Gold(I)-catalyzed rearrangement of alkynylaziridine indoles for the synthesis of spiro-tetrahydro-β-carbolines

Article abstract of DOI:10.1016/j.tet.2013.11.084

Functionalized spiro-tetrahydro-β-carbolines were formed by an efficient gold(I)-catalyzed rearrangement reaction of alkynylaziridine indoles. The reaction involved a Friedel-Crafts type intramolecular reaction of alkynylaziridine indoles, following by hydroamination of aminoallene intermediate.

Full text of DOI:10.1016/j.tet.2013.11.084

Tetrahedron 70 (2014) 702e707
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Gold(I)-catalyzed rearrangement of alkynylaziridine indoles
for the synthesis of spiro-tetrahydro-b
-carbolinesq
,b,
Yan-Fang Yang a, Lian-Hua Li a, Yu-Tao He a, Jian-Yi Luo a, Yong-Min Liang a
*
a State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, PR China
b Key Laboratory of Solid Lubrication, Lanzhou Institute of Chemical Physics, Chinese Academy of Science, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Functionalized spiro-tetrahydro-b-carbolines were formed by an efficient gold(I)-catalyzed rearrange-
Received 23 September 2013
Received in revised form 17 November 2013
Accepted 25 November 2013
Available online 6 December 2013
ment reaction of alkynylaziridine indoles. The reaction involved a FriedeleCrafts type intramolecular
reaction of alkynylaziridine indoles, following by hydroamination of aminoallene intermediate.
Ó 2013 The Authors. Published by Elsevier Ltd. All rights reserved.
Keywords:
Gold
Rearrangement
Aminoallene
Cyclization
Tetrahydro-b-carboline
1. Introduction
Tetrahydro- -carbolines (THBCs), both naturally occurring and
introduced a gold-catalyzed ring-expansion and rearrangement of
aryl-substituted N-tosyl alkynyl aziridines to di-substituted pyrrole
b
products [Scheme 1].7 In 2010, Pale reported a gold-catalyzed
tandem rearrangement-nucleophilic substitution of acetoxylated
alkynyl oxiranes and aziridines to form furans and pyrroles in the
presence of nucleophiles [Scheme 2, Eq. 1].8 Recently, the in-
vestigations developed by Pale and co-workers were carried out,
alkynyl aziridines with aryl group could be efficiently converted to
spiro[isochroman-4,2’-pyrrolines] using gold catalysts [Scheme 2,
Eq. 2].9 In continuation of our studies on spriocyclic compounds,10
synthetic ones, are highly important alkaloids with valuable bi-
ological activities and pharmaceutical applications.1 The syntheses
of structural diversities and the complexity of pharmacologically
active THBC derivatives result in a great synthetic challenge. Pic-
teteSpengler reactions have a large impact on preparing diverse
THBCs over the past century.2 In recent years, various asymmetric
catalytic examples have been developed.3 To date, only a handful of
examples for the synthesis of spiro-THBCs has been reported, es-
pecially for the 4-substituted spiro-THBCs.4 Therefore, de-
velopment of effective methods for the synthesis of 4-spiro-THBC
derivatives is desirable and challenging.
we report herein the synthesis of spiro-tetrahydro-
b-carbolines 2
from the C2-alkynylaziridine indoles 1 using gold(I) catalysis via
a
FriedeleCrafts type intramolecular reaction11 followed by
hydroamination of allenes12 [Scheme 2, Eq. 3]. In this reaction, two
In the past decade, cationic gold(I) and silver(I) complexes, both
rings with a spirocarbon can be efficiently formed.
p
and s Lewis acidities, have gained increasing interest due to their
reaction mildness and efficiency.5,6 Because aziridine building
block is so useful for the synthesis of nitrogen-containing bi-
ologically active molecules, the number of gold-catalyzed trans-
formation of aziridines has increased rapidly.7e9 In 2009, Davies
Scheme 1. Gold-catalyzed ring-expansion and rearrangement reaction.
q
This is an open-access article distributed under the terms of the Creative
Commons Attribution-NonCommercial-No Derivative Works License, which per-
mits non-commercial use, distribution, and reproduction in any medium, provided
the original author and source are credited.
2. Results and discussion
To examine our hypotheses, we chose alkynylaziridine indole 1a
as a model substrate, which was synthesized by the Mitsunobu
* Corresponding author. Tel.: þ86 931 891 2593; fax: þ86 931 891 2582; e-mail
address: liangym@lzu.edu.cn (Y.-M. Liang).
0040-4020/$ e see front matter Ó 2013 The Authors. Published by Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.11.084

Y.-F. Yang et al. / Tetrahedron 70 (2014) 702e707
703
Fig. 1. X-ray crystal structure of 2a.
catalyzed by silver catalysts afforded 51e74% yields (entries 12e15).
Further examination of solvent effects revealed that the use of 1,2-
dichloroethane (DCE), 1,4-dioxane, CH3NO2 or tetrahydrofuran
(THF) decreased the yield (entries 16e19). After the systematic
screening, the use of 5 mol % Au(PPh3)Cl and 5 mol % AgSbF6 in dry
dichloromethane at 0 ꢀC to room temperature after 5 h were con-
sidered as the optimal reaction conditions.
Scheme 2. Previous works and present work.
reaction of N-substituted-4-dimethylbenzenesulfonamide and
aziridine propargylic alcohol. First, several gold(III) catalysts were
studied. Regretfully, it was detrimental to generate the spiro-THBCs
when the catalyst was trivalent gold (Table 1, entries 1e3). Then,
studies of gold(I) catalysts were carried out. Delightedly, spiro-
THBC 2a was isolated with 56% yield when PPh3AuNTf2 was used
(entry 4). The relative configuration of product 2a was determined
by X-ray diffraction (Fig. 1).13 Other gold(I) catalysts, such as
[Au(PPh3)(MeCN)]SbF6 and [Au(JohnPhos)(MeCN)]SbF6 could also
catalyze the reaction, giving moderate yields (entries 5 and 6).
When we used AuI or Au(PPh3)Cl as catalysts, no reaction occurred
(entries 7 and 8). Experiments using Au(PPh3)Cl in combination
with AgSbF6, AgOTf, and AgBF4 were also carried out (entries 9e11).
It showed that 5 mol % of Au(PPh3)Cl/AgSbF6 was the most efficient,
with the expected product 2a in 84% yield (entry 9). The reaction
Under the modified reaction conditions, we aimed to test the
scope of the reaction and the results were shown in Table 2. The
Table 2
Gold(I)-Catalyzed synthesis of various tetrahydro-b
-carbolinesa
Table 1
Optimization of reaction conditionsa
Entry
Catalyst (5 mol %)
Solvent
Time (h)
Yieldb (%)
1
2
3
4
AuCl3
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCE
12
12
12
5
5
5
12
12
5
5
5
5
5
5
5
5
5
5
5
NR
NR
NR
56
68
68
NR
NR
84
74
81
65
74
61
51
77
70
76
68
NaAuCl4$2H2O
HAuCl4$3H2O
PPh3AuNTf2
[Au(PPh3)(MeCN)]SbF6
[Au(JohnPhos)(MeCN)]SbF6
AuI
5
6c
7
8
9
Au(PPh3)Cl
Au(PPh3)Cl, AgSbF6
Au(PPh3)Cl, AgOTf
Au(PPh3)Cl, AgBF4
AgNTf2
AgSbF6
AgOTf
10
11
12
13
14
15
16
17
18
19
AgBF4
Au(PPh3)Cl, AgSbF6
Au(PPh3)Cl, AgSbF6
Au(PPh3)Cl, AgSbF6
Au(PPh3)Cl, AgSbF6
1,4-Dioxane
CH3NO2
THF
a
The reaction was conducted by using 1a (0.1 mmol), catalyst (5 mol %) in solvent
a The reaction was carried out using 1 (0.1 mmol), Au(PPh3)Cl/AgSbF6 (5
mol%) in CH2Cl2 (3 mL) after 5h at 0 °С to room temperature. Isolated yield.
b The catalyst loading of Au(PPh3)Cl/AgSbF6 was 10 mol%.
