Using sodium acetate for the synthesis of [Au(NHC)X] complexes

Article abstract of DOI:10.1039/d0dt02240c

The role of sodium acetate in the synthesis of [Au(NHC)Cl] complexes was examined. The use of this base was also investigated for the activation of C-H and S-H bonds by experimental and computational methods. The synthetic use of NaOAc to assemble these complexes is applicable to a wide range of NHCs and proceeds under air, under mild conditions and using technical grade green solvents.

Full text of DOI:10.1039/d0dt02240c

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DOI: 10.1039/D0DT02240C
ARTICLE
Using sodium acetate for the synthesis of [Au(NHC)X] complexes§
Thomas Scattolin,a Nikolaos V. Tzourasa, Laura Falivene,b Luigi Cavallob and Steven P. Nolan*a
Received 00th January 20xx,
Accepted 00th January 20xx
The role of sodium acetate in the synthesis of [Au(NHC)Cl] complexes was examined. The use of this base was also
investigated for the activation of C-H and S-H bonds by experimental and computational methods. The synthetic use of
NaOAc to assemble these complexes is applicable to a wide range of NHCs and proceeds under air, under mild conditions
and using technical grade green solvent
DOI: 10.1039/x0xx00000x
Introduction
N-heterocyclic carbenes (NHCs), first isolated by Arduengo
in 1991, have become of paramount importance in the last two
decades as efficient organocatalysts1 and above all, have
the corresponding Ag(I) or Cu(I) derivatives (see, Scheme 1, A
and B).15
A more sustainable and user-friendly approach has been
recently reported by Gimeno16 and our group17 and permits the
direct reaction between the imidazolium salt (the free NHC
precursor) and a common gold(I) precursor ([Au(DMS)Cl] (DMS
= dimethylsulfide) or [Au(tht)Cl] (tht = tetrahydrothiophene), in
the presence of a weak base such as K2CO316a, 17a, NBu4(acac)16b
or NEt3,17b and this under mild conditions and non-anaerobic
conditions. The mechanism of action of NEt3 has been
postulated as a Concerted-Metallation-Deprotonation (CMD)–
like mechanism.
become
a privileged ligand class supporting numerous
transition metal,2 main group3 and f-block complexes.4
A
number of these compounds have become standards in
homogeneous and heterogeneous catalysis5,6 and, by virtue of
the strength of the metal-carbenic carbonbond, these have also
most recently been studied in the field of material science7 and
medicinal chemistry.8 The latter area especially studied for the
design of potent and selective anticancer8a-b and antimicrobial8a
agents.
In this context, several research groups have focused on the
synthesis and applications of well-defined organogold
compounds. Among these distinct complexes, a position of
special importance is occupied by the [Au(NHC)Cl] motif9 as it
can be elaborated into catalytic species in situ10 but more
importantly, we feel, into powerful synthons, such as
[Au(NHC)OH],11 [Au(NHC)(aryl)]12 and [Au(NHC)(acetonyl]13
complexes. The versatility of these well-defined synthons is
clear as they can be transformed into a plethora of gold-NHC
derivatives and catalysts.11-14
A. FREE CARBENE
ROUTE
N
N
N
N
N
N
[Au(DMS)Cl]
-DMS
strong base
R
R
R
R
R
R
H
Cl
Au
Cl
B. TRANSMETALLATION
ROUTE
0.5 M2O
(M = Ag, Cu)
N
N
N
N
N
N
[Au(DMS)Cl]
-MCl, -DMS
R
R
R
R
R
R
-0.5 H2O
H
Cl
M
Au
Cl
Cl
C. WEAK BASE
ROUTE
The importance of such well-defined compounds and their
emerging uses in numerous areas of synthesis are clear drivers
to develop operationally simpler assembly methods.
[Au(NHC)Cl] complexes have historically been accessed through
the free carbene route or by a transmetallation of the NHC from
N
N
N
N
N
N
[Au(DMS)Cl]
-DMS
weak base
R
R
R
R
R
R
H
H
Cl
AuCl2
Au
Cl
a. Department of Chemistry and Center for Sustainable Chemistry, Ghent University,
Krijgslaan 281 (S-3), 9000, Ghent, Belgium. E-mail: steven.nolan@ugent.be
b. Department KAUST Catalysis Centre, KCC, King Abdullah University of Science and
Technology, Thuwal-23955-6900, Saudi Arabia.
Scheme 1. Most common synthetic routes to [Au(NHC)Cl]
§ Dedicated to the memory of our friend and colleague Professor Edwin D. Stevens.
