Synthetic routes to [Au(NHC)(OH)] (NHC = N-heterocyclic carbene) complexes

Article abstract of DOI:10.1039/c2dt30294b

New procedures for the synthesis of [Au(NHC)(OH)] are reported. Initially, a two-step reaction via the digold complex [{Au(NHC)}₂(μ-OH)] [BF₄] was probed, enabling the preparation of the novel [Au(SIPr)(OH)] complex and of its previously reported congener [Au(IPr)(OH)]. After further optimization, a one-step procedure was developed.

Full text of DOI:10.1039/c2dt30294b

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COMMUNICATION
Synthetic routes to [Au(NHC)(OH)] (NHC = N-heterocyclic carbene)
complexes†‡
Adrián Gómez-Suárez, Rubén S. Ramón, Alexandra M. Z. Slawin and Steven P. Nolan*
Received 9th February 2012, Accepted 1st March 2012
DOI: 10.1039/c2dt30294b
reactions,6 and in the development of new gold-catalyzed silver-
New procedures for the synthesis of [Au(NHC)(OH)] are
reported. Initially, a two-step reaction via the digold complex
[{Au(NHC)}2(μ-OH)][BF4] was probed, enabling the prep-
aration of the novel [Au(SIPr)(OH)] complex and of its pre-
viously reported congener [Au(IPr)(OH)]. After further
optimization, a one-step procedure was developed.
free protocols among other catalytic transformations.7,8 Intrigued
by the broad reactivity of 1,3–8 we forged ahead in this area and
investigated the synthesis of new [Au(NHC)(OH)] complexes.
Following the existing procedure using KOH, thus far only 1 had
been easily isolated in pure form. As has often been the case in
our studies on NHCs, IPr appears a privileged member of this
family.9 In addition, this procedure leading to 1 proved to be
poorly scalable. In order to exploit the full range of gold-hydrox-
ide chemistry; the development of new synthetic pathways was
investigated.
Homogeneous gold catalysis has become a most intensely
studied area of research during the last decade. This interest can
be explained by the broad catalytic activity of gold complexes.1
Among organometallic AuI-catalysts, those bearing phosphines
or N-heterocyclic carbene (NHC) ligands represent the state-of-
the-art.1 During recent years, Au-complexes bearing NHC
ligands have gained increased attention as this supporting ligand
class appears to stabilize coordinatively unsaturated catalytically
active species.2
Pursuing the synthesis of new gold catalysts and following
computational studies that predicted the formation of a stable
AuI–OH species, we recently reported the synthesis of [Au(IPr)-
(OH)] (1) (IPr = 1,3-bis(2,6-diisopropyl-phenyl)imidazol-2-
ylidene), the first mononuclear AuI–hydroxide complex.3 This
new gold species was synthesized from [Au(IPr)Cl] (2) and
KOH in a 1 : 1 mixture of THF–toluene heated at 60 °C for 24 h
(eqn (1)).
The digold complex [{Au(IPr)}2(μ-OH)][BF4] (3),10 discov-
ered during the course of studies dealing with acid activation of
hydroxide 1, can be formally viewed as being composed of a cat-
ionic [Au(NHC)]+ species coordinated to the oxygen of a Au-
hydroxide. Hence, we envisioned a two-step procedure starting
from the chloride precursor 2, generating the digold species 3
then followed by formation of the hydroxide by addition of
KOH (Scheme 1). Indeed, this digold complex has been postu-
lated as a reactive intermediate in gold-catalyzed reactions invol-
ving water, such as nitrile and alkyne hydrations.10,11
ð1Þ
1 has proven a versatile synthon, granting access to a wide
range of novel organogold species under mild conditions.4
Complex 1 has been successfully used for the activation of acet-
ylenic C–H bonds,5 carboxylation and decarboxylation
Scheme 1 Proposed synthetic route leading to [Au(NHC)(OH)].
First, the digold species 3 was synthesized by addition of
AgBF4 to a solution of complex 2 in dichloromethane. After fil-
tration of the AgCl precipitate, addition of water to the inter-
mediate [Au(IPr)][BF4] afforded the digold complex 3 in 81%
yield (Scheme 2). In order to validate our hypothesis that 3
could lead to 1, 2.3 equiv of KOH were added to a solution of
EaStCHEM School of Chemistry, University of St Andrews, St Andrews,
KY16 9ST, UK. E-mail: snolan@st-andrews.ac.uk; Fax: (+44)-(0)1334-
463-808
†Dedicated to Professor David Cole-Hamilton on the occasion of his
retirement and for his outstanding contribution to transition metal
catalysis.
‡Electronic supplementary information (ESI) available: Synthetic details
and complete analytical data, NMR spectra and crystallographic data.
CCDC 856432 (4). For ESI and crystallographic data in CIF or other
electronic format see DOI: 10.1039/c2dt30294b
digold complex 3 in THF.12 After stirring for 1 h at 30 °C,13 1
H
NMR analysis of the reaction mixture confirmed full conversion
to 1 which was isolated in 86% yield. Encouraged by these
results and the high stability shown by the digold species, we
investigated the generality of the new procedure using a NHC
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Scheme 2 Synthesis of hydroxides 1 and 4 using a two-step procedure.
relative. SIPr (SIPr = 1,3-bis(2,6-diisopropyl-phenyl)imidazoli-
dine), the saturated version of IPr, was selected as the ligand and
the synthesis of [Au(SIPr)(OH)] (4) was targeted next. The
digold species [{Au(SIPr)}2(μ-OH)][BF4] (5)§ was synthesized
first. Chloride abstraction from [Au(SIPr)Cl] (6) by AgBF4 and
subsequent reaction with water afforded 5 in 83% isolated yield
(Scheme 2). The synthesis of the hydroxide-bearing 4 was next
attempted from 5.
Scheme 3 One-pot synthesis of [Au(NHC)(OH)] from [Au(NHC)Cl]
precursors.
After a reaction time of 1 h, 4 was isolated in 80% yield
(Scheme 2). This reaction represents the first successful synthesis
of Au-hydroxides bearing NHC ligands other than IPr. Crystals
suitable for single-crystal diffraction studies were obtained by
slow diffusion of pentane into a saturated THF solution of 4
(Fig. 1). As expected, 4 adopts a linear geometry, with a C1–
Au–O1 angle of 180.00(1)°, a Au–C1 bond length of 1.976(8) Å
and a Au–O1 bond length of 2.019(7) Å.14 The Au–C1 bond
distance is longer for the SIPr complexes than for the IPr com-
plexes (1.935(6) Å for hydroxide 1). This trend can also be
observed in the Au–C1bond distances in the chloro complexes 2
and 6 (1.942(3) Å for IPr and 1.979(3) Å for SIPr). These differ-
ences could possibly be due to the steric bulk of the ligands.
Computational studies using SambVca15 reveal that the %VBur is
greater for 4 (46.6) than for 1 (43.2).16 On the other hand, the
Au–O1 distance is significantly shorter for 4 compared to that
found in 1 (2.078(6) Å).
equiv of KOH were next added. We were very pleased to
observe that after stirring for 1.5 h at 30 °C, the reaction was
complete and both hydroxides 1 and 4 could be isolated in good
yields, 77% and 75% respectively using this procedure
(Scheme 3).
One further advance had to be considered. In order to avoid
the use of expensive silver salts, several chloride abstractors
were screened. During the course of this study, a control reaction
showed that if a larger excess of KOH was used, silver salts were
unnecessary and the reaction reached completion within 20 h.
As we could perform the reaction without silver salts, using
longer but still acceptable reaction times, the reaction conditions
were optimized in THF, stirring for 20 h at 30 °C, affording both
hydroxides, 1 and 4, in 75% isolated yields (Scheme 4).
Scheme 4 Optimized reaction conditions.
The faster reaction times observed when the reaction is carried
out through the intermediacy of the cationic gold species,
suggest that the rate-determining step in the reaction is the chlor-
ide abstraction from the [Au(NHC)Cl] complex. When efficient
chloride abstractors are used, e.g. silver salts, the hydroxide
exchange is faster and complexes 1 and 4 are obtained within
2 h. Whilst in the absence of a chloride abstractor, the hydroxide
exchange is slower and the reaction requires at least 20 h.
We suspect that the problem encountered with the synthesis of
Au-hydroxides bearing NHC ligands other than IPr is the
thermal stability of the intermediate species generated during the
reaction. In the original procedure for the synthesis of hydroxide
1, it was necessary to heat the reaction to 60 °C;3 whilst in the
present procedure, the temperature was reduced to 30 °C but
requires the use of a larger amount of KOH.
Fig. 1 Molecular representation of [Au(SIPr)(OH)] 4. Most H atoms
are omitted for clarity. Selected bond distances (Å) and angles (°) for 4:
Au1–O1 2.019(7), Au1–C1 1.976(8), C1–Au1–O1 180.00(1).
