Gold-catalyzed synthesis of iodofulvenes

Article abstract of DOI:10.1002/chem.201300507

We report the gold-catalyzed synthesis of highly functionalized iodofulvenes from iododialkynes under mild conditions. The catalytic cycle involves the formation of gold acetylides and vinylgold intermediates. These intermediates can then undergo an unprecedented iodine/gold exchange. This new pathway for catalyst transfer in dual gold catalysis opens up the possibility of highly regioselective transformations directed by the gold in the organogold intermediates. The resulting products are well suited for further metal-mediated coupling reactions, allowing the synthesis of extended π-systems. Iodine/gold exchange: A gold-catalyzed iodine transfer allows the efficient synthesis of benzofulvenes with iodo substituents on the fulvene core (see scheme). The new dual-activation catalysts are efficient catalysts for this new type of cycloisomerization. Copyright

Full text of DOI:10.1002/chem.201300507

DOI: 10.1002/chem.201300507
Gold-Catalyzed Synthesis of Iodofulvenes
Pascal Nçsel, Tobias Lauterbach, Matthias Rudolph, Frank Rominger, and
[
a]
A. Stephen K. Hashmi*
Abstract: We report the gold-catalyzed
synthesis of highly functionalized iodo-
fulvenes from iododialkynes under
mild conditions. The catalytic cycle in-
volves the formation of gold acetylides
and vinylgold intermediates. These in-
termediates can then undergo an un-
precedented iodine/gold exchange. This
new pathway for catalyst transfer in
dual gold catalysis opens up the possi-
bility of highly regioselective transfor-
mations directed by the gold in the or-
ganogold intermediates. The resulting
products are well suited for further
metal-mediated coupling reactions, al-
lowing the synthesis of extended p-sys-
tems.
Keywords: alkynes · benzofulvenes ·
dual activation · gold · iodination ·
vinylidenes
Introduction
philic activator, giving rise to the corresponding iodinated
derivatives. On the basis of this evident similarity between
gold and iodine, we were curious as to whether iodine is
also able to play a role in the new field of s/p dual-activa-
tion chemistry (Scheme 1). A combination of gold and
iodine instead of the dual gold catalysis might open new re-
action pathways leading to valuable iodine-containing prod-
ucts. The results of this investigation are presented in this
contribution.
Because of its exceptional ability for p-activation of unsatu-
rated organic molecules, gold is of increasing importance in
the field of transition metal catalysis. Only recently,
Zhangꢀs group and ours independently discovered a new re-
activity pattern for gold, which is based on a dual-activation
mode (Scheme 1, left). The catalytic cycle consists of a com-
[1]
Results and Discussion
The mono-iodinated diynes 2 were prepared conveniently
from the corresponding terminal alkynes 1 (Scheme 2,
Table 1). Two different methods were applied. Iodination
Scheme 1. Relationship between dual gold catalysis and conceivable
mixed gold/iodine chemistry.
bination of s-activation (to increase the nucleophilicity of
an alkyne) combined with the common electrophilic p-acti-
vation mode. From diyne starting materials, a series of inter-
[
2]
esting products can be obtained through intramolecular
[3]
and intermolecular reactions. Iodine has also attracted
Scheme 2. Iodination of diynes 1.
considerable attention as a p-activator, and there is an as-
[4]
tonishing parallel reactivity between iodine and gold. This
leads to a series of useful transformations in which iodine
with an excess of N-iodosuccinimide (NIS) and catalytic
amounts of silver nitrate in a mixture of acetone and water
furnished most of the desired iodoalkynes in good to excel-
(
as a stoichiometric reagent) can replace gold as an electro-
[5]
lent yields (Table 1, entries 1, 2, 7, 9, and 10; method A).
[
a] Dipl.-Chem. P. Nçsel, M.Sc. T. Lauterbach, Dr. M. Rudolph,
Dr. F. Rominger, Prof. Dr. A. S. K. Hashmi
+
Problems occurred with substrates bearing functional groups
(Table 1, entries 3–6, 8, 11, and 12). For these cases, a proto-
Organisch-Chemisches Institut
Ruprecht-Karls-Universitꢁt Heidelberg
Im Neuenheimer Feld 270, 69120 Heidelberg (Germany)
Fax : (+49)6221-54-4205
[6]
col involving the use of potassium hydroxide and NIS de-
livered the corresponding iodoalkynes in better yields.