(3 mL) at 0 ꢀC to room temperature.
b
Isolated yield.
JohnPhos¼(2-biphenyl)di-tert-butylphosphine.
c

704
Y.-F. Yang et al. / Tetrahedron 70 (2014) 702e707
double cyclization of indoles bearing various substituents worked
smoothly to give the corresponding spiro-THBC in moderate to
good yields. For example, the reactions of the substituted indoles
1aeg with methyl, methoxy groups furnished the spiro-THBCs
2aeg in 71e97% yields and the substituted indoles 1hej with
fluoro, chloro, bromo groups also reacted to give the products 2hej
in 79e93% yields. This result showed that indoles containing
electron-donating groups exhibited very similar reactivity in
comparison to those bearing electron-withdrawing groups. When
the substrate was alkynylaziridine benzo[g]indole, the reaction
proceeded well, and the 7,8-benzosubstituted THBC 2k was formed
in 98% yield. Because of steric hindrance, complete conversion of
alkynylaziridine benzo[e]indole 1l could be observed when in-
creasing in catalyst-loading up to 10 mol %, giving 5,6-benzosub-
stituted THBC 2l in 87% yield. While 5,6-methylenedioxyindole
derivative 1m was conducted to the standard reaction conditions,
2m was isolated in only 63% yield. Furthermore, trisubstituted
aziridine, such as aziridine 1n efficiently furnished the double-
cyclization product 2n in 89% yield. Changing the N-substitution
R2 group to methyl and ethyl have no obvious effect on the re-
action, and we can easily get the corresponding products in good
yields (2o and 2p). Replacing benzyl with allyl, which offers a more
stable protecting, increased slightly in the product yield (2a vs 2q).
When we replaced Ts with Ns-p (p-nitrobenzenesulfonyl), 1r was
easily prepared by Mitsunobu reaction.14 For the methyl-
substituented compound 1r (dr¼2.65:1), an excellent yield of
92% was isolated giving the corresponding spiro compound 2r.
When C2-alkynylaziridine pyrrole compound 1s was used
according to the standard reaction conditions, the reaction did not
occur (2s).15
Scheme 4. Mechanism for the gold(I)-catalyzed cascade reaction of alkynylaziridine
indole.
3. Conclusions
In summary, we have presented an efficient method for the
construction of spiro-THBCs. The approach uses a gold(I)-catalyzed
tandem FriedeleCrafts type addition, followed by a cyclization re-
action of the aminoallene intermediate. The very mild conditions,
good functional group compatibility and operational simplicity are
expected to make this reaction attractive to chemists. The appli-
cation of this methodology to synthesize other members of the
indole-containing motifs is currently under study in our laboratory.
To get more insight into the mechanism, we studied the in-
termediate of different compounds. Delightedly, when methyl-
substituented compound 1r (dr¼2.65:1) were conducted to
5 mol % Au(PPh3)Cl/AgSbF6 and 5 mol % AgSbF6 in dry dichloro-
methane at 0 ꢀC for 1.5 h and 3 h, intermediate 2rem were iso-
lated in 80% and 74% yield (dr¼2.65:1), respectively (Scheme 3).
When intermediate 2rem were putted into the 5 mol % Au(PPh3)
Cl/AgSbF6 and 5 mol % AgSbF6 in dry dichloromethane at 50 ꢀC for
1 h,16 corresponding product 2r were formed in 78% and 20%,
respectively. Thus, the mechanism of silver-catalyzed is similar to
the gold-catalyzed process. However, gold-catalyzed process is
more efficient than silver-catalyzed process in the second step.
4. Experimental section
4.1. General
Column chromatography was carried out on silica gel. Reagents
and solvents were purified using standard means. 1H NMR spectra
were recorded on 400 MHz in CDCl3 and 13C NMR spectra were
recorded on 100 MHz in CDCl3 using TMS as internal standard. IR
spectra were recorded on a FT-IR spectrometer and only major
peaks are reported in cmꢁ1. Melting points were determined on
a microscopic apparatus and were uncorrected. High-resolution
mass spectral analysis (HRMS) data were recorded by Electro-
Spray Ionization (ESI). The parent ions [MþH]þ, [MþNa]þ or
[MþK]þ are quoted.
Scheme 3. Experimental confirmation of reaction mechanism.
A mechanism for this gold-catalyzed rearrangement reaction is
proposed as shown in Scheme 4. Initially, alkynylaziridine moiety is
activated by dual coordination of the gold(I) ion. An intramolecular
nucleophilic addition of the indole (C3-position) to the activated
alkynylaziridine, which concerted with an anti-opening of the
aziridine part would lead to unstable cationic species intermediate
A. It undergoes a re-aromatization step to give the allenyl indole B.
4.2. General procedure for the gold-catalyzed synthesis of
spiro-tetrahydro-b-carbolines
To a dried tube, which wrapped in aluminum foil were added
Au(PPh3)Cl (2.5 mg, 0.005 mmol), AgSbF6 (1.7 mg, 0.005 mmol),
and dry CH2Cl2 (1 mL) sequentially at room temperature. The
resulting mixture was stirred at room temperature for about 0.5 h
until it became purple, which was followed by the addition of 1
(0.1 mmol) and 2 mL of dry CH2Cl2 at 0 ꢀC. The resulting mixture
was allowed to warm at room temperature. Monitored by thin-
layer chromatography, the reaction was stirred until complete
conversion of the starting material. After concentration of the
The protodemetalation of intermediate B liberates a-aminoallene C
and the metal ion. The latter could then activate the allene, pro-
moting an endo-hydroamination cyclization,12 affording vinyl gold
intermediate D. Proton transfer of intermediate D would finally
lead to the spiro-THBC 2a.

Y.-F. Yang et al. / Tetrahedron 70 (2014) 702e707
705
reaction mixture, the crude residue was purified by flash chroma-
tography on alkalescent silica gel (hexane/EtOAc¼4/1) to afford 2.
