Cycloaddition versus alkylation reactions of 2-vinylindoles with α,β-unsaturated carbonyl compounds under gold catalysis

Article abstract of DOI:10.1002/ejoc.201300725

The gold-catalyzed intermolecular Diels-Alder cycloaddition and competitive Michael addition reactions between 2-vinylindoles and enones/enals are reported. The reaction outcome strictly correlates with the electronic character of the heteroaromatic substrate. Thus, Diels-Alder cycloadducts are the sole products in the presence of less electron-rich heterocycles, whereas Michael addition adducts are observed with more electron-rich heterocycles. Plausible competitive reaction mechanisms are proposed and discussed as well. Copyright

Full text of DOI:10.1002/ejoc.201300725

FULL PAPER
DOI: 10.1002/ejoc.201300725
Cycloaddition versus Alkylation Reactions of 2-Vinylindoles with
α,β-Unsaturated Carbonyl Compounds Under Gold Catalysis
Valentina Pirovano,[a] Monica Dell’Acqua,[a] Diego Facoetti,[a] Donatella Nava,[a]
Silvia Rizzato,[b] Giorgio Abbiati,[a] and Elisabetta Rossi*[a]
Keywords: Gold / Nitrogen heterocycles / Cycloaddition / Michael addition / Diastereoselectivity
The gold-catalyzed intermolecular Diels–Alder cycloaddition
and competitive Michael addition reactions between 2-vinyl-
indoles and enones/enals are reported. The reaction outcome
strictly correlates with the electronic character of the het-
eroaromatic substrate. Thus, Diels–Alder cycloadducts are
the sole products in the presence of less electron-rich hetero-
cycles, whereas Michael addition adducts are observed with
more electron-rich heterocycles. Plausible competitive reac-
tion mechanisms are proposed and discussed as well.
sine,[9] and coumarin-fused tetrahydrocarbazoles.[10] In ad-
dition, we recently[11] described the DA cycloaddition reac-
Introduction
tions of (E)-2-vinylindole-1-carboxylic acid ethyl esters[12]
1
The Diels–Alder (DA) reaction is one of the most power-
ful methods to build both simple and complex (poly)cyclic
and (poly)heterocyclic compounds.[1] In addition to the si-
multaneous formation of two new carbon–carbon or car-
bon–heteroatom bonds, the success of the DA methodology
is predominantly a result of the high regio-, diastereo-, and
enantioselectivities observed. Excellent results, related to
the reaction mechanism, are achieved by modifying the sub-
stituents of both the diene and dienophile as well as by the
design and use of different catalytic species. Inter alia, many
DA reactions are accelerated by Lewis acid (LA) catalysts,
and catalyzed reactions often exhibit increased regio- and
stereoselectivities in comparison to uncatalyzed ones.[2] On
the other hand, it is worth noting that catalyzed reactions
may produce different products as a result of the LA em-
ployed.[3] In particular, the DA reactions of internal-exter-
nal ring dienes, which are derived from heterocyclic com-
pounds, with activated C=C dienophiles represent an at-
tractive approach to polyheterocyclic compounds.[1b–1d] In
this context, 2-vinylindole species are useful partners in
[4+2] cycloaddition reactions to provide easy access to com-
plex tetrahydrocarbazole derivatives. Beginning with the
pioneering works of Pindur,[4] the most recent findings in-
clude applications to the syntheses of composite carb-
azoles[5] and indole alkaloids such as (Ϯ)-3-epi-dasycarpi-
done,[6] pyrrolocarbazoles,[7] vinca alkaloids,[8] (+)-minfien-
with C=C dienophiles 2, (see Scheme 1). The reactions,
which were performed in toluene in the presence of 15% of
either magnesium perchlorate, scandium triflate, or boron
trifluoride as the Lewis acid catalysts, proceeded to yield
the expected diastereomeric cycloadducts (Ϯ)-3 and (Ϯ)-3Ј
with diastereoselectivities that ranged from poor to excel-
lent, depending on the substitution pattern of both the
dienes and dienophiles. In the same context, we recently
described the synthesis of tetrahydrocarbazole derivatives
through an intermolecular cycloaddition of vinyl indoles
and N-allenamides under gold catalysis.[13]
[a] Dipartimento di Scienze Farmaceutiche, Sezione di Chimica
Generale e Organica “A. Marchesini”,
21, Via Venezian, 20133 Milano, Italy
E-mail: elisabetta.rossi@unimi.it
Homepage: http://users.unimi.it/istchimorg/elisabetta.htm
[b] Dipartimento di Chimica,
19, Via Golgi, 20133 Milano, Italy
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201300725.
Scheme 1. Diels–Alder reactions of 2-vinylindoles with C=C dieno-
philes.
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With the excellent reported results for copper-catalyzed Table 1. Optimization of reaction conditions.[a]
DA reactions[14] and the recent gain in popularity of both
silver- and gold-based catalysts,[15] we were curious to test
the catalytic activity of the entire series of coinage metals
in our intermolecular DA reactions. Coinage metal salts
display σ- and π-philic properties to activate either the car-
bon–carbon or carbon–heteroatom multiple bonds.[16]
Thus, testing their performance in our reactions appeared
particularly attractive. Moreover, as the conjugate addition
of activated alkenes to indoles under gold catalysis is a well-
investigated reaction, the competitive formation of
Michael-type adducts (MA)[17] would also be evaluated.
The use of silver salts as a conventional LA in DA and aza-
DA reactions has been reported for the reactions of several
dienes with acrylonitriles[18] and imines,[19] respectively.
Entry Catalyst [mol-%]
Solvent
T
t
%
%
[°C] [h] Yield[b] de[c]
Moreover, several studies that explore the oxophilic Lewis
acidity of an Au species in 1,3-dipolar cycloaddition reac-
tions have recently been published,[20] and cycloaddition re-
actions in which a gold catalyst activates the π-bonds have
been recently reviewed.[21]
1
2
3
4
5
6
7
8
Mg(ClO4)2 (15)
Sc(OTf)3 (15)
BF3·OEt2 (15)
CuOTf (15)
toluene
CH2Cl2
toluene
toluene
CH2Cl2
toluene
CH2Cl2
toluene
toluene
toluene
toluene
toluene
CHCl3
toluene
110
r.t.
–20 1.5
r.t. 24
r.t. 120
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
24
24
77
95
92
–
95
81
94
88
–
96
86
93
83
99
43
67
84
–
CuOTf (15)
64[d]
71[d]
71
78
–
Cu(OTf)2 (15)
Cu(OTf)2 (15)
AgOTf (2)
Au(PPh3)Cl (2)
Au(PPh3)Cl/AgOTf (2)
Au(PPh3)Cl/AgSbF6 (2)
Au(PPh3)OTf (2)
96
24
24
24
24
24
24
24
24
Results and Discussion
9
10
11
12
13
14
86
89
86
75
75
By using ethyl 2-[(E)-2-p-tolylvinyl]-1H-indole-1-carb-
oxylate (1a)[11,12] and 3-buten-2-one (2a) in a model reac-
tion, we tested a series of reaction conditions for the synthe-
sis of tetrahydrocarbazoles (Ϯ)-3a and (Ϯ)-3Јa (see
Table 1).
Au(PPh3)Cl/AgOTf (2)
[e]
BINAP(AuCl)2
AgOTf (2)
/
15
16
17
18
19
20
PPh3AuNTf2
toluene
toluene
toluene
toluene
toluene
toluene
r.t.
80
80
r.t.
0
24
48
48
1.5
18
24
–
–
75[d]
60[d]
85
86
–
In all of the experiments, endo-tetrahydrocarbazole (Ϯ)-
3a was the main reaction product, and the Michael-type
adduct was neither isolated nor observed by 1H NMR
Au(IPr)Cl[e]/AgOTf (5)
Au(IPr)Cl[e]/AgSbF6 (5)
AuCl3 (2)
AuCl3 (2)
PtCl2 (2)
61
85
99
93
–
analysis of the crude reaction mixture. Our previously re-
r.t.
[11a]
ported results with Mg(ClO4)2
are included in Table 1,
[a] For Entries 1, 2, and 4–20, a solution of the catalyst in the ap-
propriate solvent (2 mL) was treated with 1a (1 equiv.) and 2a
(1.2 equiv.). At the end, the solvent was removed, and the residue
was purified by flash chromatography over silica gel. For Entry 3,
see Exp. Section. [b] Yield of combined isolated DA products.
[c] Diastereomeric excess (de) values determined using isolated
products. [d] Calculated by 1H NMR analysis of the endo/exo mix-
ture. [e] BINAP = 2,2Ј-bis(diphenylphosphanyl)-1,1Ј-binaphthyl,
IPr = 1,3-bis(diisopropylphenyl)imidazol-2-ylidene.
Entry 1, and the results of the evaluation of scandium tri-
flate (OTf) and boron trifluoride–diethyl ether, which were
selected as the best catalysts for the DA reactions of 2-vinyl-
indoles with cyclic C=C dienophiles,[11b] are listed in
Table 1, Entries 2 and 3. In our model reaction, excellent
yields were obtained with both catalysts, but better dia-
stereoselectivity resulted when the reaction was performed
in toluene at –20 °C with boron trifluoride–diethyl ether.
Next, we tested the activity of the coinage metals. Both cop-
per(I) and copper(II) triflate were active catalysts when and 11) to give yields that ranged from 96 to 86% and de
dichloromethane was used as the solvent, whereas in tolu- values from 86 to 89%. The effective catalyst was a cationic
ene only copper(II) triflate was effective (see Table 1, En- gold(I) species as suggested by the experiment performed
tries 4–7). The reactions could be performed at room tem- with isolated triphenylphosphane gold(I) triflate[22] (see
perature with a catalyst loading of 15 mol-%, and excellent Table 1, Entry 12). Toluene seemed to be the solvent of
yields and good diastereomeric excess values were achieved choice, as the reaction that was performed in chloroform
under these conditions. However, no reaction occurred with (see Table 1, Entry 13) resulted in a reduced yield and de
a catalyst loading of 5 mol-% under the conditions reported value. As a consequence, we briefly explored several cat-
in Table 1, Entries 4–7. Silver triflate gave similar good re- ionic gold species. The reaction that was performed in the
sults with a catalyst loading of 2 mol-% (see Table 1, En- presence of a bidentate phosphane ligand resulted in a
try 8), whereas triphenylphosphane gold(I) chloride was in- marked decrease in diastereoselectivity (see Table 1, En-
effective (see Table 1, Entry 9). Cationic gold(I) complexes, try 14), whereas the reaction that was carried out in the
which were generated in situ from triphenylphosphane presence of a more coordinating counterion (i.e., NTf2) was
gold(I) chloride and silver triflate or silver hexafluoro- unsuccessful (see Table 1, Entry 15). Finally, the cationic
antimonate, provided better results (see Table 1, Entries 10 species that was generated in situ from an N-heterocyclic
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Cycloaddition versus Alkylation Reactions
carbene (NHC) gold(I) chloride complex and silver triflate gold(I) at room temp. for 12 h and at 110 °C for 12 h gave
or silver hexafluoroantimonate were ineffective at room rise to 3k/3Јk in good yield but with a poor de value,
temperature but at 80 °C gave the corresponding tetra- whereas the reaction with gold(III) chloride after 24 h at
hydrocarbazoles in decreased yields and with moderate dia- room temp. afforded 3k/3Јk in poorer yield but with a de
stereoselectivities (see Table 1, Entries 16 and 17). Next, value with the exo adduct as the main reaction product.
gold(III) chloride was tested at room temperature in toluene The behavior of 4 with both gold(I) and gold(III) catalysts
to give similar results with respect to Au(PPh3)Cl/AgOTf was similar to that of N-ethoxycarbonyl derivatives 1a–1f
(see Table 1, cf. Entries 10 and 18), however, there was a and afforded 8-methoxy-2-acetyl-3-(p-tolyl)-1,2,3,4-tetra-
tangible reduction in the reaction time. Lowering the reac- hydrodibenzo[b,d]furans 5 and 5Ј in moderate overall yield
tion temperature to 0 °C did not affect yield or the dia- and with a better de value in the presence of gold(III) chlor-
stereomeric ratio (see Table 1, Entry 19). A comparison be- ide (see Table 2, Entry 11). In most of the experiments, the
tween platinum and gold-based catalysts, in which the com- gold(III) chloride catalyst appeared to be superior to the
plementarity of electrophilic activation has been demon- cationic gold(I) catalyst and provided better yields and dia-
strated,[23] was performed (see Table 1, Entry 20), but plati- stereomeric ratios. Only the reactions performed with 2b
num chloride as a catalyst was ineffective.
