Very small (3-6 atoms) gold cluster catalyzed carbon-carbon and carbon-heteroatom bond-forming reactions in solution

Article abstract of DOI:10.1002/cctc.201300695

Clusters get the gold: Atomic gold clusters Auⁿ (n=3'6) are very active species (submol) for gold atalyzed carbon'carbon and carbon heteroatom bond forming reactions of interest in organic synthesis. The gold clusters can be formed insitu or generated exsitu and introduced into the reaction media. Salts, complexes, and nanoparticles (NPs) can be used as a starting source of gold. Ts=para toluenesulfonyl. Copyright

Full text of DOI:10.1002/cctc.201300695

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DOI: 10.1002/cctc.201300695
Very Small (3–6 Atoms) Gold Cluster Catalyzed Carbon–
Carbon and Carbon–Heteroatom Bond-Forming Reactions
in Solution
Judit Oliver-Meseguer, Antonio Leyva-Pꢀrez,* and Avelino Corma*[a]
Gold catalysis has emerged in the last years as a powerful tool
in organic synthesis for the construction of new bonds, and
gold salts, complexes, and nanoparticles are used as efficient
catalysts for many reactions.[1] In-depth mechanistic studies
have confirmed that the catalytically active gold species are
those added at the beginning of many reactions, and in some
cases, organogold intermediates have been isolated and char-
acterized.[2] However, if one looks into the literature, AuIII salts,
AuI salts, and gold complexes are indistinctly used as catalysts
for a significant number of reactions, without substantial
changes in the overall activity.[1b,f] The presence of a gold
mirror at the end of the reaction is a common experimental
observation that reflects the progressive reduction of gold to
monoatomic gold and then to clusters, nanoparticles, and bulk
gold and suggests the possibility that the gold(I)/(III) species
could only be precatalysts, at least for a number of reactions.
In those cases, the catalytic entities would be formed after re-
organization and/or reduction of the starting gold species. The
aim is then to determine which are the catalytically active gold
species and how to synthesize them.[3] It was recently shown
that gold clusters generated in situ from gold salts and com-
plexes are able to catalyze reactions such as the ester-assisted
hydration of alkynes and the bromination of arenes by using
the gold clusters in only very small (parts-per-million)
amounts.[4] Opposite to nanoparticles, these very small gold
clusters are molecular entities having defined frontier orbitals,
HOMO and LUMO, ready to interact with other molecules. It
would then be of interest to investigate if gold clusters are
also good catalysts for other representative carbon–carbon
and carbon–heteroatom bond-forming reactions in solution
that have been performed previously in the presence of gold
salts and complexes.[5–8] Following this idea, herein we present
gold clusters made up of 3–6 atoms that catalyze efficiently
the phenol synthesis (CÀC),[5] the w-bromination of terminal al-
kynes (CÀBr),[6] the Conia–ene reaction (CÀC),[7] and the hydra-
tion of alkynes (CÀO).[8] The use of sub-nanometric gold parti-
cles in catalysis is generally restricted to solid-supported sys-
tems,[9] but here, the gold clusters are generated and stabilized
in solution.[10] Remarkably, the clusters are generated from
gold salts, complexes, and/or nanoparticles under the reaction
conditions, and their reactivity is equivalent to that of gold
clusters formed ex situ followed by their addition to the
reaction.
Phenol synthesis
Hashmi et al. nicely showed that alkynylfurans rearrange to
otherwise difficult to prepare phenol derivatives in the pres-
ence of gold salts or complexes[5,11] (typically 1–5 mol%). Fig-
ure 1A shows that upon performing the reaction under similar
conditions to those reported[5a] but with a lower amount of
AuCl3 (0.4 mol%), the corresponding product 2 was smoothly
1
formed after an induction time, as evidenced by H NMR spec-
troscopy at different times. Moreover, MALDI-TOF MS measure-
ments showed that gold clusters were generated in the reac-
[a] J. Oliver-Meseguer, Dr. A. Leyva-Pꢀrez, Prof. A. Corma
Instituto de Tecnologꢁa Quꢁmica
Figure 1. A) Phenol synthesis catalyzed by AuCl3 (0.4 mol%). B) Yield–time
plot for the phenol synthesis showed in scheme A above (c), and per-
centage of 3–4 atom gold clusters in solution according to MALDI-TOF MS
measurements (a). For a complete set of measurements, see Figure S1.