Figure 1 shows the solid-state molecular structure of com-
E-mail: hashmi@hashmi.de
[7]
+
pound 2l.
[
] Crystallographic investigation
In order to test the reactivity of the iodoalkynes 2, we
started an intensive screening with test substrate 2a
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201300507.
8634
ꢂ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2013, 19, 8634 – 8641

FULL PAPER
Table 1. Iodination of diynes 1.
Entry Reactant Product
Method Yield [%]
1
A
A
B
B
B
B
A
95
48
95
86
80
87
90
2
3
4
5
6
7
Figure 1. Solid-state molecular structure of compound 2l.
[
a]
Table 2. Catalyst and counterion screening.
Entry
Catalyst
Max. yield [%]
t [h]
1
2
3
4
[IPrAu-NTf
AuCl
DAC-IPr-PF
DAC-IPr-SbF
2
]
no conversion
no conversion
50
6
1
0.5
6
22 (several by-
products)
5
6
7
8
DAC-IPr-OTs
DAC-IPr-BF
DAC-IPr-NTf
BrettPhos-NTf
Au(CCCH )]
[IPrAu-NTf2]
[IPrAu-NTf ]+
6
24
4
38
79
71
1.5
2.5
5.5
2
2
+[BrettPhos-
AuIPr]
A
H
U
G
R
N
U
G
3
1
1
0
1
+
A
H
U
G
R
N
U
G
3
45
76
5
2
2
ACHTUNGTRENNUNG
[
a] Unless stated otherwise: 5 mol% catalyst or additive, 508C, dioxane,
8
9
B
91
94
c=0.08m.
(
Table 2, Figure 2). The initial experiments with cationic
[
IPrAuNTf ] and simple gold(I) chloride showed no conver-
A
2
sion of the starting material (Table 2, entries 1 and 2). Inter-
estingly, the use of s,p-dinuclear propynyl gold acetylides
[8]
(
dual-activation catalysts; DACs) led to fast consumption
of the starting material (Table 2, entries 3–7). The yield ob-
tained with these catalysts was highly dependent on the re-
action time, because of a competing degradation of the
product in the presence of the gold catalyst (see Supporting
Information for further details). With the hexafluorophos-
phate counterion, a moderate yield of 50% of a mono-iodi-
nated product was isolated (Table 2, entry 3). The structure
1
1
1
0
1
2
A
B
B
39
26
64
1
13
of the product was assigned through H and C NMR spec-
troscopy and 2D NMR experiments. In analogy to the dual-
[
2b]
activation chemistry with alkyl-substituted alkynes, a ben-
zofulvene was generated, but it contained an additional
iodine substituent. The iodine of the starting material was
transferred from the former alkyne position to the olefinic
position of the central ring of the benzofulvene core (to a
position derived from the substituted alkyne of the starting
material). To increase the yield of the iodofulvene, we
[
a]
1
3
A
64
[
a] NBS used as bromine source.
Chem. Eur. J. 2013, 19, 8634 – 8641
ꢂ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
8635

A. S. K. Hashmi et al.
high concentrations were used to increase the reaction rates.
We investigated the yield of iodofulvene 3a as a function of
the concentration (see Figure 5 and additional details in the
Supporting Information). The results clearly indicate that a
higher concentration leads to a higher yield. Because de-
composition of the iodofulvene in the presence of a gold
catalyst is an omnipresent decomposition path (isolated 3a
Figure 2. Applied ligands and catalysts.
tested different counterions for
the dual-activation catalysts. All
reactions were monitored by
gas chromatography (GC, see
Figure 3) to determine the max-
imum yield at a certain reaction
time. The use of hexafluoroan-
timonate as the counterion led
to a fast conversion of the start-
ing material, but the reaction
was
unselective
(Table 2,
entry 4). Although only slow
conversion was observed with
the
tosylate
counterion
(
Table 2, entry 5), higher reac- Figure 3. Yields of 3a with different catalysts/counterions.
tion rates and moderate yields
were feasible with the tetra-
fluoroborate anion (Table 2,
entry 6). By far the best results
were obtained with the trifli-
mide anion, which delivered
good results in a reasonable re-
action time (Table 2, entry 7).
BrettPhos as a ligand in combi-
nation with the corresponding
propynyl gold acetylide as an
additive also showed good re-
sults with the triflimide counter-
ion, but the reaction times were
slightly longer and the yields
were lower (Table 2, entry 8).