gave similar results with both catalysts (see Table 2, En-
In most cases, the coinage metal catalysts gave better dia- tries 6 and 7).
stereomeric ratios than those obtained with magnesium per-
The structures of the diastereomeric cycloadducts 3 and
chlorate and scandium triflate, and these reactions pro- 3Ј were assigned on the basis of analytical and spectro-
ceeded faster or under milder conditions (see Table 1, En- scopic data. In particular, the combination of 1D [1H
tries 1 and 2 vs. 7 and 8, 10–14, and 16–19). On the other NMR, attached proton test (APT)] and 2D (COSY,
hand, these results were comparable to those obtained un- HETCOR) experiments, which were performed at 300 or
der boron trifluoride catalysis. Although under coinage 500 MHz, with C6D6 or CDCl3 as solvents, allowed the
metal catalysis, the reactions could be performed at room complete assignment of chemical shifts and coupling con-
temperature (see Table 1, Entries 3 vs. 10 and 18). Hence, stants. The regio- and stereochemistry of the DA adducts
upon comparing the reported results, we explored the scope were assigned on the basis of spatial coupling interactions,
of the reaction under the conditions in Table 1, Entries 10 which were detected by 2D NOE experiments.[11] Moreover,
and 18 by treating vinylindoles 1a–1f[11–13] with a carbamate the structures and the endo stereochemistry of compounds
at N-1 and (E)-5-methoxy-2-(4-methylstyryl)benzofuran 3f and 5 were assigned on the same basis and unambigu-
4[13] with alkenes 2a–2e (see Table 2). The [4+2] cycload- ously confirmed by X-ray diffraction analysis of a single
dition reactions of 2-vinylbenzofurans with activated alk- crystal (see Supporting Information).
enes have been seldom reported in the literature[1c,24] but
proceed under thermal or high pressure conditions with cy- of the dienophile by the metal, and the formation of the
clic alkenones, tetracyanoethylene, and maleic anhydride. DA adduct could take place through a pseudoconcerted or
The reaction mechanism probably involves σ-activation
In almost all reported experiments, tetrahydrocarbazoles a fast stepwise mechanism (see Scheme 2).[4] In the fast
(Ϯ)-3 and (Ϯ)-3Ј were obtained in good to excellent overall stepwise path, the driving force to the exclusive formation
yields. Once again, the Michael-type addition compounds of the cycloaddition products, which avoids the formation
were neither isolated nor detected. The diastereoselectivity of the Michael-type adducts, could be related to the pres-
for the endo product remained high with 2-vinylindoles that ence of the carbamate substituent on the indole. This can
contained arenes with different electronic properties at the lower the nucleophilic character of the indole nitrogen, and
β-position (see Table 2, Entries 1 and 2). Moreover, nearly thus the relative contribution of intermediate IB with re-
endo diastereospecific reactions were attained with β-alkyl- spect to IC results in the enhanced electrophilic character of
substituted vinylindoles 1d–1f (see Table 2, Entries 3–5). In the outer carbon atom of the vinyl system. Similar concerns
these latter reactions, a small percentage of regioisomeric account for the results obtained with compound 4. Ad-
1,3-disubstituted tetrahydrocarbazoles 3ЈЈa–3ЈЈc were also ditionally, the observed endo/exo ratios could be rational-
isolated as diastereomeric mixtures (see Table 2, Notes d ized as reported for common LA-catalyzed DA reactions.
and e).[25] The introduction of a phenyl group at the β-posi- Thus, LA-catalyzed cycloadditions proceed faster than their
tion of the dienophiles resulted in an almost complete loss thermal counterparts and are often more regio- and stereo-
of diastereoselectivity with both aryl and alkyl vinylindoles selective, depending on the LA employed. In our experi-
(see Table 2, Entries 6 and 7), and a higher reaction tem- ence, the endo diastereoselectivity for the reactions of in-
perature was required when vinylindole 1e was the substrate dole-N-carbamates 1a–1f with β-unsubstituted dienophiles
(see Table 2, Entry 7). A severe drop in the diastereoselec- 2a and 2c remains consistently high or specific, which is a
tivity was also observed when crotonaldehyde and cinnam- result best explained through FMO theory.[1] The loss of
aldehyde were used as dienophiles (see Table 2, Entries 8 diastereoselectivity that is observed in the reactions with
and 9), and once again the introduction of a phenyl group dienophiles 2b and 2d is probably because of secondary or-
at the β-position of the dienophile resulted in the isolation bital interactions (SOI) between the β-phenyl substituent of
of almost equimolar amounts of endo/exo cycloadducts (see the dienophile and the π-system of the diene, with a conse-
Table 2, Entry 9). Finally, cyclic dienophile 2e appeared less quent decrease in the energy difference between the endo
reactive (see Table 2, Entry 10). The reaction with cationic and exo transition states.[1] When the C=C double bond of
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Table 2. Scope of the [4+2] cycloaddition reactions of 2-vinyl-substituted heterocycles with electrophilic alkenes.[a]
[a] Heterocycle 1 (1 equiv.) and alkene 2 (1.2 equiv.). [b] Yield of combined isolated products. [c] Diasteromeric excess values determined
using isolated products. [d] Given yields include 5, 6, and 10%, respectively, of regioisomeric 3ЈЈa, R1 = CH3; 3ЈЈb, R1 = cyclohexyl; 3ЈЈc,
R1 = n-C4H9 (unresolved mixture of diastereomers). [e] Given yields include 3, 8, and 7%, respectively, of regioisomeric 3ЈЈa–3ЈЈc. [f] Reco-
vered 1f, 25%. [g] At room temp. for 48 h and at 80 °C for 17 h. [h] Along with a mixture of unidentified tarry compounds. [i] Recovered
1e, 50%. [j] Recovered 1a, 25%. [k] At room temp. for 12 h and at 110 °C for 12 h. [l] Recovered 1a, 18%. [m] Recovered 1a, 50%.
[n] Recovered 4, 18%. [o] Recovered 4, 27%.
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Cycloaddition versus Alkylation Reactions
Scheme 2. Proposed mechanisms for DA cycloadditions.
the dienophile is secured as part of a cycle, as in 2e, the Table 3. Reactivity of vinylindoles 1g and 1h with MVK 2a.[a,b]
obtained results are erratically distributed and difficult to
rationalize, which suggests that additional factors such as
steric and electrostatic effects, closed-shell repulsions, and
secondary orbital interactions could be operative.
All these observations are in agreement with the results
from a second set of experiments in which the electronic
properties of the heterocyclic system were evaluated. Thus,
we explored the reactivity of the (E)-N-unsubstituted and
(E)-N-methyl-2-vinylindoles 1g and 1h[13] in reactions with
methyl vinyl ketone (MVK) 2a (see Table 3). A comparison
of the reactions with cationic gold(I), gold(III), and BF3 as
catalysts was accomplished. N-unsubstituted 2-vinylindoles
are reported to react thermally with electrophilic acyclic
alkenes or in the presence of silica gel or molecular sieves to
yield the single endo diastereomer, although in low yield.[4]
The reactions performed with 1g gave poor results with
all of the catalysts, and the Michael-type addition product
6a was always isolated along with DA adduct 3l, which was
obtained as a single diastereomer (see Table 3, Entries 1–3).
Working with 1h under boron trifluoride or cationic gold(I)
catalysis, the DA cycloadduct 3m was obtained in high
yields and with complete diastereoselectivity (see Table 3,
Entries 4 and 5). Conversely, the reaction of 1h under
Entry
1
Catalyst
[mol-%]
T
Overall
MA DA de[c]
[%] [%] [%]
[h] yield [%]
1
2
3
4
5
6
1g BF3·OEt2 (15)
2.5 28[d]
11
44
58
17 Ͼ99
18 Ͼ99
18 Ͼ99
1g Au(PPh3)Cl/AgOTf (2) 24 62[e]
1g AuCl3 (2)
1h BF3·OEt2 (15)
1h Au(PPh3)Cl/AgOTf (2) 24 72
1h AuCl3 (2)
24 76
4
80
trace 80 Ͼ99
trace 72 Ͼ99
24 77[f]
57
20 Ͼ99
[a] Heterocycle 1 or 4 (1 equiv.) and 2 (1.2 equiv.), toluene, room
temp. [b] Heterocycle 1 (1 equiv.) and 2 (1.5 equiv.), CH2Cl2,
–20 °C. [c] Diastereomeric excess values determined using isolated
products. [d] Along with a mixture of unidentified tarry com-
pounds. [e] Recovered 1g, 20%. [f] Recovered 1h, 14%.
gold(III) catalysis furnished a mixture of 6b and 3m (as a dependent on the catalyst employed. However, compounds
single diastereomer, see Table 3, Entry 6). Therefore, the 6a and 6b could arise from a Friedel–Craft-type of reaction
Michael-type addition and the Diels–Alder reaction were in or involve the C–H activation of the heteroaromatic system
competition when the more electron-rich 2-vinyl-1H-indole as reported in Sche of the well-known σ-acidity of boron tri-
1g was employed. When 1h was used, the reaction type was fluoride, Path A is effective under boron catalysis, and the
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E. Rossi et al.
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behaviors of 1g and 1h (relative yields of 6a/6b vs. 3l/3m) σ-acidity of cationic gold(I) species, a Friedel–Crafts-type
reflect the relative reaction rate of the MA with respect to mechanism could more realistically explain the formation
the DA reaction of N-unsubstituted and N-alkyl-substi- of the observed MA products (see Scheme 3, Path A).
tuted indoles, with the latter being less reactive than the
It is interesting to note that the mechanisms described in
former. On the other hand, a mechanism involving C–H Scheme 3, Path A and in Scheme 2 share the same type of
activation (see Scheme 3, Path B) of te heteroaromatic sys- cationic intermediate I, and the reactivity seems to be mod-
tem could not be a priori excluded under gold(III) catalysis, ulated by the relative stability of I. For the N-carbamate-
as suggested by several authors.[26] Nevertheless, under and the O-heterocycle, the outer C atom of the vinyl system
gold(I) catalysis, the Csp2–H bond activation has been dem- in intermediate I became a stronger acceptor with respect
onstrated to be consistent only for electron-deficient sub- to the same intermediate generated from the N–H substrate,
strates.[27] Moreover, 3-benzofuranyl- and 3-indolyl-gold(I) for which a fast deprotonation/rearomatization of the het-
derivatives have been isolated and characterized by Hashmi erocyclic ring could occur. Finally, indirect support to our
as stable intermediates of gold(I)-catalyzed hydroxylation hypothesis was obtained by the reactions with either ethyl
and hydroamination reactions of ortho-alkynylphenols and 2-phenyl-1H-indole-1-carboxylate (1i) or 1-methyl-2-
anilines. However, they easily undergo deauration reactions phenyl-1H-indole (1j) and MVK 2a in toluene at room tem-
and cannot be prepared from the corresponding benzo- perature in the presence of Au(PPh3)Cl/AgOTf (2 mol-%,
furan or indole derivatives and gold(I).[28] On the contrary, see Scheme 4). Under these conditions, 1i was recovered
the oxophilic character of gold(I) species has been high- from the reaction mixture even after a prolonged time
lighted by several authors, in particular by Toste with re- (96 h), whereas 1j furnished the corresponding 3-alkylated
gard to gold(I)-catalyzed Mannich reactions of azalact- indole 6c in 82% yield.
ones[20a] and by Youn with regard to the gold(I)-catalyzed
These findings appear to confirm our hypothesis that less
intramolecular cyclizations of 2-alkenyl carbonyl com- electron-rich heterocycles are the substrates of choice to
pounds.[29] Thus, considering our results, we could reason- achieve the DA adducts selectively, and a reaction pathway
ably disregard, a mechanism involving a Csp2–H activation that involves a simple addition to an α,β-unsaturated com-
step under gold(I) catalysis, and because of the well-known pound is not allowed.
