Cobalt-catalysed synthesis of highly substituted styrene derivatives via arylzincation of alkynes

Article abstract of DOI:10.1039/c2cc36676b

A new two-step procedure was developed by carbozincation of internal and terminal alkynes to synthesise highly functionalised vinylzinc bromides. Various tri and tetrasubstituted alkenes were prepared in moderate to good yields under mild reaction conditions in a stereo-selective manner. This methodology represents an interesting alternative to previously known methods. This journal is

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COMMUNICATION
Cobalt-catalysed synthesis of highly substituted styrene derivatives via
arylzincation of alkynesw
Martin Corpet and Corinne Gosmini*
Received 13th September 2012, Accepted 9th October 2012
DOI: 10.1039/c2cc36676b
A new two-step procedure was developed by carbozincation of
internal and terminal alkynes to synthesise highly functionalised
vinylzinc bromides. Various tri and tetrasubstituted alkenes were
prepared in moderate to good yields under mild reaction condi-
tions in a stereo-selective manner. This methodology represents
an interesting alternative to previously known methods.
Scheme 1 Cobalt-catalysed arylzincation of 5-decyne.
We first investigated the possibility of a one-pot procedure
allowing the carbometallation to directly take place in the
same pot as the formation of the arylzinc bromide (Scheme 1).
However, although the desired carbometallation product was
formed at room temperature, the yield was severely limited by the
formation of an untractable mixture of products incorporating
several alkene moieties (Table 1, entry 1). Changing the condi-
tions for the formation of the arylzinc bromide barely improved
the yield, and the amount of unseparable byproducts remained
high (Table 1, entry 2).
Among all the routes to alkenes, few are as convenient as
carbometallation reactions.1 These reactions allow direct for-
mation of stereodefined tri- and tetrasubstituted alkenes in a
minimum number of steps which is still very difficult to
achieve. Among those, carbozincation is especially useful, as
organozinc reagents are readily accessible, as well as very
tolerant towards functional groups. In addition, carbozinca-
tion of internal alkynes is always syn-selective.1e Although
addition of organozinc to activated alkynes has been well
studied,2–5 a single and elegant report of cobalt catalysed
arylzincation of unactivated alkynes exists.6 However, the
methodology proposed relies on a activated substrate (e.g.
aryl iodide) and tight temperature control for the synthesis of
the arylzinc species, as well as a change of solvent between the
synthesis of the arylzinc (conducted in THF) and the carbo-
zincation itself, which has to be conducted in acetonitrile to
occur. Recently, Yoshikai et al.7 showed that, under different
conditions, arylzinc species could be added across triple
bonds, but instead of furnishing the expected vinylzinc species,
the metal was transferred back to the ortho position of the
aromatic group. As our group has already reported, the
synthesis of the arylzinc species is possible in acetonitrile,
under cobalt catalysis, from the cheaper aryl bromides.8 In
addition, we have been interested in the formation of styrene
derivatives through cobalt-catalysed cross-coupling reactions
of aryl halides with vinylic substrates.9 The aforementioned
report6 spurred us to investigate the possibility for the arylzinc
synthesised under cobalt catalysis to react with alkynes to
afford trisubstituted vinylzinc species, which could then react
with various electrophiles, in a simple ‘‘bench-friendly’’ manner.
Filtration of the medium, by eliminating the excess metallic
zinc, allowed the reaction to occur with slightly improved yield
and rate (Table 1, entry 3). The use of an easily synthesised and
shelf-stable preformed CoBr2(bipy) complex instead of the simple
CoBr2 allows the rapid formation of the arylzinc bromide under
the same conditions. Moreover, the amount of unidentifiable-
products detected by GC analysis (Table 1, entry 4) is lower in
this case. Additionally, the yield increases with simple filtration of
the arylzinc compound by avoiding the rapid cyclotrimerisation
of the alkyne (Table 1, entry 5). Under these last conditions,
3 equivalents of arylzinc species, instead of 2 or 4, were necessary
to limit the amount of by-products (entries 6 and 7).
With these results in hand, the scope of the arylzincation
was then examined with various arylzinc species and alkynes
(Scheme 2) and results are reported in Table 2.
Table 1 Cobalt-catalysed arylzincation of 5-decyne: optimization of
the reaction conditions
Alkyne
Entry [Co] Zn (equiv.) Ligand added (equiv.) Filtration Yielda
1
2
3
4
5
6
7
13% 2.6
10%
None 0.33
None 0.33
None 0.33
No
No
Yes
No
Yes
Yes
Yes
53%
55%
57%
59%
75%
53%
49%
2
13% 2.6
10%b
10%b
10%b
10%b
2
2
2
2
Bipy
Bipy
Bipy
Bipy
0.33
0.33
0.25
0.5
´ ´ ´ ´
Laboratoire ‘‘Heteroelements et Coordination’’, Ecole Polytechnique,
CNRS, 91128 Palaiseau Cedex, France.
E-mail: corinne.gosmini@polytechnique.edu; Fax: +33 1-6933-4440;
Tel: +33 1-6933-4412
w Electronic supplementary information (ESI) available. See DOI:
10.1039/c2cc36676b
a
b
GC yield vs. decane as internal standard. Preformed CoBr2(bipy)
was used.
c
This journal is The Royal Society of Chemistry 2012
Chem. Commun., 2012, 48, 11561–11563 11561