Alkyl and aryl organogold com-
pounds as additives in combina-
tion with the IPr ligand were
also suitable (Table 2, entries 10
2
Figure 4. Yield of 3a in different solvents; 5 mol% DAC-IPr-NTf , 508C, c=0.04m.
and 11), but owing to the well-defined ratio and the easier
handling, we performed the further optimizations with
DAC-IPr and the triflimide ion.
Screening of different solvents at 508C with 5 mol%
DAC-IPr-NTf2 (0.04m) revealed that dioxane was best
suited for this reaction, followed by benzene (see Figure 4).
Chlorinated solvents such as chloroform and dichlorome-
thane generally proved to be unfavorable, giving low yields
and incomplete conversion. Acetone and nitromethane
showed signs of iodination of the solvent after prolonged re-
action times.
As mentioned above, a competing decomposition of the
products occurred at prolonged reaction times. Therefore,
Figure 5. Maximum yield as a function of substrate concentration.
8636
www.chemeurj.org
ꢂ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2013, 19, 8634 – 8641

Gold-Catalyzed Synthesis of Iodofulvenes
FULL PAPER
To prove the assignment of
the final products unambigu-
ously, we used single crystals of
compounds 3h and 3i for X-ray
crystal structure analysis (Fig-
[7]
ures 7 and 8).
Indeed, an
iodine shift from the former io-
doalkyne to the opposite alkyne
occurred (the iodine being at-
tached to the peri-position of
the arene).
Next, we tried to gain further
mechanistic insights. Because
2
Figure 6. Varying ratios of additive to cationic gold; dioxane, 5 mol% [IPrAuNTf ], 508C.
also decomposed slowly when subjected to the catalyst; see
Table 3. Synthesis of different iodofulvenes under optimized condition-
s.
[
a]
the Supporting Information), it is vital to prepare a large
amount of product in a short time, and this is achieved most
effectively by using high catalyst loadings and concentra-
tions. If the reaction is stopped in time, high isolated yields
can be achieved; however, this requires close monitoring of
the conversion.
Entry
1
Substrate
Product
Yield [%]
74
t [h]
2a
2.5
The effect of the relative ratio of gold organyl to additive
was also investigated (Figure 6). Increasing the amount of
additive to 20 mol% while keeping the active catalyst
2
3
2b
2c
46
52
5
5
[
IPrAuNTf ] at 5 mol% showed that an increase in additive
2
led to a prolonged induction phase; however, the maximum
yields were unaffected. When the amount of additive fell
below an equimolar ratio (0.1 mol% or 1 mol%, both in
4
5
2d
2e
72
83
4
3
combination with 5 mol% [IPrAuNTf ]) the maximum yield
decreased rapidly. This clearly demonstrated that a defined
2
1
:1 ratio is ideal for this type of transformation.
For the evaluation of the scope of the transformation, io-
doalkynes 2a–l were converted under the optimized condi-
tions, and the results are summarized in Table 3. The first
series of starting materials contained tert-butyl-substituted
alkynes (Table 3, entries 1–8). The yields for electron-neu-
tral and electron-rich substrates varied from good to moder-
ate. As mentioned above, partial degradation of the prod-
ucts under the reaction conditions might be the reason for
the slightly lower yields for substrates 3b and 3 f (Table 3,
entries 2 and 6). Electron-withdrawing substituents at the ar-
omatic core delivered high yields, regardless of whether
fluoro- (2g) or nitro-substituted (2h) arenes were converted
6
2 f
59
3.5
7
8
2g
2h
86
88
4
5
(
Table 3, entries 7 and 8).
Longer alkyl chains at the alkynes 3i and 3j delivered
only a complex mixture of products with the dual-activation
catalysts. However, switching to the bulky [BrettPhos-
[
[
b]
b]
9
2i
2j
56
12
AuNTf ] as a catalyst in combination with the corresponding
2
[
propynyl Au(BrettPhos)] gave a satisfying selectivity and
acceptable yields (Table 3, entries 8 and 9). Unfortunately,
substrates 2k and 2l with additional functional groups at the
alkyne showed decomposition regardless of which catalyst
combination was applied (Table 3, entries 11 and 12). Most
unfortunately, the bromoalkyne 2m showed no conversion
under the optimized reaction conditions (Table 3, entry 13).