The extent to which any weak base can be used to mediate this
[Au(NHC)Cl] synthesis has not been closely examined (Scheme
1, C). One weak base that could prove useful and one that has
thus far not been deployed in the “weak base approach” to M-
†
Electronic Supplementary Information (ESI) available: Synthetic procedure,
characterisation and computational data. For ESI See DOI: 10.1039/x0xx00000x
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NHC complex synthesis is NaOAc. This base is inexpensive and It is interesting to note that the activation barrierVbieewtAwrteicelenOntlhinee
significantly weaker (pKb water = 9.25) than K2CO3 or NEt3 (pKb water well-known aurate intermediate and DtOhI:e10.f1i0n3a9l/Ds0pDeTc0i2e2s40iCs
= 3.67 and 3.25, respectively).18 We hypothesised that such a considerably lower in the case of NaOAc to that found for NMe3
base might also productively be used in the weak base approach (Fig. S14 and S15 in ESI). This confirms our hypothesis that
and at the same time be a litmus test of the limitations of this NaOAc could be used but more interestingly shown that the
synthetic route.
energy barrier leading to a productive reaction depends very
It should be noted that past reports on M-NHC complex little on the strength of the base used.
synthesis have disclosed the use of this weak base but under
Spectroscopic data and theoretical calculations support
fairly harsh reaction conditions (80-120 °C for several hours) that, on the basis of the low acidity of the aurate intermediate
and above all using environmentally deleterious solvents such (pka MeCN/water ≈ 21), it is very difficult to hypothesize the in situ
as dimethyl sulfoxide19a or dimethyl formamide.19b
formation of free carbene and subsequent metallation using a
In 2017, Tunik and co-workers reported on the reaction weak base.17b
between bisbenzimidazolium salts and [Au(tht)Cl] in the
presence of NaOAc in methanol at room temperature.20 Reactivity of Au(NHC)Cl complexes towards phenylacetylene and
Unfortunately, the final complexes, because of reported poor pentafluorobenzene (C-H activation)
solubility, in this study were not fully characterised and
therefore the usefulness of the method was not recognised. We
felt NaOAc worthy of further investigation with a series of
common NHC ligand precursors.
Having shown that NaOAc could assist in the synthesis of
[Au(NHC)Cl] (2) complexes, we wondered if treating 2 with
excess NaOAc could lead to further functionalization.
The first reaction examined dealt with the activation of C-H
bonds. In the first instance, we examined the reactivity of 2 with
acidic C-H bonds of phenylacetylene (pKa water = 23.221) in the
presence of NaOAc to possibly obtain Au-alkynyl complexes of
Results and Discussion
Synthesis of Au(NHC)Cl complexes
formula [Au(NHC)(C≡CPh)](3). Compounds such as 3 are usually
obtained in a greater number of synthetic steps in reactions
involving the terminal alkyne and synthons such as
[Au(NHC)(OH)]11 or [Au(NHC)(aryl)]12 in benzene or toluene at
elevated temperature. On the other hand, the direct reaction
between terminal alkynes and [Au(L)X] (L = PR3 or NHC, X = Cl,
Br, I) complexes generally requires strong bases such as KOH,
KOtBu and NaOMe to generate Au-OR (R = H or hydrocarbyl)
bonds in situ or by action of magnesium, tin and silicon alkynyls
as transmetallating agents.22
The reaction between six different unsaturated and
saturated imidazolium salts (1a-f) with [Au(DMS)Cl] in the
presence of NaOAc (1.2 equiv.) stirring in technical grade
acetone (or green acetone) at 60 °C afforded the final
complexes 2a-f in high purity and in yields comparable to
reactions conducted using K2CO3 (Table 1).17a
Table 1. Synthesis of [Au(NHC)Cl] using NaOAc
Gratifyingly, the reaction between complexes 2a-f and
phenylacetylene in the presence of NaOAc (3 equiv.) using
ethanol as a sustainable solvent afforded the desired alkynyl
species 3a-f in excellent yields and under very mild conditions
(6h at r.t.), see Table 2.
N
N
N
N
NaOAc
R
R
R
R
[Au(DMS)Cl]
+
acetone
60 °C
H
Cl
Au
1a-f
Cl
Table 2. Synthesis of Au(I)-alkynyl (3) complexes with NaOAc
2a-f
Entry[a]
NHC·HCl
IPr·HCl (1a)
IAd·HCl (1b)
IMes·HCl (1c)
ItBu·HCl (1d)
SIPr·HCl (1e)
SIMes·HCl (1f)
Time (h)
Yield (%)
Ph
N
N
N
N
NaOAc
1
2
3
4
5
6
1
2
96
71
81
52
71
77
R
R
R
R
+
EtOH
r.t., 6h
Au
Au
H
4
Cl
4
2a-f
24
24
Ph
3a-f
[a] Reaction conditions: NHC·HCl (100 mg), [Au(DMS)Cl] (1.0 equiv.), NaOAc
(1.2 equiv.) and 1.0 mL of acetone at 60 °C.
Entry[a]
NHC
Yield (%)
Entry
NHC
Yield (%)
1
2
3
IPr (a)
94
90
85
4
5
6
ItBu (d)
88
98
92
IAd (b)
SIPr (e)
DFT calculations support the thermodynamic feasibility of the
CMD-like reaction mechanism, a pathway similar to that
recently proposed when NEt3 is used as base.17b
IMes (c)
SIMes (f)
[a] Reaction conditions: [Au(NHC)Cl] (100 mg), phenylacetylene (2 equiv.),
NaOAc (3 equiv.) and 1.0 mL of EtOH at 25 °C.
2 | J. Name., 2012, 00, 1-3
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H
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NaOAc or K2CO3
F
F
F
F
DOI: 10.1039/D0DT02240C
This category of compound has been described in the patent
literature, by Fujimura, for their luminescent properties but
their synthesis is reported using a strong base. 22c
Computational studies also permit support of a mechanism
involving base-assisted concerted mechanism for alkynyl
delivery onto gold (Fig. S16 in ESI).23 We have considered the
existence of a [Au(IPr)(OAc)] (4a) intermediary in these
reactions but have dismissed it as it is never observed in the
synthesis of 1a.
(3 equiv.)
N
N
no reaction
EtOH (or toluene)
+
r.t. or 60 °C, 24h
Au
Cl
F
(2 equiv.)
(OAc)
2a 4a
(or
)
Scheme 3. Reaction of [Au(IPr)Cl](2a) or [Au(IPr)(OAc)](4a) with
pentafluorobenzene
Supporting this conclusion, reacting [Au(IPr)Cl] (2a) in various
solvents (acetone, ethanol or methanol) at 60 °C for prolonged
reaction times (24h) in the presence of a large excess of NaOAc
(3 or 10 equiv.) never leads to the formation of [Au(IPr)(OAc)]
(4a).24 The latter is currently obtained by reaction between
acetic acid and either of the two synthons, [Au(NHC)(OH)]11 or
[Au(NHC)(acetonyl)].13
It appears that more than simple acid/base concepts are at play here
and we suspect the sterically encumbered transition state in the
CMD-like mechanism is a key element hindering formation of Au-R
bonds with more sterically demanding substrates (see Fig S17 in ESI,
for computational analysis).
To be thorough in this reactivity study, it should be stated
that 4a can be used to access 3a and represents another
example of the built-in base approach yet requires the prior
installation of the Au-OAc bond (Scheme 2). If the endgame is
the synthesis of complexes of type 3 (e.g. [Au(IPr)(C≡CPh)]),
then the use of a weak base such as NaOAc in the presence of
the alkyne and 2 represents the simplest synthetic route.
Reactivity of Au(IPr)Cl towards thiophenol (S-H activation)
To explore how far the weak base approach could be extended,
we explored the reactivity of the S-H bond of thiophenol.
Mononuclear NHC-gold-thiolato complexes are normally obtained
by treating the thiol with a strong base (i.e. NaH or KOH) and
subsequent addition of the gold precursor.26,27 The seminal paper of
Baker and co-workers27 and Corrigan and Workentin26c for the
preparation of NHC analogues of Auranofin and gold(I) complexes
bearing azide-modified arylthiolates, respectively, are noteworthy
as are the potential of such compounds in biology and medicine.
Ph
N
N
N
N
EtOH
+
r.t., 6h
The weak base approach would clearly represent a significant
advance. Indeed, [Au(IPr)Cl] (2a) and thiophenol react cleanly in the
presence of NaOAc. Under very mild conditions already deployed for
Au-alkynyl complexes (EtOH, r.t., 6h) complete conversion into the
thiolato complex 5a is obtained in an excellent 95% yield.
Spectroscopic data confirm the clean formation of the complex first
reported by Sadighi and Gray, whose procedure leads to a lower yield
(46%) and makes use of a much more laborious protocol.28
Au
Au
Ph
H
OAc
4a
3a
(93%)
Scheme 2. Synthesis of [Au(IPr)(C≡CPh)] (3a) starting from
[Au(IPr)(OAc)] (4a)
In order to extend the weak base approach to the activation
of other C-H bonds, we examined the reaction between
[Au(IPr)Cl] (2a) and pentafluorobenzene in the presence of
NaOAc or K2CO3. Pentafluorobenzene is slightly more acidic
than phenylacetylene (pka DMSO = 2425a and 28.725b, respectively)
and we have previously isolated the corresponding
[Au(IPr)(C6F5)] complex using [Au(IPr)(OH)] as a gold synthon in
the absence of external bases under mild conditions (toluene,
60 °C, 14h).11
SH
NaOAc
(3 equiv.)
N
N
N
N
+
EtOH
r.t., 6h
Au
S
Au
(2 equiv.)
Cl
2a
5a
(95%)
Disappointingly, no product was formed when 2a was reacted
with pentafluorobenzene in the presence of NaOAc or K2CO3 (3
equiv.) in both ethanol and toluene at rt or 60 °C for prolonged
reaction times (24h). The desired product was also not formed
when [Au(IPr)(OAc)] (4a) was used as the gold precursor.
Scheme 4. Straightforward synthesis of [Au(IPr)(SPh)] (5a)
Computational analysis also suggests this synthetic route is
thermodynamically very feasible and proceeds through a
different mechanism first involving base-assisted thiol
deprotonation followed by salt elimination. This mechanism is
presented in Fig. S18 in the ESI.
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described for 2a starting from 129.4 mg of IMes·HCl, 111.8 mg
of [Au(DMS)Cl] and 37.4 mg of NaOAc.
