Synthesis of diverse indole-containing scaffolds by gold(I)-catalyzed tandem reactions of 3-propargylindoles initiated by 1,2-indole migrations: Scope and computational studies

Article abstract of DOI:10.1002/chem.201001162

Similar to propargylic carboxylates and sulphides, 3-propargylindoles undergo 1,2-indole migrations under cationic gold(I) catalysis. The intermediate Au-carbenoid complex may evolve through different pathways depending on the substituents at the propargylic and terminal positions of the alkyne moiety. Thus, 3-indenylindole derivatives were easily obtained through formal iso-Nazarov or Nazarov cyclizations. DFT computations support the formation of an alkylidenecyclopropane intermediate that undergoes gold-iso-Nazarov or gold-Nazarov cyclizations upon torquoselective ring opening. In addition, 3-dienylindoles could be accessed when none of the referred pathways were accessible and so the intermediate Au-carbenoid complex evolved via a 1,2-C-H insertion reaction. We have also demonstrated that the final products can be obtained in a one-pot protocol from easily available propargylic alcohols and indoles.

Full text of DOI:10.1002/chem.201001162

DOI: 10.1002/chem.201001162
Synthesis of Diverse Indole-Containing Scaffolds by Gold(I)-Catalyzed
Tandem Reactions of 3-Propargylindoles Initiated by 1,2-Indole Migrations:
Scope and Computational Studies
Roberto Sanz,*[a] Delia Miguel,[a] Mukut Gohain,[a] Patricia Garcꢀa-Garcꢀa,[a]
Manuel A. Fernꢁndez-Rodrꢀguez,[a] Adꢁn Gonzꢁlez-Pꢂrez,[b] Olalla Nieto-Faza,[b]
ꢃngel R. de Lera,*[b] and Fꢂlix Rodrꢀguez*[c]
Dedicated to Professor Josꢀ Barluenga on the occasion of his 70th birthday
Abstract: Similar to propargylic car-
boxylates and sulphides, 3-propargylin-
doles undergo 1,2-indole migrations
under cationic gold(I) catalysis. The in-
termediate Au–carbenoid complex may
evolve through different pathways de-
pending on the substituents at the
propargylic and terminal positions of
the alkyne moiety. Thus, 3-indenylin-
dole derivatives were easily obtained
through formal iso-Nazarov or Nazarov
cyclizations. DFT computations sup-
port the formation of an alkylidenecy-
clopropane intermediate that under-
goes gold-iso-Nazarov or gold-Nazarov
cyclizations upon torquoselective ring
opening. In addition, 3-dienylindoles
could be accessed when none of the re-
ferred pathways were accessible and so
the intermediate Au–carbenoid com-
À
plex evolved via a 1,2-C H insertion
reaction. We have also demonstrated
that the final products can be obtained
in a one-pot protocol from easily avail-
able propargylic alcohols and indoles.
Keywords: gold
·
homogeneous
catalysis · indoles · reaction mecha-
nisms
Introduction
A great number of novel transformations have appeared
during the last years based on the gold-catalyzed activation
of alkynes.[1] In this field, one of the most important process-
es is the 1,2-acyl migration observed in propargylic esters
that generates a metal–carbenoid intermediate as shown in
Scheme 1 (X=OCOR).[2] These gold–carbenoid species can
undergo a variety of subsequent transformations.[3] Other
heteroatomic nucleophiles, such as a thio group, are also
able to participate in related 1,2-sulfur migration reactions
(X=SR, Scheme 1).[4] In a recent communication we report-
ed the first 1,2-migration reaction of a carbon-centered
moiety (in particular a 1,2-indole migration; X=indol-3-yl
in Scheme 1).[5]
[a] Dr. R. Sanz, Dr. D. Miguel, Dr. M. Gohain, Dr. P. Garcꢀa-Garcꢀa,
Dr. M. A. Fernꢁndez-Rodrꢀguez
ꢂrea de Quꢀmica Orgꢁnica, Departamento de Quꢀmica
Facultad de Ciencias, Universidad de Burgos
Pza. Misael BaÇuelos s/n, 09001 Burgos (Spain)
Fax : (+34)947-258831
E-mail: rsd@ubu.es
[b] A. Gonzꢁlez-Pꢃrez, Dr. O. Nieto-Faza, Prof. Dr. ꢂ. R. de Lera
Departamento de Quꢀmica Orgꢁnica, Facultad de Quꢀmica
Universidade de Vigo, Lagoas Marcosende
36310 Vigo, Galicia (Spain)
Fax : (+34)986-811940
E-mail: qolera@uvigo.es
[c] Dr. F. Rodrꢀguez
Instituto Universitario de Quꢀmica Organometꢁlica “Enrique Moles”
Universidad de Oviedo, C/Juliꢁn Claverꢀa, 8, 33006 Oviedo (Spain)
E-mail: frodriguez@uniovi.es
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201001162: Full experimental
procedures and characterization data for all the compounds reported
in this work, Cartessian coordinates and comprehensive computation-
al analysis are included.
Scheme 1. Gold-catalyzed 1,2-migration reactions.
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FULL PAPER
By contrast to those similar processes described before,
propargylic position (see the presence of two alkyl substitu-
ents at the propargylic position), we observed the formation
of a new 3-(inden-2-yl)indole 4a in 68% yield [Scheme 2,
Eq. (2)]. In this case the formation of the indene core in-
volves the reaction of the phenyl group at the terminal posi-
tion of the starting alkyne. As before, formation of indene
derivative 4a can only be explained after an initial 1,2-mi-
gration of the indole moiety. The structural assignment of
this new compound 4a, initially determined by NMR stud-
ies, was confirmed by single-crystal X-ray diffraction analy-
sis.[11] At this point it should be noted that the starting
indole derivative 1a possesses a phenyl group at the propar-
gylic position and another one at the terminal position of
the triple bond. With the results discussed above, in princi-
ple, both phenyl groups could be involved in the formation
of an indene skeleton. However, in this case only the phenyl
group at the propargylic position participates in the cycliza-
tion reaction to give exclusively indene derivative 3a.
