An Ir-Pt catalyst for the multistep preparation of functionalized indoles from the reaction of amino alcohols and alkynyl alcohols

Article abstract of DOI:10.1002/chem.201001180

The 1,2,4-trimethyltriazolylidene (ditz) ligand allows the preparation of homo- and heterodimetallic complexes of Pt₂ and Ir-Pt. These two complexes have been characterized by means of spectroscopic and diffractommetric techniques. The catalytic activity of these complexes, together with that of other Pt-based compounds, has been explored in the cyclization-addition of alkynyl alcohols and indoles. The Ir-Pt complex [{PtI₂(py)}(μ- ditz){IrI₂(Cp*)}] (py=pyridine; Cp= pentamethylcyclopentadienyl) allows the combination of an iridium-mediated oxidative cyclization of 2-(ortho-aminophenyl)ethanol to form indoles, with a further step employing a Pt-based multistep reaction that functionalizes indoles. Our results show that the Ir-Pt complex is a very active catalyst in this new multistep preparation of functionalized indoles from the reaction of an amino alcohol with alkynyl alcohols. Three in one: A heterodimetallic complex of Ir-Pt (see graphic) with a triazolyldiylidene linker has been obtained and fully characterized. The complex brings together some of the catalytic properties typically shown by Ir and Pt catalysts. A multistep reaction employing the Ir-mediated oxidative cyclization of 2-(ortho-aminophenyl)ethanol and the Pt-catalyzed cyclization-addition of alkynyl alcohols to indoles is reported.

Full text of DOI:10.1002/chem.201001180

FULL PAPER
DOI: 10.1002/chem.201001180
An Ir–Pt Catalyst for the Multistep Preparation of Functionalized Indoles
from the Reaction of Amino Alcohols and Alkynyl Alcohols
Alessandro Zanardi, Jose A. Mata, and Eduardo Peris*[a]
Abstract: The 1,2,4-trimethyltriazolyl-
idene (ditz) ligand allows the prepara-
alkynyl alcohols and indoles. The Ir–Pt
complex [{PtI2(py)}(m-ditz){IrI2A(Cp*)}]
(py=pyridine; Cp*=pentamethylcy-
clopentadienyl) allows the combination
of an iridium-mediated oxidative cycli-
zation of 2-(ortho-aminophenyl)ethanol
to form indoles, with a further step em-
ploying a Pt-based multistep reaction
that functionalizes indoles. Our results
show that the Ir–Pt complex is a very
active catalyst in this new multistep
preparation of functionalized indoles
from the reaction of an amino alcohol
with alkynyl alcohols.
G
E
G
CHTUNGTRENNUNG
tion of homo- and heterodimetallic
complexes of Pt2 and Ir–Pt. These two
complexes have been characterized by
means of spectroscopic and diffractom-
metric techniques. The catalytic activity
of these complexes, together with that
of other Pt-based compounds, has been
explored in the cyclization–addition of
Keywords: carbenes · domino reac-
tions · indoles · iridium · nitrogen
heterocycles · N ligands · platinum
Introduction
active for a wide range of organic reactions, so that the com-
bination of fundamental catalytic steps, involving simple and
accessible substrates, can lead to sophisticated molecules. In
nature, it has been shown that many enzymes contain two
metal ions which operate cooperatively.[5] As a result, dinu-
clear complexes, containing two metals in close proximity,
have become the subject of extensive investigation in order
to design new bimetallic catalysts.[4,6]
For the last three years, we have focused part of our work
on the design of well-defined, simple catalysts that facilitate
a wide variety of organic transformations.[7] In this context,
we have prepared a series of catalysts that are very active in
several tandem catalytic processes.[8–11] Among these cata-
lysts, those combining two significantly different metals al-
lowed the combination of a number of mechanistically dis-
tinct catalytic reactions, typically mediated by each of the
metals contained in the heterodimetallic unit.[9] For example,
Ir–Pd complex 1 was able to catalyze a series of reactions
typically catalyzed by Ir and Pd complexes, specifically the
dehalogenation/transfer hydrogenation of haloacetophe-
nones, the Suzuki coupling/transfer hydrogenation of p-bro-
Over the course of the last decade, chemists have been
trained to design processes with an increased awareness of
the environmental impact, in an economically beneficial
manner.[1] Within this context, click-chemistry methodolo-
gies[2] and tandem catalytic processes[3,4] have appeared as
useful synthetic tools for the improvement of the efficient
use of materials and energy. In the development of new ap-
proaches to organic molecules, the design of effective cata-
lysts plays a decisive role. In general, well-defined catalysts
are preferable to in situ-generated ones, because they often
facilitate the investigation of the reaction mechanism and
allow the further improvement of the catalytic activity by ra-
tional tuning of the properties of the catalyst. Also, in situ-
generated catalysts often need an activation time, after the
addition of an excess of the ligand (usually a phosphane), in
order to allow the formation of the active catalyst.