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benzylic position. Steric hindrance on the aryl group (entry 10),
electron-rich (entry 11) and -poor aromatic groups (entries 13
and 15) and heteroaromatic substituents (entry 14) were well
tolerated on the alkyne. Even a challenging substrate, bearing
both an electron poor aromatic group and a bulky substituent,
afforded the desired product in acceptable yield in 5 h.
However the temperature had to be raised to 50 1C (entry 15).
Phenylacetylene could also be made to react under those condi-
tions, to afford the corresponding trans-stilbene in moderate
yield (entry 16).
Scheme 2 Reaction scope under the optimized conditions.
Internal symmetrical alkynes reacted well under the opti-
mized conditions, with electron-neutral, -rich, or -poor aryl-
zinc bromides, affording the desired isolated trisubstituted
alkenes in good yield after hydrolysis (Table 2, entries 1–4).
Various functional groups were well tolerated on both
partners: nitrile (entries 3, 10 and 11), ester (entries 4, 8 and
15), methoxy (entries 2 and 11), fluoride (entry 9), methyl
(entries 10 and 11), chloride (entries 6, 13 and 14), trifluoro-
methyl (entries 10 and 15), methylsulfanyl and methyl sulfone
(entry 13). In contrast to previous reports,6 sterically hindered
alkynes could also react: while an isopropyl group failed to
impose a significant regioselectivity (entry 6), a tertiobutyl
group oriented the reaction effectively, affording a single
isomer in useful yield (entry 7). On the other hand, ortho-
substituted arylzinc bromides did not react (entry 5). When the
alkyne was a phenylacetylene derivative, the reaction was
generally high yielding and always chemoselective, affording
a single isomer, where the zinc was introduced solely at the
Finally, we tried to functionalise the newly-formed vinylzinc
compound with various electrophiles (Scheme 3). This organo-
metallic species could react almost quantitatively with
molecular iodine to afford the vinyl iodide in good isolated
yield. It could also be made to react under Negishi-type cross-
coupling conditions,10 to afford the tetrasubstituted alkene in
good yield, in a single pot, two-step procedure, from a simple
alkyne.
In conclusion, we have managed to devise a new set of
conditions to allow the synthesis of tri and tetrasubstituted
alkenes from internal and terminal alkynes, under cobalt
catalysis. The catalyst used for both the synthesis of the
arylzinc species and the carbometallation reaction is an easily
synthesised and shelf-stable CoBr2(bipy) complex. The condi-
tions for both steps are very simple, and do not necessitate
Table 2 Scope of arylzinc bromides and alkynes
Entry
ArZnBr FG
4-OMe 1a
H 1b
Alkyne
Product
Time (h)
0.5
Yielda (%)
1
2
73
76
0.5
3
4
5
4-CN 1c
4-EtO2C 1d
2-F 1e
1.5
1.25
24
69
71
nd
6
7
4-Cl 1f
H 1b
2
61b
56
1.5
8
9
4-EtO2C 1d
4-F 1g
1.5
70
76
0.75
c
This journal is The Royal Society of Chemistry 2012
11562 Chem. Commun., 2012, 48, 11561–11563