Since this new synthetic route requires, initially, the synthesis
and isolation of the digold complex, the development of a more
straightforward procedure was investigated next. As the reaction
proceeded faster and under milder conditions using a cationic
species, e.g. 5, a one-pot approach was devised. Starting from a
chloro complex [Au(NHC)Cl], using AgBF4 as chloride abstrac-
tor, the cationic gold species [Au(NHC)][BF4] was generated.
After filtration of the AgCl produced during the reaction, 2.3
5462 | Dalton Trans., 2012, 41, 5461–5463
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THF (3 mL). The reaction mixture was stirred for 24 h at 30 °C, then
filtered through Celite and concentrated under vacuum. The resulting
solid was dissolved in the minimum amount of THF (2 mL) and the
product was precipitated by addition of pentane (8 mL). The precipitate
was collected by filtration, affording 4 as a white powder in 75% yield.
1H NMR (400 MHz; CD2Cl2): δ = 7.45 (t, J = 7.8 Hz, 2H), 7.28 (d, J =
7.8 Hz, 4H), 3.99 (s, 4H), 3.06 (sept, J = 6.9 Hz, 4H), 1.41 (d, J = 6.8
Hz, 12H), 1.33 (d, J = 6.9 Hz, 12H), −0.71 (br, 1H) ppm. 13C NMR
(101 MHz; CD2Cl2): δ = 193.5, 147.2, 135.0, 130.0, 124.8, 53.7, 29.2,
25.1, 24.2 ppm. Anal. Calcd for C27H39AuN2O (604.58): C, 53.64; H,
6.50; N, 4.63. Found: C, 53.50; H, 6.36; N, 4.48.
In order to validate the scalability of the new excess KOH pro-
cedure, complexes 1 and 4 were synthesized on 1 g scale. Grati-
fyingly, the reactions reached completion within 24 h, affording
gold hydroxides 1 and 4, in 75% and 70% isolated yields,
respectively.
Conclusions
A new strategy for the synthesis of AuI-hydroxide complexes is
reported and, through optimization, insights into the reaction
mechanism leading to the formation of the gold hydroxides are
provided. A two-step procedure starting from [Au(NHC)Cl],
generating [{Au(NHC)}2(μ-OH)][BF4] and subsequent addition
of KOH afforded [Au(NHC)(OH)] in good yields (80–86%)
with short reaction times (1 h). This procedure enabled the iso-
lation of the novel [Au(SIPr)(OH)]. A one-pot reaction, without
isolation of a digold species, was then developed. Reaction via
the cationic species [Au(NHC)][BF4] also allowed the formation
of gold hydroxides in good yields (75–77%) and short reaction
times (1.5 h). In order to avoid using expensive silver salts,
[Au(NHC)(OH)] (NHC = IPr and SIPr) could be isolated in
good yields by using a simpler protocol where a larger amount
of KOH is employed. However, longer reaction times are
required due to the inefficient chloride abstraction performed by
KOH in this regime. In the end, for synthetic purposes
Ockham’s razor17 prevails, simpler is better and only a larger
excess of KOH appears to solve issues of scalability and repro-
ducibility previously encountered.
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2 (a) N. Marion and S. P. Nolan, Chem. Soc. Rev., 2008, 37, 1776–1782;
(b) S. P. Nolan, Acc. Chem. Res., 2011, 44, 91–100 and references cited.
3 S. Gaillard, A. M. Z. Slawin and S. P. Nolan, Chem. Commun., 2010, 46,
2742–2744.
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DOI: 10.1021/ar200188f.
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S. P. Nolan, Chem. Commun., 2011, 47, 5455–5457.
Further studies towards the application of this procedure in the
synthesis of new [Au(NHC)(OH)] complexes and investigations
into the properties of these novel complexes are ongoing in our
laboratories.
7 S. Gaillard, J. Bosson, R. S. Ramón, P. Nun, A. M. Z. Slawin and S.
P. Nolan, Chem.–Eur. J., 2010, 16, 13729–13740.
8 (a) S. Gaillard, P. Nun, A. M. Z. Slawin and S. P. Nolan, Organometal-
lics, 2010, 29, 5402–5408; (b) P. Nun, S. Gaillard, A. M. Z. Slawin and
S. P. Nolan, Chem. Commun., 2010, 46, 9113–9115; (c) E. Brulé,
S. Gaillard, M.-N. Rager, T. Roisnel, V. Guérineau, S. P. Nolan and
C. M. Thomas, Organometallics, 2011, 30, 2650–2653;
(d) D. Konkolewicz, S. Gaillard, A. G. West, Y. Y. Cheng, A. Gray-
Weale, T. W. Schmidt, S. P. Nolan and S. Perrier, Organometallics, 2011,
30, 1315–1318; (e) P. Nun, S. Dupuy, S. Gaillard, A. Poater, L. Cavallo
and S. P. Nolan, Catal. Sci. Technol., 2011, 1, 58–61; (f) P. Nun,
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2011, 9, 101–104; (g) S. R. Patrick, I. I. F. Boogaerts, S. Gaillard,
A. M. Z. Slawin and S. P. Nolan, Beilstein J. Org. Chem., 2011, 7, 892–
896.
Acknowledgements
The ERC (Advanced Investigator Award-FUNCAT) and the
EPSRC are gratefully acknowledged for support of this work.
Umicore AG is acknowledged for their generous gift of auric
acid. We thank Dr Sylvain Gaillard for preliminary synthetic
contributions. S.P.N. is a Royal Society Wolfson Research Merit
Award holder.
9 For the first report on the synthesis and use of IPr as supporting ligand in
catalysis, see: J. Huang and S. P. Nolan, J. Am. Chem. Soc., 1999, 121,
9889–9890.
10 R. S. Ramón, S. Gaillard, A. Poater, L. Cavallo, A. M. Z. Slawin and S.
P. Nolan, Chem.–Eur. J., 2011, 17, 1238–1246.
Notes and references
11 (a) R. S. Ramón, S. Gaillard, A. M. Z. Slawin, A. Porta, A. D’Alfonso,
G. Zanoni and S. P. Nolan, Organometallics, 2010, 29, 3665–3668;
(b) V. Merlini, S. Gaillard, A. Porta, G. Zanoni, G. Vidari and S.
P. Nolan, Tetrahedron Lett., 2011, 52, 1124–1127.
12 In order to avoid formation of chloro species 2 by traces of HCl in chlori-
nated solvents, THF was used.
13 The reactions were carried out at 30 °C rather than at rt to ensure
reproducibility.
14 As the H of the OH is disordered, no O–H length is given.
15 A. Poater, B. Cosenza, A. Correa, S. Giudice, F. Ragone, V. Scarano and
L. Cavallo, Eur. J. Inorg. Chem., 2009, 1759–1766.
16 Parameters used for SambVca calculations: (a) 3.50 Å was selected as the
value for the sphere radius, (b) 2.00 Å was considered as distances for the
metal–ligand bond, (c) usually irrelevant in crystallography, hydrogen
atoms were omitted, and (d) Bondi radii scaled by 1.17 were used.
17 Ockham’s razor (lex parsimoniae or the law of parsimony) states that
“entities must not be multiplied beyond necessity” (entia non-sunt multi-
plicanda praeter necessitatem). We find the present synthetic study to be
a good representation of this principle.
§Synthesis of [{Au(SIPr)}2(μ-OH)][BF4] (5): AgBF4 (40 mg, 204 μmol)
was added to a stirred solution of [Au(SIPr)Cl] (6) (100 mg, 160 μmol)
in dichloromethane (3 mL). The reaction mixture was stirred avoiding
the presence of light at rt for 5 min and then filtered over Celite into a
separating funnel containing distilled water (10 mL). The mixture was
shaken for 1 min. The organic phase was collected, dried over anhydrous
MgSO4 and concentrated under vacuum. The resulting solid was dis-
solved in the minimum amount of CH2Cl2 (2 mL) and the product was
precipitated by addition of pentane (8 mL). The precipitate was collected
by filtration, affording 5 as a white powder in 83% yield 1H NMR
(400 MHz; CD2Cl2): δ = 7.42 (t, J = 7.8 Hz, 4H), 7.19 (d, J = 7.8 Hz,
8H), 4.01 (s, 8H), 2.88 (sept, J = 6.9 Hz, 8H), 1.28 (d, J = 6.9 Hz, 24H),
1.16 (d, J = 6.8 Hz, 24H), 0.37 (s, 1H) ppm. 13C NMR (101 MHz;
CD2Cl2): δ = 186.1, 146.9, 134.1, 130.4, 124.9, 53.93, 53.80, 29.1,
25.2, 24.1 ppm. 19F NMR (376 MHz; CD2Cl2): δ = −154.09,
−154.14 ppm. Anal. Calcd. for C54H77Au2BF4N4O (1278.95): C, 50.71;
H, 6.07; N, 4.38. Found: C, 50.58; H, 6.00; N, 4.49.
Synthesis of [Au(SIPr)(OH)] (4): KOH (90 mg, 1.60 mmol) was
added to a stirred solution of [Au(SIPr)Cl] (6) (100 mg, 0.16 mmol) in
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Dalton Trans., 2012, 41, 5461–5463 | 5463