Carboxylate switch between hydro- and carbopalladation pathways in regiodivergent dimerization of alkynes

Article abstract of DOI:10.1002/chem.201402809

Experimental and theoretical investigation of the regiodivergent palladium-catalyzed dimerization of terminal alkynes is presented. Employment of N-heterocyclic carbene-based palladium catalyst in the presence of phosphine ligand allows for highly regio- and stereoselective head-to-head dimerization reaction. Alternatively, addition of carboxylate anion to the reaction mixture triggers selective head-to-tail coupling. Computational studies suggest that reaction proceeds via the hydropalladation pathway favoring head-to-head dimerization under neutral reaction conditions. The origin of the regioselectivity switch can be explained by the dual role of carboxylate anion. Thus, the removal of hydrogen atom by the carboxylate directs reaction from the hydropalladation to the carbopalladation pathway. Additionally, in the presence of the carboxylate anion intermediate, palladium complexes involved in the head-to-tail dimerization display higher stability compared to their analogues for the head-to-head reaction. Track changer: The regiodivergent palladium-catalyzed dimerization of terminal alkynes was studied. High regio- and stereoselectivity was achieved for both head-to-head and head-to-tail dimerization reactions. Computational studies suggest hydropalladation to favor head-to-head dimerization under neutral conditions. Addition of carboxylate anions switches the reaction from hydropalladation to carbopalladation pathway securing head-to-tail coupling (see scheme).

Full text of DOI:10.1002/chem.201402809

DOI: 10.1002/chem.201402809
Full Paper
&
Palladium Catalysis
Carboxylate Switch between Hydro- and Carbopalladation
Pathways in Regiodivergent Dimerization of Alkynes
Olga V. Zatolochnaya,[a] Evgeniy G. Gordeev,[b] Claire Jahier,[a] Valentine P. Ananikov,*[b] and
Vladimir Gevorgyan*[a]
Abstract: Experimental and theoretical investigation of the
regiodivergent palladium-catalyzed dimerization of terminal
alkynes is presented. Employment of N-heterocyclic carbene-
based palladium catalyst in the presence of phosphine
ligand allows for highly regio- and stereoselective head-to-
head dimerization reaction. Alternatively, addition of carbox-
ylate anion to the reaction mixture triggers selective head-
to-tail coupling. Computational studies suggest that reaction
proceeds via the hydropalladation pathway favoring head-
to-head dimerization under neutral reaction conditions. The
origin of the regioselectivity switch can be explained by the
dual role of carboxylate anion. Thus, the removal of hydro-
gen atom by the carboxylate directs reaction from the hy-
dropalladation to the carbopalladation pathway. Additionally,
in the presence of the carboxylate anion intermediate, palla-
dium complexes involved in the head-to-tail dimerization
display higher stability compared to their analogues for the
head-to-head reaction.
Introduction
Dimerization of alkynes is one of the most straightforward and
atom-economical methods for the synthesis of conjugated
enynes, important synthetic intermediates[1] and key structural
units found in a variety of bioactive molecules,[2] as well as
polymeric and optical materials.[3] A number of transition
metals, such as gold,[4] nickel,[5] palladium,[6] cobalt,[7] rhodi-
um,[8] iridium,[9] iron,[10] ruthenium,[11] osmium,[12] rhenium,[13]
chromium,[14] titanium,[15] zirconium,[16] hafnium,[17] scandium,
yttrium, lanthanides,[18] and actinides,[19] as well as main group
elements,[20] have shown catalytic activity in this transforma-
tion. The main challenge of alkyne dimerization is the control
of regio- and sometimes stereoselectivity due to the compet-
ing head-to-head (hh) and head-to-tail (ht) reaction modes
leading to the formation of (E)-2 or (Z)-1,4-disubsituted 3, and
gem-1,3-disubstituted 4 enynes [Eq. (1)].
Commonly accepted reaction pathways start with the oxida-
tive addition of terminal alkyne CꢀH bond into the metal
center followed by the migratory insertion of the second
alkyne molecule to form the dimeric product. Both carbometal-
lation, alkyne insertion into the metalꢀcarbon bond (path I),
and hydrometallation, alkyne insertion into the metalꢀhydro-
gen bond (path II), are equally plausible for the head-to-head
or the head-to-tail dimerizations. Therefore, no clear correlation
between the mechanistic path and the reaction selectivity has
been established to date.
Arguably, the Pd-catalyzed dimerization reaction is the most
studied. Thus, a general and selective head-to-tail dimerization
reaction toward 1,3-disubstituted enynes 4 has been devel-
oped by Trost[6a,b] (Scheme 1a). For this transformation, alkyne
carbopalladation through intermediate i was proposed to be
the major reaction path. Later, our group reported that the
agostic interaction can control regioselectivity of dimerization
favoring the head-to-head reaction[6c] (Scheme 1b). Despite the
high efficiency and selectivity of this process, it is limited to ar-
ylalkynes possessing the ortho-CꢀH bond. Employment of N-
heterocyclic carbene-based ligands allowed the Nolan group
to achieve good selectivity favoring the formation of (E)-1,4-
substituted enynes 2[6d] (Scheme 1c). However, the ratio of the
dimeric products in this method depends on both the nature
of substrate and the reaction conditions. Recently, Guo and
Han introduced a Brønsted acid-assisted dimerization reaction,
which leads to the exclusive formation of 1,3-substituted
enynes 4.[6f] In this case, hydropalladation of terminal acetylene
to form alkenylpalladium intermediate iii was proposed to be
[a] O. V. Zatolochnaya, Dr. C. Jahier, Prof. Dr. V. Gevorgyan
Department of Chemistry, University of Illinois at Chicago
845 West Taylor Street, Chicago, Illinois, 60607-7061 (USA)
E-mail: vlad@uic.edu
[b] Dr. E. G. Gordeev, Prof. Dr. V. P. Ananikov
Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences
Leninsky Prospekt 47, Moscow, 119991 (Russia)
E-mail: val@ioc.ac.ru
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201402809.
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the corresponding (E)-enyne 2a in 92% yield with perfect
regio- and stereoselectivity (Table 1, entry 1).
The generality of this transformation was then examined.
Thus, a variety of arylalkynes, such as electron-rich alkynes 1b
and 1c or electron-deficient alkynes 1d, 1e, and 1 f were
smoothly converted to (E)-1,4-disubstituted enynes in good to
high yields (entries 2–6). Importantly, the reaction was not sen-
sitive to sterics as demonstrated by a selective reaction of
ortho-substituted arylalkynes 1g and 1h (entries 7, 8). Al-
though the reaction did not proceed with 2,6-dimethylpheny-
lacetylene (1i),[22] it was efficient with 2,6-disubstituted alkynes
1j and 1k, thus eliminating agostic interactions[6c] as a possible
regioncontrolling element of this process (entries 9–11). Addi-
tionally, an employment of 1-naphthylacetylene (1l) provided
corresponding enyne in good yield (entry 12). Furthermore, al-
kynes bearing heteroaromatic substituents, such as 3-thio-
phenyl (1m), 2- and 3-pyridyl (1n, o), and 4-isoquinolyl (1p),
underwent an efficient dimerization under the developed reac-
tion conditions (entries 13–16). Gratifyingly, aliphatic alkynes
were also found to be competent substrates for the dimeriza-
tion reaction. Thus, dodecyne 1q was converted to (E)-1,4-dis-
ubstituted enyne 2q in 91% yield (entry 17). Similarly to arylal-
kynes, sterically hindered aliphatic acetylenes 1r and 1s react-
ed efficiently with selective formation of enyne products (en-
tries 18, 19). Furthermore, various functionalities, such as
ethers (entries 20, 21), alcohols (entries 22–25), acetal
(entry 26), amine (entry 27), and amide (entry 28), were well
tolerated under the reaction conditions. Notably, the reaction
was easily scalable providing comparable yield of 2a even in
the presence of 0.5 mol% of the catalyst (entry 1).