10
58
3
1
1
1
2
13
2k
2l
2m
decomposition
decomposition
no reaction
–
–
–
–
–
–
[
2
a] Unless stated otherwise: c=0.4m in dioxane, 5 mol% DAC-IPr-NTf ,
5
08C. [b] 5 mol% [BrettPhosAuNTf
2
]+5 mol% propynyl Au(Brettphos).
Chem. Eur. J. 2013, 19, 8634 – 8641
ꢂ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
8637

A. S. K. Hashmi et al.
clearly demonstrates that a direct rather than a stepwise ex-
+
[9]
change must take place, and that no “naked I ” is present.
This was confirmed by stoichiometric experiments, which
1
were monitored by H NMR under the (initial) reaction
conditions but in the absence of any cationic gold catalyst
(
Scheme 4). The formation of the corresponding gold acety-
Figure 7. Solid-state molecular structure of 3h (bond length CÀI=
.086 ꢃ).
2
Scheme 4. Exchange experiment monitored by NMR and GC-MS.
lide 5 and iodobenzene 4 was monitored. It must be men-
tioned that in the absence of a cationic gold source, this
seems to be a slow process (even after 12 h, only 60% con-
version was observed).
For further understanding of this exchange process and
the necessity for an additive (in contrast to the benzofulvene
synthesis with terminal alkynes), the reaction was performed
with 5 mol% of the non-iodinated diyne 6a and 5 mol%
Figure 8. Solid-state molecular structure of 3i (bond length CÀI=
.069 ꢃ).
2
the transformation was only possible with organogold com-
pounds as additives, it seemed unlikely that iodine would be
able to substitute the role of gold as s-activator (if this
would be the activation mode, no additional activators
would be needed). Instead, we considered the possibility of
an iodine/gold ligand exchange between the iodoalkyne 2a
and the organogold additive. We could indeed observe the
formation of iodobenzene 4 during the transformation of
substrate 2a in combination with phenyl gold as an additive
[IPrAuNTf ] (Scheme 5). Despite the absence of any further
2
gold-organyl, full conversion of the iodoalkyne 2a was ob-
served overnight, and only traces of the nonsubstituted ben-
zofulvene 7a were detected (by GC-MS).
We assume that in this case, the non-iodinated substrate
6a substitutes for the additive. After the first catalytic cycle,
the gem-diaurated compound 8 (Scheme 6) is formed, which
then enables activation of the iodoalkyne substrate through
iodine/gold exchange. Because the isolated yield was only
moderate and traces of 7a could not be separated easily,
this protocol cannot replace the use of an organogold addi-
tive.
(
Scheme 3). Furthermore, iodobenzene 4 was detected by
For the verification of this possibility, the gem-diaurated
compound 8 was synthesized and subjected to equimolar
amounts of iodophenylacetylene (Scheme 6). The quantita-
tive formation of iodofulvene 3a was observed immediately.
At the same time, both gold(I) fragments were transferred
onto phenylacetylene to form a s-/p-acetylide complex 9,
which was additionally confirmed by mass spectrometry.
Scheme 3. Formation of iodobenzene as the side product.
GC-MS in every reaction that
employed [IPrAuPh] as an or-
ganogold additive. To evaluate
whether a free cationic iodine
source is involved in this ex-
Scheme 5. Full conversion with catalytic amounts of the non-iodinated diyne.
change process, we conducted
the experiment depicted in
Scheme 3 in deuterated ben-
zene as a solvent. Even though a huge excess of deuterated
benzene was present with respect to the aryl gold com-
pound, only undeuterated iodobenzene could be detected
through GC-MS; no iodobenzene formation accompanied
by formation of the non-iodinated alkyne was detected. This
Scheme 6. Iododeauration of gem-diaurated compound 8.
8638
www.chemeurj.org
ꢂ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2013, 19, 8634 – 8641

Gold-Catalyzed Synthesis of Iodofulvenes
FULL PAPER
tiated the catalytic cycle for this
conversion.
In light of these observations,
we propose a mechanism that is
closely related to that reported
in the context of the formation
of benzofulvenes and benzo-
[2b,c]
pentalenes,
albeit involving
a different pre-equilibrium. As
depicted in Scheme 7, the cata-
lytic cycle is initiated through
ligand exchange between an or-
ganogold additive and the start-
ing iodoalkyne 2a. For this
step, dual-activation catalysts as
well as other organogold com-
pounds are needed. Without
the possibility to transfer iodine
and thereby generate the gold
acetylide 6, no initiation of the
catalysis is possible. Once suffi-
cient amounts of gold acetylide
6
are formed, a dual s-/p-acti-
vation takes place, leading, in a
-endo-dig cyclization process,
Figure 9. Crossover experiments with diynes 2a and 6d.
