Mechanistic examination of AuIII-mediated 1,5-enyne cycloisomerization by AuBr2(N-imidate)(NHC)/AgX precatalysts-is the active catalyst AuIIIor AuI?

Article abstract of DOI:10.1039/c4cy00617h

Gold(iii) catalysts mediate 1,5-enyne cycloisomerization or tandem nucleophilic substitution-1,5-enyne cycloisomerization processes in an efficient manner. This study examines the reaction kinetics of 1,5-enyne cycloisomerization, mediated by AuBr₂

Full text of DOI:10.1039/c4cy00617h

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PAPER
III
Mechanistic examination of Au -mediated 1,5-enyne
cycloisomerization by AuBr (N-imidate)(NHC)/AgX
precatalysts – is the active catalyst Au or Au ?†
2
Cite this: Catal. Sci. Technol., 2014,
III
I
4, 3524
a
b
a
Jonathan P. Reeds, Mark P. Healy‡ and Ian J. S. Fairlamb*
Gold(III) catalysts mediate 1,5-enyne cycloisomerization or tandem nucleophilic substitution-1,5-enyne
cycloisomerization processes in an efficient manner. This study examines the reaction kinetics of 1,5-enyne
cycloisomerization, mediated by AuBr
2
(N-imidate)(NHC) catalysts {where N-imidate = N-tetrafluorosuccinimide
t
Received 12th May 2014,
Accepted 3rd July 2014
(N-TFS) or N-phthalimide (N-phthal) and NHC = N,N′-di-tert-pentylimidazol-2-ylidene (I Pe)}, in the presence
III
I
of AgOTf, in comparison with Au Br
3
(NHC) and Au Br(NHC). The nature of N-imidate anion influences catalyst
(N-TFS)(NHC) to
is liberated from Au , which has been trapped by a
efficacy. NMR spectroscopic investigations have allowed the ease of reduction of AuBr
2
DOI: 10.1039/c4cy00617h
I
III
Au X(NHC) (where X = N-TFS or Br) to be examined. Br
2
III
I
www.rsc.org/catalysis
sacrificial alkene. Under working catalyst conditions cationic Au is reduced to Au .
to deliver bicyclo[3.1.0]hexene products (8). For this process,
Introduction
III
t
Au Br
coordinating anion, Ag[Al(OC(CF
selective catalyst for the tandem process. By comparison with
2
(N-TFS)(I Pe) in combination with the non-
Organic transformations catalysed by Au species are of
current interest within both the synthetic chemistry and
catalysis communities. Of the reaction classes, 1,n-enyne
3 3 4
) )
], proved an active and
1
I
t
Au Br(I Pe) (note: near-inactive for the tandem process), it
III
cycloisomerization processes (n = 5 and 6) have attracted
was shown that a Au species was required for the initial
2
notable attention. While several transition metals are able to
nucleophilic substitution reaction. However, a question that
arose from the study was the nature of the active catalyst
affect 1,n-enyne substrates, Au occupies a special position in
2
,3
III
I
this arena,
as an eclectic array of structurally diverse
species in the cycloisomerization step, i.e. is Au or Au
organic products can be formed, depending on the catalyst
and substrate identities, in addition to the reaction conditions
used.
responsible for cycloisomerization?
In this paper we examine the reaction kinetics of
1,5-enyne cycloisomerization, mediated by AuBr (N-imidate)
2
1
,6-Enyne cycloisomerization processes generally involve
6
-exo-dig cyclization and are mechanistically well under-
4
stood. 1,5-Enyne cycloisomerization processes, involving
-endo-dig cyclization, have not been examined to the same
5
extent, despite the numerous synthetic possibilities. Never-
theless, several catalyst manifolds are known to deliver differ-
ent products depending on the electronic character of the Au
centre (see Scheme 1 for selected examples). This prompted
Sun and Lin to explore the mechanisms of 1,5-enyne cyclo-
I
5
isomerization, mediated by Au , by DFT calculations (B3LYP).
In an earlier study we developed a tandem nucleophilic
6
substitution-1,5-enyne cycloisomerization process (5 → 8),
starting from propargyl alcohol (5) and allyl silane (6),
a
Department of Chemistry, University of York, Heslington, York YO10 5DD, UK.
E-mail: ian.fairlamb@york.ac.uk
b
GlaxoSmithKline, New Frontiers Science Park, Third Avenue, Harlow,
Essex CM19 5AW, UK
†
Electronic supplementary information (ESI) available: Representative NMR
spectra and other characterization data. See DOI: 10.1039/c4cy00617h
Novartis Pharmaceuticals UK Limited, Horsham Research Centre,
Wimblehurst Road, GB-Horsham, West Sussex RH12 5AB, U.K.
Scheme 1 Top: 1,5-enyne cycloisomerization showing how L can
direct selectivity (3 & 4 representative products; others possible). Bottom:
a tandem nucleophilic substitution-1,5-enyne cycloisomerization – thermal
‡
1
2
1,3-rearrangements are possible for 8 (R /R = aryl groups).
3524 | Catal. Sci. Technol., 2014, 4, 3524–3533
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1
(
(
NHC) catalysts {where N-imidate = N-tetrafluorosuccinimide
H NMR spectroscopy) and associated kinetic profile is
N-TFS) or N-phthalimide (N-phthal) and NHC = N,N′-di-tert-
shown in Fig. 2 for the reaction mediated by 1 mol%
AuBr (N-TFS)(I Pe), in the presence of either 1 or 2 mol%
2
AgOTf in DCE at 25 °C. The first equivalent (relative to
Au cat.) serves to abstract bromide from AuBr (N-TFS)(I Pe)
forming [AuBr(N-TFS)(I Pe)]OTf and AgBr in situ. The second
equivalent of AgOTf could in principle abstract another
bromide.
t
t
pentylimidazol-2-ylidene (I Pe)} in the presence of AgOTf. The
findings allow an understanding of 1,5-enyne substrate turn-
over, indicating that catalyst decomposition is an issue for
certain catalysts. It has been found that the N-imidate anion
plays a stabilizing role for effective catalysis. NMR spectro-
scopic investigations have been used to examine the degrada-
t
2
t
III
I
tion of Au to Au , which support the kinetic studies.
Examination of the kinetic profiles in Fig. 2 indicate that
there is no benefit in an additional equivalent of AgOTf.
t
Both AgOTf and AuBr (N-TFS)(I Pe) are necessary for active
2
Results and discussion
catalysis (confirmed by control experiments). The data gener-
ated by HRGC could be fitted to a pseudo-first order rate
equation using Dynafit™ (by curve fitting; regression analysis
of ln[enyne] vs. time afforded similar data), which allowed
The study is divided into two parts: (a) kinetic investigations;
(b) NMR spectroscopic investigations.
7
the observed rate (kobs) and initial rate to be determined.
(a) Kinetic investigations
t
For the reaction where the AuBr (N-TFS)(I Pe) : AgOTf was 1 : 1,
2
−
4 −1
The 1,5-enyne cycloisomerization reaction (9 → 10) examined
in these kinetic investigations is shown in Scheme 2, which
has previously been validated as a useful benchmark
it was determined that kobs = 3.14 × 10
s
and the initial rate
−
5
−3 −1
(T ) = 6.28 × 10 moldm
0
s
(standard error = 2.5%). A
marginally faster reaction was recorded when the ratio was 1 : 2
6
b
−4 −1
−5
−3 −1
reaction for testing Au catalyst efficacy (the reaction is
selective for 10 and negligible side-reactions are seen).
The catalysts used in this study are collated in Fig. 1,
which were selected from a wider library of catalysts previ-
0
(kobs = 4.16 × 10 s ; T = 8.32 × 10 moldm s ; standard
error = 3.3%).
Based on these data the ratio of the Au catalyst to Ag addi-
tive was maintained at 1 : 1 for all subsequent reactions,
which is in-keeping with the ratio commonly used for many
related cycloisomerization processes.
6
a,b
ously reported by our group.
The reaction of 9 → 10 was monitored by HRGC analysis.
The response factors are near identical for 9 and 10 (authen-
The kinetic profiles for the conversion of 9 (by HRGC),
catalyzed by five different Au catalysts, are shown in
1
ticated by H NMR spectroscopic analysis), which is expected
t
as they are isomers. The conversion of pure 9 (ascertained by
Fig. 3. The kinetic data is collated in Table 1. AuBr(I Pe),
t
t
2 2 2
AuBr (N-TFS)(I Pe), AuBr (N-phthal)(I Pe) and AuBr (N-phthal)(IMes)
show reasonable first order behaviour in 9. The catalyst
t
showing the highest observed rate is AuBr(I Pe) (kobs = 13.98 ×
−
4
−1
1
0
s
), which has an initial rate commensurate with
t
−5
−3 −1
−5
AuBr (I Pe) (T = 27.96 × 10 moldm
s
and 21.87 × 10 ,
3
0
Scheme 2 1,5-Enyne cycloisomerization reaction for the kinetic
investigations.
t
Fig. 2 Effect of AgOTf equivalents relative to AuBr
2
(N-TFS)(I Pe) in
1
,5-enyne cycloisomerisation of 9 (key: ● = 2 mol% AgOTf; ○ = 1 mol%.
AgOTf). Other details: [9] = 0.2 M, DCE, 1 mol% Au cat., 25 °C;
,5-enyne conversion was monitored by HRGC – each sample point
1
was quenched by addition of N(n-Bu)
using Dynafit™.
4
Br. The kinetic curves were fitted
Fig. 1 The structures of the catalysts used in this mechanistic study.
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t
of kobs for the AuBr (N-phthal)(I Pe) and AuBr (N-phthal)
2
2
(
IMes) catalysts, shows that the former is twice as active as
t
2
the latter (Table 1). AuBr (N-TFS)(I Pe) has a marginally
higher activity than AuBr (N-phthal)(I Pe). It is evident that
t
2
the N-imidate ligand could be playing a stabilizing role, when
comparing N-imidate-containing catalysts directly with
t
AuBr (I Pe).
3
In the course of these kinetic studies it was determined
that ‘aged’ 1,5-enyne significantly affects the kinetic profiles
recorded. Aldehyde decomposition products are formed from
1
9
(observed by H NMR, ca. 5%, after several weeks), which
could interfere with the catalysis (i.e. slowing catalytic turn-
over). It was therefore found essential to employ either freshly
prepared or purified 9 for the kinetic studies, which gave
reproducible kinetic data.
Further examination of the catalytic behaviour of
Fig. 3 Effect of 1,5-enyne concentration [9] on the kinetics in a reac-
tion mediated by various Au catalysts (1 mol%), AgOTf (1 mol%), in DCE
t
AuBr (N-phthal)(I Pe) by variation of [9] reveals an interesting
2
t
at 25 °C (key: closed circles = AuBr(I Pe); open circles = AuBr
2
(N-TFS)
(N-phthal)
(N-phthal)(IMes)). 1,5-Enyne conversion
trend (Fig. 4, Table 2).
t
t
(
(
I Pe); closed squares = AuBr
I Pe); closed triangles = AuBr
3
(I Pe); open squares = AuBr
2
Increasing [9] causes a decrease in the observed rate con-
stants, with the initial rates increasing with concentration,
relating to the change in [9] over time. At 0.5 M [9] it was nec-
essary to fit the kinetic curve to a second order rate equation,
again factoring in the Au catalyst deactivation step. The
observation is consistent with increasing [Au], which is
concomitant with increasing [9]. Given these data, product
inhibition and Au aggregation/decomposition are likely at
higher [9].
A question arising from these studies is the nature of the
active catalyst species. Therefore, a competition experiment
was devised to discern any subtle differences in catalyst
behaviour. Dimethyl allylpropargylmalonate 11 was selected
as a viable 1,6-enyne benchmark substrate, which principally
affords the cyclic products 12a and 12b (Scheme 3).
t
2
monitored by HRGC analysis – each sample point was quenched by
addition of (n-Bu) NBr. The kinetic curves were fitted using Dynafit™
4
with standard errors < 5%.
Table 1 Observed rate constants and initial rates for the cyclo-
I
III
isomerization of 4-phenyl-1-hexen-5-yne (9) by Au and Au catalysts;
data accompanying Fig. 3
−
4
−1
a
Catalyst
k
obs × 10 (s
)
Initial rate
Error (%)
t
[
[
[
[
[
AuBr(I Pe)]
13.98
—
5.52
4.49
27.96
21.87
11.04
8.97
4.2
2.3
3.0
4.2
2.0
t
b
AuBr
AuBr
AuBr
AuBr
3
2
2
2
(I Pe)]
(N-TFS)(I Pe)]
(N-phthal)(I Pe)]
(N-phthal)(IMes)] 2.07
t
t
4.14
a
−5
−3
−1
−4 −1
b
Rate at
T
0
×
10
(moldm
s
).
s
Second order,
(error 3.0%).
1obs
k =
−
1
3
−1
0
.5468 mol dm s , k2obs = 9.07 × 10
t
respectively). It is important to note that AuBr
3
(I Pe) did not
display clean first order behaviour and catalyst deactivation is
apparent after ca. 60 substrate turnovers. The kinetic profile
could, however be fitted to a second order rate equation by
curve-fitting, in which it was assumed that the Au catalyst
decomposed over time and that the rate depended on both
the concentration of 9 and Au catalyst.
The second order rate equation was deduced from initial
−
5
−3 −1
rate = k1obs[enyne] [Au] = 21.87 × 10 moldm
k
s
, where
0
0
3
−
1
−1
1obs (0.5468 mol dm s ) is the rate constant for the
equation: 9 (1,5-enyne) + Au → Au + 10 (product). The rate of
catalyst decomposition was determined by the initial rate of
−
6
−1
decomposition = k2obs[Au]
(
0
= 1.81 × 10
s , where k2obs
−
4
−1
9.07 × 10 s ) is the rate constant for the decomposition of
the Au active catalyst. The inactive Au is more likely colloidal,
as evidenced by the kinetic data and purple colouration of
the reaction mixture.
Fig. 4 Effect of 1,5-enyne concentration [9] in a reaction mediated by
t
2
AuBr (N-phthal)(I Pe) (1 mol%), AgOTf (1 mol%), in DCE at 25 °C (key: ○ =
0
.1 M 9; ● = 0.2 M 9; □ = 0.5 M 9). 1,5-Enyne conversion monitored
by GC analysis – each sample point was quenched by addition of
(n-Bu) NBr. The kinetic curves were fitted using Dynafit™.
Catalyst decomposition does not appear to hinder catalysis
III
by the other Au complexes tested in this series. Comparison
4
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Table 2 Observed rate constants for the cycloisomerization of [9] medi-
in the latter 1,6-enyne cycloisomerization reaction (12a : 12b)
t
2
ated by AuBr (N-phthal)(I Pe); data accompanying Fig. 4
as the substrate is consumed over time.
t
−3
−4 −1
a
Firstly, AuBr(I Pe) is a competent catalyst for the cyclo-
[9] (mol dm
)
k
obs × 10 (s
)
Initial rate
Error (%)
−
4
−1
isomerization of 11 → 12 (k
= 1.08 × 10
s ; T = 2.15 ×
0
obs
0
0
0
.1
.2
.5
6.15
4.49
—
6.15
8.97
19.20
1.6
4.2
5.7
−
5
−3 −1
1
0
moldm s ; standard error = 2.2%). The kinetic analy-
b
sis of the competition experiments is complicated by the
presence of two substrates and two competing catalytic
cycles, which is evident in the error analysis. This complica-
a
−5
−3 −1
b
−2
−1
3 −1
At T
0
× 10 (moldm s ). Second order k1obs = 7.68 × 10 mol dm s ,
4
−
−1
k
2obs = 2.36 × 10
s .
tion aside, the kinetic profiles are similar in all cases
t
(
see Fig. 5). Catalyst performance is reduced for AuBr(I Pe) as
III
compared to the Au catalysts – the presence of 12 slows
t
catalytic turnover in the case of AuBr(I Pe).
A plot of the ratio of 12a : 12b over the duration of the
1
,6-enyne cycloisomerization reaction, reveals an interesting
trend as a function of catalyst (Fig. 6).
Firstly, the independent 1,6-enyne cycloisomerisation of
t
1
1 → 12a/12b mediated by AuBr(I Pe) gives a ratio of ca. 1 : 3,
Scheme 3 Competition experiment of a 1,5-enyne 9 and 1,6-enyne
1. Product 11 derives from 9 and products 12a and 12b from 11. The
kinetic profiles are shown in Fig. 6 and product distributions of 12a : 12b
which does not alter appreciably over the 6 h reaction time.
The same trend is revealed in the competition experiment in
the presence of both 9 and 12, using AuBr(I Pe) as the
1
t
shown in Fig. 7.
III
catalyst. The product distribution is different for the Au
t
catalysts, with AuBr (N-TFS)(I Pe) showing a smaller ratio
(N-phthal)(I Pe). Crucially, at ca. 1.5 h the ratio of
12a/12b is identical to the AuBr(I Pe) catalyst. This finding,
2
t
1
,5-Enyne
9
(0.2 M) and 1,6-enyne 11 (0.2 M)
than AuBr
2
t
were subjected to a reaction where the only variable was
t
t
III
I
the Au catalyst {AuBr(I Pe), AuBr
2
(N-TFS)(I Pe) and
coupled with our previous observation that dual Au /Au cat-
alyst behaviour is necessary for a successful tandem nucleo-
philic/1,5-enyne cycloisomerization reaction, indicates that
Au to Au degradation under the working reaction condi-
tions, affects the ratio of products depending on distribution
of Au /Au species that are present at any given time. It may
be conjectured that liberated N-imidate anion could affect
the distribution of 12a/12b under the reaction conditions.
t
AuBr (N-phthal)(I Pe)} (Fig. 5 and Table 3). In addition to
2
6
a
examining the reactivity difference between 9 and 11, the
experiment allows one to probe the ratio of products formed
III
I
III
I
However, in control experiments we have detected liberation
III
of Br from these Au catalysts (see section b, below).
2
(
b) NMR spectroscopic investigations
NMR spectroscopic analysis allows us to discern whether
III
Au could be playing a role in the catalysis detailed earlier.
III
It has been suggested previously that Au can be reduced to
I
8
8a
Au under the reaction conditions. Nolan and co-workers
stated that the active catalyst in the hydration of alkynes and
polymerisation of styrene mediated by AuBr (NHC) type
3
I
complexes is a Au species, formed by reductive elimination
of bromide ligands. Further examination of the behaviour of
the Au catalysts described herein was deemed necessary,
especially whether any evidence for the formation of a
III
I
cationic Au catalyst species, and degradation to Au , could
be gathered.
1
H NMR spectroscopy was used to assess whether cationic
Fig.
5 Kinetic profile for the concurrent cycloisomerisation of
III
Au species were formed by a stoichiometric reaction of
4
-phenyl-1-hexen-5-yne (9) and dimethyl allylpropargylmalonate (11)
t
mediated by selected Au catalysts. Key: 1,5-enyne conversion (9, open
circles) and 1,6-enyne conversion (11, closed circles) – black =
AuBr
2
(N-TFS)(I Pe) with AgOTf in acetone-d
6
(this solvent was
t
selected to increase solubility of all the salts). The I Pe imid-
azole proton signals were the most characteristic and sensitive
to changes in the Au electronic configuration. It was necessary
to compare NMR spectra with reference materials, namely
t
t
t
2 2
AuBr(I Pe); blue = AuBr (N-TFS)(I Pe); red = AuBr (N-phthal)(I Pe).
Conditions: 0.2 M 9, 0.2 M 11 in 1,2-dichloroethane, 1 mol% Au, 1 mol%
AgOTf, 25 °C. 1,n-enyne (n = 5 or 6) conversion monitored by GC analy-
sis – each sample point was quenched by addition of (n-Bu) NBr. The
4
t
t
kinetic curves were fitted using Dynafit™ with standard errors ~ 5%.
AuBr(I Pe) and Au(N-TFS)(I Pe), as shown in Fig. 7.
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Table 3 Observed rate constants and initial rates for the concurrent cycloisomerization of 1,5-enyne (9) and 1,6-enyne (11), mediated by selected Au
catalysts; data accompanying Fig. 5
−
4
−1
a
b
Catalyst
k
obs × 10 (s
)
Rate
Error (%)
Ratio 12a : 12b
1
1.27
—
—
,5-Enyne
t
AuBr(I Pe)
2.53
3.47
5.28
5.3
2.6
4.2
—
—
—
t
c,d
AuBr
AuBr
2
(N-TFS)(I Pe)
(N-phthal)(I Pe)
t
e,f
2
1
0.28
1.08
—
—
,6-Enyne
t
AuBr(I Pe)
0.56
2.15
0.85
1.30
8.4
2.2
3.8
5.6
0.28
0.30
0.45
0.36
t
AuBr(I Pe) (1,6-enyne 11 only)
t
d,g
AuBr
AuBr
2
(N-TFS)(I Pe)
(N-phthal)(I Pe)
t
f,h
2
a
−5
−3 −1
b
c
−2
−1
3
−1
d
−5 −1
e
Rate at T
0
× 10 (moldm
s
). After 6 h. Second order k1obs = 8.685 × 10 mol dm s
.
k
2obs = 6.38 × 10 s
(error 9.2%). Second
−1
3
−1
f
−4 −1
g
−2
−1
3 h
−1
order k1obs = 0.1321 mol dm s
3
.
k
2obs = 1.52 × 10
s
(error 8.0%). Second order k1obs = 2.128 × 10 mol dm s
.
Second order k1obs =
−
2
−1
3 −1
.242 × 10 mol dm s .
Fig. 6 Product distribution from the cycloisomerization of 11 → 12a
and 12b over time {data extracted from the kinetic profiles given in
t
1
Fig. 5 – closed black circles = AuBr(I Pe); open black circles =
Fig. 7 H NMR spectroscopic analysis of the reaction of AuBr
2
(N-TFS)
t
t
t
t
AuBr(I Pe)/1.6-eyne 11 only; closed blue circles = AuBr
2
(N-TFS)(I Pe);
(I Pe) with AgOTf in acetone-d
6
over time. (a) AuBr
2
(N-TFS)(I Pe) only;
t
t
t
closed red circles = AuBr
2
(N-phthal)(I Pe)}. The trendlines added to the
(b) AuBr
2
(N-TFS)(I Pe), aged for 48 h; (c) AuBr
2
(N-TFS)(I Pe)/AgOTf (1 : 1),
t
graph serve as a guide to the eye.
10 min; (d) as for (c), 4.5 h; (e) as for (c), 22.5 h; (f) AuBr(I Pe)/AgOTf (1 : 1),
t
t
2
(
3
2.5 h; (g) solution of AuBr (I Pe) only, aged for 48 h; (h) AuBr(I Pe) only;
t
i) Au(N-TFS)(I Pe) only.
t
The AuBr(I Pe) imidazole signal shifts 0.15 ppm downfield
t
on treatment with AgOTf, giving Au(OTf)(I Pe) quantitatively
t
{
compare spectra (h) and (f), Fig. 7}. AuBr
2
(N-TFS)(I Pe) reacts
signal at slightly higher chemical shift (δ 7.52) which we sug-
gest is [Au(κ -O = CMe )(I Pe)] [Al(OC(CF ) ) ] (see ESI†).
2 3 3 4
t
t
1
t
+
−
with AgOTf to afford Au(N-TFS)(I Pe) and trace Au(OTf)(I Pe),
with no cationic Au species observed after 4.5 h {compare
III
t
The binding of the AuBr (N-TFS)(I Pe) and AgOTf toward
2
spectra (d), (e) and (i)}. The outcome is consistent with the
1-hexene in CD Cl was evaluated to reveal evidence for any
alkene–Au interaction (Table 4), in addition to showing
2
2
III
liberation of Br (as noted by a brown colouration). Further-
2
t
more, AuBr (I Pe) decomposes in solution in the absence of
whether liberated Br could be sequestered by 1-hexene. For
3
2
t
9
AgOTf, leading to the formation of AuBr(I Pe) {compare
spectra (g) and (h)}. Ageing of AuBr (N-TFS)(I Pe) led to slow
formation of trace but observable amounts of AuBr (I Pe),
AuBr(I Pe) and Au(N-TFS)(I Pe) {see spectrum (b)}. The forma-
comparison, the reported spectroscopic data of [Au(μ -H C =
2
2
t
2
4 9 6
CHC H )(IPr)][SbF ] is included in Table 4. A reduction in the
t
3
alkene proton coupling constants, relative to free 1-hexene, is
evidence for π-back donation, i.e. an increase in p character
for the orbitals at carbon.
t
t
t
19
tion of Au(N-TFS)(I Pe) is detected by F NMR spectroscopic
1
analysis (see ESI†).
A similar reaction of AuBr
in acetone-d6 afforded Au(N-TFS)(I Pe) and a new broad
The H NMR spectral data show no clear evidence for 1-hexene
t
t
2
(N-TFS)(I Pe) with Ag[Al(OC(CF
3
)
3
)
4
]
binding to neutral AuBr (N-TFS)(I Pe), in the absence of
2
t
t
AgOTf (Table 4). Upon mixing AuBr (N-TFS)(I Pe) with 1
2
3528 | Catal. Sci. Technol., 2014, 4, 3524–3533
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Paper
t
1
2 2 2
Table 4 Binding of 1-hexene to AuBr (N-TFS)(I Pe) and AgOTf in CD Cl , as determined by H NMR spectroscopic analysis (400 MHz)
a
Complex/salt
1-Hexene (equiv.)
δ H
A
(ppm)
Coupling constant (Hz)
—
AgOTf
—
2
1
1
2
5.82
6.21
5.82
6.26
6.00
6.05
17.0, 10.1, 6.7
17.7, 8.9, 6.6
17.0, 10.1, 6.7
18.0, 8.7, 6.5
17.0, 10.1, 6.7
17, 9, 4.5
t
[
[
[
[
AuBr
AuBr
AuBr
2
2
2
(N-TFS)(I Pe)]
t
(N-TFS)(I Pe)]/AgOTf
t
(N-TFS)(I Pe)]/AgOTf
Au(μ
2
-H
2
C = CHC
4
H
9
)(IPr)][SbF
6
]
1
a
The central proton (H
A
) was observed as a ddt.
t
equiv. of AgOTf, the solution turns a cloudy colour (due to
AgBr formation). Addition of 1-hexene (1 equiv.) results in a
shift of Δδ = 0.44 ppm (relative to free 1-hexene). Coupling
constants of 18.0 Hz (ΔJE–H = +1 Hz) for the trans-proton and
spectroscopic analysis revealed that AuBr
AuBr(I Bu), even in the absence of AgOTf.
3
(I Pe) degrades to
t
The presence of an N-imidate anion led to higher catalyst
efficacy (defined as leading to full substrate conversion) in
comparison with AuBr (I Pe). Of the N-imidate series,
AuBr (N-TFS)(I Pe), is the most catalytically active. The nature
of the NHC ligand exhibits a significant effect. For example,
AuBr (N-phthal)(I Pe) is twice as active as AuBr (N-phthal)(IMes).
Increasing the 1,5-enyne [9], and therefore the concentra-
tion of Au catalyst {AuBr (N-phthal)(I Pe)}, leads to catalyst
2
deactivation. Optimal catalyst performance was recorded at
[9] between 0.1–0.2 M. At 0.5 M [9] it was necessary to model
the kinetics to a second order process, again involving a cata-
lyst deactivation step. Product inhibition is also possible at
higher concentrations, and formation of Au colloids is visible
by the naked eye (purple colouration, relating to the Au
plasmon band).
It was possible to assess subtle differences in catalyst
behaviour by a concurrent cycloisomerization competition
experiment, involving 1,5-enyne 9 and 1,6-enyne 11. The for-
mer gives 10 selectively, whereas 11 afford one of two prod-
ucts, 12a or 12b. Three catalysts were tested, namely
t
10
8
.7 Hz (ΔJZ–H = −1.4 Hz) for the cis-coupling were recorded.
3
t
Addition of 2 equiv. of 1-hexene leads to a reduction in the
chemical shift (Δδ = 0.18 ppm), with little change in coupling
constants observed. The excess 1-hexene is therefore in
exchange with the alkene–Au species or alkene–Ag species.
After 24 h, the H NMR spectrum had changed significantly,
2
t
2
2
III
I
1
t
t
with a number of small I Pe imidazole signals corresponding
to Au and Au species, in addition to a large broad signal
I
III
I
(
ca. 80% of the total imidazole proton signal) in the Au
region. Another broad signal at δ 4.45–4.09 ppm was recorded,
I
which we tentatively suggest is the alkene coordinated to Au ;
the broadness in the proton signal is due to fluxionality of
t
the alkene as either Au(μ -H C = CHC H )(N-TFS)(I Pe) or the
2
2
4
9
t
+
naked cationic species [Au(μ
2
-H
2
C = CHC
4
H
9
)(I Pe)] . Signals
corresponding to free 1-hexene and a new set of proton
signals corresponding to 1,2-dibromohexane, ca. 50% abun-
dance compared to free 1-hexene, i.e. 1 equivalent. After 24 h,
there was no evidence of 1-hexene binding to Ag or Au. The
1
9
t
t
t
F NMR spectrum showed a very large broad signal
−182.2 ppm) suggesting the observed alkene complex is that
AuBr(I Pe), AuBr (N-TFS)(I Pe) and AuBr (N-phthal)(I Pe). In
2 2
all cases, 1,5-enyne 9 was found to be more reactive than
1,6-enyne 11. Further analysis of the product ratios 12a : 12b
from the 1,6-enyne cycloisomerization reaction revealed key
catalysts when compared to
AuBr(I Pe). After ca. 1.5 h, the ratios of 12a : 12b for
(
t
of Au(μ
1
2 2 4 9
-H C = CHC H )(N-TFS)(I Pe). In the absence of
t
-hexene, the decomposition of AuBr (N-TFS)(I Pe) was not
2
III
observed.
It is important to note that AgOTf alone binds to 1-hexene
Δδ = 0.39 ppm; ΔJE–H = +0.7 Hz and ΔJ
= −1.2 Hz), which
differences for the Au
t
t
t
(
AuBr (N-TFS)(I Pe) and AuBr (N-phthal)(I Pe) mirrored the
2 2
reaction mediated by AuBr(I Pe). Therefore, while Au is still
Z–H
t
t
III
is similar to the binding of AuBr
2
(N-TFS)(I Pe)/1 equiv. AgOTf.
Whilst AgBr is formed, we cannot rule out the involvement of
present, 12a is formed to a greater extent than in reactions
solely mediated by Au .
t
I
chemical equilibria with AuBr (N-TFS)(I Pe) and AgOTf. More-
2
over, under the catalytic conditions there is an excess of sub-
strate and solvent relative to the catalyst system, therefore
solubilisation of all the metal species is possible.
Our findings on the 1,5-enyne cycloisomerization process
(9 → 11) are in-keeping with the DFT calculations reported by
5
Sun and Lin. In that study, it was shown that the 1,5-enyne
cycloisomerization reaction mediated by AuCl is both kineti-
cally and thermodynamically favoured for the formation of
the bicyclo[3.1.0]hexene product, with key catalytic steps
(TS-Icomp carbene formation and TS-IIcomp hydrogen migration)
being of similar energy (Scheme 4).
(
c) Mechanistic discussion
The experimental evidence from this study indicates that
AuBr(I Pe) is the most active catalyst for 1,5-enyne cyclo-
t
isomerization in the series tested, showing first order
From our experimental findings, we propose that Br is
2
III
t
III
behaviour. The Au catalyst, AuBr (I Pe), mediates a slower
liberated from cationic Au –NHC catalyst species, affording
3
I
reaction, which was successfully modelled kinetically as a
second order process. The inclusion of a catalyst deactivation
Au –NHC catalyst species in situ. The finding is supported by
the liberation and trapping of the Br by a sacrificial alkene
2
1
step was found necessary for the analysis. The H NMR
(1-hexene) in the NMR spectroscopic investigations.
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Scheme
6
1,5-Enyne
cycloisomerization
leading
to
1,3-cyclohexadiene formation.
here, and elsewhere, mirror related observations from
other studies.
Conclusions
Scheme 4 Top: proposed mechanism for the 1,5-enyne cyclo-
isomerization 9 → 10 (a role for Ag is not shown in the mechanism,
although this cannot be ruled out). Bottom: DFT computed energies
for the intermediates and transition states for the a 1,5-enyne cyclo-
isomerization mediated by AuCl, reported by Sun and Lin.
III
I
In this paper the ability of both Au and Au catalysts to
mediate a 1,5-enyne cycloisomerization reaction has been
examined. It was necessary to understand whether Au was
III
being reduced under working catalyst conditions, especially as
the success of the tandem nucleophilic substitution-1,5-enyne
III
I
cycloisomerization relies on Au for the initial nucleophilic
Decomposition of the Au –NHC catalyst species affords Au
6a
substitution step.
The reaction kinetics for 1,5-enyne cycloisomerization,
colloids, which are most likely a moribund-form, especially as
reduced catalyst performance is seen at higher [Au] and [9]
mediated by AuBr (N-imidate)(NHC) catalysts {where
(Scheme 5).
2
N-imidate = N-tetrafluorosuccinimide (N-TFS) or N-phthalimide
The binding experiments which explored the interaction of
t
(
(
N-phthal) and NHC = N,N′-di-tert-pentylimidazol-2-ylidene
I Pe)}, in the presence of AgOTf, revealed that the nature of the
1
-hexene with AuBr
2
(N-TFS)(I Pe)/AgOTf, and AgOTf alone,
t
demonstrates that 1-hexene binding is influenced in both
cases. Crucially, 1-hexene mediates the decomposition of
N-imidate anionic ligand influences catalyst efficacy. A direct
III
t
t
comparison was made with Au Br (NHC), which exhibited
AuBr
2
(N-TFS)(I Pe) to Au(N-TFS)(I Pe), which was not observed
3
significant catalyst deactivation in the absence of the stabiliz-
in the absence of 1-hexene in CD Cl . The results taken
2
2
ing N-imidate ligand. In a concurrent cycloisomerization of
together demonstrate that unsaturated substrates are involved
I
1,5- and 1,6-enynes (9 and 11) we were able to tease out subtle
in: (i) catalyst activation to give Au , with concomitant decom-
III
differences in the product distribution (11 → 12a : 12b)
position of Au ; (ii) solubilisation of the Ag salt, which is
III
during the early stages of catalytic turnover by the Au cata-
likely non-innocent in the catalysis. Subsequently, the nature
of the coordinating ligand (and substrate and any impurities,
as shown by substrate-aging experiments) is likely to affect
catalytic turnover.
lysts. NMR spectroscopic investigations have allowed the ease
I
of reduction of AuBr (N-TFS)(NHC) to Au X(NHC) (where X =
2
N-TFS or Br) to be examined. In these experiments, 1-hexene
III
was shown to mediate Au decomposition. The liberation of
Finally, it is important to emphasise that other products
III
Br from the Au centre was trapped by this sacrificial alkene.
can result from the cycloisomerization of different
2
t
Taking together all of the results, we conclude, that under
1
(
,5-enynes, catalyzed by either AuBr(I Pe) or AuBr
2
(N-TFS)
III
I
t
3a,d
working catalyst conditions, cationic Au is reduced to Au .
I Pe). In keeping with previous observations,
we find that
I
The role of Ag has been more difficult to understand (i.e.
a 1,5-enyne containing a highly substituted carbon tether
gives a cyclohexadiene product, both in the tandem nucleo-
philic substitution-1,5-enyne cycloisomerization (13 → 14 →
beyond simple bromide abstraction). The interplay of Au and
Ag salts in 1,n-enyne cycloisomerization processes is currently
being studied within our laboratories.
1
5) and the latter independent reaction (14 → 15) (Scheme 6).
The outcome serves to highlight that the catalysts described
Experimental
General experimental details
All reactions involving silver salts were carried out in the
absence of light. Deuterated and non-deuterated
dichloromethane and acetonitrile were dried by passing
through a column of activated alumina. Where necessary
Scheme 5 Catalyst activation and deactivation pathways.
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dichloromethane Infra-red spectra were recorded on a
Unicam Research Series FT-IR spectrometer. Mass spectrome-
try was carried out using a Fisons Analytical (VG) Autospec
initial rates and standard errors and to fit curves to the
kinetic data.
1
13
instrument. H and C NMR spectra were collected on a JEOL
ECX400 spectrometer operating at 400 and 101 MHz, respec-
General procedure for the kinetic evaluation of the Au-catalysed
cycloisomerization of 4-phenyl-1-hexen-5-yne (9) by gas
chromatography
1
3
tively, and referenced to residual solvent signals. C NMR sig-
nals are singlets unless otherwise stated. All column
chromatography was performed using silica-gel (mesh 220–440)
purchased from Fluka Chemicals with the solvent systems
specified within the text. TLC analysis was performed using
Merck 5554 aluminium backed silica plates, compounds were
visualised using UV light (254 nm) and a basic aqueous solu-
tion of potassium permanganate. Melting points were mea-
sured in open capillary tubes using a Stuart SMP3 Digital
Melting Point Apparatus and are uncorrected. 1-Phenyl-2-
propyn-1-ol and AgOTf were purchased from Alfa Aesar. All
other chemicals were purchased from Sigma-Aldrich Inc. and
used without further purification unless otherwise stated. All
of the Au catalysts used in this study have been reported; see
Au complex (3.2 μmol, 0.01 equiv.) and AgOTf (0.8 mg, 3.2 μmol,
0.01 equiv.) were mixed in CH Cl (or DCE) in a screw cap
2 2
vial (1 min) and the solvent removed in vacuo. A solution of
4-phenyl-1-hexen-5-yne (9) (50.0 mg, 321 μmol, 1 equiv.) in
1,2-dichloroethane (1.60 ml, 0.20 M) was added, the vial
sealed with a rubber septum and a positive pressure of argon
applied via an argon balloon. The mixture was stirred at
25 °C in the absence of light. Samples of 10 μl were taken
via syringe and added immediately to a solution of tetra-n-
butylammonium chloride (8 mM, 20 μl) in CH Cl . Conver-
2
2
sion was determined via gas chromatography using a 1 μl
sample. The chromatogram was run with an injector temper-
ature of 250 °C and an initial oven temperature of 80 °C
6
b
our previous paper for full details.
−
1
(
0.5 min), heated to 160 °C, at a rate of 20 °C min , and
Kinetic experiments
maintained at 160 °C (1 min). The retention times were:
2.58 min for 4-phenyl-1-hexen-5-yne (9) and 3.89 min for
3-phenylbicyclo[3.1.0]hex-2-ene (10).
High resolution gas chromatographic (HRGC) analysis. GC
was carried out on a Varian 430 instrument with a Factor
Four Capillary column (VF-1 ms, 15 m, 0.25 mm) and a flame
ionisation detector. Samples of 10 μl were taken via syringe
from the reaction mixtures at the specified time points. The
samples were immediately quenched by addition of the
aliquots to a solution of tetra-n-butylammonium chloride
General procedure for the kinetic evaluation of the
Au-catalysed concurrent cycloisomerisation of 4-phenyl-1-
hexen-5-yne (9) and dimethyl allylpropargylmalonate (11) by GC.
Au complex (3.2 μmol, 0.01 equiv.) and AgOTf (0.8 mg,
3.2 μmol, 0.01 equiv.) were mixed in dichloromethane in a
screw cap vial (1 min) and the solvent removed in vacuo. A
solution of 4-phenyl-1-hexen-5-yne (9) (50.0 mg, 321 μmol,
1 equiv.) and dimethyl allylpropargylmalonate (11) (67.4 mg,
321 μmol, 1 equiv.) in 1,2-dichloroethane (1.60 ml, 0.20 M)
was added, the vial sealed with a rubber septum and a
positive pressure of argon applied via an argon balloon. The
mixture was stirred at 25 °C in the absence of light. Samples
of 10 μl were taken via syringe and added immediately to a
solution of tetra-n-butylammonium chloride (8 mM, 20 μl) in
2 2
(8 mM, 20 μl) in CH Cl . Conversion was determined via gas
chromatography using a 1 μl sample injected directly into the
instrument via syringe. Further sampling was carried out on
selected aliquots over a period of time to ensure no further
conversion occurred after quenching. The errors on the
kinetic curves are recorded in the tables detailed in the main
text (see also Tables 1–3).
Values for the integrated areas of the GC signals corre-
sponding to starting materials and products were inputted
into Microsoft Excel spreadsheet software. This software was
used to calculate percent conversions by comparison of
starting material and product signal areas. The concentration
of the species in solution was determined from the percent
conversions and the initial starting material concentration.
2 2
CH Cl (1 mL). Conversion was determined via gas chroma-
tography using a 1 μl sample. The chromatogram was run
with an injector temperature of 250 °C and an initial oven
temperature of 80 °C (0.5 min), heated to 160 °C, at a rate of
−
1
10 °C min , and maintained at 160 °C (1 min). The retention
times were: 4.04 minutes for 4-phenyl-1-hexen-5-yne (9), 7.94
minutes for 3-phenylbicyclo[3.1.0]hex-2-ene (10), 5.53 minutes
for dimethyl allylpropargylmalonate (11), 7.73 minutes for 12a
1
Selected aliquots were analysed by H NMR spectroscopy to
1
1
ensure consistency with conversions measured by GC.
Kinetic analysis. The reaction kinetics were calculated
assuming a first order kinetic model by plotting ln[enyne]
against time. Linear least-squares regression was used to
calculate observed rate constants, initial rates and standard
errors. The calculated concentrations of starting materials
and products during the course of the reactions were also
inputted into Dynafit™ software (reported by Biokin).
Nonlinear least-squares regression was used to fit the experi-
mental kinetic data to predetermined molecular mechanisms
as described in the main body of the paper. This was used to
determine the order of reaction, observed rate constants,
1
13
and 8.15 minutes for 12b. The H and C NMR spectroscopic
data for 9 and 10 (including representative NMR spectra) have
6
been previously reported.
[(1-Allylcyclohexyl)ethynyl]benzene (14). Prepared by a
1
2
protocol based on that of Zhan and co-workers.
1-Phenylethynyl cyclohexanol (13) (0.50 g, 2.5 mmol, 1 equiv.)
and allyltrimethylsilane (6) (1.19 ml, 7.5 mmol, 3 equiv.) were
mixed in acetonitrile (5 ml, dry) and FeCl
3
(anhydrous,
40 mg, 0.25 mmol, 0.1 equiv.) in acetonitrile (1 ml, dry) was
added dropwise. The reaction was stirred at 60 °C for 18 h,
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reduced in vacuo and the product purified by column
chromatography on silica gel, eluting with petroleum ether
Characterisation details are included in the main body of the
text (Table 4 gives further details). The interaction of AgOTf
with 1-hexene was examined on the same scale as above,
(
(
40–60 °C), to give the title compound as a colourless oil
0.249 g, 1.11 mmol, 44%). H NMR (400 MHz, CDCl3)
1
III
without the Au complex. See ESI† for NMR spectral data.
δ 7.44–7.40 (m, 2H), 7.32–7.23 (m, 3H), 6.05 (ddt, J = 12.4, 9.3
and 7.5 Hz, 1H), 5.12 (m, 1H), 5.09 (m, 1H), 2.26 (dt, J = 7.2
1
3
Acknowledgements
and 1.3 Hz, 2H), 1.87–1.58 (m, 7H), 1.28–1.12 (m, 3H).
C
NMR (100 MHz, CDCl ) δ 135.0, 131.6, 128.1, 127.4, 124.2,
3
We acknowledge GlaxoSmithKline, EPSRC and the Royal
Society for funding. Dr J. M. Slattery is thanked for a sample
1
3
17.1, 95.1, 83.3, 47.4, 37.6, 37.0, 26.1, 23.1. ESI+-MS m/z
+
01.1 (100%, [M + Ph] ), 279.2 (11%), 245.1 (61%), 225.2
of Ag[Al(OC(CF ) ) ] and discussions concerning this salt.
+
3 3 4
(
(
68%, [MH] ), 195.1 (20%), 167.1 (11%), 149.0 (23%), 126.0
30%). ESI+-HRMS calcd. for C17
25.1633.
This paper builds on work funded by a previous EPSRC grant
+
H
21 ([MH] ) 225.1638; found
(
EP/D078776/1).
2
t
(
4,4-Dimethylcyclohexa-1,5-dien-1-yl)benzene (15). [AuBr(I Pe)]
(
7
(
3.6 mg, 7.4 μmol, 0.02 equiv.), Ag[Al(OC(CF
.4 μmol, 0.02 equiv.) and [(1-allylcyclohexyl)ethynyl]benzene
14) (78.3 mg, 0.350 mmol, 1 equiv.) were dissolved in
3 3 4
) ) ] (76) (8.0 mg,
Notes and references
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C. Brouwer and C. He, Chem. Rev., 2008, 108, 3239–3265; (c)
Zigang Li, C. Brouwer and C. He, Chem. Rev., 2008, 108,
3351–3378; (d) E. Jiménez-Núñez and A. M. Echavarren,
Chem. Commun., 2007, 333–346.
dichloromethane (2 mL) and stirred (0 °C – r.t., 15 h). The
reaction mixture was reduced in vacuo and purified by
column chromatography on silica gel, eluting with petroleum
ether (40–60 °C), to give the title compound as a colourless
oil (64.8 mg, 0.289 mmol, 83%; 93% conversion noted
2 (a) Y. Harrak, C. Blaszykowski, M. Bernard, K. Cariou,
E. Mainetti, V. Mouriès, A. Dhimane, L. Fensterbank and
M. Malacria, J. Am. Chem. Soc., 2004, 126, 8656–8657; (b)
M. R. Luzung, J. P. Markham and F. D. Toste, J. Am. Chem.
Soc., 2004, 126, 10858–10859; (c) Y. Horino, T. Yamamoto,
K. Ueda, S. Kuroda and F. D. Toste, J. Am. Chem. Soc.,
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Curr. Chem., 2011, 302, 31–80.
3 (a) J. Sun, M. P. Conley, L. Zhang and S. A. Kozmin, J. Am.
Chem. Soc., 2006, 128, 9705–9710; (b) L. Zhang and
S. A. Kozmin, J. Am. Chem. Soc., 2004, 126, 11806–11807; (c)
V. Mamane, T. Gress, H. Krause and A. Fürstner, J. Am.
Chem. Soc., 2004, 126, 8654–8655; (d) F. Gagosz, Org. Lett.,
1
by NMR). H NMR (400 MHz, CDCl
3
) δ 7.46–7.43 (m, 2H,
aromatic CH), 7.39–7.34 (m, 2H, aromatic CH), 7.31–7.26 (m,
H, aromatic CH), 6.30 (dd, J = 9.9 and 1.8 Hz, 1H, alkene
CH d), 6.05 (app. t, J = 4.8 Hz, 1H, alkene CH c), 5.97 (d, J =
1
9
1
.9 Hz, 1H, alkene CH e), 2.36 (d, J = 4.8 Hz, 2H, CH
2
b),
.64–1.39 (m, 10H, cyclohexyl CH2). C NMR (100 MHz,
) δ 140.3 (C), 137.8 (2 peaks, alkene CH e), 134.9 (C),
28.3 (CH), 126.8 (CH), 125.3 (CH), 123.4 (alkene CH d),
22.0 (alkene CH c), 36.3 (broad, cyclohexyl CH ), 36.2
1
3
CDCl
1
1
3
2
(
2
1
alkene CH
1.8 (cyclohexyl CH
2
2
b), 33.4 (cyclohexyl C), 26.3 (cyclohexyl CH
2
),
). EI+-MS m/z 224 (100%, [M] ), 181 (7%),
67 (34%), 153 (8%), 142 (7%), 115 (6%), 91 (6%), 49 (34%).
+
2
005, 7, 4129–4132.
4
(a) N. Marion, G. Lemière, A. Correa, C. Costabile,
R. Ramón, X. Moreau, P. D. Frémont, R. Dahmane,
A. Hours, A. Lesage, J. C. Tablet, J. P. Goddard, V. Gandon,
L. Cavallo, L. Fensterbank, M. Malacira and S. P. Nolan,
Chem. – Eur. J., 2009, 15, 3243–3260; (b) E. Jiménez-Núñez
and A. M. Echavarren, Chem. Rev., 2008, 108, 3326–3350; (c)
T. Godet and P. Belmont, Synlett, 2008, 2513–2517; (d)
S. M. Ma, S. C. Yu and Z. H. Gu, Angew. Chem., Int. Ed.,
2006, 45, 200–203; (e) L. Zhang, J. Sun and S. A. Kozmin,
Adv. Synth. Catal., 2006, 348, 2271–2296; ( f ) C. Nieto-Oberhuber,
M. P. Muñoz, E. Buñuel, C. Nevado, D. J. Cárdenas
and A. M. Echavarren, Angew. Chem., Int. Ed., 2004, 43,
2402–2406.
NMR experiments
Generation of Au cationic species from AuBr (N-TFS)
III
2
t
t
(
1
1
I Pe) and AgOTf. In acetone-d
6
: AuBr
2
(N-TFS)(I Pe) (10 mg,
−
5
.36 × 10 mols) was reacted with AgOTf (3.5 mg, 1.36 ×
−
5
0
mols) in acetone-d (0.67 mL) at 25 °C. The mixture was
6
1
stirred for 1 h and then a H NMR spectrum was recorded
500 MHz). Characterisation details are included in the main
body of the text.
In CD Cl /CD
was reacted with AgOTf (7 mg, 6.8 × 10 ) or Ag[Al(OC(CF ) ) ]
(
t
−6
2
2
3 2
CN: AuBr (N-TFS)(I Pe) (5 mg, 6.8 × 10 mols)
−
6
3
3 4
−
6
(
(
7.3 mg, 6.8 × 10 mols) in CD Cl (0.6 mL) and CD CN
2 2 3
0.2 mL) at 25 °C. The mixture was stirred for 1 h and then a
1
H NMR spectrum was recorded (500 MHz). Characterisation
details are included in the main body of the text.
5 T. Fan, X. Chen, J. Sun and Z. Lin, Organometallics, 2012, 31,
4221–4227.
t
Binding of 1-hexene to AuBr
2
(N-TFS)(I Pe) and AgOTf, and
6 (a) J. P. Reeds, A. C. Whitwood, M. P. Healy and
I. J. S. Fairlamb, Organometallics, 2013, 32, 3108–3120; (b)
J. P. Reeds, A. C. Whitwood, M. P. Healy and
I. J. S. Fairlamb, Chem. Commun., 2010, 46, 2046–2049.
7 Dynafit program published by Biokin, see: P. Kuzmic,
Anal. Biochem., 1996, 237, 260–273.
t
−5
AgOTf alone. AuBr (N-TFS)(I Pe) (10 mg, 1.36 × 10 mols)
was reacted with AgOTf (3.5 mg, 1.36 × 10 mols) in CD Cl
2
−
5
2
2
(0.6 mL) for 1 h. Then, 1-hexene (3.4 μL, 2 equiv.) was added
and then NMR spectra were recorded (500 MHz). In separate
experiments the equivalents of 1-hexene were varied.
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