Gold and Palladium Mediated Bimetallic Catalysis: Mechanistic Investigation through the Isolation of the Organogold(I) Intermediates

Article abstract of DOI:10.1021/acscatal.9b02275

Au-Pd based catalytic systems are a unique couple due to the carbophilic Lewis acidity of Au and the redox properties of Pd. To gain more insight into this bimetallic couple, a synthetic and mechanistic investigation was conducted. As key substrates, ynamides (N-alkynyl allyloxycarbamates and N-alkynyl ethyloxycarbamates) were used. Essential for the mechanistic part was the isolation of the organogold(I) intermediate to validate the proposed mechanism. In total, 18 polysubstituted oxazolones and 12 organogold(I) complexes were synthesized.

Full text of DOI:10.1021/acscatal.9b02275

Subscriber access provided by BUFFALO STATE
Article
Gold and Palladium mediated bimetallic catalysis: mechanistic
investigation through the isolation of the organogold(I) intermediates
Arno Verlee, Thomas S.A. Heugebaert, Tom Van der Meer, Pavel Kerchev,
Kristof Van Hecke, Frank Van Breusegem, and Christian Victor Stevens
ACS Catal., Just Accepted Manuscript • DOI: 10.1021/acscatal.9b02275 • Publication Date (Web): 12 Jul 2019
Downloaded from pubs.acs.org on July 12, 2019
Just Accepted
“Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted
online prior to technical editing, formatting for publication and author proofing. The American Chemical
Society provides “Just Accepted” as a service to the research community to expedite the dissemination
of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in
full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully
peer reviewed, but should not be considered the official version of record. They are citable by the
Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore,
the “Just Accepted” Web site may not include all articles that will be published in the journal. After
a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web
site and published as an ASAP article. Note that technical editing may introduce minor changes
to the manuscript text and/or graphics which could affect content, and all legal disclaimers and
ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or
consequences arising from the use of information contained in these “Just Accepted” manuscripts.
is published by the American Chemical Society. 1155 Sixteenth Street N.W.,
Washington, DC 20036
Published by American Chemical Society. Copyright © American Chemical Society.
However, no copyright claim is made to original U.S. Government works, or works
produced by employees of any Commonwealth realm Crown government in the course
of their duties.

Page 1 of 11
ACS Catalysis
1
2
3
4
5
6
7
8
9
Gold and Palladium Mediated Bimetallic Catalysis: Mechanistic
Investigation Through the Isolation of the Organogold(I)
Intermediates
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
Arno Verlee,a Thomas Heugebaert, a Tom van der Meer,b Pavel Kerchev,b Kristof Van Hecke,c Frank
Van Breusegemb and Christian V. Stevens a,*
aDepartment of Green Chemistry and Technology, Faculty of Bioscience Engineering, Ghent University, Campus Coupure,
Coupure Links 653, B-9000 Ghent, Belgium.
bDepartment of Plant Systems Biology, VIB, Ghent University, Technologiepark 927, B-9000 Ghent, Belgium.
cDepartment of Chemistry, Faculty of sceinces, XStruct, Ghent University, Krijgslaan 281 (S3), B-9000, Ghent, Belgium
ABSTRACT: Au-Pd based catalytic systems are a unique couple due to the carbophilic lewis acidity of Au and the redox properties
of Pd. To gain more insight into this bimetallic couple, a synthetic and mechanistic investigation was conducted. As key substrates
ynamides (N-alkynyl allyloxycarbamates and N-alkynyl ethyloxycarbamates) were used. Essential for the mechanistic part was the
isolation of the organogold(I) intermediate to validate the proposed mechanism. In total 18, polysubstituted oxazolones and 12
organogold(I) complexes were synthesized.
KEYWORDS: oxazolones, domino reaction, bimetallic catalysis, organogold(I) intermediates, cross-coupling.
Introduction
isolated by Hammond and coworkers.9 The isolation of this
stable organogold(I) compound seemed to be a breakthrough
for gold chemistry. Not only did this compound provide the
starting point for the bimetallic catalysis of Blum and Nevado,
it also proved the proposed intermediate in gold catalyzed
cycloisomerization of this allenoate precursor. Even though,
gold catalyzed reactions have been studied and developed
vastly for the past thirty years,10-18 the mechanisms for these
reactions are mostly based on assumptions. There are only a few
intermediates that have been isolated.19-21 The problem is the
sensitivity of these intermediates to protodeauration. Therefore,
isolation of organogold compounds can be difficult, however,
as proven by Hammond and coworkers under certain conditions
organogold(I) compounds can be isolated.20
Bimetallic catalysis is a useful strategy to develop chemical
reactions which are impossible to perform using a single metal
catalyst. Essential for a process to be a bimetallic catalyzed
reaction is that both metals are catalytically used with two
different cycles which are connected by a transmetalation step.1-
5
As catalyst for the transmetalation, palladium is usually
chosen in combination with another metal catalyst, such as gold,
silver or copper. However, only a few examples are available of
cooperative catalytic Au-Pd systems.6-8 The first example of
Au-Pd bimetallic catalysis originates from 2009 and was the
“catalyzed catalysis” developed by the group of Blum (Scheme
1).6 The term catalyzed catalysis refers to a bimetallic catalytic
process in which the catalytic cycle of palladium can only start
once the catalytic cycle of the other metal, in this case gold, has
been initiated. In other words: the oxidative addition and
cycloisomerization step occur on the same substrate. As shown
in scheme 1 for the catalyzed catalysis approach, the oxidative
addition on Pd is only possible after cycloisomerization of the
allenoate precursor by Au (Scheme 1, compound A). More
recently, the group of Nevado developed a bimetallic catalytic
cross coupling between ethyl allenoate and iodobenzene.8
Although the allenoate is similar to the allyl allenoate used by
the group of Blum,6 the bimetallic method developed by the
group of Nevado is not a catalyzed catalysis approach since two
reagents are used (allenoate + iodobenzene) and is therefore
referred as a bimetallic approach (Scheme 1). Oxidative
addition occurs on iodobenzene followed by a transmetallation
step between the Pd(II) anionic complex and the cyclized
organogold intermediate.
In the past few years, there has been some progress in
isolating organogold(I) intermediates. The first method is the
procedure reported by the group of Hammond. In their approach
an ethyl ether was used which formed an ethyl oxonium
intermediate, that was detected by 1H-NMR, and resulted in the
isolation of the organogold(I) complex after removal of the
ethyl substituent with water.9 However, since water is the
nucleophile, this method will not work for compounds that are
sensitive to protodeauration. The second method is the addition
of triethylamine or other bases, the presence of a base will
prevent protodeauration. Although this method proved to be
efficient and resulted in the isolation of organogold(I)
intermediates,22-24 this approach seems not generally applicable
since only a few organogold compounds have been isolated by
this procedure so far. Therefore, it can be concluded that there
is
room
for
Intriguingly, all this work is centered around one compound,
namely the organogold(I) complex (Scheme 1, compound D)
ACS Paragon Plus Environment