In the search of more efficient methods for the prepara-
tion of complex organic architectures, there has been an in-
creasing move towards finding multitopic catalysts that are
[a] A. Zanardi, Dr. J. A. Mata, Prof. E. Peris
Departamento de Quꢀmica Inorgꢁnica y Orgꢁnica
Universitat Jaume I, 12071-Castellꢂn (Spain)
Fax : (+34)964-728-214
E-mail: jmata@qio.uji.es
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201001180.
Chem. Eur. J. 2010, 16, 13109 – 13115
ꢃ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
13109

moacetophenone, and the Suzuki-coupling/a-alkylation of p-
bromoacetophenone.[9]
(155.5 ppm). The dimetallic nature of these two complexes
was confirmed by high-resolution mass spectroscopy, in
which the main peaks were at m/z=715.1340 ([MꢀI]+, 2)
and 1092.8806 ([MꢀI]+, 3).
Based on the benefits provided by complex 1 over other
Ir–Pd catalysts and following our interest in the preparation
of multitopic catalysts for tandem reactions, we now report
on a heterodimetallic IrIII–PtII complex with a 1,2,4-trime-
thyltriazolylidene (ditz) linker.[12] We have synthesized this
complex with the aim of studying combinations of reactions
typically catalyzed by IrIII and PtII. With this in mind, we
have combined the iridium-catalyzed oxidative cyclization
of amino alcohols to form indoles[13] with the platinum-cata-
lyzed multistep reaction of indoles with alkynyl alcohols.[14]
The resulting tandem process comprises three consecutive
reactions, namely the oxidative cyclization of an amino alco-
hol to form indole, the intramolecular hydroalkoxylation of
an alkynyl alcohol to afford a cyclic enol ether, and the ad-
A complete determination of the structures of 2 and 3
was achieved by means of X-ray diffraction studies. Fig-
ures 1 and 2 show the molecular diagrams of 2 and 3, re-
spectively.
The molecular structure of 2 (Figure 1) consists of two
PtI2(py) fragments connected by a ditz bridge. The two
metal fragments present a trans-conformation with respect
ꢀ
dition of a C H bond of indole to the unsaturated moiety of
the cyclic enol ether.
Results and Discussion
Figure 1. Molecular diagram of complex 2. Ellipsoids at the 50% proba-
bility level. Hydrogen atoms have been omitted for clarity. Selected bond
Synthesis and characterization of new complexes: Dimetallic
complexes 2 and 3 were obtained as shown in Scheme 1.
The reaction of PtI2 with 1,2,4-trimethyltriazolium tetra-
fluoroborate and an excess of potassium carbonate, in re-
ꢀ
ꢀ
lengths [ꢄ] and angles [8]: Pt(1) C(1) 1.955(7), Pt(1) I(1) 2.5994(6),
ꢀ
ꢀ
Pt(1) I(2) 2.6030(7), Pt(1) N(3) 2.085(6); C(1)-Pt(1)-N(3) 178.5(3),
N(3)-Pt(1)-I(1) 91.99(17), C(1)-Pt(1)-I(2) 88.4(2), N(3)-Pt(1)-I(2)
91.50(17), I(1)-Pt(1)-I(2) 176.30(2), N(2)-C(1)-Pt(1) 127.3(5).
to the iodide ligands. The two coordination planes about the
metal centers are at an angle of 41.98, slightly lower than
that shown for the related dipalladium complex trans-
[{PdCl2(py)}2ACTHNUTRGNEUNG
(m-ditz)] (47.68).[10] The two metal centers are
quasi-coplanar with the plane of the azole ring, with a small
deviation of 3.088 shown by the torsion angle Pt(1)-C(1)-
N(2)-N(2A). The distance between the two platinum atoms
ꢀ
is 5.96 ꢄ and the Pt C distance is 1.955 ꢄ.
