Dual gold-catalyzed head-to-tail coupling of iodoalkynes

Article abstract of DOI:10.1002/chem.201406594

Various haloalkynes are converted in the presence of a dual activation gold catalyst. Via a dual activation process a completely atom economic head-totail coupling delivers gem-dihalogenated conjugated enynes as valuable building blocks for organic synthe

Full text of DOI:10.1002/chem.201406594

DOI: 10.1002/chem.201406594
Communication
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Gold Catalysis
Dual Gold-Catalyzed Head-to-Tail Coupling of Iodoalkynes
Steffen Mader,[a] Lise Molinari,[a] Matthias Rudolph,[a] Frank Rominger,[a] and
A. Stephen K. Hashmi*[a, b]
Abstract: Various haloalkynes are converted in the
presence of a dual activation gold catalyst. Via a dual
activation process a completely atom economic head-to-
tail coupling delivers gem-dihalogenated conjugated
enynes as valuable building blocks for organic synthesis.
Reactive intermediates that enable strategies for a diverse set
of downstream transformations play an important role for the
ongoing success of homogeneous gold catalysis.[1] Recently,
gold vinylidenes, resulting from the cyclization of diynes by
Scheme 1. a) Fꢀrstner’s phenanthrene synthesis; b) planned CH insertion of
benzylic CH groups.
dual catalysis[2] or by the reaction of gold acetylides with ap-
propriate leaving groups,[3] allowed the design of various syn-
thetically useful transformations. Furthermore, gold vinylidenes
derived from a 1,2-iodo migration from iodoalkynes have also
been discussed in several contributions.[4]
Inspired by a gold-catalyzed synthesis of phenanthrenes
through a formal CH insertion of aryl CH bonds at a gold vinyl-
idene (Scheme 1a)[2a] and by the observed high reactivity for
diyne-derived vinylidenes (even CH insertions of unactivated
sp3-CH bonds are possible), we assumed that a CH insertion of
a benzylic CH bond into a gold vinylidene derived by a 1,2-hal-
ogen migration might also be feasible (Scheme 1b). However,
to our surprise, a completely different pathway, namely
a head-to-tail dimerization of haloalkynes to synthetically
valuable gem-dihalogenated enyne systems, was observed. To
our knowledge, this reaction is to date unprecedented; most
probably this originates from the fact that other transition
metals are prone to redox chemistry that initiate different
types of reactivity.[5] Our study on this new type of intermolec-
ular dual gold-catalyzed process is discussed herein.
Scheme 2. Initial observation of a head-to-tail dimerization of bromoalkyne
1a.
Complete consumption of the starting material took place, but
no CH insertion or 1,2-halogen migration was observed.
Instead, the gem-dibrominated enyne 2a, resulting from an
unexpected head-to-tail alkyne dimerization of the starting
bromoalkyne, was isolated in 64% yield.[6]
Considering the structure of the product formed, we as-
sumed that a gold acetylide should be one of the intermedi-
ates of the reaction. This assumption was based on our recent
findings where we could demonstrate that gold acetylides can
be formed via ligand exchange from organogold(I) species and
haloalkynes. This process enabled the utilization of iodoalkynes
as starting materials for dual gold-catalyzed reactions with
diyne starting materials.[7] A head-to-tale dimerization of termi-
nal alkynes has recently been reported by the Zhang group,[8j]
and we could further demonstrate that s,p-dinuclear propyne–
gold acetylides (DAC=dual-activation catalysts) led to a better
efficiency of this reaction.[9] As a consequence, we considered
DAC catalysts or mixtures of organogold compounds with cat-
ionic gold species for the dimerization of haloalkynes as well.
Indeed, a significant improvement was possible by using DAC
3a and an isolated yield of 72% of 2a was obtained
(Scheme 3). It is noteworthy that even chloroalkyne 1b could
be dimerized in moderate yield under the same conditions.
As an initial test reaction, the bromoalkyne 1a was convert-
ed under Fꢀrstner’s conditions for 12 h in toluene (Scheme 2).
[a] M. Sc. S. Mader, Dr. L. Molinari, Dr. M. Rudolph, Dr. F. Rominger,+
Prof. Dr. A. S. K. Hashmi
Organisch-Chemisches Institut
Ruprecht-Karls-Universitꢀt Heidelberg
Im Neuenheimer Feld 270, 69120 Heidelberg (Germany)
Fax: (+49)6221-54-4205
E-mail: hashmi@hashmi.de
Homepage: http://www.hashmi.de
[b] Prof. Dr. A. S. K. Hashmi
Chemistry Department, Faculty of Science, King Abdulaziz University
Jeddah 21589 (Saudi Arabia)
[+] Crystallographic investigation
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201406594.
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Scheme 5. Solvent optimization.
Table 1. Catalyst optimization.
Scheme 3. Transformation of haloalkynes with dual-activation catalysts.
Entry
Catalyst
Yield [%]
1
2
3
4
5
6
7
8a
9
10
11
DAC–PF6 3a (5 mol%)
DAC–SbF6 3b (5 mol%)
DAC–OTs 3c (5 mol%)
DAC–NTf2 3d (5 mol%)
DAC–OTf 3e (5 mol%)
DAC–BF4 3 f (5 mol%)
AuCl3 (10 mol%)
40
40
52
52
47
45
12
10
14
0.5
–
Scheme 4. Conversion of iodoalkyne 1c.
AuCl (20 mol%)
[IPrAu]NTf2 (10 mol%)
[IPrAuPh] (10 mol%)
[IPrAu–propinyl] (10 mol%)
A different scenario was observed with the iodoalkyne test
substrate 1c (Scheme 4). Its conversion delivered a mixture of
different products. Among them, the desired product 2c was
obtained, but it could not be separated from several byprod-
ucts with the same polarity. The only separable compound was
a tail-to-tail dimerization product 4c in 38% yield. The struc-
ture of the obtained symmetric dialkyne was further verified
by the results of an X-ray single crystal structure analysis
(Figure 1).[10]
a) reaction in toluene, 20 h, 808C.
Lower yields were obtained with substrate 1e bearing
a methyl group in the ortho position of the aromatic moiety.
As a consequence, we performed an additional catalyst screen-
ing in acetonitrile as solvent (Table 1). In a first series of experi-
ments, different counter anions for the dual-activation catalysts
3 were applied. Indeed, a moderate counter anion effect was
observed and [NTf2]À and [OTs]À turned out to be most effi-
cient (Table 1, entries 1–6). AuCl3 and AuCl were not suitable
for this system (Table 1, entries 7 and 8), as was the case for
[IPrAu]NTf2 (entry 9). Test reactions with organogold species in
the absence of a cationic gold species showed no conversion
(Table 1, entries 10 and 11).
Under the optimized conditions, various iodoalkynes were
converted in order to evaluate the scope of the transformation.
With simple iodophenylacetylene, the corresponding enyne
could be obtained in 80% yield (Table 2, entry 1). The lower
yield for starting material 1e (52%; Table 2, entry 2) might be
due to the steric bulk of the methyl group in the ortho posi-
tion. This conclusion comes from the conversion of the corre-
Figure 1. Solid-state molecular structure of 4. Thermal ellipsoids are drawn
at 50% probability level.
To optimize the iodoalkyne dimerization, simple iodophenyl-
acetylene was converted using different solvents. For this
system no head-to-head dimerization was observed; instead,
in toluene, mono-iodinated enyne 5 was obtained as
an inseparable by-product in 20% yield (Scheme 5).
Although in THF only polymerization took place, ace-
tonitrile turned out to be a suitable solvent for a se-
lective dimerization. In this case, less than 1% yield
of the mono-iodo compound 5 was obtained (77%
yield of 2d).
Scheme 6. Stoichiometric reaction with [IPrAuPh].
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tronically comparable. Therefore the higher yield of 80% must
result from decreased steric shielding (Table 2, entry 3). The
same effect was observed for substrates 1g and 1h (Table 2,
entries 4 and 5). A tert-butyl substituent in the para position
was also well tolerated (Table 2, entry 6). Difluoro-substituted
electron-deficient substrate 1i smoothly delivered the
corresponding enyne 2i in good yield (Table 2, entry 7). Next
we considered aliphatic iodoalkynes as starting materials as
well. Indeed with iodohexyne 1j the desired product was
obtained, but yields were only moderate (Table 2, entry 8).
To gain further insights about the initiation and the catalyst
transfer step, iodophenylacetylene 1d was converted in the
presence of stoichiometric amounts of [IPrAuPh] (Scheme 6).
Indeed, the formation of the expected gold acetylide 6 could
be detected by 1H NMR spectroscopy. Analyzing the mixture
by GC-MS revealed that, besides the expected iodobenzene
(that should result from a catalyst transfer, a thermodynamically
driven halogen–metal exchange of both starting materials to
provide 6 and 7), a head-to-head dimerization also took place.
In addition, even diphenylacetylene as cross-coupling product
was detected in significant amounts, an evidence for a possible
additional redox catalytic cycle that might be in operation.[11]
Based on this finding and analogies to the synthesis of iodo-
fulvenes,[7] we postulate the mechanism that is depicted in
Scheme 7. The initiating step would be a transfer of the two
Table 2. Substrate scope.
Entry
1
1
2 (yield [%])
1d
2d (80%)
2
3
1e
2e (52%)
1 f
1c
1g
2 f (80%)
4
2c (51%)
5
2g (74%)
6
1h
2h (79%)
Scheme 7. Mechanistic proposal.
7
8
{IPrAu} fragments by the dual-activation catalyst.[9] In the next
step, the cationic gold species activates the triple bond of an-
other iodoalkyne, which is then attacked by the s-activated
gold acetylide. This intermolecular dual-catalyzed reaction de-
livers vinyl gold species II. Finally, catalyst transfer onto a new
substrate molecule releases the product and regenerates
a gold acetylide. In this step, a competing protodemetalation
can explain the formation of monoiodinated alkenes as
byproducts. The mechanism of the catalyst transfer onto
iodoalkynes remains unclear, but stoichiometric experiments,
as well as the formation of significant amounts of Glaser-type
head-to-head products in some reactions hint that a possible
1i
1j
2i (75%)
2j (55%)
sponding starting material 1 f bearing the methyl group in the
para position of the aromatic system, which should be elec-
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In conclusion, we have shown that, in the presence of
a dual-activation catalyst, haloalkynes can be dimerized in
a head-to-tail fashion. This completely atom-economic reaction
demonstrates that iodoalkynes can even serve as substrates
for dual catalyzed reactions in an intermolecular fashion. From
easily accessible iodoalkynes, gem-dihalogenated enynes,
valuable building blocks in organic synthesis, can be obtained.
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Keywords: alkenes
· alkynes · dual activation · gold ·
halogenated compounds
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Received: December 22, 2014
Published online on && &&, 0000
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Communication
COMMUNICATION
&
Gold Catalysis
S. Mader, L. Molinari, M. Rudolph,
F. Rominger, A. S. K. Hashmi*
Various haloalkynes are converted in
the presence of a dual-activation gold
catalyst. Through a dual activation
process, a completely atom-economic
head-to-tail coupling delivers gem-
dihalogenated conjugated enynes as
valuable building blocks for organic
synthesis.
&& – &&
Dual Gold-Catalyzed Head-to-Tail
Coupling of Iodoalkynes
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