Dissecting anion effects in gold(I)-catalyzed intermolecular cycloadditions

Article abstract of DOI:10.1002/adsc.201300704

From a series of gold complexes of the type [t-BuXPhosAu(MeCN)]X (X=anion), the best results in intermolecular gold(I)-catalyzed reactions are obtained with the complex with the bulky and soft anion BAr₄^F- [BAr₄^F-=3,5-bis(trifluoromethyl)phenylborate] improving the original protocols by 10-30% yield. A kinetic study on the [2+2] cycloaddition reaction of alkynes with alkenes is consistent with an scenario in which the rate-determining step is the ligand exchange to generate the (η2- phenylacetylene)gold(I) complex. We have studied in detail the subtle differences that can be attributed to the anion in this formation, which result in a substantial decrease in the formation of unproductive σ,π-(alkyne) digold(I) complexes by destabilizing the conjugated acid formed.

Full text of DOI:10.1002/adsc.201300704

UPDATES
DOI: 10.1002/adsc.201300704
Dissecting Anion Effects in Gold(I)-Catalyzed Intermolecular
Cycloadditions
Anna Homs,+a Carla Obradors,+a David Lebœuf,a and Antonio M. Echavarrena,b,*
a
Institute of Chemical Research of Catalonia (ICIQ), Av. Paꢀsos Catalans 16, 43007 Tarragona, Spain
Fax : (+34)-97-792-0225; e-mail: aechavarren@iciq.es
Departament de Quꢁmica Analꢁtica i Quꢁmica Orgꢂnica, Universitat Rovira i Virgili, C/Marcel·li Domingo s/n, 43007
b
Tarragona, Spain
+
These two authors contributed equally to this work.
Received: August 4, 2013; Revised: October 10, 2013; Published online: January 13, 2014
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201300704.
Abstract: From a series of gold complexes of the
type [t-BuXPhosAu(MeCN)]X (X=anion), the best
By using cationic gold(I) complexes with bulky li-
gands, we developed the intermolecular reaction of al-
kynes with alkenes to form regioselectively cyclo-
AHCTUNGTRENNUNG
results in intermolecular gold(I)-catalyzed reactions
are obtained with the complex with the bulky and
AHCTUNGTRENNUNG
butenes of type 3a (Scheme 1).[3,4] More recently, we
FÀ
soft anion BAr4 [BAr4FÀ =3,5-bis(trifluorometh-
have developed a synthesis of phenols 5 by the inter-
A
molecular reaction of alkynes with furans such as
by 10–30% yield. A kinetic study on the [2+2]cy-
cloaddition reaction of alkynes with alkenes is con-
sistent with an scenario in which the rate-determin-
ing step is the ligand exchange to generate the (h2-
phenylacetylene)gold(I) complex. We have studied
in detail the subtle differences that can be attribut-
ed to the anion in this formation, which result in
a substantial decrease in the formation of unpro-
ductive s,p-(alkyne)digold(I) complexes by destabi-
lizing the conjugated acid formed.
4,[5,6] as well as a synthesis of oxabicyclo
ACTHUNGTERNNU[G 3.2.1]oct-3-
enes of type 7a by cycloaddition between oxoalkene 6
and 1a.[7]
During our studies on the [2+2+2]cycloaddition of
alkynes with oxoalkenes,[7] we discovered that forma-
tion of the active gold species was more complex than
expected. Although it was possible to observe the
phenylacetylene gold(I) complex (8a) at À608C, the
resting state under the reaction conditions was the un-
reactive s,p-(phenylacetylene)digold(I) complex 9a,
which decreases the reaction efficiency (Scheme 2).
Different research groups reported the formation
of very similar digold(I) complexes and their influ-
ence on the reactivity in catalytic transformations.[8]
Keywords: cycloaddition; cyclobutenes; gold cataly-
sis; mechanistic study
Introduction
Gold(I)-catalyzed intramolecular cycloisomerization
reactions have been widely studied during the last
decade.[1] Gold(I) complexes have been found to be
powerful homogeneous catalysts for carbon-carbon,
carbon-oxygen or carbon-nitrogen bond formation
proceeding by nucleophilic additions to alkynes,
allenes and alkenes, giving access to new carbo- and
heterocyclic compounds. Despite these major advan-
ces, the development of intermolecular cycloadditions
using alkynes as the substrates has been shown to be
challenging.[2]
Scheme 1. Gold(I)-catalyzed intermolecular reactions.
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221

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Anna Homs et al.
SbF6 (A1) as catalyst, furnishing regioselectively cy-
clobutenes 3 in moderate to good yields.[3] This cyclo-
addition proceeded under mild conditions in dichloro-
methane at room temperature. Although, as expected,
the ligand had a strong influence on the selectivity,
we were surprised by the notable difference observed
when changing the counterion (Table 1). Thus, replac-
Scheme 2. Formation of s,p-digold(I) complexes from (h2-al-
kyne)gold(I) complexes (L=t-BuXPhos).
À
FÀ
ing SbF6 in A1 by BAr4 (A2) leads to an increase
Table 1. Intermolecular gold(I)-catalyzed [2+2] cycloaddi-
tion between phenylacetylene (1a) and a-methylstyrene (2a)
with different gold(I) catalysts A.[a]
In this context, we have focused on tuning the catalyst
structure to minimize the formation of digold(I) com-
plexes. In intermolecular reactions involving alkynes,
we reasoned that the use of a more bulky, non-coordi-
nating, and less basic counterion could slow down the
deprotonation of terminal alkynes to form the s-ace-
tylide gold(I) intermediates. Hence, we have pre-
pared the new gold(I) complexes [t-BuXPhosAu-
F
(MeCN)]BAr4F A2 and [IPrAu
E
the BAr4 anion [BAr4FÀ =3,5-bis(trifluoromethyl)-
FÀ
phenylborate] (Figure 1).[9] These are close relatives
Entry
XÀ
3a (Yield [%])[b]
À
1
2
3
SbF6 FÀ
80
95
62
19
26
18
BAr4
À
BF4À
4
PF6
À
5[c]
6[c]
NTf2
OTfÀ
[a]
2a/1a=2:1.
[b]
[c]
1
Yield determined by H NMR using 1,4-diacetylbenzene
as internal standard.
Catalysts generated in situ with [LAuCl] and the corre-
sponding silver salts.
À
FÀ
Figure 1. Cationic gold(I) complexes with SbF6 and BAr4
anions (BAr4FÀ =3,5-bis(trifluoromethyl)phenylborate).
of the corresponding complexes A1[10] and B1[11] with
hexafluoroantimonate anion, which have been used as
the catalysts of choice in gold(I)-catalyzed intermolec- in the yield of the cycloaddition of 1a with 2a from 80
À
ular reactions.[3,4,5,7] Since complex B2 showed slightly to 95% (Table 1, entries 1 and 2). The use of BF4 ,
À
À
better performance than B1 in the intermolecular syn- PF6 , NTf2 or OTfÀ as counterions led to 3a in lower
thesis of phenols of type 5,[5] we decided to study in yields (Table 1, entries 3–6).
detail the effect of the anion on the corresponding t-
The cycloaddition between different terminal al-
BuXPhos complexes A1 and A2. Analogous com- kynes and 2a using catalysts A1 and A2 is shown in
À
À
plexes with BF4 and PF6 anions A3 and A4 have Table 2. In most cases, yields using A2 were 10–30%
also been studied. Herein we present a mechanistic higher (Table 2), with the exception of MeO-substitut-
study of the intermolecular [2+2]cycloaddition of al- ed alkynes 1c, 1g, and 1l, which afforded the corre-
kynes with alkenes in order to understand the influ- sponding cyclobutenes in very similar yields (Table 2,
ence of the counterion on the reactivity of these pro- entries 6, 14, and 24). In the case of 1n, a lower yield
cesses. This work shows that A2 is the catalyst of was obtained (Table 2, entry 28). Cyclobutene 3a was
choice for intermolecular reactions of terminal al- also obtained in 95% yield by performing the reaction
kynes.
on a larger scale (2.0 mmol). Generating in situ A2 by
simple mixing of (t-BuXPhos)gold(I) chloride and
NaBAr4F did not mean any drop in the yield.
Results and Discussion
Improved yields were also obtained in general
when phenylacetylene (1a) was used with different al-
The [2+2]cycloaddition of alkynes with alkenes was kenes (Table 3). The reaction can also be extended to
developed using complex [t-BuXPhosAu(MeCN)] allylsilane 2d, allyl ether 2e and allyl silyl ether 2f, al-
AHCTUNGTRENNUNG
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Dissecting Anion Effects in Gold(I)-Catalyzed Intermolecular Cycloadditions
Table 2. Intermolecular gold(I)-catalyzed [2+2]cycloaddi-
tion between alkynes (1a–n) and a-methylstyrene (2a).[a]
Table 3. Intermolecular gold(I)-catalyzed [2+2] cycloaddi-
tion between phenylacetylene (1a) and alkenes 2b–f.[a]
Entry
R
Catalyst Product (Yield [%])[b]
Entry
1
Catalyst
Product (Yield [%])
1
2
3
4
5
6
7
8
Ph (1a)
A1
A2
A1
A2
3a (80)[c]
3a (95)
3b (74)[c]
3b (86)
3c (68)[c]
3c (64)
3d (75)[c]
3d (84)
3e (61)[c]
3e (91)
3f (74)[c]
3 f (97)
3g (80)
3g (78)
3h (78)[c]
3h (91)
3i (74)[c]
3i (98)
A1
3o (74)[b,c]
p-Tol (1b)
2
3
4
5
6
A2
A1
A2
A1
A2
3o (79)[b]
3p (53)[b,c]
3p (69)[b]
3q (48)[d]
3q (71)[d]
p-MeOC6H4 (1c) A1
A2
p-FC6H4 (1d)
p-ClC6H4 (1e)
p-BrC6H4 (1f)
A1
A2
A1
A2
A1
A2
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
7
8
9
A1
A2
A1
A2
3r (26)[d]
3r (31)[d]
3s (21)[d]
3s (31)[d]
m-MeOC6H4 (1g) A1
A2
m-Tol (1h)
A1
A2
A1
A2
A1
A2
A1
A2
A1
A2
A1
A2
A1
A2
m-HOC6H4 (1i)
m-FC6H4 (1j)
m-ClC6H4 (1k)
o-MeOC6H4 (1l)
3-thienyl (1m)
cyclopropyl (1n)
10
3j (67)
3j (77)
[a]
2b–f/1a=2:1.
[b]
[c]
[d]
Isolated yields.
3k (60)
3k (83)
3l (30)
Ref.[3]
1
Yield determined by H NMR using 1,4-diacetylbenzene
as internal standard.
3l (24)
3m (84)
3m (86)
3n (46)[c]
3n (35)
[a]
2a/1a–n=2:1.
[b]
[c]
Isolated yields.
Ref.[3]
though yields were modest due to the lower nucleo-
philicity of these alkenes.
Scheme 3. Gold(I)-catalyzed macrocyclization of
enyne.
a 1,14-
The yield in the macrocyclization of 1,14-enyne 10
to form 13-membered derivative 11 was also im-
proved from 57% using A1 to 82% with A2
(Scheme 3).[7]
alkenes was expected to proceed by a rate-determin-
We also explored the influence of the counterion in ing attack of the electron-rich alkene to the (h2-alk-
the intermolecular [2+2+2]cycloaddition of alkynes
yne)gold(I) complex
8
forming the cyclopropyl
with oxoalkene 6 to furnish 8-oxabicyclo[3.2.1]oct-3- gold(I) carbene 12 (Scheme 4). Then, the ring expan-
AHCTUNGTRENNUNG
enes 7a–d using A1 and A2. For this more challenging sion occurs to form benzylic carbocation 13, which
cascade reaction, we could also observe a moderate forms cyclobutene 3a after demetallation. An associa-
improvement of the yields using catalyst A2 (Table 4, tive ligand exchange between (h2-cyclobutene)gold(I)
entries 2, 4, 6, and 8).
complex 14 and the starting alkyne closes the catalytic
To define the role of the anion in intermolecular re- cycle, regenerating 8.
actions, we studied experimentally the mechanism of
However, in our previous study on the [2+2+2]cy-
the [2+2]cycloaddition between alkynes and alkenes. cloaddition of alkynes with oxoalkenes,[7] we had ob-
According to previous theoretical work,[7,12] the cata- served that the formation of the (h2-alkyne)gold(I)
lytic cycle for the [2+2]cycloaddition of alkynes with complex 8a is complicated by the competitive forma-
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Anna Homs et al.
Table 4. Intermolecular gold(I)-catalyzed cyclization of 5-
methylhex-5-en-2-one (6) with terminal alkynes (1a–h).[a]
Entry
R
Catalyst Product (Yield [%])[b]
1
2
3
4
5
6
7
8
Ph (1a)
A1
A2
A1
A2
7a (68)[c]
7a (72)
p-ClC6H4 (1e)
7b (51)[c]
7b (62)
7c (65)[c]
7c (81)
m-HOC6H4 (1i) A1
A2
A1
A2
m-Tol (1h)
7d (70)[c]
7d (72)
Figure 2. Order of the reagents in the [2+2]cycloaddition
between phenylacetylene (1a) and a-methylstyrene (2a)
with complex A2.
[a]
6/1a–h=1:3.5.
Isolated yields.
Ref.[7]
[b]
[c]
ing 15. Generation of 8 is the slowest step due to its
unstability and rapid evolution to 9 or 3a.
Monitoring the [2+2]cycloaddition reaction by
1H NMR showed a significant dependence on the
anion (Figure 3). Besides the difference in the final
yields, the reaction rate increases with the bulkinÀess
andÀthe softness of the counterion: BAr4FÀ >SbF6
>
BF4 .
Scheme 4. Mechanism of the [2+2]cycloaddition between
alkynes and alkenes considering all the gold(I) species in
ACHTUNGTRENNUNG
equilibrium.
tion of s,p-digold(I) alkyne complex 9a (Scheme 2).
Therefore, we determined the order of the reagents in
the rate equation to gain further insight in the mecha-
nism. Initial rates were calculated for each component
by H NMR using diphenylmethane as internal stan-
dard (Figure 2). First order was observed for both the
Figure 3. Kinetics of the [2+2]cycloaddition between phe-
nylacetylene (1a) and a-methylstyrene (2a) with different
gold(I) complexes (L=t-BuXPhos).
1
Analysis of the reaction mixture by 31P NMR
alkyne 1a and the gold(I) catalyst A2, whereas the re- showed only the (alkene)gold(I) complex 15 and the
action showed zero order dependence for the alkene digold complex 9. The ratio between these species
FÀ
2a.
[15]/[9] inÀcreased following the same trend: BAr4
À
These results are consistent with a scenario in (b)>SbF6 (a)>BF4 (c).À Thus, [15]/[9] drops from
À
which the actual rate-determining step is the ligand 115 (BArF4FÀ) to 30 (SbF6 ) and finally to 4 for BF4
exchange to generate the active species 8 (Scheme 4). resulting in a smaller reservoir of the cationic gold(I)
Complex A undergoes ligand exchange with 2a form- species.
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Dissecting Anion Effects in Gold(I)-Catalyzed Intermolecular Cycloadditions
À
À
The equilibrium constants for the formation of 9 10.22 ꢄ) and 77.38 for SbF6 (Au Sb 8.23 ꢄ) and the
FÀ
À
and 15 from A1 and A2 were also determined, endo- angle of the s-gold is 210.08 for BAr4
(Au B
À
À
thermic and exothermic, respectively (Scheme 5). For- 11.52 ꢄ) and 60.68 for SbF6 (Au Sb 7.34 ꢄ). Com-
plex 16 was independently prepared by reaction of
the neutral gold(I) complex with lithium phenylacety-
lide and its structure was determined by X-ray diffrac-
tion.[13,14]
We performed DFT calculations of the key com-
plexes [t-BuXPhosAu(h2-phenylacetylene)]X 8 (X=
BF4 , SbF6 , BAr4FÀ) [M06, 6-31G(d) (C, H, P, B, F)
and SDD (Au, Sb), CH2Cl2]. First, we evidenced the
steric congestion around the substrate hampering its
deprotonation depending on the counterion. We ana-
lyzed the charge distribution by electron density from
total SCF density mapped with ESP (1=0.03 eꢄ3)
and the positive charge is widely distributed around
À
À
Scheme 5. Determination of the equilibrium constants from
A to 9 and 15.
À
mation of digold(I) complex with SbF6 (9a) anion is the ligand instead of being concentrated in the metal
more favored than with BAr4 (9b), probably due to center (Figure 5). We also checked the pattern be-
FÀ
the minor stability of the bulkier conjugated acid. We tween the bulkiness of the counterion and the acidity
also checked that A2 binds stronger to 2a than A1.
of phenylacetylene by determining the Mulliken
FÀ
These results suggest that when BAr4 is used, the atomic charges. The electron density decreases with
concentration of catalytically active species 8b the anion size: BF4À <SbF6À <BAr4FÀÀ, although the
FÀ
À
(BAr4 as counteranion) is higher than with SbF6
differences are modest: 0.250 for BF4 (8c), 0.243 for
À
FÀ
(8a). We also studied the evolution of the gold(I) spe- SbF6 (8a) and 0.237 for BAr4 (8b). Presumably,
cies formed with A1 or A2 and 1a from À60 to 208C the large cation forms a more stable complex 8 with
by 31P NMR. With A1, the digold(I) complex 9a was a softer counterion as BAr4
.
FÀ
observed from À608C, becoming the only species at
Finally, we performed some additional experiments
À208C (Scheme 6). However, in the case of A2, the to exclude other mechanistic pathways.[14] We started
corresponding digold(I) complex 9b was not observed by reacting the isolable intermediates under stoichio-
until 08C. Furthermore, the catalytically active species metric conditions with a-methylstyrene (2a). Neither
8b was clearly observed up to the same temperature. complex 9 nor 16 reacted with 2a in CH2Cl2 at 238C
for 8 h in the absence or presence of A2 as a catalyst.
On the other hand, complex 15b (Figure 4) reacts
with 1a to form cyclobutene 3a in 72% (CH2Cl2,
238C, 8 h) therefore that equilibrium is not inhibiting
the process.
Complex 16 is not catalytically active for the forma-
tion of 3a by [2+2]cycloaddition, although the activity
is restored upon addition of HSbF6, which cleaves the
À
Au C bond generating the gold(I) catalyst (Table 5,
entries 1 and 2). More significantly, as we observed
before in another context,[7] digold complexes 9a and
9b are very poor catalysts for the [2+2]cycloaddition
between 1a with 2a (Table 5, entries 3 and 4), al-
though the reaction proceeds smoothly after addition
HSbF6 (Table 5, entry 5).
Scheme 6. Gold(I) species formed between phenylacetylene
(1a) and A1 or A2 from 213 to 293 K.
Complexes 15b and 9b (Figure 4) could be isolated
and were fully characterized by X-ray crystallogra- Conclusions
phy.[13] The main divergence between 9a and 9b in the
solid state (Figure 4b and c, respectively) is the radi- We have designed a new generation of gold(I) com-
FÀ
cally different position of the counterions. Whereas plexes bearing BAr4 as counterion [BAr4FÀ =3,5-
FÀ
BAr4
is located alongside the phenylacetylene bis(trifluoromethyl)phenylborate]. These have proven
À
moiety in the same plane, SbF6 is placed between to be more efficient in different intermolecular
both gold atoms bending slightly the cation entity. gold(I)-catalyzed reactions, improving the yields be-
Thus, the angle of the p-coordinated gold(I), the tween 10 and 30%. We have then studied in detail the
FÀ
À
alkyne and the counterion is 130.38 for BAr4 (Au B subtle anion effects in the gold(I)-catalyzed [2+2]cy-
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Anna Homs et al.
Figure 4. X-Ray crystal structures: (a) a-methylstyrene gold(I) complex 15b, (b) [(t-BuXPhosAu)2C CPh] CHTUGNTRENNUNG
[SbF6]À 9a (taken
from ref. ) and (c) [(t-BuXPhosAu)2C CPh] CHTUGNTERNNUNG
for clarity.
+A
ꢀ
[7]
F
+A[BAr4 ]À 9b. ORTEP plot (50% thermal ellipsoids). Hydrogens are omitted
ꢀ
cloaddition of terminal alkynes with alkenes, which lyzed reactions are obtained using [t-BuXPhosAu-
sum up in a substantial decrease in the formation of
unproductive s,p-(alkyne)digold(I) complex when the
BAr4FÀ anion is used.
(MeCN)]BAr4F as catalyst.
ACHTUNGTRENNUNG
Our kinetic study of the gold(I)-catalyzed [2+2]cy-
cloaddition reaction of terminal alkynes with alkenes
is consistent with a scenario in which the rate-
determining step is the first ligand exchange of
Experimental Section
Procedure for the Synthesis of Gold(I) Complex A2
Chloro[(2’,4’,6’-triisopropyl-1,1’-biphenyl-2-yl)di-tert-butyl-
phosphine]gold(I) (100.0 mg, 0.152 mmol) and acetonitrile
(9.5 mL, 0.183 mmol) were dissolved in dichloromethane
(6.6 mL). Then, sodium tetrakis
nyl]borate (135.0 mg, 0.152 mmol) was added and the reac-
ACHTUNGTRENNUNG[LAuACHTUNGTRENNUNG
(MeCN)]X to generate the active (h2-phenylace-
tylene)gold(I) complex, which is more stable with
softer counterions according to DFT calculations.
From a general practical perspective, we have found
ACHTUNGTRNE[NUNG 3,5-bis(trifluoromethyl)phe-
that the best results in intermolecular gold(I)-cata- tion mixture was stirred at room temperature for 30 min.
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Preparative TLC was used to purify the resulting cyclobu-
tenes.
Acknowledgements
We thank the MICINN (CTQ2010-16088/BQU and FPI fel-
lowship to A. H.), the AGAUR (project 2009 SGR 47 and
Beatriu de Pinꢀs postdoctoral fellowship to D. L.), the MEC
(FPU fellowship to C. O.), the European Research Council
(Advanced Grant No. 321066), and the ICIQ Foundation for
financial support. We also thank the ICIQ X-ray diffraction,
the Nuclear Magnetic Resonance and the Spectroscopic and
Kinetics units.
References
[1] a) L. Zhang, J. Sun, S. A. Kozmin, Adv. Synth. Catal.
2006, 348, 2271–2296; b) A. S. K. Hashmi, G. J. Hutch-
ings, Angew. Chem. 2006, 118, 8064–8105; Angew.
Chem. Int. Ed. 2006, 45, 7896–7936; c) A. Fꢅrstner,
P. W. Davies, Angew. Chem. 2007, 119, 3478–3519;
Angew. Chem. Int. Ed. 2007, 46, 3410–3449; d) A. S. K.
Hashmi, Chem. Rev. 2007, 107, 3180–3211; e) Z. Li, C.
Brouwer, C. He, Chem. Rev. 2008, 108, 3239–3265;
f) A. Arcadi, Chem. Rev. 2008, 108, 3266–3325; g) E. Ji-
mꢆnez-NfflÇez, A. M. Echavarren, Chem. Rev. 2008,
108, 3326–3350; h) D. J. Gorin, B. D. Sherry, F. D. Toste,
Chem. Rev. 2008, 108, 3351–3378; i) V. Michelet, P. Y.
Toullec, J.-P. GenÞt, Angew. Chem. 2008, 120, 4338–
4386; Angew. Chem. Int. Ed. 2008, 47, 4268–4315; j) A.
Fꢅrstner, Chem. Soc. Rev. 2009, 38, 3208–3221; k) C.
Aubert, L. Fensterbank, P. Garcia, M. Malacria, A. Si-
monneau, Chem. Rev. 2011, 111, 1954–1993; l) N.
Krause, C. Winter, Chem. Rev. 2011, 111, 1994–2009.
[2] For selected examples, see: a) C. Ferrer, C. H. M.
Amijs, A. M. Echavarren, Chem. Eur. J. 2007, 13, 1358–
1373; b) R. B. Dateer##, B. S. Shaibu, R. S. Liu, Angew.
Chem. 2012, 124, 117–121; Angew. Chem. Int. Ed. 2012,
51, 113–117; c) H.-S. Yeom, J. Koo, H.-S. Park, Y.
Wang, Y. Liang, Z.-X. Yu, S. Shin, J. Am. Chem. Soc.
2012, 134, 208–211; d) S. Kramer, T. Skrydstrup,
Angew. Chem. 2012, 124, 4759–4762; Angew. Chem.
Int. Ed. 2012, 51, 4681–4684; e) Y. Luo, K. Ji, Y. Li, L.
Zhang, J. Am. Chem. Soc. 2012, 134, 17412–17415.
[3] V. López-Carrillo, A. M. Echavarren, J. Am. Chem.
Soc. 2010, 132, 9292–9294.
Figure 5. Electron density from total SCF density mapped
with ESP (1=0.03 eꢄ3) for complexes 8 [t-BuXPhosAu(h2À-
À
FÀ
phenylacetylene)X, X=SbF6 (8a), BAr4 (8b), and BF4
(8c)].
Table 5. Regeneration of the catalytic activity in the inter-
molecular gold(I)-catalyzed [2+2]cycloaddition between 1a
and 2a in the presence of a Brønsted acid.[a]
Entry [Au] (mol%) Additive (mol%)
Yield [%][b]
1
2
3
4
5
16 (3)
16 (3)
9a (1.5)
9b (1.5)
9a (1.5)
–
–
HSbF6·6H2O (3)
–
–
75
13
13
HSbF6·6H2O (1.5%) 70
[a]
[b]
238C, 8 h.
1
Yield determined by H NMR using 1,4-diacetylbenzene
as internal standard.
The crude was filtered through Celite, then Teflon 0.22 and
concentrated to obtain a white powder; yield: 224 mg
(97%).
[4] Conceptually analogous macrocyclization by cycloaddi-
tion of alkynes with alkenes, see: C. Obradors, D.
Lebœuf, J. Aydin, A. M. Echavarren, Org. Lett. 2013,
15, 1576–1579.
[5] N. Huguet, D. Lebœuf, A. M. Echavarren, Chem. Eur.
J. 2013, 19, 6581–6585.
Procedure for the Synthesis of Cyclobutenes (3)
Alkyne (1 equiv.) and alkene (2 equiv.) were dissolved in di-
chloromethane (0.48M) and the cationic gold(I) catalyst
(3 mol%) was added. The reaction mixture was stirred at
room temperature until no alkyne was observed by TLC.
Then, it was quenched by adding a drop of a solution of
Et3N in cyclohexane (1M) and the solvent was removed.
[6] First example of an intramolecular gold-catalyzed for-
mation of phenol with a furan and an alkyne, see:
a) A. S. K. Hashmi, E. Kurpejovic, M. Wçlfle, W. Frey,
J. W. Bats, Adv. Synth. Catal. 2007, 349, 1743–1750;
b) A. S. K. Hashmi, M. C. Blanco, E. Kurpejovic, W.
Frey, J. W. Bats, Adv. Synth. Catal. 2006, 348, 709–713;
Adv. Synth. Catal. 2014, 356, 221 – 228
ꢃ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
227

UPDATES
Anna Homs et al.
c) A. S. K. Hashmi, M. C. Blanco, Eur. J. Org. Chem.
2006, 4340–4342.
m) B. Rubial, A. Ballesteros, J. M. Gonzµlez, Adv.
Synth. Catal. 2013, 355, 3337–3343.