Scheme 1. Pd-catalyzed dimerization of terminal alkynes.
the key mechanistic event (Scheme 1d). In our preliminary re-
port,[6e] we disclosed an efficient method for the head-to-head
dimerization reaction, which dramatically expanded the scope
of the previously known procedures. Based on DFT studies, we
were able to identify the reaction intermediates, which sug-
gested hydropalladation as a major reaction pathway. Subse-
quently, we found that regioselectivity of the reaction can be
inverted by the addition of carboxylates providing 1,3-substi-
tuted enyne 4 as a sole reaction product. Detailed computa-
tional studies revealed that the observed selectivity switch ori-
ginated by interchange from hydropalladation to carbopallada-
tion pathways assisted by carboxylate anions. Herein, we
report a full account of the head-to-head dimerization of ter-
minal acetylenes, as well as the theoretical rational for the ob-
served high selectivity in both head-to-head and head-to-tail
dimerization reactions.
Carboxylate effect on dimerization regioselectivity
Intrigued by Nolan’s report on base-dependent reaction selec-
tivity we investigated whether an analogous effect could be
observed in our catalytic system producing head-to-head di-
merization products (Table 2, entries 1, 2).[6d] To this end, dime-
rization of phenylacetylene in the presence of the [IPr-Pd-IPr]/
TDMPP catalytic system and base additives was tested. Thus,
the reaction performed in the presence of K2CO3 under other-
wise identical conditions afforded 2a with similar selectivity
albeit in diminished yield (entries 3, 4). A similar result was ob-
served when the less hindered IMes-based catalyst precursor
was employed (entry 5). Interestingly, commercially available
[IPrPdAllCl] complex afforded 2a in good yield with slightly al-
tered stereoselectivity of the dimerization with no effect on re-
gioselectivity, although prolonged reaction time was required
(entry 6). Head-to-head dimerization still remained a major
pathway when the reaction was run in the presence of potassi-
um or cesium carbonates (entries 7, 8). However, when a cata-
lytic amount of cesium acetate was added, clear preference for
the head-to-tail dimerization was observed delivering dimeric
products 2a and 4a as a 1:4 mixture (entry 9). In the presence
of potassium acetate the ratio was further improved (entry 11).
Ultimately, employment of cesium pivalate allowed for perfect
head-to-tail regioselectivity furnishing enyne 4a (entry 10). In
contrast to the inorganic bases, addition of pyridine sup-
Results and Discussion
Head-to-head dimerization of terminal alkynes
In continuation of our search for a highly selective Pd-cata-
lyzed head-to-head dimerization reaction of terminal acety-
lenes, we turn our attention to N-heterocyclic carbene-based
(NHC) palladium complexes as they displayed reasonable selec-
tivity in this transformation.[6d] We have found that combina-
tion of bis-N-heterocyclic carbene palladium complex, [IPr-Pd-
IPr], with electron-rich and bulky phosphine ligand TDMPP
(TDMPP=P[(2,6-OMe)2C6H3]3)[21] efficiently catalyzed the head-
to-head dimerization reaction of phenylacetylene 1a to afford
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Table 1. Palladium-catalyzed dimerization of terminal alkynes toward (E)-1,4-disubstituted enynes.[a]
Entry
1
Alkyne
Yield 2 [%][b]
Entry
15
Alkyne
Yield 2 [%][b]
56
92
1o
1p
1a
86[c]
16
78
2
3
R=OMe
1b
1c
81
92
17
18
1q
1r
91
91
R=Me
4
5
R=CN
1d
1e
82
67
19
20
1s
1t
65
71
R=COOMe
6
7
R=Cl
1 f
51
77
21
22
1u
1v
62
94
R=OMe
1g
8
R=Me
R=Me
R=F
1h
1i
81
23
24
25
26
1w
1x
1y
1z
85
88
89
93
[d]
9
–
10
11
1j
88
75
R =OMe
1k
12
1l
66
27
28
1aa
1ab
81
96
13
14
1m
1n
65
93
[a] Reaction conditions: 1 (0.5 mmol), [IPr-Pd-IPr] (2 mol%), TDMPP (2 mol%), toluene (0.5 mL), 608C. [b] Isolated yields. [c] Reaction conditions: 1a
(5 mmol), [IPr-Pd-IPr] (0.5 mol%), TDMPP (1 mol%), toluene (5.0 mL), 608C. [d] No reaction was observed.
pressed the reaction (entry 12). Moreover, employment of terti-
ary amines, such as triethylamine or DABCO, resulted in de-
composition of starting phenylacetylene. These results clearly
indicate that among all bases tested only carboxylate anion is
capable of the selectivity switch from the head-to-head to
head-to-tail dimerization path. To further verify this observa-
tion, regioselectivity of the reaction catalyzed by define com-
plexes [IPrPdPPh3][23] and [IPrPd(OPiv)2][24] was compared. Thus,
employment of [IPrPdPPh3] led to the facile formation of (E)-
1,4-diphenylenyne 2a, whereas 1,3-diphenylenyne 4a formed
predominately under [IPrPd(OPiv)2]/TDMPP catalysis (entries 13,
14).
conditions (entries 2, 3). Gradual increase of steric hindrance at
the ortho position affected the head-to-head reaction resulting
in reduced yields and selectivities in case of mono-ortho-substi-
tuted alkynes 1g and 1h and complete loss of reactivity in
case of 2,6-disubstituted phenylacetylenes 1i and 1k. Howev-
er, the corresponding head-to-tail dimerization proceeded
smoothly for mono-ortho-substituted alkynes 1g and 1h. In
case of alkyne 1i, 1,3-disubstituted enyne 4i was formed pre-
dominantly although efficiency and selectivity were dimin-
ished. In contrast, clean conversion of 2,6-dimethoxyphenylace-
tylene 1k to 1,3-disubstituted enyne 4k was observed (en-
tries 4–7). 1-Naphthylacetylene (1l) underwent both reactions
with formation of the corresponding enynes in good yields
with perfect regio- and stereoselectivity (entry 8). Further stud-
ies indicated that combination of [IPrPdAllCl] and TDMPP dis-
plays poor activity in the dimerization of aliphatic alkynes.
