Cobalt-catalyzed regio- and stereoselective intermolecular enyne coupling: An efficient route to 1,3-diene derivatives

Article abstract of DOI:10.1039/b920071a

The reaction of alkynes with vinyl arenes or vinyl trimethyl silane in the presence of a cobalt(II) complex, Zn and ZnI₂ in CH ₂Cl₂ at rt to 50 °C provides 1,3-dienes in good to excellent yields. The Royal Society of Chemistry 2010.

Full text of DOI:10.1039/b920071a

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Cobalt-catalyzed regio- and stereoselective intermolecular enyne
coupling: an efficient route to 1,3-diene derivativesw
Subramaniyan Mannathan and Chien-Hong Cheng*
Received (in Cambridge, UK) 28th September 2009, Accepted 25th November 2009
First published as an Advance Article on the web 26th January 2010
DOI: 10.1039/b920071a
The reaction of alkynes with vinyl arenes or vinyl trimethyl silane
in the presence of a cobalt(II) complex, Zn and ZnI2 in CH2Cl2 at
rt to 50 1C provides 1,3-dienes in good to excellent yields.
On treatment of styrene 2a with diphenylacetylene 1a in the
presence of CoI2 (5 mol%), dppp (5 mol%), Zn (20 mol%)
and ZnI2 (20 mol%) in dichloromethane (DCM) as solvent at
rt for 24 h, enyne coupling product 3a was obtained in 97%
yield. Control experiments revealed that the reaction did not
proceed in the absence of either CoI2/dppp or Zn and ZnI2.12
The 1,3-diene product 3a was obtained highly stereo- and
regioselectively, with the two phenyl groups of the diphenyl-
acetylene moiety cis to each other and the double bond
attaching to the styryl group exclusively in the E form. More-
over, the carbon–carbon bond formed in the product is
between the methylene carbon of styrene and an alkyne
carbon. Solvents play a major role in this reaction: CH3CN,
DMF and THF were totally inactive whereas toluene, DCE
and DCM were effective, affording product 3a in 18, 73 and
97% yields, respectively. Based on these solvent studies, it
appears that the reaction requires a polar but less coordinating
solvent which can dissolve the cobalt complex and ZnI2 but
which does not compete strongly with 1a and 2a for coordination
to the cobalt metal center.13
Transition metal-catalyzed coupling of alkenes and alkynes
has become a prevailing method for the construction of C–C
bonds in organic synthesis. These enyne coupling reactions
provide an efficient way of synthesizing substituted alkenes1
and dienes2 in a highly regio- and stereoselective manner. Of
these coupling reactions, the ene type coupling can give either
1,3- or 1,4-dienes depending on the substrates and the catalytic
conditions used.2 Despite various transition metal complexes,
including Ru, Rh, Pd, Co, Ni–Cr, Ti and Ir, being known to
catalyze the intramolecular ene type reactions,2,3 only few of
them have been used in the intermolecular version. In 1991,
Mitsudo et al. reported a ruthenium-catalyzed intermolecular
co-dimerization of electron-rich alkynes with a,b-unsaturated
alkenes to give 1,3-dienes.4 Trost’s group studied extensively
the intermolecular Alder-ene reaction of alkynes with alkenes
for the synthesis of 1,4-dienes using ruthenium complexes as
catalysts.5 Later, Ito and his co-workers reported a ruthenium-
catalyzed 1,3-diene synthesis from terminal alkynes and alkenes
via mechanistically different vinylidene ruthenium complexes
as the intermediates.6 Recently Hilt and Treutwein demonstrated
a cobalt-catalyzed intermolecular Alder-ene type reaction of
alkynes with unactivated terminal alkenes with allylic hydrogen
atoms to afford 1,4-dienes,7 while Tanaka et al. reported a
rhodium-catalyzed coupling of electron-deficient alkynes and
a,b-unsaturated alkenes to give 1,3-dienes.8
We have been involved in the coupling reactions of two
different p-components,1,9 particularly using cobalt complexes
as the catalysts.1c In view of the catalytic ability of cobalt
complexes in the reaction of alkynes with a,b-unsaturated
alkenes to give reductive coupling products by us1d,e and with
unactivated terminal alkenes with allylic hydrogen atoms to
afford 1,4-dienes by Hilt and Treutwein,7 it should be interesting
to explore the possibility of a cobalt-catalyzed enyne coupling
that can give 1,3-dienes. Herein, we wish to report that cobalt
complexes regio- and stereoselectively catalyze the intermolecular
coupling of alkynes with styrenes to afford substituted 1,3-
dienes.10 It is known that 1,3-dienes are valuable intermediates
in organic synthesis,11 most notably in Diels–Alder reactions.