Compound 3 (Figure 2) is isostructural with our previous-
ly reported complex 1,[9] with the only differences being that
the Pd atom is replaced by Pt and the Cl atoms are replaced
by I atoms. The molecule consists of a Cp*IrI2 (Cp*=pen-
Scheme 1. Py=pyridine
fluxing pyridine afforded diplatinum complex 2 as an off-
white crystalline solid, in high yield (75%). IrIII–PtII hetero-
dimetallic complex 3, was obtained by the reaction of PtI2
with triazolium–ylidene–iridium complex 4[11] and an excess
of potassium carbonate, in refluxing pyridine. Complex 3
was isolated as an orange crystalline solid in moderate yield
(41%). Both complexes are stable in the solid state and can
be handled in air.
Figure 2. Molecular diagram of complex 3. Ellipsoids at the 50% proba-
Complex 2 exhibits a characteristic 13C NMR shift at
164.1 ppm for the carbene carbon, indicating the coordina-
tion of the NHC to the metal center. Heterodimetallic com-
plex 3 shows two distinct resonances in this region due to
the carbene carbon atoms bound to Pt (164.0 ppm) and Ir
bility level. Hydrogen atoms and solvent molecules have been omitted
ꢀ
for clarity. Selected bond lengths [ꢄ] and angles [8]: Ir(1) C(2) 2.011(10),
ꢀ
ꢀ
ꢀ
ꢀ
Ir(1) I(1) 2.7213(11), Ir(1) I(2) 2.7195(11), Pt(1) C(1) 1.932(12), Pt(1)
ꢀ
ꢀ
I(3) 2.6044(12), Pt(1) I(4) 2.5987(12), Pt(1) N(4) 2.077(11); C(2)-Ir(1)-
I(1) 96.3(4), C(2)-Ir(1)-I(2) 91.4(3), C(1)-Pt(1)-I(3) 89.1(4), C(1)-Pt(1)-
I(4) 88.0(4).
13110
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Chem. Eur. J. 2010, 16, 13109 – 13115

Synthesis of Functionalized Indoles
FULL PAPER
Table 1. Catalyst screening for the reaction of indole and pent-4-yn-1-
ol.[a]
tamethylcyclopentadienyl) fragment connected to a PtI2Py
moiety by the triazolyldiylidene ligand. The structure of this
complex allows a comparison between the bond lengths to
IrIII and PtII by the same ligand, within the same compound.
These distances are 2.011 and 1.932 ꢄ for IrIII Ccarbene and
ꢀ
II
ꢀ
Pt
C
carbene, respectively. The two iodide ligands on the Pt
fragment adopt a trans configuration. The distance between
Entry
Catalyst[b]
Catalyst loading
[mol%]
T
t
Yield
[%][c]
the two metal centers is 6.04 ꢄ.
A
[8C]
[h]
1[d,e]
2[e]
3[e]
4
PtCl2
2
5
5
5
5
5
1
1
5
1
1
5
1
5
5
1
5
5
1
5
25
25
25
80
25
80
25
80
80
25
80
25
25
80
25
25
80
25
25
12
12
12
0.5
2
1
27
0.5
1
27
0.5
27
2
0.5
27
2
0.5
27
2
36
73
62
84
22
77
46
66
80
36
>95
58
71
>95
58
18
>95
75
Catalytic studies: To study the catalytic abilities of com-
plexes 2 and 3, we decided to combine two reactions typical-
ly catalyzed by iridium and platinum complexes. For this
purpose, we studied the combined oxidative cyclization of
amino alcohols to form indoles (iridium catalyzed)[13] and
the multistep reaction of indoles with alkynyl alcohols (plat-
inum catalyzed), as shown in Scheme 2.[14] In the choice of
5
PtCl2
PtCl2
PtCl2
PtCl2
PtI2
PtI2
PtI2
2
2
2
3
3
5[d]
6[d]
7[d]
8[d]
9[d]
10[d]
11
12
13
14
15
16
17
18
19
3
5
5
5
46
[a] Reaction conditions: indole (0.3 mmol), 4-pentyn-1-ol (0.36 mmol),
anisole (as an internal reference; 0.3 mmol), AgO3SCF3 (3 mol%) in
CH3CN (1.5 mL). [b] Based upon the amount of metal. [c] Yields deter-
mined by GC chromatography. [d] Without addition of AgO3SCF3.
[e] Reactions carried out in toluene.
Scheme 2.
these two reactions, we took into account the fact that, to
design a tandem reaction, it is important to study the cata-
lyst compatibility with the residual materials from the cata-
lytic steps comprising the overall process. In principle, the
reactions that we chose fulfill the requirements for compati-
bility in terms of solvent, temperature, and the nature of the
bases used. In the selection of the reactions, we also took
into account that indoles have become privileged structures
in many research areas, owing to their applications in phar-
maceuticals, fragrances, agrochemicals, pigments, and mate-
rials science,[15] and so a great deal of effort is currently de-
voted to the catalytic construction and functionalization of
indole rings.[16]
The preparation and characteri-
zation of this bis(triazolylACTHNUTRGNEiUNG dene)
complex of Pt (5) are detailed
in the Experimental Section.
As can be seen from the data
shown in Table 1, NHC-based
platinum catalysts 2, 3, and 5
display better catalytic perform-
ances than PtCl2 and PtI2, al-
though they need the addition of AgSO3CF3 in order to fa-
cilitate the process. Catalysts 2, 3, and 5 afford quantitative
conversions to the final product, in only 30 min if the reac-
tion is carried out at 808C, with a catalyst loading of
5 mol% (Table 1, entries 11, 14, and 17). The same catalysts
afford moderate to high yields (58–75%) if the reaction is
performed at room temperature, with a catalyst loading of
1 mol%, although longer reaction times are needed (27 h).
These catalytic results prompted us to widen the variety
of substrates used in this catalytic reaction. Table 2 shows
representative data that we obtained for the reaction of a
series of substituted indoles with substituted alkynyl alco-
hols. In general, catalyst 2 provided the best catalytic out-
comes, affording almost quantitative yields for all of the re-
actions carried out with N-methylindole (Table 2, entries 1,
5, and 9). Heterodimetallic complex 3, also afforded excel-
lent outcomes in all of the reactions studied. We also estab-
lished that the activity of complex 3 is also high if toluene is
Firstly, we studied the multistep reaction of indoles with
4-pentyn-1-ol, which yields an indole derivative containing a
five-membered cyclic ether at C3. This reaction was recently
described by Cheng and co-workers,[14] who also proposed
that the formation of the final product proceeds through a
Pt-catalyzed cyclization of the alkynyl alcohol followed by
the addition of indole to the resulting cyclic enol ether. Sev-
eral gold catalysts are known to catalyze this multistep pro-
cess,[17,18] although, unlike platinum, gold catalysts tend to
facilitate the double addition of indole, generating bis-
ACHTUNGTRENNUNG
(indolyl)alkane derivatives.[17] Table 1 shows representative
data that we obtained for this reaction. To obtain a repre-
sentative catalyst screening for this first set of experiments
we used several platinum complexes, including catalyst 5.
Chem. Eur. J. 2010, 16, 13109 – 13115
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13111

E. Peris et al.
Table 2. Catalytic addition reaction between indoles and alkynyl
alcohols.[a]
first process (oxidative cyclization of the amino alcohol) and
a variable time for the second (functionalization of indole).
Table 3 summarizes a selection of representative results that
we obtained for this tandem process.
Table 3. Tandem cyclization of 2-(ortho-aminophenyl)ethanol and addi-
tion of an alkynyl alcohol.[a]
Entry
R1
R2
R3
n
m
Catalyst[b]
t
Yield
[%][c]
[h]
1
2
3
4
5
6
7
8
9
10
11
12
13
14[e]
15
16[e]
17
18
Me
Me
H
H
H
H
H
H
H
H
H
H
H
Me
Me
H
H
H
H
H
H
H
2
2
1
1
1
1
3
3
3
3
1
1
2
1
1
3
3
1
1
1
1
1
1
1
2
2
2
2
1
1
1
1
1
2
2
1
2
5
2
5
2
5
2
5
2
5
2
5
3
3
3
3
3
3
3
6
6
6
3
3
8
8
12
12
15
15
5
10
10
10
10
12
>99
67
80
Me
Me
Me
Me
H
H
H
H
Me
Me
H
Me
Me
H
H
81
Entry
Catalyst
R1
R2
n
m
Indole[c,d]
[%]
t
Yield
Me
Me
H
>99
>99
67
AHCTUNGTRENNUNG
[h][e] [%][c]
1
2
3
4
5
6
7
8
9
10
11[f]
12[f]
13[f]
2 (2)
3 (2)
6 (2)
2+6 (2)
2+6 (2)
2+6 (5)
Me Me
Me Me
Me Me
Me Me
1
1
1
1
2
2
1
1
2
2
3
3
1
1
1
1
1
1
1
1
1
1
1
2
2
1
0
15
15
15
15
15
12
15
12
15
15
15
12
24
0
74
56
44
16
35
29
32
60
81 (77)
15
24
80 (74)
H
28
77
67
51
nd
nd
38
nd
nd
nd
nd
nd
nd
Me
Me
H
H
Me
H
Me
H
Me
H
93 (86)[d]
52
60
60
84
H
H
Me
Me
G
81
R
77 (72)[d]
71
3 (2)
3 (5)
3 (2)
3 (5)
3 (2)
H
H
H
H
Pr
Me
Me
Me
Me
Pr
H
Me
74 (73)[d]
50 (46)[d]
Me
[a] Reaction conditions: indole (0.3 mmol), alkynyl alcohol (0.36 mmol),
silver triflate (3%), and catalysts (1 mol%) in solvent (1.5 mL). Anisole
was used as an internal standard (0.3 mmol). The solution was heated at
808C under aerobic conditions. [b] Based upon the amount of metal pres-
ent. [c] Yields determined by GC chromatography. [d] Isolated yields in
parenthesis. [e] Reactions carried out in toluene.