[7] C. Obradors, A. M. Echavarren, Chem. Eur. J. 2013, 19,
3547–3551.
[9] A gold(I) carbene with tetrakisACHTUNTRGNEUNG[3,5-bis(trifluorome-
thyl)phenyl]borate as the counterion has been reported
[8] a) C. Wei, C. J. Li, J. Am. Chem. Soc. 2003, 125, 9584–
9585; b) V. Lavallo, G. D. Frey, S. Kousar, B. Donna-
dieu, G. Bertrand, Proc. Natl. Acad. Sci. USA 2007,
104, 13569–13573; c) P. H. Y. Cheong, P. Morganelli,
M. R. Luzung, K. N. Houk, F. D. Toste, J. Am. Chem.
Soc. 2008, 130, 4517–4526; d) T. N. Hooper, M. Green,
C. A. Russell, Chem. Commun. 2010, 46, 2313–2315;
e) A. Simonneau, F. Jaroschik, D. Lesage, M. Karanik,
R. Guillot, M. Malacria, J.-C. Tabet, J.-P. Goddard, L.
Fensterbank, V. Gandon, Y. Gimbert, Chem. Sci. 2011,
2, 2417–2422; f) A. Grirrane, H. Garcia, A. Corma, E.
lvarez, ACS Catal. 2011, 1, 1647–1653; g) T. J. Brown,
R. A. Widenhoefer, Organometallics 2011, 30, 6003–
6009; h) M. Raducan, M. Moreno, C. Bour, A. M.
Echavarren, Chem. Commun. 2012, 48, 52–54;
i) A. S. K. Hashmi, T. Lauterbach, P. Nçsel, M. H. Vil-
helmsen, M. Rudolph, F. Rominger, Chem. Eur. J.
2013, 19, 1058–1065; j) A. Gómez-Suµrez, S. Dupuis,
A. M. Z. Slawin, S. P. Nolan, Angew. Chem. 2013, 125,
972–976; Angew. Chem. Int. Ed. 2013, 52, 938–942;
k) A. Zhdanko, M. Strçbele, M. E. Maier, Chem. Eur.
J. Chem. -Eur. J. 2012, 18, 14732–14744; l) A. S. K.
Hashmi, I. Braun, P. Nçsel, J. Schädlich, M. Wieteck,
M. Rudolph, F. Rominger, Angew. Chem. 2012, 124,
4532–4536; Angew. Chem. Int. Ed. 2012, 51, 4456–4460;
À
to undergo C B cleavage to from an aryl-gold(I) com-
plex due to the high electrophilic of the metal center.
However, we never observed this behavior with com-
plex A2: S. G. Weber, D. Zahner, F. Rominger, B. F.
Straub, Chem. Commun. 2012, 48, 11325–11327.
[10] P. Pꢆrez-Galµn, N. Delpont, E. Herrero-Gómez, F. Ma-
seras, A. M. Echavarren, Chem. Eur. J. 2010, 16, 5324–
5332.
[11] C. H. M. Amijs, V. López-Carrillo, M. Raducan, P.
Pꢆrez-Galµn, C. Ferrer, A. M. Echavarren, J. Org.
Chem. 2008, 73, 7721–7730.
[12] a) C. Nieto-Oberhuber, S. López, M. P. MuÇoz, D. J.
Cµrdenas, E. BuÇuel, C. Nevado, A. M. Echavarren,
Angew. Chem. 2005, 117, 6302–6304; Angew. Chem.
Int. Ed. 2005, 44, 6146–6148; b) A. Escribano-Cuesta,
P,
Pꢆrez-Galµn, E. Herrero-Gómez, M. Sekine,
A. A. C. Braga, F. Maseras, A. M. Echavarren, Org.
Biomol. Chem. 2012, 10, 6105–6111.
[13] CCDC 953708 (12b), CCDC 953710 (9b), and CCDC
953709 (16) contain the supplementary crystallographic
data for this paper. These data can be obtained free of
charge from The Cambridge Crystallographic Data
Centre via www.ccdc.cam.ac.uk/data_request/cif.
[14] See the Supporting Information for details.
228
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