Synthesis of trans-disubstituted alkenes by cobalt-catalyzed reductive coupling of terminal alkynes with activated alkenes

Article abstract of DOI:10.1002/chem.201200779

A cobalt-catalyzed reductive coupling of terminal alkynes, RC≡CH, with activated alkenes, R'CH=CH₂, in the presence of zinc and water to give functionalized trans-disubstituted alkenes, RCH=CHCH₂CH ₂R', is described. A variety of aromatic terminal alkynes underwent reductive coupling with activated alkenes including enones, acrylates, acrylonitrile, and vinyl sulfones in the presence of a CoCl₂/P(OMe) ₃/Zn catalyst system to afford 1,2-trans-disubstituted alkenes with high regio- and stereoselectivity. Similarly, aliphatic terminal alkynes also efficiently participated in the coupling reaction with acrylates, enones, and vinyl sulfone, in the presence of the CoCl₂/P(OPh)₃/Zn system providing a mixture of 1,2-trans- and 1,1-disubstituted functionalized terminal alkene products in high yields. The scope of the reaction was also extended by the coupling of 1,3-enynes and acetylene gas with alkenes. Furthermore, a phosphine-free cobalt-catalyzed reductive coupling of terminal alkynes with enones, affording 1,2-trans-disubstituted alkenes as the major products in a high regioisomeric ratio, is demonstrated. In the reactions, less expensive and air-stable cobalt complexes, a mild reducing agent (Zn) and a simple hydrogen source (water) were used. A possible reaction mechanism involving a cobaltacyclopentene as the key intermediate is proposed. Copyright

Full text of DOI:10.1002/chem.201200779

FULL PAPER
DOI: 10.1002/chem.201200779
Synthesis of trans-Disubstituted Alkenes by Cobalt-Catalyzed Reductive
Coupling of Terminal Alkynes with Activated Alkenes
Subramaniyan Mannathan and Chien-Hong Cheng*[a]
Abstract: A cobalt-catalyzed reductive
Similarly, aliphatic terminal alkynes
also efficiently participated in the cou-
pling reaction with acrylates, enones,
and vinyl sulfone, in the presence of
by the coupling of 1,3-enynes and acet-
ACHTUNGTRENNyUNG lene gas with alkenes. Furthermore, a
ꢀ
coupling of terminal alkynes, RC CH,
with activated alkenes, R’CH=CH2, in
the presence of zinc and water to give
functionalized trans-disubstituted al-
kenes, RCH=CHCH2CH2R’, is descri-
bed. A variety of aromatic terminal al-
kynes underwent reductive coupling
with activated alkenes including
enones, acrylates, acrylonitrile, and
vinyl sulfones in the presence of a
phosphine-free cobalt-catalyzed reduc-
tive coupling of terminal alkynes with
enones, affording 1,2-trans-disubstitut-
ed alkenes as the major products in a
high regioisomeric ratio, is demonstrat-
ed. In the reactions, less expensive and
air-stable cobalt complexes, a mild re-
ducing agent (Zn) and a simple hydro-
gen source (water) were used. A possi-
ble reaction mechanism involving a co-
baltacyclopentene as the key inter-
mediate is proposed.
the CoCl2/P
ing a mixture of 1,2-trans- and 1,1-di-
substituted functionalized terminal
ACHTUNGRTEN(NUNG OPh)3/Zn system provid-
AHCTUNGTRENNUNG
alkene products in high yields. The
scope of the reaction was also extended
Keywords: alkenes · cobalt · enyne
coupling · ligands · reductive cou-
pling
CoCl2/PACHTUNGTRENNUNG(OMe)3/Zn catalyst system to
afford 1,2-trans-disubstituted alkenes
with high regio- and stereoselectivity.
