Competitive gold-activation modes in terminal alkynes: An experimental and mechanistic study

Article abstract of DOI:10.1002/chem.201304087

The competition between π- and dual σ,π-gold-activation modes is revealed in the gold(I)-catalyzed heterocyclization of 1-(o-ethynylaryl)urea. A noticeable effect of various ligands in gold complexes on the choice of these activation modes is described. The cationic [Au(IPr)]⁺ (IPr=2,6-bis(diisopropylphenyl)imidazol-2-ylidene) complex cleanly promotes the π activation of terminal alkynes, whereas [Au(PtBu₃)]⁺ favors intermediate σ,π species. In this experimental and mechanistic study, which includes kinetic and cross-over experiments, several σ-gold, σ,π-gold, and other gold polynuclear reaction intermediates have been isolated and identified by NMR spectroscopy, X-ray diffraction, or MALDI spectrometry. The ligand control in the simultaneous or alternative π- and σ,π-activation modes is also supported by deuterium-labeling experiments. Copyright

Full text of DOI:10.1002/chem.201304087

DOI: 10.1002/chem.201304087
Communication
&
Gold Catalysis
Competitive Gold-Activation Modes in Terminal Alkynes: An
Experimental and Mechanistic Study
Ana Gimeno, Ana B. Cuenca, Samuel Suꢀrez-Pantiga, Carmen Ramꢁrez de Arellano,
Mercedes Medio-Simꢂn,* and Gregorio Asensio[a]
The presence of these s,p-type complexes in [Au]+-cata-
Abstract: The competition between p- and dual s,p-gold-
lyzed reactions[5] and their formation in the course of certain
activation modes is revealed in the gold(I)-catalyzed heter-
gold–alkyne coordination studies[6] have recently received sup-
ocyclization of 1-(o-ethynylaryl)urea. A noticeable effect of
port by X-ray diffraction, NMR spectroscopy, and mass spec-
various ligands in gold complexes on the choice of these
activation modes is described. The cationic [Au(IPr)]+
trometry studies. In addition, it has been shown that such spe-
cies can act as efficient precatalysts in CꢀC-bond-forming reac-
(IPr=2,6-bis(diisopropylphenyl)imidazol-2-ylidene)
com-
tions.[7] In this context, the gold(I)-catalyzed heterocyclization
of 1-(o-ethynylaryl)ureas, recently reported by our group,[8]
constitutes a simple model to study the effect of various li-
gands in gold complexes on the selection of p- or dual s,p-ac-
tivation modes. This reaction proceeds either in a 6-exo-dig
(Markovnikov) or a 5-endo-dig (anti-Markovnikov) fashion, de-
pending on the catalyst employed (Scheme 2). The cyclization
to obtain indole 3 would entail an unfavorable build-up of
positive charge at a terminal acetylenic carbon; a process that
is difficult to regard as the major process if a p-acidic-activa-
tion mode is considered.
plex cleanly promotes the p activation of terminal alkynes,
whereas [Au(PtBu3)]+ favors intermediate s,p species.In
this experimental and mechanistic study, which includes
kinetic and cross-over experiments, several s-gold, s,p-
gold, and other gold polynuclear reaction intermediates
have been isolated and identified by NMR spectroscopy,
X-ray diffraction, or MALDI spectrometry. The ligand con-
trol in the simultaneous or alternative p- and s,p-activa-
tion modes is also supported by deuterium-labeling ex-
periments.
Herein, we report how the gold(I)-catalyzed heterocycliza-
tion of 1-(o-ethynylphenyl)urea 1 reveals a competition be-
tween the p- and s,p-gold-activation modes. Characterization,
by NMR spectroscopy and X-ray diffraction, of several aurated
intermediates and the results of s,p-gold cross-over and deute-
rium-labeling experiments are reported.