À
our reaction implies the rupture and formation of carbon
À
carbon bonds instead of rupture and formation of carbon
heteroatom bonds. This idea is based on the well-established
nucleophilic nature of indoles.[6] This characteristic of in-
doles has already been exploited by several authors to de-
velop some interesting cascade reactions based on the abili-
ty of this heterocycle to add to gold-activated alkynes or al-
lenes.[7] Our method was based on the assumption that an
indole group at the propargylic position of an alkyne could
trigger a 1,2-migration reaction similar to that involving
propargylic carboxylates or propargylic sulfides. Taking ad-
vantage of our reported procedure for the synthesis of C3-
propargylated indoles,[8] we were able to easily synthesize a
great variety of starting materials and to study the scope of
those preliminary reactions. Herein, we present a full exper-
imental and theoretical study on this novel 1,2-indole migra-
tion reaction including some new reaction pathways.
Mechanism of the reactions: As previously stated, formation
of compounds 3a and 4a seems to imply a 1,2-migration of
the indole moiety. This suggested that the reactions leading
to both of these compounds probably proceeded through
the formation of a common intermediate obtained after the
initial indole migration. Taking this into consideration we
believed that the mechanisms depicted in Scheme 3 might
account for the formation of compounds 3a and 4a. Thus,
an initial coordination of the gold complex to the triple
bond of the starting materials 1a or 2a would take place to
form intermediate 5. Intramolecular attack of the indole on
the activated alkyne may occur to give the vinyl–gold com-
plex 6, which would then become the a,b-unsaturated gold–
carbenoid complex 7 through rearrangement and 1,2-migra-
tion of the indole nucleus. At this point two reaction path-
ways are possible depending on the substitution at the b-
carbon of the gold carbenoid intermediate 7. Thus, when a
phenyl group is present at this position (path a, R1 =Ph) an
intramolecular nucleophilic attack of the phenyl group to
the carbene carbon of 7a would lead to the formation of in-
termediate 8. This transformation (7a to 8) can also be seen
as a metalla–iso-Nazarov process.[12] After formation of 8, a
rearomatization step and subsequent protodemetalation
would render the final product 3a regenerating the catalytic
gold species. The global conversion from 1a to 3a may be
considered a tandem sequence involving a 1,2-indole migra-
tion followed by a formal metalla–iso-Nazarov reaction. For
simplicity, we will call the pathway leading to the indene de-
rivative 3a the gold–iso-Nazarov mechanism (path a in
Scheme 3).
Results and Discussion
Preliminary results: We initially studied the rearrangement
of the indole derivative 1a as a model system. After a brief
screening of different catalysts we realized that complete
conversion of the starting material was achieved in less than
30 min at room temperature in the presence of catalytic
amounts of cationic gold(I) complexes.[9] Thus, 3-(1H-inden-
2-yl)-1H-indole derivative 3a was selectively obtained in
79% yield by using as catalyst the bis(trifluoromethanesul-
fonyl)imidate
derivative
[AuNTf
N
[Scheme 2,
Scheme 2. Gold-catalyzed reaction of C-3-propargylated indoles 1a and
2a.
Eq. (1)].[10] The structure of this new indole derivative 3a
was initially established after a series of NMR experiments.
An examination of the structure of compound 3a indicates
that the phenyl group at the propargylic position has been
involved in the rearrangement of 1a and, more important,
that a 1,2-indole migration has occurred at some point in
the catalytic process.
On the other hand, when the starting indole derivative
bears two alkyl groups at the propargylic positions (path b,
R1 =R2 =Et), the carbene intermediate 7b may evolve
through a Nazarov-type cyclization to give 9.[13] Alternative-
ly, an intramolecular capture of the gold-stabilized allyl
cation by the phenyl group could also be considered to ex-
plain this step.[13d,14] Ultimately, after a rearomatization and
protodemetalation, product 4a would be formed. For sim-
Surprisingly, when the same reaction was performed with
the indole derivative 2a lacking the phenyl group at the
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R. Sanz, ꢂ. R. de Lera, F. Rodrꢀguez et al.
Scheme 3. Proposed mechanism for the formation of 3a and 4a.
Scheme 4. General mechanistic proposal for the gold-mediated rear-
rangement of 3-propargylindoles with different substituents (Me, Ph) at
the internal propargylic position (one of the enantiomers of Va was arbi-
trarily chosen). The free energy values (relative to starting complexes Va
and Vb) are given in kcalmolÀ1. All computations have been carried out
at the B3LYP/6-31G(d) level and the M06/6-31G(d) level (values in
brackets).
plicity, we will call the pathway leading to indene derivative
4a the gold–Nazarov mechanism (path b in Scheme 3).
Theoretical studies: We sought to provide computational
support to the proposed mechanism for this unprecedented
1,2-indole migration upon gold activation of the alkyne in
the starting C3-propargylated indoles, in particular concern-
ing the feasibility of the alkylidenecyclopropane intermedi-
ate and its further evolution to a gold carbocation/carbe-
noid. The analysis of the transition structure for the ensuing
cyclization from the gold species could help to determine
whether a Nazarov-type or other alternative mechanisms
are operating.[15] With the computational exploration of the
mechanistic alternatives for these transformations we aimed
to establish the factors governing the switch in product dis-
tribution and also shed light on the specific role of the gold
center and the indole heterocycle, an uncommon nucleo-
phile for this kind of rearrangement of propargylic sub-
strates. For the calculations, we have chosen model systems
Va and Vb (Scheme 4, the Roman numerals corresponding
to model structures of Scheme 3 will be used throughout for
clarity), with and without a propargylic phenyl group, re-
spectively, as a compromise structure between the two sim-
plest models reported. Also for the sake of simplicity and
reduced computational cost, goldꢅs ligand was chosen to be
PH3.
optimization and harmonic analysis of the frequencies was
carried out at both DFT hybrid functional levels of theory.
Solvation effects were taken into consideration when com-
puting the reaction profiles of Scheme 4. The polarizable
continuum model (PCM)[20] was employed with dichlorome-
thane parameters in a single point energy calculation and
the molecular cavity created with the UAKS radii set. The
results, qualitatively similar to those obtained in gas phase,
are listed in the Supporting Information. All calculations
have been performed with the Gaussian09 program suite.[21]
The calculations with the hybrid meta exchange correlation
functional M06, which has shown good performance for the
study of transition-metal-catalyzed reactions,[17] provide a
comparison with the B3LYP functional (the M06 values are
shown on Scheme 4 and listed in Table 1). In general, the ac-
tivation barriers are higher with M06, except for the iso-
Nazarov reaction (see below), whereas the minima are less
stabilized, which allowed to locate intermediate VIa. Since
the interpretation of the reaction mechanism is similar using
both functionals, only the B3LYP values will be used along
the discussion.