The inset shows a magnification of the induction period when clusters
formed. C) Scheme for phenol synthesis by using AuCl as a catalyst in sub-
molar amounts under two different reaction conditions. Compound 3=2-
methylbut-3-yn-2-ol, Ts=para-toluenesulfonyl.
Universidad Politꢀcnica de Valencia-Consejo Superior
de Investigaciones Cientꢁficas
Avda. de los Naranjos s/n, 46022, Valencia (Spain)
E-mail: anleyva@itq.upv.es
acorma@itq.upv.es
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/cctc.201300695.
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tion medium during the reaction induction period and that
the reaction started only after the formation of gold clusters
comprising 3–4 atoms (Figure 1B, see also Figure S1 in the
Supporting Information).
If 3–4 atom gold clusters are the true active species for the
gold-catalyzed phenol synthesis, other gold sources that could
evolve with time to form these clusters in situ should also
show some activity.[2a] We selected AuCl as an alternative start-
ing source of gold, as it has been reported that it catalyzes the
synthesis of phenol very poorly at >1 mol% amounts.[5b] Fig-
ure 1C shows that upon adding a submolar amount (0.2–
0.4 mol%) of AuCl to the substrate, the phenol product was
obtained in a yield that was not far from that obtained with
the use of AuCl3, provided that a strong Brønsted acid was
also added. MALDI-TOF MS measurements showed that Au3À4
clusters were formed immediately after acidification of the
AuCl solution and that without acid no clusters were formed;
accordingly, the phenol synthesis did not proceed.
One can also attempt the reaction with gold nanoparticles
either in solution or supported on TiO2. Thus, we performed
the phenol synthesis with gold nanoparticles with an average
size of 3 nm (Figure S2, Supporting Information); no reaction
was observed and gold clusters were not detected in solution.
If we leached out the gold nanoparticles from the support and
then added the Brønsted acid, Au3À4 clusters were generated,
and the reaction then proceeded. It is believed that gold sup-
ported on TiO2 is not in the form of small clusters but in the
form of nanoparticles.[12] From these results, we concluded that
although 3–4 atom clusters are active, the nanoparticles are
not able to catalyze the phenol synthesis. However, it was re-
ported[13] that if gold is deposited on CeO2, besides the nano-
particles, gold clusters comprising 3–5 atoms could be stabi-
lized. If this is so, then Au-CeO2, unlike Au-TiO2, should be
active in the absence of added acid, and no induction period
should be observed. Indeed, it was reported that gold on
nanoceria (Au-CeO2) is able to catalyze the phenol synthesis,[11a]
and we observed that with a sample of Au-CeO2 prepared by
following a mild reductive process[11a] no induction period oc-
curred. These results are consistent with the possibility that
the gold clusters that form on the surface of nanocrystalline
CeO2 are the active species. Thus, taking into account all of the
above results, we could conclude that the phenol synthesis re-
action proceeds with gold clusters formed in solution or with
gold clusters present on the solid catalysts.
Figure 2. A) Conversion–time plot for the w-bromination of phenylacetylene
(4) with different amounts of the gold(I) AuPtBu3NTf2 complex catalyst. The
inset maximizes the initial time. B) Fluorescence emission spectra of the re-
action with 1-dodecyne (6) before (a), during (b), and after (c) the induction
time; irradiated at 350 nm. NBS=N-bromosuccinimide. DCM=CH2Cl2.
itoring the reaction by 31P NMR spectroscopy showed the pro-
gressive degradation of the gold complex during the reaction,
whereas 19F NMR spectroscopy showed the concomitant for-
mation of free triflimidic acid (HNTf2). According to these spec-
troscopic measurements, the degradation of AuPtBu3NTf2 pro-
vides the two elements needed for the formation and stabiliza-
tion of the gold clusters: ligand-free gold species and a strong
Brønsted acid.