Mechanistic proposals beyond the well-established p-activa-
tion mechanism for gold(I)-catalyzed reactions (Scheme 1a) are
currently gaining acceptance.[1] Toste and Houk et al., while in-
vestigating the mechanism of 1,5-allenyne cycloisomerization,
proposed the concept of dual s,p activation (Scheme 1b) to
depict a new model for the interaction between some gold(I)-
complexes and terminal alkynes.[2] Later, the groups of
Hashmi[3] and Zhang[4] independently applied this dual-activa-
tion concept to the cyclization of diynes.
The [AuCl(L)]/AgSbF6 (L=ligand) combination promotes, in
DMF at 608C, the catalytic heterocyclization of 1 into either 4-
methylene-3,4-dihydroquinazolin-2-one 2 or indole carboxa-
mide 3, depending on the ligand employed (Table 1, entries 1
and 2).
Specifically, 5 mol% of the bulky NHC-based (NHC=N-heter-
ocyclic carbene) complex [Au(IPr)]SbF6 (IPr=2,6-bis(diisopro-
pylphenyl)imidazol-2-ylidene) afforded exclusively the 6-exo-
dig N-3-attack product 2 (>95%). In contrast, the use of [Au-
(PtBu3)]SbF6 led to indole 3 in 80% yield. The more common
[Au(PPh3)]SbF6 afforded an almost equimolecular mixture of 2
and 3 (Table 1, entry 3). These results represent a general
trend, in which the ancillary ligand has a significant influence
on the selectivity of the reaction (see Table 1, entries 4–6).[9]
Complexation to a gold center perturbs the structure of the
alkyne ligand by elongation of the CꢁC bond and a concomi-
tant deviation from linear geometry.[10,11] In the case of asym-
metrically substituted alkynes, particularly terminal acetylenes,
this interaction leads to a displacement of the gold center
termed as the h2!h1 slippage.[12] This displacement, in turn,
leads to an unsymmetrical activation of the acetylene towards
nucleophilic attack.[13] The gold–alkyne coordination is also ex-
pected to lower the pKa of the acetylenic CꢀH proton.[14]
Scheme 1. a) Canonical p-gold and b) dual s,p-gold activation.
[a] A. Gimeno, Dr. A. B. Cuenca, Dr. S. Suꢀrez-Pantiga, Dr. C. R. de Arellano,
Dr. M. Medio-Simꢁn, Prof. Dr. G. Asensio
Departamento de Quꢂmica Orgꢀnica, Universidad de Valencia
Avda. Vicent Andrꢃs Estellꢃs s/n 46100-Burjassot
Valencia (Spain)
Fax: (+34)963544939
E-mail: Mercedes.Medio@uv.es
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201304087.
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Communication
The aurated indole 5 displays
1H signal at d=6.36 ppm, as-
a
signed to the C3 hydrogen (Hb);
the lack of H–H coupling for Hb
was consistent with C2 metala-
tion. No trace of compound 2
(or its aurated derivative) could
be observed. To ascertain the in-
Scheme 2. Gold(I)-catalyzed heterocyclization of urea 1.
Table 1. Screening of ligands and conditions in the AuI-catalyzed hetero-
cyclization of 1.
Entry
Catalytic S
system
2
[%][a]
3
[%][a]
[5 mol%]
1
2
3
4
5
6
7
[Au(IPr)]SbF6
>95
20
53
>95
30
>95
–
<5
80
47
<5
70
<5
32
[Au(PtBu3)]SbF6
[Au(PPh3)]SbF6
[Au(tBuXPhos)]SbF6
[Au(PMes3)]SbF6
[Au(LPO)]SbF6
[Au(IPr)]SbF6/Et3N[b]
Scheme 3. Synthesis of 2-aurated indole 5.
