Carbene transfer from triazolylidene gold complexes as a potent strategy for inducing high catalytic activity

Article abstract of DOI:10.1021/ja406999p

A series of gold(I) complexes [AuCl(trz)] were synthesized that contain 1,2,3-triazolylidene (trz) ligands with variable wingtip groups. In the presence of AgBF₄, these complexes undergo ligand redistribution to yield cationic complexes [Au(trz)₂]BF₄ in high yields as a result of efficient carbene transfer. Identical reactivity patterns were detected for carbene gold complexes comprised of Arduengo-type IMes ligands (IMes = N,N′-dimesityl-imidazol-2-ylidene). Reaction of cationic complexes [Au(trz)₂]⁺ with [AuCl(trz′)] afforded the heteroleptic complex [Au(trz)(trz′)]⁺ and [AuCl(trz)] (trz, trz′ = triazolylidene ligands with different wingtip groups). Carbene transfer occurs spontaneously, yet is markeldy rate-enhanced in the presence of Ag⁺. The facile carbene transfer was exploited as a catalyst activation process to form active gold species for the aldol condensation of isocyanides and aldehydes to form oxazolines. The catalytic activity is strongly dependent on the presence of Ag⁺ ions to initiate catalyst activation. High turnovers (10⁵) and turnover frequencies (10 ⁴ h^-1) were accomplished. Structural analysis at early stages of the reaction support the critical role of triazolylidene dissociation to activate the precatalyst and dynamic light scattering revealed the presence of nanoparticles (±100 nm diameter) as potential catalytically active species. Furthermore, the triazolylidene scaffold had no impact on the diastereoselectivity of the oxazoline formation, and chiral triazolylidenes did not induce any asymmetry in the product. The facile dissociation of carbenes from [AuCl(carbene)] in the presence of Ag⁺ ions suggests a less stable Au-C_carbene interaction than often assumed, with potential implications for gold-catalyzed reactions that employ a silver salt as (putative) halide scavenger.

Full text of DOI:10.1021/ja406999p

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Article
Carbene Transfer from Triazolylidene Gold Complexes
as a Potent Strategy for Inducing High Catalytic Activity
Daniel Canseco-Gonzalez, Ana Petronilho, Helge Müller-
Bunz, Kohsuke Ohmatsu, Takashi Ooi, and Martin Albrecht
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/ja406999p • Publication Date (Web): 31 Jul 2013
Downloaded from http://pubs.acs.org on August 17, 2013
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Carbene Transfer from Triazolylidene Gold Complexes as a Potent Strategy for Inducing
High Catalytic Activity
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Daniel CansecoꢀGonzalez,† Ana Petronilho,† Helge MuellerꢀBunz,† Kohsuke Ohmatsu,‡ Takashi
Ooi,‡ and Martin Albrecht*†
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† School of Chemistry and Chemical Biology, University College Dublin, Belfield, Dublin 4,
Ireland
‡ Department of Applied Chemistry, Graduate School of Engineering, Nagoya University,
Nagoya, 464ꢀ8603, Japan
Abstract. A series of gold(I) complexes [AuCl(trz)] were synthesized that contain 1,2,3ꢀ
triazolylidene (trz) ligands with variable wingtip groups. In the presence of AgBF4, these
complexes undergo ligand redistribution to yield cationic complexes [Au(trz)2]BF4 in high yields
as a result of efficient carbene transfer. Identical reactivity patterns were detected for carbene
gold complexes comprised of Arduengoꢀtype IMes ligands (IMes = N,N’ꢀdimesitylꢀimidazolꢀ2ꢀ
ylidene). Reaction of cationic complexes [Au(trz)2]+ with [AuCl(trz’)] afforded the heteroleptic
complex [Au(trz)(trz’)]+ and [AuCl(trz)] (trz, trz’ = triazolylidene ligands with different wingtip
groups). Carbene transfer occurs spontaneously, yet is markeldy rateꢀenhanced in the presence of
Ag+. The facile carbene transfer was exploited as a catalyst activation process to form active gold
species for the aldol condensation of isocyanides and aldehydes to form oxazolines. The catalytic
activity is strongly dependent on the presence of Ag+ ions to initiate catalyst activation. High
turnovers (105) and turnover frequencies (104 h–1) were accomplished. Structural analysis at early
stages of the reaction support the critical role of triazolylidene dissociation to activate the preꢀ
catalyst and dynamic light scattering revealed the presence of nanoparticles (±100 nm diameter)
as potential catalytically active species. Furthermore, the triazolylidene scaffold had no impact
on the diastereoselectivity of the oxazoline formation, and chiral triazolylidenes did not induce
any asymmetry in the product. The facile dissociation of carbenes from [AuCl(carbene)] in the
presence of Ag+ ions suggests a less stable Au–Ccarbene interaction than often assumed, with
potential implications for goldꢀcatalyzed reactions that employ a silver salt as (putative) halide
scavenger.
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Introduction
Catalysis using gold complexes has become one of the most vibrant areas of modern synthesis.1,2
In line with progress in the catalytic application of other (late) transition metals, the catalytic
chemistry of gold has been strongly stimulated by the availability of Nꢀheterocyclic carbenes
(NHCs)3 as paramount and potent ligands in catalysis4 and beyond.5,6 These NHC ligands convey
properties and constraints that are often complementary to the ubiquitous phosphine ligand
classes.7 For example, NHCs stabilize highly unusual and hitherto elusive reactive species.8
Their success as spectator ligands has generally been associated with two key parameters: the
strong donor ability and the high covalent contribution to the metal bond, which is markedly
higher than in metal bonding of other dative ligands such as neutral Nꢀ and Pꢀdonors.8,9 Tight
metalꢀligand bonding has been assumed to impart high robustness of the catalytically active
species and thus an essential factor for accomplishing large catalytic turnover numbers.10 This
bonding situation is thus in sharp contrast to the dative bonding of phosphines, which are
kinetically labile and undergo dissociation and reꢀcoordination to a (catalytically active) metal
center.11
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Early work has demonstrated the susceptibility of carbene ligands towards degradation,
especially in redox processes and hydrogenations.12 The presence of alkyl or hydride groups at
the metal center has been demonstrated to induce reductive azolium elimination, and likewise,
the reverse process has been used to synthesize metal carbene complexes.13 Typically, a given set
of conditions favors the carbene formation or the carbene dissociation, and only rarely, carbene
dissociation has been demonstrated to be a microscopically reversible process.14 In addition,
recent transmetalation studies indicate that carbene transfer may occur from a range of different
metals in addition to the most frequently used silver carbene intermediates,15 suggesting that the
M–NHC bond may be less tight than often assumed. By using triazolylidenes16 as synthetically
versatile analogues of Arduengoꢀtype imidazolylidenes for the development of powerful catalytic
systems,17 we have recently provided evidence that PdCl2 and CuCl are leaving groups in the
corresponding carbene complexes,18,19 thus providing access to catalytically active species where
the triazolylidene ligand may not be bound to the active site. We have now expanded this
concept and report here on gold triazolylidene complexes as catalyst precursors for the catalytic
synthesis of oxazolines. Evidence is provided for triazolylidene dissociation from the gold
coordination sphere as a pivotal step in catalyst activation. Similar carbene transfer is also
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observed in Arduengoꢀtype NHC gold systems, which has implications for a broad range of
goldꢀ (and indeed other metalꢀ)catalyzed reactions starting from carbene metal catalyst
precursors.
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Results and discussion
Synthesis of triazolylidene gold complexes. The neutral gold(I) triazolylidene complexes 2a–f
were synthesized from the corresponding 1,2,3ꢀtriazolium halides and Ag2O and subsequent
transmetalation with AuCl(SMe2) (Scheme 1), according to established procedures.17c When
starting from triazolium halides rather than tetrafluoroborate salts, additives are generally not
required for the complex formation and yields of 2a–f were generally good (60–80%). An
exception was the metalation of triazolium salt 1d with tertꢀbutyl wingtips. Complex 2d was
only obtained in moderate yields upon addition of (NMeEt3)I to the reaction mixture and after
prolonged reaction times. Complexes 2a–f are air and moisture stable in solution and in the solid
state.