192e194 ꢀC; 1H NMR (400 MHz, CDCl3):
d
7.65 (d, J¼8.0 Hz, 2H),
7.33e7.25 (m, 5H), 7.15 (d, J¼8.0 Hz, 2H), 6.89 (d, J¼7.2 Hz, 2H), 6.81
(d, J¼7.6 Hz, 2H), 6.70 (d, J¼7.2 Hz, 1H), 6.50 (t, J¼7.6 Hz, 1H), 6.42
(d, J¼8.0 Hz, 1H), 5.56 (s, 1H), 5.48 (d, Jab¼18.0 Hz, 1H), 5.41 (d,
Jab¼18.0 Hz, 1H), 4.62 (d, J¼14.4 Hz, 1H), 4.35 (d, Jab¼13.2 Hz, 1H),
4.29 (d, Jab¼13.6 Hz, 1H), 3.95 (d, Jab¼11.2 Hz, 1H), 3.86 (d,
Jab¼11.6 Hz, 1H), 3.81 (d, J¼14.0 Hz, 1H), 2.45 (s, 3H), 2.43 (s, 3H),
4.3. Characterization data of products
4.3.1. 9-Benzyl-40-methyl-10,2-ditosyl-1,10,2,3,50,9-hexahydro-spiro
[pyrido[3,4-b]indole-4,20-pyrrole](2a). Yellow solid; mp: 192e
194 ꢀC; 1H NMR (400 MHz, CDCl3):
d
7.68 (d, J¼8.0 Hz, 2H),
2.26 (s, 3H), 1.80 (s, 3H); 13C NMR (100 MHz, CDCl3):
d 144.0, 142.8,
7.35e7.26 (m, 5H), 7.10e7.04 (m, 5H), 6.97e6.93 (m, 1H), 6.66 (d,
J¼8.0 Hz, 2H), 6.58e6.54 (m, 1H), 6.44 (d, J¼7.6 Hz, 1H), 5.56 (s, 1H),
5.27 (d, Jab¼16.8 Hz, 1H), 5.19 (d, Jab¼16.4 Hz, 1H), 4.67 (d,
J¼14.0 Hz, 1H), 4.39 (d, Jab¼13.2 Hz, 1H), 4.31 (d, Jab¼13.6 Hz, 1H),
3.97 (d, Jab¼11.6 Hz,1H), 3.90 (d, Jab¼11.6 Hz,1H), 3.82 (d, J¼14.0 Hz,
1H), 2.44 (s, 3H), 2.19 (s, 3H), 1.81 (s, 3H); 13C NMR (100 MHz,
138.5,136.1,135.2,133.5,132.3,131.5,129.9,129.1,128.6,127.6,127.5,
127.0, 126.1, 125.0, 124.5, 120.6, 120.0, 117.0, 110.8, 72.0, 58.6, 54.3,
48.6, 42.9, 21.5, 21.3, 19.6, 14.0; IR (KBr, cmꢁ1) 2918, 1599, 1449,
1336, 1159, 750, 663; HRMS (ESI) m/z: calcd for C37H37N3O4S2:
MþNa¼674.2118; found: 674.2132.
CDCl3):
d
144.0, 142.8, 136.8, 136.3, 135.7, 133.4, 131.9, 131.5, 130.0,
4.3.6. 9-Benzyl-5-methoxy-40-methyl-10,2-ditosyl-1,10,2,3,50,9-
129.0, 128.5, 127.8, 127.5, 126.9, 126.1, 125.4, 121.1, 119.8, 118.7, 110.2,
109.3, 71.8, 58.7, 54.4, 47.0, 43.0, 21.6, 21.2,14.0; IR (KBr, cmꢁ1) 2919,
1597, 1455, 1337, 1159, 750, 661; HRMS (ESI) m/z: calcd for
hexahydrospiro[pyrido[3,4-b]indole-4,20-pyrrole] (2f). Yellow solid;
mp: 184e186 ꢀC; 1H NMR (400 MHz, CDCl3):
d
7.67 (d, J¼8.0 Hz,
2H), 7.34e7.28 (m, 5H), 7.05 (d, J¼7.2 Hz, 2H), 7.00 (d, J¼8.4 Hz, 2H),
6.87 (t, J¼8.0 Hz, 1H), 6.71 (d, J¼8.0 Hz, 1H), 6.65 (d, J¼8.0 Hz, 2H),
5.90 (d, J¼7.6 Hz, 1H), 5.62 (s, 1H), 5.23 (d, Jab¼16.8 Hz, 1H), 5.17 (d,
Jab¼16.8 Hz, 1H), 4.62 (d, J¼14.0 Hz, 1H), 4.33 (d, Jab¼12.4 Hz, 1H),
4.20 (d, Jab¼12.4 Hz, 1H), 3.97 (d, Jab¼11.6 Hz, 1H), 3.87 (d,
Jab¼11.6 Hz, 1H), 3.76 (d, J¼14.0 Hz, 1H), 3.27 (s, 3H), 2.43 (s, 3H),
C
36H35N3O4S2: MþH¼638.2142; found: 638.2160.
4.3.2. 9-Benzyl-40,5-dimethyl-10,2-ditosyl-1,10,2,3,50,9-hexahydro-
spiro[pyrido[3,4-b]indole-4,20-pyrrole] (2b). Yellow solid; mp:
198e200 ꢀC; 1H NMR (400 MHz, CDCl3):
d
7.64 (d, J¼8.4 Hz, 2H),
7.34 (d, J¼8.0 Hz, 2H), 7.29e7.23 (m, 5H), 7.00e6.94 (m, 6H), 6.63 (d,
J¼6.4 Hz, 1H), 5.76 (s, 1H), 5.22 (s, 2H), 4.55 (d, J¼14.0 Hz, 1H), 4.28
(d, Jab¼13.2 Hz, 1H), 4.07 (d, Jab¼13.2 Hz, 1H), 3.84e3.72 (m, 3H),
2.46 (s, 3H), 2.34 (s, 3H), 2.08 (s, 3H), 1.78 (s, 3H); 13C NMR
2.18 (s, 3H), 1.78 (s, 3H); 13C NMR (100 MHz, CDCl3):
d 152.7, 143.9,
142.0, 138.2, 136.9, 133.4, 132.0, 131.2, 130.0, 129.0, 128.7, 127.8,
127.7, 127.0, 126.0, 122.4, 116.6, 110.0, 102.5, 100.1, 72.6, 59.1, 56.0,
54.6, 47.1, 43.3, 21.5, 21.2, 14.2; IR (KBr, cmꢁ1) 2920, 1637, 1444,
(100 MHz, CDCl3):
d
144.1, 142.9, 137.3, 136.8, 136.6, 132.9, 132.6,
1326, 1157, 1031; HRMS (ESI) m/z: calcd for
MþNa¼690.2067; found: 690.2079.
C37H37N3O5S2:
132.0, 131.2, 131.0, 129.9, 129.0, 128.8, 127.7, 127.6, 127.2, 125.9,
125.6, 122.4, 121.9, 111.2, 107.0, 73.3, 57.9, 55.7, 46.8, 43.5, 21.6, 21.4,
20.6, 14.2; IR (KBr, cmꢁ1) 2918, 1727, 1451, 1344, 1160, 753, 665;
HRMS (ESI) m/z: calcd for C37H37N3O4S2: MþNa¼674.2118; found:
674.2134.