If we start with the hypothesis that the active gold species
are formed from the initial gold complex, then those active
gold species should be detected if the reaction starts and pro-
ceeds, that is, after the induction time. To check this, the bro-
mination of the aliphatic, nonchromophoric alkyne 1-dodecyne
(6) was performed and followed by GC–MS and absorption
and emission UV/Vis spectroscopy. According to the jellium
model, gold clusters absorb and emit in a particular wave-
length as a function of their size.[14] Figure 2B shows the fluo-
rescence emission spectra of the reaction mixture irradiated at
350 nm before, during, and after the induction time. The for-
mation of gold clusters is clearly observed when the bromina-
w-Bromination of alkynes
The activation of alkynes by Lewis acid gold catalysts not only
proceeds through a p fashion, as for phenol synthesis and
many other examples,[1f] but also in a s fashion through slip-
page mechanisms. The w-bromination of terminal alkynes cata-
lyzed by gold complexes in solution is a representative exam-
ple of the s activation of alkynes.[6] Figure 2A shows that upon
performing the reaction in the presence of AuPtBu3NTf2 (Tf=
trifluoromethanesulfonyl) and by systematically decreasing the
amount of gold from 2 to 0.1 mol%, a reaction induction time
appeared. Excellent yields of 5 were obtained in all cases. Mon-
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tion of 1-dodecyne (6) starts but not before, and the size of
the clusters formed was calculated to be 3–5 gold atoms ac-
cording to the jellium model.[13] Furthermore, MALDI-TOF MS
experiments confirmed the presence of chemical entities with
m/z=1060, which corresponds to Au5 species (Figure S3, Sup-
porting Information).
that the catalytically active gold clusters are cationic in nature,
as previously assessed by experimental and computational
methods.[15]
To confirm the above results, we tested the w-bromination
of 4 with different Au clusters prepared by an external labora-
tory.[16] The results show that Au3À5 and Au5À7 clusters are
active species not only for the bromination but also for the hy-
dration of the triple bond (Figure S6a, Supporting Information),
whereas the 2–3 atom gold clusters show an induction period.
Fluorescence measurements unveiled that this induction
period corresponds to the agglomeration of the Au2À3 clusters
to form catalytically active Au3À7 clusters (Figure S6b, Support-
ing Information).
Figure 3 shows that colloidal gold nanoparticles (10Æ
2.5) nm in size were also able to catalyze the w-bromination of
phenylacetylene provided that HCl was added to the aqueous
colloidal solution. UV/Vis spectroscopy and fluorescence meas-
urements confirmed the formation of 5 atom gold clusters
Ester-assisted hydration of alkynes with HCl-treated gold
colloids
If 3–5 atom gold clusters are formed from gold nanoparticles
after the addition of HCl, acid-treated gold colloids should be
able to catalyze other Lewis acid catalyzed reactions involving
the same gold clusters such as the ester-assisted hydration of
alkynes that has been reported to be catalyzed by 3–5 atom
gold clusters in parts-per-billion amounts.[7] Figure 4 shows
that HCl-treated gold colloids approximately 5 and 10 nm in
size catalyze the formation of 10 without an induction time
Figure 3. A) Bromination–hydration cascade with (10Æ2.5) nm gold colloidal
aqueous solution (0.25 mm, 0.1 mol%) treated with concentrated HCl
(1 mol%). B) Photograph and corresponding absorption UV/Vis spectra of
the Au colloid before and after the addition of HCl.
after the addition of HCl to the gold nanoparticles and the
complete absence of the original plasmon band at approxi-
mately 550 nm, as shown in Figure 3B (see also Figure S4, Sup-
porting Information, for the fluorescence and MALDI-TOF MS
measurements). An excess amount of NBS together with water
present in the reaction medium allowed the in situ gold-cata-
lyzed hydration of the bromoalkyne to give a,a’-dibromoke-
tone 8 in a single step in reasonable yield after two consecu-
tive gold-catalyzed reactions, one involving s activation and
the other involving p activation.[6] Note that product 8 was ob-
tained under the same reaction conditions upon starting di-
rectly from bromoalkyne 5 and not from acetophenone 9,
which confirmed that the w-bromination proceeds before
hydration.
Figure 4. Yield–time plot for the ester-assisted hydration reaction catalyzed
by gold clusters generated from different colloidal solutions after HCl
treatment.
with an excellent turnover number and turnover frequency
(TON=10100 and TOF=5930 hÀ1, respectively), whereas gold
colloidal nanoparticles alone do not catalyze the ester-assisted
hydration of alkynes. The absence of an induction time indi-
cates that gold salts (chloride) are not formed after the addi-
tion of HCl to the colloidal nanoparticles, because in the pres-
ence of AuCl or AuCl3, an induction time before the reaction
should be observed.[4a] Notably, the reaction rate was faster for
smaller (ꢀ5 nm) colloids than for larger (ꢀ10 nm) colloids. Ad-
ditional UV/Vis spectrophotometric and MALDI-TOF MS meas-
urements together with z-potential values showed that the
The photograph in Figure 3B show that, visually, the red
gold colloidal solution turns transparent after acid treatment.