Thus, reaction of dodecyne (1q) delivered a mixture of dimeric
products favoring (E)-1,4-disubstituted enyne 2p in moderate
yield only (entry 9). Other tested aliphatic substrates did not di-
In order to investigate the generality of the observed car-
boxylate anion effect, the reactivity of several other alkynes
was tested using the [IPrPdAllCl]/TDMPP catalytic system with
(method B) or without CsOPiv (method A, Table 3). Thus, elec-
tron-rich (1b) or neutral (1c) para-substituted alkynes were
converted to the corresponding enynes 2b,c or 4b,c with high
efficiency and regioselectivity depending on the employed
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merize under these conditions. On the other hand, addition of
catalytic amount of CsOPiv into the reaction mixture promoted
the head-to-tail dimerization of alkylalkynes. Hence, linear al-
kynes 1q and 1u were selectively converted to the corre-
sponding 1,3-disubstituted enynes (entries 9, 11). Similarly to
the reactivity of arylsubstituted alkynes, sterically demanding
aliphatic alkynes underwent the head-to-tail dimerization with
slightly decreased selectivity (entries 10, 12). The direct com-
parison of these two catalytic systems clearly demonstrates
a dramatic effect of carboxylate anion on the regioselectivity
of the Pd-catalyzed dimerization reaction. Thus, under the
base-free conditions, terminal alkynes selectively undergo
head-to-head dimerization reaction, whereas in the presence
of carboxylate anion under otherwise identical conditions their
head-to-tail dimerization becomes a predominant process.
Table 2. Investigation of the base effect on the selectivity of the Pd-cata-
lyzed dimerization of terminal alkynes.[a]
Entry Catalyst
Ligand
Base
t
[h]
2a/3a/4a[b] Yield
[%][c]
1[d]
2[d]
3
Pd(OAc)2
Pd(OAc)2
IMes·HCl CsCO3
IMes·HCl K2CO3
2
2
2
2
9
93:7:0
98[6d]
98[6d]
92
63
56
69:5:26
100:0:0
99:1:0
99:1:0[f]
[IPr-Pd-IPr]
[IPr-Pd-IPr]
[Pd(IMes)2]
[IPrPdAllCl]
[IPrPdAllCl]
[IPrPdAllCl]
[IPrPdAllCl]
[IPrPdAllCl]
[IPrPdAllCl]
[IPrPdAllCl]
[IPrPdPPh3]
TDMPP
TDMPP
TDMPP
TDMPP
TDMPP
TDMPP
TDMPP
TDMPP
TDMPP
TDMPP
–
–
4[e]
5[e]
6
K2CO3
K2CO3
–
K2CO3
Cs2CO3
CsOAc
CsOPiv
KOAc
24 96:4:0[f]
12 97:0:7
12 100:0:0
1
1
1
94
62
7[e]
8[e]
9
10
11
12
13
14
83[g]
70[g]
62
20:0:80
0:0:100
10:0:90
–
97:0:3
5:0:95[f]
64[g]
Investigation of the reaction mechanism
[h]
pyridine 16
–
–
1
1
87[g]
80[g]
Having established methods for the selective head-to-head
and head-to-tail dimerization reactions of terminal alkynes, we
turned our attention to the investigation of the origin of the
observed regioselectivity switch. To this end, the reaction
mechanism was studied computationally. Theoretical calcula-
tions were carried out at the B3LYP/6-311G(d)&SDD level in
order to locate intermediate complexes and transition states.
Free energy surfaces DG of the computed catalytic cycles will
be discussed for detailed comparison of head-to-
[IPrPd(OPiv)2] TDMPP
[a] Reaction conditions: catalyst (2 mol%), ligand (2 mol%), base
(2 mol%), toluene (1m), 608C. [b] Determined by GC/MS and NMR spec-
troscopy. [c] Isolated yield. [d] Reaction conditions: catalyst (1 mol%),
ligand (2 mol%), base (2 equiv), DMA (1m), 808C; from ref. [6d].
[e] 2 equiv of base was used. [f] Formation of a small amount of diphenyl-
diyne was observed. [g] NMR yield of the major isomer. [h] No reaction
was observed.
head and head-to-tail dimerization.[25]
Table 3. Carboxylate effect in palladium-catalyzed dimerization of terminal alkynes.
Head-to-head dimerization of alkynes
It is generally considered that the dimerization of ter-
minal alkynes starts with the formation of p-complex
A, in which the first molecule of the alkyne is bound
to the L-Pd0 center (Scheme 2, L=NHC). Coordination
of the alkyne is followed by the oxidative addition of
CꢀH bond via the transition state B-TS leading to the
formation of hydrido complex C. According to the
calculated energy surface, this process was found to
Entry
1
Alkyne
Method A
Method B
yield 2 [%][a,c]
yield 4 [%][b,c]
1a
94 (96:4:0)
62
2
3
4
5
R=OMe
R=Me
R=OMe
R=Me
1b
1c
1g
1h
77
88
85 (5:0:95)
88
80
97
45 (83:0:17)
52 (70:0:30)
be endothermic with the energy change of DGA!C
=
¼
14.8 kcalmolꢀ1 and activation barrier of DG
=
A!B-TS
[d]
17.6 kcalmolꢀ1 (Figure 1). Available coordination va-
cancy and the labile structure of complex C provides
access to four different reaction channels: head-to-
head dimerization by either the carbopalladation or
hydropalladation path (Scheme 2A), and head-to-tail
dimerization through either the carbopalladation or
hydropalladation path (Scheme 2B). In the present
study, we have located all intermediate species and
transition states for complete characterization of
these reaction pathways (Figure 2).
6
7
R=Me
R=OMe
1i
1k
–
–
37 (15:0:85)
78 (2:0:98)
[d]
8
1l
65
80
9
1q
1s
58 (83:7:10)
93
[d]
10
–
65[e] (9:0:91)
[d]
11
1u
–
83
[d]
12
1z
–
81 (19:0:81)
Coordination of the second alkyne molecule fur-
nished the p-complexes D-hh, D’-hh, D-ht, D’-ht,
which differ by the orientation of alkyne molecule
around PdꢀC and PdꢀH bonds (Figures 1 and 2). Car-
bopalladation involves complexes D-hh and D-ht,
whereas hydropalladation originated from complexes
[a] Reaction conditions for method A: 1 (0.5 mmol), [IPrPdAllCl] (2 mol%), TDMPP
(2 mol%), toluene (0.5 mL), 608C. [b] Reaction conditions for method B: 1 (0.5 mmol),
[IPrPdAllCl] (2 mol%), TDMPP (2 mol%), CsOPiv (2 mol%), toluene (0.5 mL), 608C.
[c] Isolated yields. Ratio of 2/3/4 is shown in parentheses if more than one isomer was
formed. [d] No reaction was observed. [e] NMR yield.
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Scheme 2. Proposed mechanism for the Pd-catalyzed: a) head-to-head, and b) head-to-tail dimerization of terminal alkynes.
Figure 1. Calculated free-energy surface (DG, kcalmolꢀ1) of Pd-catalyzed head-to-head and head-to-tail dimerization of terminal alkynes at the B3LYP/6-
311G(d)&SDD level (see Scheme 2 for structures and Figure 2 for molecular geometries).
