A Remarkably Simple Hybrid Surfactant-NHC Ligand, Its Gold-Complex, and Application in Micellar Catalysis

Article abstract of DOI:10.1002/chem.201502542

A combination of an N-heterocyclic carbene (NHC) ligand and a structurally simple surfactant has been realized, the hybrid surfactant-NHC. The related gold complex was synthesized, fully characterized, and applied in catalysis. This remarkably simple strategy allows, in combination with a co-surfactant, the application of gold catalysis in water. Just merge it! The hybrid of a surfactant and an N-heterocyclic carbene (NHC) ligand is reported and applied for the synthesis of the derived gold complex (see scheme). The new resulting NHC-based metallosurfactant can interact with surfactants to form micelles and allows micellar catalysis for gold catalysis in water.

Full text of DOI:10.1002/chem.201502542

DOI: 10.1002/chem.201502542
Communication
&
Green Chemistry
A Remarkably Simple Hybrid Surfactant–NHC Ligand, Its Gold-
Complex, and Application in Micellar Catalysis
Andreas Rühling,[a] Hans-Joachim Galla,[b] and Frank Glorius*[a]
ample, phosphines and amines as ligands.[8] However, only
Abstract: A combination of an N-heterocyclic carbene
a few publications describe the use of N-heterocyclic carbenes
(NHC) ligand and a structurally simple surfactant has been
(NHCs) as ligands in micellar catalysis.[9] In terms of metallosur-
realized, the hybrid surfactant–NHC. The related gold com-
factants there is only one single report, describing the use of
plex was synthesized, fully characterized, and applied in
a metal–NHC species. In this case, the NHC is bound by the
catalysis. This remarkably simple strategy allows, in combi-
metal to the surfactant, and the properties of the rather com-
nation with a co-surfactant, the application of gold cataly-
plex surfactant are unrelated to the NHC ligand.[10] As our
sis in water.
group is interested in the design and application of NHCs in
new and undescribed fields, not only in the term of catalysis,
we envisioned combining the properties of a surfactant with
Nowadays the majority of reactions in organic chemistry are
conducted in organic solvents, often to ensure a good solubili-
ty of the reaction partners and catalysts. Therefore, organic sol-
vents account for the biggest part of the waste generated
during the reaction and its workup.[1] Hence it is highly desira-
ble to reduce the amount of required solvent, or as an alterna-
tive to use more environmentally friendly solvents, with water,
as Nature’s favorite solvent, being a logical and green choice.[2]
Different approaches were established to transfer organic reac-
tions into water as the reaction medium, including phase-
transfer catalysis,[3] water soluble
an NHC, thus forming a new hybrid surfactant–NHC ligand.
This new ligand would allow the interaction with a much sim-
pler and commercially available surfactant and still offer the
characteristic advantages of the NHC ligands (Figure 1).[11] The
main advantage offered by this system would be the separa-
tion of the hydrophobic part of the surfactant and the nitro-
gen substituents, thus allowing on demand modifications of
the ligand head group without influencing the properties of
the surfactant, which are located in the backbone of the
ligand.
catalysts,[4] and micellar arrays,[5]
which mimic organic solvents as
the reaction medium. Micellar
arrays are spontaneously formed
by amphiphilic species (surfac-
tants) in water even at very low
concentrations.[6]
Well-studied
and established surfactants, for
example, are sodium dodecyl
sulfate (SDS) and TPGS-750m,[7]
a tailor-made surfactant estab-
lished by Lipshutz et al.
Several reports describe the
incorporation of metal catalysts
in micellar arrays using, for ex-
Figure 1. Combination of an NHC ligand and a surfactant.
Based on our recent report on NHCs[12] with long alkyl
chains in the backbone for the stabilization of nanoparticles,
we decided to combine the cationic surfactant CTAB and the
NHC IPr for three reasons:
[a] A. Rühling, Prof. Dr. F. Glorius
Westfälische Wilhelms-Universität Münster
Organisch-Chemisches Institut
Corrensstrasse 40, 48149 Münster (Germany)
E-mail: glorius@uni-muenster.de
1) CTAB together with SDS is one of the cheapest commercial-
ly available surfactants and is well understood;[13] addition-
ally it offers the same charge as IPr·HCl at the head group.
2) IPr, which has been studied in detail, is stable as a free car-
bene, and forms robust and catalytically active complexes
with gold.[14]
[b] Prof. Dr. H.-J. Galla
Westfälische Wilhelms-Universität Münster
Institut für Biochemie
Wilhelm-Klemm-Straße 2, 48149 Münster (Germany)
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201502542.
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Scheme 1. Synthesis of the hybrid surfactant–NHC ligand 1 and the corresponding gold-complex 4. THT=tetrahydrothiophene.
3) The head group and backbone would offer an orthogonal
and simple set of signals by NMR spectroscopy, which
would simplify the analysis, under micellar conditions.
Table 1. Initial screening.[a]
The new hybrid surfactant–NHC ligand 1 can be easily synthe-
sized by a two-step, one-pot procedure starting from formami-
dine 2 and a-bromoketone 3 in a moderate 75% yield.[15] The
corresponding AuI-complex 4 was then prepared in 86% yield
by using a procedure reported by Nolan et al. (Scheme 1).[16]
The new complex is air and moisture stable for months and
was fully analyzed. We moved on and tried to apply 4 as a cata-
lyst in a micelle, to prove our concept of combining a NHC
and a surfactant in one ligand to be valid. We chose the hydra-
tion of 1,2-diphenylacteylene to be our benchmark reaction for
two main reasons: 1) Nolan et al. showed with this reaction
the tremendous potential of AuI–NHC complexes in catalysis[17]
and 2) as the reaction is carried out in aqueous media it offers
the perfect opportunity to test and compare our micellar ap-
proach.
Entry
Surfactant
4/AgBF4 [mol%]
Conversion [%][b]
1
2
3
4
5
6
7
8[c]
9[d]
10[e]
11[f]
DPPC
CTAB
SDS
TPGS-750-M
SDS
SDS
–
SDS
SDS
1
1
1
1
15
0
>95
trace
trace
trace
trace
trace
>95
0
no AgBF4
no 4
1
1
1
1
1
SDS
SDS
trace
[a] DPPC=dipalmitoylphosphatidylcholine; CTAB=cetyltrimethylammoni-
um bromide. TPGS-750m=DL-a-Tocopherol methoxypolyethylene glycol
succinate. All reactions were run on a 0.5 mmol scale at a substrate con-
centration of 1m. [b] Determined by GCMS. [c] With 0.125 wt.% SDS
(below CMC of SDS). [d] With 0.5 wt.% of SDS. [e] Reaction performed at
room temperature. [f] Standard [IPrAuCl] was used instead of 4.
In the initial test reaction 1,2-diphenylacetylene was reacted
in the presence of 1 mol% (4), 1 mol% AgBF4, and 2.5 wt.% of
a given surfactant (Table 1). When a cationic (Table 1, entry 2)
or a neutral surfactant (entries 1 and 4) was used, no reaction
or only low conversion could be observed, while the anionic
surfactant (entry 3) showed a conversion greater than 95%.
The anionic head group seems to be crucial for the cationic
AuI complex to insert into the micelle, as an attractive interac-
tion between the positive and negative charges is beneficial.
In comparison, the cationic AuI complex and a positive surfac-
tant’s head group could repel each other. Control experiments
(entries 5 to 7) showed that all three components are necessa-
ry for the reaction. If the surfactant was used in amounts
below the CMC (critical micelle concentration) (entry 8) only
traces could be observed by GCMS, an indicator that a micelle
is needed for reactivity. Applying the standard gold complex
[Au(IPr)Cl] ended up in only trace amounts of product
(entry 11). This strengthens our hypothesis about the interac-
tion between the surfactant and the cationic AuI complex,
which is generated in situ from 4 and AgBF4. Without the two
long alkyl chains in the backbone of the ligand no interaction
between the hydrophobic parts is feasible and therefore no in-
corporation into the micelle is possible. Further optimization
studies showed that a surfactant concentration as low as
0.5 wt.% is sufficient for a conversion greater than 95%
(entry 9). With the optimized conditions in hand, we focused
on the substrate scope of our transformation (Scheme 2). Des-
oxybenzoin 5a was obtained in high yield, and could be even
increased to 94% on a 5 mmol scale with a reduced catalyst
loading of only 0.1 mol%. This demonstrates the high efficien-
cy and robustness of our hybrid surfactant–NHC approach.
Only moderate yields between 30 to 59% (5b–e) were ob-
tained, when the starting material was a terminal alkyne. An
exception in this case was 5k with a high yield of 89%. The
functional-group tolerance of our transformation represents
a nice feature set for further functionalization, esters (5g,
61%), bromines (5h, 82%), protected amines (5j, 85%), and al-
cohols (5l, 87%) were tolerated without problems and the cor-
responding products were obtained in moderate to high
yields.
Assuming that the mechanism of this transformation is
equivalent to the one in organic solvents,[18] the type of self-as-
sembly and interaction remains unclear. To answer these ques-
tions we conducted three sets of experiments. At first dynam-
ic-light scattering (DLS) measurements provided insight if
a change of size occurs, when the SDS micelles are interacting
with either 1 or 4 (Figure 2). In both cases a clear formation of
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er, keeping in mind that the active complex during
the catalysis is positively charged like 1, a stronger in-
teraction in comparison to 4 is viable. From the re-
sults of DLS and film balance measurements we can
conclude that, under the reaction conditions the for-
mation of a mixed micelle, with a head-to-head ori-
entation of the two components is the most likely
scenario. At last we wanted to address the level of
immersion of the active gold complex into the mi-
celle. Therefore, we synthesized derivatives of 4 with
different chain lengths (shorter: C7H15; longer: C15H31)
in the backbone and measured kinetics of our stan-
dard reaction (Figure 4). A short chain in the back-
bone of our hybrid surfactant-NHC would force the
gold atom of 4 to be immersed in the micelle while
a long chain would bring the gold atom out of the
micelle. In both cases the reaction rate should de-
crease, as the two reactants get separated. If the
chain length is optimal the gold atom would be
placed directly in the boundary layer of the micelle
and the highest reaction rate should be observed.
As assumed, the cationic 4 shows the highest reac-
tion rate, which indicates that the gold atom is locat-
ed in the boundary layer of the micelle. To support
our hypothesis that we create mixed micelles with
Scheme 2. All reactions were run on a 0.5 mmol scale at a substrate concentration of
1m. Given yields, are isolated yields; [a] Reaction performed on a 5 mmol scale with
0.1 mol% [Au] and [Ag] at 808C for 2 days. [b] Yields determined by GC-FID with Mesity-
lene as the internal standard; [c] Ratio determined by H NMR spectroscopy. [d] 2 mol%
of [Au] and [Ag] used, reaction run for 2 days.
1
a larger species, potentially two, is visible. Notably the species
look to be the same for 1 and 4, which indicates a similar inter-
action between SDS and our surfactant ligand or the related
gold metallosurfactant. Next we performed film balance meas-
urements to prove the attractive interaction between SDS and
1 or 4. If a stable film formation is viable electrostatic interac-
tions demand a head-to-head assembly of SDS and 1 or 4
(Figure 3). SDS and 1 clearly form a stable film in a two to one
mixture, which is indicated by the plateau in the surface pres-
sure at higher pressure. The combination of SDS and 4 shows
not such a clear plateau, but still a change in the slope at
higher pressure, which proves the film formation. As 4 bears
a less polar head group than 1, this result is expected. Howev-
Figure 3. Film balance measurements of SDS and in combination with 1 or
4. c: SDS pure; c: SDS, Sur-IPr-HBr (2:1); c: SDS, Sur-IPr-Au-Br (2:1).
Figure 2. DLS measurements of SDS and in combination with 1 or 4. c:
SDS pure; c: SDS, Sur-IPr-HBr (2:1); c: SDS, Sur-IPr-Au-Br (2:1). Milli-Q.
Water (pH 5.6) 3.3 cm2 minÀ1, 208C.
^
Figure 4. Kinetics of our model reaction with different alkyl chain lengths.
:
~
&
C7-IPr; : C11-IPr; : C15-IPr.
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right: zoom with a 50nm scale bar).
Acknowledgement
Generous financial support by the European Research Council
under the European Community’s Seventh Framework Pro-
gram (FP7 2007—2013)/ERC Grant Agreement 25936, and by
the DFG (Leibniz Award) is acknowledged. We also thank Cor-
nelia Weitkamp for great experimental support, S. Wulff for
measuring DLS and Film balance, Dr. M. Peterlechner for meas-
uring TEM images and Dr. C. Richter for helpful discussions.
Keywords: gold catalysis · green chemistry · micelles · N-
heterocyclic carbenes · surfactant
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Received: June 30, 2015
Published online on July 27, 2015
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