[a] Reaction conditions: 2-(ortho-aminophenyl)ethanol (0.33 mmol),
silver triflate (0.03 mmol), anisole (as an internal reference; 0.25 mmol)
in toluene (800 mL) at 1108C. After 12 h, alkynyl alcohol (0.38 mmol)
was added. [b] Based upon the amount of metal. [c] Yields determined
by GC chromatography. [d] Yield of the indole intermediate as deter-
mined before addition of the alkynyl alcohol. nd=not determined
[e] Total time, referring to the two steps (the first step was always 12 h).
[f] Reaction temperature of 808C.
used as the solvent, with catalytic outcomes very close to
those shown for reactions carried out in acetonitrile (see,
Table 2, entries 14 and 16). This result is interesting because
we have observed that toluene is a good solvent for the iri-
dium-catalyzed oxidative cyclization of amino alcohols to
form indole,[11] so the combination of the Pt- and Ir-cata-
lyzed processes seems to be possible, at least in terms of sol-
vent compatibility.
Having proved the activity of our Pt catalysts in the cata-
lytic reaction between indoles and alkynyl alcohols, we
thought that the combination of this multistep process with
the oxidative cyclization of amino alcohols to form indoles
might constitute a valuable illustration of the ability of our
Ir–Pt complex 3 to incorporate a further step into the, al-
ready complex, catalytic reaction. Despite the great interest
shown towards indole derivatives and the efforts that are
currently being made towards the search for catalytic pro-
cesses for the construction and functionalization of indole
rings, we found very few examples in which functionalized
indoles are obtained from multistep reactions employing
amino alcohols.[11,19] The reactions were carried out in a
single pot, following a sequential procedure. First we used 2-
(ortho-aminophenyl)ethanol as the starting material to form
indole and then we added the alkynyl alcohol, to provide
the corresponding functionalized molecule. The reactions
were carried out in toluene, at 1108C, leaving 12 h for the
As can be seen from the data shown in Table 3, catalyst 3
provided good yields of the functionalized indoles when dif-
ferent alkynyl alcohols were used (yields in the range 60–
81%). These data are remarkable, especially if we take into
account the complexity of the overall process. As expected,
diplatinum complex 2 did not afford the formation of the
final products, due to its inability to facilitate the oxidative
cyclization of the amino alcohol. Furthermore, a mixture of
the two homodimetallic complexes of Pt (2) and Ir (6)[11], af-
forded a much lower yield than that provided by heterodi-
metallic complex
3 (compare Table 3, entries 4–6 with
Table 3, entries 2, 9 and 10). This result is comparable with
the catalytic outcomes shown by other ditz-based heterodi-
metallic complexes reported by us when compared to mix-
tures of their homodimetallic counterparts[9,11,20] and sup-
ports the idea that some catalytic cooperativity between the
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Synthesis of Functionalized Indoles
FULL PAPER
two vicinal metals may be at work. The results shown for iri-
dium complexes 6 and [(IrCp*Cl2)2], which afford low (ca.
30%, for [(IrCp*Cl2)2], Table 3, entries 7 and 8) to moderate
(56%, for complex 6, Table 3, entry 3) yields of the final
product, are remarkable, since, in contrast to what we ex-
pected, they demonstrate that these complexes also show ac-
tivity in the final step of the reaction. Remarkably, the activ-
ity of complex 3 is entirely unaffected by the addition of
metallic Hg,[21] lending support to a homogeneous reaction
mechanism.
Experimental Section
General procedures: 1,2,4-Trimethyltriazolium tetrafluoroborate,[22] o-xy-
lenebis(N-n-butyl)triazolium diiodide[23] and complex 6[11] were prepared
according to literature procedures. All other reagents and solvents were
used as received from commercial suppliers. Synthesis and catalytic ex-
periments were carried out under aerobic conditions, without solvent
pre-treatment. NMR spectra were recorded on Varian spectrometers op-
erating at 300 or 500 MHz (1H NMR) and 75 or 125 MHz (13C NMR), re-
spectively, and referenced to SiMe4 (d in ppm and J in Hertz). NMR
spectra were recorded at room temperature in CDCl3, unless otherwise
stated. A QTOF I (quadrupole–hexapole–TOF) mass spectrometer with
an orthogonal Z-spray-electrospray interface (Micromass, Manchester,
UK) was used. The drying gas, as well as the nebulizing gas, was nitrogen
at a flow of 400 and 80 Lhꢀ1, respectively. The temperature of the source
block was set to 1208C and the desolvation temperature to 1508C. A ca-
pillary voltage of 3.5 kV was used in the positive scan mode and the cone
voltage was set to 30 V. Mass calibration was performed by using a solu-
tion of sodium iodide in isopropanol/water (50:50) from m/z=150 to
1000 a.m.u. Sample solutions (ꢁ 1ꢅ10ꢀ4 m) in dichloromethane/methanol
(50:50) were infused through a syringe pump directly connected to the
interface at a flow rate of 10 mLminꢀ1. A solution of 3,5-diiodo-l-tyrosine
(1 mgmLꢀ1) was used as the lock mass. Elemental analyses were carried
out on a EuroEA3000 Eurovector Analyser. A gas chromatograph GC-
2010 (Shimadzu) equipped with an FID and a Teknokroma (TRB-5MS,
30 m x 0.25 mm x 0.25 mm) column was used. A gas chromatograph/Mass
spectrometer GCMS-QP2010 (Shimadzu) equipped with a Teknokroma
(TRB-5MS, 30 m x 0.25 mm x 0.25 mm) column was also used.
Conclusion
Herein, we have prepared two new dimetallic complexes
containing the dicarbene ligand ditz. The preparation of
these two new complexes illustrates the high versatility of
this ditopic ligand. The easy access to Ir–Pt heterodimetallic
complex 3 allowed us to study a tandem process employing
the combination of mechanistically distinct processes that
are typically catalyzed by Ir or Pt. We have first shown that
all of our Pt-based complexes show high activity in the cycli-
zation–addition reactions of alkynyl alcohols with indoles.
The presence of the Ir-fragment in complex 3 allows the ad-
dition of a further step to this reaction, since it can then be
started from 2-(ortho-aminophenyl)ethanol, which is trans-
formed into indole by an Ir-mediated oxidative cyclization
process and then reacts with the alkynyl alcohol in a Pt-
mediated reaction.
Synthesis of 2: A mixture of 1,2,4-trimethyltriazolium tetrafluoroborate
(60 mg, 0.21 mmol), PtI2 (180 mg, 0.42 mmol), and K2CO3 (221 mg,
1.6 mmol) was heated at reflux for three hours in pyridine (3 mL). The
reaction mixture was then filtered through Celite, and the solvent was re-
moved under vacuum. Pure compound 2 (170 mg, 70%) was obtained as
a light yellow solid after recrystallization from dichloromethane/n-hex-
anes (1:9; 2 mLꢅ2). 1H NMR (500 MHz, C6D6): d=8.91 (d, JH,H
=
3
The ability of Ir–Pt complex 3 to perform this combined
reaction confirms the wide ranging applicability of ditz-
based heterodimetallic complexes for the design of new and
complex tandem processes. The preparation of substituted
indoles from the direct reaction of 2-(ortho-aminophenyl)-
5.0 Hz, 4H; Py), 6.55 (t, 3JH,H =7.5 Hz, 2H; Py), 6.27 (t, 3JH,H =6.5 Hz,
4H; Py), 4.63 (s, 3H; NCH3), 3.38 ppm (s, 6H; NCH3); 13C NMR
ꢀ
(75 MHz, CDCl3): d=164.1 (NCN Pt), 153.5, 138.2, 125.2 (Py), 40.4,
+
ꢀ
37.0 ppm ( CH3); ES-MS (25 V): m/z: 1189.1 [M+Na] ; ESI-TOF-MS
(positive mode): m/z calcd (monoisotopic peak): 715.1335; found:
715.1340; er =0.7 ppm.
ACHTUNGTRENNUNGethanol and alkynyl alcohols is an unprecedented process
Synthesis of 3: A mixture of compound 4 (120 mg, 0.2 mmol), PtI2
(100 mg, 0.22 mmol), NaI (150 mg, 1 mmol), and K2CO3 (83 mg,
0.6 mmol) was heated for three hours in pyridine (3 mL) at 808C. The re-
action mixture was then filtered through Celite and the solvent was re-
moved under vacuum. The excess of salt was eliminated by dissolving the
crude in dichloromethane and filtering the solution. Pure compound 3
(110 mg, 41%) was obtained as a light yellow solid after precipitation
from n-hexanes. 1H NMR (500 MHz, CD2Cl2): d=8.90 (d, 3JH,H =5.0 Hz,
2H; Py), 7.75 (t, 3JH,H =7.0 Hz, 1H; Py), 7.33 (t, 3JH,H =6.5 Hz, 2H; Py),
4.27 (s, 3H; NCH3), 4.24 (s, 3H; NCH3), 4.23 (s, 3H; NCH3), 1.79 ppm (s,
ꢀ
that may have some industrial applications. As we have pre-
viously shown for other heterodimetallic ditz-based com-
plexes,[9,11] the use of 3 provides better catalytic outcomes
than the use of mixtures of the corresponding homodimetal-
lic catalysts (2 and 6), suggesting that some catalytic cooper-
ativity may be at work between the two vicinal metals. The
results presented in this work, together with our previously
reported results on the use of the ditz ligand for the prepa-
ration of ditopic catalysts,[9,11,20] confirm the abundant appli-
cations of this ligand for the preparation of catalysts suitable
for mediating complicated tandem catalytic processes. In a
context in which the search for reactions with a reduced en-
vironmental impact in an economically beneficial manner is
one of the first priorities of synthetic chemistry, we strongly
believe that the design of well-defined, effective, multitopic
catalysts constitutes a valuable route of exploration with
foreseeable profitable results.
15H;
C5ACTHNGUTERNNUG
(CH3)5); 13C NMR (125 MHz, CDCl3): d=164.0 (Ccarbene Ir),
ꢀ
155.5 (Ccarbene Pt), 153.5, 138.1, 125.2 (Py), 91.6 (C
5ACHTUNGTRENN(NUG CH3)5), 45.4 (NCH3),
41.8 (NCH3), 8.9 ppm (C5A(CH3)5); ESI-TOF-MS (positive mode): m/z
CTHUNGTRENNUNG
calcd (monoisotopic peak): 1092.8785; found: 1092.8806; er =1.92 ppm.
Synthesis of 5: A mixture of o-xylenebis(N-n-butyl)triazolium diiodide
(200 mg, 0.47 mmol), PtI2 (210 mg, 0. 47 mmol), and NaOAc (77 mg,
0.94 mmol) was heated at reflux for five hours in acetonitrile (5 mL). The
reaction mixture was then filtered through Celite and the solvent was re-
moved under vacuum. Pure compound 5 (275 mg, 73%) was obtained as
a white crystalline solid after recrystallization from acetone/diethyl ether
1
(1:9). H NMR (500 MHz, CD3CN): d=8.42 (s, 2H; NCH), 7.77 (m, 2H;
2
2
Ph), 7.51 (m, 2H; Ph), 6.68 (d, JH,H =14.5 Hz, 2H; CH2), 5.15 (d, JH,H
=
15.0 Hz, 2H; CH2), 4.67 (m, 2H; CH2, nBu), 4.18 (m, 2H; CH2, nBu),
2.02 (m, 2H; CH2, nBu), 1.97 (m, 2H; CH2, nBu), 1.46 (m, 4H; CH2,
nBu), 0.98 ppm (t, 3JH,H =7.5 Hz, 6H; CH3, nBu); 13C NMR (125 MHz,
ꢀ
CD3CN): d=156.6 (NCH), 143.5 (JPt,C =203.0 Hz, Ccarbene Pt), 135.6,
133.0, 131.7 (Ph), 52.7 (CH2), 49.13, 31.1, 20.7, 14.0 ppm (nBu); ES-MS
Chem. Eur. J. 2010, 16, 13109 – 13115
ꢃ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
13113

E. Peris et al.
(25 V): m/z: 716.0 [MꢀI+CH3CN]+; ESI-TOF-MS (positive mode): m/z
calcd (monoisotopic peak): 715.1335; found: 715.1340; er =0.69 ppm.
this paper. These data can be obtained free of charge from The Cam-
bridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_
request/cif.