5
This is a strong evidence for the catalyst transfer also
being facilitated by the transfer of I instead of a proton. To
to the formation of the reactive gold vinylidene II. At this
stage, two possible pathways are reasonable. On the basis of
+
further underline this assump-
tion, we submitted a 50:50 mix-
ture of the iodinated compound
2
a and terminal alkyne 6d to
the catalyst. The relative distri-
bution of the reaction com-
pounds during the course of the
reaction is depicted in Figure 9.
It became clear that the trans-
formation of the iodinated 2a
was significantly faster than the
conversion of the terminal
alkyne 6d. Furthermore, the
transformation of the iodoal-
kyne delivered mainly the iodi-
nated product, with only traces
of 7a formed. This can be ex-
plained by
a faster catalyst
transfer between the iodoal-
kyne and organogold intermedi-
ate, which finally delivered the
iodinated fulvene 3a. Only
after the consumption of the
major part of 2a did the slower
catalyst transfer between the
terminal alkyne 6d and the or-
ganogold intermediates take
place; this then activated 6d
through s-activation, which ini-
Scheme 7. Mechanistic rationale.
Chem. Eur. J. 2013, 19, 8634 – 8641
ꢂ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
8639

A. S. K. Hashmi et al.
our recently published results on the intermolecular CH in-
[3b]
sertion of unactivated alkanes,
pathway A, in which a
direct CH insertion into vinylidene II delivers the mono-aur-
ated species 10, should be favored. Nevertheless, pathway B,
which includes a stepwise reaction, is also reasonable. This
mechanistic alternative would
Scheme 9. Iodination of fulvene 7 with Barluengaꢀs reagent.
be started by an initial [1,5]-hy-
dride shift to the electrophilic
vinylidene carbon to furnish
cation III, which is stabilized by
the gold atom. The next step
consists of addition of the vinyl
gold double bond onto the
cation, followed by elimination
of the gold complex under re-
Scheme 10. Consecutive one-pot reaction.
lease of a monogold species;
thus, species 10 is formed, which exists in equilibrium with
the corresponding gem-di-
agent gave 3a in a low yield, as expected in the range of the
corresponding reaction with the isolated benzofulvene.
To demonstrate the applicability of iodofulvenes as cross-
coupling partners, compound 3a was coupled successfully
with phenylacetylene 11 in a Sonogashira reaction to afford
12 in high yield (Scheme 11).
aurated species 8. Whereas most of the elementary steps are
similar to those involved in the formation of benzofulvenes
from terminal alkynes, there is a big difference in the cata-
lyst transfer step. This takes place between the iodoalkyne
starting material 2a and the vinyl gold intermediate 10 with
formation of iodofulvene 3a and generation of another ace-
tylide molecule 6.
We also investigated the possibility of using an external
iodine source in conjunction with the unfunctionalized ter-
minal alkynes 1, rather than employing the iodoalkynes 2 as
starting materials. In the case of NIS and 5 mol% of a dual-
activation catalyst, no conversion to the final product was
observed (by using GC-MS); only the intermediate iodoal-
kyne 2a was formed even after prolonged reaction times
Scheme 11. Sonogashira coupling with iodofulvene 3a.
(
Scheme 8). The same result was obtained with [P-
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
(tBu) AuNTf ], a catalyst system that was recently applied
Conclusion
3
2
[
10]
for an iodination/nucleophilic addition sequence.
This
might be explained by the blocking of the catalyst by NIS or
small amounts of free succinimide.
The possibility of an iodine/gold exchange instead of the
normal proton/gold exchange for the catalyst transfer step
opens up new pathways in the
field of dual gold catalysis.
From simple iodoalkynes as
starting materials, it is possible
to transfer the iodine into the
final product in a highly regio-
selective fashion. Owing to the
direct gold/iodine exchange in
Scheme 8. Attempts at a one-pot iodination strategy.
the last step of the catalytic
cycle, the position of the gold
On the other hand, the direct electrophilic iodination of
after the cyclization determines the position of the iodine in
the product. This elementary step, which was previously un-
known in gold chemistry, might open up new strategies for
the design of gold-catalyzed reactions with iodinated prod-
ucts as targets. In this investigation, iodofulvenes were ac-
cessible with much higher efficiency than through classical
iodination strategies. The final products can be further func-
tionalized easily in cross-coupling reactions, making them at-
tractive as building blocks for expanded p-systems.
the respective fulvene 7 using the Barluenga reagent
[11]
IPy BF4
gave the desired iodofulvene 3a, albeit in low
2
yield (Scheme 9).
Finally, we attempted a consecutive one-pot reaction
Scheme 10). This approach also furnished the desired prod-
uct 3a without isolation of the intermediary benzofulvene 7.
However, with NIS as the iodination reagent, the reaction
did not reach full conversion, and the decomposition of the
remaining reactants was also observed. The Barluenga re-
(
8640
www.chemeurj.org
ꢂ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2013, 19, 8634 – 8641

Gold-Catalyzed Synthesis of Iodofulvenes
FULL PAPER
e) A. S. K. Hashmi, Angew. Chem. 2005, 117, 7150–7154; Angew.
Chem. Int. Ed. 2005, 44, 6990–6993; f) A. S. K. Hashmi, G. Hutch-
ings, Angew. Chem. 2006, 118, 8064–8105; Angew. Chem. Int. Ed.
Experimental Section
Representative procedure for the synthesis of iodoalkyne 2a employing
: N-iodosuccinimide (1.12 g, 4.98 mmol) and silver nitrate
32.6 mg, 5 mol%, 192 mmol) were added to a solution of terminal alkyne
2006, 45, 7896–7936; g) D. J. Gorin, F. D. Toste, Nature 2007, 446,
395–403; h) A. Fꢄrstner, P. W. Davies, Angew. Chem. 2007, 119,
3478–3519; Angew. Chem. Int. Ed. 2007, 46, 3410–3449; i) E. Jimꢅ-
NIS/AgNO
(
1
(
3
a (700 mg, 3.84 mmol) in a mixture of acetone (50 mL) and water
nez-NfflÇez, A. M. Echavarren, Chem. Commun. 2007, 333–346;
j) A. S. K. Hashmi, Chem. Rev. 2007, 107, 3180–3211; k) Z. Li, C.
Brouwer, C. He, Chem. Rev. 2008, 108, 3239–3265; l) A. Arcadi,
Chem. Rev. 2008, 108, 3266–3325; m) H. C. Shen, Tetrahedron 2008,
0.5 mL). The mixture was stirred for 2 h at room temperature, and then
the crude product was purified by flash column chromatography (SiO
petrol ether (PE)), giving 2a (1.13 g, 3.66 mmol, 95%) as a yellow solid.
2
,
1
R
f
=0.47 (PE); m.p. 628C; H NMR (300 MHz, CD
2
Cl
.18–7.29 (m, 2H), 7.35–7.41 ppm (m, 2H); C NMR (75 MHz, CD
d=10.1 (s), 28.5 (s), 31.2 (q, 3 C), 77.8 (s), 93.4 (s), 103.9 (s), 126.3 (s),
2
): d=1.53 (s, 9H),
6
4, 3885–3909; n) H. C. Shen, Tetrahedron 2008, 64, 7847–7870;
1
3
7
2
Cl ):
2
o) A. S. K. Hashmi, Angew. Chem. 2010, 122, 5360–5369; Angew.
Chem. Int. Ed. 2010, 49, 5232–5241; p) A. Corma, A. Leyva-Pꢅrez,
M. J. Sabater, Chem. Rev. 2011, 111, 1657–1712; q) M. Rudolph,
A. S. K. Hashmi, Chem. Soc. Rev. 2012, 41, 2448–2462.
1
3
1
2
27.5 (d), 128.1 (s), 128.9 (d), 131.6 (d), 132.6 ppm (d); IR (film): n˜ =
060, 2969, 2926, 2897, 2866, 2239, 2210, 2175, 1471, 1454, 1362, 1295,
217, 756 cm ; MS (EI (+), 70 eV): m/z (%): 308 (57) [M] , 293 (56),
À1
+
[
2] a) L. Ye, Y. Wang, D. H. Aue, L. Zhang, J. Am. Chem. Soc. 2012,
67 (15), 212(13), 166 (48), 165 (100), 162 (29); HRMS (EI (+), 70 eV):
1
34, 31–34; b) A. S. K. Hashmi, I. Braun, P. Nçsel, J. Schꢁdlich, M.
Wieteck, M. Rudolph, F. Rominger, Angew. Chem. 2012, 124, 4532–
536; Angew. Chem. Int. Ed. 2012, 51, 4456–4460; c) A. S. K.
+
+
m/z calcd for C14H13I : 308.0056 [M] ; found: 308.0070
.
Representative procedure for the synthesis of iodoalkyne 2c employing
NIS/KOH: Potassium hydroxide (87.0 mg, 1.55 mmol) was added to a sol-
ution of alkyne 1c (150 mg, 619 mmol) in anhydrous methanol (10 mL) at
8C. After stirring for 20 min, N-iodosuccinimide (167 mg, 743 mmol) was
added portion-wise. The suspension was stirred for 30 min at room tem-
perature. Dichloromethane was then added and the mixture was washed
4
Hashmi, M. Wieteck, I. Braun, P. Nçsel, L. Jongbloed, M. Rudolph,
F. Rominger, Adv. Synth. Catal. 2012, 354, 555–562; d) M. M. Hans-
mann, M. Rudolph, F. Rominger, A. S. K. Hashmi, Angew. Chem.
0
2
013, 125, 2653–2659; Angew. Chem. Int. Ed. 2013, 52, 2593–2598;
e) M. M. Hansmann, F. Rominger, A. S. K. Hashmi, Chem. Sci.
013, 4, 1552–1559.
with brine. The organic layer was dried over MgSO
4
and filtered; subse-
2
quent evaporation of the solvent gave 2c (217 mg, 588 mmol, 95%) as a
[
3] a) A. S. K. Hashmi, I. Braun, M. Rudolph, F. Rominger, Organome-
tallics 2012, 31, 644–661; b) A. S. K. Hashmi, M. Wieteck, I. Braun,
M. Rudolph, F. Rominger, Angew. Chem. 2012, 124, 10785–10789;
Angew. Chem. Int. Ed. 2012, 51, 10633–10637.
4] S. Hummel, S. F. Kirsch, Beilstein J. Org. Chem. 2011, 7, 847–859.
5] M. Jurí cˇ ek, K. Stout, P. H. J. Kouwer, A. E. Rowan, Org Lett. 2011,
1
yellow solid. M.p. 1058C; H NMR (300 MHz, CDCl
.85 (s, 3H), 3.87 (s, 3H), 6.83 (s, 1H), 6.86 ppm (s, 1H); C NMR
75 MHz, CD Cl ): d=7.6 (s), 28.3 (s), 31.2 (s), 31.3 (q, 3 C), 56.1 (q, 2
C), 93.3 (s), 102.0 (s), 113.6 (d), 114.4 (d), 119.0 (s), 121.2 (s), 148.2 (s),
3
): d=1.36 (s, 9H),
1
3
3
(
2
2
[
[
1
1
7
3
C
49.5 ppm (s); IR (KBr): n˜ =3432, 3087, 2967, 2864, 2603, 2222, 1599,
558, 1508, 1463, 1395, 1349, 1254, 1221, 1120, 1033, 1004, 913, 860, 830,
1
3, 3494–3497.
À1
50, 735, 702, 664, 612, 543, 526, 436 cm ; MS (EI (+), 70 eV): m/z (%):
[
6] M. V. Russo, C. Lo Sterzo, P. Franceschini, G. Biagini, A. Furlani, J.
Organomet. Chem. 2001, 619, 49–61.
+
68 (100) [M] , 353 (28); HRMS (EI (+), 70 eV): m/z calcd for
+
+
16
H
17IO
2
: 368.0268 [M] ; found: 368.0281
.
[
7] CCDC-923612 (2l), CCDC-923613 (3h), and CCDC-923614 (3i),
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.
Representative procedure for the synthesis of iodofulvene 3a: The gold
catalyst DAC-IPr-NTf (13.1 mg, 8.76 mmol, 5 mol%) was added to a sol-
ution of iodoalkyne 2a (54.0 mg, 175 mmol) in anhydrous dioxane
0.35 mL, 0.5m). The reaction mixture was stirred at 508C for 2.5 h until
2
(
complete conversion was achieved. The solvent was removed under re-
duced pressure and the crude product was purified by flash column chro-
[8] A. S. K. Hashmi, T. Lauterbach, P. Nçsel, M. Højer Vilhelmsen, M.
Rudolph, F. Rominger, Chem. Eur. J. 2013, 19, 1058–1065.
[9] For reports on the reaction of organo gold compounds with I re-
+
matography on silica gel (PE) to give iodofulvene 3a as yellow oil
1
(
40.0 mg, 130 mmol, 74%). R
f
(PE)=0.47; H NMR (300 MHz, CD
2
Cl
2
):
agents, see: a) F. Gagosz, A. Buzas, Synlett 2006, 2727–2730; b) S. F.
Kirsch, J. T. Binder, B. Crone, A. Duschek, T. T. Haug, C. Liebert,
H. Menz, Angew. Chem. 2007, 119, 2360–2363; Angew. Chem. Int.
Ed. 2007, 46, 2310–2313; c) M. Yu, G. Z. Zhang, L. M. Zhang, Org.
Lett. 2007, 9, 2147–2150; d) M. Schuler, F. Silva, C. Bobbio, A. Tess-
ier, V. Gouverneur, Angew. Chem. 2008, 120, 8045–8048; Angew.
Chem. Int. Ed. 2008, 47, 7927–7930; e) M. Yu, G. Z. Zhang, L. M.
Zhang, Tetrahedron 2009, 65, 1846–1855; f) L. W. Ye, L. M. Zhang,
Org. Lett. 2009, 11, 3646–3649; g) L.-P. Liu, G. B. Hammond, Chem.
Asian J. 2009, 4, 1230–1236; h) A. S. K. Hashmi, T. D. Ramamurthi,
F. Rominger, J. Organomet. Chem. 2009, 694, 592–597; i) A. S. K.
Hashmi, T. D. Ramamurthi, M. H. Todd, A. S.-K. Tsang, K. Graf,
Aust. J. Chem. 2010, 63, 1619–1626; j) M. S. Hadfield, A.-L. Lee,
Org. Lett. 2010, 12, 484–487; k) B. Gockel, N. Krause, Eur. J. Org.
Chem. 2010, 311–316; l) H. H. Liao, R. S. Liu, Chem. Commun.
d=1.43 (s, 6H), 2.96 (d, J=2.9 Hz, 2H), 6.56 (t, J=2.9 Hz, 1H), 7.15–
1
3
7
.20 (m, 2H), 7.31–7.36 (m, 1H), 7.50–7.53 ppm (m, 1H); C NMR
(
75 MHz, CD Cl ): d=26.4 (q, 2 C), 39.5 (s), 57.4 (t), 77.1 (q), 121.1 (d),
2
2
1
1
1
2
21.8 (d), 125.1 (d), 128.4 (d), 129.9 (s), 133.1 (d), 147.8 (s), 150.6 (s),
64.8 ppm (s); IR (film): n˜ =3066, 2923, 2901, 2863, 1706, 1600, 1461,
À1
433, 1199, 917, 758, 708 cm ; UV/Vis (DCM): lmax (log e)=246 (5.15),
67 (5.21), 302 (4.57), 314 (4.44), 354 nm (4.33); MS (EI (+), 70 eV): m/z
+
(
(
%): 308 (70) [M] , 293 (89), 267 (12), 217 (12), 212(11), 181 (27), 166
81), 165 (100), 162 (21); HRMS (EI (+), 70 eV): m/z calcd for C14H13I :
+
+
3
08.0056 [M] ; found: 308.0056.
Acknowledgements
2
011, 47, 1339–1341; P. Kothandaraman, S. R. Mothe, S. S. Toh,
P. W. Chan, J. Org. Chem. 2011, 76, 7633–7640.
10] A. Leyva-Pꢅrez, P. Rubio-Marquꢅs, S. S. Al-Deyab, S. I. Al-Resayes,
A. Corma, ACS Catal. 2011, 1, 601–606.
This work was supported by the Deutsche Forschungsgemeinschaft (SFB
23). Gold salts were generously donated by Umicore AG & Co. KG.
[
[
6
11] J. Barluenga, Pure Appl. Chem. 1999, 71, 431–436.
[
1] For representative reviews on gold catalysis, see: a) G. Dyker,
Angew. Chem. 2000, 112, 4407–4409; Angew. Chem. Int. Ed. 2000,
3
2
9, 4237–4239; b) A. S. K. Hashmi, Hung. Build. Bull. Gold. Bull.
003, 36, 3–9; c) A. S. K. Hashmi, Gold Bull. 2004, 37, 51–65; d) A.
Received: February 7, 2013
Revised: March 29, 2013
Hoffmann-Rçder, N. Krause, Org. Biomol. Chem. 2005, 3, 387–391;
Published online: May 7, 2013
Chem. Eur. J. 2013, 19, 8634 – 8641
ꢂ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
8641