D’-hh and D’-ht. All these complexes have similar relative ener-
gies with the largest deviation of DG=4.3 kcalmolꢀ1 observed
between D-ht and D’-ht. Due to the small energy difference,
all of the proposed pathways should be further considered. Ac-
cordingly, carbopalladation was found to be an exothermic
actions. However, alkynes insertion into the PdꢀC bond re-
¼
¼
quires DG D-hh!E-TS-hh =18.6 kcalmolꢀ1 and DG
=
D-ht!E-TS-ht
23.3 kcalmolꢀ1. Hydropalladation is also an exothermic process
with a similar energy gain of DGD’-hh!F’-hh =ꢀ16.9 kcalmolꢀ1 for
head-to-head and DGD’-ht!F’-ht =ꢀ16.0 kcalmolꢀ1 for head-to-
tail dimerizations. However, the activation barriers for alkyne
insertion into the PdꢀH bond were dramatically lower com-
process for both head-to-head (DGD-hh!F-hh =ꢀ13.9 kcalmolꢀ1
)
and head-to-tail (DGD-ht!F-ht =ꢀ11.1 kcalmolꢀ1) dimerization re-
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Figure 2. Optimized molecular structures of reaction intermediates at the B3LYP/6-311G(d)&SDD level (normal mode corresponding to imaginary frequency in
the transition state is shown, hydrogen atoms of the complexes are omitted for clarity with the exception of the reacting H atoms). See the Supporting Infor-
mation for the geometric parameters.
pared to that for alkyne insertion into the PdꢀC bond. Thus, it
only required 2.1 and 1.9 kcalmolꢀ1 of activation energy for
head-to-head and head-to-tail dimerizations, respectively.
Therefore, the activation barriers calculated for the hydropalla-
dation pathway are an order of magnitude lower than the cor-
responding barriers for the carbopalladation path.
higher relative energy on the potential energy surface 24.2,
25.3, 38.0 and 42.4 kcalmolꢀ1 for E’-TS-hh, E’-TS-ht, E-TS-hh,
and E-TS-ht, respectively (Figures 1 and 3). The charges on the
carbon atoms of the acetylenide PdꢀCa ꢁCb group, which are
equal to approximately ꢀ0.15a/ꢀ0.06b for carbopalladation (E-
TS-hh and E-TS-ht) and about ꢀ0.16a/ꢀ0.19b for hydropallada-
tion (E’-TS-hh and E’-TS-ht) do not depend on the regioselec-
tivity of the insertion of the second alkyne molecule. In con-
trast, significant changes in the electron density localization
were observed for the carbon atoms of the alkyne molecule
coordinated as p-complex. Particularly, for the highest-in-
energy transition state E-TS-ht, the charges on the carbon
atoms were found to be ꢀ0.353 and +0.071. Notably, it was
the only case with the positive charge on the alkyne carbon
atom. For the E’-TS-hh, E’-TS-ht, and E-TS-hh transition states,
significant differences in the charge of the carbon atoms
bound in p-fashion were also observed with the values in the
range of ꢀ0.029 to ꢀ0.275.
In all cases, the insertion of the second alkyne molecule
took place through the concerted-type transition states
(Figure 3). For the hydropalladation pathway, the lower-in-
energy transition state E’-TS-hh was characterized with a short-
er PdꢀC bond of 2.103 ꢁ and longer CꢀH bond of 1.817 ꢁ
compared to the corresponding interatomic distances of E’-TS-
ht. In case of the carbopalladation pathway, the more favora-
ble transition state E-TS-hh possesses a longer PdꢀC bond of
2.216 ꢁ and shorter CꢀC bond of 1.936 ꢁ, compared to that of
E-TS-ht. It is interesting to note the change in the delocaliza-
tion of electron density associated with the different mecha-
nisms. Thus, an increase in the negative charge on the metal
atom ꢀ0.003, ꢀ0.016, ꢀ0.026, ꢀ0.057, is accompanied with
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represents the most favorable
transformation on the overall
energy surface. This result is in
agreement with the experimen-
tal findings.
Hydro-/carbopalladation mech-
anism switch
A facile reaction is an important
advantage of the hydropallada-
tion pathway governed by small
activation barriers. However,
since the activation barriers are
low, the difference in the activa-
tion energies between head-to-
head and head-to-tail dimeriza-
tions is also negligible. In prac-
tice, this suggests that regiose-
lectivity of the reaction proceed-
ing through the hydropallada-
tion mechanism would be diffi-
Figure 3. Interatomic distances and atomic NBO charges (in parenthesis) for optimized molecular structures of E-
TS-hh, E’-TS-hh, E-TS-ht and E’-TS-ht calculated at the B3LYP/6-311G(d)&SDD level (other atoms are omitted for
clarity; normal mode corresponding to imaginary frequency in the transition state is indicated by arrows).
cult to control. Therefore, the
outcome of the reaction would
depend on several factors, such
as reaction conditions, nature of
The last step of the catalytic cycle involves the reductive
elimination with the formation of product 2 for the head-to-
head dimerization and product 4 for the head-to-tail dimeriza-
tion. This step proceeds easily by overcoming corresponding
substituents in the reagents, ligands, etc. In contrast, the car-
bopalladation mechanism was characterized with high activa-
tion barriers, which resulted in a larger difference between en-
ergies of the transition states corresponding to head-to-head
and head-to-tail dimerizations. Particularly, the difference be-
tween E’-TS-hh and E’-TS-ht was only 1.1 kcalmolꢀ1 for the hy-
dropalladation path, whereas the difference between E-TS-hh
and E-TS-ht was 4.4 kcalmolꢀ1 for the carbopalladation path-
way (Figure 1). As evident from the calculations, in order to
direct alkyne insertion into the PdꢀC bond, the hydropallada-
tion path should be deactivated. Potentially, addition of a suita-
ble base that will interact with hydrogen ligand would deacti-
vate PdꢀH bond. In order to test this hypothesis, acetate anion
was employed to simulate the interaction of palladium acetyle-
nide with mild carboxylate base. For mimicking the reaction in
polar media, a complete dissociation of ions was considered
(Scheme 3, path a). Additionally, a model for reaction in regular
organic solvents with low or medium polarity, which most
likely would involve ion pairs, was also studied (Scheme 3,
path b). Full-size IPr-NHC ligand was involved in the calcula-
tions.
¼
activation barriers in the range of DG F!G-TS =0.7–5.2 kcal
molꢀ1 (Figure 1). For the F-ht!H-ht reaction the barrier of
<1 kcalmolꢀ1 was estimated, as the direct transformation to-
wards the product was observed. Transition state G-TS-ht was
not localized due to a very shallow energy surface.
In all cases, formation of complexes H-hh, H-ht, H’-hh and
H’-ht is a highly exothermic process with the energy gain of
>30 kcalmolꢀ1 relative to that of complexes F-hh, F-ht, F’-hh
and F’-ht, and with energy gain of >22 kcalmolꢀ1 relative to
initial point of the catalytic cycle A. The change in the free
energy between points A and H ensures the overall driving
force of the dimerization reaction. Additionally, comparison of
relative energy of complexes H-hh, H’-hh with H-ht, H’-ht indi-
cated that the products of head-to-head dimerization are more
stable by approximately 5 kcalmolꢀ1. Dissociation of the prod-
uct and coordination of new molecule of alkyne 1 completes
the turnover of the catalytic cycle (Scheme 2).
Analysis of the calculated energy surface clearly indicated
that hydropalladation is the kinetically preferred reaction path-
way for both head-to-head and head-to-tail dimerizations. Sub-
stantial energy difference in the calculated activation barriers
indicates that alkyne insertion into the PdꢀH bond will occur
wherever possible. Alkyne insertion into the PdꢀC bond may
only take place if PdꢀH would be unavailable for the insertion.
Among the studied reaction pathways, the head-to-head
alkyne dimerization through the hydropalladation mechanism
Scheme 3. Interaction of complex C with acetate anion.
Chem. Eur. J. 2014, 20, 9578 – 9588
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Complete dissociation involv-
ing anionic Pd species in the
catalytic cycle
The process involving complete
dissociation of ions was consid-
ered first (Scheme 3, path a). The
calculations revealed that proton
removal from complex C leading
to the formation of acetic acid
and anionic complex C(ꢀ) is an
energetically favorable process
with DGC!C(ꢀ) =ꢀ19.8 kcalmolꢀ1
(Figure 4). Coordination of the
second alkyne molecule to C(ꢀ)
gave p-complexes D(ꢀ)-hh and
D(ꢀ)-ht depending on the orien-
tation of the second alkyne mol-
ecule. Notably, D(ꢀ)-ht was
found to be considerably more
stable than D(ꢀ)-hh by 5.5 kcal
molꢀ1 on the calculated energy
surface.
Figure 4. Calculated energy surface (DG, kcalmolꢀ1) of anionic Pd-catalyzed head-to-head and head-to-tail dimeri-
zation of terminal alkynes; different reaction paths are denoted by different colors (see the Supporting Informa-
tion for a scheme of the catalytic cycle and optimized structures); calculated at the B3LYP/6-311G(d)&SDD level.
Due to the absence of PdꢀH
bonds, only the carbopalladation
pathway was possible for the lo-
cated p-complexes. Thus, formation of palladium complexes
F(ꢀ)-hh and F(ꢀ)-ht via transition states E(ꢀ)-TS-hh and E(ꢀ)-
These results suggest that in case of ion-pair structures,
head-to-head dimerization may be disfavored due to instability
of the intermediate complex. Observed elimination of one of
the alkyne molecules from the coordination sphere of palladi-
um might be attributed to the induced steric strain after the
coordination of acetate anion to the palladium complex. Com-
plex D-hh should be more sensitive to the steric effects due to
the existing interactions of alkyne substituent R with the NHC
ligand (Scheme 4). In the analogous complex D-ht, the steric
strain is relived due to opposite alignments of substituent R. A
TS-ht were found to be an exothermic process (DGD-hh!F-hh
=
ꢀ20.8 kcalmolꢀ1, DGD-ht!F-ht =ꢀ11.3 kcalmolꢀ1) requiring 24.7
and 38.4 kcalmolꢀ1 of activation energy, respectively. Therefore,
under the anionic manifold, the dimerization proceeds via the
carbopalladation route, whereas a competitive hydropallada-
tion path is eliminated. The overall energy surface indicates
that the head-to-head dimerization remains more favorable
compared to the head-to-tail dimerization in this case.
Interaction with base and formation of the ion pair
Another possible interaction of complex C with acetate ion in-
volves formation of the ion-pair complex (Scheme 3, path b).
The calculations carried out with the PdꢀO length of 2.20 ꢁ in-
dicated that formation of the ion-pair complex is possible
since the computed difference in free energies for this event is
small (DG= +0.7 kcalmolꢀ1). Furthermore, geometry optimiza-
tion for coordination of the second alkyne molecule and for-
mation of complex D-ht with bound acetate ligand (D-ht+
AcO(ꢀ)) revealed a plausible structure in which the hydrogen
atom had migrated from Pd to the oxygen atom of the carbox-
ylate group (Figure 5a). Within this complex, both alkyne units
remained bound to the metal rendering the possibility for
head-to-tail dimerization. In contrast, during the geometry op-
timization of the analogous complex corresponding to the
head-to-head dimerization mechanism, dissociation of one of
the alkyne molecules was observed (Figure 5b). This process
involved movement of the hydrogen atom from the carboxyl-
ate group to the neighboring acetylenide residue.
Figure 5. Comparison of optimized molecular structures of: a) D-ht, D-
ht+AcO(ꢀ), and b) D-hh and D-hh+AcO(ꢀ).
Chem. Eur. J. 2014, 20, 9578 – 9588
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similar effect was observed in the calculated pathway for the
anionic complex. Thus, D(ꢀ)-hh was found to be higher in
energy by DG= +5.5 kcalmolꢀ1 compared to D(ꢀ)-ht
(Figure 5). Notably, the calculated energy difference for the
via the carbopalladation pathway was found to be preferential
for the carboxylate-assisted reaction. We believe that this ob-
servation might have an impact beyond dimerization of acety-
lenes. Particularly, it would provide a basis for the develop-
ment of selective processes in which hydro- and carbometalla-
tion are competing reaction pathways.
Experimental Section
Scheme 4. Steric strain in the complexes D-hh and D-ht.
Dimerization of phenylacetylene using [IPr-Pd-IPr]/TDMPP
An oven-dried 1 mL Wheaton microreactor was loaded with [IPr-
Pd-IPr] (8.9 mg, 0.01 mmol, 2 mol%) and tris(2,6-dimethoxyphenyl)-
phosphine (4.4 mg, 0.01 mmol, 2 mol%). Anhydrous toluene
(0.5 mL) was added followed by phenylacetylene 1a (55 mL,
0.5 mmol). The reaction mixture was stirred at 608C for 2 h. The re-
action course was monitored by GC/MS analysis. After the reaction
completion, the reaction mixture was filtered through a short
celite plug and concentrated. The product was purified by column
chromatography (eluent: 100% hexanes) to afford 2a (47 mg,
complexes D-hh/D-ht and D’-hh/D’-ht was much smaller in
the reaction without acetate ion additive (Figure 1). Thus, addi-
tion of the acetate ion played a dual role in the studied
system: 1) removal of hydrogen atom from palladium, thus de-
activating the favorable hydropalladation pathway; and 2) im-
posing larger difference in the stability of palladium complexes
involved in head-to-tail and head-to-head dimerizations. There-
fore, the calculations strongly suggest that head-to-tail dimeri-
zation is a more favorable process in the case of ion-pair inter-
mediates.
1
92%) as a white solid. H NMR (500 MHz, CDCl3): d=7.53–7.49 (m,
2H), 7.47–7.43 (m, 2H), 7.39–7.29 (m, 6H), 7.07 (d, J=16.3 Hz, 1H),
6.42 ppm (d, J=16.2 Hz, 1H); 13C NMR (125 MHz, CDCl3): d=141.3,
136.4, 131.5, 128.8, 128.6, 128.4, 128.2, 126.3, 123.4, 108.2, 91.8,
88.9 ppm; HRMS (ESI) calcd for C16H12 [M]+: 204.0939; found:
204.0945.
Conclusion
A highly regio- and stereoselective method for the palladium-
catalyzed head-to-head dimerization reaction of terminal al-
kynes toward 1,4-disubstituted enynes has been developed.
This methodology is general for a variety of terminal acety-
lenes possessing various functional groups, such as aryl, heter-
oaryl, alkyl, hydroxyl, ether, acetal, amino, and amido groups.
Another feature of this method is its insensitivity to sterics, as
bulky aryl or aliphatic substrates can be efficiently converted
to the corresponding enynes. The reaction is also easily scala-
ble and operates under mild conditions. It was found that
combination of several NHC-based palladium precursors with
phosphine additives selectively promotes head-to-head dimeri-
zation of terminal acetylenes. However, addition of carboxylate
anion to the catalytic system dramatically affects the selectivity
favoring the head-to-tail dimerization reaction. The effect of
carboxylate was found to be general for a wide range of termi-
nal alkynes, including sterically demanding aromatic or aliphat-
ic substrates. DFT calculations revealed that under neutral reac-
tion conditions, the hydropalladation pathway is kinetically
preferred over the carbopalladation path for both head-to-
head and head-to-tail dimerizations. Analysis of the calculated
energy surfaces indicated that head-to-head alkyne dimeriza-
tion is the most favorable among the routes studied. However,
it has been found that the formation of anionic Pd complexes
or ion pairs in the presence of carboxylate anion deactivates
the hydropalladation pathway. Furthermore, only intermediates
leading to the head-to-tail dimerization were located upon op-
timization of ion-paired structures. Coordination of second
alkyne molecule in head-to-head fashion was restricted by the
steric demand of the corresponding intermediates. Therefore,
based on computational studies, the head-to-tail dimerization
Dimerization of phenylacetylene using [IPrPdAllCl]/TDMPP
(method A)
An oven-dried 1 mL Wheaton microreactor was loaded with [IPrP-
dAllCl] (5.7 mg, 0.01 mmol, 2 mol%) and tris(2,6-dimethoxyphenyl)-
phosphine (4.4 mg, 0.01 mmol, 2 mol%). Anhydrous toluene
(0.5 mL) was added followed by phenylacetylene 1a (55 mL,
0.5 mmol). The reaction mixture was stirred at 608C for 24 h. The
reaction course was monitored by GC/MS analysis. After the reac-
tion completion, the reaction mixture was concentrated and fil-
tered through a short silica gel plug. The product was purified by
column chromatography (eluent: 100% hexanes) to afford the
product (48 mg, 94%) as a mixture of 2a/3a=96:4.
Dimerization of phenylacetylene using [IPrPdAllCl]/TDMPP/
CsOPiv (method B)
An oven-dried 1 mL Wheaton microreactor was loaded with [IPrP-
dAllCl] (5.7 mg, 0.01 mmol, 2 mol%), tris(2,6-dimethoxyphenyl)-
phosphine (4.4 mg, 0.01 mmol, 2 mol%), and cesium pivalate
(2.3 mg, 0.01 mmol, 2 mol%). Anhydrous toluene (0.5 mL) was
added followed by phenylacetylene 1a (55 mL, 0.5 mmol). The reac-
tion mixture was stirred at 608C for 3 h. The reaction course was
monitored by GC/MS analysis. After completion, the reaction mix-
ture was concentrated and filtered through a short silica gel plug.
The product was purified by column chromatography (eluent:
100% hexanes) to afford 4a (32 mg, 62%) as a colorless oil.
1H NMR (500 MHz, CDCl3): d=7.75–7.70 (m, 2H), 7.56–7.53 (m, 2H),
7.42–7.32 (m, 6H), 6.01 (d, J=1.0 Hz, 1H), 5.79 ppm (d, J=1.0 Hz,
1H); 13C NMR (125 MHz, CDCl3): d=137.3, 131.7, 130.6, 128.4,
128.3, 126.1, 123.1, 120.6, 90.8, 88.6 ppm; HRMS (ESI) calcd for
C16H12 [M]+: 204.09390 found: 204.0941.
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136; j) M. Schafer, J. Wolf, H. Werner, Dalton Trans. 2005, 1468; k) W.
Weng, C. Guo, R. Celenligil-Cetin, B. M. Foxman, O. V. Ozerov, Chem.
Commun. 2006, 197; l) J.-i. Ito, M. Kitase, H. Nishiyama, Organometallics
2007, 26, 6412; m) T. Nishimura, X.-X. Guo, K. Ohnishi, T. Hayashi, Adv.
Synth. Catal. 2007, 349, 2669; n) T. Katagiri, H. Tsurugi, T. Satoh, M.
Miura, Chem. Commun. 2008, 3405; o) H. M. Peng, J. Zhao, X. Li, Adv.
Synth. Catal. 2009, 351, 1371; p) K. Mochizuki, K. Sakai, T. Kochi, F. Kakiu-
chi, Synthesis 2013, 45, 2088; q) L. Rubio-Pꢄrez, R. Azpꢅroz, A. Di Giu-
seppe, V. Polo, R. Castarlenas, J. J. Pꢄrez-Torrente, L. A. Oro, Chem. Eur. J.
2013, 19, 15304; r) H.-D. Xu, R.-W. Zhang, X. Li, S. Huang, W. Tang, W.-H.
Hu, Org. Lett. 2013, 15, 840.
Acknowledgements
The support of the National Science Foundation (CHE-1112055)
and Russian Foundation for Basic Research (RFBR 13-03-01210,
14-03-31752) is gratefully acknowledged.
Keywords: alkyne dimerization · carbopalladation · density
functional calculations · hydropalladation · palladium
[9] a) C.-H. Jun, Z. Lu, R. H. Crabtree, Tetrahedron Lett. 1992, 33, 7119; b) T.
Ohmura, S.-i. Yorozuya, Y. Yamamoto, N. Miyaura, Organometallics 2000,
19, 365; c) R. Ghosh, X. Zhang, P. Achord, T. J. Emge, K. Krogh-Jespersen,
A. S. Goldman, J. Am. Chem. Soc. 2007, 129, 853; d) K. Ogata, A. Toyota,
J. Organomet. Chem. 2007, 692, 4139; e) M. Ciclosi, F. Estevan, P. Lahuer-
ta, V. Passarelli, J. Pꢄrez-Prieto, M. Sanaffl, Adv. Synth. Catal. 2008, 350,
234; f) M. Ez-Zoubir, F. L. B. d’Herouville, J. A. Brown, V. Ratovelomana-
na-Vidal, V. Michelet, Chem. Commun. 2010, 46, 6332; g) C. D. Forsyth,
W. J. Kerr, L. C. Paterson, Synlett 2013, 24, 587.
[1] a) S. Saito, M. M. Salter, V. Gevorgyan, N. Tsuboya, K. Tando, Y. Yamamo-
to, J. Am. Chem. Soc. 1996, 118, 3970; b) V. Gevorgyan, A. Takeda, Y. Ya-
mamoto, J. Am. Chem. Soc. 1997, 119, 11313; c) V. Gevorgyan, O. V. Za-
tolochnaya, in Transition-Metal Mediated Aromatic Ring Construction
(Ed.: K. Tanaka), Wiley, New York, 2013, p.355; d) B. Kang, D.-h. Kim, Y.
Do, S. Chang, Org. Lett. 2003, 5, 3041; e) P. Wessig, G. Mueller, Chem.
Rev. 2008, 108, 2051; f) M. P. Huestis, L. Chan, D. R. Stuart, K. Fagnou,
Angew. Chem. 2011, 123, 1374; Angew. Chem. Int. Ed. 2011, 50, 1338;
g) H. Kinoshita, T. Ishikawa, K. Miura, Org. Lett. 2011, 13, 6192; h) H.
Zhou, C. Moberg, J. Am. Chem. Soc. 2012, 134, 15992; i) H. Zhou, C.
Moberg, Org. Lett. 2013, 15, 1444.
[10] a) G. C. Midya, S. Paladhi, K. Dhara, J. Dash, Chem. Commun. 2011, 47,
6698; b) G. C. Midya, B. Parasar, K. Dhara, J. Dash, Org. Biomol. Chem.
2014, 12, 1812.
[2] a) K. C. Nicolaou, W.-M. Dai, S.-C. Tsay, V. A. Estevez, W. Wrasidlo, Science
1992, 256, 1172; b) H. Hꢂbner, C. Haubmann, W. Utz, P. Gmeiner, J. Med.
Chem. 2000, 43, 756; c) D. J. Faulkner, Nat. Prod. Rep. 2001, 18, 1R; d) M.
Dçrfler, N. Tschammer, K. Hamperl, H. Hꢂbner, P. Gmeiner, J. Med. Chem.
2008, 51, 6829; e) T. H. Jones, R. M. M. Adams, T. F. Spande, H. M. Garraf-
fo, T. Kaneko, T. R. Schultz, J. Nat. Prod. 2012, 75, 1930; f) C. Hiller, R. C.
Kling, F. W. Heinemann, K. Meyer, H. Hꢂbner, P. Gmeiner, J. Med. Chem.
2013, 56, 5130.
[3] a) N. N. P. Moonen, C. Boudon, J.-P. Gisselbrecht, P. Seiler, M. Gross, F.
Diederich, Angew. Chem. 2002, 114, 3170; Angew. Chem. Int. Ed. 2002,
41, 3044; b) H. Katayama, M. Nakayama, T. Nakano, C. Wada, K. Akamat-
su, F. Ozawa, Macromolecules 2004, 37, 13; c) Y. Takayama, C. Delas, K.
Muraoka, M. Uemura, F. Sato, J. Am. Chem. Soc. 2003, 125, 14163; d) Y.
Liu, M. Nishiura, Y. Wang, Z. Hou, J. Am. Chem. Soc. 2006, 128, 5592;
e) Y. Zhao, N. Zhou, A. D. Slepkov, S. C. Ciulei, R. McDonald, F. A. Heg-
mann, R. R. Tykwinski, Helv. Chim. Acta 2007, 90, 909; f) G. S. Pilzak, B.
van Lagen, C. C. J. Hendrikx, E. J. R. Sudhçlter, H. Zuilhof, Chem. Eur. J.
2008, 14, 7939; g) G. S. Pilzak, J. Baggerman, B. van Lagen, M. A. Posthu-
mus, E. J. R. Sudhçlter, H. Zuilhof, Chem. Eur. J. 2009, 15, 2296.
[11] a) C. Bianchini, M. Peruzzini, F. Zanobini, P. Frediani, A. Albinati, J. Am.
Chem. Soc. 1991, 113, 5453; b) A. M. Echavarren, J. Lo’pez, A. Santos, J.
Montoya, J. Organomet. Chem. 1991, 414, 393; c) C. Slugovc, K. Mereiter,
E. Zobetz, R. Schmid, K. Kirchner, Organometallics 1996, 15, 5275;
d) C. S. Yi, N. Liu, Organometallics 1996, 15, 3968; e) C. S. Yi, N. Liu, Orga-
nometallics 1998, 17, 3158; f) W. Baratta, W. A. Herrmann, P. Rigo, J.
Schwarz, J. Organomet. Chem. 2000, 593–594, 489; g) M. Bassetti, S.
Marini, F. Tortorella, V. Cadierno, J. Dꢅez, M. P. Gamasa, J. Gimeno, J. Or-
ganomet. Chem. 2000, 593–594, 292; h) K. Melis, D. De Vos, P. Jacobs, F.
Verpoort, J. Organomet. Chem. 2002, 659, 159; i) Y. Gao, R. J. Puddephatt,
Inorg. Chim. Acta 2003, 350, 101; j) X. Chen, P. Xue, H. H. Y. Sung, I. D.
Williams, M. Peruzzini, C. Bianchini, G. Jia, Organometallics 2005, 24,
4330; k) H. Katayama, H. Yari, M. Tanaka, F. Ozawa, Chem. Commun.
2005, 4336; l) M. Bassetti, C. Pasquini, A. Raneri, D. Rosato, J. Org. Chem.
2007, 72, 4558; m) M. Daniels, R. U. Kirss, J. Organomet. Chem. 2007,
692, 1716; n) A. Hijazi, K. Parkhomenko, J.-P. Djukic, A. Chemmi, M. Pfeff-
er, Adv. Synth. Catal. 2008, 350, 1493; o) J.-H. Lee, K. G. Caulton, J. Orga-
nomet. Chem. 2008, 693, 1664; p) A. Prades, M. n. Viciano, M. Sanaffl, E.
Peris, Organometallics 2008, 27, 4254; q) C.-K. Chen, H.-C. Tong, C.-Y.
Chen Hsu, C.-Y. Lee, Y. H. Fong, Y.-S. Chuang, Y.-H. Lo, Y.-C. Lin, Y. Wang,
Organometallics 2009, 28, 3358; r) M. Jimꢄnez-Tenorio, M. C. Puerta, P.
Valerga, Organometallics 2009, 28, 2787; s) J. Tripathy, M. Bhattacharjee,
Tetrahedron Lett. 2009, 50, 4863; t) L. D. Field, A. M. Magill, T. K. Shearer,
S. J. Dalgarno, M. M. Bhadbhade, Eur. J. Inorg. Chem. 2011, 3503; u) A.
Coniglio, M. Bassetti, S. E. Garcꢅa-Garrido, J. Gimeno, Adv. Synth. Catal.
2012, 354, 148; v) B. Powala, C. Pietraszuk, Catal. Lett. 2014, 144, 413.
[12] a) P. Barbaro, C. Bianchini, M. Peruzzini, A. Polo, F. Zanobini, P. Frediani,
Inorg. Chim. Acta 1994, 220, 5; b) M. A. Esteruelas, L. A. Oro, N. Ruiz, Or-
ganometallics 1994, 13, 1507; c) J. Alós, T. BolaÇo, M. A. Esteruelas, M.
Olivµn, E. OÇate, M. Valencia, Inorg. Chem. 2013, 52, 6199.
[4] S. Sun, J. Kroll, Y. Luo, L. Zhang, Synlett 2012, 54.
[5] S. Ogoshi, M. Ueta, M.-a. Oka, H. Kurosawa, Chem. Commun. 2004, 2732.
[6] a) B. M. Trost, C. Chan, G. Ruhter, J. Am. Chem. Soc. 1987, 109, 3486;
b) B. M. Trost, M. T. Sorum, C. Chan, G. Rꢂhter, J. Am. Chem. Soc. 1997,
119, 698; c) M. Rubina, V. Gevorgyan, J. Am. Chem. Soc. 2001, 123,
11107; d) C. Yang, S. P. Nolan, J. Org. Chem. 2002, 67, 591; e) C. Jahier,
O. V. Zatolochnaya, N. V. Zvyagintsev, V. P. Ananikov, V. Gevorgyan, Org.
Lett. 2012, 14, 2846; f) T. Chen, C. Guo, M. Goto, L.-B. Han, Chem.
Commun. 2013, 49, 7498; g) C. Xu, W. Du, Y. Zeng, B. Dai, H. Guo, Org.
Lett. 2014, 16, 948; for related transformations, see: h) B. M. Trost, A. J.
Frontier, J. Am. Chem. Soc. 2000, 122, 11727; i) U. Lꢂcking, A. Pfaltz, Syn-
lett 2000, 1261; j) V. Gevorgyan, U. Radhakrishnan, A. Takeda, M. Rubina,
M. Rubin, Y. Yamamoto, J. Org. Chem. 2001, 66, 2835; k) Y.-T. Wu, W.-C.
Lin, C.-J. Liu, C.-Y. Wu, Adv. Synth. Catal. 2008, 350, 1841; l) B. M. Trost,
B. R. Taft, J. T. Masters, J.-P. Lumb, J. Am. Chem. Soc. 2011, 133, 8502;
m) B. M. Trost, J.-P. Lumb, J. M. Azzarelli, J. Am. Chem. Soc. 2011, 133,
740; n) B. M. Trost, G. Dong, J. Am. Chem. Soc. 2010, 132, 16403.
[7] a) G. Hilt, W. Hess, T. Vogler, C. Hengst, J. Organomet. Chem. 2005, 690,
5170; b) T. Sakurada, Y.-k. Sugiyama, S. Okamoto, J. Org. Chem. 2013, 78,
3583.
[13] A. Kawata, Y. Kuninobu, K. Takai, Chem. Lett. 2009, 38, 836.
[14] N. Hagihara, M. Tamura, H. Yamazaki, M. Fujiwara, Bull. Chem. Soc. Jpn.
1961, 34, 892.
[15] a) M. Akita, H. Yasuda, A. Nakamura, Bull. Chem. Soc. Jpn. 1984, 57, 480;
b) G. V. Oshovsky, B. Hessen, J. N. H. Reek, B. d. Bruin, Organometallics
2011, 30, 6067.
[16] a) A. D. Horton, J. Chem. Soc. Chem. Commun. 1992, 185; b) R. H. Platel,
L. L. Schafer, Chem. Commun. 2012, 48, 10609.
[17] M. Yoshida, R. F. Jordan, Organometallics 1997, 16, 4508.
[8] a) H. Singer, G. Wilkinson, J. Chem. Soc. A 1968, 849; b) S. Yoshikawa, J.
Kiji, J. Furukawa, Makromol. Chem. 1977, 178, 1077; c) L. Carlton, G.
Read, J. Chem. Soc. Perkin Trans. 1 1978, 1631; d) I. P. Kovalev, K. V. Yev-
dakov, Y. A. Strelenko, M. G. Vinogradov, G. I. Nikishin, J. Organomet.
Chem. 1990, 386, 139; e) J. Ohshita, K. Furumori, A. Matsuguchi, M. Ishi-
kawa, J. Org. Chem. 1990, 55, 3277; f) W. T. Boese, A. S. Goldman, Orga-
nometallics 1991, 10, 782; g) P. Krꢂger, H. Werner, Eur. J. Inorg. Chem.
2004, 481; h) M. Schꢃfer, J. Wolf, H. Werner, Organometallics 2004, 23,
5713; i) C.-C. Lee, Y.-C. Lin, Y.-H. Liu, Y. Wang, Organometallics 2005, 24,
[18] a) K. H. Den Haan, Y. Wielstra, J. H. Teuben, Organometallics 1987, 6,
2053; b) R. Duchateau, C. T. van Wee, J. H. Teuben, Organometallics
1996, 15, 2291; c) M. Nishiura, Z. Hou, Y. Wakatsuki, T. Yamaki, T. Miya-
moto, J. Am. Chem. Soc. 2003, 125, 1184; d) K. Komeyama, K. Takehira,
K. Takaki, Synthesis 2004, 1062; e) M. Nishiura, Z. Hou, J. Mol. Catal. A
2004, 213, 101; f) K. Komeyama, T. Kawabata, K. Takehira, K. Takaki, J.
Org. Chem. 2005, 70, 7260; g) R. M. Gauvin, L. Delevoye, R. A. Hassan, J.
Keldenich, A. Mortreux, Inorg. Chem. 2007, 46, 1062; h) S. Ge, V. F. Q.
Chem. Eur. J. 2014, 20, 9578 – 9588
www.chemeurj.org
9587
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
Norambuena, B. Hessen, Organometallics 2007, 26, 6508; i) S. Ge, A.
Meetsma, B. Hessen, Organometallics 2009, 28, 719.
TDMPP to the reaction mixture led to the slight improvement of the re-
action yield. See ref. [6e].
[19] a) T. Straub, A. Haskel, M. S. Eisen, J. Am. Chem. Soc. 1995, 117, 6364;
b) J. Q. Wang, A. K. Dash, J. C. Berthet, M. Ephritikhine, M. S. Eisen, Orga-
nometallics 1999, 18, 2407; c) A. K. Dash, J. X. Wang, J. C. Berthet, M.
Ephritikhine, M. S. Eisen, J. Organomet. Chem. 2000, 604, 83; d) A. K.
Dash, I. Gourevich, J. Q. Wang, J. Wang, M. Kapon, M. S. Eisen, Organo-
metallics 2001, 20, 5084; e) J. Q. Wang, M. S. Eisen, J. Organomet. Chem.
2003, 670, 97.
[22] In our preliminary communication (ref. [6e]), we reported 71% yield for
this entry, which unfortunately we were not able to reproduce.
[23] S. Fantasia, S. P. Nolan, Chem. Eur. J. 2008, 14, 6987.
[24] a) D. R. Jensen, M. J. Schultz, J. A. Mueller, M. S. Sigman, Angew. Chem.
2003, 115, 3940; Angew. Chem. Int. Ed. 2003, 42, 3810; b) J. A. Mueller,
C. P. Goller, M. S. Sigman, J. Am. Chem. Soc. 2004, 126, 9724.
[25] See the Supporting Information for the DE energy surface.
[20] a) A. V. Korolev, I. A. Guzei, R. F. Jordan, J. Am. Chem. Soc. 1999, 121,
11605; b) A. K. Dash, M. S. Eisen, Org. Lett. 2000, 2, 737.
[21] The role of TDMPP is not well understood. Thus, the dimerization of
phenylacetylene is perfectly regio- and stereoselective in the presence
of [IPr-Pd-IPr] complex without any additives. However, addition of
Received: March 27, 2014
Published online on July 10, 2014
Chem. Eur. J. 2014, 20, 9578 – 9588
www.chemeurj.org
9588
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim