Stereo- A nd regioselective dimerization of alkynes to enynes by bimetallic syn-carbopalladation

Article abstract of DOI:10.1021/acscatal.1c00473

Enynes are important motifs in bioactive compounds. They can be synthesized by alkynea'alkyne couplings for which a number of mechanisms have been suggested depending on catalyst type and dominant product isomers. Regarding bimetallic pathways, hydrometalations and anti-carbopalladations have been discussed to account for the formation of geminally substituted and (Z)-configured enynes, respectively. Here we report a bimetallic alkynea'alkyne coupling that yields (E)-configured enynes. An unusual type of acetylide Pd bridging was found in putative catalytic intermediates which is arguably responsible for the regio- A nd stereochemical reaction outcome. Mechanistic studies suggest that a double μa'κ:η2 acetylide bridging enables a bimetallic syn-carbometalation. Interestingly, depending on the reaction conditions, it is also possible to form the geminal regioisomer as major product with the same catalyst. This regiodivergent outcome is explained by bi-versus monometallic reaction pathways.

Full text of DOI:10.1021/acscatal.1c00473

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Research Article
Stereo- and Regioselective Dimerization of Alkynes to Enynes by
Bimetallic Syn-Carbopalladation
Camilla Pfeffer, Nick Wannenmacher, Wolfgang Frey, and René Peters*
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ABSTRACT: Enynes are important motifs in bioactive com-
pounds. They can be synthesized by alkyne−alkyne couplings for
which a number of mechanisms have been suggested depending on
catalyst type and dominant product isomers. Regarding bimetallic
pathways, hydrometalations and anti-carbopalladations have been
discussed to account for the formation of geminally substituted and
(Z)-configured enynes, respectively. Here we report a bimetallic
alkyne−alkyne coupling that yields (E)-configured enynes. An
unusual type of acetylide Pd bridging was found in putative
catalytic intermediates which is arguably responsible for the regio- and stereochemical reaction outcome. Mechanistic studies suggest
that a double μ−κ:η2 acetylide bridging enables a bimetallic syn-carbometalation. Interestingly, depending on the reaction
conditions, it is also possible to form the geminal regioisomer as major product with the same catalyst. This regiodivergent outcome
is explained by bi- versus monometallic reaction pathways.
KEYWORDS: bimetallic catalysis, carbopalladation, enynes, ferrocene, palladacycle, regioisomers
syntheses of (Z)-2 (mechanism 4)).20 Other mechanisms
INTRODUCTION
■
involve mono-4,21 or bismetal22 vinylidene intermediates
Conjugated enynes are established as high-value building
blocks.1 In addition, the enyne motif is present in a number of
resulting in (E)-2 and (Z)-2 (not depicted). Head-to-tail
both natural and artificial biologically active compounds.2 An
dimerization of 1 to give regioisomeric 3 was explained by
monometallic syn-carbometalation23 (mechanism 1b) and by
atom-economic way to synthesize conjugated enynes is the
bimetallic hydrometalation as key steps (mechanism 3).24
Regarding the use of Pd catalysts, monometallic Pd
complexes bearing sterically demanding phosphine ligands
were reported in 1987 by Trost et al. to be highly selective
dimerization of alkynes 1.3 A number of catalysts with, for
example, iron,4−6 ruthenium,7 cobalt,8,6b rhodium,9 iridium,10
palladium,3,11−15 gold,16 yttrium,17 and main group metal
centers,18 have been reported for this purpose. The major
challenge is the control of regio- and stereoselectivity in this
C,C-coupling.