Conclusions
View Article Online
DOI: 10.1039/D0DT02240C
In summary, we have shown that a very weak base, NaOAc,
can be used to enable the formation of [Au(NHC)Cl] complexes
under mild conditions and in high yields. The protocol using
NaOAc proves highly efficient in processes involving C-H and S-
H bond auration but is substrate specific for C-H bond
activation. We suspect sterics dictate the feasibility of the
reaction in this case. Studies aimed at extending this simple
weak base protocol to related and varied organometallic
systems are on-going in our laboratories.
Reaction time: 4 hours. Yield: 165.1 mg (81%).
1H NMR (400 MHz, CDCl3): δ (ppm) = 7.09 (s, 2H), 6.99 (s, 4H),
2.34 (s, 6H), 2.10 (s, 12H).
The data are in agreement with the reported values.17a
Synthesis of [Au(ItBu)Cl] (2d)
Complex 2d was prepared in an analogous manner to that
described for 2a starting from 109.2 mg of ItBu·HCl, 148.4 mg of
[Au(DMS)Cl] and 49.6 mg of NaOAc.
Reaction time: 4 hours. Yield: 108.3 mg (52%).
1H NMR (400 MHz, CDCl3): δ (ppm) = 7.09 (s, 2H), 1.87 (s, 18H).
The data are in agreement with the reported values.17a
Experimental
Materials and methods
All complex syntheses were performed in air. Solvents and all
other reagents were purchased and used as received without
further purification unless otherwise stated. 1H and 13C{1H}
Nuclear Magnetic Resonance (NMR) spectra were recorded on
a Bruker Advance 400 Ultrashield spectrometer at 298K.
Chemical shifts (expressed by parts per million) are referenced
to residual solvent peaks.
Synthesis of [Au(SIPr)Cl] (2e)
Complex 2e was prepared in an analogous manner to that
described for 2a starting from 99.3 mg of SIPr·HCl, 68.5 mg of
[Au(DMS)Cl] and 22.9 mg of NaOAc.
Reaction time: 24 hours. Yield: 102.4 mg (71%).
1H NMR (400 MHz, CDCl3): δ (ppm) = 7.42 (t, J= 7.7 Hz, 2H), 7.25
(d, J = 7.7 Hz, 4H), 4.05 (s, 4H), 3.06 (sept, J = 6.9 Hz, 4H), 1.42
(d, J= 6.9 Hz, 12H), 1.33 (d, J= 6.9 Hz, 12H).
The data are in agreement with the reported values.17a
Synthesis of [Au(IPr)Cl] (2a)
A vial was charged, under air, with 101.4 mg of IPr·HCl (1a,
0.2386 mmol), 70.3 mg of [Au(DMS)Cl] (0.239 mmol) and
suspended in acetone (1 mL).
The mixture was stirred at 60 °C for 10 min and then 23.5 of
NaOAc (0.287 mmol, 1.2 equiv.) was added. The reaction
mixture was stirred at 60°C for 50 min.
Synthesis of [Au(SIMes)Cl] (2f)
Complex 2c was prepared in an analogous manner to that
described for 2a starting from 117.8 mg of SIMes·HCl, 101.2 mg
of [Au(DMS)Cl] and 33.8 mg of NaOAc.
Reaction time: 24 hours. Yield: 142.5 mg (77%).
1H NMR (400 MHz, CDCl3): δ (ppm) = 6.94 (s,4H), 3.98 (s, 4H),
2.32 (s, 12H), 2.30 (s, 6H).
After this time the solvent was removed in vacuo and
dichloromethane was added (2 mL).
The data are in agreement with the reported values.17a
The mixture was filtered through silica (the pad of silica was
washed with dichloromethane 3x1mL). The solvent was
concentrated and pentane (3 mL) was added, affording a white
solid which was washed with further portions of pentane
(3x1mL) and dried under vacuum.
Synthesis of [Au(IPr)(C≡CPh)] (3a)
A vial was charged, under air, with 106.8 mg of [Au(IPr)Cl] (2a,
0.1719 mmol), 42.3 mg of NaOAc (0.516 mmol, 3 equiv.), 35.4
mg of phenylacetylene (38.1 μL, 0.345 mmol, 2 equiv.) and
suspended in ethanol (1 mL). The reaction mixture was stirred
at room temperature for 6 hours. After this time the solvent was
removed in vacuo and dichloromethane was added (2 mL).
The mixture was filtered on a millipore membrane filter and
addition of pentane (3 mL) to the concentrated solution yields
the final complex 3a as a white solid which was filtered and
dried under vacuum.
Yield: 142.0 mg (96 %).
1H NMR (400 MHz, CDCl3): δ (ppm) = 7.50 (t, J = 7.8 Hz, 2H), 7.29
(d, J = 7.8 Hz, 4H), 7.16 (s, 2H), 2.56 (sept, J = 6.9 Hz, 4H), 1.34
(d, J = 6.9 Hz, 12H), 1.22 (d, J = 6.9 Hz, 12H).
The data are in agreement with the reported values.17a
Synthesis of [Au(IAd)Cl] (2b)
Complex 2b was prepared in an analogous manner to that
described for 2a starting from 109.2 mg of IAd·HCl, 86.1 mg of
[Au(DMS)Cl] and 28.8 mg of NaOAc.
Yield: 110.8 mg (94 %).
1H NMR (400 MHz, CDCl3): δ (ppm) = 7.49 (t, J = 7.8 Hz, 2H), 7.32
– 7.28 (m, 6H), 7.12 (s, 2H), 7.11-7.01 (m, 3H), 2.70–2.51 (hept,
J = 6.9 Hz, 4H), 1.38 (d, J = 6.9 Hz, 12H), 1.21 (d, J = 6.9 Hz, 12H).
The data are in agreement with the reported values.22c
Reaction time: 2 hours. Yield: 118.2 mg (71%).
1H NMR (400 MHz, CDCl3): δ (ppm) = 7.48 (d, J = 1.7 Hz, 2H),
2.35 (m, 6H), 2.29 (m, 12H), 1.81 (m, 12H).
The data are in agreement with the reported values.29
Synthesis of [Au(IAd)(C≡CPh)] (3b)
Synthesis of [Au(IMes)Cl] (2c)
Complex 3b was prepared in an analogous manner to that
described for 3a starting from 101.7 mg of 2b, 36.4 mg of
phenylacetylene and 43.9 mg of NaOAc.
Complex 2c was prepared in an analogous manner to that
4 | J. Name., 2012, 00, 1-3
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Reaction time: 6 hours. Yield: 103.4 mg (90%).
COMMUNICATION
1H NMR (400 MHz, CDCl3): δ (ppm) = 7.49 (t, J = 7.8VHiewz,A2rtHicl)e,O7n.l3in2e
1H NMR (400 MHz, CDCl3): δ (ppm) = 7.53-7.50 (m, 2H), 7.25- – 7.28 (m, 6H), 7.12 (s, 2H), 7.11-7.01 (mD, O3HI: 1),0.210.7309–/D20.5D1T0(2h2e4p0tC,
7.13 (m, 3H), 7.07 (s, 2H), 2.57 (m, 12H), 2.28(m, 6H), 1.78 (m, J = 6.9 Hz, 4H), 1.38 (d, J = 6.9 Hz, 12H), 1.21 (d, J = 6.9 Hz, 12H).
12H).
The data are in agreement with the reported values.22c
The data are in agreement with the reported values.22c
Reaction of [Au(IPr)Cl] (2a) with pentafluorobenzene
Synthesis of [Au(IMes)(C≡CPh)] (3c)
A vial was charged, under air, with 85.2 mg of [Au(IPr)Cl] (2a,
Complex 3c was prepared in an analogous manner to that
0.1372 mmol), 0.412 mmol (3 equiv.) of NaOAc or K2CO3, 46.1
described for 3a starting from 102.6 mg of 2c, 39.0 mg of mg of pentafluorobenzene (30.5 μL, 0.274 mmol, 2 equiv.) and
phenylacetylene and 47.0 mg of NaOAc.
Reaction time: 6 hours. Yield: 98.3 mg (85%).
1H NMR (400 MHz, CDCl3): δ (ppm) = 7.35-7.32 (m, 2H), 7.12- to the desired product was observed.
suspended in ethanol or toluene (1 mL). The reaction mixture
was stirred at 60 °C for 24 hours. After this time no conversion
7.07 (m, 3H), 7.06 (s, 2H), 6.99 (s, 4H), 2.35 (s, 6H), 2.12 (s, 12H).
The data are in agreement with the reported values.22c
Reaction of [Au(IPr)OAc] (4a) with pentafluorobenzene
A vial was charged, under air, with 32.4 mg of [Au(IPr)OAc] (4a,
0.0503 mmol), 16.9 mg of pentafluorobenzene (11.2 μL, 0.100
mmol, 2 equiv.) and suspended in ethanol or toluene (0.5 mL).
Synthesis of [Au(ItBu)(C≡CPh)] (3d)
Complex 3d was prepared in an analogous manner to that
described for 3a starting from 107.0 mg of 2d, 53.0 mg of The reaction mixture was stirred at 60 °C for 24 hours. After this
phenylacetylene and 63.8 mg of NaOAc.
time no conversion to the desired product was observed.
Reaction time: 6 hours. Yield: 109.1 mg (88%).
1H NMR (400 MHz, CDCl3): δ (ppm) = 7.53-7.49 (m, 2H), 7.24- Synthesis of [Au(IPr)(SPh)] (5a)
7.11 (m, 3H), 7.06 (s, 2H), 1.89 (s, 18H).
A vial was charged, under air, with 50.9 mg of [Au(IPr)Cl] (2a,
The data are in agreement with the reported values.22c
0.0820 mmol), 20.2 mg of NaOAc (0.246 mmol, 3 equiv.), 18.1
mg of thiophenol (16.7 μL, 0.164 mmol, 2 equiv.) and suspended
in ethanol (0.5 mL). The reaction mixture was stirred at room
temperature for 6 hours. After this time the solvent was
Synthesis of [Au(SIPr)(C≡CPh)] (3e)
Complex 3e was prepared in an analogous manner to that
described for 3a starting from 138.5 mg of 2e, 45.4 mg of removed in vacuo and dichloromethane was added (1 mL).
phenylacetylene and 54.7 mg of NaOAc.