To explore the scope of the reaction, the coupling of various
substituted styrenes with diphenylacetylene 1a was investigated.
Thus, treating 4-bromo- and 3-chloro-substituted styrenes,
2b–c with 1a under the standard conditions (see Table 1,
footnote a) furnished 3b–c in 92 and 94% yields, respectively
(entries 2 and 3). The reaction of vinyl silane 2d with 1a gave
3d in 64% yield (entry 4). The extension of enyne coupling to
3-methoxy and 3-formyl substituted styrenes, 2e–f, with 1a
were also successful, affording products 3e–f in 88 and 85%
yields, respectively (entries 5 and 6).
The present catalytic reaction can also be applied to a
variety of unsymmetrical internal alkynes. When methyl-
phenylacetylene 1b was treated with styrene (2a), two regio-
isomeric dienes 3g/3g0 were obtained with a regioisomeric
ratio of 90 : 10 in 91% combined yield (entry 7). Similarly,
the reaction of 1b with 4-bromostyrene (2b) afforded 3h/3h0
also with a regioisomeric ratio of 90 : 10 in 95% combined
yield (entry 8). Likewise, ethyl- and n-butylphenylacetylene, 1c
and 1d, respectively, coupled with 2a to provide products 3i
and 3j in 90 and 97% yield (entries 9 and 10). Arylhexyne, 1e,
with an electron withdrawing 4-acetyl substituent also under-
went coupling reaction with 2a to give 3k in 90% yield (entry 11).
It should be noted that products 3i and 3k were obtained in a
completely regioselective fashion but the E : Z ratios of the
styrene double bond were 91 : 9 and 88 : 12, respectively, whereas
complete regio- and stereoselectivity was found for product
3j. Heteroaromatic unsymmetrical alkyne, 3-(1-pentynyl)-
thiophene (1f) also successfully participated in the coupling
with 2a to afford 3l in 75% yield (entry 12). In addition, alkyne
Department of Chemistry, National Tsing Hua University,
Hsinchu 30013, Taiwan. E-mail: chcheng@mx.nthu.edu.tw;
Fax: +886-3-5724698; Tel: +886-3-5721454
w Electronic supplementary information (ESI) available: General
experimental procedure, spectral data (1H, 13C NMR and HRMS)
and copies of 1H and 13C NMR spectra of all compounds. See DOI:
10.1039/b920071a
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Table 1 Results of the coupling of alkynes 1 and alkenes 2a
Entry
1
1
2
Product 3
Yield (%)b
97 (99)
1a
1a
2a
3a
3b
2
2b
92
3
1a
1a
2c
2d
3c
3d
94
4
5
64c
1a
2e
3e
88
6
1a
1b
1b
2f
3f
85
7
8
2a
2b
3g (3g0)
3h (3h0)
91 (90 : 10)d
95 (90 : 10)d
9
10
11
1c
1d
2a
2a
3i
3j
90 (91 : 9)e
97
1e
2a
3k
90f (88 : 12)e
12
13
14
1f
2a
2a
3l
75g
91g
1g
3m
1h
1i
1j
2a
2a
2a
3n (3n0)
3o
78h (495 : 5)d
84h
15
16
3p (3p0)
82h (2 : 1)d
17
1k
2b
3q
38i
a
Unless otherwise stated, the reaction conditions are alkyne 1 (1.0 mmol), alkene 2 (1.2 mmol), CoI2 (5 mol%), dppp (5 mol%), Zn (20 mol%) and
b
ZnI2 (20 mol%) and DCM (1.5 mL) at rt for 24 h. Isolated yields; yield in parentheses was determined by an 1H NMR integration method using
c
mesitylene as an internal standard. Reaction time was 36 h. Regioisomeric ratio. E : Z ratio of the styrene double bond. Co(dppe)Br2
d
e
f
g
h
(5 mol%) in DCE at 80 1C for 20 h. Co(dppe)Br2 (5 mol%) for 36 h. Co(dppe)Br2 (5 mol%)/2,20-bipyridine (5 mol%) at
i
50 1C. Co(dppe)Cl2 (5 mol%)/P(2-furyl)3 (5 mol%) 50 1C for 36 h.