catalysts for the formation of the geminal products 3.25
A
carbometalation pathway was postulated (mechanism 2b).26
In general, three different isomers can be formed in such
homodimerizations of alkynes (eq 1).3,11,12 Whereas (E)- and
(Z)-configured enynes 2 are generated by “head-to-head”
dimerization, the geminal regioisomer 3 is formed by “head-to-
tail” dimerization.3,11,12
In contrast, Nolan et al. could form (E)-2 with high
selectivity using a Pd−NHC complex in the presence of an
excess of Cs2CO3 as base.12 Gevorgyan et al. also utilized a
Pd−NHC complex but in the presence of an additional
electron-rich phosphine ligand to preferentially form (E)-2.13
DFT calculations showed that this reaction is likely to proceed
via hydropalladation (mechanism 1). Depending on a
carboxylate additive, product 3 was also available, most likely
by carbopalladation (mechanism 2b).13 Moreover, Guo and
Han reported a combination of a Pd bisphosphine complex
Depending on the type of catalyst, different reaction
mechanisms have been suggested in order to explain the
attained regio- and stereoselectivities.11 (E)-2 is often formed
by hydro- or carbometalation pathways of monomeric metal
acetylide acetylene complexes (Scheme 1, mechanisms 1a and
2a, respectively),11,14,19 as both key steps proceed as syn-
additions. In contrast, bimetallic acetylide/alkyne intermedi-
ates can undergo anti-additions resulting in stereoselective
Received: February 2, 2021
Revised: April 12, 2021
Published: April 21, 2021
© 2021 The Authors. Published by
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bimetallic catalysis (mechanisms 3 and 4), (E)-2 was
stereoselectively formed, very likely proceeding via a
bispalladium complex.28 A novel type of acetylide bridging
for bis-Pd complexes29 was found in putative catalytic
intermediates. Our studies suggest that a double μ−κ:η2
acetylide bridging allows for a cooperative bimetallic syn-
carbometalation, while in the above-mentioned previous
bimetallic carbometalation approaches, only (Z)-2 was
accessible by anti-additions. Contrariwise, depending on the
reaction conditions, it is also possible to form regioisomer 3 as
major product with the same catalyst. This regiodivergent
outcome is explained by a monometallic pathway for the
formation of 3.
Scheme 1. Common Mechanisms for Alkyne Dimerizations
and Comparison to This Work
RESULTS AND DISCUSSION
■
Optimization of the Selective Formation of (E)-2. The
chloride-bridged ferrocene-based palladacycle precatalysts
[FIP-Cl]2 (FIP = ferrocenyl imidazoline palladacycle) and
[FBIP-Cl]2 (FBIP = ferrocenediyl bisimidazoline bispallada-
cycle), which were previously developed by our group30,31 and
are accessible in high yields and in few steps, were studied as
precatalysts. They were activated by different silver salts for
chloride anion exchange by our previously described
protocols.30,31 The activated complexes were initially inves-
tigated in the dimerization of 1a in chlorobenzene at 50 °C
(Table 1). The best results were achieved by activation with
AgOAc. Using 5.0 mol % of precatalyst, a mixture of all three
isomers (E)-2a, (Z)-2a, and 3 was formed in low yields and
with a moderate preference for (E)-2a. With the FIP catalyst, a
higher yield (36%, entry 1) and a higher selectivity for
dimerization versus tri/oligomerization was noticed (48%
conversion), whereas FBIP showed higher catalytic activity
(99% conversion), but the product mixture was much more
complex (yield of dimer: 20%, entry 2).
A solvent screening was then performed, and with
acetonitrile, a higher activity, dimerization yield, and selectivity
for (E)-2a was found (entry 3). Improved selectivities were
attained by slightly reducing the reaction temperature to 45 °C
(entry 4) and using acetic acid (0.5 equiv) which was added to
speed the protonolysis of generated Pd−vinyl bonds (entry 5).
A similar result was obtained with NaOAc as additive (entry
6), probably due to generation of HOAc in the course of the
catalytic cycle. Adding water (5.0 equiv) instead, this effect was
not found (entry 7). Adding both NaOAc and H2O, yield and
selectivity were improved (entry 8). The product yield was
further increased by additional HOAc (entry 9). Surprisingly,
by reducing the precatalyst loading to 2 mol %, yield and
selectivity were improved to synthetically useful values (entries
10 and 11). This is at least partly explained by no detectable
alkyne trimerization as side reaction with the decreased catalyst
amount. Finally a yield of 91% and an isomeric ratio (E)-2a/
(Z)-2a/3 of 94/5/1 was accomplished. No hydrogenation
products were detected that might point to the formation of
metal hydride intermediates.