Reaction time: 6 hours. Yield: 154.4 mg (92%).
1H NMR (400 MHz, CDCl3): δ (ppm) = 7.41 (t, J= 7.7 Hz, 2H), 7.27- the final complex 5a as a white solid which was filtered and
7.24 (m, 2H), 7.24 (d, J = 7.7 Hz, 4H), 7.11-7.02 (m, 3H), 3.99 (s, dried under vacuum.
The mixture was filtered on a millipore membrane filter and
addition of pentane (2 mL) to the concentrated solution yields
4H), 3.09 (sept, J = 6.9 Hz, 4H), 1.46 (d, J= 6.9 Hz, 12H), 1.34 (d, Yield: 54.1 mg (95%).
J= 6.9 Hz, 12H).
1H NMR (400 MHz, CDCl3): δ (ppm) = 7.54 (t, J = 7.8 Hz, 2H), 7.31
(d, J = 7.8 Hz, 4H), 7.19 (s, 2H), 6.86-6.83 (m, 2H), 6.78-6.74 (m,
3H), 2.67–2.58 (hept, J = 6.9 Hz, 4H), 1.34 (d, J = 6.9 Hz, 12H),
1.23 (d, J = 6.9 Hz, 12H).
The data are in agreement with the reported values.22c
Synthesis of [Au(SIMes)(C≡CPh)] (3f)
The data are in agreement with the reported values.28
Complex 3f was prepared in an analogous manner to that
described for 3a starting from 149.5 mg of 2f, 56.7 mg of
phenylacetylene and 68.3 mg of NaOAc.
Reaction time: 6 hours. Yield: 149.9 mg (98%).
1H NMR (400 MHz, CDCl3): δ (ppm) = 7.28-7.24 (m, 2H), 7.17- the PBE0-D3 level of theory.31 The standard split-valence basis
Computational details
Geometries were optimized with the Gaussian09 package30 at
7.02 (m, 3H), 6.80 (s,4H), 3.94 (s, 4H), 2.37 (s, 6H), 1.84 (s, 12H). set with a polarization function of Ahlrichs and coworkers was
The data are in agreement with the reported values.22c
used for H, C, N, O, F, S and Cl atoms (SVP keyword in
Gaussian)32 while the quasi relativistic small-core Stuttgart
effective core potential (ECP) was used for Au (SDD keyword in
Gaussian09). The reported free energies have been obtained via
single point energy calculations with the triple-ζ basis set of
Ahlrichs for main group atoms atoms (TZVP keyword in
Gaussian09).33 Solvent effects, acetone and ethanol, were
included using the PCM method.34 To this PBE0-D3/TZVP
electronic energy in solvent, zero point and thermal corrections
were added from the gas-phase frequency calculations at the
PBE0-D3/SVP level.
Synthesis of [Au(IPr)(CCPh)] (3a) starting from [Au(IPr)(OAc)] (4a)
A vial was charged, under air, with 27.6 mg of [Au(IPr)OAc] (4a,
0.0428 mmol), 8.7 mg of phenylacetylene (9.4 μL, 0.0856 mmol,
2 equiv.) and suspended in ethanol (0.5 mL). The reaction
mixture was stirred at room temperature for 6 hours. After this
time the solvent was removed in vacuo and dichloromethane
was added (1 mL).
Addition of pentane (2 mL) to the concentrated solution yields
the final complex 3a as a white solid which was filtered and
dried under vacuum.
Yield: 27.2 mg (93 %).
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Journal Name
15 N-Heterocyclic Carbenes in Catalytic Organic Synthesis, S. P.
Conflicts of interest
There are no conflicts to declare.
View Article Online
Nolan and C. S. J. Cazin (Eds.) Science of Synthesis, Thieme,
DOI: 10.1039/D0DT02240C
Stuttgart, Germany, 2016.
16 (a) R. Visbal, A. Laguna and M. C. Gimeno, Chem. Commun.,
2013, 49, 5642-5644; (b) A. Johnson and M. C. Gimeno, Chem.
Commun., 2016, 52, 9664-9667.
Acknowledgements
17 (a) A. Collado, A. Collado, A. Goméz-Suárez, A. R. Martin, A. M.
Z. Slawin and S. P. Nolan, Chem. Comm., 2013, 49, 5541-5543;
(b) N. V. Tzouras, F. Nahra, L. Falivene, L. Cavallo, M. Saab, K.
Van Hecke, A. Collado, C. J. Collett, A. D. Smith, C. S. J. Cazin
and S. P. Nolan, Chem. Eur. J., 2020, 26, 4515-4519.
18 Handbook of Chemistry and Physics 97th Edition, ed. W. M.
Haynes, CRC Press, 2017, 953-963.