ACS Catalysis
Organogold(I)
Page 2 of 11
Catalyzed catalysis
Bimetallic catalysis
1
2
3
4
5
6
7
8
R4
O
O
O
O
R4= allyl
R4= ethyl
[Au], [Pd]
R1
R1
O
O
R2
[Au], [Pd]
R1
R2
R2
R3
R3
R3
Ar
B
)
allenoate
C
( )
(
X
P
P
[Au],
[Pd0]
Pd0
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
O
R4
O
[Au], Et-I
PdII
O
R1
Ar
X
R4= Et
R4 = allyl
[Pd0]
L
O
X
R1
R1
O
O
R2
X
R3
Pd
R2
R2
Ar
PdII
I
P
X
P
R3
R3
[Au]
P
[Au]
P
A
(
)
R4= Et
Aq. work-up
I-Ar
Blum group
Nevado group
O
R1
O
+ EtOH
R2
R3
[Au]
D
(
)
Hammond group
Scheme 1. Au-Pd catalyzed catalysis and bimetallic catalysis as developed by the group of Blum6 and Nevado8 based on the
organogold(I) compound of Hammond and co-workers.9
a) Hashmi et al. and Istrate et al.
improvement and for more efficient procedures to obtain
O
organogold(I) compounds.
O
R1
R1
In our attempt to develop a catalyzed catalysis approach, an
ynamide based precursor was chosen or more precisely an N-
alkynyl carbamate (Scheme 2). These N-alkynyl carbamates25,26
are easy to synthesize in only two steps and in good total yields.
The selected precursor is similar to the one from the group of
Hammond,9 however, there are some essential differences.
Firstly, N-alkynyl carbamates would undergo a 5-endo-dig
cyclization instead of a 5-endo-trig cycloisomerization.
Secondly, carbamates are used instead of esters and an alkyne
is activated instead of an allene resulting in the oxazolone
skeleton.
[Au]
N
O
N
O
CH2Cl2, 40 °C
R2
R2
O
R1
N
O
[Au]
R2
b) This work
O
O
R1
R1
N
N
O
Au Pd
O
O
CH2Cl2, RT
R1
R1
R3
EWG
R2
N
N
O
R2
L
O
PdII
R1
R2
R2
OTf
N
O
Ynamide
N-alkynyl carbamate
[Au]
R2
Scheme 2. Core structure of the N-alkynyl carbamate used
in this research.
Isolation of Organogol(I) complex
Oxazolones are attractive building blocks in organic
synthesis and are present in different pharmacological active
compounds. The combination of N-alkynyl carbamates and
gold catalysis has been successfully developed for the synthesis
of disubstituted oxazolones, by Hashmi et al.27 and Istrate et
al.28 (Scheme 3a) and for trisubstituted oxazolones through a
palladium catalyzed π-activation and cross-coupling with aryl
or allyl halides.29,30
Scheme 3. a) gold catalyzed synthesis of oxazolones b)
bimetallic catalyzed synthesis of oxazolones.
Important for these cycloisomerizations was the presence of
the tert-butyl group of the N-alkynyl carbamate, since this tert-
butyl group is dissociated from the intermediate resulting in the
desired oxazolone. By replacing the tert-butyl group by an allyl
ACS Paragon Plus Environment

Page 3 of 11
ACS Catalysis
group, the allyl group would be prone to oxidative addition after the desired compound and a deallylated compound or only the
1
2
3
4
5
6
7
8
cyclization. Subsequent transmetalation with the organo-gold
intermediate, followed by reductive elimination would result in
a trisubstituted oxazolone (Scheme 3b). Since this is an example
of catalyzed catalysis, the reaction will result in a high atom
economy, and is therefore a more sustainable method compared
to the earlier mentioned palladium cross-coupling reactions
with allyl halides.
deallylated compound. Therefore, the use of a bimetallic Au-Pd
system should provide more control over this migration leading
to the desired product.
To validate the proposed mechanism, it seemed essential to
isolate the organogold(I) intermediate. With this intermediate,
the second cycle can be simulated through a palladium cross-
coupling reaction with [{Pd(η3-allyl)Cl}2]. However, the
isolation of this intermediate proved to be more troublesome
compared to previous organogold(I) complexes. Apparently,
the intermediate was more prone to protodeauration. Therefore,
we tried to develop a new method to isolate this organogold(I)
intermediate to prove the mechanism and to provide alternative
procedures toward organogold(I) compounds that are sensitive
to protodeauration.
Our hypothesis for a catalyzed catalysis system, is based on
the difficulty of the migration since there is no pericyclic system
present for these cycloisomerized N-alkynyl carbamates. This
is in contrast to the more common allyl migrations, which
proceed via a concerted sigmatropic rearrangement,31-40
however, these N-alkynyl precursor needs to proceed through a
dissociative pathway. Although this is possible with just a gold
catalyst,41-44 the formed cationic allyl species are not always
stable enough to undergo the migration resulting in a mixture of
Table 1. Catalyst screening.a
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
The isolation of this intermediate would provide evidence for
the proposed mechanisms of Hashmi et al.27 and Istrate et al.28
who reported the synthesis of disubstituted oxazolones via a
gold catalyzed cycloisomerization (Scheme 3a). Besides the
fact that isolation of this organogold compound validates the
proposed mechanisms, they also show interesting synthetic
possibilities. For example, organogold(I) compounds are useful
O
O
O
[Au]/[Pd]
N
O
N
N
O
O
+
CH2Cl2, T (°C)
precursors
for
cross-coupling
reactions
through
transmetallation with palladium45-51 or nickel.52 It is this
transmetallation that is also important for bimetallic catalysis.
1a
2a
3a
Herein we would like to show our progress in developing a
catalyzed catalysis approach for polysubstituted oxazolones and
the mechanistic investigations which are highly linked to the
development of a new procedure toward organogold(I)
compounds. Essential for the organogold(I) complex was the
absence of protons in the reaction media as will be explained in
further detail in this article.
Entry [Cat]
(10 mol %)
AuCl3
[Pd]
Temp Yield (%)
(°C)
(10 mol %)
2a 3a
1
2
3
4
5
/
/
/
/
/
40
40
40
40
40
3
-
17
40
> 99
3
H[AuCl4]
AgOTf
PTSA
-
Results and discussion
-
The synthetic approach for the N-alkynyl allyloxycarbamates
is similar to the reported synthesis by Istrate et al.28 for the
synthesis of N-alkynyl tert-butoxycarbamates. A copper
[AuCl(PPh3)]
/AgOTf
26 57
6
7
8
9
[AuCl(PPh3)]
/AgTFAb
/
/
40
40
r.t.
r.t.
r.t.
33 67
catalyzed coupling of
a
bromoalkyne with an
allyloxycarbamate resulted in the desired precursors. The yields
of the precursors (7 – 83 %) were in the same range as reported
for the N-alkynyl tert-butoxycarbamates. Compound 1a was
used as a model substrate for the catalyst screening (Table 1).
In the first seven entries, different single-metal catalysts were
tested. Although, [AuCl(PPh3)]/AgOTf resulted in 26 % of the
desired product (2a) the main product formed was compound
3a (Table 1, entry 5); changing the counterion hardly showed
any difference (Table 1, entry 5 vs 6). When AgOTf (10 mol %)
was used, a full conversion to 3a was obtained (Table 1, entry
3), while other catalysts proved to be ineffective. However, if a
bimetallic system was used (Table 1, entry 8), the selectivity of
the reaction switched to compound 2a. When switching to a
Au(III) catalyst, the yield decreased drastically even for
different palladium catalysts (Table 1, entry 10-11). Therefore,
the ideal combination seemed to be a catalytic system of Au(I)
and Pd(0). Important to mention is that the reaction proceeds at
a 5 % catalyst loading (Table 1, entry 14). However, also
AgOTf in combination with Pd(dba)2 proved to be a successful
combination (Table 1, entry 12), although the reaction with Ag-
Pd was slower (> 1h) compared to the Au-Pd combination (< 5
min). In order to validate an unambiguous Au-Pd catalytic
cycle, the reaction was also conducted using NaOTf instead of
AgOTf. The change in salt resulted in the same yield and thus
proves an unambiguous Au-Pd bimetallic system (Table 1,
[AuCl(IPr)]/
AgOTf
4
3
8
7
[AuCl(PPh3)] [Pd2(dba)3]
/AgOTf
92
93
[AuCl(PPh3)] [Pd(dba)2]
/AgOTf
10
11
12
13
AuCl3
AuCl3
AgOTf
[Pd2(dba)3]
37 26
[Pd(PPh3)2Cl2] r.t.
[Pd(dba)2]c
9
40
8
r.t.
r.t.
92
7
[AuCl(PPh3)] [Pd(dba)2]
/AgOTf
10
14
[AuCl(PPh3)] [Pd(dba)2]d
/AgOTf
r.t.
97
3
15
16
/
[Pd(dba)2]
r.t.
r.t.
-
-
[AuCl(PPh3)] [Pd(dba)2]e
96
4
/NaOTf
a
1
Yield determined by H-NMR the reaction was left stirring
for 2 hours, bTFA= trifluoroacetate, c reaction took more than 1
d
hour to reach completion. 5 mol % was used, reaction was
completed in < 5 min. e reaction took approximately 1 hour to
reach completion.
ACS Paragon Plus Environment

ACS Catalysis
entry 16). If NaOTf is used, the reaction is slower compared to
Page 4 of 11
Furthermore, a transmetallation step has been observed for tert-
butyl carbamate in combination with gold(I) and [{Pd(η3-
allyl)Cl}2] (Table 4, entry 2), and the yield of the palladium(II)
catalyzed reaction is lower compared to the bimetallic process
(Table 4, entry 1 vs Table 1, entry 14).
1
2
3
4
AgOTf (less to 5 minutes for [AuCl(PPh3)]/AgOTf to
approximately an hour for [AuCl(PPh3)]/NaOTf), this is
probably linked to a slower anion exchange rate when NaOTf
is used instead of AgOTf to abstract the chloride counterion
from [AuCl(PPh3)].
5
Table 3. Mechanistic experiments part I
Having an efficient procedure at hand, we applied this
method to different N-alkynyl allyloxycarbamates. As shown in
table 2, the yields were generally good, and the procedure
proved to be tolerant to different substituents. The only
exceptions are entry 11 and 12, which resulted in small amounts
of the non-alkylated compound leading to a decreased yield for
both reactions due to the required separation. Furthermore, beta
substituted allyl moieties could be used as migrating group as
well (Table 2, entry 13 and14).
6
7
8
9
Entry Crossover experiments
Non-crossover
Crossover
1
O
O
O
Bn
Ph
Bn
Ph
Bn
Ph
N
O
N
O
N
O
Me
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
Ph
Ph
Ph
1a
+
1a
:
:
1o
[Pd(dba)2] (5 mol %)
CH2Cl2, rt
(1)
O
(-)
O
+
+
O
O
O
N
O
N
N
Me
Me
Table 2. Synthesis of trisubstituted oxazolonesa
Ph
Ph
1m
Ph
1d
1m
(1)
(-)
O
O
R1
R1
[Au]/[Pd]
N
N
O
Non-crossover
Crossover
O
2
R3
O
O
O
CH2Cl2, RT
Bn
Ph
Bn
N
Bn
N
O
R2
N
Me
O
O
R3
2
R2
[AuCl(PPh3)], AgOTf,
[Pd(dba)2] (5 mol %)
Ph
Ph
1
Ph
1a
2a
:
2o
(0.6)
(0.4)
CH2Cl2, rt
+
Entry Comp. R1
R2
R3
2
Yield
(%)b
O
O
O
Ph
Ph
N
O
N
N
Me
O
O
Me
1
1a
1b
1c
1d
1e
1f
Bn
Bn
Bn
iPr
iPr
iPr
Ph
Ph
Ph
Phenyl
c-hexenyl
Hexyl
H
2a
2b
2c
2d
2e
2f
84
70
77
74
66
64
60
55
56
72
48
33
75
70
Ph
Ph
Ph
1m
2m
:
2d
(0.6)
(0.4)
2
H
3
H
Non-crossover
Crossover
3
4
Phenyl
c-hexenyl
Hexyl
H
O
O
O
Et
Et
Et
5
H
N
O
N
O
N
O
[AuCl(PPh3)], AgOTf,
[Pd(dba)2] (5 mol %)
Et
Me
Et
Me
Et
6
H
:
:
4a
4a
4c
(1)
(-)
+
CH2Cl2, rt
O
O
O
7
1g
1h
1i
Phenyl
c-hexenyl
Hexyl
H
2g
2h
2i
nPr
nPr
nPr
N
O
N
O
N
O
8
H
nPr
4b
nPr
4b
nPr
4d
Me
(1)
(-)
9
H
10
11
12
13
1j
Allyl Phenyl
Allyl c-hexenyl
Allyl Hexyl
H
2j
1k
1l
H
2k
2l
OTf
R1
H
O
Pd0
1m
1n
Ph
Ph
Phenyl
Me
Me
2m
2n
N
O
O
Ph3PAu
14
c-hexenyl
R1
R2
O
N
L
II
a
O
R1
PdII
all the reactions were carried out with 5 mol % of
N
O
O
[AuCl(PPh3)], AgOTf and [Pd(dba)2]. b isolated yield.
R2
R1
N
OTf
Au(I)
cycle
Pd
[Au]
O
cycle
R2
2
To gain more insight into the reaction, a mechanistic
investigation was conducted (Table 3 and 4). From the result
shown in table 3 entry 1 it can be concluded that a palladium
first reaction does not occur since no exchange of the allyl
groups occurred (at the used catalysts concentration) in the
absence of gold, while crossover products were detected for the
bimetallic method (Table 3, entry 2). The same effect was
observed for the carbamates instead of the N-alkynyl
allyloxycarbamates (Table 3, entry 3). This indicates that
oxophillic activation of the carbamate resulting in deallylation
is not taking place at this catalyst concentration. Next to that,
[Pd(dba)2] is unable to catalyze the reaction (Table 1, entry 17),
however, we cannot claim that the palladium(II) complex which
is formed during the reaction (after oxidative addition) is unable
to catalyze the cycloisomerization (Table 4, entry 1).
Nevertheless, the palladium(II) complex is only formed after
cycloisomerization through gold(I) since only palladium(0)
species are present at the beginning of the reaction.
Ph3PAu
R2
III
I
O
R1
N
O
[Au]
O
PdII
R1
R2
N
O
L
IV
R2
1
Scheme 4. Proposed mechanism for the Au-Pd bimetallic
catalysis or “catalyzed catalysis”.
The proposed mechanism is displayed in Scheme 4.
Activation of the triple bond (I) by gold(I) will induce a 5-endo-
dig cycloisomerization resulting in the allyloxonium ion (II).
This allyloxonium ion is prone to deallylation, as was already
observed in the absence of palladium which resulted in the
deallylated product (compound 3a, see Table 1, entry 4 and 6).
However, in the presence of a palladium(0) catalyst, oxidative
ACS Paragon Plus Environment

Page 5 of 11
ACS Catalysis
addition occurs (III) followed by transmetallation (IV) and In our first attempt an N-alkynyl tert-butyloxycarbamate was
1
2
3
4
5
6
7
8
reductive elimination resulting in the desired product. This
mechanism is similar as observed by the group of Blum for their
5-endo-trig cycloisomerization followed by palladium assisted
allyl migration6,53 and is further supported by our own findings
(Table 3 and 4). However, since these results could not give
exclusive evidence for an unambiguous gold-palladium
mechanism, we tried to isolate the organogold(I) intermediate
(III) to verify the cross-coupling between the palladium(II)
complex and the organogold(I) intermediate (III).
used (Table 5, entry 1). However, the tert-butyl group is more
likely to fragment in a tert-butyl cation which results in the
formation of isobutene and
a proton. Therefore, the
protodeaurated product was the main product. Furthermore,
adding a base to the reaction medium could not prevent
protodeauration and resulted in a complex mixture (Table 5,
entry 2). The protocol of the Hammond group9 also resulted in
protodeauration (Table 5, entry 3). In this procedure, the
fragmentation of the ethyl group is dependent on the presence
of water as a nucleophile and so the formation of protons in the
reaction mixture is inevitable. Therefore, dry dichloromethane
was used, to prevent water in the reaction mixture, and silver
triflate was replaced to sodium triflate. During the reaction,
sodium chloride would be formed, and the chloride ion could
function as the nucleophile instead of water. Unfortunately,
only low yields were obtained (15 %) although protodeauration
was not observed (Table 5, entry 4). In a next attempt, sodium
iodide was used as a nucleophile source. Although this was an
improvement compared to the previous result, the yield was still
unsatisfactory (Table 5, entry 5). However, switching to dry
acetone improved the yield drastically (Table 5, entry 6).
Sodium iodide is highly soluble in acetone; therefore, this salt
could serve as an excellent source for iodide ions, resulting in
an improved yield (Table 5, entry 5 vs 6).
9
Table 4. Mechanistic experiments part II
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
Entry Compound
1a
Conditions
Yield
1
70 % (3a)
[{Pd(η3-allyl)Cl}2] (5 %),
NaOTf (20 %), dba (10 %),
CH2Cl2
Table 5. Screening for a procedure toward organogold(I)
complexes
O
O
R1
R3
R1
N
O
Additives
N
+
O
[AuCl(PPh3)]
Although the yield toward compound 7 was improved, the
isolation of these compounds proved to be troublesome.
Normally, purification of these compounds is conducted with
normal phase chromatography, however, for the formed
organogold(I) compound (7) the use of silica resulted in
protodeauration. In order to solve this problem, reversed phase
chromatography, a C-18 column, was used. Another, possibility
would be to use deactivated silica, however, this was not
verified. Interestingly, no protodeauration could be observed
even though water:acetonitrile was used as mobile phase. This
indicates that if an acidic environment can be prevented,
protodeauration will be minimized. With the organogold(I)
compound 7a (R1= Bn, R2= Ph)) we tried to simulate the
transmetallation as proposed in scheme 3. As cross-coupling
reagent [{PdCl(η3-allyl)}2] (1.2 eq.) was used. To mimic the
conditions of the proposed palladium cycle (Scheme 3), AgOTf
(1.1 eq.) was added to replace the chloride counterion and
dibenzylidenacetone (dba) to function as ligand, the solvent was
dichloromethane. The transmetallation reaction resulted in full
conversion to compound 2a, which was confirmed by LC-MS
and 1H-NMR. This result together with the mechanistic
investigation of table 3 and 4 are consistent with the proposed
mechanism.
Solvent, r.t.
LAu
R2
R2
5
6
7
Entry
R1/R2/R3
Conditions
Yield
(%)
1
2
3
4
5
6
Bn/Ph/tBu AgOTf, DCM
Tracea
Bn/Ph/tBu AgOTf, DCM, Et3N
-
Bn/Ph/Et
Bn/Ph/Et
Bn/Ph/Et
Bn/Ph/Et
AgOTf, DCM/H2O
NaOTf, DCM (dry)
Tracea
15b
27b
AgOTf, NaI, DCM (dry)
AgOTf, NaI, Acetone (dry)
85b
a protodeauration, b determined by 1H-NMR
2
25 % (2a)
68 % (3a)
O
Bn
AuPPh3Cl
(5
%),1eq.
N
O
[{Pd(η3-allyl)Cl}2], 1.5 eq.
NaOTf, 2 eq.dba, CH2Cl2
Ph
1p
3
1p
1eq.
[{Pd(η3-allyl)Cl}2], - (2a)
1.5 eq. NaOTf, 2eq. dba,
CH2Cl2
97 % (3a)
ACS Paragon Plus Environment

ACS Catalysis
Page 6 of 11
Intrigued by the results obtained in table 5, we tried to
evaluate our method for different N-alkynyl
Table 6. synthesis of different organogold(I) compounds
1
2
3
4
5
6
7
8
9
ethyloxycarbamates. The results are depicted in table 6. In
general, the yields are good even when different phosphine
ligands are used (Table 6, entry 9-12). Furthermore, the reaction
is tolerant to different substituents, indicating that the procedure
is generally applicable to different substrates. The structures of
O
O
R1
R1
N
O
1.5 eq. NaI
N
+
O
[Au(L)OTf]
Acetone (dry), r.t., 6h
LAu
R2
R2
1
compounds 7 were characterized through H-NMR, 13C-NMR
5
6
7
and 31P-NMR. Furthermore, crystals were obtained for
compound 7g and 7l, which were analyzed by X-ray
crystallography to confirm the proposed structures (Figure 1a
and 1b). Most likely this method can be used to isolate other
organogold compounds that are sensitive to protodeauration.
Entry
R1
R2
L
7
Yield (%)
67
1
Benzyl
Benzyl
Phenyl
Phenyl
Butyl
Phenyl
Hexyl
Phenyl
Hexyl
Phenyl
Hexyl
Phenyl
Hexyl
Phenyl
Phenyl
Phenyl
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
XPhosb
XPhosb
7a
7b
7c
7d
7e
7f
7g
7h
7i
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
2
57
3
60
4
71
a)
5
56
6
Butyl
47
7
Allyl
60
8
Allyl
54
9
Allyl
75
10
11
Phenyl
Allyl
7j
50
tBuXPhosc 7k
tBuXPhosc 7l
82
12
a
Phenyl
Phenyl
85
b
isolated yield,
triisopropylbiphenyl,
triisopropylbiphenyl, [Au(L)OTf] was was prepared by mixing
1.05 eq. of [AuCl(L)] with 1 eq. of AgOTf in dry acetone
2-Dicyclohexylphosphino-2′,4′,6′-
2-Di-tert-butylphosphino-2′,4′,6′-
c
To valorize the use of these organogold(I) complexes, a
second cross-coupling reaction was conducted with iodoarene
as reagents. Gold and palladium cross-coupling reactions are
not new in chemistry although they only have been explored on
a limited substrate scope: arylgold(I) complexes and the
Hammond complex. Hence, we tried to develop a palladium
mediated cross-coupling for our organogold(I) compounds. In
first instance, the [Pd(PPh3)2Cl2] was used (Table 7, entry 1)
analogously to the group of Sestelo.45,46 However, the Pd(II)
catalysts proved to be inefficient for this cross-coupling
reaction (Table 7, entry 1-3). Therefore, we switched to
[Pd(PPh3)4], which resulted in a first positive result (Table 7,
entry 4). Increasing the temperature and changing the solvent to
dioxane further increased the conversion to 93 % (Table 7, entry
9). Intriguingly, the reaction does not need dry solvents or an
inert atmosphere which is linked to the stability of the isolated
organogold compounds if not exposed to an acidic
environment.
b)
Figure 1. Crystal structure of compound a) 7g and b) 7l.
The proposed mechanism for the synthesis of the
organogold(I) complexes is shown in scheme 5. First gold(I) π-
activates the triple bond followed by cycloisomerization
resulting in the oxonium intermediate. Essential for the reaction
is the minimization of protons in the reaction media. Therefore,
sodium iodide was used as iodide precursor, which functions as
a nucleophile instead of water. After fragmentation of the ethyl
group through nucleophilic attack, the organogold(I) compound
was isolated.
ACS Paragon Plus Environment

Page 7 of 11
ACS Catalysis
O
O
O
[AuCl(L)] + AgOTf
R1
R1
[Pd(PPh3)4]
(10 mol %)
R3
1
2
3
4
5
6
7
8
9
N
N
O
Acetone (dry)
10 min, )))
+
Au(L)
Dioxane, 45 °C
12h
R2
R2
I
R3
O
O
7
8
9
R1
R1
[Au(L)OTf]
Ent 5 (R1/R2)
ry
R3
Me
9
Yield (%)a
N
O
N
O
OTf
(L)Au
R2
1
2
3
4
5g (Allyl/Ph)
9a
9b
9c
9d
75
79
51b
93
R2
5d (Ph/Hexyl)
5d (Ph/Hexyl)
5d (Ph/Hexyl)
H
NH2
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
Me
O
a Isolated yield, b compound could not be purified completely
O
R1
R1
TfO
N
N
NaI
Conclusion
O
O
The use of N-alkynyl carbamates as a precursor for a
catalyzed catalysis approach was developed including a
detailed mechanistic investigation. Essential to validate the
proposed mechanism was the isolation of the organogold(I)
complex that is supposed to undergo the transmetallation.
However, this organogold(I) complex was very sensitive to
protodeauration, and therefore impossible to isolate with the
procedures known today. Therefore, a new procedure was
developed to isolate this organogold(I) intermediate. The
essential part of this method was to prevent protodeauration.
This was achieved by using sodium iodide to deliver the iodide
ion as nucleophile for the fragmentation of the ethyl substituent.
Furthermore, the complexes needed to be purified by reversed
phase chromatography to prevent protodeauration. The
isolation of the organogold(I) compound enabled us to provide
additional support for one step of the proposed catalytic cycle.
Next to that, these organogold(I) compounds were used as
precursors for a palladium catalyzed cross coupling with
iodoarenes. In total, 14 oxazolones were prepared by the
catalyzed catalysis approach together with 12 organogold(I)
compounds, which are the proposed intermediates in the
bimetallic process, and 4 oxazolones via a palladium catalyzed
cross coupling reaction all in good yields.
Au(L)
Au(L)
R2
R2
NaOTf, Et-I
Scheme 5. proposed mechanism for the isolation of the
organogold(I) complex.
Table 7. screening for a palladium catalyzed cross-coupling
reaction with 5g
O
O
N
N
Me
[Pd]
O
O
+
Au(L)
Solvent, 12h
I
7g
8
9
Entry
[Pd]
Solvent
Temp
(°C)
Yield
(%)a
(10 mol %)
[PdCl2(PPh3)]
[PdOAc2]
1
2
3
4
5
6
7
8
9
THF
r.t.
r.t.
r.t.
r.t.
r.t.
45
45
45
45
-
THF
-
[Pd(ƞ3-allyl)Cl(IPr)]
THF
-
[Pd2(dba)3]
THF
trace
27
73
82
85
93
[Pd(PPh3)4]
THF
AUTHOR INFORMATION
[Pd(PPh3)4]
THF
Corresponding Author
[Pd(PPh3)4]
MeCN
CH2Cl2
Dioxane
* Email: Christian V. Stevens - Chris.Stevens@UGent.be
[Pd(PPh3)4]
[Pd(PPh3)4]
Present Addresses
a yield determined by 1H-NMR
aDepartment of Green Chemistry and Technology, Faculty
of Bioscience Engineering, Ghent University, Campus
Coupure, Coupure Links 653, B-9000 Ghent, Belgium.
bDepartment of Plant Systems Biology, VIB, Ghent
University, Technologiepark 927, B-9000 Ghent, Belgium.
cDepartment of Chemistry, Faculty of sceinces, XStruct,
Ghent University, Krijgslaan 281 (S3), B-9000, Ghent,
BelgiumAuthor Contributions
With the optimized conditions in hand, we tried to extrapolate
this method to synthesize four different tri-substituted
oxazolones all leading to good yields (Table 8). Furthermore,
even a free amino group is tolerated which was also observed
by other research groups palladium catalyzed cross-coupling
reactions with organogold(I) complexes.45,47 However, the yield
of the iodo aniline is lower (Table 8, entry 3) since the reaction
did not reach full conversion. Based on this result, it is possible
to confirm that these organogold(I) complexes can also be used
as a reagent for cross-coupling with palladium.
The manuscript was written through contributions of all authors. /
All authors have given approval to the final version of the
manuscript.
Table 8: synthesis of polysubstituted oxazolones through a
palladium catalyzed cross-coupling.
Funding Sources
This work was supported by grants from Ghent University:
“Bijzonder Onderzoeksfonds”.
ACS Paragon Plus Environment

ACS Catalysis
Page 8 of 11
(16) Ranieri, B.; Escofet, I.; Echavarren, A. M., Anatomy
of gold catalysts: facts and myths. Org. Biomol. Chem. 2015,
13, 7103-7118.
ASSOCIATED CONTENT
Supporting Information
1
2
3
4
5
6
7
8
Experimental procedure, characterization data, and H and 13C
NMR spectra and X-ray data. “This material is available free of
charge via the Internet at http://pubs.acs.org.”
1
(17) Fürstner, A., Gold and platinum catalysis—a
convenient tool for generating molecular complexity. Chem.
Soc. Rev. 2009, 38, 3208-3221.
ACKNOWLEDGMENT
This work was supported by grants from Ghent University:
“Bijzonder Onderzoeksfonds”.
(18) Fürstner, A.; Davies, P. W., Catalytic Carbophilic
Activation: Catalysis by Platinum and Gold πꢀAcids. Angew.
Chem., Int. Ed. 2007, 46, 3410-3449.
9
(19) Hashmi, A. S. K., Homogeneous Gold Catalysis
REFERENCES
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
Beyond
Assumptions
and
Proposals—Characterized
(1)
Hirner, J. J.; Shi, Y.; Blum, S. A., Organogold
Intermediates. Angew. Chem., Int. Ed. 2010, 49, 5232-5241.
Reactivity with Palladium, Nickel, and Rhodium:
Transmetalation, Cross-Coupling, and Dual Catalysis. Acc.
Chem. Res. 2011, 44, 603-613.
(20) Liu, L.-P.; Hammond, G. B., Recent advances in the
isolation and reactivity of organogold complexes. Chem. Soc.
Rev. 2012, 41, 3129-3139.
(2)
Pérez-Temprano, M. H.; Casares, J. A.; Espinet, P.,
(21) Brown, T. J.; Weber, D.; Gagné, M. R.; Widenhoefer,
R. A., Mechanistic Analysis of Gold(I)-Catalyzed
Intramolecular Allene Hydroalkoxylation Reveals an Off-Cycle
Bis(gold) Vinyl Species and Reversible C–O Bond Formation.
J. Am. Chem. Soc. 2012, 134, 9134-9137.
Bimetallic Catalysis using Transition and Groupꢀ11 Metals: An
Emerging Tool for CC Coupling and Other Reactions. Chem.
Eur. J. 2012, 18, 1864-1884.
(3)
Allen, A. E.; MacMillan, D. W. C., Synergistic
catalysis: A powerful synthetic strategy for new reaction
development. Chem. Sci. 2012, 3, 633-658.
(22) LaLonde, R. L.; Brenzovich, J. W. E.; Benitez, D.;
Tkatchouk, E.; Kelley, K.; Goddard, I. I. I. W. A.; Toste, F. D.,
Alkylgold complexes by the intramolecular aminoauration of
unactivated alkenes. Chem. Sci. 2010, 1, 226-233.
(4)
C and C–X coupling reactions. Chem. Sci. 2017, 8, 1705-1718.
(5) Blum, S. A. In Gold Catalysis: An Homogeneous
Pye, D. R.; Mankad, N. P., Bimetallic catalysis for C–
(23) Hashmi, A. S. K.; Schuster, A. M.; Rominger, F.,
Gold Catalysis: Isolation of Vinylgold Complexes Derived
from Alkynes. Angew. Chem., Int. Ed. 2009, 48, 8247-8249.
Approach; Dean F. Toste, V. M., Ed.; World Scientific: 2014,
p 393-412.
(6)
Shi, Y.; Roth, K. E.; Ramgren, S. D.; Blum, S. A.,
(24) Hashmi, A. S. K.; Ramamurthi, T. D.; Rominger, F.,
On the Trapping of Vinylgold Intermediates. Adv. Synth. Catal.
2010, 352, 971-975.
Catalyzed Catalysis Using Carbophilic Lewis Acidic Gold and
Lewis Basic Palladium: Synthesis of Substituted Butenolides
and Isocoumarins. J. Am. Chem. Soc. 2009, 131, 18022-18023.
(25) DeKorver, K. A.; Li, H.; Lohse, A. G.; Hayashi, R.;
Lu, Z.; Zhang, Y.; Hsung, R. P., Ynamides: A Modern
Functional Group For The New Millennium. Chem. Rev. 2010,
110, 5064-5106.
(7)
Al-Amin, M.; Johnson, J. S.; Blum, S. A., Selectivity,
Compatibility, Downstream Functionalization, and Silver
Effect in the Gold and Palladium Dual-Catalytic Synthesis of
Lactones. Organometallics 2014, 33, 5448-5456.
(26) Evano, G.; Coste, A.; Jouvin, K., Ynamides: Versatile
Tools in Organic Synthesis. Angew. Chem., Int. Ed. 2010, 49,
2840-2859.
(8)
García-Domínguez, P.; Nevado, C., Au–Pd Bimetallic
Catalysis: The Importance of Anionic Ligands in Catalyst
Speciation. J. Am. Chem. Soc. 2016, 138, 3266-3269.
(27) Hashmi, A. S. K.; Salathé, R.; Frey, W., Gold-
Catalyzed Cyclization of N-Alkynyl Carbamates. Synlett 2007,
2007, 1763-1766.
(9)
Liu, L.-P.; Xu, B.; Mashuta, M. S.; Hammond, G. B.,
Synthesis and Structural Characterization of Stable
Organogold(I) Compounds. Evidence for the Mechanism of
Gold-Catalyzed Cyclizations. J. Am. Chem. Soc. 2008, 130,
17642-17643.
(28) Istrate, F. M.; Buzas, A. K.; Jurberg, I. D.;
Odabachian, Y.; Gagosz, F., Synthesis of Functionalized
Oxazolones by a Sequence of Cu(II)- and Au(I)-Catalyzed
Transformations. Org. Lett. 2008, 10, 925-928.
(10) Hashmi, A. S. K., Homogeneous gold catalysts and
alkynes: A successful liaison. Gold Bull. 2003, 36, 3-9.
(29) Lu, Z.; Cui, W.; Xia, S.; Bai, Y.; Luo, F.; Zhu, G.,
Preparation of 3,4,5-Trisubstituted Oxazolones by Pd-
Catalyzed Coupling of N-Alkynyl tert-Butyloxycarbamates
with Aryl Halides and Related Electrophiles. J. Org. Chem.
2012, 77, 9871-9877.
(11) Rudolph, M.; Hashmi, A. S. K., Heterocycles from
gold catalysis. Chem. Commun. 2011, 47, 6536-6544.
(12) Gorin, D. J.; Sherry, B. D.; Toste, F. D., Ligand
Effects in Homogeneous Au Catalysis. Chem. Rev. 2008, 108,
3351-3378.
(30) Lu, Z.; Xu, X.; Yang, Z.; Kong, L.; Zhu, G., Approach
to highly functionalized oxazolones by a Pd-catalyzed
cyclization of N-alkynyl tert-butyloxycarbamates. Tetrahedron
Lett. 2012, 53, 3433-3436.
(13) Dorel, R.; Echavarren, A. M., Gold(I)-Catalyzed
Activation of Alkynes for the Construction of Molecular
Complexity. Chem. Rev. 2015, 115, 9028-9072.
(14) Jiménez-Núñez, E.; Echavarren, A. M., Molecular
diversity through gold catalysis with alkynes. Chem. Commun.
2007, 333-346.
(31) Istrate, F. M.; Gagosz, F., Synthesis of Functionalized
Pyrroles
via
Gold(I)-Catalyzed
aza-Claisen-Type
Rearrangement. Org. Lett. 2007, 9, 3181-3184.
(15) Obradors, C.; Echavarren, A. M., Intriguing
mechanistic labyrinths in gold(i) catalysis. Chem. Commun.
2014, 50, 16-28.
(32) Heugebaert, T. S. A.; Stevens, C. V., Gold(III)
Chloride Catalyzed Synthesis of 1-Cyanoisoindoles. Org. Lett.
2009, 11, 5018-5021.
ACS Paragon Plus Environment

Page 9 of 11
ACS Catalysis
(33) Heugebaert, T. S. A.; Vervaecke, L. P. D.; Stevens, C. Benzo[b]furans:
Gold(I)-Catalyzed
5-endo-dig-
1
V., Gold(iii) chloride catalysed synthesis of 5-alkylidene-
Cyclization/Rearrangement of Alkylic Oxonium Intermediates.
2
dihydrothiazoles. Org. Biomol. Chem. 2011, 9, 4791-4794.
Chem. Eur. J. 2013, 19, 12504-12511.
3
4
5
6
(34) Ueda, M.; Sato, A.; Ikeda, Y.; Miyoshi, T.; Naito, T.;
Miyata, O., Direct Synthesis of Trisubstituted Isoxazoles
through Gold-Catalyzed Domino Reaction of Alkynyl Oxime
Ethers. Org. Lett. 2010, 12, 2594-2597.
(44) Li, D.-Y.; Wei, Y.; Marek, I.; Tang, X.-Y.; Shi, M.,
Gold(i)-catalyzed
cycloisomerization
of
vinylidenecyclopropane-enes via carbene or non-carbene
processes. Chem. Sci. 2015, 6, 5519-5525.
7
8
9
(35) Istrate, F. M.; Gagosz, F., Gold(I)-catalyzed
formation of furans by a Claisen-type rearrangement of ynenyl
allyl ethers. Beilstein J. Org. Chem. 2011, 7, 878-885.
(45) Peña-López, M.; Sarandeses, L. A.; Pérez Sestelo, J.,
Organogold(I) Phosphanes in Palladium-Catalyzed Cross-
Coupling Reactions in Aqueous Media. Eur. J. Org. Chem.
2013, 2013, 2545-2554.
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
(36) Majumdar, K. C.; Hazra, S.; Roy, B., Gold-catalyzed
heteroannulation and allyl migration: synthesis of highly
functionalized indole derivatives. Tetrahedron Lett. 2011, 52,
6697-6701.
(46) Peña-López, M.; Ayán-Varela, M.; Sarandeses, L. A.;
PérezꢀSestelo, J., Palladium-Catalyzed Cross-Coupling
Reactions of Organogold(I) Reagents with Organic
Electrophiles. Chem. Eur. J. 2010, 16, 9905-9909.
(37) Ackermann, M.; Bucher, J.; Rappold, M.; Graf, K.;
Rominger, F.; Hashmi, A. S. K., [3,3]-Sigmatropic
Rearrangement Step in the Gold-Catalyzed Cyclization of
Allyl-(ortho-alkinylphenyl)methyl Ethers. Chem. Asian J.
2013, 8, 1786-1794.
(47) Hashmi, A. S. K.; Döpp, R.; Lothschütz, C.; Rudolph,
M.; Riedel, D.; Rominger, F., Scope and Limitations of
Palladium-Catalyzed
Cross-Coupling
Reactions
with
Organogold Compounds. Adv. Synth. Catal. 2010, 352, 1307-
1314.
(38) Debrouwer, W.; Seigneur, R. A. J.; Heugebaert, T. S.
A.; Stevens, C. V., Gold superacid-catalyzed preparation of
benzo[c]thiophenes. Chem. Commun. 2015, 51, 729-732.
(48) Shi, Y.; Ramgren, S. D.; Blum, S. A., Palladium-
Catalyzed Carboauration of Alkynes and Palladium/Gold
Cross-Coupling. Organometallics 2009, 28, 1275-1277.
(39) Sugita, S.; Ueda, M.; Doi, N.; Takeda, N.; Miyata, O.,
Gold-catalyzed sequential cyclization/rearrangement reaction
of O-allyl hydroxamates: atom economical synthesis of 3-
hydroxyisoxazoles. Tetrahedron Lett. 2016, 57, 1786-1789.
(49) Pankajakshan, S.; Loh, T.-P., Base-Free Palladium-
Catalyzed Sonogashira Coupling Using Organogold
Complexes. Chem. Asian J. 2011, 6, 2291-2295.
(40) Verlee, A.; Heugebaert, T.; van der Meer, T.;
Kerchev, P.; Van Breusegem, F.; Stevens, C. V., Domino
(50) Toledo, A.; Meana, I.; Albéniz , A. C., Formal Gold-
to-Gold Transmetalation of an Alkynyl Group Mediated by
Palladium: A Bisalkynyl Gold Complex as a Ligand to
Palladium. Chem. Eur. J. 2015, 21, 13216-13220.
reaction of
a
gold
catalyzed 5-endo-dig
cyclization and a [3,3]-sigmatropic rearrangement towards
polysubstituted pyrazoles. Org. Biomol. Chem. 2018, 16, 9359-
9363.
(51) delPozo, J.; Carrasco, D.; Pérez-Temprano, M. H.;
García-Melchor, M.; Álvarez, R.; Casares, J. A.; Espinet, P.,
Stille Coupling Involving Bulky Groups Feasible with Gold
Cocatalyst. Angew. Chem., Int. Ed. 2013, 52, 2189-2193.
(41) Renault, J.; Qian, Z.; Uriac, P.; Gouault, N.,
Electrophilic carbon transfer in gold catalysis: synthesis of
substituted chromones. Tetrahedron Lett. 2011, 52, 2476-2479.
(52) Hirner, J. J.; Blum, S. A., Nickel-Catalyzed Cross-
Coupling of Organogold Reagents. Organometallics 2011, 30,
1299-1302.
(42) Hashmi, A. S. K.; Lothschütz, C.; Döpp, R.;
Ackermann, M.; De Buck Becker, J.; Rudolph, M.; Scholz, C.;
Rominger, F., On Homogeneous Gold/Palladium Catalytic
Systems. Adv. Synth. Catal. 2012, 354, 133-147.
(53) Al-Amin, M.; Roth, K. E.; Blum, S. A., Mechanistic
Studies of Gold and Palladium Cooperative Dual-Catalytic
Cross-Coupling Systems. ACS Catal. 2014, 4, 622-629.
(43) BlancoꢀJaimes, M. C.; Weingand, V.; Rominger, F.;
Hashmi, A. S. K., From Ynamides to Highly Substituted
ACS Paragon Plus Environment

ACS Catalysis
Page 10 of 11
1
2
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
ACS Paragon Plus Environment

Page 11 of 11
ACS Catalysis
Table of contents
1
2
3
4
5
6
7
R3
O
O
if R3= Allyl
R1
R3
R1
O
R1
N
O
[Au(L)OTf]
[Pd(dba)2]
N
OTf
N
O
O
R2
(L)Au
R2
R2
if R3= Ethyl
NaI
8
9
O
O
R3
R1
N
R1
[Pd(PPh3)4]
ArI
I
N
+
+
O
[AuI(L)]
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
O
NaOTf
(L)Au
Ar
R2
R2
11
ACS Paragon Plus Environment