and a phosphinic acid to provide (E)-2 which is believed to
proceed via hydrometalation.23
In contrast to these studies employing neutral ligands,
Shaughnessy et al. studied the use of acetate-bridged aliphatic
C,P-palladacycle catalysts, which were effective in (E)-selective
couplings of propargylic alcohols and amines.27 Under the
reported reaction conditions, an acetate/acetylide-bridged
dimeric palladacycle 4 was identified (Figure 1). By X-ray
analysis the acetylide ligand was found to undergo an
unprecedented μ−κ1-coordination to both Pd(II) centers.
Herein we report a regiodivergent dimerization of alkynes 1
using a ferrocene-based C,N-palladacycle catalyst. In contrast
to the above-mentioned previous studies making use of
Scope of the (E)-Selective Dimerization. The con-
ditions described in Table 1/entry 11 were then used to
investigate the applicability to other terminal alkyne substrates
(Table 2). Using aromatic alkynes, substituents displaying
different electronic effects were all accommodated. Aromatic
alkynes bearing σ- (entries 3, 4, 9, 11, 12) and π-acceptors
(entry 5) thus provided useful to good yields and good to
excellent stereo- and regioselectivities. With an unsubstituted
Ph residue, a nearly quantitative yield and high selectivities
Figure 1. μ−κ1-Acetylide-bridged bis-Pd complex found in the
alkyne−alkyne coupling by Shaughnessy et al.27
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Table 1. Development of Regio- and Stereoselective Dimerization of Terminal Alkynes
a
b
no.
[Pd(II)Cl]2 (X)
additives (Z)
solvent
T (°C)
yield (%)
(E)/(Z)-2a/3
1
2
3
4
5
6
7
8
FIP (5.0)
FBIP (5.0)
FIP (5.0)
FIP (5.0)
FIP (5.0)
FIP (5.0)
FIP (5.0)
FIP (5.0)
FIP (5.0)
FIP (2.0)
FIP (2.0)
-
-
-
-
PhCl
PhCl
50
50
50
45
45
45
45
45
45
45
45
36
20
64
60
60
69
64
73
78
88
91
61/25/14
69/16/15
72/7/21
80/9/11
85/7/8
84/5/11
60/11/29
90/1/9
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
HOAc (0.5)
NaOAc (0.5)
H2O (5.0)
NaOAc (0.5), H2O (5.0)
HOAc (0.5), NaOAc (1.0), H2O (5.0)
HOAc (0.5), NaOAc (1.0), H2O (5.0)
9
10
11
86/4/10
93/5/2
94/5/1
HOAc (0.5), NaOAc (3.0), H2O (5.0)
a
b
1
1
Yield of the mixture of (E)-2a, (Z)-2a, and 3 determined by H NMR using mesitylene as internal standard. Isomeric ratio determined by H
NMR of the crude mixture.
were obtained (entry 2). σ- (entries 1, 13) and π-donors
(entries 6, 7,32 8, 10, 12) as well as an extended π-system
(entry 14) were also well tolerated and gave rise to good to
high yields and selectivities. Noteworthy is that an ortho-
substituent was also well tolerated as well as conjugated enyne
substrate 1n, which formed product (E)-2n with exclusive
stereo- and regioselectivity yet in moderate yield. Unfortu-
nately, trimethylsilylacetylene (entry 16) as well as aliphatic
alkynes (not shown) gave no dimerization product.
Regioselective Synthesis of Geminal Regioisomer 3.
During the optimization of the stereo- and regioselective
synthesis of (E)-2a, a strong solvent effect on the reaction
outcome was noted. Particularly interesting was the finding
that regiodivergency is enabled simply by performing the
dimerization in ethyl acetate (Table 3). In the absence of
additives at 50 °C a moderate preference for the formation of 3
was found (entry 1). Reducing the reaction temperature to 30
°C increased the regioselectivity yet at the expense of a low
yield (entry 2). Nevertheless, in the presence of water (30
equiv) not only was the regioselectivity further improved, but
also the dimerization yield was enhanced to 75% (entry 3).
The conditions of Table 3/entry 3 were applied to six
different substrates (Table 4). In general, acceptor and donor
substituents on the aromatic ring were tolerated in para and
meta positions, albeit product yields and regioselectivity were
lower than for the (E)-selective dimerization. 1p was the most
difficult substrate in terms of product yield. However, it should
be mentioned that 3p has, to our knowledge, never been
prepared previously by alkyne dimerization, maybe as a result
of the strong +M effect of the N-acetyl substituent.
Mechanistic Studies. To learn more about the title
reaction, kinetic studies were performed. Blackmond’s
Reaction Progress Kinetic Analysis (RPKA)33 was applied
using fluorine-containing substrate 1c in order to enable the
use of 19F NMR spectroscopy for monitoring (for details of the
kinetic studies, see Supporting Information). In analogy to the
so-called “same excess” protocol,33 catalyst robustness and
product influence were studied. The initial concentrations for
the different measurements are shown in Table 5.
Figure 2 shows the corresponding reaction profiles using a
decay of the concentration of 1c. Experiment K1 (Table 5,
blue curve in Figure 2) serves as standard experiment for
comparison. In experiment K2 (red curves) the starting
concentration of 1c corresponds to the concentration at 50%
conversion in K1.33 A time shift shows, that this experiment
proceeded faster than K1 which might suggest a partial catalyst
decomposition during the first 50% of conversion in the
standard experiment. In a further experiment K3 (green
curves) the starting point as in K2 was used except that 50 mol
% of product 2c was added, because in the reference
experiment K1 also around 50% product was present after
50% conversion. In K3 the reaction proceeded even somewhat
faster than found for K2, indicating a small product
acceleration. This is tentatively assigned to a catalyst
stabilization by the product.
Variable Time Normalization Analysis (VTNA) developed
34
́
by Bures was used to determine the empirical rate law. The
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Table 2. Investigation of Substrate Scope and Limitations
Table 3. Optimization of the Regioselective Synthesis of 3
a
b
no.
Z
T (°C)
yield (%)
(E)/(Z)-2a/3
1
2
3
-
-
30
50
30
30
50
31
75
31/13/56
18/8/74
14/5/81
c
a
1
Yield of the mixture of (E)-2a, (Z)-2a, and 3 determined by H
b
NMR using mesitylene as internal standard. Isomeric ratio
determined by H NMR of the crude mixture. Reaction time: 48 h.
c
1
Table 4. Application of Different Substrates in the
Regioselective Synthesis of 3
a
1
Yield of the mixture of (E)-2a, (Z)-2a, and 3 determined by H
b
NMR using mesitylene as internal standard. Isomeric ratio
determined by H NMR of the crude mixture. 5.0 mol % of [FIP-
c
1
Cl]2 was used.
Table 5. Initial Concentrations for the Reaction Progress
Kinetic Analysis (RPKA)
a
1
Yield of the mixture of (E)-2a, (Z)-2a, and 3 determined by H
b
NMR using mesitylene as internal standard. Isomeric ratio
determined by H NMR of the crude mixture. 5.0 mol % of [FIP-
c
1
Cl]2 was used.
[1c]
(mol/L)
[FIP2]-OAc-CC-p-F-C6H4
[2c]
(mol/L)
experiment
(mol/L)
reaction depicted in Table 5/K1 was studied in MeCN-d3 in
six experiments at 45 °C for 14 h using different initial
concentrations of catalyst, substrate 1c, acetic acid, sodium
acetate, and water monitoring the concentration of 1c by 19F
NMR spectroscopy (for details, see Supporting Information).
The best overlay for the normalization of the time scale axis
was achieved with the following equation:
K1 (standard)
K2 (same excess)
0.1
0.05
0.05
0.002
0.002
0.002
-
-
K3
0.05
(product addition)
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Scheme 3. Stoichiometric Formation of the Acetate/
Acetylide-Bridged Dimer [FIP]2-OAc-1e
The suggested structure was confirmed by single-crystal X-
ray analysis (Figure 3). Two closely related conformers were
Figure 2. Reaction profiles monitoring 1c using Blackmond’s
protocol33 under the initial conditions of Table 5.
r = kobs[catalyst]0.8[1c]2.0[HOAc]0.0[NaOAc]0.2[H2O]0.0
The nearly first-order kinetic dependence in catalyst can be
explained by a bimetallic active catalyst species formed from
the bimetallic catalyst [FIP-OAc]2 (generated from [FIP-Cl]2
by AgOAc).30f,h The zero-order kinetic dependence in acetic
acid and water suggests that an expected protonation step is
not turnover-limiting under the developed reaction conditions.
The second-order kinetic dependence in alkyne seems to
suggest that the coupling event, i.e., the C−C-bond-forming
step, is rate-limiting.
Based on the kinetic studies as well as spectroscopic
investigations and deuteration experiments shown below, the
following catalytic cycle (depicted for substrate 1a) is
proposed (Scheme 2). According to this mechanism, [FIP-
Scheme 2. Proposed Simplified Catalytic Cycle for the
Regioselective Synthesis of (E)-2a
Figure 3. X-ray crystal structure analysis of the μ−κCα:η2 acetylide-
bridged bis-Pd complex [FIP]2-OAc-CCR (R = p-O2N−C6H4). A
visualization using thermal ellipsoids is shown in the Supporting
Information.
found. In these structures, the acetate ligand acts as a μ−κ2
bridge, and the acetylide as μ−κCα:η2 bridge between both
Pd(II) centers, which to our knowledge is without precedent
for Pd(II) catalysts. The asymmetric bridging mode should
result in an uneven charge distribution for both metal
centers.35 The acetylide bridging mode thus differs significantly
from the bis-Pd−acetylide complex 4 by Shaughnessy et al.27
shown in the Introduction.
Step I in the proposed catalytic cycle (Scheme 2) involves
the subsequent formation of a C2-symmetric bisacetylide-
bridged bis-Pd(II) complex [FIP-CCR]2 from [FIP]2-OAc-
CCR. Also in this case it was possible to form complex [FIP-
CCR]2 stoichiometrically (Scheme 4).
OAc]2 is initially transformed into the acetate/acetylide-
bridged dimer [FIP]2-OAc-CCR (CCR = acetylide), which
could be detected by ESI mass spectrometry during the
catalytic reaction (R = p-Tol: m/z = 1506.1067; found:
1506.1034). To receive more information about the inter-
action of the catalyst with a terminal alkyne, [FIP-Cl]2 was
treated with AgOAc (2 equiv) and a stoichiometric amount of
acetylene 1e (1 equiv). The defined complex [FIP]2-OAc-CCR
(R = p-O2N−C6H4) was formed under these conditions in
quantitative yield (Scheme 3).
Treating [FIP-Cl]2 with silver tosylate and subsequently
with acetylene 1a in the absence of acetate/HOAc provided
[FIP-CCR]2 (R = p-Tol) in 90% yield. The 1H NMR spectrum
of this compound shows a single set of signals. In combination
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1560.1490, see Supporting Information) next to [FIP]2-OAc-
CCp-Tol.
Scheme 4. Stoichiometric Formation of the Bis-Acetylide-
Bridged Dimer [FIP-CCp-Tol]2
The next step III involves the protonolysis of the Pd−C
bonds. Based on the empirical rate law shown above, the
detected (and isolated) catalytic intermediates [FIP]2-OAc-
CCp-Tol and FIP-CCp-Tol, as well as the equilibrium with
slow product formation shown in Scheme 5, it is unlikely that
this step is rate-limiting.
Deuteration experiments were performed employing deu-
terated acetylene (Scheme 6). The deuteration degree
determined after a reaction time of just 3 h to minimize H/
D-exchanges after product formation was found to be very low
for both positions HA and HB.
with ESI-MS results we suggest a C2-symmetric dimeric
structure with bis-μ−κCα:η2 acetylide bridging.
By ESI-MS, {[FIP]2-CCR}+ (R = p-Tol; m/z = 1445.0897;
found: 1445.0893, see Supporting Information) was detected
during the catalytic reaction, which might be formed by
eliminating one bridging acetylide ligand from [FIP-CCR]2.
[FIP-CCR]2 was found to be relatively stable in MeCN36 but
rapidly decomposed in chloroform and other solvents such as
chlorobenzene or ethyl acetate to give free ferrocene ligand
Scheme 6. Deuteration Experiments under (E)-Selective
Conditions Using Deuterated Acetylene 1a-D as the Only
D+ Source
1
and Pd(0). Yield determination was performed by H NMR
using an internal standard.
Treating [FIP-CCp-Tol]2 with a stoichiometric amount of
1a in the presence of the aqueous acetate buffer resulted in a
rapid equilibrium with [FIP]2-OAc-CCp-Tol, in which the
latter is dominating (ratio 1:4, Scheme 5). Within 1 min, a
Using AcOD and D2O as D+ sources (Scheme 7, top),
identical deuteration levels of 68% were found for HA and HB.
Scheme 5. Rapid Equilibrium between [FIP-CCp-Tol]2 and
[FIP]2-OAc-CCp-Tol and Slow Product Formation
Scheme 7. Deuteration Experiments under (E)-Selective
Conditions Using AcOD and D2O as the D+ Source
ratio of 1:3 was already noticed. After 5 min, 2% of product
(E)-2a was found, after 60 min 8%. This result also suggests
that C−C bond formation is slow. Moreover, during catalysis
[FIP]2-OAc-CCp-Tol was identified as major catalyst species,
probably representing the catalytic resting state.
Comparison of the initial reaction rates caused by [FIP-
OAc]2, [FIP]2-OAc-CCp-Tol, and [FIP-CCp-Tol]2 showed
very similar catalytic activity and productivity for all of them,
suggesting that they are all catalytically relevant (for details, see
Supporting Information).
In step II of the catalytic cycle (Scheme 2), an intra-
molecular bimetallic syn-carbopalladation step is expected, in
which one acetylide acts as nucleophile attacking the side-on
coordinated alkyne moiety of the other acetylide. The resulting
vinyl−Pd2 intermediate or more likely its precursor [FIP-CCp-
Tol]2 with the predicted isotopic pattern was detected by ESI-
MS during the catalytic reaction (m/z = 1560.1445; found:
The difference from a complete deuteration level can be
explained by the use of nondeuterated 1a, which releases a
proton during the Pd−acetylide formation but mainly by
residual water in the NaOAc used. Using commercial
“anhydrous” NaOAc gave deuteration levels of about 50%,
and drying it under high vacuum increased these values to
68%. The assumption is further confirmed by the use of
deuterated proton sources (DOAc, D2O) in combination with
deuterated acetylene 1a-D, which provided deuteration levels
of around 80% (Scheme 7, bottom).
In contrast, for the regioselective synthesis of 3 in EtOAc as
solvent, we propose the mechanism depicted in Scheme 8, in
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deuterated than HA in trans position. A syn-palladation is thus
dominating, as expected for a concerted insertion mecha-
nism.37
Scheme 8. Proposed Simplified Catalytic Cycle for the
Regioselective Synthesis of 3
In the second experiment, deuterated acetylene substrate 1a-
D was utilized in the presence of an excess of H2O. As
expected, now position HA in 3 is significantly more deuterated
than HB. The fact that the unexpected geometrical isomers are
also formed in significant quantities in both experiments may
be explained by H/D exchange of the alkyne via Pd−acetylide
formation/protonolysis and time-dependent H scrambling, in
agreement with the literature.6a
In the third experiment, deuterated acetylene substrate 1a-D
was utilized in the presence of excess D2O. As expected, both
terminal olefins positions were deuterated in product 3.
Again VTNA was used to determine the empirical rate law.34
The reaction reported in Table 4, entry 3, using 1c as
substrate, was monitored in EtOAc-d8 at 30 °C for 14 h by 19
F
NMR employing different concentrations of catalyst, 1c, and
water (for details, see Supporting Information). The following
empirical rate law was determined:
r = kobs[catalyst]0.4[1c]2.0[H2O]0.0
analogy to mechanism 2b)13 in Scheme 1. Like in the
mechanism for the stereo- and regioselective formation of (E)-
2 discussed above, the mechanism starts by formation of
intermediate [FIP]2-OAc-CCR. A subsequent acetylene
coordination could give monometallic complex FIP-CCR-
HCCR, in accordance to the observed regioselectivity. The
steric demand of the ferrocene ligand is expected to be a key
reason to cause R in the acetylene to point away from the
ferrocene moiety in order to minimize repulsion.
To probe this interpretation of a monometallic mechanism,
deuteration experiments were also performed in this case
(Scheme 9). In the first experiment, nondeuterated acetylene
was used in the presence of an excess of D2O.
The approximately half-order kinetic dependence in catalyst
supports a monometallic active catalyst species formed from
the bimetallic catalyst [FIP-OAc]2. Again the rate law might be
explained by a rate-determining C−C bond formation.
The fact that different mechanisms are involved depending
on the solvent medium (product (E)-2a in MeCN via a
bimetallic mechanism and product 3 in EtOAc via a
monometallic mechanism) might be roughly explained by
the stability of [FIP-CCR]2, the key catalytic intermediate for
the suggested bimetallic pathway. As shown above, it was
found to be relatively stable in MeCN but not in EtOAc.
CONCLUSION
In agreement with mechanism 2b, in product 3 the position
of HB cis to the acetylene moiety is significantly more
■
In summary, we have reported a regiodivergent dimerization of
alkynes to form enynes employing a C,N-palladacycle catalyst.
In contrast to previous studies using bimetallic catalysts, (E)-
configured enynes were stereoselectively formed, very likely
proceeding via a bis-palladium complex. A novel type of
acetylide bis-Pd bridging was found in putative catalytic
intermediates. Our studies suggest that a double μ−κ:η2
acetylide bridging enables a novel cooperative bimetallic syn-
carbometalation pathway. However, depending on the reaction
conditions, it is also possible to form the geminal regioisomer
as major product utilizing the same catalyst. This might be
related to the stability of the bis-Pd−bis-acetylide intermediate
[FIP-CCR]2 in MeCN which could be essential for the
suggested bimetallic pathway. This intermediate was found to
be unstable in other solvents including EtOAc, where
formation of free ferrocene ligand and Pd black was noticed.38
Scheme 9. Deuteration Experiments under Conditions
Favoring the Formation of 3 Using Different Sources
ASSOCIATED CONTENT
■
sı
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acscatal.1c00473.
Experimental details, spectral data, and copies of 1H and
13C NMR spectra of all new compounds (PDF)
CIF files for [FIP]2-OAc-CCR (R = p-O2N−C6H4)
(CIF)
5502
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ACS Catal. 2021, 11, 5496−5505

ACS Catalysis
AUTHOR INFORMATION
pubs.acs.org/acscatalysis
Research Article
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Commun. 2011, 47, 6698−6700.
■
Corresponding Author
̈
René Peters − Institut fur Organische Chemie, Universität
Stuttgart, D-70569 Stuttgart, Germany; orcid.org/0000-
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0002-6668-4017; Email: rene.peters@oc.uni-stuttgart.de
Authors
Camilla Pfeffer − Institut fu
Stuttgart, D-70569 Stuttgart, Germany
Nick Wannenmacher − Institut fur Organische Chemie,
Universität Stuttgart, D-70569 Stuttgart, Germany
r Organische Chemie, Universität
̈
r Organische Chemie, Universität
̈
Wolfgang Frey − Institut fu
̈
Stuttgart, D-70569 Stuttgart, Germany
Complete contact information is available at:
https://pubs.acs.org/10.1021/acscatal.1c00473
Author Contributions
The manuscript was written through contributions of all
authors. All authors have given approval to the final version of
the manuscript.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank Prof. Dr. Johannes Kästner and M. Sc. Juliane
Heitkämper (both from University of Stuttgart, Institute for
Theoretical Chemistry) as well as M. Sc. Konstantin Dorst and
Dr. Carmen Schrapel (both from University of Stuttgart,
Institute for Organic Chemistry) for helpful discussions.
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