We gratefully acknowledge VLAIO (SBO project
CO2PERATE), the Special Research Fund (BOF) of Ghent
University for starting and project grants to SPN, and project
grant (01N03217) to KVH and MS. KVH thanks the Hercules
Foundation (project AUGE/11/029). Umicore AG is gratefully
acknowledged for generous gifts of materials.
19 (a) P. V. Thong, D. T. Thom and N. T. T. Chi, Vietnam J. Chem.,
2018, 56, 146-151; (b) S. Kobialka, C. Müller-Tautges, M.T. S.
Schmidt, G. Schnakenburg, O. Hollóczki, B. Kirchner and M.
Engeser, Inorg. Chem., 2015, 54, 6100-6111.
20 A. A. Penney, G. L. Starova, E. V. Grachova, V.V. Sizov, M. A.
Kinzhalov and S. P. Tunik, Inorg. Chem., 2017, 56, 14771-
14787.
21 (a) A. Jr. Streitwieser and D. M. E. Ruben, J. Am. Chem. Soc.,
1971, 93, 1794-1795; (b) Acids and Bases: Solvent Effects on
Acid-base Strength 1st Edition, ed. B. G. Cox, Oxford
University Press, UK, 2013, 130-140.
Notes and references
1
2
(a) N-Heterocyclic Carbenes in Organocatalysis, ed. A. T. Biju,
Wiley-VCH, 2019; (b) N. Marion, S. Díez-González and S. P.
Nolan, Angew. Chem. Int. Ed. 2007, 46, 2988-3000; (c) T.
Scattolin and S. P. Nolan, Trends Chem., 2020, DOI:
10.1016/j.trechm.2020.06.001.
(a) M. N. Hopkinson, C. Richter, M. Schedler and F. Glorius,
Nature, 2014, 510, 485-496; (b) P. de Frémont, N. Marion and
S. P. Nolan, Coord. Chem. Rev., 2009, 253, 862-892.
3
4
5
6
7
8
A. Doddi, M. Peters and M. Tamm, Chem. Rev., 2019, 119, 22 (a) I. Mármol, P. Castellnou, R. Alvarez, M. C. Gimeno, M. J.
6994-7112.
Rodríguez-Yoldi and E. Cerrada, Eur. J. Med. Chem., 2019, 183,
111661; (b) K. Klauke, S. Werner and F. Mohr, Eur. J. Inorg.
Chem., 2018, 1053-1056; (c) O. Fujimura, K. Fukunaga, T.
Honma, T. Machida, T. Takahashi, US Pat., US 8137821B2,
2012.
Y. Pan, X. Jiang, Y-M. So, C. T. To and G. He, Catalysts, 2020,10,
71.
S. Díez-González, N. Marion and S. P. Nolan, Chem. Rev., 2009,
109, 3612-3676.
K. V. S. Ranganath, S. Onitsuka, A. K. Kumar and J. Inanaga, 23 The high pKa water value of phenylacetylene (23.221a) exclude
Catal. Sci. Technol., 2013, 3, 2161-2181.
C. A. Smith, M. R. Narouz, P. A. Lummis, I. Singh, A. Nazemi,
its deprotonation by sodium acetate (pka water HOAc = 4.7518)
before interaction with the NHC-gold(I) precursor.
C.-H. Li and C. M. Crudden, Chem. Rev., 2019, 119, 4986-5056. 24 DFT calculations confirm the failure to convert [Au(IPr)Cl] into
(a) I. Ott, Adv. Inorg. Chem., 2020, 75, 121-148; (b) T. Scattolin,
[Au(IPr)OAc] with a ΔG°acetone of +4.7 kcal/mol.
I. Caligiuri, N. Mouawad, M. El Boustani, N. Demitri, 25 (a) M. Simonetti, D. M. Cannas and I. Larrosa, Adv.
F. Rizzolio and F. Visentin, Eur. J. Med. Chem., 2019, 179, 325-
334; (c) ) T. Scattolin, S. Giust, P. Bergamini, I. Caligiuri, L.
Organomet. Chem., 2017, 67, 299-399; (b) F. G. Bordwell, Acc.
Chem. Res., 1988, 21, 456-463.
Canovese, N. Demitri, R. Gambari, I. Lampronti, F. Rizzolio 26 (a) P. de Frémont, E. D. Stevens, M. D. Eelman, D. E. Fogg and
and F. Visentin, Appl. Organomet. Chem., 2019, 33, e4902; (e)
T. Scattolin, E. Bortolamiol, F. Visentin, S. Palazzolo, I. Caligiuri,
T. Perin, V. Canzonieri, N. Demitri, F. Rizzolio and A. Togni,
Chem. Eur. J., 2020, DOI: 10.1002/chem.202002199.
S. P. Nolan, Acc. Chem. Res. 2011, 44, 91-100.
S. P. Nolan, Organometallics, 2006, 25, 5824-5828; (b) R. E.
Cordero-Rivera, D. Rendón-Nava, C. Ángel-Jijón, O. R. Suárez-
Castillo and D. Mendoza-Espinosa, Organometallics, 2020,
DOI: 10.1021/acs.organomet.0c00118; (c) V. Somasundaram,
P. N. Gunawardene, A. M. Polgar, M. S. Workentin and J. F.
Corrigan, Inorg. Chem., 2018, 57, 11184-11192.