Introduction
(Scheme 1a).[5a] Since then, we have demonstrated the re-
ductive coupling of various alkenes with different p compo-
nents including different alkynes, alkenes, imines, allenes,
and nitriles.[5b–i] An important finding from Montgomeryꢀs
group involving nickel catalysis provided an efficient
method for the reductive coupling of alkynes with enones,
and alkynes with enals, to synthesize di- and trisubstituted
alkenes (Scheme 1b).[6] In the meantime, Micalizio et al.
also reported a titanium alkoxide mediated bimolecular cou-
pling of internal alkynes with unactivated alkenes to synthe-
size trisubstituted alkenes and polyenes (Scheme 1c).[7] Re-
cently, Hilt and Treutwein found an Alder-ene-type coupling
of internal alkynes and terminal alkenes to afford 1,4-dienes
in the presence of a cobalt catalyst.[8] In addition to these in-
termolecular versions, intramolecular reductive cyclization
of enynes is also known in the literature.[5b,9] In this case, if
terminal alkynyl groups were employed, the reductive cycli-
zation products containing an exo 1,1-disubstituted instead
of an endo 1,2-disubstituted alkenyl group were obtained.
In the reported metal-catalyzed intermolecular coupling
reactions of alkynes with alkenes, the scope of alkynes was
predominantly limited to internal alkynes. The coupling of
internal alkynes with alkenes generally leads to trisubstitut-
ed alkenes (Scheme 1) and hence, the synthesis of trans-di-
Alkenes are useful compounds in a large number of synthet-
ic applications and also found in the structure of numerous
natural products and pharmaceutical agents.[1] In recognition
of the importance of these compounds, their regio- and ster-
eoselective preparation has been a great challenge, and
many ingenious and selective methods have been devised
over the years.[2] Nevertheless, there is still a need for a
mild, convenient, and highly selective method for the syn-
thesis of di-, tri-, and tetrasubstituted alkenes.
Transition-metal-catalyzed intermolecular coupling of al-
kynes and alkenes to regio- and stereoACTHNUTRGNEUNGselectively give substi-
tuted alkenes is a highly atom-economic and environmental-
ly friendly method in organic synthesis.[3] In this reaction,
Alder-ene and reductive coupling products are of two famil-
iar types. Trostꢀs group extensively studied the intermolecu-
lar Alder-ene-type reaction of alkynes with alkenes for the
synthesis of 1,4-dienes by using ruthenium complexes as the
catalyst.[4] In 2002, we reported a cobalt-catalyzed intermo-
lecular reductive coupling of internal alkynes with activated
alkenes to afford trisubstituted alkenes by using water as
the proton source and zinc as the reducing agent
AHCTUNGTREGsNNNU ubstituted alkenes remains demanding. Earlier reports
[a] Dr. S. Mannathan, Prof. Dr. C.-H. Cheng
Department of Chemistry
from the literature illustrate that functionalized trans-disub-
stituted alkenes can also be obtained by conjugate addition
of vinyl metal species to activated alkenes including enones
and enoates.[10] These reactions required stoichiometric
amounts of vinyl metal species that were prepared either by
hydrometalation of terminal alkynes (zirconium is the most
National Tsing Hua University
Hsinchu, 30013 (Taiwan)
Fax : (+886)3572-4698
E-mail: chcheng@mx.nthu.edu.tw
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201200779.
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Scheme 1. Previous reports on the reductive coupling of alkynes with alkenes. COD=1,5-cyclooctadiene.