Zeta-potential measurements (Figure S5, Supporting Informa-
tion) revealed that the typical negative potential of stable col-
loidal solutions (ꢀÀ10 meV) changed to positive values after
the addition of the acid. It is well accepted that alkyne s or p
activation by gold involves Lewis species, so it is not surprising
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formation of the clusters depends on the nanoparticle size, as
smaller nanoparticles formed clusters more rapidly.
ployed instead of AuCl3, a similar result was obtained. MALDI-
TOF MS measurements showed the instantaneous and prefer-
ential formation of Au5 species from AuCl and AuCl3, provided
that HOTf was present in the reaction mixture (Figure S7, Sup-
porting Information). Our results strongly suggest that gold
clusters are also able to catalyze the Conia–ene reaction with
TON=3500, which is two orders of magnitude higher than
that previously reported by using AuPPh3OTf under the same
reaction conditions.[7]
Conia–ene reaction
Figure 5A shows the Conia–ene reaction, an early example of
gold-catalyzed carbon–carbon bond formation.[7] In pioneering
work, Toste et al. showed that the gold(I) AuPPh3OTf complex
(3 mol%) catalyzed the intramolecular formation of 12, where-
as AuCl3 was a very unselective catalyst, and only 30% of 12
In more specific experiments, it was studied whether the
gold AuPPh3OTf complex acted merely as a source of the gold
clusters or was stable under the reaction conditions. Kinetic ex-
periments with the use of AuPPh3OTf as the catalyst did not
show any induction time, and Figure 5B shows that a clear
first-order dependence of the reaction with respect to the AuP-
Ph3OTf catalyst was observed upon plotting the initial reaction
rate versus the amount of gold complex. In situ 31P NMR and
19F NMR spectroscopy measurements of the AuPPh3OTf-cata-
lyzed reaction showed that the original signals of the complex
remained unaltered after the reaction (Figure S8, Supporting
Information) and that a mixture of HOTf, PPh3, and AuCl3 dis-
solved in CD2Cl2 showed different signals to those obtained
with the gold complex. Both the kinetic and spectroscopic re-
sults indicated that AuPPh3OTf does not decompose under the
reaction conditions and that it acts as a Lewis acid species by
itself. In any case, as shown above, gold clusters are also active
in this reaction, and their TON is two orders of magnitude
higher than that of AuPPh3OTf.
Hydration of alkynes
The use of gold catalysts in amounts lower than 0.1 mol% is
rarely reported for gold-catalyzed organic reactions except for
reactions involving the formation of carbon–oxygen bonds.[16]
For instance, Nolan et al. nicely showed that the hydration of
alkynes could be catalyzed by a gold(I)–carbene complex in
parts-per-million amounts, and this is one of the most efficient
gold-catalyzed processes reported so far.[8] Upon performing
a kinetic study of the gold(I)–carbene-catalyzed hydration of
diphenylacetylene (13), we observed a clear induction time, as
shown in Figure 6A,B. This result suggests that the gold–car-
bene complex may not be the actual active species but a very
efficient precursor. It was reported that strong acids or silver
salts are responsible for the formation of catalytically active
gold species form the original gold source, which supports our
results.[17] Upon following the hydration of nonchromophoric
1-octyne (15) by GC–MS in combination with UV/Vis spectros-
copy, it was found that the reaction started only after 3–
5 atom clusters were formed and not before, as shown in
Figure 6C.
Figure 5. A) Results of the gold-catalyzed Conia–ene reaction of alkyne 11
with different gold catalysts. B) Initial rate dependence on the concentration
of the initial AuPPh3OTf complex catalyst. C) Initial rate dependence on the
concentration of initial AuCl treated with HOTf. Lines are a guide for the
eye.