4.3.7. 9-Benzyl-6-methoxy-40-methyl-10,2-ditosyl-1,10,2,3,50,9-
hexahydrospiro[pyrido[3,4-b]indole-4,20-pyrrole] (2g). Yellow solid;
mp: 164e166 ꢀC; 1H NMR (400 MHz, CDCl3):
d
7.69 (d, J¼8.0 Hz,
2H), 7.35e7.28 (m, 5H), 7.08 (d, J¼6.8 Hz, 2H), 7.00 (d, J¼8.4 Hz, 2H),
6.96 (d, J¼8.8 Hz,1H), 6.63e6.57 (m, 3H), 5.73 (d, J¼2.0 Hz,1H), 5.56
(s, 1H), 5.23 (d, Jab¼16.8 Hz, 1H), 5.16 (d, Jab¼16.4 Hz, 1H), 4.67 (d,
J¼14.0 Hz, 1H), 4.44 (d, Jab¼13.2 Hz, 1H), 4.26 (d, Jab¼13.6 Hz, 1H),
3.99 (d, Jab¼11.6 Hz,1H), 3.91 (d, Jab¼11.6 Hz,1H), 3.82 (d, J¼14.4 Hz,
1H), 3.49 (s, 3H), 2.44 (s, 3H), 2.18 (s, 3H), 1.82 (s, 3H); 13C NMR
4.3.3. 9-Benzyl-40,6-dimethyl-10,2-ditosyl-1,10,2,3,50,9-hexahydro-
spiro[pyrido[3,4-b]indole-4,20-pyrrole] (2c). Yellow solid; mp:
194e196 ꢀC; 1H NMR (400 MHz, CDCl3):
d
7.68 (d, J¼8.4 Hz, 2H),
7.36e7.28 (m, 5H), 7.07 (d, J¼6.8 Hz, 2H), 6.99e6.94 (m, 3H),
6.74e6.72 (m, 1H), 6.61 (d, J¼8.0 Hz, 2H), 5.98 (s, 1H), 5.55 (s, 1H),
5.25 (d, Jab¼16.8 Hz,1H), 5.17 (d, Jab¼16.8 Hz,1H), 4.67 (d, J¼14.0 Hz,
1H), 4.45 (d, J¼13.6 Hz, 1H), 4.29 (d, J¼13.6 Hz, 1H), 4.00e3.89 (m,
2H), 3.80 (d, J¼14.0 Hz, 1H), 2.44 (s, 3H), 2.16 (s, 3H), 2.01 (s, 3H),
(100 MHz, CDCl3):
d 153.5, 144.0, 142.8, 136.9, 135.4, 133.5, 132.8,
131.4, 131.3, 130.0, 129.0, 128.4, 127.8, 127.5, 126.9, 126.1, 110.7, 110.1,
109.5, 100.6, 71.9, 58.8, 54.8, 54.6, 47.2, 43.1, 21.6, 21.1, 15.3; IR (KBr,
cmꢁ1) 2920, 1595, 1452, 1339,1160, 754, 665; HRMS (ESI) m/z: calcd
for C37H37N3O5S2: MþNa¼690.2067; found: 690.2083.
1.82 (s, 3H); 13C NMR (100 MHz, CDCl3):
d 144.0, 142.4, 136.9, 135.5,
134.6, 133.4, 132.1, 131.3, 130.0, 129.0, 128.4, 128.2, 127.7, 127.6,
126.8, 126.0, 125.7, 122.7, 118.4, 109.4, 109.0, 71.8, 58.8, 54.6, 47.0,
43.0, 21.5, 21.1, 14.0; IR (KBr, cmꢁ1) 2918, 1596, 1449, 1338,
1159, 752, 662; HRMS (ESI) m/z: calcd for
MþNa¼674.2118; found: 674.2136.
4.3.8. 9-Benzyl-7-fluoro-40-methyl-10,2-ditosyl-1,10,2,3,50,9-hexa-hy-
drospiro[pyrido[3,4-b]indole-4,20-pyrrole] (2h). Yellow solid; mp:
C37H37N3O4S2:
188e190 ꢀC; 1H NMR (400 MHz, CDCl3):
d
7.68 (d, J¼8.0 Hz, 2H),
7.53e7.27 (m, 5H), 7.06 (d, J¼7.2 Hz, 2H), 7.02 (d, J¼8.4 Hz, 2H),
6.99e6.95 (m, 1H), 6.69e6.64 (m, 3H), 5.89 (dd, J¼2.4 Hz, 9.6 Hz,
1H), 5.54 (s, 1H), 5.24 (d, Jab¼16.8 Hz, 1H), 5.17 (d, Jab¼16.8 Hz, 1H),
4.68 (d, J¼14.0 Hz, 1H), 4.44 (d, Jab¼13.6 Hz, 1H), 4.30 (d,
Jab¼13.6 Hz, 1H), 3.98 (d, Jab¼12.0 Hz, 1H), 3.91 (d, Jab¼12.0 Hz, 1H),
3.82 (d, J¼14.0 Hz, 1H), 2.44 (s, 3H), 2.19 (s, 3H), 1.83 (s, 3H); 13C
4.3.4. 9-Benzyl-40,7-dimethyl-10,2-ditosyl-1,10,2,3,50,9-hexahydro-
spiro[pyrido[3,4-b]indole-4,20-pyrrole] (2d). Yellow solid; mp:
193e194 ꢀC; 1H NMR (400 MHz, CDCl3):
d
7.67 (d, J¼8.4 Hz, 2H),
7.35e7.28 (m, 5H), 7.06 (d, J¼8.0 Hz, 4H), 6.89 (s, 1H), 6.69 (d,
J¼8.0 Hz, 2H), 6.40 (d, Jab¼8.0 Hz, 1H), 6.32 (d, Jab¼8.0 Hz, 1H), 5.54
(s, 1H), 5.24 (d, Jab¼16.8 Hz, 1H), 5.16 (d, Jab¼16.8 Hz, 1H), 4.63 (d,
J¼14.0 Hz, 1H), 4.39e4.29 (q, J¼13.6 Hz, 2H), 3.95 (d, Jab¼11.6 Hz,
1H), 3.87 (d, Jab¼11.6 Hz, 1H), 3.78 (d, J¼14.0 Hz, 1H), 2.44 (s, 3H),
2.32 (s, 3H), 2.21 (s, 3H), 1.80 (s, 3H); 13C NMR (100 MHz, CDCl3):
NMR (100 MHz, CDCl3):
d
143.5 (d, J¼110 Hz, CF), 136.5, 135.6, 134.0,
133.5, 132.7, 131.8, 130.0, 129.1, 128.5, 128.0, 127.5, 127.3, 126.7, 126.1,
126.0, 110.0 (d, J¼9.0 Hz), 109.4 (d, J¼27.0 Hz), 103.9 (d, J¼24.0 Hz),
71.5, 58.8, 54.6, 47.3, 43.0, 21.5, 21.1, 13.9; IR (KBr, cmꢁ1) 2919,
1595, 1451, 1340, 1160, 754, 664; HRMS (ESI) m/z: calcd for
d
144.0, 142.7, 136.9, 136.7, 135.8, 133.4, 131.3, 131.2, 131.1, 130.0,
129.0,128.4,127.7, 127.6, 127.5, 127.0, 126.0, 123.3, 121.6, 118.3, 110.2,
109.1, 71.8, 58.7, 54.3, 46.8, 42.9, 21.7, 21.6, 21.3, 13.9; IR (KBr, cmꢁ1
2918, 1597, 1452, 1336, 1159, 754, 661; HRMS (ESI) m/z: calcd for
37H37N3O4S2: MþNa¼674.2118; found: 674.2134.
C36H34FN3O4S2: MþNa¼678.1867; found: 678.1876.
)
4.3.9. 9-Benzyl-7-chloro-40-methyl-10,2-ditosyl-1,10,2,3,50,9-hexa-hy-
C
drospiro[pyrido[3,4-b]indole-4,20-pyrrole] (2i). Yellow solid; mp:
202e204 ꢀC; 1H NMR (400 MHz, CDCl3):
7.35e7.30 (m, 5H), 7.07 (d, J¼8.0 Hz, 3H), 7.02 (d, J¼8.0 Hz, 2H), 6.69
(d, J¼8.0 Hz, 2H), 6.51 (dd, J¼1.2, 8.4 Hz, 1H), 6.31 (d, J¼8.4 Hz, 1H),
d
7.67 (d, J¼8.4 Hz, 2H),
4.3.5. 9-Benzyl-40,8-dimethyl-10,2-ditosyl-1,10,2,3,50,9-hexahydro-
spiro[pyrido[3,4-b]indole-4,20-pyrrole] (2e). White solid; mp:

706
Y.-F. Yang et al. / Tetrahedron 70 (2014) 702e707
5.55 (s, 1H), 5.21 (d, Jab¼16.8 Hz, 1H), 5.15 (d, Jab¼16.8 Hz, 1H), 4.65
(d, J¼14.4 Hz, 1H), 4.40 (d, Jab¼13.6 Hz, 1H), 4.29 (d, Jab¼13.2 Hz,
1H), 3.96 (d, Jab¼12.0 Hz, 1H), 3.89 (d, Jab¼12.0 Hz, 1H), 3.80 (d,
J¼14.0 Hz, 1H), 2.44 (s, 3H), 2.25 (s, 3H), 1.81 (s, 3H); 13C NMR
119.8, 110.2, 100.5, 97.6, 90.7, 71.7, 58.8, 54.6, 47.4, 43.1, 21.5, 21.2,
13.9; IR (KBr, cmꢁ1) 2919, 1643, 1466, 1336, 1160, 1035, 757, 666;
HRMS (ESI) m/z: calcd for C37H35N3O6S2: MþNa¼704.1859; found:
704.1871.
(100 MHz, CDCl3):
d 144.1, 143.3, 136.7, 136.2, 135.7, 133.5, 133.0,
131.8, 130.0, 129.1, 128.5, 128.0, 127.5, 127.4, 126.9, 126.1, 124.2,
120.5, 119.4, 110.5, 109.2, 71.5, 58.8, 54.3, 47.2, 42.9, 21.5, 21.2, 13.9;
IR (KBr, cmꢁ1) 2919, 1598, 1451, 1335, 1159, 754, 662; HRMS (ESI) m/
z: calcd for C36H34ClN3O4S2: MþNa¼694.1571; found: 694.1585.
4.3.14. 90-Benzyl-1,20-ditosyl-1,10,20,30,4,5,6,7,7a,90-decahydro-spiro
[indole-2,40-pyrido[3,4-b]indole] (2n). White solid; mp: 212e
214 ꢀC; 1H NMR (400 MHz, CDCl3):
d
7.71 (d, J¼8.0 Hz, 2H),
7.36e7.28 (m, 5H), 7.12 (d, J¼7.2 Hz, 2H), 7.06 (d, J¼8.4 Hz, 1H),
6.92e6.86 (m, 3H), 6.48 (d, J¼8.0 Hz, 2H), 6.43 (t, J¼7.6 Hz, 1H), 6.27
(d, J¼8.0 Hz, 1H), 5.45 (s, 1H), 5.28 (d, Jab¼16.4 Hz, 1H), 5.20 (d,
Jab¼16.4 Hz, 1H), 4.66 (d, J¼14.0 Hz, 1H), 4.35e4.32 (m, 1H), 3.94 (s,
2H), 3.87 (d, J¼14.0 Hz, 1H), 2.89e2.87 (m, 1H), 2.51e2.47 (m, 1H),
2.44 (s, 3H), 2.11 (s, 3H), 2.08e2.07 (m, 1H), 1.93e1.86 (m, 2H),
4.3.10. 9-Benzyl-6-bromo-40-methyl-10,2-ditosyl-1,10,2,3,50,9-
hexahydrospiro[pyrido[3,4-b]indole-4,20-pyrrole] (2j). White solid;
mp: 218e220 ꢀC; 1H NMR (400 MHz, CDCl3):
d
7.68 (d, J¼8.4 Hz,
2H), 7.35e7.30 (m, 5H), 7.07 (d, J¼6.8 Hz, 2H), 7.00e6.92 (m, 4H),
6.66 (d, J¼8.0 Hz, 2H), 6.26 (s, 1H), 5.53 (s, 1H), 5.24 (d, Jab¼16.8 Hz,
1H), 5.17 (d, Jab¼16.8 Hz, 1H), 4.68 (d, J¼14.4 Hz, 1H), 4.47 (d,
Jab¼13.6 Hz, 1H), 4.28 (d, Jab¼13.6 Hz, 1H), 3.99 (d, Jab¼12.0 Hz, 1H),
3.92 (d, Jab¼11.6 Hz, 1H), 3.81 (d, J¼14.0 Hz, 1H), 2.44 (s, 3H), 2.21 (s,
1.56e1.33 (m, 3H); 13C NMR (100 MHz, CDCl3):
d 144.0, 142.4, 138.7,
136.8, 136.0, 133.5, 132.8, 130.0, 129.0, 128.1, 127.8, 127.6, 127.0,
126.2, 126.1, 122.6, 120.8, 119.7, 118.8, 109.2, 109.0, 71.8, 60.4, 55.9,
47.1, 42.8, 38.0, 28.1, 26.4, 24.1, 21.6, 21.1, 14.2; IR (KBr, cmꢁ1) 2931,
1598, 1455, 1339, 1159, 754, 660; HRMS (ESI) m/z: calcd for
3H), 1.84 (s, 3H); 13C NMR (100 MHz, CDCl3):
d 144.1, 143.1, 136.3,
135.2,134.8,133.8,133.4,131.9,130.0,129.1,128.6,128.1,127.5,127.3,
127.1, 126.5, 126.1, 123.9, 121.3, 113.4, 110.8, 109.7, 71.4, 58.9, 54.6,
47.3, 42.9, 21.6, 21.3, 14.0; IR (KBr, cmꢁ1) 2918, 1598, 1455, 1159, 754,
663; C36H34BrN3O4S2: MþNa¼738.1066; found: 738.1071.
C
39H39N3O4S2: MþNa¼700.2274; found: 700.2295.
4.3.15. 40,9-Dimethyl-10,2-ditosyl-1,10,2,3,50,9-hexahydrospiro-[pyrido
[3,4-b]indole-4,20-pyrrole] (2o). Yellow solid; mp: 160e162 ꢀC; 1H
NMR (400 MHz, CDCl3):
d
7.76 (d, J¼8.0 Hz, 2H), 7.38 (d, J¼8.0 Hz,
4.3.11. 11-Benzyl-40-methyl-10,9-ditosyl-10,50,8,9,10,11-hexa-hydro-
2H), 7.16 (d, J¼8.4 Hz, 1H), 7.07e7.01 (m, 3H), 6.76 (d, J¼8.0 Hz, 2H),
6.60 (t, J¼7.6 Hz, 1H), 6.50 (d, J¼7.6 Hz, 1H), 5.52 (s, 1H), 4.70 (d,
J¼14.0 Hz, 1H), 4.35 (d, Jab¼13.2 Hz, 1H), 4.28 (d, Jab¼13.6 Hz, 1H),
3.95e3.85 (m, 3H), 3.62 (d, J¼5.2 Hz, 3H), 2.45 (s, 3H), 2.23 (s, 3H),
spiro[benzo[g]pyrido[3,4-b]indole-7,20-pyrrole] (2k). Yellow solid;
mp: 120e122 ꢀC; 1H NMR (400 MHz, CDCl3):
d 7.99e7.97 (m, 1H),
7.77e7.74 (m, 1H), 7.70 (d, J¼8.0 Hz, 2H), 7.36e7.28 (m, 7H), 7.13 (d,
J¼7.2 Hz, 2H), 7.05 (d, J¼8.4 Hz, 2H), 6.94 (d, J¼8.8 Hz, 1H), 6.57 (d,
J¼8.4 Hz, 1H), 6.50 (d, J¼8.0 Hz, 2H), 5.75e5.60 (m, 3H), 4.75 (d,
J¼14.0 Hz, 1H), 4.46 (d, Jab¼13.6 Hz, 1H), 4.37 (d, Jab¼13.2 Hz, 1H),
4.04e3.93 (m, 3H), 2.43 (s, 3H), 1.97 (s, 3H), 1.86 (s, 3H); 13C NMR
1.79 (s, 3H); 13C NMR (100 MHz, CDCl3):
d 144.0, 142.7, 136.8, 135.9,
133.4, 131.8, 131.4, 129.9, 128.5, 127.6, 127.0, 125.1, 120.9, 119.5, 118.7,
109.8, 108.7, 71.9, 58.6, 54.4, 42.9, 29.7, 21.5, 21.2, 13.9; IR (KBr,
cmꢁ1) 2918, 1624, 1450, 1383, 1159, 665; HRMS (ESI) m/z: calcd for
(100 MHz, CDCl3):
d
144.0, 142.9, 136.7, 135.8, 133.7, 131.6, 131.4,
C
30H31N3O4S2: MþNa¼584.1648; found: 584.1660.
130.9, 130.0, 129.8, 129.3, 128.9, 128.4, 127.9, 127.8, 127.5, 127.0,
125.6, 125.4, 123.3, 123.0, 122.1, 121.5, 120.4, 118.0, 111.6, 71.9, 58.8,
54.6, 49.9, 43.0, 21.5, 21.0, 14.0; IR (KBr, cmꢁ1) 2919, 1598, 1447,
1349, 1160, 749, 664; HRMS (ESI) m/z: calcd for C40H37N3O4S2:
MþNa¼710.2118; found: 710.2132.
4.3.16. 9-Ethyl-40-methyl-10,2-ditosyl-1,10,2,3,50,9-hexahydro-spiro
[pyrido[3,4-b]indole-4,20-pyrrole] (2p). White solid; mp: 156e
158 ꢀC; 1H NMR (400 MHz, CDCl3):
d
7.76 (d, J¼8.4 Hz, 2H), 7.39 (d,
J¼8.0 Hz, 2H), 7.17 (d, J¼8.4 Hz, 1H), 7.02e6.98 (m, 3H), 6.69 (d,
J¼8.0 Hz, 2H), 6.55 (t, J¼7.2 Hz, 1H), 6.43 (d, J¼8.0 Hz, 1H), 5.54 (s,
1H), 4.69 (d, J¼13.6 Hz, 1H), 4.38 (d, Jab¼13.2 Hz, 1H), 4.29 (d,
Jab¼13.6 Hz, 1H), 4.08 (d, Jab¼18.0 Hz, 1H), 4.05 (d, Jab¼18.0 Hz, 1H),
3.96e3.88 (m, 3H), 2.46 (s, 3H), 2.21 (s, 3H), 1.80 (s, 3H), 1.37 (t,
4.3.12. 7-Benzyl-40-methyl-10,9-ditosyl-10,50,7,8,9,10-hexahydro-spiro
[benzo[e]pyrido[3,4-b]indole-11,20-pyrrole] (2l). Yellow solid; mp:
191e193 ꢀC; 1H NMR (400 MHz, CDCl3):
d
7.71 (d, J¼8.0 Hz, 2H),
7.66 (d, J¼8.0 Hz, 1H), 7.44e7.24 (m, 8H), 7.15 (t, J¼7.2 Hz, 1H), 7.02
(d, J¼6.8 Hz, 2H), 6.95 (t, J¼7.2 Hz, 1H), 6.72 (d, J¼8.4 Hz, 2H), 6.21
(d, J¼8.0 Hz, 2H), 5.86 (s, 1H), 5.39 (d, Jab¼16.8 Hz, 1H), 5.33 (d,
Jab¼17.2 Hz, 1H), 4.70 (d, J¼14.0 Hz, 1H), 4.64 (d, Jab¼14.0 Hz, 1H),
4.35 (d, Jab¼13.6 Hz, 1H), 4.06 (d, Jab¼11.6 Hz, 1H), 3.94 (d,
Jab¼12.0 Hz, 1H), 3.90 (d, J¼14.0 Hz, 1H), 2.44 (s, 3H), 1.95 (s, 3H),
J¼7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3):
d 144.0, 142.6, 135.8,
135.5, 133.5, 131.4, 131.2, 130.0, 128.5, 127.6, 126.9, 125.5, 120.8,
119.5, 118.8, 109.5, 108.8, 71.8, 58.7, 54.5, 42.7, 38.2, 21.6, 21.2, 15.5,
13.9; IR (KBr, cmꢁ1) 2919, 1598, 1455, 1338, 1159, 750, 664; HRMS
(ESI) m/z: calcd for
598.1814.
C
31H33N3O4S2: MþNa¼598.1805; found:
1.92 (s, 3H); 13C NMR (100 MHz, CDCl3):
d 144.1, 142.0, 136.5, 135.6,
133.4,133.3,131.2, 130.2, 130.0, 129.6, 129.1, 127.9, 127.8, 127.7, 127.5,
126.5, 125.9, 125.2, 124.7, 123.4, 122.6, 121.1, 112.3, 110.8, 73.2, 58.7,
56.5, 47.1, 43.8, 21.6, 21.0,14.3; IR (KBr, cmꢁ1) 2919,1597,1452,1344,
1159, 750, 677; HRMS (ESI) m/z: calcd for
MþNa¼710.2118; found: 710.2130.
4.3.17. 9-Allyl-40-methyl-10,2-ditosyl-1,10,2,3,50,9-hexahydro-spiro
[pyrido[3,4-b]indole-4,20-pyrrole] (2q). Yellow solid; mp: 76e78 ꢀC;
1H NMR (400 MHz, CDCl3):
d
7.74 (d, J¼8.4 Hz, 2H), 7.38 (d, J¼8.0 Hz,
C
40H37N3O4S2:
2H), 7.14 (d, J¼8.0 Hz, 1H), 7.05e6.99 (m, 3H), 6.73 (d, J¼8.0 Hz, 2H),
6.58 (t, J¼7.6 Hz, 1H), 6.46 (d, J¼7.6 Hz, 1H), 5.97e5.88 (m, 1H), 5.53
(s, 1H), 5.19 (d, J¼10.4 Hz, 1H), 4.92 (d, J¼17.2 Hz, 1H), 4.64e4.62 (m,
2H), 4.37 (d, Jab¼13.6 Hz, 1H), 4.79 (d, Jab¼13.2 Hz, 1H), 3.96e3.86
4.3.13. 5-Benzyl-40-methyl-10,7-ditosyl-10,5,50,6,7,8-hexahydro-spiro
[[1,3]dioxolo[4,5-f]pyrido[3,4-b]indole-9,20-pyrrole]
(2m). Yellow
solid; mp: 220e222 ꢀC; 1H NMR (400 MHz, CDCl3):
7.68 (d,
(m, 3H), 3.50e3.45 (m,1H), 2.46 (s, 3H), 2.22 (s, 3H),1.80 (s, 3H); 13
C
d
NMR (100 MHz, CDCl3): d 144.0, 142.7, 136.1, 135.8, 133.5, 132.6,
J¼8.0 Hz, 2H), 7.35e7.28 (m, 5H), 7.08e7.05 (m, 4H), 6.72 (d,
J¼8.0 Hz, 2H), 6.53 (s, 1H), 5.80 (d, Jab¼1.2 Hz, 1H), 5.73 (d,
Jab¼1.2 Hz, 1H), 5.69 (s, 1H), 5.54 (d, J¼1.2 Hz, 1H), 5.13 (s, 2H), 4.64
(d, J¼14.0 Hz, 1H), 4.41 (d, Jab¼13.2 Hz, 1H), 4.28 (d, Jab¼13.6 Hz,
1H), 3.95 (d, Jab¼12.0 Hz, 1H), 3.88 (d, Jab¼12.0 Hz, 1H), 3.80 (d,
J¼14.0 Hz, 1H), 2.44 (s, 3H), 2.23 (s, 3H), 1.81 (s, 3H); 13C NMR
131.7, 131.4, 130.0, 128.5, 127.6, 126.9, 125.3, 121.0, 119.7, 118.7, 116.9,
110.1, 109.0, 71.9, 58.6, 54.4, 45.6, 42.8, 21.6, 21.2, 13.9; IR (KBr,
cmꢁ1) 2919, 1725, 1596, 1458, 1338, 1160, 751, 662; HRMS (ESI) m/z:
calcd for C32H33N3O4S2: MþNa¼610.1805; found: 610.1812.
4.3.18. 9-Benzyl-3,40-dimethyl-2-(4-nitrophenylsulfonyl)-10-tosyl-
1,10,2,3,50,9-hexahydrospiro[pyrido[3,4-b]indole-4,20-pyrrole]
(2r). White solid; mp: 152e154 ꢀC; 1H NMR (400 MHz, CDCl3):
(100 MHz, CDCl3):
d 144.3, 144.0, 142.7, 142.3, 136.6, 135.8, 133.6,
131.5, 131.3, 130.6, 130.0, 129.0, 128.4, 127.9, 127.6, 127.5, 127.0, 126.1,

Y.-F. Yang et al. / Tetrahedron 70 (2014) 702e707
707
Givskov, M.; Nielsen, T. E. Chem.dEur. J. 2012, 18, 16793e16800; (g) Ascic, E.;
Hansen, C. L.; Le Quement, S. T.; Nielsen, T. E. Chem. Commun. 2012, 3345e3347;
(h) Sinha, M. K.; Khoury, K.; Herdtweck, E.; Domling, A. Chem.dEur. J. 2013, 19,
d
8.33 (d, J¼8.8 Hz, 2H), 8.15 (d, J¼8.8 Hz, 2H), 7.33e7.25 (m, 3H),
7.18 (d, J¼8.4 Hz, 1H), 7.09 (d, J¼6.4 Hz, 2H), 7.00 (t, J¼8.0 Hz, 1H),
6.63e6.55 (m, 4H), 6.43 (d, J¼8.0 Hz, 2H), 5.48 (s, 1H), 5.36 (d,
Jab¼16.8 Hz, 1H), 5.27 (d, Jab¼16.8 Hz, 1H), 4.70 (d, J¼15.6 Hz, 1H),
4.43 (d, J¼15.2 Hz, 1H), 4.29 (d, Jab¼15.2 Hz, 1H), 4.22 (d,
Jab¼15.2 Hz, 1H), 3.48 (dd, J¼7.2, 14.0 Hz, 1H), 2.08 (s, 3H), 1.90 (s,
€
8048e8052.
3. For recent papers on THBCs: (a) Bandini, M.; Melloni, A.; Piccinelli, F.; Sinisi, R.;
Tommasi, S.; Umani-Ronchi, A. J. Am. Chem. Soc. 2006, 128, 1424e1425; (b)
Angeli, M.; Bandini, M.; Garelli, A.; Piccinelli, F.; Tommasi, S.; Umani-Ronchi, A.
Org. Biomol. Chem. 2006, 4, 3291e3296; (c) Li, C.-F.; Liu, H.; Liao, J.; Cao, Y.-J.;
3H), 1.15 (d, J¼6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3):
d 150.0,
ꢀ
Liu, X.-P.; Xiao, W.-J. Org. Lett. 2007, 9, 1847e1850; (d) Bondzic, B. P.; Eilbracht, P.
Org. Lett. 2008, 10, 3433e3436; (e) Cai, Q.; Zhao, Z.-A.; You, S.-L. Angew. Chem.,
Int. Ed. 2009, 48, 7428e7431; (f) Bandini, M.; Eichholzer, A.; Gualandi, A.;
Quinto, T.; Savoia, D. ChemCatChem 2010, 2, 661e665; (g) Arai, T.; Wasai, M.;
Yokoyama, N. J. Org. Chem. 2011, 76, 2909e2912; (h) Cai, Q.; Liang, X.-W.; Wang,
S.-G.; You, S.-L. Org. Biomol. Chem. 2013, 11, 1602e1605; (i) Song, H.; Liu, Y.;
Wang, Q. Org. Lett. 2013, 15, 3274e3277.
145.2,142.1,136.4,136.2,134.2,129.1,129.0,128.1,127.9,127.3,126.6,
126.1, 125.8, 124.1, 121.2, 119.9, 119.0, 109.3, 103.0, 74.0, 65.8,
59.7, 59.2, 47.0, 21.0, 16.2, 14.3; IR (KBr, cmꢁ1) 2989, 1533, 1454,
1348, 1157, 736; HRMS (ESI) m/z: calcd for
MþH¼683.1993; found: 683.2004.
C36H34N4O6S2:
4. (a) Wang, S.-G.; Zhang, W.; You, S.-L. Org. Lett. 2013, 15, 1488e1491; (b) Zhang,
Y. Q.; Zhu, D.-Y.; Jiao, Z.-W.; Li, B.-S.; Zhang, F.-M.; Tu, Y.-Q.; Bi, Z. Org. Lett. 2011,
13, 3458e3461.
4.3.19. N-(3-(9-benzyl-3-methyl-2-(4-nitrophenylsulfonyl)-2,3-
dihydro-1H-pyrido[3,4-b]indol-4(9H)-ylidene)-2-methylallyl)-4-
methylbenzenesulfonamide (2rem). Yellow solid; mp: 82e84 ꢀC;
^
5. For recent reviews on gold-catalysis: (a) Michelet, V.; Toullec, P. Y.; Genet, J.-P.
Angew. Chem., Int. Ed. 2008, 47, 4268e4315; (b) Muzart, J. Tetrahedron 2008, 64,
5815e5849; (c) Li, Z.; Brouwer, C.; He, C. Chem. Rev. 2008, 108, 3239e3265; (d)
Arcadi, A. Chem. Rev. 2008, 108, 3266e3325; (e) Gorin, D. J.; Sherry, B. D.; Toste,
F. D. Chem. Rev. 2008, 108, 3351e3378; (f) Hashmi, A. S. K.; Rudolph, M. Chem.
Soc. Rev. 2008, 37, 1766e1775; (g) Belmont, P.; Parker, E. Eur. J. Org. Chem. 2009,
6075e6089; (h) Hashmi, A. S. K. Angew. Chem., Int. Ed. 2010, 49, 5232e5241; (i)
Alcaide, B.; Almendros, P.; Alonso, J. M. Org. Biomol. Chem. 2011, 9, 4405e4416;
2.65:1 dr value. 1H NMR (400 MHz, CDCl3):
d
[7.98 (d, J¼8.8 Hz),
7.89 (d, J¼8.8 Hz), 2H], 7.79 (d, J¼8.4 Hz,1H), 7.72e7.68 (m, 2H), 7.56
(d, J¼8.8 Hz, 1H), 7.32e7.27 (m, 6H), 7.20e7.15 (m, 2H), 7.04e6.96
(m, 3H), 5.33e5.28 (m, 1H), 5.20e5.15 (m, 1H), [5.10 (h), 4.76 (h),
1H], 4.89e4.76 (m, 2H), 4.46e4.37 (m, 1H), 3.74e3.52 (m, 2H), [2.41
(s), 2.38 (s), 3H], [1.83 (s), 1.77 (s), 3H], [1.47 (d, J¼6.8 Hz), 1.36 (d,
ꢀ
(j) Corma, A.; Leyva-Perez, A.; Sabater, M. J. Chem. Rev. 2011, 111, 1657e1712; (k)
ꢀ
Boorman, T. C.; Larrosa, I. Chem. Soc. Rev. 2011, 40, 1910e1925; (l) Leyva-Perez,
A.; Corma, A. Angew. Chem., Int. Ed. 2012, 51, 614e635; (m) Gulevich, A. V.;
Dudnik, A. S.; Chernyak, N.; Gevorgyan, V. Chem. Rev. 2013, 113, 3084e3213.
6. For recent reviews on silver-catalysis: (a) Halbes-Letinois, U.; Weibel, J.-M.;
Pale, P. Chem. Soc. Rev. 2007, 36, 759e769; (b) Weibel, J.-M.; Blanc, A.; Pale, P.
Chem. Rev. 2008, 108, 3149e3173; (c) Yamamoto, Y. Chem. Rev. 2008, 108,
J¼6.8 Hz), 3H]; 13C NMR (100 MHz, CDCl3):
d 195.8, 149.6, 144.7,
143.5, 137.2, 136.5, 129.8, 129.1, 128.1, 127.0, 126.4, 126.2, 124.6,
123.9, 123.5, 123.0, 120.6, 119.2, 109.4, 103.9, 101.5, 52.3, 46.9, 46.3,
38.0, 21.4, 20.6, 17.8; IR (KBr, cmꢁ1) 3296, 3062, 2927, 1604, 1530,
1454, 1349, 1159, 1092, 855, 737.
ꢀ
~
3199e3222; (d) Alvarez-Corral, M.; Munoz-Dorado, M.; Rodríguez-García, I.
Chem. Rev. 2008, 108, 3174e3198.
7. For gold-catalyzed rearrangements of alkynyl aziridines: (a) Davies, P. W.;
Martin, N. Org. Lett. 2009, 11, 2293e2296; (b) Chen, D.-D.; Hou, X.-L.; Dai, L.-X.
Tetrahedron Lett. 2009, 50, 6944e6946; (c) Du, X.; Xie, X.; Liu, Y. J. Org. Chem.
2010, 75, 510e513.
Acknowledgements
8. Blanc, A.; Alix, A.; Weibel, J.-M.; Pale, P. Eur. J. Org. Chem. 2010, 1644e1647.
9. (a) Kern, N.; Blanc, A.; Weibel, J.-M.; Pale, P. Chem. Commun. 2011, 6665e6667;
(b) Kern, N.; Blanc, A.; Miaskiewicz, S.; Robinette, M.; Weibel, J.-M.; Pale, P. J.
Org. Chem. 2012, 77, 4323e4341.
10. (a) Shu, X.-Z.; Liu, X.-Y.; Ji, K.-G.; Xiao, H.-Q.; Liang, Y.-M. Chem.dEur. J. 2008, 14,
5282e5289; (b) Yang, Y.-F.; Shu, X.-Z.; Luo, J.-Y.; Ali, S.; Liang, Y.-M. Chem.dEur.
J. 2012, 18, 8600e8604.
Financial support from National Natural Science Foundation
(NSF 21072080 and 21272101), National Basic Research Program of
China (973 Program) 2010CB833203, ‘111’ program of MOE and
PCSIRT: IRT1138 for financial support.
11. For gold or silver-catalyzed FriedeleCrafts type reactions on aziridine: (a) Bera,
M.; Roy, S. Tetrahedron Lett. 2007, 48, 7144e7146; (b) Sun, X.; Sun, W.; Fan, R.;
Wu, J. Adv. Synth. Catal. 2007, 349, 2151e2155.
Supplementary data
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2013.11.084. These data include MOL files
and InChIKeys of the most important compounds described in this
article.
12. For gold-catalyzed hydroamination of allenes: (a) Morita, N.; Krause, N. Org.
Lett. 2004, 6, 4121e4123; (b) Widenhoefer, R. A.; Han, X. Eur. J. Org. Chem. 2006,
4555e4563; (c) Morita, N.; Krause, N. Eur. J. Org. Chem. 2006, 4634e4641; (d)
Zhang, Z.; Liu, C.; Kinder, R. E.; Han, X.; Qian, H.; Widenhoefer, R. A. J. Am. Chem.
Soc. 2006, 128, 9066e9073; (e) LaLonde, R. L.; Sherry, B. D.; Kang, E. J.; Toste, F.
D. J. Am. Chem. Soc. 2007, 129, 2452e2453; (f) Wang, Z. J.; Benitez, D.;
Tkatchouk, E.; Goddard, W. A., III; Toste, F. D. J. Am. Chem. Soc. 2010, 132,
References and notes
€
13064e13071; (g) Pflasterer, D.; Dolbundalchok, P.; Rafique, S.; Rudolph, M.;
Rominger, F.; Hashmi, A. S. K. Adv. Synth. Catal. 2013, 355, 1383e1393; (h)
Hannedouche, J.; Schulz, E. Chem.dEur. J. 2013, 19, 4972e4985.
13. CCDC 949427 (2a) contains the supplementary crystallographic data for this
paper. These data can be obtained free of charge from the Cambridge Crys-
tallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
1. (a) Kam, T.-S.; Sim, K.-M. Phytochemistry 1998, 47, 145e147; (b) Chen, F.-E.;
Huang, J. Chem. Rev. 2005, 105, 4671e4706; (c) Peng, W.; Wang, Z.; Xu, A. Curr.
Med. Chem. 2007, 14, 479e500; (d) El-Sayed, M.; Verpoorte, R. Phytochem. Rev.
2007, 6, 277e305; (e) Edwankar, R. V.; Edwankar, C. R.; Namjoshi, O. A.; De-
schamps, J. R.; Cook, J. M. J. Nat. Prod. 2012, 75, 181e188; (f) Lesma, G.; Cecchi,
R.; Cagnotto, A.; Gobbi, M.; Meneghetti, F.; Musolino, M.; Sacchetti, A.; Silvani,
A. J. Org. Chem. 2013, 78, 2600e2610.
14. Raghavan, S.; Babu, V. S. Tetrahedron 2011, 67, 2044e2050.
15. The electrophilic aromatic substitution reaction of pyrroles occurs pre-
dominantly at an a-carbon atom. For the reactivity of pyrrole heterocycles, see:
2. For recent reviews on PicteteSpengler reactions: (a) Cox, E. D.; Cook, J. M.
Chem. Rev. 1995, 95, 1797e1842; (b) Nielsen, T. E.; Diness, F.; Meldal, M. Curr.
Opin. Drug Discovery Dev. 2003, 6, 801e814; (c) Bandini, M.; Emer, E.; Tommasi,
(a) Trofimov, B. A.; Nedolya, N. A. In Comprehensive Heterocyclic Chemistry III;
Jones, G., Ramsden, C. A., Eds.; Elsevier: Amsterdam, The Netherlands, 2008;
Vol. 3, pp 45e268; (b) Tsuchimoto, T. Chem.dEur. J. 2011, 17, 4064e4075.
16. There was no reaction below 50 ꢀC, this process need more energy than one-
pot reaction.
€
S.; Umani-Ronchi, A. Eur. J. Org. Chem. 2006, 3527e3544; (d) Stockigt, J.; An-
tonchick, A. P.; Wu, F.; Waldmann, H. Angew. Chem., Int. Ed. 2011, 50,
8538e8564 For recent papers on PicteteSpengler reactions: (e) Bondzic, B. P.;
Eilbracht, P. Org. Biomol. Chem. 2008, 6, 4059e4063; (f) Komnatnyy, V. V.;