common) or metal–halogen exchange of vinyl halides.[11]
Thus, it would be highly significant for organic synthesis if
mild and convenient methods with a wide scope of sub-
strates could be developed for the direct coupling of termi-
nal alkynes with alkenes to synthesize stereoselective 1,2-
disubstituted alkenes in one pot without utilizing either hy-
drometalation or a metal–halogen exchange strategy.[12]
Our continuing interest in the metal-catalyzed reductive
coupling of p-components[5,13] prompted us to take the chal-
lenge to find a method for the intermolecular reductive cou-
pling of terminal alkynes with activated alkenes. Herein, we
report that cobalt complexes with suitable ligands can cata-
lyze the reductive coupling of terminal alkynes and activat-
ed alkenes to give functionalized trans-disubstituted alkenes
in good to excellent yields.[14]
but CoBr2 and CoI2 did not afford the reductive coupling
product (Table 1, entries 3–5). Encouraged by this result, we
next examined the reaction in the presence of various types
of phosphine ligands with CoCl2 (10 mol%). Among them,
the electron-deficient monodentate phosphine ligands
Table 1. Effect of cobalt complexes on the reductive coupling of phenyl
acetylene (1a) with ethyl acrylate (2a).[a]
Entry
Catalyst
[CoI2A(PPh3)2]
[CoI2A(dppe)]
CoI2
CoBr2
CoCl2
CoCl2
CoCl2
CoCl2
CoCl2
CoCl2
CoI2
T [8C]
Ligand
Yield [%][b,c]
1
2
3
4
5
6
7
8
9
G
N
80
60
60
60
60
60
60
60
60
40
40
40
3PPh3
–
–
–
–
8
R
–
–
–
–
Results and Discussion
5P
5P
5P
5P
5P
5P
2P
N
26
31
40
61
93 (89)
87
73
Optimization studies: In the search for the effective catalytic
conditions, we examined the reaction with various cobalt
10
11
12
complexes (10 mol%) including [CoI
2ACHTUNGTNERNUG(PPh3)2], [CoI2ACHTUNGTERN(NUGN dppe)],
CoCl2
[CoCl2A(PPh3)2], and [CoCl2A(dppe)] (dppe=1,2-bis(diphenyl-
C
CHTUNGTRENNUNG
phosphino)ethane; Table 1, entries 1 and 2). Unfortunately,
all the phosphine complexes afforded only homocyclotri-
ACHTUNGTRENNUNGmerization products of 1a and failed to provide the coupling
product 3aa. We then carried out the reductive coupling of
1a and 2a in the presence of simple cobalt(II) halides. To
our surprise, CoCl2 was effective, giving 3aa in 8% yield,
[a] Reaction conditions: phenylacetylene (1a; 1.00 mmol), ethyl acrylate
(2a; 1.50 mmol), cobalt complex (0.10 mmol, 10 mol%), ligand (0.30–
0.50 mmol, 30–50 mol%), Zn (2.75 mmol), H2O (1.00 mmol), CH3CN
(2.00 mL), at 40–808C for 16 h. [b] Yields were measured from the crude
products by the 1H NMR spectroscopic integration method by using me-
sitylene as an internal standard. [c] Isolated yield is provided in parenthe-
sis.
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Synthesis of trans-Disubstituted Alkenes
FULL PAPER
Table 2. Results of cobalt-catalyzed reductive coupling of terminal
(50 mol%) PACHTUNGTRENNUNG(2-furyl)3, PACHTUNGTRENGU(N OPh)3, PACHTUNGERTNNG(NU O-nBu)3, and PACTHNUGTREN(NUNG OMe)3
alkyne 1a with various activated alkenes 2a–j.[a]
were active in providing the reductive coupling product 3aa
in 26, 31, 40, and 61% yields, respectively (Table 1, en-
tries 6–9). In all these reactions, the homocyclotrimerization
products of 1a were observed as the major side products. To
suppress these products and to increase the yield of 3aa, the
reaction was carried out at a lower temperature, 408C, for
Entry
1
2
Product 3
Yield [%][b]
(3/3’)
AHCTUNGTRENNUNG
16 h in the presence of PACHTNUTRGNE(UNG OMe)3 with CoCl2. As expected,
85
78
the reductive coupling product 3aa was observed in 93%
1H NMR spectroscopic yield (89% isolated yield) with a
minor amount of the homotrimerization products of 1a
(Table 1, entry 10). A further decrease of the temperature
led to lower yield. From these optimization studies, it is re-
vealed that the reaction temperature and the nature of the
phosphine ligand affect the product yield. Particularly, the
2
coordination of the electron-deficient PACTHNURTGNENG(U OMe)3 ligand to the
3
4
85
cobalt center plays a key role to suppress the formation of
homotrimerization products of 1a even at lower tempera-
tures.
The reaction is highly regio- and stereoselective with the
b-carbon atom of the acrylate group attached to the unsub-
stituted terminal alkyne carbon atom and the phenyl and
ACHTUNGTRENNUNG(CH2)2CO2Et groups are trans to each other. In this reac-
tion, water acts as the proton source and zinc acts as the re-
ducing agent. Based on these optimization studies, we chose
83[c]
87[c]
5
6
7
AHCTUNGTRENGN(UN >95:5)
90[c]
(>95:5)
the conditions CoCl2 (10 mol%), PACHTNUTRGNE(NUG OMe)3 (50 mol%), Zn
G
(2.75 mmol), and H2O (1.00 mmol) in CH3CN at 408C for
16 h for the reductive coupling of aromatic terminal alkynes
with activated alkenes (Table 2).
91[d]
AHCTUNGTRENGN(UN >95:5)
Reductive coupling of phenyl acetylene (1a) with activated
alkenes (2b–j):[15] In addition to ethyl acrylate (2a), other
acrylates, such as methyl acrylate (2b) and n-butyl acrylate
(2c) under the optimized reaction conditions, also efficiently
reacted with 1a to provide reductive coupling products 3ab
and 3ac in 85 and 78% yields, respectively (Table 2, en-
tries 1 and 2). To explore the scope of the reaction, we next
examined the reaction of various activated alkenes 2d–j
with 1a under the optimized reaction conditions (Table 2,
entries 3–5). Phenyl vinyl sulfone (2d) provided the coupling
product 3ad in 85% yield (Table 2, entry 3). Likewise,
8
9
85[d]
89[d]
[a] Unless otherwise mentioned, all the reactions were carried out by
using terminal alkynes 1 (1.00 mmol) and alkenes 2 (1.50 mmol) in the
presence of CoCl2 (10 mol%), PACHTUNTRGNE(UNG OMe)3 (50 mol%), Zn (2.75 mmol), and
H2O (1.00 mmol) in CH3CN (2.00 mL) at 408C for 16 h. [b] Isolated
yields; only regioisomer 3 was observed, unless otherwise mentioned.
[c] The reaction was carried out in the presence of ZnI2 (30 mol%).
[d] AgSbF6 (15 mol%) and ZnI2 (15 mol%) were used instead of ZnI2
(30 mol%).
acryloACHTUNGTRENNUNGnitrile (2e) also reacted with 1a in the presence of a
catalytic amount of ZnI2 to afford 3ae in 83% yield
(Table 2, entry 4). Without ZnI2, product 3ae was obtained
only in 71% yield.
Reaction of 1a with ethyl vinyl ketone (2 f) under the
CoCl2/PACHTUNGTRENNUNG(OMe)3 precatalyst system did not afford the reduc-
tive coupling product 3af. However, in the presence of a cat-
alytic amount of ZnI2,[5b] the reaction proceeded well to fur-
nish 3af in 83% yield (Table 2, entry 5). Notably, it also
gave 1,1-disubstituted alkene 3af’ in approximately 4%
yield. Similarly, methyl vinyl ketone (2g) gave 3ag in high
yield (Table 2, entry 6). Substituted vinyl ketones, 2h and 2i
also worked well providing coupling products 3ah and 3ai
in 91 and 85% yields, respectively (Table 2, entries 7 and 8).
Likewise, cyclic enone 2-cyclohexenone (2j) participated to
give 3aj in 89% yield (Table 2, entry 9). It is important to
mention that for the reaction of 2h–j a catalytic amount of
AgSbF6 and ZnI2 is required to further improve the product
yield. Without AgSbF6, the products 3ah, 3ai, and 3aj were
obtained in 85, 75, and 82% yields, respectively. The pres-
ence of AgSbF6 and ZnI2 are essential for this reaction,
which indicates that a cationic cobalt complex works as an
active catalytic species. It is necessary to point out that the
application of a silver salt in the present reductive coupling
reaction is restricted only to substituted enones, whereas in
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S. Mannathan and C.-H. Cheng
Table 3. Results of cobalt-catalyzed reductive coupling of terminal alkynes 1a–p with
various activated alkenes 2a–j.[a]
the case of unsubstituted enones, no improvement
in the yield was observed. It is noteworthy that
the present catalytic reductive coupling reaction is
applied to various alkenes including vinyl ketones,
acrylates, acrylonitrile, and vinyl sulfone, whereas
in the reported nickel-catalyzed reductive coupling
reaction, only enones and enals were demonstra-
ted.[6c]
Entry
1
1
2
Product 3
Yield [%][b]
(3/3’)
94[c]
ACHTUNGTRENNUNG(>95:5)
2 f
Reductive coupling of terminal alkynes (1b–q)
with activated alkenes (2b–j): To evaluate the
scope of the reductive coupling reaction of termi-
nal alkynes with alkenes, we examined a range of
aromatic terminal alkynes under the optimized re-
action conditions. As expected, the CoCl2/
P(OMe)3 system showed good compatibility with
both halo-substituted and electron-donating-
group-substituted aromatic terminal alkynes (1b–
e) affording the respective products (3bf, 3cf, 3dg,
and 3ed) in good to excellent yield (Table 3, en-
tries 1–4). Correspondingly, para-tolylacetylene
(1 f) gave the product 3 fa in 92% yield (Table 3,
entry 5). 2-Ethynyl-6-methoxynaphthalene (1g)
provided the disubstituted alkene 3gb in 82%
yield (Table 3, entry 6). Heteroaromatic alkyne 3-
ethynylthiophene (1h) coupled with 2 f to furnish
3hf in good yield (Table 3, entry 7). Similarly, di-
91[c]
ACHTUNGTRENNUNG(>95:5)
2
2 f
2g
83[c]
ACHTUNGTRENNUNG(>95:5)
3[f]
4
5
2d
2a
88
92
ACHTUNGTRENNUNGsubstituted aromatic terminal alkynes including 1i,
1j, and 1k provided the corresponding products
3if–kf in 85–91% yields (Table 3, entries 8–10).
Aliphatic terminal alkynes also successfully par-
ticipated in the reductive coupling reactions. How-
ever, a different combination of CoCl2 (10 mol%)
6
7
8
2b
2 f
2 f
82
88[c]
ACHTUNGTRENNUNG(>95:5)
with triphenyl phosphite PACHTUNRGTNEUNG(OPh)3 (20 mol%) is re-
quired to achieve the coupling reaction in high
product yield. Thus, the reaction of 1-hexyne (1l)
with acrylate (2a) in the presence of the CoCl2/
P(OPh)3 system afforded regioisomeric reductive
coupling products 3la/3la’ in 85% isolated yield in
a 50:50 regioisomeric ratio (Table 3, entry 11). Ex-
citingly, when 1-hexyne (1l) was treated with 2-cy-
clohexenone (2j), a better regioselectivity of 3lj/
3lj’ was observed, that is, an 87:13 ratio, with 82%
yield (Table 3, entry 12). In a similar fashion, bulk-
ier aliphatic alkyne, 3,3’-dimethyl-1-butyne (1m)
furnished 1,2-trans-disubstituted alkene 3mj exclu-
sively in 87% yield (Table 3, entry 13). An aliphat-
ic terminal alkyne bearing a functional group was
also tolerated in the reaction. Thus, hex-5-yn-1-ol
(1n) reacted with 2 f to give the respective cou-
pling products 3nf/3nf’ in 88% yield with a regio-
85[c]
ACHTUNGTRENNUNG(>95:5)
87[c]
ACHTUNGTRENNUNG(>95:5)
9
2 f
2 f
91[c]
ACHTUNGTRENNUNG(>95:5)
10
85
11[d]
2a
2j
ACHTUNGTRENNUNG
ACHTUNGTRENNUNGisomeric ratio of 50:50 (Table 3, entry 14). Enynes
effectively participated in the reductive coupling
reaction and afforded 1,3-dienes in nearly single
regioisomeric form. For example, 1-ethynyl cyclo-
hexene (1o) and 2-methylbut-1-en-3-yne (1p) un-
derwent highly regioselective coupling with 2d to
12[d]
1l
ACHTUNGTRENNUNG(87:13)
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Synthesis of trans-Disubstituted Alkenes
FULL PAPER
lytic reaction is likely initiated by the reduction of
CoII to CoI by Zn dust. Coordination of 1a and 2a
to the CoI center followed by oxidative cyclization
then gives cobaltacyclopentene intermediate 5.
Protonation of 5 by water affords reductive cou-
pling product 3aa and a CoIII species that is re-
duced by Zn to generate CoI. A similar reaction
mechanism is also expected for the reductive cou-
pling of other terminal alkynes with alkenes. Inter-
mediate 5’ accounts for the formation of products
3’.
Table 3. (Continued)
Entry
1
2
Product 3
Yield [%][b]
(3/3’)
13[d]
2j
87[e]
88[c]
14[d]
15[d]
2 f
AHCTUNGTRENNUNG
Reductive coupling of terminal alkynes (1) with
enones (2) by using [CoCl2ACTHUNTGRNEUNG(neo)]: During the
2d
AHCTUNGTRENNUNG
course of our investigation on reductive coupling
of terminal alkynes with alkenes, we found that
the phosphine-free cobalt catalyst system [CoCl2-
92
AHCTUNGTRENGN(UN >95:5)
16[d]
17[d]
2d
2d
AHCTUNGTRENNUNG
(neo)][16] (neo=neocuproine=2,9-dimethyl-1,10-
77
phenanthroline) effectively catalyzed the reductive
coupling of terminal alkynes with enones, affording
1,2-trans-disubstituted alkenes as the major prod-
ucts in a high regioisomeric ratio (Scheme 3, and
see Table 2 for the structures). This catalyst system
significantly decreased the catalyst loading to
5 mol% and afforded the 1,2-trans disubstituted al-
kenes 3kj and 3lj exclusively in single isomeric
form. Moreover, it also shows high regioselectivity
[a] Unless otherwise mentioned, all the reactions were carried out by using terminal
alkynes 1 (1.00 mmol) and alkenes 2 (1.50 mmol) in the presence of CoCl2 (10 mol%),
PACHTUNGTRENNUNG(OMe)3 (50 mol%), Zn (2.75 mmol), and H2O (1.00 mmol) in CH3CN (2.00 mL) at
408C for 16 h. [b] Isolated yields; only regioisomer 3 was observed, unless otherwise
mentioned. [c] The reaction was carried out in the presence of ZnI2 (30 mol%).
[d] For entries 11–17, PACHTUNGTRENNUNG(OPh)3 (20 mol%) was used as the ligand instead of PACHTUGNTREN(NUGN OMe)3.
[e] AgSbF6 (15 mol%)+ZnI2 (15 mol%) were used instead of ZnI2 (30 mol%). [f] A
trace amount of debrominated reductive coupling product was also observed.
give 3od and 3pd in 87 and
92% yield, respectively, with a
regioisomeric ratio of >95:5
(Table 3, entries 15 and 16). Fi-
nally, the scope of the reaction
was extended by coupling 2d
with acetylene gas (1q) to
afford the terminal alkene 3qd
in
77%
yield
(Table 3,
Scheme 3. Synthesis of 1,2-trans-disubstituted alkenes by using [CoCl2ACTHNUTRGNE(NUG neo)] as the catalyst system.
entry 17).
Proposed mechanism: A possi-
ble reaction mechanism for the present cobalt-catalyzed re-
ductive coupling reaction is proposed in Scheme 2. The cata-
for the coupling of aromatic terminal alkynes with enones.
However, the [CoCl2A(neo)] system is limited only to enones
CTHUNGTRENNUNG
and it is not suitable for the coupling of terminal alkynes
with acrylates, acrylonitrile, and vinyl sulfone.
The functionalized trans-disubstituted alkenes obtained
from the present cobalt-catalyzed reductive coupling reac-
tion are highly useful synthetic intermediates in organic syn-
thesis and their applications in various organic transforma-
tion reactions are well known in literature (Scheme 4).[17]
Conclusion
We have successfully developed a synthetically very useful
cobalt-catalyzed reductive coupling of terminal alkynes with
activated alkenes to provide various trans-disubstituted al-
Scheme 2. Proposed mechanism.
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S. Mannathan and C.-H. Cheng
gioisomers was determined by
1H NMR spectroscopic analysis of the
unpurified sample.
For the coupling of acetylene gas with
vinyl sulfone, the reaction was carried
out by using CoCl2 (0.100 mmol,
10 mol%),
PACTHUNGTRENNU(G OPh)3 (0.200 mmol,
20 mol%), Zn powder (2.75 mmol),
and H2O (1.00 mmol) in the presence
of an acetylene atmosphere (1 atm) in
CH3CN (2.0 mL) at 608C for 16 h.
Acknowledgements
Scheme 4. Organic transformation reactions of functionalized trans-disubstituted alkenes.
We thank the National Science Coun-
cil of Republic of China (NSC-100-
2119M-007-002) for support of this
research.
kenes in good to excellent yields. In the reaction, less expen-
sive and air-stable cobalt catalysts, a very mild reducing
agent (Zn), and one of the simplest hydrogen sources
(water) were used. The present catalytic reaction is success-
fully applied to a wide range of alkenes, such as vinyl ke-
tones, acrylonitrile, acrylates, and vinyl sulfone, and also to
both aromatic and aliphatic terminal alkynes. In addition,
we have demonstrated a phosphine-free cobalt catalyst
system for the reductive coupling of terminal alkynes with
enones to synthesize 1,2-trans-disubstituted alkenes in high
regio- and stereoselectivity. Overall, we believe that the
present manuscript represents a great advance to the chem-
istry of enyne coupling reactions.
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Experimental Section
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General procedure for the reductive coupling of aromatic terminal al-
kynes with acrylates and vinyl sulfone: A sealed tube (20 mL) containing
CoCl2 (0.10 mmol, 10 mol%) and zinc powder (2.75 mmol) was evacuat-
ed and purged with nitrogen gas three times. Freshly distilled CH3CN
(2.0 mL) and PACHTUNGTRENNUNG(OMe)3 (0.50 mmol, 50 mol%) were added and the mix-
ture was stirred until the solution became green. Then, the alkyne
(1.00 mmol), acrylate or vinyl sulfone (dissolved in 0.50 mL of CH3CN;
1.20 mmol), and H2O (1.00 mmol) were sequentially added by syringe.
The reaction mixture was stirred at 408C for 16 h and was then cooled,
diluted with dichloromethane, and stirred in air for 10 min. The mixture
was filtered through a Celite and silica gel pad and washed with dichloro-
methane. The filtrate was concentrated to afford the crude alkene. The
ratio of regioisomers was determined by 1H NMR spectroscopic analysis
of the unpurified sample. Later, the crude residue was purified on a silica
gel column by using n-hexane/ethyl acetate as the eluent to afford the de-
sired product 3.
For the coupling of aromatic terminal alkynes with acrylonitrile or
enones, the reaction was carried out by using CoCl2 (0.100 mmol,
10 mol%), PACHTUNGTRENNUNG(OMe)3 (0.500 mmol, 50 mol%), Zn powder (2.75 mmol),
ZnI2 (0.300 mmol, 30 mol%), and H2O (1.00 mmol) in CH3CN (2.0 mL)
at 408C for 16 h.
A similar reaction procedure was followed for the reaction of aliphatic
terminal alkynes (1.50 mmol) with activated alkenes (1.00 mmol), such as
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lizio, Nat. Chem. 2010, 2, 638.
acrylate, vinyl sulfone, and enone, but
(0.200 mmol, 20 mol%) was used instead of P
lytic amount of ZnI2 (0.300 mmol, 30 mol%) was used. The ratio of re-
a
different ligand
PACTHNGUTRENU(NG OPh)3
AHCTUNRTGEG(NUNN OMe)3. For enones, a cata-
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Synthesis of trans-Disubstituted Alkenes
FULL PAPER
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[15] We did not observe any reductive coupling reactions of alkenes with
acetonitrile under the CoCl2/P(OR)3/Zn system.
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Received: March 8, 2012
Revised: June 10, 2012
Published online: && &&, 0000
[13] a) T. T. Jayanth, C.-H. Cheng, Angew. Chem. 2007, 119, 6025;
Angew. Chem. Int. Ed. 2007, 46, 5921; b) S. Mannathan, M. Jegan-
Chem. Eur. J. 2012, 00, 0 – 0
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www.chemeurj.org
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S. Mannathan and C.-H. Cheng
Ligands
S. Mannathan,
C.-H. Cheng* ................. &&&& — &&&&
Synthesis of trans-Disubstituted
Alkenes by Cobalt-Catalyzed Reduc-
tive Coupling of Terminal Alkynes
with Activated Alkenes
Activate your alkenes! Cobalt com-
plexes with suitable ligands catalyze
the reductive coupling of terminal
alkynes with activated alkenes in the
presence of zinc and water to give 1,2-
trans-disubstituted alkenes in good to
excellent yields (see scheme).
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ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 0000, 00, 0 – 0
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These are not the final page numbers!