R'
R'
I–
1. Ag2O
2. [Au(SMe2)Cl]
N
N
N
N
+
Au Cl
N
N
R
1
R
2
R
R'
Mes
3,4,5-(MeO)3-C6H2 4-(MeO)-C6H4
Ph
tBu
a
b
c
d
e
f
Mes
Ph
tBu
Ph
tBu
adamantyl
adamantyl
Scheme 1 Synthesis of neutral triazolylidene gold(I) complexes 2.
Successful metalation of the triazolium salts is spectroscopically indicated by the disappearance
of the lowꢀfield triazolium proton resonance in the 1H NMR spectrum and a slight upfield shift of
the N–CH3 resonance. The goldꢀbound carbon appears in the δC 152–166 range, in agreement
with previously related complexes17c and significantly upfield shifted in comparison with
imidazolꢀ2ꢀylidene analogues (166ꢀ195 ppm)20 or 1,2,4ꢀtriazolylidene gold(I) complexes (168ꢀ
178 ppm).20a,21 Complexes 2a, 2b, 2d and 2e were analyzed by singleꢀcrystal Xꢀray diffraction
(Fig. 1), which revelaed the expected linear coordination geometry around the Au center. The
AuꢀCtrz distances (1.980–1.993 Å) and the AuꢀCl bond lengths (2.282–2.290 Å) are within
expectation (Table 1).17c When compared to sterically identical Arduengoꢀtype imidazolylidene
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complexes, a slight but consistent increase of the AuꢀCl bond length is noted, which reflects the
stronger trans influence of the triazolylidene ligand.22 For example, the AuꢀCl bond length
measures 2.2833(8) Å in 2a compared to 2.2756(12) Å in AuCl(IMes),20c and 2.2898(10) Å in
2d vs. 2.2742(7) Å in AuCl(ItBu) (IMes = 1,3ꢀdimesitylꢀ2ꢀimidazolylidene, ItBu = 1,3ꢀdiꢀtꢀ
butylꢀ2ꢀimidazolylidene).20a
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Fig. 1 ORTEP diagrams of complex 2a,b,d,e (50% probability level; coꢀcrystallized solvent molecules and
hydrogen atoms omitted for clarity; only one crystallographically independent molecule of a shown).
Table 1 Selected bond lengths [Å] and angles [°] in complexes 2a, 2b, 2d, and 2e.
complex
2a
Au–C(1)
1.980(3)
1.987(3)
1.993(4)
1.990(2)
Au–Cl(1)
2.2833(8)
2.2821(7)
2.2898(10)
2.2881(6)
C(1)–Au–Cl(1)
176.95(10)
179.36(9)
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174.25(12)
178.03(7)
2d
2e
Amideꢀfunctionalized triazolium salts gave different products upon metalation. In addition to the
diagnostic features established for complexes 2a–f, NMR spectra of complex 2g derived from
the enantiopure triazolium bromide 1g23 revealed the absence of the amide proton resonance.
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Moreover microanalysis indicated the halideꢀfree molecular formula. Based on these data, a
bimetallic complex was inferred with a bridged ligand coordination mode (Scheme 2). This
bonding mode was also observed upon auration of the triazolium salt 1h containing a Bocꢀ
protected amine wingtip group. Complex 2h displayed similar spectroscopic features as 2g,
including the absence of the NH resonance. Furthermore, a single crystal Xꢀray analysis of
complex 2h confirmed the dimeric connectivity pattern (Fig. 2).24
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Ph
Bz
N
Ph
Au
N
N
Ph
Ph
1. Ag2O
2. [Au(SMe2)Cl]
Ph
Ph
N
Ph
N
Ph
+
Ph
Au
Br–
N
Ph
N
N
N
Ph
N
N
Ph
Ph
Bz
NH
Bz
Ph
Ph
1g
2g
Mes
Boc
NH
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N
Cl–
N
N
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2. [Au(SMe2)Cl]
N
Au
N
+
N
N
N
Au
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N
Mes
Boc
Mes
1h
2h
Scheme 2 Synthesis of the dimetallic complex 2g and 2h.
Fig. 2 ORTEP presentation of complex 2h (50%
level), Au–C1 2.003(8) Å, Au–N4b 2.026(7) Å,
C1–Au–N1 179.3(3)°.
The chloride ligand in complexes 2a–f is readily substituted. For example, the cationic
phosphineꢀligated carbene gold(I) complex 3 was obtained from 2a and PPh3 in the presence of
AgBF4 as halide scavenger (Scheme 3). This ligand exchange induced a small upfield shift of the
N3ꢀbound methyl proton resonances by 0.17 ppm and a substantial 15 ppm deshielding of the
carbenic signal to δC 177.0 ppm (2JPC = 122 Hz). The JPC coupling constant is slightly smaller
than that observed for the analogous complex containing an Arduengoꢀtype carbene ligand,25 in
agreement with a stronger trans influence of the triazolylidene. The 31P NMR chemical shift in 3
is 40.9 ppm, similar to imidazolylidene analogues.25 In the crystal structure of 3 (Fig. 3), the Au–
Ctrz bond is about 0.05 Å longer than in the neutral analogue 2a (2.028(3) Å vs 1.980(3) Å) due
to the stronger trans influence of PPh3 vs Cl–.
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BF4
Mes
Mes
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PPh3, AgBF4
N
N
N
N
Au Cl
Au PPh3
N
N
Mes
Mes
2a
3
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Scheme 3 Synthesis of complex 3.
Fig. 3 Xꢀray structure of complex 3 (50% probability,
hydrogens and anion omitted for clarity); Au1–C1 2.028(3)
Å, Au1–P1 2.2795(7) Å, C1–Au–P1 174.05(8)°.
Two homoleptic bis(carbene) gold(I) complexes were prepared from the corresponding
triazolylidene silver intermediates by transmetalation with only half an equivalent of
AuCl(SMe2) (Scheme 4). Complex 4a bearing mesityl wingtips was obtained in 73% yield,
while complex 4e was less efficient (30% yield) even when the reaction was stirred for extended
periods because of competitive formation of the mono(triazolylidene) gold complex 2e.26 A oneꢀ
pot synthesis without isolation of the silver carbene intermediate did not improve the yield and
complex 2e was the dominant product (80% conversion). A diagnostic signature of the
bis(carbene) complex 4a is the magnetic inequivalence of the orthoꢀmethyl protons (
δH 1.82 and
1.76 ppm) and the aromatic CMes–H protons ( H 6.92 and 6.86 ppm). No such desymmetrization
δ
was noted for the mono(triazolylidene) gold complex 2a. Likewise, free rotation of the
adamantyl wingtips is restricted in 4e as indicated by the AB doublet centered at δH 1.62 and
13
1.44 ppm for the methylene groups. Furthermore, the C NMR data showed a lowfield AuꢀCtrz
signal at 175.8 ppm and 166.5 ppm for 4a and 4e, respectively, which corresponds to a 13 ppm
downfield shift compared to the corresponding mono(triazolylidene) analogues 2a and 2e. Xꢀray
diffraction analysis of single crystals of 4e confirmed the bonding of two triazolylidene ligands
to the gold center (Fig. 4). The AuꢀCtrz bond distance (2.029(4) Å) is similar to the bond length
observed in the phosphine complex 3a and thus slightly longer in the cationic complexes than in
2e. Similar differences were observed in neutral mono(carbene) vs cationic bis(carbene) gold
complexes of Arduengoꢀtype NHCs.21b,25,27
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R'
R'
N
I–
N
N
2
+
2
Au Cl
N
N
N
R
1a
1e
R
2a
2e
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1. Ag2O
2. [Au(SMe2)Cl]
AgBF4
X
R
30–73%
R'
76–95%
X = BF4
–
X = ICl2
N
N
N
N
N
Au
N
R'
4a (R = R' = Mes)
4e (R = Adamantyl, R' = Ph)
R
Scheme 4 Synthesis of bis(triazolylidene) gold(I) complexes 4a and 4e.
Fig. 4 ORTEP representation of one of the two crystallographically independent molecules of 4e (50% probability
–
level, Cl–/ICl2 anion, coꢀcrystallized Et2O and hydrogen atoms omitted for clarity); Au1–C1 2.029(4) Å, C1–Au1–
C20 179.42(15)°.
Carbene transfer. Alternatively, the bis(carbene) gold complexes were formed by reacting the
gold complexes 2a or 2e with AgBF4 (Scheme 4). This procedure is straightforward and afforded
the bis(carbene) complexes 4c and 4e in higher yields (95% and 76% respectively) and much
better selectivity than via direct transmetalation (cf complex 4e). No formation of byꢀproducts
such as triazolium salts was observed. The spectroscopic data of the products are identical,
irrespective of the nature of the nonꢀcoordinating anion (Cl–/ICl2 in the transmetalation, BF4 in
the AgBF4ꢀmediated route). Silverꢀassisted formation of complexes 4 from 2 implies a carbene
transfer from one Au center to another, indicating that the Au–Ctrz bond is not very strong in the
presence of Ag+ ions and that dissociation is facile.
–
–
The kinetic lability of the carbene ligand in the triazolylidene gold complexes was further
1
demonstrated by mixing 4a and the gold complex 2e (Scheme 5). H NMR spectroscopy
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revealed unreacted 4a by the diagnostic aromatic resonances at 6.93 and 6.87 ppm for the
mesityl protons after 1 h. Furthermore, formation of the monocarbene gold complex 2a was
indicated in 5% by the appearance of the pertinent resonances (3.90 ppm for the N3ꢀbound
methyl group). In addition, a new heteroleptic gold complex 5 formed in small quantities (ca.
5%). Complex 5 is characterized by a lowfield signal (δH 4.11 ppm for the N3ꢀmethyl group),
and an AB doublet for the adamantyl wingtip at 1.67 ppm and 1.48 ppm (2JHH = 12.4 Hz)
indicating a hindered rotation of this group as expected for bis(carbene) complexes (cf 4e).
Subsequent addition of AgBF4 (10 mol%) to this reaction mixture induced a marked increase of
2a to about 40% and a concomitant decrease of 4a within 1 h. These results highlight that
carbene transfer occurs spontaneously, albeit slowly, and is strongly promoted by Ag+ ions.
Similar reactivity patterns have been established for triazolyidene palladium complexes in
Suzuki crossꢀcoupling catalysis,18 and in copper complexes for Huisgen cycloaddition reactions,
where the catalytically active species presumably consists of a ligandless CuCl species generated
by triazolylidene dissociation.19
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BF4
BF4
N
N
N N
N
N
Cl
Cl
+
+
Au
Au
Au
Au
40 °C, 1h
N
N
N
N
N
N
N N
N
N
N N
4a
2e
2a
5
95%
60%
no AgBF4
10% AgBF4
5%
40%
Scheme 5 Carbene transfer from bis(carbene) gold complex 4a to 2e.
It is worth noting that this transfer process is not exclusive to triazolylidenes and also applies to
Arduengoꢀtype carbene gold complexes (Scheme 6, Fig. 5).28 Thus exposure of AuCl(IMes)20b to
AgBF4 afforded the homoleptic complex 6 in high yield. The aromatic HMes and Himid protons
and also the paraꢀpositioned Ar–CH3 group appear at essentially identical frequency as in the
mono(carbene) gold precursor (ꢀδ < 0.12 ppm), and only the ortho methyl protons shift upfield
by a diagnostic 0.4 ppm (δ
H = 1.69 ppm in 6). The moderate shifts render 1H NMR spectroscopy
less suitable for probing the carbene transfer. More diagnostic is the characteristic 10 ppm
downfield resonance in the 13C NMR spectrum (δC 185.3 ppm in 6 vs 173.6 ppm in the
monocarbene gold complex), similar to the shifts observed for monoꢀ vs bis(triazolylidene)
complexes (see above) and also related heteroleptic bis(imidazolylidene) gold complexes.25
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BF4
Mes
Mes
Mes
6
7
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9
N
N
AgBF4
2
Au Cl
Au
N
N
N
Mes
[AuCl(IMes)]
Mes
Mes
6
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Scheme 6 Synthesis of bis(IMes) gold complex 6 via carbene transfer.
Fig. 5 Molecular structure of 6 (50% probability, hydrogens and anion omitted for clarity); Au(1)ꢀC(1) 2.007(2) Å,
C(1)A–Au(1)–C(1)B 176.32(10)°.
Catalytic synthesis of oxazolines. The carbene transfer reactivity patterns have specific
relevance in catalysis, especially in forming ligandless and hence highly reactive gold centers,29
and we have exploited this concept in oxazoline synthesis. The new triazolylidene gold
complexes are effective catalyst precursors for the aldol condensation of isocyanoacetate and
aldehydes to afford oxazolines.30,31 An initial set of experiments was carried out using
benzaldehyde and methyl isocyanoacetate as model substrates in order to determine the activity
of the different gold complexes and the relevance of additives (Table 2). The results indicate that
the phosphine triazolylidene gold(I) complex 3a and the bis(triazolylidene) gold(I) complex 4a
are poor catalyst precursors (entries 2, 3) while the neutral monocarbene gold complex 2a
provides access to a moderately active species (entry 1). Addition of AgBF4, in particular in
combination with NEtiPr2 as a Brønsted base31,32 accelerated catalytic transformations
significantly (entries 4–6). Interestingly, this is a synergistic effect, as addition of only a base is
detrimental to conversions (entry 5). The use of a base shifted the product distribution from an
essentially 1:1 cis/trans ratio to 3:1 in favour of the trans isomer. Conversion gradually raises
upon increasing the base concentration from 2 equiv (vs 2a) to 10 equiv, while selectivity is
slightly lower with 2 equiv base, but remains unaltered in the 5–30 equiv range. Moreover, a
50/50 product ratio did not isomerize under catalytic conditions in the presence of NEtiPr2,
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indicating that the change of selectivity in the absence/presence of the amine is a consequence of
a modification of the catalytically competent species rather than a postꢀcatalytic process. In
contrast, the reaction temperature had no impact on the stereoselectivity of the condensation
(entries 6–9). However, the reaction temperature directly correlated with the conversion rate.
While reactions at 0 °C required almost 24 h to reach completion, full conversions were
accomplished within only 30 min at 40 °C under otherwise identical conditions.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Table 2 Evaluation of triazolylidene gold complexes as catalyst precursorsa)
O
C
O
N
cat. [Au]
H
N
+
COOMe
additive
Ph
COOMe
entry
[Au]
2a
3a
4a
2a
2a
2a
2a
2a
2a
additive
time (h)
24
Temp °C conv. (%)b)
cis/trans b)
48/52
44/56
ꢀꢀꢀ
1
2
3
4
5
6
7
8
9
ꢀꢀꢀ
ꢀꢀꢀ
ꢀꢀꢀ
20
20
20
20
20
20
0
72
10
0
24
24
AgBF4
24
96
9
48/52
23/77
27/73
39/61
26/74
24/76
NEtiPr2
24
AgBF4, NEtiPr2
AgBF4
6
96
9
22
AgBF4, NEtiPr2
AgBF4, NEtiPr2
22
0
98
96
0.5
40
a)
General conditions: benzaldehyde (1.52 mmol), methyl isocyanoacetate (1.38 mmol), 2a (14 ꢁmol), CH2Cl2 (4
mL); as indicated: AgBF4 (16 ꢁmol), base (166 ꢁmol).
b) Conversions and cis/trans ratio determined by 1H NMR spectroscopy.
Control experiments were performed in order to determine whether the condensation is goldꢀ
catalyzed. Catalytic runs using K[N(SiMe3)2] in the absence or presence of the triazolium salt 1a
gave no oxazoline product within 20 h, indicating that the condensation is unlikely to be baseꢀ
catalyzed nor organoꢀcatalyzed by an inꢀsitu generated triazolylidene. The latter may be initiated
by ligand dissociation from the gold complexes 2a. Simple AuCl(SMe2) gave only marginal
conversions (13% in 20 h).
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The beneficial effect of AgBF4 was intriguing, especially when considering its role in mediating
the formation of bis(triazolylidene) complexes such as 4. We therefore performed a series of
experiments to clarify the role of the silver additive with a particular focus on the early stages of
the catalytic reaction. Thus complex 2a did not yield any oxazoline in the absence of AgBF4
within the first 10 min, but 75% conversion were reached with equimolar quantities of 2a and
AgBF4 (Table 3, entries 1,2).33 The role of Ag+ is usually to scavenge a halide in the catalyst
activation step,34 and we thus prepared the isonitrile complex 7 as a potential first intermediate in
the catalytic cycle (Scheme 7).35 Even though 7 should, not require AgBF4 to turn over if the
triazolylidene is a mere spectator ligand, this complex is completely inactive within 10 min
under standard conditions and only accomplishes moderate conversions once AgBF4 is added
(28% conversion, entries 3,4). Hence Ag+ appears to have a role beyond abstracting the chloride
from complex 2a and is involved in removing the triazolylidene from the gold coordination
sphere.36 These observations together with the high yield of bis(triazolylidene) complexes 4 from
2a in the presence of AgBF4 suggests that triazolylidene dissociation from the gold complex is
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
relevant for generating the catalytically active species.
C
BF4
Mes
Mes
N
CO2Me
N
N
N
N
Cl
Au
C
N
Au
AgBF4
N
N
CO2Me
Mes
Mes
2a
7
Scheme 7 Synthesis of cationic triazolylidene complex 7
Table 3 Catalytic synthesis of oxazolines with various triazolylidene gold complexes a)
entry
[Au]
AgBF4 (equiv)
conv’n (%)b) cis/transb)
1
2
3
4
5
6
7
8
0
1
0
73
0
ꢀꢀꢀ
25/75
ꢀꢀꢀ
2a
2a
0
7
1
28
0
36/64
---
7
0
4a
1
59
94
0
36/64
28/72
ꢀꢀꢀ
4a
4a
10
0
AuCl(SMe2)
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a) Benzaldehyde (1.5 mmol), methyl isocyanoacetate (1.4 mmol), [Au] (14 ꢁmol), base (0.17 mmol), equiv AgBF4
b)
1
relative to [Au], CH2Cl2 (4 mL), 40 °C, 10 min Conversions and cis/trans ratio determined by H NMR
6
7
spectroscopy.
8
9
Based on this presumption, the catalytic inactivity of the bis(carbene) complex 4a is not
unexpected (entries 5–7). With added AgBF4 (1 equiv per Au), activity is resumed, albeit
relatively low (59% after 10 min). Performance is substantially increased, however, when 10
equiv AgBF4 were added (94%). This reactivity pattern is commensurate with triazolylidene
dissociation as catalyst activation step, yielding predominantly a weakly active mono(carbene)
complex at low Ag/4a ratio, and inducing dissociation of both carbene ligands at higher Ag/4a
ratios to give an active species identical to that obtained from 2a and AgBF4. Since the free
carbene is catalytically silent (vide supra), these results taken together strongly suggest that the
catalytically active species is a triazolylideneꢀfree species, either a ligandless ‘hot’ Au+ ion or a
gold aggregate (cluster or nanoparticle).37 Small gold clusters have been recently reported to be
extraordinary active in C–C bond forming reactions.38 Further support for the formation of
aggregates was obtained from analysis of the catalytic reaction mixture by dynamic light
scattering, revealing the presence of particles in the 100 nm range once AgBF4 was added to a
solution containing complex 2a and the substrate (Fig. S1). Repetitive experiments indicated
consistently similarly sized particles, suggesting that additives (carbenes, triazolium salts, or
amine) may be involved in stabilizing the particles and in preventing the formation of larger
aggregates.39 Such a model provides a rationale for the synergistic effect of Ag+ as carbene
transfer agent and the base as particle stabilizer in catalytic reactions (cf Table 2). While the
formation of smaller (and presumably more active) particles cannot be excluded due to the
intrinsic principles of light scattering, these data reveal that aggregation of the ligandless gold
ions is occurring under catalytic conditions. It is worth noting that these in situ generated
nanoparticles induce substantially higher catalytic activity than AuCl(SMe2), which probably
suffers from aggregation in CH2Cl2 as the solvent for this catalytic reaction (entry 8).
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Carbene dissociation from complex 2a was further confirmed by NMR spectroscopy. Under
catalytically relevant conditions (1 equiv AgBF4, 40 °C) the mono(triazolylidene) complex
furnishes 5–10% of 4a within 10 min, as indicated by the appearance of the characteristic
resonances at 6.92 and 6.86 ppm for the aromatic mesityl protons and the inequivalence of the
three CH3 groups of the mesityl wingtip group.40 These results underline the kinetic lability of
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the AuꢀCtrz bond and support the formation of an active Au species via triazolylidene
dissociation in the presence of Ag+.
7
8
9
Evaluation of complexes 2a–g (Table 4, entries 1–6) revealed no direct correlation between
catalytic activity (TON, TOF) and the steric or electronic properties of the triazolylidene wingtip
groups. For example, sterically demanding adamantyl/phenyl substituents induce similar activity
as two mesityl groups (entries 1,5). Furthermore, only very minor differences were observed in
cis/trans selectivity of product formation, suggesting that the triazolylidene wingtip groups are
not involved the condensation step. When using the chiral triazolylidene gold complex 2g, no
asymmetric induction was observed and the obtained product mixture was racemic according to
chiral HPLC analysis. The absence of any enantioꢀ or diastereoselective control even with 2g
suggests a common catalytic species from complexes 2a–g that is not related to the triazolylidene
ligand, in agreement with carbene dissociation as catalyst activation step.41 The rate of
dissociation is likely dependent on the wingtip groups, hence providing a rationale for the
different activities (yet identical selectivities) observed with complexes 2a–g. Accordingly, the
activities observed in the series of complexes reflect the lability of the carbene ligand rather than
the ligandꢀinduced differences at the gold center. Thus, methoxyꢀsubstituted aryl wingtip groups
(2b) or tBu wingtips (2d) imparted highest activity and gave complete conversion within 5 min
(entries 2,4). Activity differences for these two complexes unveiled only when reducing the
catalyst loading from 1 to 0.5 mol%. Under these conditions, catalysis initiated by complex 2b
was significantly faster and achieved full conversion within 30 min while complex 2d required
about twice as long (entries 7,8). Timeꢀconversion profiles (Fig. S2) provided pertinent turnover
frequencies (TOFs). At 50% conversion, complex 2b reached a TOF50 = 2000 h–1. To the best of
our knowledge this is the highest activity reported for catalytic oxazoline synthesis to date.30,31
Further lowering the catalyst loading to 0.01 mol% is possible, though reaction time has to be
considerably extended to accomplish the 10,000 turnovers for full conversion (2d, entry 9).
Further lowering of catalyst loading was not productive (entry 10).
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Table 4 Catalytic activity of different gold complexes a)
O
C
O
N
cat. [Au]
H
N
+
COOMe
NEtiPr, AgBF4
Ph
COOMe
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entry
[Au]
2a
2b
2c
loading (mol%)
time (h)
0.5
conv’n (%)b) cis/trans b) TON TOF50 (h–1)c)
1
2
3
4
5
6
7
8
9
10
1
98
98
98
96
98
98
95
97
96
< 2
24/76
27/73
30/70
25/75
24/76
24/76
26/74
24/76
27/73
ꢀꢀꢀ
98
98
660
>1200
160
1
0.08
1.5
1
98
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1
0.08
0.5
96
>1200
800
2d
2e
1
98
1
1
98
400
2f
0.5
0.5
0.01
0.001
0.5
190
194
9600
ꢀꢀꢀ
2000
350
2b
2d
2b
2d
1
44
1100
ꢀꢀꢀ
240
a) General conditions: benzaldehyde (1.52 mmol), methyl isocyanoacetate (1.38 mmol), AgBF4 (16 ꢁmol), [Au] (14
ꢁmol), base (166 ꢁmol), CH2Cl2 (4 mL).
b) Conversions and cis/trans ratio determined by 1H NMR spectroscopy.
c) TOF50 = turnover frequency at 50% conversion.
The substrate scope was investigated with the catalyst precursors 2b and 2g (Table 5).
Benzaldehydes with electron donating and withdrawing substituents were converted well and no
significant electronic differentiation was noted. Bulky tBuCHO was poorly converted,
presumably due to steric limitations. However these restrictions increased substantially the
selectivity towards the trans diastereoisomer, lending further support to a substrateꢀcontrolled
regioselectivity of the condensation and a marginal role of the triazolylidene ligand in the
catalytic cycle, if any. In agreement with such a reactivity pattern, earlier work has demonstrated
the critical role of (chiral) anions in determining the product selectivity in the protodeauration
step of related condensation reactions.42
Table 5 Substrate scope for the catalytic aldol condensation with complexes 2b and 2g.a)
C
O
O
N
cat. [Au]
N
+
COOMe
R
H
AgBF4, NiPr2Et
R
COOMe
Entry Complex
R
conv’n (%)b) cis/trans (%)b)
> 95 28/72
1
C6H5
2b
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2
3
C6H5
4ꢀMeOꢀC6H4
4ꢀMeOꢀC6H4
4ꢀNO2ꢀC6H4
4ꢀNO2ꢀC6H4
4ꢀClꢀC6H4
4ꢀClꢀC6H4
tBu
> 95
93
25/75
37/63
20/80
35/65
16/84
39/61
30/70
5/95
2g
2b
2g
2b
2g
2b
2g
2b
2g
4
84
5
> 95
91
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
6
7
> 95
78
8
9
20
10
tBu
46
0/100
a)
Aldehyde (1.5 mmol), methyl isocyanoacetate (1.4 mmol), AgBF4 (16 ꢁmol), [Au] (14 ꢁmol), NiPr2Et (0.17
mmol), CH2Cl2 (4 mL), RT, 18 h; b) Conversions and cis/trans ratio determined by 1H NMR spectroscopy.
Conclusions
Triazolylidene gold complexes are precursors for highly active catalysts for the synthesis of
oxazolines. Mechanistic investigations and stereoselective considerations provide strong
evidence for triazolylidene dissociation as a critical step of catalyst activation. This dissociation
is facilitated by the presence of AgBF4 as carbene transfer mediator, a role of silver that is often
underestimated in metal catalyzed reaction and that reaches significantly beyond classical halide
scavenging. Once activated, appreciable turnover numbers (105) and frequencies (104 h–1) are
achieved. The carbene transfer is spontaneous, albeit slow, and considerably accelerated in the
presence of Ag+ ions. Transfer is not restricted to triazolylidenes and is also demonstrated for the
more frequently used IMes as representative of Arduengoꢀtype NHCs. These results call into
question the often cited and generally assumed stability of the Au–CNHC bond in catalytic
applications, in particular when silver salts are used as additives.43,44 Carbene dissociation
processes as demonstrated here provide ligandless metal centers that impart high catalytic
activity. Noteworthy, in such a model the different observed catalytic activities do not reflect
ligandꢀinduced changes at the metal center, but different dissociation propensities of the ligands
in the activation step. Such reactivity patterns may be relevant beyond goldꢀcentered NHC
chemistry and warrant a cautionary note when assuming a ‘strong’ or ‘kinetically inert’ bonding
of NHCs to metal centers, especially to coinage metals. Metalꢀtriggered ligand dissociation
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provides interesting perspectives, e.g. for supramolecular chemistry (selfꢀassembly) and for
generating latent catalysts that can be activated selectively, a process that is much harder to
achieve with other neutral donor ligand systems such as imines or phosphines.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
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43
44
45
46
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49
50
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Experimental section
General. 1ꢀ(3,4,5,ꢀtrimethoxyphenyl)ꢀ4ꢀ(4ꢀmethoxyphenyl)ꢀ1,2,3ꢀtriazole45 and the triazolium
salts 1a,46 1c,47 1g,23 and AuCl(IMes)20c were described previously. The synthesis of all new
triazoles and triazolium salts is reported in the supporting information. All solvents used for the
reactions were purified using an alumina/catalyst column system (Thermovac Co.). Ag2O was
freshly prepared according to literature procedures.48 All other reagents are commercially
available and were used as received. Unless specified otherwise, NMR spectra were recorded at
25 °C on Varian Innova spectrometers operating at 300, 400 or 500 MHz (1H NMR) and 75, 100
or 125 MHz (13C{1H} NMR), respectively. Chemical shifts (δ in ppm, coupling constants J in
Hz) were referenced to residual solvent resonances. Assignments are based on homoꢀ and
heteronuclear shift correlation spectroscopy. Elemental analyses were performed by the
Microanalytical Laboratory at University College Dublin, Ireland, by using an Exeter Analytical
CEꢀ440 Elemental Analyzer.
General procedure for the synthesis of the gold carbene complexes 2. Triazolium salt 1 (1.0
eq), Ag2O (0.5 eq) and AuCl(SMe2) (1.0 eq) in dry CH2Cl2 were stirred in CH2Cl2 in the dark at
room temperature for 24 h and filtered through Celite. The solvent was removed in vacuo the
residue was washed with pentane (25 mL) and dried, then reꢀdissolved in CH2Cl2 (2 mL) and
precipitated with pentane (50 mL). The precipitate was collected by filtration and passed through
a short pad of SiO2. Elution with dry CH2Cl2, and solvent evaporation yielded pure complex 2.
Complex 2a. According to the general method, the title compound was obtained from 1a (125
mg, 0.28 mmol), Ag2O (33 mg, 0.14 mmol), and AuCl(SMe2) (82 mg, 0.28 mmol) in dry CH2Cl2
1
(30 mL) as a white solid (92 mg, 60%). H NMR (CDCl3, 500 MHz): δ 7.03 (s, 4H, HMes), 3.90
(s, 3H, NCH3), 2.38 (s, 6H, ArCH3), 2.10 (s, 12H, ArCH3). 13C{1H} NMR (CDCl3, 125 MHz): δ
162.0 (Ctrz–Au), 146.1 (Ctrz–Mes), 141.1, 140.9, 138.1, 135.7, 134.3, 129.6, 129.3, 122.3 (8 ×
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CMes), 36.9 (NCH3), 21.5, 21.4, 20.3, 17.6 (4 x Ar–CH3). 1H NMR (CD2Cl2, 500 MHz): δ 7.00 (s,
2H, HMes), 7.09 (s, 2H, HMes), 3.90 (s, 3H, NCH3), 2.41 (s, 3H, ArCH3), 2.39 (s, 3H, ArCH3),
2.13 (s, 6H, ArCH3), 2.10 (s, 6H, ArCH3). 13C{1H} NMR (CD2Cl2, 125 MHz): δ 162.4 (Ctrz–Au),
146.4 (Ctrz–Mes), 141.7, 141.6, 138.6, 134.9, 129.9, 129.6, 129.3, 122.7 (8 × CMes), 37.4 (NCH3),
21.7, 21.6, 20.4, 17.8 (4 x Ar–CH3). Anal. Calcd for C21H25AuClN3 (551.86): C, 45.70; H, 4.57;
N, 7.61. Found: C, 45.77; H, 4.37; N, 7.55.
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Complex 2b. According to the general method, reaction of 1b (166 mg, 0.34 mmol), Ag2O (41
mg, 0.17 mmol), and AuCl(SMe2) (100 mg, 0.34 mmol) in dry CH2Cl2 (30 mL) gave 2b as a
1
3
yellow solid (160 mg, 80%). H NMR (CDCl3, 500 MHz): δ 7.61 (d, JHH = 9.0 Hz, 2HAr), 7.60
3
(s, 2HAr), 7.02 (d, JHH = 9.0 Hz, 2HAr), 4.18 (s, 3H, NCH3), 3.95 (s, 6H, OCH3), 3.92 (s, 3H,
OCH3), 3.89 (s, 3H, OCH3). 13C{1H} NMR (CDCl3, 125 MHz): δ 161.5, 131.2, 114.9, 113.2 (4 ×
CAr), 153.7, 139.7, 134.5, 101.8 (4 × CAr), 156.7 (CtrzꢀAu), 147.8 (Ctrz–Ar), 61.2 (OCH3), 56.9
(OCH3), 55.7 (OCH3), 38.1 (NCH3). Anal. Calcd for C19H21AuClN3O4 (587.80): C, 38.82; H,
3.60; N, 7.15. Found: C, 38.58; H, 3.30; N, 7.05.
Complex 2c. According to the general method, reaction of 1c (120 mg, 0.33 mmol), Ag2O (40
mg, 0.16 mmol), and AuCl(SMe2) (98 mg, 0.33 mmol) in dry CH2Cl2 (30 mL) yielded 2c as an
1
3
offꢀwhite solid (107 mg, 70%). H NMR (CDCl3 500 MHz): δ 8.05 (d, JHH = 7.0 Hz, 2H, HAr),
3
13
7.68 (d, JHH = 6.5 Hz, 2H, HAr), 7.56–7.50 (m, 6H, HAr), 4.18 (s, 3H, NCH3). C{1H} NMR
(CDCl3, 100 MHz): δ 157.3 (Ctrz–Au), 147.8 (Ctrz–Ph), 139.2, 130.6, 130.4, 129.9, 129.7, 129.4,
126.4, 124.3 (8 × CAr), 38.3 (NCH3). Anal. Calcd for C15H13AuClN3 (467.70): C, 38.52; H, 2.80;
N, 8.98. Found: C, 38.37; H, 2.50; N, 8.77.
Complex 2d. According to the general method, 1d (150 mg, 0.46 mmol), Ag2O (54 mg, 0.23
mmol), AuCl(SMe2) (136 mg, 0.46 mmol) and [NEt3Me]I (11 mg, 0.046 mmol) were reacted in
dry CH2Cl2 (30 mL) for 72 h. Complex 2d was obtained as a white solid (90 mg, 45%). 1H NMR
(CDCl3, 500 MHz): δ 4.22 (s, 3H, NCH3), 1.93, 1.67 (2 × (s, 9H CꢀCH3). 13C{1H} NMR
(CDCl3, 125 MHz): δ 157.7 (Ctrz–Au), 152.7 (Ctrz–tBu), 64.8 (NꢀCMe3), 40.9 (NCH3), 32.1 (Cꢀ
CMe3), 32.0, 30.9 (2 × CꢀCH3). Anal. Calcd for C11H21AuClN3 (427.72): C, 30.89; H, 4.95; N,
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9.82. Found: C, 30.70; H, 4.59; N, 9.62. H NMR (CD2Cl2, 500 MHz): δ 4.20 (s, 3H, NCH3),
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1.92, 1.66 (2 × (s, 9H CꢀCH3). 13C{1H} NMR (CD2Cl2, 125 MHz): δ 155.0 (Ctrz–Au), 152.6
(Ctrz–tBu), 64.9 (NꢀCMe3), 41.3 (NCH3), 32.3 (CꢀCMe3), 32.1, 31.0 (2 × CꢀCH3).
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Complex 2e. According to the general method, reaction of 1e (73 mg, 0.17 mmol), Ag2O (20
mg, 0.08 mmol), and AuCl(SMe2) (52 mg, 0.17 mmol) in dry CH2Cl2 (30 mL) gave 2e as a white
solid (70 mg, 77%). 1H NMR (CDCl3, 500 MHz): δ 7.64 (bs, 2HAr), 7.50 (bs, 3HAr), 4.06 (s, 3H,
NCH3), 2.66 (m, 6H, CH2 ada), 2.32 (bs, 3H, CHada), 1.81 (m, 6H, CH2 ada). 13C{1H} NMR
(CDCl3, 125 MHz): δ 152.8 (Ctrz–Au), 147.7 (Ctrz–Ph), 130.3, 129.8, 129.2, 127.4 (4 x CPh), 65.3
(CadaꢀN), 43.3 (CH2 ada), 37.8 (NCH3), 35.9 (CH2 ada), 30.0 (CHada). Anal. Calcd for
C19H23AuClN3 (525.82): C, 43.40; H, 4.41; N, 7.99. Found: C, 44.13; H, 4.22; N, 7.76.
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Complex 2f. The title compound was obtained according to the general method from 1f (100
mg, 0.25 mmol), Ag2O (29 mg, 0.13 mmol), and AuCl(SMe2) (78 mg, 0.25 mmol) in dry CH2Cl2
(30 mL) as a white solid (86 mg, 65%). 1H NMR (CDCl3, 500 MHz): δ 4.21 (s, 3H, NCH3), 2.64
(m, 6H, CH2 ada), 2.28 (bs, 3H, CHada), 1.81 (m, 6H, CH2 ada), 1.67 (s, 9H, CꢀCH3). 13C{1H} NMR
(CDCl3, 125 MHz): δ 154.5 (Ctrz–Au), 151.5 (Ctrz–tBu), 65.2 (CadaꢀN), 43.3 (CH2 ada), 40.9
(NCH3), 36.0 (CH2 ada), 31.9 (CꢀCMe3), 32.0 (CꢀCH3), 30.0 (CHada). Anal. Calcd for
C17H27AuClN3 (505.83): C, 40.37; H, 5.38; N, 8.31. Found: C, 40.33; H, 5.22; N, 8.28.
Complex 2g
1g (94 mg, 0.12 mmol) was mixed with Ag2O (14 mg, 0.06 mmol) and stirred for one hour in dry
CH2Cl2 (30 mL) at room temperature. AuCl(SMe2) (36 mg, 0.12 mmol) was added to the
reaction mixture and stirred for additional 16 h. The workup and purification were carried out
according to the general method to yield 2g as a white solid (69 mg, 62%). 1H NMR (CDCl3, 600
MHz) δ 8.22 (br, 2H, HAr), 8.20–7.98 (m, 6H, HAr), 7.61 (m, 2H, HAr ), 7.47–7.43 (m, 6H, HAr),
7.37–7.22 (m, 4H, HAr), 7.20–7.00 (m, 9H, HAr), 6.60–6.45 (m, 7H, HAr), 4.50, 4.21 (2 × AB
2
3
doublet, JHH = 14.3 Hz, 2H, NCH2Ph), 3.34 (d, 1H, JHH = 15.4 Hz, N1CHCHαβPh ), 3.03 (dd,
1H, 3JHH = 15.4 Hz, N1CHCHαβPh). 13C NMR (150 MHz, CDCl3) δ 166.4 (NC=O), 165.9 (Ctrz–
Au), 139.6, 135.3, 132.5, 132.3, 132.2, 131.8, 131.3, 130.5, 129.8, 129.4, 129.2, 129.1, 129.0,
128.9, 128.8, 128.7, 128.6, 128.5, 128.4, 128.3, 128.0, 127.9, 127.8, 127.7, 127.5, 127.4, 127.3,
127.0 (all CAr), 68.9 (N1CHCHαβPh), 68.7 (NCPh2), 54.3 (NCH2Ph), 36.2 (NCHCHαβPh). Anal.
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Calcd for (C49H39AuN4O)2 (1866.6): C, 65.62; H, 4.38; N, 6.25. Found: C, 65.52; H, 4.62; N,
6.03.
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Complex 2h. Complex 2h was obtained according to the general procedure from triazolium salt
1h (110 mg, 0.30 mmol), freshly prepared Ag2O (139 mg, 0.60 mmol), and AuCl(SMe2) (90 mg,
0.30 mmol) in dry CH2Cl2 (25 mL). The mixture was stirred in the dark for 5 h and filtered
through Celite. The solvent was concentrated to 1 mL and treated with pentane (150 mL). A
white precipitate formed after storage at 4 °C for 16 h. This solid was collected by decantation
and was dried in vacuo (60 mg, 36%). Recrystallized by slow diffusion of pentane into a CH2Cl2
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solution of 2h yielded single crystals suitable for Xꢀray diffraction analysis. H NMR (CDCl3,
400 MHz) δ 6.92 (s, 2H, HAr), 4.71 (s, 2H, CH2N), 4.39 (NCH3), 2.30 (s, 3H, Ar–CH3), 2.00 (s,
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6H, Ar–CH3), 1.17 (s, 9H, CH3 Boc). C{1H} NMR (CDCl3, 100 MHz): 163.5 (N–C=O), 163.3
(Ctrz–Au), 150.6 (Ctrz–alkyl), 137.9, 136.3, 134.6, 129.3 (4 × CMes), 76.3 (CMe3), 42.8 (CH2N),
37.5 (NCH3), 28.8 (CH3 Boc), 21.3, 18.0 (2 × Ar–CH3). HRꢀMS (ES+) Calcd for C36H51Au2N8O4
[M+H]+: 1053.3364. Found 1053.3409. Calcd for (C18H25AuN4O2)2 (1052.8): C, 41.07; H, 4.79;
N, 10.64. Found: C, 41.10; H, 4.81; N, 10.48.
Complex 3. Complex 2a (50 mg, 0.09 mmol), PPh3 (24 mg, 0.09 mmol), and AgBF4 (35 mg,
0.18 mmol) in dry CH2Cl2 (30 mL) were stirred in the dark for 4 h, and then passed through by a
small pad of Celite and eluted with CH2Cl2 (7 mL). After evaporation of all the volatiles the
residue was washed with pentane (20 mL), dissolved in CH2Cl2 (0.5 mL), and passed through a
short pad of Celite. Elution with CH2Cl2 (7 mL) and evaporation of the solvent afforded pure 3
1
3
as a white powder (62 mg, 80%). H NMR (CDCl3, 500 MHz): δ 7.52 (t, JHH = 7.2 Hz, 3H,
3
3
3
HPPh3), 7.40 (t, JHH = 7.2 Hz, 6H, HPPh3), 7.16 (dd, JHH = 7.2 Hz, JHP = 12.8 Hz, 6H, HPh3P),
7.07 (s, 4H, HMes), 4.07 (s, 3H, NCH3), 2.41, 2.38 (2 × s, 3H, ArCH3), 2.18, 2.13 (2 × s, 6H,
ArCH3). 31P{1H} NMR (CDCl3, 162 MHz): δ 40.9 (s, PPh3). 13C{1H} NMR (CDCl3, 125 MHz):
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δ 177.0 (d, JCP = 122.1 Hz, Ctrz–Au), 147.4 (Ctrz–Mes), 141.4, 141.3, 138.3, 135.8, 134.7 (5 ×
CMes), 134.1 (d, 3JCP = 13.7 Hz, CHPPh3), 132.3 (d, 4JCP = 2.5 Hz, CHPPh3), 129.7 (CMes), 129.5 (d,
2JCP = 14.5 Hz, CHPPh3), 128.5 (d, 1JCP = 57.4 Hz, CPPh3), 121.6 (CMes), 37.7 (NCH3), 21.5, 20.5,
20.4, 17.7 (3 × Ar–CH3). Anal. Calcd for C39H40AuPN3BF4 (865.50): C, 54.12; H, 4.66; N, 4.86.
Found: C, 53.73; H, 4.46; N, 4.55.
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Complex 4a. Method A: Triazolium salt 1a (200 mg, 0.45 mmol), and Ag2O (55 mg, 0.23 mmol)
in dry CH2Cl2 (10 mL) were stirred in the dark for 24 h. AuCl(SMe2) (66 mg, 0.22 mmol) was
added and the solution was stirred for 48 h and filtered through Celite. The solvent was removed
in vacuo then the residue was washed with pentane (25 mL) and dried, then reꢀdissolved in
CH2Cl2 (2 mL) and precipitated with pentane (50 mL). The solid was collected by filtration
under air then dried over vacuum to yield 4a as a yellow solid (150 mg, 73%). Microanalysis
indicates a 1:7 mixture of chloride and dichloroiodate(I) anions; Anal. Calcd for 7/8
C42H50N6AuICl2 (1033.66) + 1/8 C42H50N6AuICl2 (1033.66): C, 49.78; H, 4.97; N, 8.29. Found:
C, 49.79; H, 4.74; N, 8.17.
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Method B: Complex 2a (50 mg, 0.09 mmol), and AgBF4 (18 mg, 0.09 mmol) in dry CH2Cl2 (10
mL) were stirred in the dark for 12 h at RT. The solution was passed through a short pad of
Celite and eluted with CH2Cl2 (5 mL) and concentrated to approximately 1 mL. Addition of
pentane (50 mL) afforded 4a as a white powder. The solid was collected by filtration and dried
under vacuum (40 mg, 95%). Anal. Calcd for C42H50N6AuBF4 (922.66) × 0.5H2O: C, 54.14; H,
5.52; N, 9.02. Found: C, 54.10; H, 5.28; N, 8.66.
Spectroscopic analyses were identical for both products: 1H NMR (CDCl3, 400 MHz): δ 6.92 (s,
4H, HMes), 6.86 (s, 4H, HMes), 3.88 (s, 6H, NCH3), 2.42 (s, 12H, ArCH3), 1.82 (s, 12H, ArCH3),
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1.76 (s, 12H, ArCH3). C{1H} NMR (CDCl3, 100 MHz): δ 175.8 (Ctrz–Au), 146.7 (Ctrz–Mes),
140.6, 140.4, 138.0, 135.6, 134.2, 129.2, 128.9, 122.1 (8 × CMes), 37.1 (NCH3), 21.6, 21.5, 20.1,
17.3 (4 × Ar–CH3).
Complex 4e. Method A: Triazolium salt 1e (200 mg, 0.47 mmol), and Ag2O (55 mg, 0.23 mmol)
in dry CH2Cl2 (10 mL) were stirred in the dark for 24 h. AuCl(SMe2) (70 mg, 0.24 mmol) was
added and the solution was stirred for 48 h and filtered through Celite. The solvent was removed
in vacuo the residue was washed with pentane (25 mL) and dried, then reꢀdissolved in CH2Cl2 (2
mL) and precipitated with pentane (50 mL). The solid was collected by filtration under air then
dried in vacuum to yield a yellow solid comprised of a mixture of 2e and 4e (152 mg, ca. 1:1).
Pure 4e was obtained from recrystallization by slow diffusion of Et2O into a saturated solution of
complex 4e in acetone (64 mg, 30%). Microanalysis indicates a 3:2 mixture of chloride and
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dichloroiodate(I) anions; Anal. Calcd for 0.6 C38H46AuN6[Cl2I] (981.59) + 0.4 C38H46AuN6[Cl]
(819.23): C, 51.62; H, 5.24; N, 9.50. Found: C, 51.65; H, 5.50; N, 8.95.
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Method B: Complex 2e (40 mg, 0.08 mmol), and AgBF4 (15 mg, 0.08 mmol) in dry CH2Cl2 (10
mL) were stirred in the dark for 12 h at 40 °C. The solution was passed through a short pad of
Celite and eluted with CH2Cl2 (5 mL) and concentrated to approximately 1 mL. Addition of
pentane (50 mL) afforded 4e as a white powder. The solid was collected by filtration and dried
under vacuum. (25 mg, 76%). Anal. Calcd for C38H46AuBF4N6 (870.57) × 0.5H2O: C, 51.89; H,
5.39; N, 9.55. Found: C, 51.80; H, 5.22; N, 9.16.
Spectroscopic analyses were identical for both products: 1H NMR (CDCl3, 400 MHz): δ 7.63 (d,
3JHH = 7.2 Hz, 4H, HPh), 7.51–7.45 (m, 6H, HPh), 4.11 (s, 6H, NCH3), 2.37 (br s, 12H, CH2 ada),
2.06 (br s, 6H, CHada), 1.63, 1.48 (2 × AB doublet, 2JHH = 12.4 Hz, 12H, CH2 ada). 13C{1H} NMR
(CDCl3, 100 MHz): δ 166.5 (Ctrz–Au), 149.0 (Ctrz–Ph), 130.4, 130.1, 129.6, 127.6 (4 × CPh), 64.8
(Cada–N), 43.4 (CH2 ada), 38.0 (NCH3), 35.7 (CH2 ada), 29.7 (CHada).
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Complex 6. AuCl(IMes) (100 mg, 0.18 mmol), and AgBF4 (35 mg, 0.18 mmol) in dry CH2Cl2
(10 mL) were stirred in the dark for 12 h at 40 °C. The solution was passed through a short pad
of Celite, eluted with CH2Cl2 (5 mL) and concentrated to 1 mL. Addition of pentane (50 mL)
afforded 6 as a white powder, which was collected by filtration and dried under vacuum (75 mg,
83%). 1H NMR (CDCl3, 400 MHz): δ 7.10 (s, 4H, Himi), 6.88 (s, 8H, HMes), 2.43 (s, 12H,
ArCH3), 1.69 (s, 24H, ArCH3). 13C{1H} NMR (CDCl3, 100 MHz): δ 185.3 (Cimi–Au), 139.5,
134.7, 134.3, 129.3 (4 × CMes), 123.3 (Himi), 21.4, 17.3 (2 x Ar–CH3). Anal. Calcd for
C42H48N4AuBF4 (892.63): C, 56.51; H, 5.42; N, 6.28. Found: C, 56.45; H, 5.26; N, 6.15.
Complex 7. Complex 2a (50 mg, 0.09 mmol), methyl isocyanoacetate (11 mg, 0.11 mmol), and
AgBF4 (35 mg, 0.18 mmol) in CD2Cl2 (2.0 mL) were stirred in the dark for 16 h, and then passed
through a small pad of Celite and eluted with CD2Cl2 (0.5 mL). 1H NMR (CD2Cl2, 400 MHz): δ
7.11 (s, 4H, HMes), 4.55 (s, 2H, CNCH2), 3.95 (s, 3H, NCH3), 3.80 (s, 3H, COOCH3), 2.41, 2.39
(2 x s, 3H, ArCH3), 2.11, 2.08 (2 x s, 6H, ArCH3). 13C{1H} NMR (CD2Cl2, 125 MHz): δ 167.9
(COO), 163.0 (Ctrz–Au), 148.5 (Ctrz–Mes), 142.3, 142.2, 138.5, 135.5, 134.7, 130.2, 129.8, 121.4
(8 x CMes), 54.5 (CH3), 46.1 (broad, CNCH2), 37.7 (NCH3), 21.7, 21.6, 20.5, 17.7 (4 x Ar–CH3),
AuꢀCN not resolved.
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General procedure for the catalytic synthesis of oxazolines. In a typical procedure,
benzaldehyde (0.15 mL, 1.5 mmol), methyl isocyanoacetate (0.130 mL, 1.4 mmol), complex 2
(14
ꢁ
mol, 1 mol%), and NEtiPr2 (24
ꢁL, 0.17 mmol) were dissolved in CH2Cl2 (3.2 mL). A
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solution of AgBF4 (0.8 mL, 20 mM in CH2Cl2/MeOH 4:1, 16
ꢁ
mol) was added and the reaction
was stirred at 40 °C protected from light. Samples were taken at indicated times by removing 0.1
mL of the reaction mixture by syringe and dilution with CDCl3 (0.7 mL) for analysis by 1H NMR
spectroscopy.
Crystallographic details. Crystal data for complexes 2a, 2b, 2d, 2e, 2h, 3, 4e and 6 were
collected by using an Agilent Technologies SuperNova A diffractometer fitted with an Atlas
detector. 2a, 2b, 2e, 3, 4e and 6 were measured with MoꢀKα radiation (0.71073 Å), 2d and 2h
with CuꢀKα (1.54178 Å). A complete dataset was collected, assuming that the Friedel pairs are
not equivalent. An analytical numeric absorption correction was performed.49 The structures
were solved by direct methods using SHELXSꢀ97 and refined by fullꢀmatrix leastꢀsquares fitting
on F2 for all data using SHELXLꢀ97.50 Hydrogen atoms were added at calculated positions and
refined by using a riding model. Anisotropic thermal displacement parameters were used for all
nonhydrogen atoms. Crystallographic details are compiled in the supporting information (Tables
S1ꢀS8). CCDC numbers 945559–945566 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.
Associated Content
Supporting Information: Experimental procedures for the triazolium salts, DLS data,
representative timeꢀconversion profiles and crystallographic details for all reported structures.
This material is available free of charge via the Internet at http://pubs.acs.org.
Acknowledgements
We thank Thomas de Jong for the synthesis of ligand 1h. This work was financially supported by
the ERC (StG 208561, PoC 324609), Science Foundation Ireland, and the JSPS Funding
Program for Next Generation WorldꢀLeading Researchers.
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Author Information
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Corresponding author: Eꢀmail: martin.albrecht@ucd.ie; Fax: +35317162501; Phone:
+35317162504.
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References
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(4) For reviews on NHC gold complexes: (a) Marion, N.; Nolan, S. P. Chem. Soc. Rev. 2008,
37, 1776–1782. (b) Raubenheimer, H. G.; Cronje, S. Chem. Soc. Rev. 2008, 37, 1998–
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(26) The transmetalation of triazolylidene silver complexes with AuCl(SMe2) afforded
complexes 4 as bis(triazolylidene) gold cations with an inseparable mixture of chloride and
dichloroiodate(I) [ICl2]– anions. The presence of the two different counterions was
confirmed by microanalysis and by Xꢀray analysis of single crystals of 4e, providing
identical ratios of Cl– vs [ICl2]–. The formation of dichloroiodate from the iodide of the
triazolium salt and chlorides from AuCl(SMe2) suggests a thus far neglected background
redoxꢀreaction in addition to the transmetalation process.
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(32) Similar effects were observed when using proton sponge (1,8ꢀ(NMe2)2ꢀnaphthalene) as a
5
6
base instead of NEtiPr2.
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(33) AgBF4 on its own is inactive (< 5% conversion); moderate activity was noted in the
9
presence of NEtiPr2 (48% conversion, cf 73% when starting with 2a).
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(40) Four additional signals for the N3ꢀmethyl bound triazolylidene species were detected in the
range of 3.9–4.1 ppm (25% ratio for the four peaks together). Some of these signals may
reflect the formation of silver triazolylidene complexes from carbene transfer.
(41) Absence of enantioselectivity may also be associated with racemization of the ligand
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condensation step.
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