Computational details: Stationary points along the V to IX
transformation for the two reacting systems have been locat-
ed using DFT in its Kohn–Sham approach, with the
B3LYP[16] and M06 functionals,[17] and a 6-31G(d) basis
set[18] for the main group atoms and the LANL2DZ electron
core potential[19] and associated basis set for gold. Geometry
Theoretical results: The results of our computational study
are summarized in Scheme 4 and the relative and activation
free energies for the proposed paths are collected in Table 1.
Gold coordination to the alkyne in the first step can take
place either anti or syn to the indole heterocycle, which gen-
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Gold(I)-Catalyzed Tandem Reactions
FULL PAPER
Table 1. Relative and activation free energies (in kcalmolÀ1) for the sta-
tionary points of the mechanisms depicted in Figure 1 in gas phase.[a]
olefin due to the minimization
of the steric interactions of the
indole and rotating phenyl
groups upon cyclopropane ring
opening. The evolution of VIIb
to VIIIb via a gold-stabilized
pentadienyl cation cyclization
(gold-Nazarov process)[13,15e–g]
is expected, given the proximi-
DGrel
DG#
DGrel
DG#
Va
0.00
Vb
0.00
tsVa
4.26 (4.26)
4.26
tsVb
6.15 (6.92)
6.15 (6.92)
(4.26)
VIa
tsVIa
VIIa
–
–
[b] (1.62)
[b] (4.20)
VIb
5.33 (6.51)
[b]
–
(2.58) tsVIb 10.49 (14.81) 5.16 (8.30)
À9.65 (À8.22)
VIIb
À5.47
(À1.74)
tsVIIa À0.23 (0.08)
9.42
(8.31)
tsVIIb 5.42 (7.74)
10.88
(9.47)
À
ty of the C1’ C2’ olefin and
the terminal phenyl group in
the conformation adopted by
VIb after the indole migration
is complete. As explained, fol-
lowing the ring opening of
VIb, the developing allylic
strain between the terminal Ph
and the indole heterocycle re-
sults in the rotation of the C1’-
C2’-C3’-Ph dihedral being cou-
pled with the ring opening in
VIb and affording an helical
structure VIIb (P from the
VIIIa À12.08
(À17.44)
IXb
À7.89
(À8.87)
[a] All computations have been carried out at the B3LYP/6-31G(d) and
the M06/6-31G(d) level (values in brackets). [b] The missing values (de-
noted as –) correspond to the B3LYP barrierless process tsVa to VIIa il-
lustrated in the Supporting Information (Figure S1). The free energy
values in dichloromethane solution (PCM) can be found in the Support-
ing Information.
Figure 1. Gas-phase computed
(B3LYP/6-31G(d)) geometries
of TSVa and VIIa.
erates two families of isomers for each system. Only the
pathways that start from the anti coordination of gold and
lead to the E olefin in VI will be discussed.[22] Although
energy differences are not significant for the minima in
these alternate paths, the equivalent mechanisms starting
from syn coordination (see Supporting Information) and
providing a Z gold-substituted olefin are globally higher in
energy (about 5 kcalmolÀ1 for the first transition states).
Starting from V, the first step involves a capture at C2’ of
the gold-activated alkyne by nucleophilic attack of the
configuration of Vb shown in Scheme 4). Thus, the following
VIIb to IXb concerted electrocyclization benefits from the
already enforced helical conformation resulting in
a
10.88 kcalmolÀ1 reaction barrier.
The aromaticity of the transition structures has often been
utilized for the characterization of pericyclic molecular rear-
rangements. A useful magnitude to estimate the aromaticity
is the nucleus-independent chemical shift (NICS)[27] with
large negative NICS values corresponding to diatropic ring
currents related to aromaticity (À9.7 for benzene at the ring
center) and positive values associated to paratropic ring cur-
rents and antiaromaticity. The NICS at the ring center of
tsVIIb (À10.4 ppm) confirms its aromatic character and
therefore the rearrangement can be considered as a 4peÀ
electrocyclic process.
The evolution of VIIa would take place by electrocyclic
ring closure involving the phenyl ring cis to the gold-con-
taining carbon atom. In this alternative gold-iso-Nazarov[12]
reaction the gold-stabilized cation is located at the terminus
of the cyclizing system. The initial selectivity of the p gold
alkyne coordination (anti to the indole) leads to a Z double
bond (the bulky phenyl group on C1’ tends to rotate out-
wards in the 4-electron ring opening of VIa, away from the
indole, in order to reduce the steric strain in VIIa) and to an
s-trans conformation of the adjacent bond. This directly re-
sults in a helical pentadienyl cation structure poised to un-
dergo an electrocyclic ring closure.[15]
À
indole C3 position, resulting in the formation of a new C C
bond through an early transition state (see Scheme 4). The
fate of the system after this low-energy transition state
(4.26 kcalmolÀ1 for tsVa and 6.15 kcalmolÀ1 for tsVb), how-
ever, depends on the substitution pattern at the propargylic
position. The system with alkyl substituents evolves to an al-
kylidenecyclopropane intermediate VIb. Worthy of note,
À
whereas the C1’ C2’ bond is longer (1.58 ꢆ) and the formed
À
C3 C2’ is shorter (1.49 ꢆ) than those of cyclopropane
[23]
À
(1.51 ꢆ), the C3 C1’ bond is elongated to 1.62 ꢆ, favor-
À
ing the ensuing rearrangement with C3 C1’ scission. Inter-
mediate VIb is then connected to the “gold-carbenoid”[24]
VIIb through tsVIb, in the rate-limiting step of the tandem
rearrangement. In this transition state the alkylidene group
on the cyclopropane ring smoothly rotates to minimize the
steric interaction between the phenyl and the indole rings in
VIIb.
This picture is somewhat modified for the analog system
with a phenyl group at C1’. The spirocycle VIa and the cor-
responding ring-opening transition state tsVIa, which would
connect it to VIIa, could only be located as stationary points
on the potential energy surface corresponding to Va using
the M06 functional.[25]
Thus, both mechanisms converge in structures VII, for-
mally cationic gold species within conjugated pentadienyl
systems. For the phenyl-substituted propargylic system we
find that the VIa to VIIa process is also torquoselective and
affords intermediate VIIa (Figure 1) with Z geometry of the
The computed energy values for these transition states
confirm that the gold-iso-Nazarov is favored over the alter-
native gold-Nazarov reaction channel available from the
twisted s-cis conformation of VIIa (Scheme 4 and Support-
ing Information). The energy barrier for the favored cycliza-
tion of VIIa, 9.42 kcalmolÀ1 is 2.29 kcalmolÀ1 lower than the
alternative ring closure that would involve the external Ph
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R. Sanz, ꢂ. R. de Lera, F. Rodrꢀguez et al.
group (11.71 kcalmolÀ1). Moreover, it is 3.67 kcalmolÀ1
more favorable than yet another gold-iso-Nazarov reaction
available from the initial syn coordination of gold to the
alkyne (see Supporting Information).[28] The preference for
the cyclization leading to VIIIa is also reinforced by the ex-
pected high barrier of bond rotation to the proper s-cis con-
formation required by the pentadienyl cation extended to
the terminal phenyl group. The calculated NICS[27] at the
ring center of tsVIIa with a value of À9.2 ppm, indicates
likewise the electrocyclic nature of the process.
are summarized in Table 2. These data show that the process
is efficient with alkynes 1 having indole-groups with a wide
range of substitution patterns. Thus, substrates bearing N-
methylindole (Table 2, entries 1–5), indole (Table 2, en-
tries 6–7), 2-methylindole (Table 2, entry 11), 1,2-dimethylin-
dole (Table 2, entries 12–14) as well as 1-methyl-2-phenylin-
dole and 1,2-diphenylindole (Table 2, entries 15–17) effi-
ciently furnished the indenyl adducts 3. Interestingly, start-
ing materials 1h–j containing less nucleophilic indole moiet-
ies (those with electron-withdrawing substituents at C-5 of
the indole ring) also underwent the migration/iso-Nazarov
tandem sequence to finally afford the corresponding indenes
3h–j in good yields (Table 2, entries 8–10). Moreover, vari-
ous aromatic and linear or branched aliphatic substituents
were also well tolerated at both the propargylic (R4 in
Scheme of Table 2) and the terminal position of the triple
bond (R5 in Scheme of Table 2). The isomerization of indole
derivatives 1r–u having a terminal alkyne moiety was also
investigated (Table 2, entries 18–21). Reactions of these sub-
strates in the presence of catalytic amounts of [AuNTf2-
A last step from VIIIa and IXb, which already exhibit the
main structural motif of the products, to IIIa and IVb is re-
quired to recover the aromaticity of the systems. Proton ab-
straction on VIIIa and IXb can be mediated by a soft base
À
resulting in the weakening of the Au C bond and formation
of the final indenylindole derivative. The gold catalyst can
then be released again to the solution and reincorporated
into the catalytic cycle.
To summarize this section, our computational studies con-
firm the anticipated overall mechanistic picture, comprising
three major steps: a) the electrophilic addition of the gold-
activated alkyne to the indole ring with formation of the al-
kylidenecyclopropane intermediate, b) its further evolution
by indole-induced torquoselective 4peÀ-electrocyclic ring
opening to a gold carbocation/carbenoid, and c) the 4peÀ-
electrocyclic ring closure of the gold-stabilized carbocation
species in processes that can be considered as gold variants
of the Nazarov or iso-Nazarov reactions. The analysis of the
aromaticity of the transition structures for the cyclization is
consistent with the consideration of the processes as pericy-
clic reactions. Whereas the systems with dialkyl groups at
the propargylic position follow the Nazarov manifold, the
presence of an aryl group at this position induces a shift in
the mechanism, which now follows the iso-Nazarov pathway
in preference over the alternative Nazarov, thus explaining
the product distribution with otherwise similar substrates.
The lower activation energy for the rate-limiting gold-iso-
Nazarov reaction relative to the aura-Nazarov explains the
higher temperatures required for the rearrangement of the
propargylic substrates substituted with dialkylgroups 2 com-
pared with the alkyl–aryl analogue 1.
AHCTUNTGREGN(NUN Ph3P)] under the optimized conditions followed the same
reaction pathway previously observed for internal alkynes to
furnish the observed compounds 3r–u. However, it should
be noted that in accordance with the observations of other
authors,[4] in these cases the reaction initially furnishes a
mixture of two regioisomeric indenes which could be con-
verted into the desired indene derivatives 3r–u by simple
treatment of the crude of the reaction with 5 mol% of p-tol-
uenesulfonic acid. Interestingly, functionalized alkynes 1v
and 1w,[29] bearing a phenylthio and an ester group, respec-
tively at the triple bond, also gave the expected indene de-
rivatives 3v–w in high yield (Table 2, entries 22 and 23).
Moreover, reaction of starting material 1x, which contains a
free alcohol in the alkyl chain of the substituent at the triple
bond, occurred in the same fashion to give the indenyl
adduct 3x in high yield (Table 2, entry 24). It should be
noted that in this particular case we did not observe the for-
mation of products coming from an also possible 5-endo-hy-
droalkoxylation reaction of the carbon-carbon triple
bond.[30] Structural assignments of all new compounds were
based on a series of NMR studies or established by analogy.
Additionally, the structures of 3c and 3e were confirmed by
single-crystal X-ray diffraction analysis.[11]
To test the capability of heteroaromatic substituents to
participate in the iso-Nazarov cyclization of the tandem pro-
cess we turned our attention to the rearrangement of com-
pounds 10a–b possessing a thiophene group at the propar-
gylic position. Pleasantly, reactions of these substrates under
the optimized conditions occurred in high yields to provide
exclusively the corresponding 5-indolylcyclopenta[b]thio-
phene derivatives 11a–b (Scheme 5). Moreover, these ex-
periments demonstrate that the method here described is
appropriate not only for the synthesis of indene derivatives
but also for the synthesis of other fused-bicyclic compounds.
Scope of the gold-catalyzed tandem reactions: After having
established the mechanisms and conditions for the transfor-
mation of C3-propargylated indoles 1a and 2a to 3-(inden-
2-yl)indole derivatives 3a and 4a, the scope and limitations
of these novel catalytic tandem processes have been ex-
plored. Most of the reactions were performed in the pres-
ence of [AuNTf2ACHTUNGTRENNUNG(Ph3P)] that was the catalyst of choice due
to its availability and ease of handling.
Synthesis of 3-(1H-inden-2-yl)-1H-indoles 3 by tandem 1,2-
indole migration/gold-iso-Nazarov reaction: Reaction of a
series of indole derivatives 1 possessing both an aromatic
and an aliphatic substituent at the propargylic positions and
either aromatic or aliphatic groups at the alkyne terminus
were conducted under the optimized conditions. The results
Synthesis of 3-(inden-2-yl)indoles 4 by tandem 1,2-indole
migration/gold-Nazarov reaction: Having studied the scope
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Gold(I)-Catalyzed Tandem Reactions
FULL PAPER
Table 2. Preparation of 3-(1H-inden-2-yl)-1H-indoles 3 by gold-catalyzed
tandem 1,2-indole migration/iso-Nazarov reactions of C3-propargylated
indole derivatives 1.[a]
propargylic position, was conducted to evaluate the scope of
this transformation (Table 3). The results revealed that the
tandem process occurs with several C3-propargylated in-
doles 2 bearing indole moieties such as N-methylindole
(Table 3, entries 1–3), indole (Table 3, entry 4), 2-methylin-
dole (Table 3, entry 5), 2-phenylindole (Table 3, entry 6) and
1,2-dimethylindole (Table 3, entries 7–8). Moreover, both
linear and branched aliphatic substituents were also well tol-
erated at the propargylic carbon (R3 and R4 in scheme of
Table 3). Structural assignments of all cycloadducts 4 were
based on a series of NMR experiments. Additionally, the
structure of 4b was confirmed by single-crystal X-ray dif-
fraction analysis.[11]
Entry
1
R1 R2 R3
R4
R5
R6
3
Yield
[%][b]
1
2
3
4
5
6
7
8
1a Me
1b Me
1c Me
1d Me
1e Me
H
H
H
H
H
H
H
H
H
H
Me
H
H
H
H
H
H
H
Et
Ph
Ph
Ph
H
H
H
H
3a 79
3b 75
3c 76
3d 73
nPr
iPr
iPr
Me
nPr
Me
nBu
nBu
Ph
nBu
nBu
nBu
nBu
Ph
Ph
Ph
nBu
Ph
Ph
Table 3. Preparation of 3-(inden-2-yl)indoles 4 by gold-catalyzed tandem
1,2-indole migration/Nazarov-type cyclization of C3-propargylated indole
derivatives 2.[a]
Cl 3e 79[c]
1 f
1g
1h
1i
1j
1k
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
3 f 60
3g 66
3h 75
3i 70
3j 69
3k 68
3l 68[c]
3m 70
3n 67
3o 73[d]
3p 78
3q 86
3r 83
3s 71
CO2Me Me
CO2Me Et
9
10
11
12
13
14
15
16
17
18[e]
19[e]
20[e]
21[e]
22
23
24
Br
H
H
H
H
H
H
H
H
H
H
H
H
H
H
Me
Me
Me
Et
nPr
Me
Et
cC6H11 Ph
cC3H5
Et
1l Me Me
1m Me Me
1n Me Me
1o Me Ph
1p Me Ph
1q Ph Ph
Entry
2
R1
R2
R3
R4
4
Yield [%][b]
1
2
3
4
5
6
7
8
2a
2b
2c
2d
2e
2 f
2g
2h
Me
Me
Me
H
H
H
H
H
H
H
Me
Ph
Me
Me
Et
Et
Me
4a
4b
4c
4d
4e
4 f
4g
4h
68
82
87
75
80
77
72
81
Me
Me
Me
Me
cC3H5
Me
Me
1r Me
H
H
H
H
H
cC3H5
cC3H5
cC3H5
cC3H5
Me
1s
1t
1u
H
H
H
Ph
Ph
Ph
H
H
H
Et
cC3H5
cC3H5 SPh
cC3H5 CO2Et
Cl 3t 70
H
H
H
H
3u 84
3v 84
3w 75
3x 76
1v Me
1w Me
1x Me
Me
Me
cC3H5
cC3H5
ACHTUGNRTNE(NUNG CH2)2OH
[a] Reactions stirred at reflux until consumption of the starting material
(1–24 h), as judged by GC-MS analysis. [b] Yield of isolated product
based on the corresponding starting indole 2.
[a] Reactions stirred at room temperature until consumption of the start-
ing material (0.5–7 h), as judged by GC-MS analysis. [b] Yield of isolated
product based on the corresponding starting indole 1. [c] Reaction per-
formed with [AuCl
ACHTUNGTRENNUNG(Ph3P)]/AgSbF6 as catalyst. [d] Reaction performed
with [AuNTf2A(SPhos)] as catalyst (SPhos=2-dicyclohexylphosphino-2’,6’-
CHTUNGTRENNUNG
dimethoxybiphenyl). [e] The crude reaction mixture was treated with
PTSA (5 mol%) in acetonitrile at reflux after the complete consumption
of the corresponding starting indole 1.
To further test the scope of the process we explored the
reaction with starting materials where the substituent at the
terminal position of the alkyne was different from a simple
phenyl group. We were pleased to find that indole deriva-
tives 12a–b, bearing a 3-thienyl group at the alkyne termi-
nus, afforded the corresponding 5-indolylcyclopenta[b]thio-
phene derivatives 13a–b in high yields [Scheme 6, Eq. (1)].
The structure of compound 13b and thus the regioselectivity
of the cyclization regarding the thiophene ring was con-
firmed by single-crystal X-ray diffraction analysis.[11] Not
only heteroaromatic groups but also simple olefins can par-
take in the tandem process as demonstrated in the isomeri-
zation of 14. In this case, a tetrahydroindene cycloadduct 15
was formed in excellent yield [Scheme 6, Eq. (2)]. Again,
these reactions demonstrate that a range of fused bicyclic
skeletons can be accessed by this tandem 1,2-indole migra-
tion/Nazarov cyclization reaction.
Scheme 5. Gold-catalyzed tandem 1,2-indole migration/iso-Nazarov reac-
tions of indole derivatives 10a-b.
of the gold-catalyzed isomerization reactions of substrates 1,
we turned our attention to the tandem 1,2-indole migration/
Nazarov cyclization process. The reaction of a series of rep-
resentative alkynes 2, all of which contain a phenyl group at
the alkyne terminus and two aliphatic substituents at the
We were also intrigued about the mechanism that would
follow an intermediate 7 (see Scheme 3) in which both
mechanisms, the metalla-iso-Nazarov and the Nazarov
mechanisms, are possible. Thus, we designed an experiment
Chem. Eur. J. 2010, 16, 9818 – 9828
ꢄ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
9823

R. Sanz, ꢂ. R. de Lera, F. Rodrꢀguez et al.
À
Scheme 7. Gold-catalyzed tandem 1,2-indole migration/1,2-C H insertion
reactions of indole derivatives 19.
Table 4. Synthesis of 3-(1,3-dien-2-yl)indoles 20 by gold-catalyzed
À
tandem 1,2-indole migration/1,2-C H insertion reactions of C-3-propar-
gylated indole derivatives 19.[a]
Entry 19
R1
R2
R3
R4
R5
20
Yield [%][b]
1
2
3
4
5
19a Me
H
Me
2,6-F2C6H4 nPr 20a 89
19b Me Ph Me
19c Me Ph cC3H5 cC3H5
19d Me Ph Me Me
19e Me Me cC3H5 cC3H5
cC3H5
nPr 20b 85
nPr 20c 91
nBu 20d 64
nPr 20e 56[c]
[a] Reactions stirred at RT until consumption of the starting material (7–
16 h), as judged by GC-MS analysis. [b] Yield of isolated product based
on the corresponding starting indole 19. [c] 36 h at reflux.
this kind of evolution of the gold–carbenoid intermediate
could also be possible with indoles 1 possessing an alkyl
group at the terminal position of the triple bond (see
Table 2, entries 4–5, 7–10, and 14). However, in those cases
the more favored gold-iso-Nazarov operates to give the cor-
responding products 3 and we did not observe the formation
of the alternative products 20.
Scheme 6. Gold-catalyzed tandem 1,2-indole migration/Nazarov cycliza-
tion reactions of indole derivatives 12, 14 and 16.
by using the biphenyl-substituted starting materials 16a–b
[Scheme 6, Eq. (3)]. After the initial 1,2-migration of the
indole moiety an intermediate 18 (analogous to 7 in
Scheme 3) should be formed. This intermediate could
evolve through a gold-iso-Nazarov mechanism (path a in
Scheme 3) or through a gold-Nazarov mechanism (path b in
Scheme 3). However, we only observed the formation of
compounds 17a–b indicating the preference of the Nazarov
mechanism in this highly congested case.
One-pot procedure for the synthesis of compounds 3, 4, 11
and 20 from indoles and propargylic alcohols: Taking into
account that all the starting indole-containing alkyne deriva-
tives were synthesized from the corresponding propargylic
alcohols by our reported Brønsted acid-catalyzed proce-
dure,[32] we wondered if it would be possible to access
indene derivatives 3 (gold-iso-Nazarov products) or 4 (gold-
Nazarov products) from readily available starting materials,
such as alkynols 23, by using a concurrent tandem catalysis
protocol.[33] Thus, as shown in Table 5, the consecutive reac-
tion of indoles 22 and propargylic alcohols 23 with PTSA
Synthesis of 3-dienylindoles 20 by tandem 1,2-indole migra-
À
tion/1,2-C H insertion reactions: Finally, we wondered if
the proposed gold–carbene intermediate 7 (Scheme 3) could
evolve trough new reaction pathways when the gold-iso-
Nazarov and the gold-Nazarov cyclization were not possible.
To this end, indole 19a that contains a 2,6-disubstitued
phenyl group at the propargylic position and an alkyl group
at terminal position of the triple bond, as well as indoles
19b–e, bearing only alkyl substituents at those positions,
were tested under the standard conditions (Scheme 7 and
Table 4). With all these substrates a new evolution of the in-
termediate gold–carbenoid complex 21 (analogous to 7 in
(5 mol%) and [AuNTf2ACHTNUGTRNE(GNU Ph3P)] (5 mol%) in CH2Cl2 at room
temperature, led to the formation of 3-indenylindoles 3 or 4
in good yields. Notably, this one-pot procedure does not re-
quire any solvent change or removal of PTSA prior to the
addition of the gold catalyst.[34] By following this strategy
the isolation of starting alkynes 1 or 2 is avoided, and the re-
action can be performed from readily available propargylic
alcohols and indoles in a straightforward manner. Some of
the previously prepared 3-indenylindoles 3 or 4 have been
synthesized by this one-pot protocol and in addition, two
À
Scheme 3) was observed consisting on a 1,2-C H insertion
reaction to finally furnish 3-dienylindole derivatives 20 as
mixtures of geometric isomers.[31] It should be noted that
9824
www.chemeurj.org
ꢄ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2010, 16, 9818 – 9828

Gold(I)-Catalyzed Tandem Reactions
FULL PAPER
Table 5. One-pot preparation of 3-indenylindoles 3 and 4 from indoles 22 and propargylic alcohols 23.[a]
rov-type pentadienyl cycliza-
tion. In addition, DFT calcula-
tions reveal that after the initial
indole attack on the activated
alkyne, the alkylidenecyclopro-
pane derivative obtained rear-
ranges through a torqueselec-
tive electrocyclic ring opening
to furnish a gold carbocation/
carbenoid. The subsequent elec-
trocyclic ring closures can be
considered as gold variants of
the Nazarov or iso-Nazarov re-
actions. Interestingly, we found
that it is also possible to per-
form these reactions following
a concurrent tandem catalysis
protocol starting from readily
Entry
22
R1
R2
23
R3
R4
R5
Product
Yield [%][b]
1
2
3
4
5
6
7
8
22a
22a
22b
22c
22d
22a
22c
22d
Me
Me
H
H
H
H
Me
Me
H
Me
Me
23a
23b
23c
23d
23e
23 f
23 f
23 f
iPr
cC3H5
Me
cC3H5
Et
cC3H5
cC3H5
cC3H5
Ph
Ph
Ph
Ph
Ph
Me
Me
Me
Ph
H
nBu
Ph
nBu
Ph
3c
3r
3g
3y
3z
4c
4e
4h
70
70
50[c]
68
51
69
72
70
H
Me
Me
H
Ph
Ph
Me
[a] All reactions were conducted by stirring at RT an equimolecular mixture of indole 22 and alkynol 23 in the
presence of the appropriate catalyst until consumption of the starting material as judged by GC-MS analysis
(global reaction time: 2–24 h. See Supporting Information). [b] Yield of isolated product based on the corre- available propargylic alcohols
sponding starting indole 22. [c] After the addition of the gold catalyst, the mixture was stirred at reflux for
48 h.
and indoles, thus avoiding the
isolation of the C3-propargylin-
doles. Also, a new evolution of
the gold–carbene intermediate
À
new derivatives 3 (compounds 3y–z in Table 5, entries 4 and
5) have been obtained.