was obtained with a higher loading (10 mol%) of the gold salt
after complete conversion.[7]
To assess the evolution of the carbene–gold complex, we
1
Upon changing the amount of AuCl and AuCl3 introduced to
0.02 mol%, no conversion was observed. However, good yields
were obtained if 0.2 mol% of HOTf was added to the gold-
containing reaction. Fluorescence analysis showed emission
bands corresponding to 3–6 atom gold clusters as soon as the
gold(III) salt and the acid were mixed, and if AuCl was em-
followed the reaction by in situ H NMR, 13C NMR, and 19F NMR
spectroscopy in [D8]-1,4-dioxane, and the loss of the original
signals corresponding to the complex, together with the ap-
pearance of new signals corresponding to the free carbene,
was observed as the reaction evolved under typical heating
conditions (1208C; Figure S9, Supporting Information). These
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Figure 7. A) Conia–ene reaction catalyzed by AuIPrCl (2 mol%) and HOTf
(10 equiv.) at 308C. B) w-Bromination of alkynes catalyzed by AuIPrCl
(2 mol%) and HOTf (10 equiv.) at 308C.
for previously reported reactions can only be assessed after ac-
curate kinetic studies, in situ and ex situ spectroscopic meas-
urements, and comparison with preformed gold clusters, as
the stability of gold salts and complexes can vary depending
on the type of catalyst and the experimental conditions. The
results here reported could be expanded not only to other
gold-catalyzed reactions but also to other catalytic metal
systems.
Experimental Section
Synthesis of 2,3-dihydro-5-methyl-2-[(4-methylphenyl)sulfonyl]-
1H-isoindol-4-ol (2) by using AuCl3: Alkyne
1 (72.3 mg,
Figure 6. A) Hydration of diphenylacetylene (13) in the presence of the
gold(I)–carbene AuIPrCl complex (50 ppm) and a silver salt as the catalyst.
B) Kinetic profile. The inset shows a magnification of the induction period.
C) Absorption UV/Vis and the corresponding emission (inset) spectra for the
AuIPrCl-catalyzed hydration of 1-octyne (15) just after the induction time.
0.25 mmol) was added to solution of the AuCl3 catalyst
a
(0.4 mol%) in CD3CN at room temperature. The reaction was fol-
lowed by 1H NMR spectroscopy until a conversion of 56% was
1
reached. H NMR (300 MHz, CDCl3): d=7.76 (d, J=8.7 Hz, 2H), 7.31
(d, J=8.7 Hz, 2H), 6.97 (d, J=7.8 Hz, 1H), 6.61 (d, J=7.8 Hz, 1H),
4.52 (q, J=2.4 Hz, 2H), 2.45 (s, 3H), 2.22 (s, 3H), 2.10 ppm (t, J=
2.4 Hz, 1H).
results suggest that the gold(I) carbene decomposes under the
reaction conditions, and as 3–5 atom gold–alkyne clusters are
formed after an induction time, the latter could be the catalyti-
cally active gold species. If this is so, the gold(I) carbene com-
plex should be an excellent precatalyst for other reactions cat-
alyzed by Au clusters, provided that they decompose in a simi-
lar way. In accordance, phenol synthesis was recently per-
formed by using gold carbenes.[17b,18b] Figure 7 shows that
upon using this carbene complex as a catalyst for the Conia–
ene reaction (Figure 7A) and for the w-bromination of alkynes
(Figure 7B) good yields of the product were obtained. In all
cases, the reaction started just after the gold carbene had de-
composed and the gold clusters had formed (Figure S10, Sup-
porting Information). These results strongly suggest the forma-
tion of catalytically active 3–5 atom gold clusters from the
gold(I) carbene AuIPrCl [IPr=1,3-bis(2,6-diisopropylphenyl)imi-
dazol-2-ylidene] complex under acidic conditions.[4,16] The de-
composition of carbene metal complexes under a variety of re-
action conditions has been previously reported.[18]
Synthesis of 2,3-dihydro-5-methyl-2-[(4-methylphenyl)sulfonyl]-
1H-isoindol-4-ol (2) by using AuCl and acid: Alkyne 1 (37 mg,
0.125 mmol) was added to a solution of AuCl/HCl or HNTf2
(0.2 mol%) in CD3CN at room temperature. The reaction was fol-
lowed by 1H NMR spectroscopy until a conversion of 42 or 30%
was reached, respectively.
w-Bromination: AuPtBu3NTf2 (13.6 mg, 0.02 mmol) and NBS
(355.6 mg, 2 mmol) were placed in a vial equipped with a magnetic
stir bar. The vial was closed with a septum cap and then anhydrous
CH2Cl2 (DCM, 2 mL) and the corresponding alkyne, phenylacetylene
(4; 220 mL, 2 mmol) or dodecyne (6; 428 mL, 2 mmol), were added.
The resulting suspension was placed in a preheated oil bath at
308C and stirred. Aliquots were periodically taken and diluted for
GC and UV/Vis analysis in diethyl ether by using dodecane as an
external standard. For analysis by NMR spectroscopy, the reaction
was performed in CD3CN. Product characterization was performed
by comparison with pure compounds.
Cascade bromination–hydration reaction with different sizes of
Au clusters: NBS (22.5 mg, 0.125 mmol) was placed in a vial
equipped with a magnetic stir bar. The vial was closed with
a septum cap and then DCM (0.25 mL) and phenylacetylene (4;
14 mL, 0.125 mmol) were added. Then, an aqueous solution of Au
clusters (100 ppm from a commercial aqueous dilution of 0.1 mm
In summary, small gold clusters containing 3–6 atoms (sub-
molar) catalyze different carbon–carbon and carbon–heteroa-
tom bond-forming reactions. They can be formed in situ from
gold salts, complexes, and nanoparticles under acidic condi-
tions. A sound determination of possible clusters in solution
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for Au2À3, 0.15 mm for Au3À5, and 0.05 mm for Au5À7) was added,
and the mixture was stirred in a preheated oil bath at 308C. Direct
analysis by GC–MS by using dodecane as an external standard was
performed, and product characterization was performed by com-
parison with pure compounds.
Acknowledgements
Financial support by the Severo Ochoa program and Consolider-
Ingenio 2010 (proyecto MULTICAT) from Ministerio de Ciencia e In-
novaciꢂn (MCIINN) is acknowledged. J. O.-M. thanks Instituto de
Tecnologꢁa Quꢁmica (ITQ) for a postgraduate scholarship. A. L.-P.
thanks Consejo Superior de Investigaciones Cientꢁficas (CSIC) for
a contract.
Ester-assisted hydration of 2-methylbut-3-yn-2-yl heptanoate (9)
with gold colloids: Alkyne 9 (50 mg, 0.25 mmol) and 2-methylbut-
3-yn-2-ol (3; 1 mL, 10 mmol) were placed in a 2 mL vial equipped
with a magnetic stir bar. The vial was sealed, and the resulting mix-
ture was stirred for 30 min at room temperature. After 30 min, the
Au colloid solution (50 ppm from a commercial aqueous dilution
of 2.5ꢂ10À4 m) was added, and the resulting mixture was stirred at
room temperature. Aliquots of 25 mL were periodically removed, di-
luted in n-hexane, and analyzed by GC to follow the progress of
the reaction by using dodecane as an external standard. Product
Keywords: carbon–carbon bond formation
heteroatom bond formation · gold · molecular clusters ·
nanoparticles
·
carbon–
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1
10 was characterized by GC–MS and H NMR, 13C NMR, and DEPT
spectroscopy, and the corresponding spectra agree with those pre-
viously reported.[2] Rf =0.65 (n-hexane/ethyl acetate, 8:2); 1H NMR
(300 MHz, CDCl3): d=2.26 (dd, J=9.6, 9.6 Hz, 2H), 2.04 (s, 3H),
1.61–1.51 (m, 2H), 1.39 (s, 6H), 1.24 (m, 6H), 0.84–0.80 ppm (m,
3H); 13C NMR (75 MHz, CDCl3): d=206.7 (C), 173.0 (C), 83.3 (C), 34.2
(CH2), 31.2 (CH2), 28.6 (CH2), 24.6 (CH2), 23.4 (2CH3), 23.2 (CH3), 22.3
(CH2), 13.8 ppm (CH3); GC–MS: m/z (%): 215 (1) [M+H]+·, 171 (17),
130, (1), 113 (100), 85 (29), 57 (9), 43 (23).
Conia–ene reaction: A solution of the corresponding catalyst
(20 mm, 2 mL, 0.02 mol%) in acetonitrile (for AuCl or AuCl3) or DCM
(for AuPPh3OTf, prepared by metathesis between AuPPh3Cl and
AgOTf) and a solution of triflic acid (200 mm, 2 mL, 0.2 mol%) in
acetonitrile were added to a sealed vial equipped with a magnetic
stir bar. The vial was placed in a preheated oil bath at 308C and
a solution of alkyne 11 (18.2 mg, 0.1 mmol) in anhydrous DCM
(250 mL, 0.4m) was added. The resulting mixture was stirred at that
temperature and aliquots of 10 mL were periodically removed, di-
luted in diethyl ether, and analyzed by GC–MS to follow the prog-
ress of the reaction by using dodecane as an external standard.