Scheme 3. Plausible reaction mechanisms for MA reactions.
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Cycloaddition versus Alkylation Reactions
Scheme 4. Alkylation of indoles under cationic gold(I) catalysis.
nuclear correlation (HETCOR), NOESY] were used, where appro-
priate, to aid in the assignment of structures. Low-resolution MS
spectra were recorded with a Thermo-Finnigan LCQ advantage AP
electrospray/ion trap-equipped instrument using a syringe pump
device to directly inject the sample solutions. 1-Methyl-2-phenyl-
1H-indole (1j) was commercially available and was used as pur-
chased. 2-Vinylindoles 1a–1h and 2-vinylbenzofuran 4 are known
compounds.[11–13] CCDC-934078 and -934079 contain the supple-
mentary crystallographic data for this paper. These data can be
obtained free of charge from The Cambridge Crystallographic
Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
Conclusions
This work compared the efficiency of coinage metal salts
and complexes to traditional Lewis acid as catalysts in
intermolecular DA reactions of vinyl heterocycles with acti-
vated alkenes. The most efficient catalysts were the cationic
gold(I) complex Au(PPh3)Cl/AgOTf and gold(III) chloride,
which gave results comparable to those obtained with the
best performing traditional LA (boron trifluoride–diethyl
ether). The only benefit was that the reactions with the
coinage metals were performed at room temperature instead
of at –20 °C, which was necessary with boron trifluoride.
Despite this, by exploring the scope of the reaction, we were
able to realize the synthesis of new compounds that are use-
ful in medicinal and natural product chemistry. Moreover,
the results reported in this study describe and point out
several features about the reactivity of 2-vinyl heteroarom-
Ethyl 2-Phenyl-1H-indole-1-carboxylate (1i): To a suspension of
NaH (60% in mineral oil, 208 mg, 5.2 mmol) in tetrahydrofuran
(THF, 10 mL) was added 2-phenyl-1H-indole (0.5 g, 2.6 mmol) at
0 °C, and the mixture was stirred for 30 min. Then, ethyl chloro-
formate (423 mg, 0.373 mL, 3.9 mmol) was added dropwise. The
resulting mixture was warmed to room temperature and stirred for
4 h. After that time, water (10 mL) was slowly added, and the aque-
atics and α,β-unsaturated carbonyl compounds under gold ous layer was extracted with ethyl acetate (3ϫ 20 mL). The com-
bined organic layers were dried with Na2SO4, filtered, and concen-
trated under vacuum to yield 1i (0.629 g, 91%), which was used
without any further purification, as a white solid; m.p. 38.1–
catalysis. In all the studied reactions, the gold catalysts
acted as an effective σ-philic Lewis acid that was able to
activate the enone/enal partner. However, the final outcome
of the reaction (DA vs. MA adduct) seemed to be mainly
governed by the relative stability of the cationic aurate in-
termediate I. Moreover, we highlighted that conceivably the
two catalysts assumed different behaviors in the presence of
more electron-rich heterocycles and act as C–H or as σ-
activators.
38.7 °C. IR (KBr): ν = 3051, 2991, 2905, 1729, 1562, 1456, 1376,
˜
1328, 1222 cm–1. 1H NMR (200 MHz, CDCl3): δ = 8.24 (d, J =
8.4 Hz, 1 H), 7.59 (m, 1 H), 7.57–7.25 (m, 7 H), 6.62 (s, 1 H), 4.23
(q, J = 7.0 Hz, 2 H), 1.12 (t, J = 7.0 Hz, 3 H) ppm. 13C NMR
(50.3 MHz, CDCl3): δ = 151.9 (Cq), 140.8 (Cq), 137.5 (Cq), 134.7
(Cq), 129.7 (Cq), 129.1 (CH), 128.0 (CH), 127.9 (CH), 124.7 (CH),
123.4 (CH), 120.8 (CH), 115.7 (CH), 110.8 (CH), 63.2 (CH2), 13.9
(CH3) ppm. MS (ESI+): m/z (%) = 266 (100) [M + 1]+.
1-Methyl-2-phenyl-1H-indole (1j):[13] To a suspension of NaH (60%
in mineral oil, 0.11 mg, 2.86 mmol) in dry N,N-dimethylformamide
(DMF, 5 mL) was added 2-phenyl-1H-indole (0.5 g, 2.6 mmol) at
0 °C, and the mixture was stirred for 30 min. Then, methyl iodide
(369 mg, 0.163 mL, 2.6 mmol) was added dropwise. The resulting
mixture was warmed to room temperature and stirred for 24 h.
After that time, water (20 mL) was slowly added, and the aqueous
layer was extracted with ethyl acetate (3ϫ 20 mL). The combined
organic layers were dried with Na2SO4, filtered, and concentrated
under vacuum to yield 1j (0.485 g, 90%), which used without any
further purification, as a white solid; m.p. 99–101 °C. 1H NMR
(200 MHz, CDCl3): δ = 7.68–7.12 (m, 9 H), 6.57 (s, 1 H), 3.76 (s,
3 H) ppm.
Experimental Section
General Methods: All chemicals and solvents were commercially
available and used after distillation or treatment with drying agents.
Silica gel F254 thin layer plates were employed for thin layer
chromatography (TLC). Silica gel 40–63 micron/60 Å was em-
ployed for flash column chromatography. Melting points were mea-
sured with a Perkin–Elmer DSC 6 calorimeter at a heating rate of
5 °C/min. Infrared spectra were recorded with a Perkin–Elmer
FTIR 16 PC spectrometer using KBr tablets or NaCl dishes. The
1H and 13C NMR spectroscopic data were recorded with a Varian-
Gemini 200, a Bruker 300, or a Bruker 500 Avance spectrometer
at room temperature. CDCl3 or C6D6 were used as the solvent, and
the residual solvent peaks were used as the internal reference. The
APT sequence was used to distinguish the methine and methyl car-
bon signals from those arising from methylene and quaternary car-
bon atoms. Two-dimensional NMR experiments [COSY, hetero-
General Procedure for Gold-Catalyzed [4+2] Cycloaddition Reac-
tions: To a solution of either AuPPh3Cl (2.0 mol-%) and AgOTf
(2.0 mol-%) or AuCl3 (2.0 mol-%) in toluene (1 mL/0.2 mmol of
catalyst) were added dienes 1a–1h or 4 (1.0 equiv.) and dienophiles
Eur. J. Org. Chem. 2013, 6267–6279
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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6273

E. Rossi et al.
FULL PAPER
2a–2e (1.2 or 2.4 equiv.), and the solution was stirred at the appro-
priate temperature for the stated time. The solvent was then re-
moved in vacuo, and the residue was purified by flash column
chromatography over silica gel.
(؎)-(trans)-Ethyl 3-Acetyl-2-(4-fluorophenyl)-3,4-dihydro-1H-carb-
azole-9(2H)-carboxylate (3Јb): White solid; m.p. 161.7–161.9 °C. IR
(KBr): ν = 3447, 2917, 2849, 1735, 1212 cm–1. 1H NMR (500 MHz,
˜
CDCl3): δ = 8.16 (d, J = 8.1 Hz, 1 H), 7.43 (d, J = 7.1 Hz, 1 H),
7.35–7.26 (m, 4 H), 7.06–7.03 (m, 2 H), 4.48 (q, J = 7.1 Hz, 2 H),
3.52 (dd, J = 4.9, 18.2 Hz, 1 H), 3.35 (ddd, J = 5.5, 10.5, 21.0 Hz,
1 H), 3.23 (ddd, J = 5.5, 10.5, 21.0 Hz, 1 H), 3.14 (m, 1 H), 2.99
General Procedure for BF3·OEt2-Catalyzed [4+2] Cycloaddition Re-
actions: To a nitrogen-flushed solution of 1a or 1g–1h (1.0 equiv.)
and 2a (1.5 equiv.) in toluene (1 mL/0.2 mmol) was added
BF3·OEt2 (15 mol-%) at –20 °C, and the mixture was stirred at the
same temperature for the stated time. The solvent was then re-
moved in vacuo, and the residue was purified by flash column
chromatography over silica gel.
(m, 1 H), 2.93 (m, 1 H), 1.97 (s, 3 H), 1.46 (t, J = 7.1 Hz, 3 H) ppm.
1
13C NMR (125.75 MHz, CDCl3): δ = 210.4 (Cq), 161.0 (d, JC,F
=
4
245 Hz, Cq), 151.2 (Cq), 138.1 (d, JC,F = 4 Hz, Cq), 135.2 (Cq),
133.4 (Cq), 128.4 (d, JC,F = 8 Hz, CH), 128.3 (Cq), 123.4 (CH),
3
122.3 (CH), 117.0 (CH), 115.0 (CH), 114.9 (d, 2JC,F = 21 Hz, CH),
114.3 (Cq), 62.3 (CH2), 52.2 (CH), 42.4 (CH), 32.7 (CH2), 29.5
(CH3), 23.6 (CH2), 13.7 (CH3) ppm. MS (ESI+): m/z (%) = 380
(100) [M + 1]+. C23H22FNO3 (379.42): calcd. C 72.81, H 5.84, N
3.69; found C 72.78, H 5.81, N 3.72.
Reactions of 1a and 2a with Gold(I) Complex and Gold(III) Chlor-
ide: The general procedure was followed using AuPPh3Cl (3.3 mg,
0.0066 mmol), AgOTf (1.7 mg, 0.0066 mmol), (E)-ethyl 2-(4-meth-
ylstyryl)-1H-indole-1-carboxylate (1a, 100 mg, 0.33 mmol) and 3-
buten-2-one (2a, 27.8 mg, 0.40 mmol) at room temperature for
24 h. Purification of the residue (hexane/ethyl acetate, 98:2–95:5)
progressively yielded 3Јa (8 mg, 7%) and 3a (110 mg, 89%). The
same general procedure was performed using AuCl3 (2.0 mg,
0.0066 mmol) at room temperature for 1.5 h to yield 3Јa (9 mg, 7%)
and 3a (114 mg, 92%).
(؎)-(cis)-Ethyl
3-Acetyl-2-(4-fluorophenyl)-3,4-dihydro-1H-carb-
azole-9(2H)-carboxylate (3b): White solid; m.p. 151.7–152.2 °C. IR
(KBr): ν = 3424, 2920, 2849, 1721, 1702, 1209 cm–1. 1H NMR
˜
(500 MHz, CDCl3): δ = 8.21 (d, J = 8.2 Hz, 1 H), 7.48 (d, J =
7.8 Hz, 1 H), 7.33 (m, 2 H), 7.10 (m, 2 H), 6.93 (m, 2 H), 4.52 (m,
2 H), 3.82 (m, 1 H), 3.61 (m, 1 H), 3.54 (m, 1 H), 3.17 (m, 1 H),
2.95 (dd, J = 5.3, 16.6 Hz, 1 H), 2.84 (m, 1 H), 2.17 (s, 3 H), 1.51
(t, J = 7.1 Hz, 3 H) ppm. 13C NMR (125.75 MHz, CDCl3): δ =
208.7 (Cq), 161.1 (d, 1JC,F = 245 Hz, Cq), 151.3 (Cq), 136.5 (d, 4JC,F
(؎)-(trans)-Ethyl
3-Acetyl-2-(p-tolyl)-3,4-dihydro-1H-carbazole-
9(2H)-carboxylate (3Јa):[11a] White solid; m.p. 165.9–166.2 °C. IR
(KBr): ν = 3052, 2916, 2849, 1723 cm–1. 1H NMR (500 MHz,
˜
3
= 3 Hz, Cq), 135.5 (Cq), 133.5 (Cq), 128.7 (d, JC,F = 8 Hz, CH),
C6D6): δ = 8.63 (d, J = 8.2 Hz, 1 H), 7.47 (m, 2 H), 7.38 (m, 1 H),
7.08 (d, J = 7.9 Hz, 2 H), 7.17 (d, J = 7.9 Hz, 2 H), 4.23 (m, 2 H),
3.44 (dd, J = 5.0, 17.5 Hz, 1 H), 3.19 (ddd, J = 5.0, 10.5, 10.5 Hz,
1 H), 3.10 (dd, J = 10.5, 17.5 Hz, 1 H), 2.93 (ddd, J = 4.0, 10.5,
10.5 Hz, 1 H), 2.87 (dd, J = 10.5, 15.6 Hz, 1 H), 2.76 (dd, J = 4.0,
15.6 Hz, 1 H), 2.21 (s, 3 H), 1.72 (s, 3 H), 0.99 (t, J = 7.1 Hz, 3
H) ppm. 13C NMR (125.75 MHz, C6D6): δ = 209.0 (Cq), 151.6
(Cq), 140.7 (Cq), 136.5 (Cq), 136.2 (Cq), 134.4 (Cq), 129.6 (Cq),
129.4 (CH), 128.0 (CH), 124.1 (CH), 123.0 (CH), 117.8 (CH), 115.2
(CH), 115.2 (Cq), 62.4 (CH2), 52.4 (CH), 43.6 (CH), 33.9 (CH2),
29.7 (CH3), 24.5 (CH2), 20.8 (CH3), 19.3 (CH3) ppm. MS (ESI+):
m/z (%) = 376 (40) [M + 1]+, 304 (100).
128.5 (Cq), 123.4 (CH), 122.3 (CH), 117.1 (CH), 115.0 (CH), 114.9
2
(Cq), 114.6 (d, JC,F = 21 Hz, CH), 62.3 (CH2), 50.6 (CH), 39.6
(CH), 30.7 (CH2), 28.8 (CH3), 19.5 (CH2), 13.7 (CH3) ppm. MS
(ESI+): m/z (%) = 380 (100) [M + 1]+, 355 (40), 279 (30).
C23H22FNO3 (379.42): calcd. C 72.81, H 5.84, N 3.69; found C
72.73, H 5.76, N 3.62.
Reactions of 1c and 2a with Gold(I) Complex and Gold(III) Chloride:
The general procedure was followed using AuPPh3Cl (3.1 mg,
0.0062 mmol), AgOTf (1.6 mg, 0.0062 mmol), (E)-ethyl 2-(4-meth-
oxystyryl)-1H-indole-1-carboxylate (1c, 100 mg, 0.31 mmol), and
3-buten-2-one (2a, 26.0 mg, 0.37 mmol) at room temperature for
24 h. Purification of the residue (hexane/ethyl acetate, 98:2–95:5)
progressively yielded 3Јc (14 mg, 12%) and 3c (100 mg, 82%). The
same procedure was performed using AuCl3 (1.9 mg, 0.0062 mmol)
at room temperature for 18 h to yield 3Јc (2 mg, 1%) and 3c
(104 mg, 61%).
(؎)-(cis)-Ethyl
3-Acetyl-2-(p-tolyl)-3,4-dihydro-1H-carbazole-
9(2H)-carboxylate (3a):[11a] White solid; m.p. 141.6–142.7 °C. IR
(KBr): ν = 3054, 2921, 1722, 1701 cm–1. 1H NMR (300 MHz,
˜
C6D6): δ = 8.61 (d, J = 8.3 Hz, 1 H), 7.32–7.50 (m, 3 H), 6.96 (d,
J = 7.9 Hz, 2 H), 7.16 (d, J = 7.9 Hz, 2 H), 4.1 (q, J = 7.1 Hz, 2
H), 3.80 (dd, J = 4.0, 17.6 Hz, 1 H), 3.55 (ddd, J = 4.0, 4.0, 6.6 Hz,
1 H), 3.50 (dd, J = 6.6, 17.6 Hz, 1 H), 2.98 (dd, J = 7.3, 18.1 Hz,
1 H), 2.80 (m, 1 H), 2.78 (dd, J = 5.5, 18.1 Hz, 1 H), 2.14 (s, 3 H),
1.83 (s, 3 H), 1.02 (t, J = 7.1 Hz, 3 H) ppm. 13C NMR (75.45 MHz,
C6D6): δ = 209.0 (Cq), 152.4 (Cq), 139.6 (Cq), 137.1 (Cq), 136.6
(Cq), 135.1 (Cq), 130.1 (Cq), 129.6 (CH), 127.9 (CH), 124.5 (CH),
123.4 (CH), 118.3 (CH), 116.5 (CH), 116.1 (Cq), 62.8 (CH2), 51.5
(CH), 41.2 (CH), 31.7 (CH2), 30.4 (CH3), 29.3 (CH3), 21.1 (CH2),
14.2 (CH3) ppm. MS (ESI+): m/z (%) = 376 (25) [M + 1]+, 304
(100), 100 (70).
(؎)-(trans)-Ethyl
3-Acetyl-2-(4-methoxyphenyl)-3,4-dihydro-1H-
carbazole-9(2H)-carboxylate (3Јc): Yellow solid; m.p. 161.2–
162.8 °C. IR (KBr): ν = 3436, 2918, 1724, 1703, 1513, 1211,
˜
1
1031 cm–1. H NMR (500 MHz, CDCl3): δ = 8.17 (d, J = 8.0 Hz,
1 H), 7.43 (d, J = 7.7 Hz, 1 H), 7.34–7.26 (m, 2 H), 7.23 (m, 2 H),
6.90 (m, 2 H), 4.47 (q, J = 7.1 Hz, 2 H), 3.83 (s, 3 H), 3.50 (dd, J
= 5.2, 18.1 Hz, 1 H), 3.28 (ddd, J = 5.2, 10.5, 21.0 Hz, 1 H), 3.21
(m, 1 H), 3.16 (m, 1 H), 2.94 (m, 2 H), 1.94 (s, 3 H), 1.45 (t, J =
7.1 Hz, 3 H) ppm. 13C NMR (125.75 MHz, CDCl3): δ = 210.9 (Cq),
157.8 (Cq), 151.2 (Cq), 135.3 (Cq), 134.3 (Cq), 133.7 (Cq), 128.4
(Cq), 128.0 (CH), 123.3 (CH), 122.2 (CH), 117.0 (CH), 114.9 (CH),
114.4 (Cq), 113.4 (CH), 62.2 (CH2), 54.6 (CH), 52.4 (CH3), 42.5
(CH), 32.8 (CH2), 29.5 (CH3), 23.6 (CH2), 13.7 (CH3) ppm. MS
(ESI+): m/z (%) = 392 (20) [M + 1]+, 414 (25) [M + Na]+.
C24H25NO4 (391.46): calcd. C 73.64, H 6.44, N 3.58; found C
73.61, H 6.40, N 3.62.
Reactions of 1b and 2a with Gold(I) Complex and Gold(III) Chlor-
ide: The general procedure was followed using AuPPh3Cl (3.2 mg,
0.0064 mmol), AgOTf (1.6 mg, 0.0064 mmol), (E)-ethyl 2-(4-
fluorostyryl)-1H-indole-1-carboxylate (1b, 100 mg, 0.32 mmol),
and 3-buten-2-one (2a, 27.0 mg, 0.38 mmol) at room temperature
for 24 h. Purification of the residue (hexane/ethyl acetate, 98:2–
95:5) progressively yielded 3Јb (11 mg, 9%) and 3b (97 mg, 80%).
The same general procedure was performed using AuCl3 (1.9 mg,
0.0064 mmol) at room temperature for 1.5 h to yield 3Јb (7 mg, 6%)
and 3b (104 mg, 85%).
(؎)-(cis)-Ethyl 3-Acetyl-2-(4-methoxyphenyl)-3,4-dihydro-1H-carb-
azole-9(2H)-carboxylate (3c): Yellow solid; m.p. 167.8–168.8 °C. IR
(KBr): ν = 3430, 2909, 1724, 1699, 1611, 1512, 1339, 1251 cm–1.
˜
1H NMR (500 MHz, CDCl3): δ = 8.22 (d, J = 8.1 Hz, 1 H), 7.48
6274
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© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2013, 6267–6279

Cycloaddition versus Alkylation Reactions
(d, J = 7.2 Hz, 1 H), 7.35–7.28 (m, 2 H), 7.05 (d, J = 8.7 Hz, 2 H),
28 h. Purification of the residue (hexane/ethyl acetate, 99:1–98:2)
6.78 (m, 2 H), 4.51 (m, 2 H), 3.81 (m, 1 H), 3.77 (s, 3 H), 3.60 (m,
progressively yielded 3ЈЈb (7 mg, 6%) and 3e (92 mg, 74%). The
1 H), 3.52 (m, 1 H), 3.16 (m, 1 H), 2.93 (dd, J = 5.2, 16.6 Hz, 1 same procedure was performed using AuCl3 (2.0 mg, 0.0067 mmol)
H), 2.85 (m, 1 H), 2.17 (s, 3 H), 1.50 (t, J = 7.1 Hz, 3 H) ppm. 13C at room temperature for 3 h to yield 3ЈЈb (10 mg, 8%) and 3e
NMR (125.75 MHz, CDCl3): δ = 209.1 (Cq), 157.8 (Cq), 151.3 (Cq),
135.5 (Cq), 133.7 (Cq), 132.8 (Cq), 128.6 (Cq), 128.1 (CH), 123.3
(CH), 122.2 (CH), 117.1 (CH), 115.0 (Cq), 114.9 (CH) 113.1 (CH),
62.2 (CH2), 54.5 (CH), 50.8 (CH3), 39.6 (CH), 30.8 (CH2), 28.8
(CH3), 19.4 (CH2), 13.7 (CH3) ppm. MS (ESI+): m/z (%) = 392
(10) [M + 1]+, 414 (100) [M + Na]+. C24H25NO4 (391.46): calcd. C
73.64, H 6.44, N 3.58; found C 73.60, H 6.42, N 3.60.
(109 mg, 87%).
Ethyl 4-Acetyl-2-cyclohexyl-3,4-dihydro-1H-carbazole-9(2H)-carb-
oxylate (3ЈЈb): White solid; m.p. 87.5–88.6 °C. IR (KBr): ν = 3583,
˜
3293, 2922, 1731, 1457, 1376, 1268, 1218, 1117, 746 cm–1. 1H NMR
(500 MHz, C6D6, major diastereomer): δ = 8.51 (d, J = 8.3 Hz, 1
H), 7.54 (d, J = 7.7 Hz, 1 H), 7.37 (td, J = 1.1, 7.2 Hz, 1 H), 7.26
(m, 1 H), 4.15 (m, 2 H), 3.85 (m, 1 H), 3.18 (m, 1 H), 2.68 (m, 1
H), 2.02 (m, 1 H), 1.94 (s, 3 H), 1.85–1.67 (m, 5 H), 1.47–1.10 (m,
8 H), 1.07 (t, J = 7.1 Hz, 3 H) ppm. 13C NMR (125.75 MHz, C6D6,
major diastereomer): δ = 208.0 (Cq), 150.9 (Cq), 136.9 (Cq), 135.8
(Cq), 128.2 (Cq), 123.3 (CH), 122.6 (CH), 117.7 (CH), 115.3 (CH),
114.3 (Cq), 61.7 (CH2), 49.6 (CH), 41.8 (CH), 39.0 (CH), 29.7
(CH2), 29.5 (CH2), 29.3 (CH2), 29.2 (CH2), 29.0 (CH2), 28.5 (CH2),
26.0 (CH2), 24.5 (CH3), 13.2 (CH3) ppm. MS (ESI+): m/z (%) =
368 (100) [M + 1]+, 390 (90) [M + Na]+.
Reactions of 1d and 2a with Gold(I) Complex and Gold(III) Chlor-
ide: The general procedure was followed using AuPPh3Cl (4.3 mg,
0.0086 mmol), AgOTf (2.2 mg, 0.0086 mmol), (E)-ethyl 2-propen-
ylindole-1-carboxylate (1d, 100 mg, 0.43 mmol), and 3-buten-2-one
(2a, 36.2 mg, 0.51 mmol) at room temperature for 24 h. Purification
of the residue (toluene/hexane, 92:8) progressively yielded 3ЈЈa
(7 mg, 5%), 3Јd (2 mg, 2%), and 3d (111 mg, 86%). The same pro-
cedure was performed using AuCl3 (2.6 mg, 0.0086 mmol) at room
temperature for 2 h to yield 3ЈЈa (4 mg, 3%) and 3d (126 mg, 96%).
(؎)-(cis)-Ethyl
3-Acetyl-2-cyclohexyl-3,4-dihydro-1H-carbazole-
Ethyl 4-Acetyl-2-methyl-3,4-dihydro-1H-carbazole-9(2H)-carboxyl-
9(2H)-carboxylate (3e): White solid; m.p. 100.6–101.7 °C. IR
ate (3ЈЈa):[11a,25] Yellow oil. IR (neat): ν = 3076, 2953, 2917, 2884,
(KBr): ν = 3400, 2924, 1730, 1456, 1347, 1327, 1210, 1144, 1042,
˜
˜
1735, 1703 cm–1. 1H NMR (300 MHz, C6D6, major diastereomer):
δ = 8.50 (d, J = 8.3 Hz, 1 H), 7.49 (d, J = 7.6 Hz, 1 H), 7.32 (m, 2
H), 4.14 (q, J = 7.1 Hz, 2 H), 3.83 (m, 1 H), 3.17 (m, 1 H), 2.50
(ddd, J = 3.0, 10.8, 17.9 Hz, 1 H), 1.88 (s, 3 H), 1.80 (m, 1 H), 1.57
(m, 1 H), 1.27 (t, J = 12.2 Hz, 1 H), 1.06 (t, J = 7.1 Hz, 3 H), 0.95
745 cm–1. H NMR (500 MHz, C6D6): δ = 8.57 (d, J = 8.2 Hz, 1
1
H), 7.49 (d, J = 7.7 Hz, 1 H), 7.42 (td, J = 1.2, 7.2 Hz, 1 H), 7.36
(td, J = 1.0, 7.2 Hz, 1 H), 4.11 (m, 2 H), 3.52 (dd, J = 8.2, 18.0 Hz,
1 H), 3.28 (dd, J = 5.3, 18.0 Hz, 1 H), 2.97 (dd, J = 4.1, 16.6 Hz,
1 H), 2.85 (m, 1 H), 2.70 (dd, J = 6.2, 16.6 Hz, 1 H), 2.09 (d, J =
(d, J = 6.6 Hz, 3 H) ppm. 13C NMR (75.45 MHz, C6D6, major 12.6 Hz, 1 H), 1.88 (m, 4 H), 1.82–1.68 (m, 5 H), 1.31–1.21 (m, 3
diastereomer): δ = 208.7 (Cq), 151.9 (Cq), 137.4 (Cq), 136.8 (Cq),
H), 1.04 (t, J = 7.7 Hz, 3 H), 0.97 (m, 2 H) ppm. 13C NMR
129.3 (Cq), 124.4 (CH), 123.6 (CH), 118.8 (CH), 116.3 (CH), 115.1 (125.75 MHz, C6D6): δ = 207.1 (Cq), 151.0 (Cq), 135.9 (Cq), 135.4
(Cq), 62.8 (CH2), 50.4 (CH), 34.8 (CH2), 34.2 (CH2), 29.7 (CH), (Cq), 129.0 (Cq), 123.1 (CH), 122.1 (CH), 116.8 (CH), 115.4 (CH),
25.6 (CH3), 21.9 (CH3), 14.3 (CH3) ppm. MS (ESI+): m/z (%) = 113.5 (Cq), 61.6 (CH2), 48.8 (CH), 41.9 (CH), 40.7 (CH), 38.5
300 (100) [M + 1]+.
(CH3), 31.5 (CH2), 31.0 (CH2), 27.5 (CH2), 26.0 (CH2), 25.9 (CH2),
25.8 (CH2), 25.7 (CH2), 13.1 (CH3) ppm. MS (ESI+): m/z (%) =
368 (48) [M + 1]+, 390 (100) [M + Na]+. C23H29NO3 (367.48):
calcd. C 75.17, H 7.95, N 3.81; found C 75.08, H 7.91, N 3.82.
(؎)-(trans)-Ethyl
3-Acetyl-2-methyl-3,4-dihydro-1H-carbazole-
9(2H)-carboxylate (3Јd): Yellow oil. IR (neat): ν = 3074, 2952, 2934,
˜
2874, 1734, 1702 cm–1. H NMR (500 MHz, C6D6): δ = 8.56 (d, J
1
= 8.2 Hz, 1 H), 7.43–7.34 (m, 3 H), 4.14 (q, J = 7.1 Hz, 2 H), 3.22
Reactions of 1f and 2a with Gold(I) Complex and Gold(III) Chloride:
(dd, J = 4.9, 17.9 Hz, 1 H), 2.67 (m, 2 H), 2.57 (m, 1 H), 2.27 (ddd, The general procedure was followed using AuPPh3Cl (3.7 mg,
J = 5.4, 9.9, 19.8 Hz, 1 H), 2.15 (m, 1 H), 1.92 (s, 3 H), 1.07 (t, J
= 7.1 Hz, 3 H), 0.96 (d, J = 6.5 Hz, 3 H) ppm. 13C NMR
(125.75 MHz, C6D6): δ = 208.8 (Cq), 150.9 (Cq), 135.6 (Cq), 133.7
0.0074 mmol), AgOTf (1.9 mg, 0.0074 mmol), (E)-ethyl 2-(hex-1-
enyl)-1H-indole-1-carboxylate (1f, 100 mg, 0.37 mmol), and 3-
buten-2-one (2a, 31.0 mg, 0.44 mmol) at room temperature for
(Cq), 129.0 (Cq), 123.2 (CH), 122.2 (CH), 117.0 (CH), 115.2 (CH), 24 h. Purification of the residue (hexane/ethyl acetate, 99:1–98:2)
114.3 (Cq), 61.6 (CH2), 52.4 (CH), 32.5 (Cq), 30.7 (CH), 28.6 progressively yielded 3ЈЈc (13 mg, 10%) and 3f (91 mg, 72%). The
(CH3), 23.1 (CH2), 18.8 (CH3), 13.2 (CH3) ppm. MS (ESI+): m/z
same procedure was performed using AuCl3 (1.9 mg, 0.0064 mmol)
at room temperature for 5 h to yield 3ЈЈc (10 mg, 7%), 3f (70 mg,
55%).
(%) = 300 (100) [M + 1]+.
(؎)-(cis)-Ethyl 3-Acetyl-2-methyl-3,4-dihydro-1H-carbazole-9(2H)-
carboxylate (3d):[11a,25] Pink solid; m.p. 88.2 °C. IR (KBr): ν =
Ethyl 4-Acetyl-2-n-butyl-3,4-dihydro-1H-carbazole-9(2H)-carboxyl-
˜
3034, 2914, 2873, 1727, 1706 cm–1. 1H NMR (500 MHz, CDCl3):
δ = 8.14 (d, J = 7.6 Hz, 1 H), 7.46 (d, J = 6.9 Hz, 1 H), 7.32 (m, 2
H), 4.51 (q, J = 7.1 Hz, 2 H), 3.28 (m, 1 H), 3.07 (m, 1 H), 2.90
ate (3ЈЈc):[11a,25] Yellow oil. IR (neat): ν = 2957, 2928, 2859,
˜
1
1736 cm–1. H NMR (300 MHz, CDCl3, major diastereomer): δ =
8.14 (d, J = 7.9 Hz, 1 H), 7.25 (m, 3 H), 4.51 (m, 2 H), 3.84 (m, 1
(m, 2 H), 2.79 (m, 2 H), 2.29 (s, 3 H), 1.51 (t, J = 7.1 Hz, 3 H), H), 3.32 (m, 1 H), 2.61 (m, 1 H), 2.21 (m, 1 H), 2.09 (s, 3 H), 1.81
0.94 (d, J = 7.0 Hz, 3 H) ppm. 13C NMR (125.75 MHz, CDCl3):
(m, 1 H), 1.52 (t, J = 7.1 Hz, 3 H), 1.36–1.30 (m, 7 H), 0.95 (t, J
210.0 (Cq), 152.0 (Cq), 136.1 (Cq), 133.6 (Cq), 129.5 (Cq), 123.7 = 6.8 Hz, 3 H) ppm. 13C NMR (75.45 MHz, CDCl3, major dia-
(CH), 122.8 (CH), 117.7 (CH), 115.5 (CH), 114.7 (Cq), 62.8 (CH2), stereomer): δ = 211.5 (Cq), 152.3 (Cq), 137.9 (Cq), 136.4 (Cq), 128.8
50.7 (CH), 33.3 (CH2), 29.3 (CH3), 28.5 (CH), 18.3 (CH2), 14.6
(CH3), 14.4 (CH3) ppm. MS [atmospheric pressure chemical ioniza-
tion (APCI+)]: m/z (%) = 300 (100) [M + 1]+.
(Cq), 124.3 (CH), 123.5 (CH), 118.5 (CH), 116.1 (CH), 115.1 (Cq),
63.4 (CH2), 50.2 (CH), 36.6 (CH2), 34.9 (CH), 33.5 (CH2), 32.6
(CH2), 29.5 (CH2), 26.5 (CH3), 23.3 (CH2), 14.8 (CH3), 14.5
(CH3) ppm. MS (ESI+): m/z (%) = 364 (100) [M + Na]+, 296 (40).
Reactions of 1e and 2a with Gold(I) Complex and Gold(III) Chloride:
The general procedure was followed using AuPPh3Cl (3.4 mg,
0.0067 mmol), AgOTf (1.7 mg, 0.0067 mmol), (E)-ethyl 2-(2-cyclo-
hexylvinyl)-1H-indole-1-carboxylate (1e, 100 mg, 0.34 mmol), and
(؎)-(cis)-Ethyl 3-Acetyl-2-n-butyl-3,4-dihydro-1H-carbazole-9(2H)-
carboxylate (3f):[11a,25] Yellow oil. IR (neat): ν = 2955, 2926, 2870,
˜
1735, 1707 cm–1. 1H NMR (300 MHz, CDCl3): δ = 8.12 (d, J =
3-buten-2-one (2a, 28.3 mg, 0.41 mmol) at room temperature for 7.1 Hz, 1 H), 7.38 (m, 3 H), 4.52 (q, J = 7.1 Hz, 2 H), 3.19 (m, 2
Eur. J. Org. Chem. 2013, 6267–6279
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
6275

E. Rossi et al.
FULL PAPER
H), 2.83 (m, 3 H), 2.48 (m, 1 H), 2.28 (s, 3 H), 1.49 (t, J = 7.1 Hz, 7.10 (m, 6 H), 6.88 (t, J = 7.3 Hz, 1 H), 6.42 (d, J = 7.7 Hz, 1 H),
3 H), 1.25 (m, 6 H), 0.88 (m, 3 H) ppm. 13C NMR (75.45 MHz, 4.59–4.47 (m, 2 H), 4.22 (m, 1 H), 3.27 (ddd, J = 1.5, 5.5, 8.3 Hz,
CDCl3): δ = 210.5 (Cq), 152.4 (Cq), 136.4 (Cq), 134.4 (Cq), 129.9 1 H), 3.06–2.87 (m, 2 H), 2.24 (m, 1 H), 1.80–1.17 (m, 11 H), 1.76
(Cq), 124.1 (CH), 123.2 (CH), 118.1 (CH), 115.9 (CH), 115.5 (Cq), (s, 3 H), 1.52 (t, J = 7.0 Hz, 3 H) ppm. 13C NMR (50.3 MHz,
63.2 (CH2), 51.4 (CH), 35.6 (CH), 30.7 (CH2), 30.1 (CH2), 29.1
CDCl3): δ = 213.9 (Cq), 152.3 (Cq), 142.5 (Cq), 136.4 (Cq), 136.3
(CH3), 28.8 (CH2), 23.2 (CH2), 19.6 (CH2), 14.8 (CH3), 14.4 (Cq), 129.0 (CH), 128.8 (Cq), 128.5 (CH), 127.3 (CH), 123.6 (CH),
(CH3) ppm. MS (ESI+): m/z (%) = 364 (100) [M + Na]+.
122.7 (CH), 119.9 (CH), 118.1 (Cq), 115.5 (CH), 63.1 (CH2), 60.4
(CH), 46.2 (CH), 43.3 (CH), 40.0 (CH), 33.5 (CH3), 32.3 (CH2),
27.1 (CH2), 27.0 (CH2), 26.9 (CH2), 26.8 (CH2), 25.8 (CH2), 14.7
(CH3) ppm. MS (ESI+): m/z (%) = 444 (100) [M + 1]+. C29H33NO3
(443.58): calcd. C 78.52, H 7.50, N 3.16; found C 78.48, H 7.42, N
3.05.
Reactions of 1a and 2b with Gold(I) Complex and Gold(III) Chlor-
ide: The general procedure was followed using AuPPh3Cl (3.3 mg,
0.0066 mmol), AgOTf (1.7 mg, 0.0066 mmol), (E)-ethyl 2-(4-meth-
ylstyryl)-1H-indole-1-carboxylate (1a, 100 mg, 0.33 mmol), and
(E)-4-phenylbut-3-en-2-one (2b, 58.0 mg, 0.40 mmol) at room tem-
perature for 24 h. Purification of the residue (hexane/ethyl acetate,
95:5) progressively yielded 3Јg (65 mg, 43%) and 3g (62 mg, 41%).
The same procedure was performed using AuCl3 (2.0 mg,
0.0066 mmol) at room temperature for 1.5 h to yield 3Јg (62 mg,
42%) and 3g (65 mg, 44%).
(؎)-(cis)-Ethyl
3-Acetyl-2-cyclohexyl-4-phenyl-3,4-dihydro-1H-
carbazole-9(2H)-carboxylate (3h): Yellow solid; m.p. 157.8–
159.9 °C. IR (KBr): ν = 3443, 2930, 1733, 1706, 1374, 1047 cm–1.
˜
1H NMR (200 MHz, CDCl3): δ = 8.14 (d, J = 8.4 Hz, 1 H), 7.22
(m, 5 H), 7.02 (m, 3 H), 4.52 (m, 3 H), 3.36 (dd, J = 6.2, 18.3 Hz,
1 H), 3.16 (m, 2 H), 2.28 (s, 3 H), 1.94 (m, 1 H), 1.80–0.70 (m, 11
H), 1.51 (t, J = 7.0 Hz, 3 H) ppm. 13C NMR (50.3 MHz, CDCl3):
δ = 209.3 (Cq), 152.3 (Cq), 143.5 (Cq), 138.2 (Cq), 136.6 (Cq), 129.3
(Cq), 128.7 (CH), 128.3 (CH), 126.8 (CH), 123.9 (CH), 122.9 (CH),
118.4 (CH), 115.8 (CH), 115.2 (Cq), 63.1 (CH2), 55.7 (CH), 40.2
(CH), 39.5 (CH), 38.0 (CH), 32.0 (CH2), 31.4 (CH2), 30.6 (CH3),
28.0 (CH2), 26.6 (CH2), 26.5 (CH2), 26.4 (CH2), 14.7 (CH3) ppm.
MS (ESI+): m/z (%) = 444 (90) [M + 1]+, 466 (100) [M + Na]+.
C29H33NO3 (443.58): calcd. C 78.52, H 7.50, N 3.16; found C
78.43, H 7.46, N 3.12.
(؎)-(trans)-Ethyl 3-Acetyl-4-phenyl-2-(p-tolyl)-3,4-dihydro-1H-carb-
azole-9(2H)-carboxylate (3Јg): White solid; m.p. 189.8–190.6 °C. IR
(KBr): ν = 3437, 2927, 1728, 1705, 1343, 1043 cm–1. 1H NMR
˜
(300 MHz, CDCl3): δ = 8.15 (d, J = 8.4 Hz, 1 H), 7.35–7.10 (m, 10
H), 6.95 (t, J = 7.3 Hz, 1 H), 6.53 (d, J = 7.8 Hz, 1 H), 4.60–4.38
(m, 3 H), 3.55 (m, 1 H), 3.36 (m, 3 H), 2.35 (s, 3 H), 1.47 (t, J =
7.1 Hz, 3 H), 1.35 (s, 3 H) ppm. 13C NMR (75.45 MHz, CDCl3): δ
= 212.6 (Cq), 152.3 (Cq), 142.6 (Cq), 139.6 (Cq), 137.1 (Cq), 136.6
(Cq), 135.8 (Cq), 129.8 (CH), 129.2 (CH), 128.9 (Cq), 128.7 (CH),
128.2 (CH), 127.5 (CH), 124.0 (CH), 122.9 (CH), 120.2 (CH), 118.5
(Cq), 115.7 (CH), 63.4 (CH2), 63.3 (CH), 45.7 (CH), 45.0 (CH),
34.11 (CH), 34.08 (CH2), 21.4 (CH3), 14.9 (CH3) ppm. MS (ESI+):
m/z (%) = 452 (20) [M + 1]+, 474 (40) [M + Na]+. C30H29NO3
(451.56): calcd. C 79.80, H 6.47, N 3.10; found C 79.71, H 6.39, N
2.97.
Reactions of 1a and 2c with Gold(I) Complex and Gold(III) Chloride:
The general procedure was followed using AuPPh3Cl (3.3 mg,
0.0066 mmol), AgOTf (1.7 mg, 0.0066 mmol), (E)-ethyl 2-(4-meth-
ylstyryl)-1H-indole-1-carboxylate (1a, 100 mg, 0.33 mmol), and
prop-2-enal (2c, 22.2 mg, 0.40 mmol) at room temperature for 24 h.
Purification of the residue (hexane/ethyl acetate, 98:2–95:5) pro-
gressively yielded 3Јi (29 mg, 24%) and 3i (78 mg, 65%). The same
procedure was performed using AuCl3 (2.0 mg, 0.0066 mmol) at
room temperature for 1.5 h to yield 3Јi (22 mg, 18%) and 3i (93 mg,
78%).
(؎)-(cis)-Ethyl 3-Acetyl-4-phenyl-2-(p-tolyl)-3,4-dihydro-1H-carb-
azole-9(2H)-carboxylate (3g): White solid; m.p. 184.8–185.9 °C. IR
(KBr): ν = 3437, 2920, 1731, 1703, 1376, 1051 cm–1. 1H NMR
˜
(300 MHz, CDCl3): δ = 8.20 (d, J = 8.4 Hz, 1 H), 7.27 (m, 6 H),
7.05 (m, 5 H), 6.85 (d, J = 7.8 Hz, 1 H), 4.53 (m, 3 H), 3.66 (d, J
= 6.5 Hz, 2 H), 3.56 (m, 1 H), 3.36 (t, J = 4.2 Hz, 1 H), 2.32 (s, 3
H), 1.99 (s, 3 H), 1.53 (t, J = 7.1 Hz, 3 H) ppm. 13C NMR
(75.45 MHz, CDCl3): δ = 208.9 (Cq), 152.4 (Cq), 143.6 (Cq), 139.2
(Cq), 136.9 (Cq), 136.8 (Cq), 136.5 (Cq), 129.6 (CH), 129.3 (Cq),
129.01 (CH), 128.98 (CH), 128.0 (CH), 127.2 (CH), 124.1 (CH),
123.1 (CH), 119.5 (CH), 117.2 (Cq), 115.9 (CH), 63.4 (CH2), 61.2
(CH), 39.9 (CH), 39.1 (CH), 31.6 (CH), 29.8 (CH2), 21.4 (CH3),
14.8 (CH3) ppm. MS (ESI+): m/z (%) = 452 (35) [M + 1]+, 474
(100) [M + Na]+. C30H29NO3 (451.56): calcd. C 79.80, H 6.47, N
3.10; found C 79.77, H 6.43, N 2.03.
(؎)-(trans)-Ethyl
3-Formyl-2-(p-tolyl)-3,4-dihydro-1H-carbazole-
9(2H)-carboxylate (3Јi): White oil. IR (neat): ν = 3436, 2916, 2725,
˜
1728, 1619, 1457, 1376, 1398, 1212, 1142 cm–1. 1H NMR
(500 MHz, CDCl3): δ = 9.62 (d, J = 2 Hz, 1 H), 8.19 (d, J = 8.1 Hz,
1 H), 7.47 (d, J = 7.1 Hz, 1 H), 7.35–7.27 (m, 2 H), 7.23–7.14 (m,
4 H), 4.48 (q, J = 7.1 Hz, 2 H), 3.52 (dd, J = 5.92, 18.1 Hz, 1 H),
3.44 (m, 1 H), 3.24 (m, 1 H), 3.10–2.97 (m, 2 H), 2.88 (m, 1 H),
2.37 (s, 3 H), 1.46 (t, J = 7.1 Hz, 3 H) ppm. 13C NMR
(125.75 MHz, CDCl3): δ = 203.2 (CH), 151.2 (Cq), 138.7 (Cq),
136.0 (Cq), 135.3 (Cq), 133.6 (Cq), 128.9 (CH), 128.5 (Cq), 126.8
(CH), 123.4 (CH), 122.3 (CH), 117.1 (CH), 114.9 (CH), 114.0 (Cq),
62.3 (CH2), 50.5 (CH), 40.6 (CH), 31.8 (CH2), 20.3 (CH3), 19.9
(CH2), 13.7 (CH3) ppm. MS (ESI+): m/z (%) = 362 (70) [M + 1]+,
384.3 (75) [M + Na]+. C23H23NO3 (361.43): calcd. C 76.43, H 6.41,
N 3.88; found C 76.38, H 6.37, N 3.91.
Reactions of 1e and 2b with Gold(I) Complex and Gold(III) Chloride:
The general procedure was followed using AuPPh3Cl (2.1 mg,
0.0042 mmol), AgOTf (1.1 mg, 0.0042 mmol), (E)-ethyl 2-(2-cyclo-
hexylvinyl)-1H-indole-1-carboxylate (1e, 62 mg, 0.21 mmol), and
(E)-4-phenylbut-3-en-2-one (2b, 36.6 mg, 0.25 mmol) at room tem-
perature for 48 h and then at 80 °C for 17 h. Purification of the
residue (hexane/ethyl acetate, 97:3) progressively yielded 3Јh
(24 mg, 26%) and 3h (25 mg, 27%). The same procedure was per-
formed using AuCl3 (1.3 mg, 0.0042 mmol) at room temperature
for 48 h and then at 80 °C for 17 h to yield progressively 1e (31 mg,
50%), 3Јh (20 mg, 22%), and 3h (15 mg, 16%).
(؎)-(cis)-Ethyl
3-Formyl-2-(p-tolyl)-3,4-dihydro-1H-carbazole-
9(2H)-carboxylate (3i): Yellow solid; m.p. 141.7–142.4 °C. IR
(KBr): ν = 3430, 2916, 2690, 1727, 1614, 1378, 1336, 1206,
˜
1
1035 cm–1. H NMR (500 MHz, CDCl3): δ = 9.85 (d, J = 0.8 Hz,
1 H), 8.20 (d, J = 8.1 Hz, 1 H), 7.49 (d, J = 7.2 Hz, 1 H), 7.36–
7.29 (m, 2 H), 7.15–7.10 (m, 4 H), 4.52 (m, 2 H), 3.84 (m, 1 H),
(؎)-(trans)-Ethyl 3-Acetyl-2-cyclohexyl-4-phenyl-3,4-dihydro-1H- 3.63 (dd, J = 6.2, 18.4 Hz, 1 H), 3.52 (dd, J = 6.2, 18.4 Hz, 1 H),
carbazole-9(2H)-carboxylate (3Јh): Yellow solid; m.p. 145.8– 3.10 (m, 1 H), 3.01 (dd, J = 5.4, 16.5 Hz, 1 H), 2.94 (dd, J = 7.2,
147.0 °C. IR (KBr): ν = 3436, 2924, 1729, 1711, 1350, 1041 cm–1. 16.5 Hz, 1 H), 2.34 (s, 3 H), 1.51 (t, J = 7.1 Hz, 3 H) ppm. 13C
˜
1H NMR (200 MHz, CDCl3): δ = 8.06 (d, J = 8.4 Hz, 1 H), 7.33–
NMR (125.75 MHz, CDCl3): δ = 202.7 (CH), 151.2 (Cq), 137.4
6276
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© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2013, 6267–6279

Cycloaddition versus Alkylation Reactions
(Cq), 136.0 (Cq), 135.5 (Cq), 133.6 (Cq), 128.7 (CH), 128.5 (Cq),
(Cq), 134.3 (Cq), 129.7 (CH), 129.5 (Cq), 128.8 (CH), 124.4 (CH),
127.0 (CH), 123.4 (CH), 122.3 (CH), 117.2 (CH), 114.9 (CH), 114.7 123.3 (CH), 119.2 (CH), 118.7 (Cq), 116.4 (CH), 62.9 (CH2), 62.4
(Cq), 62.3 (CH2), 49.9 (CH), 39.1 (CH), 29.5 (CH2), 20.3 (CH3), (Cq), 44.4 (CH), 39.1 (CH), 30.1 (CH2), 29.4 (CH2), 24.5 (CH2),
18.8 (CH2), 13.7 (CH3) ppm. MS (ESI+): m/z (%) = 362 (60) [M + 24.3 (CH2), 21.1 (CH3), 14.3 (CH3) ppm. MS (ESI+): m/z (%) =
1]+. C23H23NO3 (361.43): calcd. C 76.43, H 6.41, N 3.88; found C 402 (100) [M + 1]+. C26H27NO3 (401.50): calcd. C 77.78, H 6.78,
76.41, H 6.40, N 3.90.
N 3.49; found C 77.75, H 6.69, N 3.43.
Reactions of 1a and 2d with Gold(I) Complex and Gold(III) Chlor-
ide: The general procedure was followed using AuPPh3Cl (3.3 mg,
0.0066 mmol), AgOTf (1.7 mg, 0.0066 mmol), (E)-ethyl 2-(4-meth-
ylstyryl)-1H-indole-1-carboxylate (1a, 100 mg, 0.33 mmol), and
(E)-3-phenylprop-2-enal (2d, 52.3 mg, 0.40 mmol) at room tem-
perature for 24 h. Purification of the residue (toluene/hexane,
90:10) progressively yielded 3Јj (45.5 mg, 32%) and 3j (55.5 mg,
38%). The same procedure was performed using AuCl3 (2.0 mg,
0.0066 mmol) at room temperature for 48 h to yield progressively
1a (25 mg, 25%), 3Јj (30 mg, 21%), and 3j (59 mg, 41%).
(؎)-(3a,4-cis)-Ethyl
3a-Formyl-4-(p-tolyl)-1,3,3a,4,5,10c-hexahy-
drocyclopenta[c]carbazole-6(2H)-carboxylate (3k):[11b] Yellow solid;
m.p. 130–131 °C. IR (KBr): ν = 3052, 2942, 2871, 2699, 1735, 1615,
˜
1514, 1475 cm–1. 1H NMR (300 MHz, C6D6): δ = 9.68 (s, 1 H),
8.60 (d, J = 8.1 Hz, 1 H), 7.51 (d, J = 7.5 Hz, 1 H), 7.43 (m, 1 H),
7.36 (m, 1 H), 7.19 (d, J = 7.8 Hz, 2 H), 7.01 (d, J = 7.8 Hz, 2 H),
4.05 (q, J = 7.1 Hz, 2 H), 3.81 (dd, J = 18.4, 9.6 Hz, 1 H), 3.46 (m,
2 H), 3.08 (dd, J = 9.6, 5.5 Hz, 1 H), 2.35 (m, 1 H), 2.18 (s, 3 H),
1.96 (m, 1 H), 1.75 (m, 3 H), 1.58 (m, 1 H), 0.97 (t, J = 7.1 Hz, 3
H) ppm. 13C NMR (75.45 MHz, C6D6): δ = 203.0 (CH), 152.0 (Cq),
139.1 (Cq), 137.2 (Cq), 136.8 (Cq), 134.5 (Cq), 129.9 (Cq), 129.7
(CH), 129.5 (CH), 124.5 (CH), 123.3 (CH), 119.0 (CH), 118.9 (Cq),
116.5 (CH), 62.8 (CH2), 60.0 (Cq), 44.9 (CH), 39.3 (CH), 32.3
(CH2), 31.2 (CH2), 31.0 (CH2), 24.0 (CH2), 21.1 (CH3), 14.2
(CH3) ppm. MS (ESI+): m/z (%) = 402 (100) [M + 1]+. C26H27NO3
(401.50): calcd. C 77.78, H 6.78, N 3.49; found C 77.62, H 6.83, N
3.47.
(؎)-(trans)-Ethyl
3-Formyl-4-phenyl-2-(p-tolyl)-3,4-dihydro-1H-
carbazole-9(2H)-carboxylate (3Јj):[11a] Yellow oil. IR (neat): ν =
˜
2906, 2895, 2786, 1732 cm–1. 1H NMR (300 MHz, C6D6): δ = 9.36
(d, J = 2.9 Hz, 1 H), 8.56 (m, 1 H), 6.94–7.33 (m, 12 H), 4.61 (m,
1 H), 4.10 (m, 2 H), 3.52 (ddd, J = 1.5, 5.0, 17.8 Hz, 1 H), 3.28
(m, 2 H), 3.11 (ddd, J = 5.0, 11.3, 11.4 Hz, 1 H), 2.20 (s, 3 H), 1.01
(t, J = 7.1 Hz, 3 H) ppm. 13C NMR (75.45 MHz, C6D6): δ = 202.7
(CH), 152.0 (Cq), 142.8 (Cq), 139.0 (Cq), 137.1 (Cq), 137.0 (Cq),
135.7 (Cq), 130.3 (CH), 129.4 (Cq), 129.3 (CH), 129.1 (CH), 128.1
(CH), 127.4 (CH), 124.3 (CH), 123.3 (CH), 120.5 (CH), 118.4 (Cq),
116.1 (CH), 63.0 (CH2), 61.1 (CH), 44.1 (CH), 42.3 (CH), 35.2
(CH2), 21.2 (CH3), 14.3 (CH3) ppm. MS (ESI+): m/z (%) = 460
(100) [M + Na]+.
Reactions of 4 and 2a with Gold(I) Complex and Gold(III) Chloride:
The general procedure was followed using AuPPh3Cl (3.8 mg,
0.0076 mmol), AgOTf (2.0 mg, 0.0076 mmol), (E)-5-methoxy-2-(4-
methylstyryl)benzofuran (4, 100 mg, 0.38 mmol), and 2a (52.2 mg,
0.46 mmol) at room temperature for 24 h. Purification of the resi-
due (hexane/ethyl acetate, 98:2–95:5) progressively yielded unre-
acted 4 (18 mg, 18%), 5Ј (17 mg, 13%), and 5 (61 mg, 48%). The
same procedure was performed using AuCl3 (2.3 mg, 0.0076 mmol)
at room temperature for 24 h to yield unreacted 4 (27 mg, 27%),
5Ј (3 mg, 2%), and 5 (62 mg, 49%).
(؎)-(cis)-Ethyl 3-Formyl-4-phenyl-2-(p-tolyl)-3,4-dihydro-1H-carb-
azole-9(2H)-carboxylate (3j):[11a] Yellow oil. IR (neat): ν = 3027,
˜
1
2924, 2853, 1734 cm–1. H NMR (300 MHz, C6D6): δ = 9.74 (d, J
= 1 Hz, 1 H), 8.56 (d, J = 8.3 Hz, 1 H), 6.97–7.35 (m, 12 H), 4.87
(d, J = 2.9 Hz, 1 H), 4.14 (m, 2 H), 3.67 (m, 2 H), 3.56 (m, 1 H),
3.07 (m, 1 H), 2.17 (s, 3 H), 1.06 (t, J = 7.1 Hz, 3 H) ppm. 13C
NMR (75.45 MHz, C6D6): δ = 201.5 (CH), 152.0 (Cq), 143.2 (Cq),
139.0 (Cq), 137.2 (Cq), 136.6 (Cq), 136.5 (Cq), 129.7 (CH), 129.5
(Cq), 129.1 (CH), 129.0 (CH), 128.2 (CH), 127.2 (CH), 124.6 (CH),
123.5 (CH), 119.7 (CH), 117.1 (Cq), 116.3 (CH), 63.0 (CH2), 60.3
(CH), 38.6 (CH), 37.4 (CH), 29.3 (CH2), 21.1 (CH3), 14.2
(CH3) ppm. MS (ESI+): m/z (%) = 460 (100) [M + Na]+.
(؎)-(trans)-8-Methoxy-2-acetyl-3-(p-tolyl)-1,2,3,4-tetrahydrodi-
benzo[b,d]furan (5Ј): Yellow solid; m.p. 134.7–135.1 °C. IR (KBr):
ν = 3419, 2922, 1712, 1609, 1459, 1356, 1201, 1029, 834 cm–1. H
1
˜
NMR (500 MHz, C6D6): δ = 7.42 (d, J = 8.8 Hz, 1 H), 7.04 (m, 5
H), 6.98 (dd, J = 2.5, 8.8 Hz, 1 H), 3.64 (s, 3 H), 3.15 (ddd, J =
5.6, 10.3, 21.3 Hz, 1 H), 2.91 (dd, J = 5.6, 16.6 Hz, 1 H), 2.83–2.71
(m, 3 H), 2.57 (dd, J = 4.0, 14.0 Hz, 1 H), 2.21 (s, 3 H), 1.66 (s, 3
H) ppm. 13C NMR (125.75 MHz, C6D6): δ = 207.9 (Cq), 155.7
(Cq), 152.9 (Cq), 149.3 (Cq), 139.3 (Cq), 135.5 (Cq), 128.7 (CH),
128.5 (Cq), 127.0 (CH), 110.9 (CH), 110.8 (CH), 110.7 (Cq), 101.3
(CH), 54.6 (CH3), 52.2 (CH), 42.1 (CH), 30.8 (CH2), 29.0 (CH3),
23.1 (CH2), 20.0 (CH3) ppm. MS (ESI+): m/z (%) = 335 (100) [M
+ 1]+, 357 (55) [M + Na]+. C22H22O3 (334.41): calcd. C 79.02, H
6.63; found C 78. 98, H 6.61.
Reactions of 1a and 2e with Gold(I) Complex and Gold(III) Chloride:
The general procedure was followed using AuPPh3Cl (3.3 mg,
0.0066 mmol), AgOTf (1.7 mg, 0.0066 mmol), (E)-ethyl 2-(4-meth-
ylstyryl)-1H-indole-1-carboxylate (1a, 100 mg, 0.33 mmol), and 1-
cyclopentencarbaldehyde (2e, 47.2 mg, 0.50 mmol) at room tem-
perature for 12 h and at 110 °C for 12 h. Purification of the residue
(toluene/hexane, 80:20) progressively yielded 1a (18 mg, 18%), 3Јk
(47 mg, 35%), and 3k (61 mg, 46%). The same procedure was per-
formed using AuCl3 (2.0 mg, 0.0066 mmol) at room temperature
for 24 h to yield progressively 1a (50 mg, 50%), 3Јk (12 mg, 9%),
and 3k (20 mg, 15%).
(؎)-(cis)-8-Methoxy-2-acetyl-3-(p-tolyl)-1,2,3,4-tetrahydrodibenzo-
[b,d]furan (5): Yellow solid; m.p. 137.1–138.4 °C. IR (KBr): ν =
˜
3389, 2915, 1704, 1614, 1480, 1385, 1205, 1026, 803 cm–1. 1H NMR
(500 MHz, C6D6): δ = 7.41 (d, J = 8.8 Hz, 1 H), 7.06 (m, 3 H),
6.97 (m, 3 H), 3.59 (s, 3 H), 3.46 (m, 1 H), 3.21 (m, 1 H), 3.03 (dd,
J = 5.8, 16.4 Hz, 1 H), 2.90 (m, 1 H), 2.67 (m, 2 H), 2.14 (s, 3 H),
1.80 (s, 3 H) ppm. 13C NMR (125.75 MHz, C6D6): δ = 206.1 (Cq),
(؎)-(3a,4-trans)-Ethyl 3a-Formyl-4-(p-tolyl)-1,3,3a,4,5,10c-hexahy-
drocyclopenta[c]carbazole-6(2H)-carboxylate (3Јk):[11b] Yellow oil.
IR (neat): ν = 3047, 2934, 2871, 2693, 1728, 1612, 1513, 1458 cm–1.
˜
1H NMR (300 MHz, C6D6): δ = 9.46 (s, 1 H), 8.59 (d, J = 8.2 Hz, 155.7 (Cq), 153.3 (Cq), 149.6 (Cq), 137.7 (Cq), 135.6 (Cq), 128.5
1 H), 7.52 (d, J = 7.5 Hz, 1 H), 7.42 (m, 1 H), 7.34 (m, 1 H), 7.12
(d, J = 8.0 Hz, 2 H), 7.05 (d, J = 8.0 Hz, 2 H), 4.10 (q, J = 7.1 Hz,
2 H), 3.56 (m, 1 H), 3.39 (m, 2 H), 3.22 (m, 1 H), 2.21 (s, 3 H),
(CH), 127.0 (CH), 111.4 (Cq), 111.1 (CH), 110.9 (CH), 101.2 (CH),
54.6 (CH3), 50.9 (CH), 39.7 (CH), 28.3 (CH2), 28.1 (CH3), 20.0
(CH3), 19.5 (CH2) ppm (Note: a Cq signal was under the C6D6
2.17 (m, 1 H), 1.92 (m, 2 H), 1.84 (m, 1 H), 1.60 (m, 1 H), 1.47 residue signal.) MS (ESI+): m/z (%) = 335 (100) [M + 1]+, 357 (70)
(m, 1 H), 1.01 (t, J = 7.1 Hz, 3 H) ppm. 13C NMR (75.45 MHz,
C6D6): δ = 203.8 (CH), 152.0 (Cq), 138.6 (Cq), 137.2 (Cq), 136.9
[M + Na]+. C22H22O3 (334.41): calcd. C 79.02, H 6.63; found C
78.95, H 6.59.
Eur. J. Org. Chem. 2013, 6267–6279
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
6277

E. Rossi et al.
FULL PAPER
Reactions of 1g and 2a with Gold(I) Complex, Gold(III) Chloride,
and Boron Trifluoride–Diethyl Ether: The general procedure was
followed using AuPPh3Cl (4.3 mg, 0.0086 mmol), AgOTf (2.2 mg,
(d, J = 8.1 Hz, 2 H), 7.32–7.03 (m, 6 H), 6.88 (d, J = 16.6 Hz, 1
H), 3.80 (s, 3 H), 3.18 (m, 2 H), 2.83 (m, 2 H), 2.39 (s, 3 H), 2.14
(s, 3 H) ppm. 13C NMR (50.3 MHz, CDCl3): δ = 208.8 (Cq), 138.1
0.0086 mmol), (E)-2-(4-methylstyryl)-1H-indole (1g, 100 mg, (Cq), 138.0 (Cq), 134.8 (Cq), 134.7 (Cq), 132.6 (CH), 129.7 (CH),
0.43 mmol), and 2a (36.0 mg, 0.51 mmol) at room temperature for
24 h. Purification of the residue (hexane/ethyl acetate, 95:5–92:8)
progressively yielded unreacted 1g (20 mg, 20%), 6a (57 mg, 44%),
and 3l (23 mg, 18%). The same procedure was performed using
127.8 (Cq), 126.53 (CH), 122.4 (CH), 119.5 (CH), 118.8 (CH), 116.7
(CH), 113.5 (Cq), 109.3 (CH), 44.7 (CH2), 31.2 (CH3), 30.3 (CH3),
21.5 (CH3), 19.4 (CH2) ppm. MS (ESI+): m/z (%) = 318 (100) [M
+ 1]+. C22H23NO (317.42): calcd. C 83.24, H 7.30, N 4.41; found
AuCl3 (2.6 mg, 0.0086 mmol) at room temperature for 24 h to yield C 83.21, H 7.30, N 4.43.
progressively 6a (76 mg, 58%) and 3l (24 mg, 18%). The general
(؎)-(cis)-3-Acetyl-9-methyl-2-(p-tolyl)-3,4-dihydro-1H-carbazole
procedure for the BF3·OEt2-catalyzed reaction was followed using
(E)-2-(4-methylstyryl)-1H-indole (1g, 100 mg, 0.43 mmol) and 3-
buten-2-one (2a, 45.0 mg, 0.64 mmol) in toluene (2 mL). BF3·OEt2
(8.5 mg, 0.06 mmol) was added at –20 °C, and the mixture was
stirred at the same temperature for 2.5 h. Purification of the residue
(hexane/ethyl acetate, 95:5) progressively yielded 6a (14 mg, 11%)
and 3l (22 mg, 17%).
(3m): Yellow solid; m.p. 167.3–168.1 °C. IR (KBr): ν = 3048, 3023,
˜
2908, 1698, 1514, 1472, 1349, 1161 cm–1. 1H NMR (200 MHz,
CDCl3): δ = 7.52 (d, J = 7.7 Hz, 1 H), 7.35–6.95 (m, 7 H), 3.77 (m,
1 H), 3.66 (s, 3 H), 3.28–3.07 (m, 3 H), 2.96 (m, 2 H), 2.28 (s, 3
H), 2.10 (s, 3 H) ppm. 13C NMR (50.3 MHz, CDCl3): δ = 210.5
(Cq), 139.0 (Cq), 137.6 (Cq), 136.8 (Cq), 135.0 (Cq), 129.3 (CH),
128.0 (CH), 127.0 (Cq), 121.1 (CH), 119.1 (CH), 118.0 (CH), 108.9
(CH), 107.8 (Cq), 52.5 (CH), 41.0 (CH), 29.7 (CH3), 29.4 (CH3),
28.1 (CH2), 21.2 (CH3), 21.1 (CH2) ppm. MS (ESI+): m/z (%) =
318 (100) [M + 1]+. C22H23NO (317.42): calcd. C 83.24, H 7.30, N
4.41; found C 83.19, H 7.27, N 4.46.
(E)-2-(4-Methylstyryl)-3-(3Ј-oxo-butyl)-1H-indole (6a): Yellow oil.
IR (neat): ν = 3361, 2919, 1703, 1451, 1116 cm–1. 1H NMR
˜
(200 MHz, CDCl3): δ = 8.10 (s, 1 H), 7.53 (d, J = 7.7 Hz, 1 H),
7.43 (d, J = 8.1 Hz, 2 H), 7.34–7.01 (m, 6 H), 6.79 (d, J = 16.5 Hz,
1 H), 3.14 (t, J = 7.5 Hz, 2 H), 2.82 (t, J = 7.5 Hz, 2 H), 2.35 (s, 3
H), 2.13 (s, 3 H) ppm. 13C NMR (50.3 MHz, CDCl3): δ = 208.7
(Cq), 137.9 (Cq), 136.8 (Cq), 134.5 (Cq), 132.8 (Cq), 129.7 (CH),
128.9 (Cq), 126.5 (CH), 126.4 (CH), 123.3 (CH), 119.9 (CH), 118.9
(CH), 116.2 (CH), 115.6 (Cq), 110.8 (CH), 44.8 (CH2), 30.4 (CH3),
21.5 (CH3), 18.4 (CH2) ppm. MS (ESI+): m/z (%) = 304 (100) [M
+ 1]+. C21H21NO (303.40): calcd. C 83.13, H 6.98, N 4.62; found
C 83.08, H 6.95, N 4.63.
Reactions of 1j and 2a To Afford 1-Methyl-2-phenyl-3-(3Ј-oxobut-
yl)-1H-indole (6c): To
a solution of AuPPh3Cl (3.76 mg,
0.0076 mmol) and AgOTf (1.95 mg, 0.0076 mmol) in toluene
(1 mL) were added 1-methyl-2-phenyl-1H-indole (1j, 100 mg,
0.48 mmol) and 2a (36.4 mg, 0.52 mmol). The solution was stirred
at room temperature for 96 h. The solvent was then removed in
vacuo, and the residue was purified by flash column chromatog-
raphy over silica gel (hexane/ethyl acetate, 98:2–95:5) to yield 6c
1
(؎)-(cis)-3-Acetyl-2-(p-tolyl)-3,4-dihydro-1H-carbazole (3l): Yellow
(109 mg, 82%) as a yellow oil. H NMR (200 MHz, CDCl3): δ =
oil. IR (neat): ν = 3392, 2912, 1699, 1154 cm–1. 1H NMR
˜
7.67–7.13 (m, 9 H), 3.59 (s, 3 H), 3.02 (m, 2 H), 2.71 (m, 2 H), 2.07
(s, 3 H) ppm. 13C NMR (50.4 MHz, CDCl3): δ = 208.6 (Cq), 138.2
(Cq), 137.5 (Cq), 132.2 (Cq), 130.8 (CH), 128.7 (CH), 128.4 (CH),
127.6 (Cq), 122.0 (CH), 119.6 (CH), 119.0 (CH), 112.0 (Cq), 109.6
(CH), 45.1 (CH2), 30.9 (CH3), 30.0 (CH3), 19.3 (CH2) ppm. MS
(ESI+): m/z (%) = 278 (20) [M + 1]+, 300 (45) [M + Na]+.
C19H19NO (277.36): calcd. C 82.28, H 6.90, N 5.05; found C 82.26,
H 6.89, N 5.02.
[400 MHz, [D6]DMSO (dimethyl sulfoxide)]: δ = 10.75 (s, 1 H),
7.38 (d, J = 7.4 Hz, 1 H), 7.29 (d, J = 8.0 Hz, 1 H), 7.06–6.88 (m,
6 H), 3.81 (pseudo-q, 1 H), 3.36 (dd, J = 6.4, 16.8 Hz, 1 H), 3.25
(pseudo-q, 1 H), 3.00 (dd, J = 3.6, 16.8 Hz, 1 H), 2.81 (dd, J = 5.3,
16.0 Hz, 1 H), 2.66 (dd, J = 9.4, 16.0 Hz, 1 H), 2.21 (s, 3 H), 2.16
(s, 3 H) ppm. 13C NMR (100.4 MHz, [D6]DMSO): δ = 209.8 (Cq),
139.6 (Cq), 136.7 (Cq), 135.9 (Cq), 134.0 (Cq), 129.2 (CH), 127.9
(CH), 127.5 (Cq), 120.7 (CH), 118.7 (CH), 117.7 (CH), 111.2 (CH),
107.4 (Cq), 52.0 (CH), 39.7 (CH), 29.6 (CH3), 29.1 (CH2), 21.0
Supporting Information (see footnote on the first page of this arti-
cle): Copies of the 1H and 13C NMR spectra, 2D NMR experi-
ments, and X-ray crystallographic data.
(CH3), 20.0 (CH2) ppm. MS (ESI+): m/z (%)
= 304 (100)
[M + 1]+. C21H21NO (303.40): calcd. C 83.13, H 6.98, N 4.62;
found C 83.06, H 6.92, N 4.67.
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Reactions of 1h and 2a with Gold(I) Complex, Gold(III) Chloride,
and Boron Trifluoride–Diethyl Ether: The general procedure was
followed using AuPPh3Cl (4.0 mg, 0.008 mmol), AgOTf (2.1 mg,
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was followed using (E)-2-(4-methylstyryl)-1-methylindole (1h,
100 mg, 0.40 mmol) and 2a (42.0 mg, 0.60 mmol) in toluene
(2 mL). BF3·OEt2 (8.5 mg, 0.06 mmol) was added at –20 °C, and
the mixture was stirred at the same temperature for 4 h. Purifica-
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Yellow oil. IR (neat): ν = 3050, 3023, 2921, 1713, 1511, 1469, 1362,
˜
1
1161 cm–1. H NMR (200 MHz, CDCl3): δ = 7.56 (m, 1 H), 7.44
6278
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© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Received: May 17, 2013
Published Online: August 6, 2013
Eur. J. Org. Chem. 2013, 6267–6279
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
6279