Cyclization–addition reaction of indole with alkynyl alcohol: A capped
vessel containing a stirrer bar was charged with indole (0.3 mmol), alkyn-
yl alcohol (0.36 mmol), silver triflate (3%), anisole (as an internal refer-
ence; 0.3 mmol), and catalyst (1%) in acetonitrile (1.5 mL). The solution
was heated to 808C for the appropriate length of time. During the reac-
tion, yields and conversions were determined by GC chromatography.
Products and intermediates were characterized by GC/MS. Isolated prod-
ucts were characterized by 1H and 13C NMR spectroscopy after purifica-
tion by column chromatography using mixtures of n-hexanes and ethyl
acetate.
Acknowledgements
We are grateful for financial support from the MCINN of Spain
(CTQ2008-04460) and Bancaixa (P1.1B2007-04 and Ref. P1.1B2008-16).
We would also like to thank the Generalitat Valenciana for a fellowship
(A. Zanardi). The authors are grateful to the Serveis Centrals d’Instru-
mentaciꢂ Cientꢀfica (SCIC) of the Universitat Jaume I for providing us
with spectroscopic and X-ray facilities.
Sequential oxidation–cyclization of amino alcohol into indole and func-
tionalization with alkynyl alcohol: A capped vessel containing a stirrer
bar was charged with 2-(ortho-aminophenyl)ethanol (0.33 mmol), silver
triflate (0.03 mmol), anisole (as an internal reference; 0.3 mmol), and cat-
alyst (2%) in toluene (800 mL). The solution was heated to 1108C for the
appropriate length of time. After complete conversion to the indole, the
alkynyl alcohol (0.38 mmol) was added and the final solution was stirred,
at the same temperature, for an additional 3 h. During the reaction,
yields, and conversions were determined by GC chromatography. Prod-
ucts and intermediates were characterized by GC/MS. Isolated products
were characterized by 1H and 13C NMR spectroscopy after purification
by column chromatography using mixtures of n-hexanes and ethyl ace-
tate.
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Table 4. Crystallographic data and structure refinement for complexes 2
and 3.[a]
2
3
formula
Mr
T [K]
C15H19I4N5Pt2
1167.13
293(2)
C20H29I4IrPtN4
1305.29
293(2)
crystal system
space group
a [ꢄ]
b [ꢄ]
c [ꢄ]
monoclinic
C2/c
26.404(3)
10.9836(12)
8.9600(10)
90
monoclinic
P21/n
14.7970(8)
9.2108(5)
23.6378(13)
90
a [8]
b [8]
90.232(2)
90
2598.5(5)
4
2.983
15.517
98.665(1)
90
3184.9(3)
4
2.722
12.624
g [8]
V [ꢄ3]
Z
1calcd [Mgmꢀ3
]
m
N
]
total/unique reflns.
Rint
2985/2423
0.0297
7304/4882
0.0429
parameters/restraints
R/Rw (I>2s)
119/0
0.0324/0.0750
1.037
ꢀ1.108/1.266
314/0
0.0535/0.1168
1.068
ꢀ1.737/2.824
GOF
Min/max residual density [eꢄꢀ3
]
[a] R=ꢀjjFo jꢀjFc jj/ꢀjFo j for all I>3s(I); Rw=[ꢀw(jFojꢀjFcj)2/
1
2
ꢀwF2o] =
.
13114
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ꢃ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2010, 16, 13109 – 13115

Synthesis of Functionalized Indoles
FULL PAPER
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10506.
WI, 2000.
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6713–6725.
[25] SAINT, Bruker Analytical X-ray System, version 5.0, Madison, WI,
1998.
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[23] J. R. Miecznikowski, R. H. Crabtree, Polyhedron 2004, 23, 2857–
2872.
Received: May 3, 2010
Published online: September 30, 2010
Chem. Eur. J. 2010, 16, 13109 – 13115
ꢃ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
13115