Methyl 1-acetylcyclopentanecarboxylate (12) was characterized by
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tion of a very high turnover number, see: b) M. C. Blanco-Jaimes,
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1
GC–MS and H NMR, 13C NMR, and DEPT spectroscopy after purifi-
cation by column chromatography, and the corresponding spectra
agree with those previously reported.[4] 1H NMR (300 MHz, CDCl3):
d=5.29 (t, J=2.4 Hz, 1H), 5.22 (t, J=2.4 Hz, 1H), 3.74 (s, 3H), 2.43
(m, 3H), 2.21 (s, 3H), 2.16 (s, 1H), 1.71 ppm (m, 2H); 13C NMR
(75 MHz, CDCl3): d=203.5 (C), 171.7 (C), 148.7 (C), 112.2 (CH2), 70.4
(C), 52.6 (CH3), 35.0 (CH2), 33.9 (CH2), 26.6 (CH3), 24.1 ppm (CH2).
NMR reaction experiments were performed in CD2Cl2.
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Hydration of diphenylacetylene (13): According to a modified lit-
erature procedure,[5] [(IPr)AuCl] (31 mL of a 1 mgmLÀ1 solution in
THF, 0.05 mmol, 50 ppm) was added to 1,4-dioxane (660 mL) in
a sealed 2 mL reaction vial equipped with a magnetic stir bar.
Then, AgSbF6 (tip of a spatula) was added, and the reaction mix-
ture was stirred for 1 min. Alkyne 13 (1 mmol, 1 equiv.) was added,
followed by the addition of distilled H2O (330 mL). The reaction
mixture was heated for 30 h at 1208C. Aliquots of 25 mL were peri-
odically removed, diluted in DCM, and analyzed by GC–MS to
follow the progress of the reaction by using dodecane as an exter-
nal standard. Rf =0.63 (n-hexane/EtOAc, 8:2).
[10] Y. Shichibu, K. Konishi, Small 2010, 6, 1216–1220.
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Rominger, Adv. Synth. Catal. 2010, 352, 1315–1337; c) A. S. K. Hashmi,
M. Ghanbari, M. Rudolph, F. Rominger, Chem. Eur. J. 2012, 18, 8113–
8119. Recently, better turnover numbers have been reported for a more
difficult substrate type: d) A. S. K. Hashmi, A. Loos, S. Doherty, J. G.
Knight, K. J. Robson, F. Rominger, Adv. Synth. Catal. 2011, 353, 749–759.
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ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ChemCatChem 0000, 00, 1 – 7
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CHEMCATCHEM
COMMUNICATIONS
www.chemcatchem.org
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nometallics 2013, 32, 1106–1111; c) S. G. Weber, F. Rominger, B. F.
Straub, Eur. J. Inorg. Chem. 2012, 2863–2867.
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[16] Three different aqueous solutions containing: a) 2–3 Gold atom clus-
ters; b) 3–5 gold atom clusters; c) 5–7 gold atom clusters, were pur-
chased from NANOGAP. See M. J. Rodrꢆguez-Vꢄzquez, C. Vazquez-Vaz-
quez, J. Rivas, M. A. Lopez-Quintela, Eur. Phys. J. D 2009, 52, 23–26.
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dov, H. Zhang, X. Liu, J. L. Petersen, X. Shi, J. Am. Chem. Soc. 2012, 134,
Received: August 20, 2013
Published online on && &&, 0000
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These are not the final page numbers!

COMMUNICATIONS
J. Oliver-Meseguer, A. Leyva-Pꢀrez,*
A. Corma*
Clusters get the gold: Atomic gold
clusters Aun (n=3–6) are very active
species (sub-mol%) for gold-catalyzed
carbon–carbon and carbon–heteroatom
bond-forming reactions of interest in
organic synthesis. The gold clusters can
be formed in situ or generated ex situ
and introduced into the reaction media.
Salts, complexes, and nanoparticles
(NPs) can be used as a starting source
of gold. Ts=para-toluenesulfonyl.
&& – &&
Very Small (3–6 Atoms) Gold Cluster
Catalyzed Carbon–Carbon and
Carbon–Heteroatom Bond-Forming
Reactions in Solution
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ChemCatChem 0000, 00, 1 – 7
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8
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ÞÞ
These are not the final page numbers!