9
10 M. M. Mastandrea, N. Mellonie, P. Giacinto, A. Collado, S. P.
Nolan, G. P. Miscione, A. Bottoni and M. Bandini, Angew.
Chem. Int. Ed., 2015, 54, 14885-14889.
11 S. Gaillard, A. M. Z. Slawin and S. P. Nolan, Chem. Commun.,
2010, 46, 2742-2744.
12 N. V. Tzouras, M. Saab, W. Janssens, T. Cauwenbergh, K. Van
Hecke, F. Nahra and S. P. Nolan, Chem. Eur. J., 2020, 26, 5541-
5551.
27 M. V. Baker, P. J. Barnard, S. J. Berners-Price, S. K. Brayshaw,
J. L. Hickey, B. W. Skelton and A. H. White, J. Organomet.
Chem., 2005, 690, 5625-5635.
28 T. J. Robilotto, J. Bacsa, T. G. Gray and J. P. Sadighi, Angew.
Chem. Int. Ed., 2012, 51, 12077-12080.
29 P. de Fre´mont, N. M. Scott, E. D. Stevens and S. P. Nolan,
Organometallics, 2005, 24, 2411-2418.
30 M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A.
Robb, J. R. Cheeseman, G. Scalmani, V. Barone, B. Mennucci,
G. A. Petersson, H. Nakatsuji, M. Caricato, X. Li, H. P.
Hratchian, A. F. Izmaylov, J. Bloino, G. Zheng, J. L.
13 D. Gasperini, A. Collado, A. Goméz-Suárez, D. B. Cordes, A. M.
Z. Slawin and S. P. Nolan, Chem. Eur. J., 2015, 21, 5403-5412.
14 (a) R. M. P. Veenboer, L. M. Azofra, D. Gasperini, A. Collado, D.
B. Cordes, A. M. Z. Slawin, L. Cavallo and S. P. Nolan, Dalton
Trans., 2019, 48, 7693-7703; (b) C. M. Zinser, F. Nahra, L.
Falivene, M.Brill, D. B. Cordes, A. M. Z. Slawin, L. Cavallo, C. S.
J. Cazin and S. P. Nolan, Chem. Commun., 2019, 55, 6799-
6802.
Sonnenberg, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J.
Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H.
Nakai, T. Vreven, J. A. Montgomery, J. E. Peralta, F. Ogliaro,
M. Bearpark, J. J. Heyd, E. Brothers, K. N. Kudin, V. N.
Staroverov, R. Kobayashi, J. Normand, K. Raghavachari, A.
Rendell, J. C. Burant, S. S. Iyengar, J. Tomasi, M. Cossi, N.
Rega, J. M. Millam, M. Klene, J. E. Knox, J. B. Cross, V.
6 | J. Name., 2012, 00, 1-3
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Bakken, C. Adamo, J. Jaramillo, R. Gomperts, R. E. Stratmann,
O. Yazyev, A. J. Austin, R. Cammi, C. Pomelli, J. W. R.
Ochterski, L. Martin, K. Morokuma, V. G. Zakrzewski, G. A.
Voth, P. Salvador, J. J. Dannenberg, S. Dapprich, A. D.
Daniels, Ö. Farkas, J. B. Foresman, J. V. Ortiz, J. Cioslowski
and D. J. Fox, Gaussian 09 Revision A.1, Gaussian, Inc.,
Wallingford, CT, 2009.
View Article Online
DOI: 10.1039/D0DT02240C
31 (a) C. Adamo and V. Barone, J. Chem. Phys., 1999, 110, 6158-
6170; (b) S. J. Grimme, Comp. Chem., 2004, 25, 1463-1473.
32 A. Schaefer, H. Horn and R. J. Ahlrichs, J. Chem. Phys., 1992,
97, 2571-2577.
33 (a) W. R. Wadt and P. J. Hay, J. Chem. Phys., 1985, 82, 284-
298; (b) P. J. Hay, and W. R. Wadt, J. Chem. Phys., 1985, 82,
299-310.
34 (a) J. Tomasi and M. Persico, Chem. Rev., 1994, 94, 2027–
2094; (b) V. Barone and M. Cossi, J. Phys. Chem. A, 1998,
102, 1995–2001.
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DOI: 10.1039/D0DT02240C
TOC entry
N
N
N
N
R
Ph
C
C
H
R
R
R
or
[Au(DMS)Cl]
NaOAc
N
N
PhS
H
R
or
R
Au
S
N
N
Au
R
R
acetone
60 °C
NaOAc
EtOH, r.t., 6h
C
Au
H
Cl
C
Cl
Ph
The role of sodium acetate in the preparation of [Au(NHC)Cl] complexes is examined. This
inexpensive weak base is capable of promoting C-H and S-H activation processes and leads to Au-
alkynyl and Au-thiolato derivatives in high yields under very mild conditions using technical grade
green solvents in air.