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is also compatible with both electron-rich and electron-
deficient substituents attached to alkynes, unlike the reactions
catalyzed by ruthenium4 and rhodium complexes.8
We thank the National Science Council of Republic of
China (NSC-96-2113-M-007-020-MY3) for support of this
research.
Notes and references
1 (a) S. Ikeda, Acc. Chem. Res., 2000, 33, 511; (b) J. Montgomery,
Angew. Chem., Int. Ed., 2004, 43, 3890; (c) M. Jeganmohan and
C.-H. Cheng, Chem.–Eur. J., 2008, 14, 10876; (d) C.-C. Wang,
P.-S. Lin and C.-H. Cheng, J. Am. Chem. Soc., 2002, 124, 9696;
(e) H.-T. Chang, T. T. Jayanth, C.-C. Wang and C.-H. Cheng,
J. Am. Chem. Soc., 2007, 129, 12032; (f) H. A. Reichard and
G. C. Micalizio, Angew. Chem., Int. Ed., 2007, 46, 1440;
(g) A. Herath, B. B. Thompson and J. Montgomery, J. Am. Chem.
Soc., 2007, 129, 8712; (h) C.-C. Wang, P.-S. Lin and C.-H. Cheng,
Tetrahedron Lett., 2004, 45, 6203.
2 (a) C. Aubert, O. Buisine and M. Malacria, Chem. Rev., 2002, 102,
813; (b) B. M. Trost, F. D. Toste and A. B. Pinkerton, Chem. Rev.,
2001, 101, 2067; (c) B. M. Trost, M. U. Ferderiksen and
M. T. Rudd, Angew. Chem., Int. Ed., 2005, 44, 6630;
(d) D. B. Grotjahn, in Comprehensive Organometallic
Chemistry II, ed. E. W. Abel, F. G. A. Stone, G. Wilkinson and
L. Hegedus, Pergamon Press, Oxford, 1995, vol. 12, p. 741;
(e) N. E. Schore, Chem. Rev., 1988, 88, 1081; (f) V. Michelet,
P. Y. Toullec and J.-P. Genet, Angew. Chem., Int. Ed., 2008, 47,
4268.
Scheme 1
1g containing a hydroxy functional group underwent coupling
with 2a to give product 3m in 91% yield (entry 13).
The standard reaction conditions were also employed for
the coupling of electron deficient alkyne 1h with 2a, but no
corresponding diene product was observed. We then carried
out the reaction using Co(dppe)Br2, Zn and ZnI2 as the
catalyst system.7 Again, we did not get the expected coupling
product 3n. However, when we added electron donating
bidentate nitrogen ligand 2,20-bipyridine to the reaction system,
the catalytic reaction proceeded to provide product 3n/3n0 in
30% combined yield with complete stereoselectivity with
a regioisomeric ratio of 495 : 5. The reaction yield was
improved up to 78% by increasing the reaction temperature
to 50 1C (entry 14). Similarly, methyl oct-2-ynoate (1i) reacted
with 2a under the same conditions to give the expected
product 3o in 84% yield with complete regio- and stereo-
selectivity (entry 15). For ethyl 3-phenylpropiolate (1j), regio-
isomeric products 3p/3p0 were obtained in a ratio of 2 : 1 in
82% combined yield (entry 16). Symmetrical dimethoxy-
butyne 1k also underwent coupling reaction with 2b to afford
product 3q in 38% yield (entry 17). In this case, the reaction
was carried out in the presence of Co(dppe)Cl2 and 1 equiv.
of electron-withdrawing ligand P(2-furyl)3.11 Other cobalt catalyst
systems used in Table 1 are not suitable for this coupling reaction.
It is noteworthy that for the reaction of styrene 2a with electron
deficient alkynes, 1h–j and the reaction of 2b with aliphatic alkyne
1k, a high reaction temperature is crucial to obtain high product
yields. We should also mention here that the present enyne
coupling reaction is not suitable for terminal alkynes leading to
a facile homocyclotrimerization of the alkynes under the standard
reaction conditions.
3 (a) Ni–Cr: B. M. Trost and J. M. Tour, J. Am. Chem. Soc., 1988,
110, 5231; (b) Co: M. E. Krafft, A. M. Wilson, O. A. Dasse, L. V.