View Article Online
Table 2 (continued )
Entry
ArZnBr FG
Alkyne
Product
Time (h)
Yielda (%)
10
4-CF3 1h
1
82
11
12
4-Me 1i
1
1
73
80
4-OMe 1a
13
14
4-SMe 1j
H 1b
2.5
4
91
77
15
3,5-DiCF3 1k
H 1b
5
48c
63
16
0.75
a
Isolated yield. In all cases the E : Z ratio was >99 : 1 in favor of the depicted isomer (only one isomer detected by GC and 1H NMR).
b
c
Regioselectivity: 6 : 4 (3fb/3fb0). Reaction at 50 1C.
G. Wang, S. Mohan, C. Wang and H. Hattori, Acc. Chem. Res.,
2008, 41, 1474; (e) A. B. Flynn and W. W. Ogilvie, Chem. Rev.,
2007, 107, 4698; (f) K. Itami and J. Yoshida, in The Chemistry of
Organomagnesium Compounds, ed. Z. Rappoport and I. Marek,
John Wiley & Sons, Chichester, 2008; (g) B. H. Lipshutz and
S. Sengupta, Org. React., 1992, 41, 135.
2 For the reaction on propynoate derivatives see: (a) R. Shintani,
T. Yamagami and T. Hayashi, Org. Lett., 2006, 8, 4799;
(b) R. Shintani and T. Hayashi, Org. Lett., 2005, 7, 2071;
(c) S. Xue, L. He, Y.-K. Liu, K.-Z. Han and Q.-X. Guo, Synthesis,
2006, 666.
3 For the reaction on alkynyl sulfoxides: (a) G. Sklute, C. Bolm and
I. Marek, Org. Lett., 2007, 9, 1259; (b) N. Maezaki, H. Sawamoto,
R. Yoshigami, T. Suzuki and T. Tanaka, Org. Lett., 2003, 5,
1345.
4 For the reaction on phenylacetylene derivatives see: (a) T. Studemann,
Scheme 3 Post-functionalisation of the vinylzinc.
¨
M. Ibrahim-Ouali and P. Knochel, Tetrahedron, 1998, 54, 1299;
tight temperature control, distilled solvents, or any other
particular precautions, making this methodology an inter-
esting tool for the selective synthesis of alkenes. Further
investigations are being conducted in our laboratory as to
the characteristics and use of the CoBr2(bipy) complex for
arylzinc synthesis and reactivity, as well as other reactions.
(b) T. Studemann and P. Knochel, Angew. Chem., Int. Ed., 1998,
36, 93; (c) H. Yasui, T. Nishikawa, H. Yorimitsu and K. Oshima,
Bull. Chem. Soc. Jpn., 2006, 79, 1271.
5 For the reaction on ynamides see: B. Gourdet and H. W. Lam,
J. Am. Chem. Soc., 2009, 131, 3802.
6 K. Murakami, H. Yorimitsu and K. Oshima, Org. Lett., 2009,
11, 2373.
¨
7 B.-H. Tan, J. Dong and N. Yoshikai, Angew. Chem., Int. Ed., 2012,
51, 9610.
Notes and references
8 (a) H. Fillon, C. Gosmini and J. Pe
Soc., 2003, 125, 3867; (b) I. Kazmierski, C. Gosmini, J.-M.
Paris and J. Perichon, Tetrahedron Lett., 2003, 44, 6417;
(c) C. Gosmini, M. Amatore, S. Claudel and J. Perichon, Synlett,
2005, 2171.
´
richon, J. Am. Chem.
1 (a) P. Knochel, in Comprehensive Organic Synthesis, ed. B. M.
Trost, I. Fleming and M. F. Semmelhack, Pergamon Press, New
York, 1991, vol. 4, ch. 4.4, pp. 865–911; (b) I. Marek, N. Chinkov
and D. Banon-Tenne, in Metal-Catalyzed Cross-Coupling Reac-
tions, ed. A. de Meijere and F. Diederich, Wiley-VCH, Weinheim,
2004, pp. 395–478; (c) I. Marek and J.-F. Normant, in Transition
Metal for Organic Synthesis, ed. M. Beller and C. Bolm, Wiley-
VCH, Weinheim, 1998, pp. 514–522; (d) E. Negishi, Z. Huang,
´
´
9 (a) M. Amatore, C. Gosmini and J. Perichon, Eur. J. Org. Chem.,
2005, 989; (b) A. Moncomble, P. Le Floch, A. Lledos and
C. Gosmini, J. Org. Chem., 2012, 77, 5056.
10 E. Negishi, Acc. Chem. Res., 1982, 15, 340.
c
This journal is The Royal Society of Chemistry 2012
Chem. Commun., 2012, 48, 11561–11563 11563