Cobalt-Catalyzed gem-Cross-Dimerization of Terminal Alkynes

Article abstract of DOI:10.1021/acscatal.9b05078

Transition-metal-catalyzed dimerization of two different terminal alkynes provides an atom-economic synthesis of valuable conjugated 1,3-enynes. Despite many catalyst systems developed, the state-of-the-art solutions are still limited to special alkynes. A practical catalyst, which could be used to cross-dimerize general aryl alkynes and aliphatic alkynes, is still highly desired. Herein we present the earth-abundant Co(II)-catalyzed highly gem-selective cross-dimerization of aryl alkynes and aliphatic alkynes or gas acetylene under mild reaction conditions. Conjugated 1,3-enynes with various useful functional groups can be prepared in high yields. The application of Co(OAc)₂ and t-butyl group substituted triphos ligand is essential to distinguish the alkynes at different steps and realize the gem-selectivity.

Full text of DOI:10.1021/acscatal.9b05078

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Article
Cobalt-Catalyzed gem-Cross-Dimerization of Terminal Alkynes
Jia-Feng Chen, and Changkun Li
ACS Catal., Just Accepted Manuscript • DOI: 10.1021/acscatal.9b05078 • Publication Date (Web): 28 Feb 2020
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Cobalt-Catalyzed gem-Cross-Dimerization of
Terminal Alkynes
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Jia-Feng Chen, Changkun Li*
Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs, School of Chemistry and
Chemical Engineering. Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240,
China.
KEYWORDS. Terminal Alkynes, Cross-dimerization, Cobalt, Triphos, 1,3-enynes
ABSTRACT. Transition-metal-catalyzed dimerization of two different terminal alkynes provides
an atom-economic synthesis of valuable conjugated 1,3-enynes. Despite many catalyst systems
developed, the state-of-the-art solutions are still limited to special alkynes. A practical catalyst,
which could be used to cross-dimerize general aryl alkynes and aliphatic alkynes, is still highly
desired. Herein we present the earth-abundant Co(II)-catalyzed highly gem-selective cross-
dimerization of aryl alkynes and aliphatic alkynes or gas acetylene under mild reaction conditions.
Conjugated 1,3-enynes with various useful functional groups can be prepared in high yields. The
applying of Co(OAc)2 and t-butyl group substituted triphos ligand is essential to distinguish the
alkynes at different steps and realize the gem-selectivity.
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INTRODUCTION
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The cross-coupling of two molecules with similar reactivities is a big challenge in organic
synthesis. An extremely sophisticated distinguishing between the two reaction partners has to be
designed to achieve the cross-coupling over homo-coupling.1 Terminal alkynes are very versatile
building blocks in organic synthesis, which could be used to prepare a variety of important organic
molecules.2 However, the precise control in the coupling of terminal alkynes is very challenging.
The oxidative cross-coupling of aryl alkynes and aliphatic alkynes has only been reported recently
with gold or Cu complexes, in which a discrimination of the acidities of alkynes by the catalysts
is the key for the cross-selectivity (scheme 1, A).3 Conjugated 1,3-enynes are not only found in
many natural products and biologically active molecules,4 but also very useful intermediates to
prepare aromatic rings, heteocycles, allenes and other structures.5 Among the many synthetic
methods, transition-metal-catalyzed dimerization of terminal alkynes provides an efficient and
atom-economic synthetic route to 1,3-enynes. The cross-dimerization of two different terminal
alkynes is more complicated than the oxidative cross-coupling.6 Besides the donor/acceptor
selection processes, the control of regioselectivity is another concern. Although several transition-
metals have been reported to catalyze the cross-dimerization of terminal alkynes, the state-of-the-
art solution is that only very special substrates can be utilized. Bulky silyl-group substituted
terminal alkynes as donor alkynes7 and propargylic alcohols or amines as better acceptor alkynes8
have to be applied to realize the cross-selectivity, but the scope of the alkynes is limited
accordingly (scheme 1, B). A practical cross-dimerization of more general aryl alkynes and
aliphatic alkynes is highly desirable.9 Herein, we report an earth-abundant-metal cobalt-catalyzed
highly selective cross-dimerization of sterically and electronically unremarkable aryl or alkenyl
alkynes and aliphatic alkynes to prepare a variety of gem-1,3-enynes with useful functional groups
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in high yields under mild reaction conditions (scheme 1, C). Moreover, simple gas acetylene could
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be utilized in this transformation.
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Scheme 1. The Cross-coupling of Two Different Terminal Alkynes.
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A:
Au Cu
Oxidative Cross-Coupling of Terminal Alkynes,
or
R1
H
H
R1
R2
R1
R2
R1
R2
Au or Cu
[O]
+
cross-coupling product
homo-coupling products
R2
B:
Pd Rh Ru Fe
or
1,3-Enyne synthesis by atom economic cross-dimerization,
R1
,
,
H
R2
donor alkyne
+
catalyst control
R2
or
R2
H
R1
R1
linear-Z or E
acceptor alkyne
gem
Challenge:
homo-dimerization avoiding
regioselectivity, gem or linear (Z, E)
donor/acceptor distinguishing
State-of-the-art solution:
X
R3Si
X = OH or NPg
H
as donor
as acceptor
C, This work
: Co(OAc)2/triphos-catalyzed cross-dimerization
Me
Me
Me
Co(OAc)2
R1
H +
H
R2
R2
triphos
P
R1
R1 = Ar, alkenyl
R2 = alkyl, H
PPh2
triphos
PPh2
earth-abundant cobalt
easily available ligand
broad function tolarence high product yields
To develop a selective cross-dimerization of two different terminal alkynes, the catalyst has to
control three processes in case of metal acetylide mechanism: 1) selective metal-acetylide
formation with one of the two terminal alkynes; 2) coordination of metal-acetylide with only the
other alkyne to avoid homo-dimerization; 3) regioselectivity in the acceptor alkyne (gem or linear)
(Figure 1). During our investigation on the Co(I)-catalyzed enol ester formation between alkynes
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and carboxylic acids,10 we observed the 1,3-enyne formation from phenylacetylene with
Co(OAc)2/triphos when no reducing Zn was added. We were aware that the OAc ligand in the
Co(II)/triphos complex may function as an internal base to promote the cobalt-acetylide formation.
The weakly basic acetate may help distinguish between two different terminal alkynes by the
acidity difference. The steric hindrance in the Co(OAc)2/triphos complexes could control the
coordination of the second alkynes. Bulky groups at phosphorus atoms as well as the backbone
structure in the triphos ligands are able to help select smaller aliphatic alkynes. The regioselectivity
of the products could be controlled by the steric factors in the ligands. Accordingly,
Co(OAc)2/triphos combination might be used to catalyze the selective cross-dimerization of aryl
alkynes and aliphatic alkynes.
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Selection 1
Selection 2
Selection 3
R1
R2
H
or
R2
R1
R2
H
H
R1
or
MLn
H
R1
MLn
R1
MLn
R2
R2
H
R1
The function of Co(OAc)2/triphos
Selection 1
internal acetate as a weak base
selective metal-acetylide formation with aryl alkynes
R2
R2
P
OAc
OAc
Selection 2
R1
P
Co
steric and electronic turning at R1 and R2
P
R2
R2
selective coordiantion with smaller aliphatic alkynes
Selection 3
the steric control of ligands backbone and substitutions
gem-selectivity
Figure 1. The Selective Processes and the Requirements for Selective Catalyst.
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RESULTS AND DISCUSSION
Condition Optimization
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To test our hypothesis, we started the study with phenylacetylene 1a and ester-functionalized
aliphatic alkyne 2a as the model substrates with 1.3 : 1 ratio (Table 1). With Co(OAc)2· 4H2O and
triphos L1 as catalyst, cross-dimerization product 3aa was isolated in 79% yield. Protic solvent
acetic acid was proven to be the key to avoid the oligomers formation. Small amount of head-to-
head regiomer 3aa' and homo-dimer 2a' were detected by comparation with samples synthesized
independently. To improve the selectivity, seven other triphos ligands (L2 to L8) were synthesized
and examined. When L2 with four Cy groups was used, the reaction becomes much slower, while
better regioselectivity was observed (entry 2). L3 with two phenyl rings in the skeleton leads to
higher regioselectivity than L1 (entry 3). However, the amount of homo-dimer 2a' increases. The
Cy groups in L4 slow down the reaction (61 % yield) and give better selectivity. The influence of
substitution at the middle P atom is also examined. Bulkier Cy and t-butyl groups in the triphos
ligand L5 and L6 lead to inhibition of undesired linear regiomer and homo-dimerization products
(entries 5 and 6). Nevertheless, more 3aa' and 2a' were obtained in case L7 with a smaller methyl
group was applied. Finally, L8 with five Cy groups makes this reaction be less reactive (entry 8).