K. Bonaga, Y. Y. Cheung, Z. Fu, B. Shao and J. L. Scott,
Tetrahedron Lett., 1998, 39, 5911; (c) Ir: S. Kezuka, T. Okada,
E. Niou and R. Takeuchi, Org. Lett., 2005, 7, 1711.
4 T. Mitsudo, S.-W. Zhang, M. Nagao and Y. Watanabe, J. Chem.
Soc., Chem. Commun., 1991, 598.
5 (a) B. M. Trost and A. Indolese, J. Am. Chem. Soc., 1993, 115,
4361; (b) B. M. Trost, A. F. Indolese, T. J. J. Muller and
¨
B. Treptow, J. Am. Chem. Soc., 1995, 117, 615; (c) B. M. Trost,
T. J. J. Muller and J. Martinez, J. Am. Chem. Soc., 1995, 117, 1888;
¨
(d) B. M. Trost, M. Machacek and M. J. Schnaderbeck, Org. Lett.,
2000, 2, 1761; (e) B. M. Trost, H. C. Shen and A. B. Pinkerton,
Chem.–Eur. J., 2002, 8, 2341; (f) B. M. Trost and M. R. Machacek,
Angew. Chem., Int. Ed., 2002, 41, 4693; (g) B. M. Trost,
M. R. Machacek and Z. T. Ball, Org. Lett., 2003, 5, 1895.
6 M. Murakami, M. Ubukata and Y. Ito, Tetrahedron Lett., 1998,
39, 7361.
7 G. Hilt and J. Treutwein, Angew. Chem., 2007, 119, 8653; G. Hilt
and J. Treutwein, Angew. Chem., Int. Ed., 2007, 46, 8500.
8 Y. Shibata, M. Hirano and K. Tanaka, Org. Lett., 2008, 10,
2829.
9 (a) H.-T. Chang, T. T. Jayanth and C.-H. Cheng, J. Am. Chem.
Soc., 2007, 129, 4166; (b) D. K. Rayabarapu and C.-H. Cheng,
Chem.–Eur. J., 2003, 9, 3164; (c) D. K. Rayabarapu, T. Sambaiah
and C.-H. Cheng, Angew. Chem., Int. Ed., 2001, 40, 1286;
(d) C.-H. Yeh, R. P. Korivi and C.-H. Cheng, Angew. Chem.,
Int. Ed., 2008, 47, 4892; (e) D. J. Huang, L. P. Li,
D. K. Rayabarapu, T. Sambaiah and C.-H. Cheng, Chem.–Eur.
J., 2000, 6, 3706.
10 For another method to synthesise 1,4-diaryl substituted 1,3-dienes,
see: A. T. Lindhardt, M. Louise, H. Mantel and T. Skrydstrup,
Angew. Chem., Int. Ed., 2008, 47, 2668.
11 (a) Y. Yang, S.-F. Zhu, H.-F. Duan, C.-Y. Zhou, L. X. Wang and
Q.-L. Zhou, J. Am. Chem. Soc., 2007, 129, 2248;
(b) C. Dockendorff, S. Sahli, M. Olsen, L. Milhau and
M. Lautens, J. Am. Chem. Soc., 2005, 127, 15028.
12 For optimization studies of various cobalt complexes in different
solvents, see the ESIw; dppe = bis(triphenylphosphino)ethane;
dppp = bis(triphenylphosphino)propane; P(2-furyl)3 = tris-
(2-furyl)phosphine.
13 I.-F. Duan, J.-S. Shaio, S. S. Cheng, K. F. Liou and C.-H. Cheng,
J. Chem. Soc., Chem. Commun., 1991, 1347.
A possible reaction mechanism for the enyne coupling is shown
in Scheme 1. Reduction of CoII to CoI by zinc powder initiates the
catalytic reaction. Highly chemoselective coordination of
an alkyne 1 and an alkene 2 to the CoI center2a followed by
regioselective oxidative cyclometalation yields cobaltacyclo-
pentene intermediate 4. Subsequent b-hydride elimination of
intermediate 4 gives 5 and reductive elimination affords the 1,3-
diene 3 and CoI which can be further used for the catalytic cycle.
In conclusion, we have demonstrated that cobalt complexes
efficiently catalyze the intermolecular enyne coupling reaction
to give 1,3-dienes in good to excellent yields. The results
considerably extend the scope of the catalytic ability of cobalt
complexes in the enyne coupling reaction. This coupling
reaction proceeds with high regio- and stereoselectivity and
ꢀc
This journal is The Royal Society of Chemistry 2010
Chem. Commun., 2010, 46, 1923–1925 | 1925