As shown in Scheme 8, this method is also convenient for
the synthesis of fused-bicyclic compounds such as 13b and
dienyl derivatives such as 20c from easily available starting
materials.
through a 1,2-C H insertion reaction to give 3-dienylindoles
has been observed in those cases where the favored Nazarov
or iso-Nazarov reactions are not possible. Many of the 3-
functionalized indole derivatives are novel compounds that
combine two common drug scaffolds, the indole and the
indene moieties, and therefore hold considerable potential
as biologically active products thus justifying the further de-
velopment of this powerful complexity-generating reaction.
Experimental Section
General: All reactions were carried out under nitrogen atmosphere in
oven-dried glassware with magnetic stirring. CH2Cl2 was analytical grade,
diethyl ether, ethyl acetate and hexane, were obtained from commercial
suppliers and used without further purification. TLC was performed on
aluminium-backed plates coated with silica gel 60 (230–240 mesh) with
F254 indicator. The spots were visualized with UV light (254 nm) and/or
staining with Ce/Mo reagent or phosphomolybdic acid solution and sub-
sequent heating. 1H and 13C NMR spectra were recorded at 300 (or 400)
and 75.4 (or 100.6) MHz, respectively, and measured at room tempera-
ture or at 508C as specified. Chemical shifts in 1H NMR spectra are re-
ported in ppm using residual solvent peak as reference (CHCl3: d 7.16).
Data are reported as follows: chemical shift, multiplicity (s: singlet, brs:
broad singlet, d: doublet, t: triplet, q: quartet, qt: quintuplet, m: multip-
let, dd: double doublet, dt: double triplet, td: triple doublet, ABq: AB
quartet), coupling constant (J in Hz) and integration. 13C NMR spectra
were recorded using broadband proton decoupling and chemical shifts
are reported in ppm using residual solvent peaks as reference (CDCl3: d
77.16). High resolution mass spectra (HRMS) were recorded on a Micro-
mass Autospec spectrometer using EI at 70 eV. Melting points were mea-
sured using open capillary rubes and are uncorrected. GC-MS and low
resolution mass spectra (LRMS) measurements were recorded on a Agi-
lent 6890N/5973 Network GC System, equipped with a HP-5MS column.
Scheme 8. One-pot synthesis of compounds 13b and 20c.
Conclusion
In summary, we have shown for the first time that a carbon-
centered nucleophile such as the indole nucleus is able to
participate in gold-catalyzed 1,2-migration reactions of prop-
argylic systems. The gold–carbenoid intermediates selective-
ly undergo further cyclizations to give 3-(inden-2-yl)indoles.
Depending on the substituents at the propargylic and termi-
nal positions of the starting 3-propargylindole two different
reaction pathways may operate, an iso-Nazarov or a Naza-
Typical procedure for the gold(I)-catalyzed tandem 1,2-indole migration/
iso-Nazarov reactions of alkynes 1 and 10
3-(3-Ethyl-1-phenyl-1H-inden-2-yl)-1-methyl-1H-indole (3a): To a solu-
tion of 3-(1,1-diethyl-3-phenyl-prop-2-ynyl)-1-methyl-1H-indole (1a)
Chem. Eur. J. 2010, 16, 9818 – 9828
ꢄ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
9825

R. Sanz, ꢂ. R. de Lera, F. Rodrꢀguez et al.
(175 mg, 0.5 mmol) in analytical grade CH2Cl2 (1 mL) was added
[AuNTf2A(Ph3P)] (18.5 mg, 0.025 mmol, 5 mol%) at room temperature
General procedure for the one-pot protocol from indoles 22 and alkynols
23: To a solution of the appropriate indole 22 (0.5 mmol) and alkynol 23
(0.5 mmol) in analytical grade CH2Cl2 (1 mL), PTSA (4.8 mg,
0.025 mmol, 5 mol%) was added at room temperature under a nitrogen
atmosphere. The resulting mixture was stirred at room temperature until
complete conversion (monitored by GC-MS and/or TLC). Then [AuNTf2-
CHTUNGTRENNUNG
under a nitrogen atmosphere. The resulting mixture was stirred at room
temperature for 1 h (complete conversion was monitored by GC-MS and/
or TLC). After removing of the solvent, the crude was purified by
column chromatography on silica gel using hexane/diethyl ether 7:1 to
afford 3a (138 mg, 79%) as a white solid. M.p. 134–1368C; Rf =0.35
(hexane/diethyl ether 5:1); 1H NMR (300 MHz, CDCl3, 258C): d=1.41
(dt, J=7.5 Hz, 3H; CH3), 2.88 (q, J=7.5 Hz, 2H; CH2), 3.67 (s, 3H;
NCH3), 5.10 (s, 1H; CHPh), 6.72 (s, 1H; NCH), 7.05–7.33 (m, 10H;
ArH), 7.43 (td, J=7.5, 1.2 Hz, 1H; ArH), 7.56 (d, J=7.5 Hz, 1H; ArH),
7.77 ppm (d, J=7.5 Hz, 1H; ArH); 13C NMR (75.4 MHz, CDCl3, 258C):
d=14.1, 20.0, 32.8, 58.9, 109.4, 111.1, 119.2, 119.4, 120.5, 121.6, 123.9,
124.7, 126.5, 126.7, 127.6, 127.8, 128.3, 128.4, 136.8, 138.9, 140.6, 141.1,
145.4, 148.9 ppm; LRMS(EI): m/z (%): 349 (8) [M]+, 320 (100); HRMS
(EI): m/z: calcd for C26H23N: 349.1830; found: 349.1830; elemental analy-
sis calcd (%) for C26H23N: C 89.36, H 6.63, N 4.01; found: C 89.15, H
6.65, N 3.98.
AHCTUNTGREG(NUNN Ph3P)] (18.5 mg, 0.025 mmol, 5 mol%) was added and the resulting
slurry was stirred at room temperature until complete conversion (moni-
tored by GC-MS and/or TLC). After removing of the solvent, the crude
was purified by column chromatography on silica gel or neutral alumi-
num oxide using the appropriate mixture of hexane and diethyl ether or
ethyl acetate as eluent to afford compounds 3, 4, 13 or 20 in the yields re-
ported in Table 5 and Scheme 8.
Acknowledgements
We grateful thank MEC/FEDER (CTQ2007-61436/BQU and CTQ2009-
09949/BQU) and Junta de Castilla y Leꢈn (BU021A09 and GR-172) for
financial support. We are also grateful to MEC (FPU predoctoral fellow-
ship to D.M., “Young Foreign Researchers” contract (SB2006-0215) to
M.G., “Ramꢈn y Cajal” contract to M.A.F.R., and “Juan de la Cierva”
contract to P.G.G.) and Fundaciꢈn Ramꢈn Areces (predoctoral fellow-
ship to A.G.P.). We are indebted to the Centro de Supercomputaciꢈn de
Galicia (CESGA) for generous allocation of computational resources.
Typical procedure for the gold(I)-catalyzed tandem 1,2-indole migration/
Nazarov reactions of alkynes 2, 12, 14, and 16
3-(1,1-Diethyl-1H-inden-2-yl)-1-methyl-1H-indole (4a): To a solution of
3-(1,1-diethyl-3-phenyl-prop-2-ynyl)-1-methyl-1H-indole (2a) (151 mg,
0.5 mmol) in analytical grade CH2Cl2 (1 mL) was added [AuNTf2ACTHNUTRGNENUG(Ph3P)]
(18.5 mg, 0.025 mmol, 5 mol%) at room temperature under a nitrogen at-
mosphere. The resulting mixture was stirred at reflux for 24 h (complete
conversion monitored by GC-MS and/or TLC). After removing of the
solvent, the crude was purified by column chromatography on silica gel
using hexane/diethyl ether 10:1 to afford 4a (102 mg, 68%) as a white
solid. M.p. 133–1358C; Rf =0.33 (hexane/diethyl ether 9:1); 1H NMR
(300 MHz, CDCl3, 258C): d=0.37 (t, J=7.3 Hz, 6H; 2 ꢇ CH3CH2), 2.05
(q, J=7.3 Hz, 2H; CH3CH2), 2.06 (q, J=7.3 Hz, 2H; CH3CH2), 3.86 (s,
3H; NCH3), 7.14–7.41 (m, 9H;=CH and ArH), 8.09 ppm (dd, J=4.5,
4.0 Hz, 1H; ArH); 13C NMR (75.4 MHz, CDCl3, 258C): d=8.4, 32.0,
31.2, 60.8, 109.5, 111.2, 119.9, 120.2, 121.0, 121.3, 122.3, 124.0, 126.2,
126.4, 126.6, 127.4, 137.2, 145.7, 145.9, 149.9 ppm; LRMS (EI): m/z (%):
301 (94) [M]+, 286 (10), 272 (100), 256 (33), 241 (10); HRMS (EI): m/z:
calcd for C22H23N: 301.1830; found: 301.1829.
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2007, 119, 3478–3519; Angew. Chem. Int. Ed. 2007, 46, 3410–3449;
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Typical procedure for the gold(I)-catalyzed tandem 1,2-indole migration/
À
1,2-C H insertion reactions of alkynes 19
3-(1,1-Dicyclopropylhepta-1,3-dien-2-yl)-1-methyl-2-phenyl-1H-indole
(20c): To
phenyl-1H-indole (19c) (191 mg, 0.5 mmol) in analytical grade CH2Cl2
(1 mL) was added [AuNTf2A(Ph3P)] (18.5 mg, 0.025 mmol, 5 mol%) at
a solution of 3-(1,1-dicyclopropyl-hept-2-ynyl)-1-methyl-2-
CTHUNGTRENNUNG
room temperature under a nitrogen atmosphere. The resulting mixture
was stirred at room temperature for 16 h (complete conversion moni-
tored by GC-MS and/or TLC). After removing of the solvent, the crude
was purified by column chromatography on silica gel using hexane/dieth-
yl ether 50:1 to afford 20c (174 mg, 91%) as a colorless oil (mixture of
isomers E/Z, ~2:1); Rf =0.15 (hexane); 1H NMR (300 MHz, CDCl3,
258C): d=0.08–1.33 (m, 12H maj + 12H min), 0.75 (t, J=7.4 Hz, 3H
min; CH3ACHTUNGTRENNUNG(CH2)2), 0.84 (t, J=7.4 Hz, 3H maj; CH3CAHTUNGTRNE(NUGN CH2)2), 1.62–1.74 (m,
1H min; CH3CH2CHH), 1.78–1.95 (m, 1H min; CH3CH2CHH), 1.99–2.11
(m, 2H maj; CH3CH2CH2), 3.74 (s, 3H min; NCH3), 3.78 (s, 3H maj;
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NCH3), 5.22–5.34 (m, 1H maj + 1H min; CH3ACTHUNGTRNEUNG(CH2)2CH), 6.13 (d, J=
11.5 Hz, 1H min;=CCH), 6.94 (dt, J=15.4, 1.3 Hz, 1H maj;=CCH),
7.09–7.18 (m, 1H maj + 1H min; ArH), 7.23–7.61 ppm (m, 8H maj +
8H min; ArH); 13C NMR (75.4 MHz, CDCl3, 258C): d=5.5 (maj), 5.8
(min), 6.0 (min), 6.08 (min), 6.13 (maj), 6.4 (maj), 11.5 (maj), 12.9 (min),
13.8 (maj), 14.2 (min), 15.3 (min), 16.2 (maj), 22.7 (min), 22.8 (maj), 30.9
(min), 31.4 (min), 31.5 (maj), 35.4 (maj), 109.27 (maj), 109. 31 (min),
114.2 (maj), 116.0 (min), 119.27 (maj), 119.33 (min), 120.6 (min), 120.8
(maj), 121.5 (maj), 121.6 (min), 127.37 (maj), 127.40 (min), 127.7 (min),
127.9 (maj), 128.0 (min), 128.3 (maj), 130.0 (maj), 130.1 (maj), 130.3
(min), 130.5 (maj), 130.7 (min), 130.8 (min), 131.5 (maj), 132.7 (maj),
132.8 (min), 137.5 (min), 137.7 (maj), 137.9 (min), 138.8 (maj), 139.3
(maj), 140.9 ppm (min); LRMS (EI): m/z (%): 381 (15) [M]+, 338 (100),
207 (94).
9826
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Chem. Eur. J. 2010, 16, 9818 – 9828

Gold(I)-Catalyzed Tandem Reactions
FULL PAPER
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À
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G
E
R
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[29] Prepared from indole 1r by lithiation with nBuLi in THF and fur-
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À
À
Chem. Eur. J. 2010, 16, 9818 – 9828
ꢄ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
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[34] No more than 1 equiv of starting alkynol should be used for the al-
kylation step as we have observed that an excess of the propargylic
alcohol has a deleterious effect on the gold catalysis.
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Received: April 30, 2010
Published online: July 19, 2010
9828
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Chem. Eur. J. 2010, 16, 9818 – 9828