The investigation of the homo-dimerization of 1a and 2a independently with different triphos
ligands further supports this trend (see SI). In the comparing experiments, [Rh(cod)Cl]2/L98c and
Pd(OAc)2/L108b, which are selective catalysts to cross-dimerize aryl alkyne (alkenyl alkyne) with
propargyl alcohols, are not able to cross-dimerize aryl alkyne and simple aliphatic alkynes
selectively (entries 9 and 10). The yield of cross-dimerization product 3aa could be further
improved to 90% when a 1 : 1 mixture of THF and acetic acid was used as the solvent, and 2.5
mol % of cobalt catalyst does not decrease the efficiency (entry 11).
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Table 1. Optimization of The Co(II)-Catalyzed Cross-dimerization Reaction of Terminal
Alkynesa
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R
Ph
R
H
H
5 mol% metal salts
+
R
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1a
L
5 mol%
Ph
Ph
3aa'
3aa
+
AcOH, 30 oC, 12 h
R
2a
2a'
R
R = (CH2)3CO2Me
R1
P
1
2
R1
P
L7
L8
, R = Me, R = Ph
1
2
PR2
PR2
, R = Cy, R = Cy
2
2
PR2
PR2
2
2
1
2
L3
L4
L5
L6
, R = Ph, R = Ph
OMe
1
2
, R = Ph, R = Cy
PPh3
P
1
2
1
2
3
L1
L2
, R = Cy, R = Ph
, R = Ph, R = Ph
OMe
1
2
1
2
L10
, R = t-Bu, R = Ph
L9
, R = Ph, R = Cy
entry
1
catalyst
L
yield(3aa) (%)b
3aa/3aa'/2a'c
23/4/1
37/0/1
30/1/6
68/0/1
12/0/1
25/0/1
24/3/8
45/0/1
9/2/1
Co(OAc)2· 4H2O
Co(OAc)2· 4H2O
Co(OAc)2· 4H2O
Co(OAc)2· 4H2O
Co(OAc)2· 4H2O
Co(OAc)2· 4H2O
Co(OAc)2· 4H2O
Co(OAc)2· 4H2O
[Rh(cod)Cl]2
L1
L2
L3
L4
L5
L6
L7
L8
L9
L10
L6
79
30
70
61
80
83
52
10
25
13
90
2
3
4
5
6
7
8
9d
10e
11f
Pd(OAc)2
10/1/8
Co(OAc)2· 4H2O
25/0/1
aConditions: 1a (0.65 mmol, 1.3 equiv), 2a (0.5 mmol, 1.0 equiv), AcOH (1.0 mL).
bIsolated yield. cThe ratio of 3aa/ 3aa'/2a' was determined with crude 1H NMR analysis.
din dichloromethane at 40 oC. ein benzene at rt. f2.5 mol% Co(OAc)2· 4H2O in 1: 1 THF/AcOH
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Scope of Alkynes
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With the optimized reaction condition in hand, the scope of the donor aryl alkynes was examined
(Scheme 2). A variety of aryl alkynes with functional groups at para-position on the phenyl ring
were checked firstly. Electron-rich t-Bu, MeO, and NHCOCH3 could be tolerated as shown in 3ba
to 3da. Halogen-substituted aryl alkynes react smoothly to give the cross-dimerization products
3ea to 3ga in high yields. Strong electron-withdrawing aldehyde, nitro, cyano and carboxylic acid
functions have no negative effect to the yields of the reactions (3ha to 3ka). Bromide at ortho- or
meta and free hydroxyl group at meta position can also be tolerated (3la, 3ma and 3na). Terminal
alkynes with 1-naththyl, 2 or 3-thiophenyl and 3-pyridyl groups were all transformed to the enynes
3oa to 3ra in high yields. Alkenyl alkynes could also react with aliphatic alkyne 2a to give the
dienynes 3sa to 3ua.
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The scope of acceptor aliphatic alkynes was further checked as shown in Scheme 3. Different
from the previous reports that only propargyl alcohols and amines can be used as acceptor alkynes,8
phenylacetylene 1a react with simple n-butyl and benzyl substituted alkynes to give the 1,3-enynes
3ab and 3ac in high yields. Branched cyclohexyl and cyclopropyl groups have no negative effect
to the yields of 3ad and 3ae. Various functional groups, cyano, hydroxyl, carboxylic acid and
phthalimide, can all be tolerated in 3af to 3ai. Primary, secondary and tertiary propargyl alcohols
could be converted to enynes smoothly (3aj to 3an). Free and Boc-protected propargyl amines as
well as propargyl ether participate in this cross-dimerization reaction as the acceptor alkynes (3ao
to 3aq). 3ar with a tosylate function is prepared in high yield, which can be used in further
alkylation transformation. Finally, diynes 2s and 2t could be transformed to the bis-enynes 3as
and 3at respectively when 2.5 equivalent phenylacetylene 1a was used.
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Scheme 2. The Scope of Donor-alkynesa
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1
R
H
2.5 mol% Co(OAc)2 4H2O
L6
2.5 mol%
+
H
THF/AcOH, 30 oC, 12 h
Me
R
MeO2C
2a
Me
Me
3ba-3ua
CO2Me
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P
L6
PPh2
PPh2
3ba
3ga
, 86%
R = CF3,
R = CHO,
R = NO2,
, 90%
R = t-Bu,
R = MeO,
R = NHCOCH3,
, 90%
3ha
, 89%
3ca
, 83%
3ia
, 81%
3da
b
3ea
, 91%
3fa
, 85%
3ja
, 85%
R = F,
R = Br,
R = CN,
b
3ka
R = COOH,
, 83%
R
CO2Me
Br
R
CO2Me
CO2Me
CO2Me
3oa
, 86%
b
b
3la
, 88%
3ma
, 80%
R = Br,
3na
, 86%
R = OH,
S
S
CO2Me
CO2Me
N
CO2Me
3ra
, 83%
3qa
, 75%
3pa
, 85%
OH
Me
3sa
, 83% CO2Me
CO2Me
3ta
, 83%
3ua
, 82% CO2Me
aConditions: 2a (0.5 mmol, 1.0 equiv), 1 (0.65 mmol, 1.3 equiv), THF/AcOH (1:1, 1.0 mL). bat 60 oC.
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Scheme 3. The Scope of Acceptor-alkynesa
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1a
2
Ph
R
H
2.5 mol % Co(OAc)2 4H2O
L6
2.5 mol %
R
+
THF/AcOH, 30 oC, 12 h
Me
Ph
H
Me
Me
3ab-3at
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P
L6
PPh2
PPh2
b
3af
R = CN,
, 82%
3ab
, 89%
, 92%
, 91%
R = n-C4H9,
3ac
3ad
R = Bn,
R = Cy,
R
3ag
R = CH2OH,
R = COOH,
, 88%
R
3
3ah
, 86%
Ph
Ph
Ph
3ae
R = cyclopropyl,
, 74%
3ai
, 91%
R = Nphth,
1
2
3aj
, 80%
R = R = H,
OH
1
2
OH
R1 R2
3ak
, 75%
R = H, R = Ph,
1
2
Ph
3al
, 83%
R = R = CH3,
1
2
3am
, 75%
R = CH3, R = vinyl,
3an
, 71%
Ph
Ph
R
OTs
R1 R2
Ph
Ph
3ar
, 86%
, 3ao
R = NHBoc , 79%
1
2
d
3as
, 71%
R = R = H,
c
, 3ap
, 71%
R = NH2
R1 = Ph, R2 = CO2Me
3aq
, 78%
R = OBn,
d
3at
, 75%
aConditions: 2a (0.5 mmol, 1.0 equiv), 1 (0.65 mmol, 1.3 equiv), THF/AcOH (1:1, 1.0 mL).
bat 60 oC. cCH3CN (1.0 ml) as solvent, 60 oC. d2.5 equivalent of 1a (1.25 mmol) was used.
Inspired by the possible acidity difference directed cross-selectivity, we further examined the
reaction of gas acetylene as a donor or acceptor alkyne. To the best of our knowledge, there is no
cross-dimerization of simple acetylene gas with other alkynes before. Considering the acidity
sequence (aryl alkyne > acetylene > alkyl alkyne), simple acetylene could be used as an acceptor
to react with aryl alkynes or a donor with aliphatic alkynes. Higher reaction temperature and
catalyst loading are required to convert phenylacetylene 1a to enyne 5 probably because of the
easier coordination of small gas acetylene with cobalt complex. The scope of aryl alkyne is
summarized in Scheme 4. Various functional groups at different positions on the phenyl ring could
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be tolerated and compounds 5a to 5g were isolated in high yields. Small amount of 5' with two
acetylene coupled could be observed and the ratio of 5’ increases for electron-deficient aryl alkynes
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(5e to 5g). A vinyl group was also installed on the 1-naphthyl, 3-pyridyl and alkenyl alkynes
smoothly (5h to 5k). 25% acetate of 5k was isolated under the standard condition, which comes
from the further esterification with solvent acetic acid. The reactions between acetylene (donor
alkyne) and alkyl alkynes produces only trace amount of desired 1,3-enynes, probably because
acetylene itself is easier to react with the possible cobalt-acetylide intermediate than alkyl alkynes.
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Scheme 4. The scope of gas acetylene as acceptor-alkynea
5 mol % Co(OAc)2 4H2O
L6
5 mol %
R
H + H
H
or
Ar
AcOH, 60 oC, 12 h
Ar
1
4
5a' 5k'
-
5a 5k
-
Me
Me
Me
P
L6
PPh2
PPh2
5a
R = H, , 85%, 14.5 : 1
5e
R = 4-NO2, , 89%, 6.5 : 1
5b
R = 4-MeO, , 78%, 14.5 : 1
5f
R = 4-CN, , 76%, 2.5 : 1
5c
R = 3-OH, , 83%, 13.5 : 1
5g
R = 4-CHO, , 79%, 4.5 : 1
R
5d
R = 4-Br, , 85%, 10.5 : 1
OH
N
b
5h
, 83%, 13.5 : 1
5i
, 80%, 8.5 : 1
5j
, 76%, 9 : 1
5k
, 52% , 12.5 : 1
aConditions: 1 (1 mmol, 1.0 equiv), balloon pressure acetylene, AcOH (2.0 mL). b25% of acetate of 5k was isolated.
Large Scale Synthesis
To prove the practicality of this cobalt-catalyzed cross-dimerization reaction, gram-scale
synthesis of different 1,3-enynes was conducted (scheme 5). 50 mmol of 1-hexyne 2c was
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converted to 7.62 g of 3ac (83%) with 60 mmol of phenyl acetylene 1a. The catalyst loading could
be decreased to 1 mol % when the reaction was run at 60 oC. Similarly, 3av could be prepared in
7 gram scale and the existence of free hydroxyl group requires 2 mol% cobalt catalyst. Finally,
enyne 5a was synthesized in 2 gram scale with balloon pressure acetylene and 2 mol% catalyst.
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Scheme 5. Gram-scale synthesis.
2 mol % Co(OAc)2 4H2O
L6
1 mol % Co(OAc)2 4H2O
L6
2 mol %
OH
1 mol %
n-Bu
OH
2c
2v
H
n-Bu
THF/HOAc, 60 oC, 12 h
Ph
THF/HOAc, 60 oC, 12 h
Ph
3av
3ac
, 83%, 7.62 g
, 82%, 7.06 g
Ph
H
50 mmol scale
50 mmol scale
1a
2 mol % Co(OAc)2 4H2O
L6
(ballon)
2 mol %
H
H
HOAc, 60 oC, 12 h
5a
, 79%, 1.99 g
20 mmol scale
Ph
Mechanism Studies
D-Labeling experiments were conducted to explore the reaction mechanism (scheme 6).
When both D-labeled 1a-D and 2u-D were subjected to the standard condition in acetic acid and
THF, 3au was isolated with 92% yield, in which the hydrogen (Ha) cis to alkyne is 98% proton
(eq 1). A protonation of the cobalt-carbon bond by the solvent acetic acid may occur. Meanwhile,
the hydrogen (Hb) cis to alkyl group is assigned to be 27% proton and a slow exchange with acetic
acid for the aliphatic terminal alkyne is proposed. On the contrast, when the reaction of 1a and 2u
was carried out in AcOD, only 56% of 3au was obtained after the same reaction time (12 hours)
(eq 2). The relatively slow reaction in AcOD may suggest that the protonation with acetic acid is
involved in the rate-determine step. The 8% of D incorporation of Hb could be explained by the
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slower exchange of aliphatic alkyne with solvent acetic acid. 37% H incorporation at Ha may come
from the small amount of water and 1a, although much more D+ is in the solvent AcOD. To exclude
the possibility that aromatic alkynes have the fast H/D exchange with solvent and then protonate
the alkenyl-cobalt intermediate, reaction of 1c-D and 2a was conducted in acetic acid (eq 3). After
40 minutes, 3ca could be isolated in 69% yield and 30% of 1c was recovered with 80% D/H
exchange. No any D-incorporation in 3ca further supports the protonation with solvent acetic acid.
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Scheme 6. D-Labeling Experiments
Ph
1a-D
D
H
Ph
2.5 mol% Co(OAc)2 4H2O
L6
THF/AcOH, 30 oC, 12 h
2.5 mol%
+
Ha(D)
(1)
(2)
98% H, 2% D
n-C8H17
D
H
n-C8H17
3au
Hb(D)
2u-D
27% H, 73% D
, 92%
Ph
1a
Ph
2.5 mol% Co(OAc)2 4H2O
L6
2.5 mol%
+
THF/AcOD, 30 oC, 12 h
a
37% H, 63% D
92% H, 8% D
H (D)
n-C8H17
n-C8H17
2u
b
H (D)
3au
, 56%
MeO2C
100% H
Hb(D)
1c-D
D>95%
D
C H
4-MeO
6
4
2.5 mol% Co(OAc)2 4H2O
L6
2.5 mol%
Ha(D)
+
H
THF/AcOH, 30 oC, 40 min
(3)
100% H
MeO
MeO2C
3ca
, 69%
3
2a
+
C H
4-MeO
H(D)
80% H, 20% D
30% recovery
6
4
To get more insight into the reaction mechanism, the single crystal X-ray analysis of the catalyst
was conducted. Co(OBz)2-L6 was selected for its better solubility in organic solvents than
Co(OAc)2-L6. A crystal of Co(OBz)2-L6 was obtained from THF and hexane. In the crystal
structure of Co(OBz)2-L6 as shown in Scheme 7 (left), the cobalt complex adopts a 5-coordinate
square pyramidal geometry, with two acetate groups, one of the side phosphorus atom and the
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middle phosphorus atom of L6 in one plane.11 The axial position was occupied by the other side
phosphorus atom in L6. The carboxylates are bound to cobalt in a 1 mode. Another complex was
isolated when Co(OBz)2 and L6 were mixed in the presence of air. The crystal structure of the
complex reveals that one of the side phosphorus atom was oxidized. In the solid state, the complex
OL6·Co(OBz)2·H2O adopts a distorted octahedral geometry, with the phosphine oxide oxygen
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and the water oxygen at the axial direction (scheme 7, right). OL6·Co(OBz)2·H2O is not active
in the cross-dimerization reaction, which could explain why the reaction cannot be carried out in
the air.
Scheme 7. The crystal structures of Co(OBz)2-L6 and O=L6·Co(OBz)2·H2O with thermal
ellipsoids at 30% probability. All hydrogens and solvent were omitted for clarity.
Ph
P
O
Ph
P
Ph
Ph
Ph
Ph
BzO
Ph
P
P
P
P
t-Bu
OBz
t-Bu
OBz
Ph
BzO
Co
OH2
Co(OBz)2 H2O
Co
L6
Co(OBz)2-
L6
O=
Mechanistic Proposal
Based on the experiments above and literature reports, one catalytic cycle was proposed in
scheme 8. One of the acetate in the 17-electron complex A dissociates to form a cationic complex
A'. Aryl alkyne 1 and aliphatic alkyne 2 compete to coordinate with complex A' to form cationic
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intermediate B. Deprotonation of terminal alkyne assisted by inter- or intramolecular acetate
generates the Co(II)-acetylide C and release acetic acid.12 More acidic aryl or alkenyl alkyne 1 is
easier to participate in this step, which accounts for the facts that 1 reacts as the donor alkyne and
only trace amount of homo-dimerization products of aliphatic alkynes 2 can be detected. An
equilibrium between C and cationic C' exists. Another alkyne further coordinates with
intermediate C' to form D. At this time, less hindered aliphatic alkyne 2 is preferred because of
the steric hindrance in L6. The bulky substituents on the triphos ligands, especially the t-Bu group
at the middle P, make the Ar and R groups in 1 and 2 locate at the less hindered direction, which
is crucial for the gem-selectivity. The regioselectivity may decrease when R is relatively bigger
and t-Bu group in L6 was replaced by smaller group. Alkenyl-cobalt intermediate E was formed
by migrative insertion of Co-acetylide bond to alkyne 2 and the coordination of acetate anion.
From E, further migrative insertion into alkyne 2 could generates trimer or oligomers.13 The
applying of acetic acid as solvent is the key for the selective dimerization. Protonation of E with
acetic acid releases the products 3 and regenerates the catalyst A. The attempts to isolate
intermediates C and E were not successful. However, high resolution ESI-MS was applied to
provide supports for these possible reaction intermediates (see SI). When phenylacetylene 1a was
added into the mixture of Co(OAc)2 and L6, a peak at 829.1976 could be observed, which matches
with the radical cation peak of intermediate C (829.1964, calculated). A low peak at 955.2661
could be found after the addition of acceptor alkyne 2a, which indicates the formation of
intermediate E (955.2645, calculated). Complex A could be oxidized in air to form inactive
complex F, which was characterized by single crystal X-ray diffraction analysis.
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Scheme 8. Mechanistic Proposal
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-
(D)H
+
AcO
3
Ph
P
Ph
P
Ph
Ph
Ph
Ph
Ar
P
Ph
R
Ph
Ph
Ph
P
P
Ph
AcO
t-Bu
OAc
P
P
P
P
Co
A'
Ph
AcO
t-Bu
Co
Co
t-Bu
9
H
OAc
A
, confirmed by X-ray
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AcOH(D)
Ar
H
R
1
O2
H2O
Ar
-
+
AcO
E
E
, detected by HR-ESI
Ph
Ph
Ph
Ph
, 955.2661, observed
955.2645, calculated
P
P
Ph
O
P
P
Ph
Ph
AcO
t-Bu
H
Co
P
P
Ph
AcO
t-Bu
OAc
Co
OH2
B
Ar
AcOH
F
, confirmed by X-ray
-
+
AcO
Ph
Ph
Ph
-
+
Ph
P
AcO
P
2
Ph
Ph
Ph
H
R
Ph
P
P
P
P
P
P
t-Bu
t-Bu
Ph
Ph
Ph
Ph
Co
Co
H
P
OAc
t-Bu
Co
Ar
Ar
C
C
R
, detected by HR-ESI
Ar
C'
D
, 829.1976, observed
829.1964, calculated
In conclusion, we have developed a Co(OAc)2/triphos catalyst system for the selective cross-
dimerization between aryl or alkenyl alkynes and aliphatic alkynes. Conjugated 1,3-enynes with a
variety of useful functional groups can be prepared in high yields under mild condition. Gas
acetylene is also applied to this atom-economic cross-dimerization reaction for the first time. The
use of cobalt acetate and easily available bulky tridentate phosphine ligands is crucial to
distinguish alkynes at different reaction steps and control the regioselectivity. The structure of the
catalyst was elucidated by single crystal X-ray diffraction analysis. D-Labeling experiments and
high-resolution ESI-MS were applied to support the proposed mechanism. Extension of acceptors
and a chiral version of the triphos ligand are under investigation in our group.
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ASSOCIATED CONTENT
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AUTHOR INFORMATION
Corresponding Author
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*Email: chkli@sjtu.edu.cn
Notes
The authors declare no competing financial interests.
Supporting Information. Detailed experimental procedures, characterization data, copies of 1H,
13C NMR spectra, and X-ray crystal structure. This material is available free of charge via the
Internet at http://pubs.acs.org. CCDC 1897113 and 1897114 contain the supplementary crystallo-
graphic data for this paper. These data can be obtained free of charge via
www.ccdc.cam.ac.uk/data_request/cif. brief
ACKNOWLEDGMENT
This work is supported by the “Thousand Youth Talents Plan”, National Natural Science
Foundation of China (NSFC) (Grant 21602130), and Shanghai Jiao Tong University.
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2.5 mol % Co(OAc)2 4H2O
L
2.5 mol %
R1
H
R2
+
H
R2
THF/AcOH, 30 oC, 12 h
Me
R1
R1 = Ar, alkenyl R2 = alkyl, H
up to 92% yield
Me
Me
9
P
earth-abundant catalyst
broad function tolarence
easily available ligand
high product yields
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L
PPh2
PPh2
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