pharmaceutical agents.[10] Most
previous indole syntheses focused on the construction of
indole ring alone.[11] It would be more efficient to couple
indole annulation with other transformations in a cascade
manner. The propargylic alcohol 1 has been used by Chan and
We began our investigation by examining various tran-
sition-metal catalysts which might mediate the cyclization of
6a in the presence of the alkene 7a (Table 1). Cationic
rhodium(I) catalysts or neutral rhodium(I) catalysts without
CO did not provide any desired product (entries 1–3). High
yield of the product 8a could be obtained by using the
[{Rh(CO)2Cl}2] complex as the catalyst in either the presence
or absence of a CO balloon (entries 4 and 5). When the
amount of alkene was reduced from 2 to 1.2 equivalents,
a slightly lower yield was observed (entry 6). No cyclopropa-
nation products were formed when other metal complexes
were employed (entries 7–10). In some cases, the hydro-
amidation product 4 was observed, and was consistent with
[*] Dr. X. Li, H. Li, W. Song, P.-S. Tseng, Dr. L.-y. Liu, Prof. Dr. W. Tang
School of Pharmacy, University of Wisconsin-Madison
Madison, WI 53705-2222 (USA)
E-mail: wtang@pharmacy.wisc.edu
Dr. L.-y. Liu
Institute of Elemento-Organic Chemistry, College of Chemistry
Nankai University
Tianjin, 300071 (P.R. China)
E-mail: liulingyan@nankai.edu.cn
Dr. I. A. Guzei, Prof. Dr. W. Tang
Department of Chemistry, University of Wisconsin-Madison
Madison, WI 53706 (USA)
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201505329.
Angew. Chem. Int. Ed. 2015, 54, 12905 –12908
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
12905

.
Angewandte
Communications
Table 1: Screening reaction conditions for cyclopropanation.[a]
Table 2: Scope of alkenes for the tandem indole annulation/cyclo-
propanation with 6a.[a]
Entry Substrate 7
Product 8 (d.r.)[b]
Yield [%][c]
Entry
Conditions
Yield [%][b]
1
2
3
4
5
7a, R=MeO
7b, R=H
7c, R=Me
7d, R=tBu
7e, R=CF3
8a (20:1)
8b (20:1)
8c (20:1)
8d (20:1)
8e
80
48
68
1
2
3
4
5
6
7
8
9
[Rh(cod)2]BF4 (5 mol%)
[Rh(PPh3)3Cl] (5 mol%)
[{Rh(cod)Cl}2] (5 mol%)
[{Rh(CO)2Cl}2] (5 mol%), CO (1 atm)
[{Rh(CO)2Cl}2] (5 mol%)
[{Rh(CO)2Cl}2] (5 mol%)
[{Ir(cod)Cl}2] (5 mol%)
Pd(OAc)2 (5 mol%)
0
0
0
82
86
77[c]
0
0
0
0
70
20[b]
6
7
7 f
8 f (20:1)
8g (20:1)
78
70
PtCl2 (5 mol%)
[Au(PPh3)Cl] (5 mol%)
10
[a] Reaction conditions: dichloroethane (DCE), 6a (1.0 equiv), 7a
(2.0 equiv), RT, 12–20 h, unless noted otherwise. [b] The yield was
determined by H NMR analysis of the crude reaction mixture using
1
7g
CH2Br2 as the internal standard. [c] 7a (1.2 equiv). cod=1,5-cyclo-
octadiene.
previous reports.[12a–c,13] The tosyl group of 8a can be removed
as shown in the Supporting Information.
8
9
10
7h, R1 =Me, R2 =H
8h, (20:1)
8i, (20:1)
63
52
87
7i, R1 =CH2OH, R2 =H
We then examined the scope with respect to the alkenes,
using 6a as the carbene precursor. Various styrenes with
a para substituent participated in the cyclopropanation and
yielded exclusively the cis diastereoisomer (Table 2,
entries 1–4). The reactivity of electron-poor styrene was
lower than that of electron-rich styrene (entry 1 versus
entry 5). Styrenes with multiple substituents or an ortho sub-
stituent were also tolerated (entries 6 and 7). The structure of
8 f[22] was unambiguously determined by X-ray analysis.
Trisubstituted cyclopropanes (8h–j) were successfully pre-
pared from 1,1-disubstituted alkenes (entries 8–10). Notably,
the free alcohols in 7i and 7j were tolerated under the
standard reaction conditions. Heterocycles such as indole
could also be introduced to the diaryl cyclopropane products
(entry 11). Unfortunately, the 1,2-disubstituted alkene 7l did
not participate in the cyclopropanation. No cyclopropanation
was observed by using alkenes with just an alkyl substituent,
including both electron-rich vinyl ethers and electron-poor
enones.
7j, R1 =CH2OH, R2 =MeO 8j, (20:1)
11[d]
12
7k
8k (20:1)
60
0
7l (E/Z=1:1)
–
[a] Conditions: [{Rh(CO)2Cl}2] (5 mol%), DCE, 6a (1.0 equiv), 7
(2.0 equiv), RT, 12–20 h, unless noted otherwise. [b] Determined by
1H NMR analysis of crude product. [c] Isolated yield. [d] Substrate 9 f
(Table 3) was employed in this case.
Table 3: Scope of propargylic alcohols for the tandem indole annulation/
cyclopropanation.[a]
We next explored the scope with respect to the prop-
argylic alcohols. The aryl sulfonyl group did not have an
obvious effect to the tandem annulation/cyclopropanation
(Table 3, entries 1–5). The R1 group could be a hydrogen or
other alkyl groups (entries 6–8). Substituents could be
introduced to the benzene ring of the substrate 9i (entry 9).
Notably, the aryl bromide in 9i could be tolerated for
rhodium-catalyzed reactions.
The dienes 11a and 11b participated in the cyclopropa-
nation and afforded the corresponding vinylcyclopropanes 12,
which could undergo Cope rearrangement to yield the
cyclohepta[b]indole 14a or 14b, respectively (Scheme 3).[17]
Cyclohepta[b]indole is present in a number of natural
products[18] and bioactive pharmaceutical agents.[19]
Entry
9
10 (d.r.)[b]
Yield [%][c]
1
2
3
4
5
6
7
8
9
9a, R1 =Me, R2 =H, Ar=Ph
10a (20:1)
10b (20:1)
10c (20:1)
72
77
72
73
75
66
81
77
71
9b, R1 =Me, R2 =H, Ar=4-FC6H4
9c, R1 =Me, R2 =H, Ar=4-tBuC6H4
9d, R1 =Me, R2 =H, Ar=4-MeOC6H4 10d (20:1)
9e, R1 =Me, R2 =H, Ar=1-naphthyl
9 f, R1 =R2 =H, Ar=4-MeC6H4
10e (20:1)
10 f (20:1)
10g (5:1)
10h (5:1)
10i (20:1)
9g, R1 =Et, R2 =H, Ar=4-MeC6H4
9h, R1 =nBu, R2 =H, Ar=4-MeC6H4
9i, R1 =Me, R2 =Br, Ar=4-MeC6H4
[a] Reaction conditions: [{Rh(CO)2Cl}2] (5 mol%), DCE, 9 (1.0 equiv), 7a
(2.0 equiv), RT, 12–20 h, unless noted otherwise. [b] Determined by
1H NMR analysis of the crude reaction mixture. [c] Yield of isolated
product.
In addition to various arylsulfonyl groups shown in
Table 3, we also explored the effect of other electron-with-
12906 www.angewandte.org
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2015, 54, 12905 –12908

Angewandte
Chemie
Scheme 4. Proposed mechanism for the formation of rhodium(I)
carbenes and their divergent reactivity.
Scheme 3. Sequential indole annulation, cyclopropanation, and Cope
rearrangement.
the indole dimerization (Table 4). In addition to the Boc
group, another alkoxy carbonyl group (entry 2) or acyl group
(entry 3) also facilitated the formation of the dimer 16. It is
also interesting to note that the carbene intermediate cannot
be trapped by an intramolecularly tethered alkene (entry 3).
The R1 substituent can be either a hydrogen, ethyl, isopropyl,
butyl, or phenyl group (entries 4–8). Dimeric indoles with
a bromine substituent on the benzene ring could also be
prepared (entry 9). The E and Z isomers were easily sepa-
rated by column chromatography in several cases. The
structures of the dimeric indoles were unambiguously deter-
mined by X-ray analysis of (E)-16b[22] and (Z)-16b.[22]
The mechanism of the indole annulation/cyclopropana-
tion or dimerization is proposed in Scheme 4. Coordination of
the metal catalyst to alkyne in 1 will induce nucleophilic
attack of the aniline nitrogen atom to form the adduct 17.[12a–c]
This process is promoted by an electron-withdrawing ligand,
such as CO, on the rhodium(I) complexes.[7] Protonation to
form the hydroamidation product 4 occurrs for most p-acidic
transition metals.[12a–c] Elimination of water proceeds to yield
the carbene intermediate 18, which undergoes either cyclo-
propanation or dimerization, depending on the nature the
E group. We propose that the chemoselectivity may arise
from the ability of the carbonyl group in 18b to better
coordinate to rhodium(I) carbenes. The cis-selective cyclo-
propanation, based on the X-ray structure of 8 f and NMR
data, is presumably because both aryl substituents prefer to be
away from the metal complex, and is consistent with gold-
catalyzed 1,2-acyloxy migration of propargylic esters/inter-
molecular cyclopropanation.[21]
drawing groups on the aniline nucleophile for the tandem
annulation/cyclopropanation. Under the standard reaction
conditions outlined in Table 3, no cyclopropanation product
was observed for the substrate 15a (Table 4) in the presence
of different styrenes. Instead, trace amounts of the dimeric
indole 16a were obtained in the presence or absence of
styrenes. The yield of the dimeric indole was improved
dramatically by simply attaching a CO balloon to the reaction
flask (entry 1). Under these reaction conditions, we previ-
ously did not observe any dimeric indole for 6a, having a tosyl
group on the nitrogen atom (Table 1, entry 4). No dimeriza-
tion products were formed when other metal complexes
shown in entries 7–10 of Table 1 were employed.
Dimerization of carbenes is generally considered as a side
reaction.[20] Given the high yield of 16a and the potential
utility of indole derivatives, we further examined the scope of
Table 4: Scope of indole dimerization.[a]
Entry
1
15
16 (E/Z)[b]
Yield [%][c]
81
15a,
R1 =Me, R2 =H,
R3 =tBuO
16a (1.4:1)
2
3
4
5
6
7
8
9
15b,
15c,
15d,
15e,
15 f,
15g,
15h,
15i,
R1 =Me, R2 =H,
R3 =MeO
16b (1.2:1)
16c (1.4:1)
16d (1.2:1)
16e (1.3:1)
16 f (1.3:1)
16g (1.5:1)
16h (1.1:1)
16i (1.3:1)
81
R1 =Me, R2 =H,
82
3
=
R =CH2 CHCH2CH2
In summary, various cyclopropanes with cis-1,2-diaryl
substituents were prepared stereoselectively from propargylic
alcohol derivatives by a tandem indole annulation and
cyclopropanation. The enantioselective version of this cas-
cade process is currently under investigation in our labora-
tory. Divergent reactivity was observed when the aniline
nitrogen atom of the substrate is attached to different
electron-withdrawing groups. Computational studies are
ongoing to elucidate the origin of the intriguing chemo-
selectivity.
R1 =R2 =H,
88
R3 =tBuO
R1 =Et, R2 =H,
R3 =tBuO
47;[d] 35[e]
74
R1 =iPr, R2 =H,
R3 =tBuO
R1 =nBu, R2 =H,
R3 =tBuO
46;[d] 34[e]
33;[d] 27[e]
92
R1 =Ph, R2 =H,
R3 =tBuO
R1 =Me, R2 =Br,
R3 =tBuO
[a] Reaction conditions: [{Rh(CO)2Cl}2] (5 mol%), CO (1 atm), DCE,
15a, 608C, 10 h, unless noted otherwise. [b] Determined by 1H NMR
analysis of the crude reaction mixture. [c] Yield of the two isolated two
isomers. [d] Yield of the isolated E isomer. [e] Yield of the isolated
Z isomer.
Acknowledgements
We thank the NIH (R01GM088285) and the University of
Wisconsin-Madison for financial support. L.-y.L. thanks
Angew. Chem. Int. Ed. 2015, 54, 12905 –12908
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org 12907

.
Angewandte
Communications
Amardeil, L. Djakovitch, J.-C. Hierso, Chem. Soc. Rev. 2012, 41,
3929.
Chinese Scholarship Council for financial support of a visiting
scholar position at UW.
[12] a) P. Kothandaraman, W. Rao, S. J. Foo, P. W. H. Chan, Angew.
Chem. Int. Ed. 2010, 49, 4619; Angew. Chem. 2010, 122, 4723;
b) P. Kothandaraman, S. R. Mothe, S. S. M. Toh, P. W. H. Chan,
J. Org. Chem. 2011, 76, 7633; c) D. Susanti, F. Koh, J. A. Kusuma,
P. Kothandaraman, P. W. H. Chan, J. Org. Chem. 2012, 77, 7166;
d) P. Kothandaraman, B. Q. Koh, T. Limpanuparb, H. Hirao,
P. W. H. Chan, Chem. Eur. J. 2013, 19, 1978.
Keywords: carbenes · cyclizations · heterocycles · rhodium ·
synthetic methods
How to cite: Angew. Chem. Int. Ed. 2015, 54, 12905–12908
Angew. Chem. 2015, 127, 13097–13100
[13] H. Li, X. Li, H.-Y. Wang, G. N. Winston-McPherson, H.-m. J.
Geng, I. A. Guzei, W. Tang, Chem. Commun. 2014, 50, 12293.
[14] a) T. L. Holton, H. Shechter, J. Org. Chem. 1995, 60, 4725; b) M.
McGuiness, H. Shechter, Tetrahedron Lett. 2002, 43, 8425;
c) M. I. Javed, M. Brewer, Org. Lett. 2007, 9, 1789; d) D. C.
Moebius, J. S. Kingsbury, J. Am. Chem. Soc. 2009, 131, 878.
[15] For selected reviews on cyclopropanations, see: a) H. Lebel, J.-F.
Marcoux, C. Molinaro, A. B. Charette, Chem. Rev. 2003, 103,
977; b) H. Y. Kim, P. J. Walsh, Acc. Chem. Res. 2012, 45, 1533;
c) G. Bartoli, G. Bencivenni, R. Dalpozzo, Synthesis 2014, 979.
[16] For selected reviews on the importance and utility of cyclo-
propanes, see: a) H. U. Reissig, R. Zimmer, Chem. Rev. 2003,
103, 1151; b) M. Nakamura, H. Isobe, E. Nakamura, Chem. Rev.
2003, 103, 1295; c) M. Rubin, M. Rubina, V. Gevorgyan, Chem.
Rev. 2007, 107, 3117; d) D. Y. K. Chen, R. H. Pouwer, J.-A.
Richard, Chem. Soc. Rev. 2012, 41, 4631; e) P. Tang, Y. Qin,
Synthesis 2012, 2969; f) D. J. Mack, J. T. Njardarson, ACS Catal.
2013, 3, 272; g) T. F. Schneider, J. Kaschel, D. B. Werz, Angew.
Chem. Int. Ed. 2014, 53, 5504; Angew. Chem. 2014, 126, 5608;
h) M. A. Cavitt, L. H. Phun, S. France, Chem. Soc. Rev. 2014, 43,
804; i) H. K. Grover, M. R. Emmett, M. A. Kerr, Org. Biomol.
Chem. 2015, 13, 655.
[17] a) X. Han, H. Li, R. P. Hughes, J. Wu, Angew. Chem. Int. Ed.
2012, 51, 10390; Angew. Chem. 2012, 124, 10536; b) D. Shu, W.
Song, X. Li, W. Tang, Angew. Chem. Int. Ed. 2013, 52, 3237;
Angew. Chem. 2013, 125, 3319.
[18] a) A. Shafiee, A. Ahond, A. M. Bui, Y. Langlois, C. Riche, P.
Potier, Tetrahedron Lett. 1976, 17, 921; b) M. Andriantsiferana,
R. Besselievre, C. Riche, H. P. Husson, Tetrahedron Lett. 1977,
18, 2587; c) A. R. Carroll, E. Hyde, J. Smith, R. J. Quinn, G.
Guymer, P. I. Forster, J. Org. Chem. 2005, 70, 1096; d) T.
Taniguchi, C. L. Martin, K. Monde, K. Nakanishi, N. Berova,
L. E. Overman, J. Nat. Prod. 2009, 72, 430.
[19] a) A. D. Napper, J. Hixon, T. McDonagh, K. Keavey, J. F. Pons, J.
Barker, W. T. Yau, P. Amouzegh, A. Flegg, E. Hamelin, R. J.
Thomas, M. Kates, S. Jones, M. A. Navia, J. Saunders, P. S.
DiStefano, R. Curtis, J. Med. Chem. 2005, 48, 8045; b) T. Barf, F.
Lehmann, K. Hammer, S. Haile, E. Axen, C. Medina, J.
Uppenberg, S. Svensson, L. Rondahl, T. Lundbaeck, Bioorg.
Med. Chem. Lett. 2009, 19, 1745; c) E. Yamuna, R. A. Kumar, M.
Zeller, K. J. R. Prasad, Eur. J. Med. Chem. 2012, 47, 228.
[20] a) A. Del Zotto, W. Baratta, G. Verardo, P. Rigo, Eur. J. Org.
Chem. 2000, 2795; b) D. M. Hodgson, D. Angrish, Chem. Eur. J.
2007, 13, 3470; c) C. Vovard-Le Bray, S. Derien, P. H. Dixneuf,
Angew. Chem. Int. Ed. 2009, 48, 1439; Angew. Chem. 2009, 121,
1467.
[21] M. J. Johansson, D. J. Gorin, S. T. Staben, F. D. Toste, J. Am.
Chem. Soc. 2005, 127, 18002.
[22] CCDC 1042160 (8 f), 1042158 ((E)-16b), and 1042159 ((Z)-16b)
contain the supplementary crystallographic data for this paper.
These data are provided free of charge by The Cambridge
Crystallographic Data Centre.
[1] For selected reviews on reactions involving metal carbenes, see:
a) M. P. Doyle, Chem. Rev. 1986, 86, 919; b) A. Padwa, S. F.
Hornbuckle, Chem. Rev. 1991, 91, 263; c) A. Padwa, M. D.
Weingarten, Chem. Rev. 1996, 96, 223; d) M. P. Doyle, D. C.
Forbes, Chem. Rev. 1998, 98, 911; e) H. M. L. Davies, R. E. J.
Beckwith, Chem. Rev. 2003, 103, 2861; f) H. M. L. Davies, S. J.
Hedley, Chem. Soc. Rev. 2007, 36, 1109; g) H. M. L. Davies, J. R.
Manning, Nature 2008, 451, 417; h) P. de FrØmont, N. Marion,
S. P. Nolan, Coord. Chem. Rev. 2009, 253, 862; i) H. M. L. Davies,
J. R. Denton, Chem. Soc. Rev. 2009, 38, 3061; j) G. C. Vougiou-
kalakis, R. H. Grubbs, Chem. Rev. 2010, 110, 1746.
[2] For selected reviews, see: a) T. Ye, M. A. McKervey, Chem. Rev.
1994, 94, 1091; b) M. P. Doyle, M. A. McKervey, T. Ye, Modern
Catalytic Methods for Organic Synthesis with Diazo Compounds,
Wiley, New York, 1998; c) Z. Zhang, J. Wang, Tetrahedron 2008,
64, 6577.
[3] a) J. Barluenga, R. Vicente, L. A. Lopez, E. Rubio, M. Tomas, C.
Alvarez-Rua, J. Am. Chem. Soc. 2004, 126, 470; b) J. Barluenga,
R. Vicente, P. Barrio, L. A. Lopez, M. Tomas, J. Am. Chem. Soc.
2004, 126, 5974; c) J. Barluenga, R. Vicente, L. A. Lopez, M.
Tomas, J. Am. Chem. Soc. 2006, 128, 7050; d) T. Nishimura, Y.
Maeda, T. Hayashi, Angew. Chem. Int. Ed. 2010, 49, 7324;
Angew. Chem. 2010, 122, 7482.
[4] a) H. Werner, J. Organomet. Chem. 1995, 500, 331; b) T.
Nishimura, T. Kawamoto, M. Nagaosa, H. Kumamoto, T.
Hayashi, Angew. Chem. Int. Ed. 2010, 49, 1638; Angew. Chem.
2010, 122, 1682; c) Y. Shibata, K. Noguchi, K. Tanaka, Org. Lett.
2010, 12, 5596.
[5] a) X.-Z. Shu, S. Huang, D. Shu, I. A. Guzei, W. Tang, Angew.
Chem. Int. Ed. 2011, 50, 8153; Angew. Chem. 2011, 123, 8303;
b) X.-Z. Shu, X. Li, D. Shu, S. Huang, C. M. Schienebeck, X.
Zhou, P. J. Robichaux, W. Tang, J. Am. Chem. Soc. 2012, 134,
5211; c) X.-Z. Shu, C. M. Schienebeck, W. Song, I. A. Guzei, W.
Tang, Angew. Chem. Int. Ed. 2013, 52, 13601; Angew. Chem.
2013, 125, 13846; d) X. Xu, P. Liu, X.-Z. Shu, W. Tang, K. N.
Houk, J. Am. Chem. Soc. 2013, 135, 9271.
[6] a) Y. Shibata, K. Noguchi, K. Tanaka, J. Am. Chem. Soc. 2010,
132, 7896; b) C. Brancour, T. Fukuyama, Y. Ohta, I. Ryu, A. L.
Dhimane, L. Fensterbank, M. Malacria, Chem. Commun. 2010,
46, 5470; c) T. Fukuyama, Y. Ohta, C. Brancour, K. Miyagawa, I.
Ryu, A.-L. Dhimane, L. Fensterbank, M. Malacria, Chem. Eur. J.
2012, 18, 7243.
[7] X.-Z. Shu, D. Shu, C. M. Schienebeck, W. Tang, Chem. Soc. Rev.
2012, 41, 7698.
[8] X. Li, W. Song, W. Tang, J. Am. Chem. Soc. 2013, 135, 16797.
[9] T. Haven, G. Kubik, S. Haubenreisser, M. Niggemann, Angew.
Chem. Int. Ed. 2013, 52, 4016; Angew. Chem. 2013, 125, 4108.
[10] For selected reviews on the bioactivity of indoles, see: a) S.-M.
Li, Nat. Prod. Rep. 2010, 27, 57; b) N. A. S. Ali, B. A. Dar, V.
Pradhan, M. Farooqui, Mini-Rev. Med. Chem. 2013, 13, 1792;
c) N. K. Kaushik, N. Kaushik, P. Attri, N. Kumar, C. H. Kim,
A. K. Verma, E. H. Choi, Molecules 2013, 18, 6620.
[11] For selected reviews on indole synthesis, see: a) J. Barluenga, F.
Rodriguez, F. J. Fananas, Chem. Asian J. 2009, 4, 1036; b) D. F.
Taber, P. K. Tirunahari, Tetrahedron 2011, 67, 7195; c) R.
Vicente, Org. Biomol. Chem. 2011, 9, 6469; d) M. Platon, R.
Received: June 10, 2015
Revised: July 27, 2015
Published online: September 7, 2015
12908 www.angewandte.org
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2015, 54, 12905 –12908