volvement of two gold(I) entities in the formation of the
indole ring, and to determine the order of the catalyst, a series
of kinetic experiments[17]was carried out. The [Au(PtBu3)]NTf2-
catalyzed reaction of urea 1 was, overall, second order with re-
spect to gold.[18] For comparison, a similar kinetic study of the
[Au(IPr)]NTf2-catalyzed cyclization of 1 into dihydroquinazolin-
2-one 2 was performed. Despite the reverse cyclization mode
promoted by this later complex, the reaction showed the same
order with respect to the catalyst (see the Supporting Informa-
tion). To test whether the order of the catalyst is related to the
activation mode of the [Au(IPr)]NTf2 complex, s-acetylide 6
was prepared. This acetylide could still progress into com-
pound 2, or the formation of indole 3 could prevail even in
this case. It was found that acetylide 6 quantitatively provides
the 2-aurated indole 7 (Scheme 4) in a similar fashion to the re-
action of complex 4. The identity of species 7 was confirmed
by both NMR spectroscopy and X-ray diffraction (Figure 1; for
[a] 1H NMR spectroscopy calculated 2/3 proportions. Complete conver-
sion of 1 was observed in all cases. [b] 10 mol% of Et3N was used. Mes=
mesityl.
Exploring the latter phenomenon, we began by carrying out
the catalytic heterocyclization of 1 in the presence of a base.
Remarkably, for [Au(IPr)]SbF6 (5 mol%), the cyclization in the
presence of 10 mol% Et3N afforded indole 3 as the sole prod-
uct; a clear reversal from the base-free conditions (compare
Table 1, entries 1 and 7). However, the reaction was sluggish,
reaching only 32% conversion.
The acidity of the acetylenic CꢀH proton and the change in
selectivity induced by the presence of a base raised the possi-
bility of a gold–acetylide species as an intermediate in the 5-
endo-dig ring closure of 1. Therefore, the s-gold complex of
1 was prepared and its behavior was evaluated. Tri-tert-butyl-
phosphine gold–acetylide 4 was obtained by treating 2-ethy-
nylaniline with [AuCl(PtBu3)] in the presence of Et3N, followed
by the reaction with phenylisocyanate. Complex 4 was stable
in DMF and did not spontaneously undergo any reaction.[15]
Scheme 4. Synthesis of 2-metalated indole 7
Nevertheless, in the presence of a catalytic amount of [Au-
[16]
(PtBu3)]NTf2
(NTf2 =bis(trifluoromethanesulfonyl)imidate) in
color version, please see web).[19] Interestingly, the structure
showed the expected linear coordination geometry (C-Au-CNHC
176.7(3)8) and, in addition, a relatively short N1ꢀH···Au distance
that could be ascribed to an intramolecular NꢀH···Au hydrogen
bond.[20]
[D7]DMF at 258C, complete conversion of 4 into new species 5
was observed. Compound 5 was identified by NMR spectrosco-
py as the 2-metalated indole (Scheme 3), which afforded 3
upon treatment with trifluoromethanesulfonic acid (HOTf).
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Figure 1. X-ray plot of one of the two independent molecules of 7 (H1···Au1
2.27(2) ꢄ, N1···Au1 3.098(7) ꢄ, and N1ꢀH1···Au1 156(3)8).
Figure 2. X-ray crystal structure of 8, hydrogen atoms are omitted for clarity.
The experiments shown in Scheme 3 and 4 suggest that the
intermediacy of a gold–acetylide[21] may indeed be responsible
for the production of 3, but involvement of this gold–acetylide
in the formation of the quinazolin-2-one 2 appears to be un-
likely. Moreover, these experiments also suggest that the classi-
cal p activation in the [Au(IPr)]NTf2-catalyzed formation of 2 is
not related to the rate-limiting step.[1b,3a,b,22–24]
The structure shows a dinuclear s,p-acetylide gold com-
pound, with a h1,h2-acetylide ligand s bonded to one (IPr)Au
fragment (Au1ꢀC2 2.009(18) ꢄ) and p bonded to a second
(IPr)Au group (Au2ꢀC2 2.21(3) ꢄ, Au2ꢀC3 2.44(3) ꢄ).
As with the previously described s,p-gold complexes,[6] the
two chemically distinct s- and p-LAu fragments in complex 8
displayed, in CD2Cl2, a single set of 1H and 13C resonances,
a fact attributable to their fast exchange, which might proceed
Next, we investigated whether the preformed gold–acety-
lides would undergo N-1 nucleophilic 5-endo-dig ring closure.
In principle, the gold–acetylides should not undergo any nu-
cleophilic attack, but coordination of a second cationic metal
fragment[2,5b,7] is expected to generate a more electron-defi-
cient s,p-bimetallic species. This prompted us to study the role
(if any) of 1-s,p-dinuclear species in the formation of com-
pound 3. A mixture of stoichiometric amounts of [Au(IPr)]SbF6
and s-acetylide 6 (selected for its higher stability) in CD2Cl2
cleanly afforded the bimetallic species 8. This solvent appears
to inhibit further evolution of 8 and allowed for its isolation
(Scheme 5). Single crystals suitable for X-ray diffraction were
obtained from the same solution at low temperature
(Figure 2).[25]
via
a more symmetrical gem-diaurated transition state.
However, a solution of 8 in DMF afforded, after 2 h at 258C,
>95% of the 2-aurated indole carboxamide 7, lending support
to the participation of the s,p complexes in the formation of
indole 3 (Scheme 5).
The conversion of 8 into the metalated indole 7 raised the
possibility of tracing the fate of the individual LAu units in the
cyclization process by means of a cross-over experiment.[26]
Hence, IPrAu–acetylide 6 was subjected to one equivalent of
[Au{P(tBu)3}]NTf2 in [D7]DMF at 258C, in the presence of Et3N.
After 2 h, full conversion of 6 into a 1.3:1 mixture of the 2-
1
metalated indoles 5 and 7 was observed by H NMR spectros-
copy (Scheme 6). Despite the presence of a base, fast C3 pro-
todeauration takes place at
258C. Once again, this result is
taken as evidence of an ex-
change of the two LAu frag-
ments, with the initially p-coor-
dinated [Au(PtBu3)]+ exchanging
into the s-acetylide position in
the proposed s,p species.
To prevent the rapid C3 proto-
deauration and to trap the possi-
ble C2,3-dimetallated indole, we
followed
a
low-temperature
(ꢀ308C) reaction involving ace-
tylide 4 with [Au(PtBu3)]NTf2 in
the presence of Et3N. After 4.5 h,
the intensity of the signals corre-
sponding to 4 diminished and
Scheme 5. Synthesis of s,p-complex 8 and its conversion to aurated indole 7.
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These labeling experiments ascertain that p coordination of
[Au(IPr)]+ activates the alkyne in such a way that 6-exo-dig nu-
cleophilic attack occurs faster than the formation of the
s gold–acetylide. Accordingly, the label is preserved in com-
pound [D]-2 and the intermediacy of an s-acetylide species
can be discarded in the formation of quinazolin-2-one 2, as
previously inferred from the reactivity of the preformed acety-
lide 6. In contrast, when the alkyne is activated by [Au-
(PtBu3)]SbF6, the loss of the acetylene CꢀH proton in the for-
mation of the s,p-gold complex becomes favored with respect
to the direct nucleophilic attack, giving rise to the indole 3 as
the major product.
Scheme 6. Cross-over experiment between acetylide 6 and [Au{P(tBu)3}]NTf2.
a new species 9, with a similar NMR spectroscopy pattern to
species 5, was identified in the reaction mixture. This new spe-
cies lacked protons at both the C2 and C3 positions. The pres-
ence of [Au(PtBu3)] at the C3 position of 9 reinforces the idea
of the existence of an alternative non-gem evolution of the s,p
complex 8 into compound 3.[27] It is worth noting that MALDI
spectrometry revealed the presence of three LAu fragments
(Scheme 7). Unfortunately, even though the X-ray structure of
A plausible explanation for the divergent reaction pathways
found for [Au(IPr)]+ and [Au(PtBu3)]+ might have its origin in
the different features of the corresponding initial p complexes.
[29]
The bulky IPr ligand, with a high % Vburied value (44.5) and
a short gold–ligand distance (Au–Ccarbene 1.942 ꢄ),[30] could in-
terfere with the aryl terminus of 1 (Figure 3a), thus forcing
Scheme 7. Newly identified polyaurated species in the low-temperature stoi-
chiometric reaction of 4.
Figure 3. Comparative representation of the coordination of 1 to [Au(IPr)]+
and [AuP(tBu)3)]+.
9 also shows three gold atoms, all attempts to obtain a high-
quality[28] single crystal of this complex failed.
The fate of the acetylenic CꢀH proton was determined by
using urea [D]-1 (81% D), deuterated at the terminal alkyne.
Compound [D]-1 was subjected to 5 mol% of [Au(PtBu3)]SbF6
at 608C in DMF. In a similar fashion to the non-labeled sub-
strate, the reaction gave a 1:4 mixture of 2 and 3 with no deu-
terium being incorporated into the products. A full D/H ex-
change was also observed in the [Au(IPr)]+-catalyzed reaction.
To address the possibility of the D-label loss through a mislead-
ing D/H scrambling with acidic protons in the medium, the re-
actions were repeated at 08C. Stoichiometric amounts of LAu+
were employed to achieve measurable conversions. Indeed,
when [D]-1 was subjected to [Au(IPr)]SbF6 at 08C, a 60% con-
version into [D]-2 (81% D), with full retention of the label, was
observed. Conversely, the experiment carried out in the pres-
ence of [Au(PtBu3)]SbF6 gave 40% of compound 3, which ex-
hibited complete loss of deuterium at both the C2 and C3 po-
sitions (Scheme 8).
a more asymmetric alkyne activation, leading to a greater
build-up of positive charge at the benzylic carbon in 1 and,
consequently, a faster 6-exo attack with preferential formation
of compound 2. In contrast, the steric bulk of (PtBu3)[31] is locat-
ed away from the alkyne coordination area (Figure 3b). This
could result in a negligible slippage of the metal center and
a diminished ability to accelerate the 6-exo-dig nucleophilic
attack, thus allowing the formation of the dinuclear s,p-gold
complex.
Accordingly, other ligands that are highly hindered[32] or that
have a high % Vburied value would be expected to display be-
havior similar to that of IPr. As proof of concept, tBuXPhos
(XPhos=2-dicyclohexylphosphino-2’,4’,6’-triisopropylbiphenyl)
and tris(2,4-di-tert-butylphenyl)phosphite were tested. In both
cases, the cyclization of 1 led to compound 2 with 96 and
92% yield, respectively. Indeed, the low-temperature (08C) re-
actions with [D]-1 in the presence of these ligands proceeded
through the 6-exo-dig cycliza-
tion[33] with retention of the deu-
terium label.
In summary, we have isolated
and identified by NMR spectros-
copy, X-ray diffraction, or MALDI
spectrometry several aurated re-
action intermediates (s-gold,
s,p-gold, and other gold poly-
Scheme 8. Low-temperature reactions with [D]-1.
nuclear species) involved in the
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pp. 1–88; b) A. Fꢆrstner, P. W. Davies, Angew. Chem. 2007, 119, 3478–
3519; Angew. Chem. Int. Ed. 2007, 46, 3410–3449.
[13] a) O. Eisenstein, R. Hoffmann, J. Am. Chem. Soc. 1981, 103, 4308–4320;
b) H. M. Senn, P. E. Blçchl, A. Togni, J. Am. Chem. Soc. 2000, 122, 4098–
4107.
[14] As a guide, the acetylene coordination to copper lowers the pKa of the
terminal CꢀH proton by up to 9.8 units, see: F. Himo, T. Lovell, R. Hil-
graf, V. V. Rostovtsev, L. Noodleman, K. B. Sharpless, V. V. Fokin, J. Am.
Chem. Soc. 2005, 127, 210–216.
[15] Complex 4 is an example of an unusual gold–acetylide bearing a C2
nucleophilic heteroatom susceptible to cyclization. For a similar exam-
ple, see: P. P. Sharp, M. G. Banwell, J. Renner, K. Lohmann, A. C. Willis,
Org. Lett. 2013, 15, 2616–2619.
heterocyclization of 1-(oethynylaryl)urea 1. The behavior of
these species and cross-over or deuterium-labeling experi-
ments in the divergent 6-exo- or 5-endo-cyclization pathways
of compound 1 reveal ligand control in the simultaneous or al-
ternative p- and s,p-activation modes of terminal alkynes in
gold-catalyzed reactions. The results presented herein, includ-
ing a preliminary kinetic study, contribute to a better under-
standing of the mechanisms of gold(I) catalysis. Work is in
progress to determine the effect of different ligands and coun-
terions on the kinetic behavior and reactivity of alkynes with
cationic gold(I) complexes.
[16] Au{P(tBu)3}]NTf2 was employed to avoid any moisture from the hygro-
scopic AgSbF6.
A control experiment certified that both [Au{P-
(tBu)3}]NTf2 and [Au(PtBu3)]SbF6 behave in the same way in the hetero-
cyclization of 1.
Acknowledgements
[17] Z. J. Wang, D. Benitez, E. Tkatchouk, W. A. Goddard III, F. D. Toste, J. Am.
Chem. Soc. 2010, 132, 13064–13071.
[18] Isolated [Au(L)]NTf2, instead of [Au(L)]SbF6, gold complexes were used
to assure the precise concentration of catalyst employed.
[19] CCDC-953982 (7) and CCDC-953983 (8) contain the supplementary crys-
tallographic data for this paper. These data can be obtained free of
charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
[20] Nonconventional hydrogen bonds with gold have been already de-
scribed, see: a) E. S. Kryachko, J. Mol. Struct. 2008, 880, 23–30; for
a recent contribution dealing with NꢀH···AuI hydrogen bonds, see:
b) L. M. Scherf, S. A. Baer, F. Kraus, S. M. Bawaked, H. Schmidbaur, Inorg.
Chem. 2013, 52, 2157–2161.
This work was supported by the Spanish Ministerio de Ciencia
e Innovaciꢂn, European Community Founds (FEDER), and Gen-
eralitat Valenciana Grants (CTQ 2010-19999), Consolider-Ingen-
io2010 (CSD2007-00006) and (ACOMP-2013/185). We thank
(A.G.) the Generalitat Valenciana for a fellowship. We acknowl-
edge the SCSIE (Universidad de Valencia) for access to instru-
mental facilities.
Keywords: acetylides
· alkynes · dual activation · gold
intermediates · ligand effects
[21] The role of gold–acetylides as catalysts for the heterocyclization of
1 was excluded by performing control experiments.
[1] a) I. Braun, A. M. Asiri, A. S. K. Hashmi, ACS Catal. 2013, 3, 1902–1907;
b) A. Gꢂmez-Suꢀrez, S. P. Nolan, Angew. Chem. 2012, 124, 8278–8281;
Angew. Chem. Int. Ed. 2012, 51, 8156–8159, and references cited there-
in; c) A. S. K. Hashmi, Angew. Chem. 2010, 122, 5360–5369; Angew.
Chem. Int. Ed. 2010, 49, 5232–5241.
[22] The participation of dinuclear AuI species, owing to the high aurophilic-
ity of gold, must be considered in the rate-determining step.
[23] a) H. Schmidbaur, Gold Bull. 2000, 33, 3–10; b) H. Schmidbaur, A. Schier,
Chem. Soc. Rev. 2008, 37, 1931–1951; c) H. Schmidbaur, A. Schier, Chem.
Soc. Rev. 2012, 41, 370–412.
[2] P. H-Y. Cheong, P. Morganelli, M. R. Luzung, K. N. Houk, F. D. Toste, J. Am.
Chem. Soc. 2008, 130, 4517–4626.
[24] For examples of gem-diaurated species, see: a) D. Weber, M. A. Tarselli,
M. R. Gagnꢇ, Angew. Chem. 2009, 121, 5843–5846; Angew. Chem. Int.
Ed. 2009, 48, 5733–5736; b) G. Seidel, C. W. Lehmann, A. Fꢆrstner,
Angew. Chem. 2010, 122, 8644–8648; Angew. Chem. Int. Ed. 2010, 49,
8466–8470; c) S. K. Hashmi, I. Braun, P. Nçsel, J. Schꢈdlich, M. Wieteck,
M. Rudolph, F. Rominger, Angew. Chem. 2012, 124, 4532–4536; Angew.
Chem. Int. Ed. 2012, 51, 4456–4460; d) Y. Chen, M. Chen, Y. Liu, Angew.
Chem. 2012, 124, 6285–6290; Angew. Chem. Int. Ed. 2012, 51, 6181–
6186; e) A. S. K. Hashmi, M. Wieteck, I. Braun, P. Nçsel, L. Jongbloed, M.
Rudolph, F. Rominger, Adv. Synth. Catal. 2012, 354, 555–562; f) T. J.
Brown, D. Weber, M. R. Gagnꢇ, R. A. Widenhoefer, J. Am. Chem. Soc.
2012, 134, 9134–9137; g) D. Weber, T. D. Jones, L. L. Adduci, M. R.
Gagnꢇ, Angew. Chem. 2012, 124, 2502–2506; Angew. Chem. Int. Ed.
2012, 51, 2452–2456; h) J. E. Heckler, M. Zeller, A. D. Hunter, T. G. Gray,
Angew. Chem. 2012, 124, 6026–6030; Angew. Chem. Int. Ed. 2012, 51,
5924–5928; i) S. K. Hashmi, M. Wieteck, I. Braun, M. Rudolph, F. Roming-
er, Angew. Chem. 2012, 124, 10785–10789; Angew. Chem. Int. Ed. 2012,
51, 10633–10637; j) A. Zhdanko, M. E. Maier, Chem. Eur. J. 2013, 19,
3932–3942; k) A. Zhdanko, M. E. Maier, Organometallics 2013, 32,
2000–2006; l) A. Gꢂmez-Suꢀrez, S. Dupuy, A. M. Z. Slawin, S. P. Nolan,
Angew. Chem. 2013, 125, 972–976; Angew. Chem. Int. Ed. 2013, 52,
938–942; m) D. Weber, M. R. Gagnꢇ, Chem. Sci. 2013, 4, 335–338.
[25] Relevant data for the crystal structures of 7 and 8 is given in the Sup-
porting Information.
[3] a) A. S. K. Hashmi, I. Braun, M. Rudolph, F. Rominger, Organometallics
2012, 31, 644–661; b) M. M. Hansmann, M. Rudolph, F. Rominger,
A. S. K. Hashmi, Angew. Chem. 2013, 125, 2653–2659; Angew. Chem. Int.
Ed. 2013, 52, 2593–2598, and references cited therein. A similar dual
gold-activation process was also proposed by Gagosz et al., see: c) Y.
Odabachian, X. F. Le Goff, F. Gagosz, Chem. Eur. J. 2009, 15, 8966–8970.
[4] a) Y. Wang, A. Yepremyan, S. Ghorai, R. Todd, D. H. Aue, L. Zhang,
Angew. Chem. 2013, 125, 7949–7953; Angew. Chem. Int. Ed. 2013, 52,
7795–7799, and references cited therein.
[5] a) A. Grirrane, H. Garcꢁa, A. Corma, E. ꢅlvarez, ACS Catal. 2011, 1, 1647–
1653; b) A. Simonneau, F. Jaroschik, D. Lesage, M. Karanik, R. Guillot, M.
Malacria, J.-C. Tabet, J.-P. Goddard, L. Fensterbank, V. Gandon, Y. Gim-
bert, Chem. Sci. 2011, 2, 2417–2422; c) A. Grirrane, H. Garcia, A. Corma,
E. ꢅlvarez, Chem. Eur. J. 2013, 19, 12239–12244.
[6] a) T. N. Hooper, M. Green, C. A. Russell, Chem. Commun. 2010, 46, 2313–
2315; b) T. J. Brown, R. A. Widenhoefer, Organometallics 2011, 30, 6003–
6009.
[7] a) A. S. K. Hashmi, T. Lauterbach, P. Nçsel, M. H. Vilhelmsen, M. Rudolph,
F. Rominger, Chem. Eur. J. 2013, 19, 1058–1065.
[8] A. Gimeno, M. Medio-Simꢂn, C. R. de Arellano, G. Asensio, A. B. Cuenca,
Org. Lett. 2010, 12, 1900–1903.
[9] No reaction took place when compounds 2 and 3 were subjected to
several AuI catalysts. This result suggests that thermodynamic equilibra-
tion does not contribute to the product ratios observed.
[26] No C3 metalation of 5 was observed after 5 h under the same condi-
tions.
[10] a) M. J. S. Dewar, Bull. Soc. Chim. Fr. 1951, 18, 71–79; b) J. Chatt, L. A.
Duncanson, J. Chem. Soc. 1953, 2939–2947; c) M. S. Nechaev, V. M.
Rayꢂn, G. Frenking, J. Phys. Chem. A 2004, 108, 3134–3142.
[11] a) H. Schmidbaur, A. Schier, Organometallics 2010, 29, 2–23; b) S.
Flꢆgge, A. Anoop, R. Goddard, W. Thiel, A. Fꢆrstner, Chem. Eur. J. 2009,
15, 8558–8565.
[27] B. T. Worrell, J. A. Malik, V. V. Fokin, Science 2013, 340, 457–460.
[28] The structure of 9 shows three gold atoms bonded to the indole frag-
ment, as proposed in Scheme 7; however, extensive disorder of a large
part of the molecule rendered the structure unsatisfactory and, there-
fore, quantitative aspects are not discussed (see the Supporting Infor-
mation for unit-cell details). The incorporation of three LAu cation units
could result in the formation of the anticipated C2,3-diaurated indole
[12] a) D. M. P. Mingos in Comprehensive Organometallic Chemistry, Vol. 3
(Eds.: G. Wilkinson, F. G. A. Stone, E. W. Abel), Pergamon, Oxford, 1982,
Chem. Eur. J. 2014, 20, 683 – 688
www.chemeurj.org
687
ꢃ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Communication
(through s,p activation), followed by the coordination of an extra LAu
owing to its high basicity.
[29] H. Clavier, S. P. Nolan, Chem. Commun. 2010, 46, 841–861.
[30] P. de Frꢇmont, N. M. Scott, E. D. Stevens, S. P. Nolan, Organometallics
2005, 24, 2411–2418.
[33] In these two cases, the corresponding Csp-deuterated benzoxazine de-
rivative, the 6-exo-dig ring closure product of the urea oxygen, was also
detected (see the Supporting Information for additional details).
[31] H. Schmidbaur, B. Brachthauser, O. Steigelmann, H. Beruda, Chem. Ber.
1992, 125, 2705–2710.
Received: October 18, 2013
[32] A. Z. Gonzꢀlez, F. D. Toste, Org. Lett. 2010, 12, 200–203.
Published online on December 6, 2013
Chem. Eur. J. 2014, 20, 683 – 688
www.chemeurj.org
688
ꢃ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim