Internal Alkyne Regio- and Chemoselectivity using a Zwitterionic N-Heterocyclic Carbene Gold Catalyst in a Silver-Free Alkyne Hydration Reaction

Article abstract of DOI:10.1002/adsc.201601013

An alkyne hydration of terminal and internal alkynes is reported using a zwitterionic N-heterocyclic carbene gold catalyst [(BNHC)Au(SMe₂)] in the absence of silver and Br?nsted acid additives. The hydration demonstrates good regioselectivity in alkyne hydration and chemoselectivity for internal alkynes vs. terminal. In addition, (BNHC)Au(SMe₂) performs a propargyl alcohol hydration to predominantly form α-hydroxymethyl ketone over the more common Meyer–Schuster rearrangement product. While complex (BNHC)Au(SMe₂) is active without silver additives, addition of silver hexafluoroantimonate (AgSbF₆) increases reaction rate and decreases selectivity for internal alkyne hydration over terminal substrates. To the best of our knowledge, the rate enhancement of (BNHC)Au(SMe₂) by AgSbF₆is the first such demonstration of a silver effect for a “halide-free” Au catalyst. (Figure presented.).

Full text of DOI:10.1002/adsc.201601013

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DOI: 10.1002/adsc.201601013
Internal Alkyne Regio- and Chemoselectivity using a Zwitterionic
N-Heterocyclic Carbene Gold Catalyst in a Silver-Free Alkyne
Hydration Reaction
a
a
a
Kushan C. Weerasiri, Danmin Chen, Derek I. Wozniak,
a,
and Graham E. Dobereiner *
Department of Chemistry, Temple University, Philadelphia, Pennsylvania 19122, USA
a
Fax : (+1)-215-204-7118; e-mail: dob@temple.edu
Received: September 12, 2016; Revised: November 1, 2016; Published online: && &&, 0000
Abstract: An alkyne hydration of terminal and inter- silver additives, addition of silver hexafluoroantimo-
nal alkynes is reported using a zwitterionic N-hetero- nate (AgSbF ) increases reaction rate and decreases
6
cyclic carbene gold catalyst [(BNHC)Au(SMe )] in selectivity for internal alkyne hydration over termi-
2
the absence of silver and Brønsted acid additives. nal substrates. To the best of our knowledge, the rate
The hydration demonstrates good regioselectivity in enhancement of (BNHC)Au(SMe ) by AgSbF is the
2
6
alkyne hydration and chemoselectivity for internal first such demonstration of a silver effect for
alkynes vs. terminal. In addition, (BNHC)Au(SMe2) a “halide-free” Au catalyst.
performs a propargyl alcohol hydration to predomi-
nantly form a-hydroxymethyl ketone over the more
common Meyer–Schuster rearrangement product. Keywords: alkynes; gold; N-heterocyclic carbenes;
While complex (BNHC)Au(SMe ) is active without regioselectivity; silver
2
Introduction
directly participate in a gold catalytic cycle. For exam-
[19]
ple, Zhdanko and Maier found that Ag effects are
Gold catalysts for alkyne functionalization have yield- limited to influencing concentrations of organogold
[
1–8]
+
ed many valuable methods for organic synthesis,
intermediates or H in Au-catalyzed alkyne hydroal-
but regioselective hydration of internal alkynes re- koxylation. AgSbF itself is an active catalyst for ter-
6
[
9]
[10–14]
[25,26]
mains challenging despite several
al and experimental mechanistic explorations of Au a monometallic Ag hydration of internal alkynes.
alkyne reactions. In general, hydration catalysts are Mechanistic questions and regioselectivity issues
less reactive towards internal alkynes relative to ter- extend to Ag-free alkyne hydrations and related func-
computation- minal alkyne hydration,
but we are unaware of
[
9]
minal groups and demonstrate low regioselectivity.
tionalization reactions. One of the first Au-catalyzed
One complication in designing selective Au cata- alkyne hydration systems, a silver-free mixture of
lysts is the complex role of various additives such as [(PPh )AuCH ] and concentrated sulfuric acid, was
3
3
the Ag promoters employed in many Au-catalyzed re- poorly reactive towards internal alkynes relative to
+
[27]
actions. Silver salts, assumed to generate [L-Au] via terminal alkynes.
halide abstraction from Au-X, were found to exhibit [(Ph P)AuCl] is competent for terminal alkyne hydra-
In the absence of additives,
3
[28]
a further “silver effect” by Shi and co-workers where tion, but not for hydration of diphenylacetylene.
L-Au] cannot perform internal alkyne hydration in The silver-free (L)AuNTf2
+
[29,30]
[
alkyne hydration
[
10]
the absence of a silver co-catalyst.
In constrast, system exhibits moderate regioselectivity for internal
have reported a silver-free alkyne substrates. In the related hydrocarboxylation
[
15–18]
Nolan and co-workers
pre-catalyst [{Au(IPr)} (m-OH)][BF ] (A) active for reaction of internal alkynes with benzoic acid cata-
2
4
[
19–23]
the hydration of internal alkynes. Various studies
lyzed by A, Nolan and co-workers report “good to
have shown that Ag can react with gold precatalysts, complete regioselectivity” results from favored addi-
forming either low-activity chloride-bridged digold tion at the more electrophilic carbon of the alkyne
[
18]
complexes as a result of incomplete halide abstrac- triple bond – similar to the regioselectivity exhibit-
[
20]
[22,24]
tion or Au/Ag heterobimetallic species,
but to ed by alkyne hydration catalyzed by the [(IPr)AuCl]/
[5,31]
the best of our knowledge Ag has not been shown to AgSbF system.
Given the range of selectivity in
6
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these examples, Ag additives appear to be only one of
many factors with potential relevance to regioselectiv- 1 (Figure 1) featuring Tammꢁs BNHC ligand is effec-
ity and chemoselectivity. tive in alkyne hydration in the absence of silver and
We find that the zwitterionic gold (I) complex
Another potential influence on reaction selectivity acid additives, and that the regioselectivity of internal
may be dimer formation. In one case, speciation of alkyne hydration with 1 is among the highest report-
a gold hydroalkoxylation catalyst as a monometallic ed. Additionally, hydration with 1 demonstrates un-
or bimetallic species depends on the steric encum- usual chemoselectivity compared to existing systems.
[
14,32]
brance of the ancillary ligand,
and different path-
ways may well demonstrate different reaction selec-
tivity in alkyne hydration. Another complicating issue Results and Discussion
[
5,11,33–36]
is the role of counteranions in catalysis.
Coun-
teranions are commonly introduced by mixing Au Zwitterionic [(BNHC)Au(SMe )] (1) was synthesized
2
[
43]
precatalysts with Ag salts of weakly-coordinating following a modified literature procedure. Reaction
anions (WCAs) such as SbF . Besides Ag, other salts of commercially available IPr with n-BuLi and
6
of WCAs can influence the rate of alkyne hydration B(C F ) afforded the BNHC as a lithium salt, which
6
5 3
(
e.g., KCTf ) even in reactions without Au halide pre- was then reacted with Me SAuCl to form 1. The com-
3 2
[37]
cursors. Among other potential roles, anion X may plex in the solid state (Figure 2) demonstrates a near-
influence reactivity by forming tight [L-Au-X] ion linear geometry [C(3)–Au(1)–S(1) 176.72(11)8] consis-
[
38–40]
pairs with cationic Au intermediates
and may fa- tent with BNHC-Au structures reported by Tamm
[43]
cilitate protodeauration in alkyne hydroalkoxyla- and co-workers.
tion. Brønsted and Lewis acids can each influence
rates of Au-catalyzed hydration. The formation of plexes with a conventional WCA, {BAr , tetrakis[3,5-
[11]
For catalysis comparison, two [(NHC)Au][X] com-
[
41]
F
4
Brønsted acid HX in situ could also play a role in dic- bis(trifluoromethyl)phenyl]borate}, were also pre-
F
4
tating product distributions, given the known hydra- pared. [(IPr)Au(tht)][BAr ] (2a; tht=tetrahydrothio-
[
42]
tion activity of strong acids.
In developing new selective alkyne hydration meth-
ods, we sought a gold catalyst system that minimizes
complications arising from both Ag additives and
+
WCAs. Since commonly-proposed [L-Au(I)] inter-
mediates are cationic, some weakly-coordinating
anionic species is necessary for charge balance. One
emerging approach is the use of dative ligands cova-
lently attached to weakly-coordinating anionic resi-
dues, rather than relying on an exogeneous WCA.
Several zwitterionic organometallic complexes of
[43–46]
Au
have now been prepared, each featuring
weakly-coordinating anionic ligands that bind in
a dative fashion. For example, Tamm and co-work-
[43]
ers
have prepared an anionic N-heterocyclic car-
bene (BNHC) that is covalently attached to a weakly-
coordinating borato substituent. Zwitterionic organo-
[
43]
[47]
metallic complexes of Au and Ir were successful-
ly used by Tamm in homogeneous catalysis. Given the
activity of BNHC-Au catalysts in the rearrangement
[43]
of an enyne, we chose to study Au alkyne hydration
catalysts incorporating the Tamm BNHC ligand.
Figure 2. Thermal ellipsoid plot of [(BNHC)Au(SMe )] (1).
2
Ellipsoids are drawn at the 50% probability level. Selected
bond lengths (ꢂ) and angles (deg): Au(1)–C(3) 2.022(4),
Au(1)–S(1) 2.3077(13), S(1)–C(31) 1.794(6), S(1)–C(30)
1
1
.809(6), N(1)–C(3) 1.354(5), N(1)–C(6) 1.417(5), N(2)–C(3)
.331(5), N(2)–C(7) 1.385(5), B(1)–C(6) 1.652(6); C(3)–
Au(1)–S(1) 176.72(11), C(31)–S(1)–C(30) 100.4(3), C(31)–
S(1)–Au(1) 105.9(2), C(30)–S(1)–Au(1) 102.9(2), C(3)–
N(1)–C(6) 111.5(3), C(3)–N(2)–C(7) 109.3(3), N(2)–C(3)–
N(1) 106.3(3), N(2)–C(3)–Au(1) 128.5(3), N(1)–C(3)–Au(1)
1
25.1(3), C(7)–C(6)–N(1) 102.7(3), C(7)–C(6)–B(1) 121.7(4),
Figure 1. [(NHC)Au(I)] complexes.
N(1)–C(6)–B(1) 135.5(3), C(6)–C(7)–N(2) 110.1(4).
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phene) was prepared by treating (tht)AuCl with
Various catalyst loadings of 1 were also studied.
F
NaBAr and IPr. The synthesis of [(IPr)Au(PPh )] When the catalyst loading was reduced to 0.5 mol%,
4
3
F
[
BAr ] (2b) required the reaction of (tht)AuCl with 1000 ppm, and 100 ppm, reaction yields dropped to
4
F
NaBAr 4 and PPh followed by the addition of IPr.
25%, 2%, and 0%, respectively. Changing the solvent
3
To compare the alkyne hydration activity of zwitter- did not improve the yield, but reaction in the less
[
48]
ionic 1 to other Au catalysts, catalytic runs were per- toxic dioxane alternative cyclopentyl methyl ether
formed with diphenylacetylene as the substrate produced the ketone in very good (85%) yield. Re-
(
Table 1), since it has been widely used as a bench- placing 1,4-dioxane with THF produced a 63% yield,
[15]
mark of activity. Alkyne hydration was performed while use of MeOH as solvent resulted in MeOH ad-
in a mixture of 1,4-dioxane and water (2:1) at 808C dition to the alkyne. Temperatures below 808C re-
for 18 h, conditions previously optimized with gold(I) duced the benzyl phenyl ketone yield while elevated
[5]
systems. 1 converted diphenylacetylene to the corre- temperatures did not produce higher yields.
sponding ketone in excellent yield (Table 1). We note Unlike many other alkyne hydration precatalysts,
that 1 is air stable and reactions were conducted Ag salts are not required to activate zwitterionic pre-
under aerobic conditions unless otherwise noted. Di- catalyst 1 via halide abstraction. Nevertheless, to in-
[
10]
phenylacetylene was hydrated to the corresponding vestigate any further role of silver salts in internal
ketone in identical amounts under either aerobic or alkyne hydration, AgSbF was added to the reaction
6
anaerobic conditions.
of 1. When 1 mol% of AgSbF was used with 1 mol%
6
Ph PAuCl failed as a catalyst even in the presence of 1, the rate of the reaction was significantly in-
3
F
of NaBAr , AgOTf or AgSbF , with no more than creased (Figure 3). A 90-minute induction period was
4
6
2% obtained (Table 1, entries 3–6). Addition of PPh3 observed in the absence of silver salt, while 1 mol%
did not improve the reaction (Table 1, entry 7). AgSbF6 shortens the induction period to approxi-
IPrAuCl produced diphenylacetylene hydration in ex- mately 1 hour. Increasing the silver loading to
cellent yield in the presence of AgSbF6 (Table 1, 2 mol% did not improve the rate of the reaction fur-
entry 9) confirming earlier results of Nolan and co- ther. Addition of NaSbF did not appear to accelerate
6
[5]
workers. The silver-free halide abstracting agent the rate of hydration. We note that AgSbF alone
NaBAr 4 was not effective in activating the IPrAuCl, does not hydrate internal alkynes under these condi-
6
F
only affording 8% yield of the corresponding ketone tions. In an attempt to isolate a potential Au/Ag bi-
(
Table 1, entry 10), and again addition of PPh result- metallic complex, a 1:1 mixture of 1 and AgSbF was
3
6
ed in no reaction (Table 1, entry 11). 2b afforded no stirred in a mixture of 1,4-dioxane and H O (2:1, 1.5
2
reaction (Table 1, entry 12) while 2a produced 4% mL) at 808C for 3 h but no adducts or bimetallic spe-
yield (Table 1, entry 13).
cies were observed – only starting material was recov-
ered.
With optimized reaction conditions in hand, the
substrate scope of catalyst 1 was examined (Table 2).
[a]
Table 1. Screen of Au complexes for alkyne hydration.
[b]
Entry
Au complex
Yield [%]
92 [
1
2
3
4
5
6
7
8
9
[(BNHC)Au(SMe )], 1
None
2
c]
NR
Ph PAuCl
NR
NR
2
3
F
Ph PAuCl/NaBAr
3
4
Ph PAuCl/AgOTf
3
Ph PAuCl/AgSbF
2
3
6
Ph PAuCl/AgSbF /PPh
NR
NR
94
3
6
3
IPrAuCl
IPrAuCl/AgSbF6
IPrAuCl/NaBAr
IPrAuCl/NaBAr /PPh
[(IPr)Au(PPh )][BAr ], 2b
[(IPr)Au(tht)][BAr ], 2a
F
10
11
12
13
8
4
F
NR
NR
4
4
3
F
3
4
F
4
[
a]
Reaction conditions: Au complex (1 mol%) and diphenyl-
ACHTUNGTRENNUNGa cetylene (0.5 mmol) 1,4-dioxane:H O (2:1, 1.5 mL),
Figure 3. Plot of yield (%) vs. time (min) for the hydration
of diphenylacetylene using 1 either with or without AgSbF6.
2
8
08C, 18 h.
Conditions: 1 (5 mmol), AgSbF (5 mmol or none) and diphe-
6
[
[
b]
1
Reaction yield determined by H NMR.
NR=no reaction.
nylacetylene (0.5 mmol), 1,4-dioxane:H O (2:1, 1.5 mL),
2
c]
1
808C. Reaction yield determined by H NMR.
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Table 2. Substrate scope of alkyne hydration of internal al- more electron-rich carbon. The ester group was re-
[a]
kynes.
tained during this hydration, highlighting the mild
nature of the catalytic conditions. An internal aliphat-
ic alkyne, 5-decyne, was also hydrated in very good
yield (Table 2, entry 4). Diphenylacetylene with an
acyl substituent underwent the hydration to form one
ketone isomer predominantly in a 1:4.5 4e :4e ratio
a
b
(
Table 2, entry 5). A substrate with a chloro substitu-
ent was unreactive and may be incompatible with the
catalytic protocol (Table 2, entry 6).
Reactivity of several terminal alkynes was also
tested under aerobic conditions (Table 3). Relative to
internal alkynes, terminal alkynes afforded lower con-
versions over 18 h using catalyst 1, contrary to what
[
27]
has been observed with other systems. Phenylacety-
lene was hydrated to form acetophenone in 62% yield
(
Table 3, entry 1). Surprisingly, a much lower (4%)
yield of acetophenone was observed under anaerobic
conditions – an effect not seen for internal alkyne hy-
dration with 1. Electronic effects strongly influence
reactivity with 88% and 38% yield achieved with
a methyl-substituted and a fluoro-substituted sub-
strate, respectively (Table 3, entries 2 and 3). An alkyl
substituted terminal alkyne, 1-decyne, was converted
in excellent yield (Table 3, entry 4). 1-Phenyl-2-
propyn-1-ol was hydrated and yielded 44% of the cor-
responding a-hydroxymethyl ketone (Table 3, entry 5)
Table 3. Substrate scope of alkyne hydration of terminal al-
[a]
kynes.
[
[
a]
b]
Reaction conditions: 1 (5 mmol) and substrate (0.5 mmol)
in a mixture of 1,4-dioxane and H O (2:1, 1.5 mL) were
2
stirred at 808C for 18 h.
Reaction yields and regioselectivities determined by
1
H NMR.
In order to test the regioselectivity of the system, sev-
eral internal alkyne hydrations were performed under
aerobic conditions. The regioselectivity of these reac-
tions was determined by comparing our spectra with
literature data (see the Supporting Information).
Both 3b and 3c were converted to products quantita-
tively (Table 2, entries 2 and 3). Reaction of 1-phenyl-
1
-hexyne afforded a 1:7.3 4b :4bb product ratio
a
(
Table 2, entry 2), a relatively high regioselectivity for
[9]
the hydration of an aryl alkyl substituted alkyne,
and the opposite selectivity of that expected under
[
41]
acid-catalyzed hydration conditions. In the case of
ethyl phenylpropiolate, only one ketone isomer was
formed (along with its enol tautomer in a 4.7:1 ratio;
Table 2, entry 3), reflecting the strong thermodynamic
preference of this regioisomer, rather than the cata-
lyst systemꢁs overall preference for hydration at the
[a]
Reaction conditions: 1 (5 mmol) and substrate (0.5 mmol)
in a mixture of 1,4-dioxane and H O (2:1, 1.5 mL) were
2
stirred at 808C for 18 h.
[b]
Reaction yields and regioselectivities determined by
1
H NMR.
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as well as 28% yield of the a,b-unsaturated aldehyde,
k , the product expected from the Meyer–Schuster
4
b
[49]
rearrangement. The 1.6:1 ratio of products obtained
in entry 5 is informative from a mechanistic stand-
point. Shi and co-workers state that gold(I) catalysts
are ineffective towards propargyl alcohol hydration to
[
10]
form a-hydroxymethyl ketones,
while Nolan and
co-workers find [{Au(IPr)} (m-OH)][BF ] to be an
2
4
active catalyst to exclusively form the Meyer–Schuster
[
15]
rearrangement product.
As mentioned above, 18-hour conversions obtained
for internal alkynes were higher than for terminal al-
kynes. To test the chemoselectivity of 1, an equimolar
mixture of diphenylacetylene and phenylacetylene
was reacted under the same aerobic reaction condi-
tions as in Table 1 (1 mol% Au loading relative to the
sum of alkynes present). The reaction favored hydra-
tion of the internal alkyne, producing benzyl phenyl
ketone to acetophenone in a 5.2:1 ratio with 59%
combined yield. The relative concentrations of phe-
nylacetylene and diphenylacetylene over time
(
Figure 4, top) show that initial, slow hydration of
phenylacetylene is eventually outpaced by hydration
of internal alkyne after 6 hours. The overall reaction
rate is considerably slower than internal-only hydra-
tion (Figure 3) despite identical Au/alkyne loading
(
1 mol%). Adding AgSbF to the reaction significant-
6
ly increased the initial rate of phenylacetylene hydra-
tion, but like the silver-free reaction terminal hydra-
tion eventually slows and is outpaced by internal hy-
dration. The faster initial phenylacetylene hydration
results in a benzyl phenyl ketone to acetophenone
ratio of 1.8:1 (77% overall yield). Competition reac-
tions under nitrogen were very low yielding, suggest-
ing that terminal alkyne inhibits internal hydration
under anaerobic conditions.
Figure 4. (Top) Plot of yield (%) vs. time (h) for a 1:1 phe-
nylacetylene:diphenylacetylene competition experiment.
Conditions:
1
(2.5 mmol),
and
diphenylacetylene
(
(
0.25 mmol), phenylacetylene (0.25 mmol), 1,4-dioxane:H O
2:1, 1.5 mL), 808C. (Bottom) Plot of yield (%) vs. time (h)
2
for a 1:1 phenylacetylene: diphenylacetylene competition
experiment in the presence of AgSbF . Conditions: same as
6
above but with AgSbF (2.5 mmol). Reaction yield deter-
6
1
mined by H NMR. Average of at least two runs.
In our hands, the aerobic phenylacetylene/diphenyl-
ACHTUNGTRENNUNGa cetylene competition reaction performed with
[5]
IPrAuCl/AgSbF6 surprisingly produced very low selectivity pattern. A major difference between
yield (3%) of acetophenone and 0% benzyl phenyl [{Au(IPr)} (m-OH)][X] (A) and catalyst 1 is seen for
2
ketone. Since IPrAuCl/AgSbF6 efficiently hydrates hydration of 1-phenyl-2-propyn-1-ol: A exclusively
both phenylacetylene and diphenylacetylene in single- forms the Meyer–Schuster product, while 1 predomi-
substrate runs, the catalyst inhibition stems from nantly forms a-hydroxymethyl ketone 4ia (Table 3,
some effect upon combining these two substrates in entry 5). The presence of a silver salt, the structure of
our competition experiment.
the ancillary ligand, and the nature of the weakly-co-
Although the ancillary ligand in 1 is a modification ordinating anion may all contribute to the differences
of the IPr ligand used in the systems of Nolan and co- in activity between 1 and the Nolan system. Direct
[5]
workers, the selectivity observed using catalyst 1 dif- structural and reactivity comparisons to 1 via prepara-
fers from that reported by Nolan for the [IPrAuCl]/ tion of Au dimers from 1 have thus far not been suc-
[5]
AgSbF system. Particularly surprising is the differ- cessful.
6
ence between [IPrAuCl]/AgSbF and catalyst 1 when
While catalyst 1 may be used without external addi-
6
both terminal and internal alkynes are present. Com- tives, experimental evidence suggests 1 undergoes
paring the regioselectivity of 1-catalyzed alkyne hy- changes in situ to become kinetically competent for
dration to Nolanꢁs [{Au(IPr)} (m-OH)][BF ] (A) internal alkyne hydration. The induction period ap-
2
4
[31]
system suggests a similar preference for nucleophil- parent in the kinetic profile of catalyst 1 (Figure 3) is
ic attack at the more electrophilic alkyne carbon, consistent with an in situ generation of a catalyst
[
18]
where hydrocarboxylation using A shows the same active for internal alkyne hydration. The exclusion of
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oxygen does not appear to influence the overall yield Experimental Section
of the internal alkyne hydration, and either anaerobic
or aerobic conditions are tolerated. Interestingly, the Preparation of (BNHC)Li(THF)2
kinetic profile for conversion of a terminal alkyne
This compound was synthesized following a modified litera-
does not demonstrate an induction period of the same
magnitude under the aerobic conditions of the inter-
molecular competition experiment. No conversion of
[43]
ture procedure.
.000 mmol) in 20 mL of toluene was added n-butyllithium
0.4 mL, 1 mmol) at À358C. The reaction mixture was al-
To
a
solution of IPr (0.3965 g,
1
(
terminal alkynes is seen under anaerobic conditions, lowed to come to room temperature and stir for 4 h. A solu-
suggesting some possible role of oxygen in the activa- tion of B(C (0.5389 g, 1.000 mmol) in 5 mL of toluene
F )
6 5 3
tion process prior to reaction of terminal substrates.
Based on the time course data in Figure 4, the che-
moselectivity effect of silver reflects an accelerating
influence on the relative rate of terminal hydration
relative to internal alkynes. At this stage we do not
have evidence to support a direct role for Ag in Au
catalysis, nor an informed hypothesis as to the origin
of substrate-dependent rate acceleration. Effects pre-
was then added to the reaction, and the mixture was stirred
at room temperature overnight. THF was slowly added to
the resulting suspension until it became a clear solution and
stirring was continued for 6 h. The resulting white precipi-
tate was vacuum filtered, washed with pentane, and dried
under vacuum to afford (BNHC)Li(THF) ; yield: 92%.
2
1
H NMR (500 MHz, CD Cl ): d=0.96 (d, J=7.5 Hz, 6H),
2
2
0
7
.98 (d, J=7.5 Hz, 6H), 1.11 (d, J=7.0 Hz, 6H), 1.14 (d, J=
.0 Hz, 6H), 1.62 (m, 8H), 2.82 (sept, J=7.0 Hz, 2H), 3.04
[
19]
viously suggested, such as coordinating to Au poi- (m, 8H), 3.11 (sept, J=7.0 Hz, 2H), 6.25 (br s, 1H), 7.06 (d,
+
sons or indirect influences upon Au or H concentra- J=7.5 Hz, 2H), 7.18 (t, J=7.5 Hz, 1H), 7.24 (d, J=8.0 Hz,
1
1
tion are possible. Another possible influence is a coun- 2H), 7.38 (m, 1H); B NMR (500 MHz, CD
Cl
2
): d=À15.8;
2
1
9
À
F NMR (400 MHz, CD Cl ): d=À167.3 (t, J=19.6 Hz,
terion effect, where SbF6 acts as a proton shuttle or
2
2
[
11]
6F), À162.6 (t, J=21.2 Hz, 3F), À129.1 (s).
a
hydrogen bond acceptor.
However, adding
NaSbF did not accelerate the rate of hydration.
6
Preparation of (BNHC)Au(SMe ) (1)
Regardless of the true role of silver in situ, the re-
sults from this study suggest that silver effects can in-
fluence reaction outcomes, even for reactions of
2
A
100-mL round-bottomed flask was charged with
(
BNHC)Li(THF) (0.525 g, 0.500 mmol) and [ClAu(SMe )]
2
2
“
halide-free” catalysts. Besides the good regioselectiv- (0.152 g, 0.500 mmol) and toluene (20 mL, cooled to À358C)
ity and unusual chemoselectivity reported here, the in the absence of light. The reaction mixture was stirred for
influence of AgSbF on relative rates and induction 2 h and allowed to warm to room temperature during this
6
time. The resulting mixture was filtered through Celite and
periods observed should be of use to others in devel-
the solvent was removed under vacuum. The crude product
oping new gold-catalyzed reactions.
was recrystallized from dichloromethane/pentane solution at
1
À358C to afford (BNHC)Au(SMe ); yield: 45%. H NMR
2
(
500 MHz, CD Cl ): d=0.93 (d, J=7.0 Hz, 6H), 1.16 (d, J=
2 2
Conclusions
7.0 Hz, 6H), 1.26 (d, J=7.0 Hz, 6H), 1.31 (d, J=6.5 Hz,
6H), 2.15 (s, 6H), 2.65 (sept, J=7.0 Hz, 2H), 2.90 (sept, J=
6.5 Hz, 2H), 6.45 (s, 1H), 7.10 (d, J=8.0 Hz, 2H), 7.27 (d,
Gold complex 1 acts as an efficient catalyst for hydra-
tion of terminal and internal alkynes without the need J=8.0 Hz, 2H), 7.39 (t, J=7.5 Hz, 1H), 7.46 (t, J=7.5 Hz,
for silver and acid additives. Other gold complexes 1H); C NMR (500 MHz, CD Cl ): d=21.7, 22.7, 23.6, 24.3,
with exogeneous weakly-coordinating anions (2a and 26.7, 27.5, 28.1, 123.0, 123.7, 129.6, 130.0, 130.3(m), 133.9,
1
3
2
2
1
35.5 (m), 136.2, 137.5 (m), 139.6 (m), 146.1, 147.3, 147.7
2
b) were ineffective for silver-free alkyne hydration
1
1
(
m), 149.6 (m), 174.2; B NMR (500 MHz, CD Cl ): d=
2 2
compared to 1, highlighting the value of the BNHC
ligand to gold catalysis. Regioselectivity for internal
alkyne hydration with 1 is among the highest report-
ed, and internal substrates were more efficiently hy-
drated than terminal ones. Despite the use of
À16.0; anal. calcd. for C H AuBF N S: C 48.72, H 3.56, N
4
7
41
15
2
2
.41; found: C 48.25, H 3.52, N 2.16. Crystallographic data
and details of the collection for complex 1 are reported in
the Supporting Information. CCDC 1444084 contains the
supplementary crystallographic data for this paper. These
data can be obtained free of charge from The Cambridge
a “halide-free” catalyst precursor, AgSbF accelerates
6
the rate of hydration. In a substrate competition ex- Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_-
periment, the rate enhancement of silver was greater request/cif.
for terminal alkynes relative to internal ones. A
mechanistic investigation is now underway to better Preparation of [NHCAu(tht)][BAr ] (2a)
understand the origin of the unusual behavior of 1, in-
cluding the differences between aerobic and anaero-
bic reactivity.
F
4
A
dichloromethane solution of AuCl(SC H ) (30.0 mg,
4 8
F
0
.102 mmol), NaBAr
(90.0 mg, 0.102 mmol), and IPr
4
(
40.0 mg, 0.103 mmol) were stirred in a vial for 3 h. The mix-
ture was filtered through Celite and the solvent was re-
moved under vacuum. The crude product was recrystallized
from dichloromethane/pentane solution twice to afford
F
1
[
NHCAu(tht)][BAr ]; yield: 35%. H NMR (500 MHz,
4
Adv. Synth. Catal. 0000, 000, 0 – 0
6
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ÞÞ
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FULL PAPERS
asc.wiley-vch.de
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[
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General Procedure for the Alkyne Hydration
[
[
[
6
A vial was charged with (BNHC)Au(SMe ) (1) (0.0057 g,
2
0.005 mmol) followed by 1 mL of 1,4-dioxane, diphenylace-
6
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2
1
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Acknowledgment is made to the Donors of the American
Chemical Society Petroleum Research Fund for support of
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Internal Alkyne Regio- and Chemoselectivity using
a Zwitterionic N-Heterocyclic Carbene Gold Catalyst in
a Silver-Free Alkyne Hydration Reaction
9
Adv. Synth. Catal. 2016, 358, 1 – 9
Kushan C. Weerasiri, Danmin Chen, Derek I. Wozniak,
Graham E. Dobereiner*
Adv. Synth. Catal. 0000, 000, 0 – 0
9
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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