Arylmagnesiation of alkynes catalyzed cooperatively by iron and copper complexes

Article abstract of DOI:10.1021/ja0542136

Iron and copper complexes cooperatively catalyzed the arylmagnesiation of unfunctionalized alkynes including dialkylacetylenes, where the presence of both iron and copper catalysts is essential for high yields of 2-aryl-1-alkenylmagnesium bromides. Copyright

Full text of DOI:10.1021/ja0542136

Published on Web 11/17/2005
Arylmagnesiation of Alkynes Catalyzed Cooperatively by Iron and
Copper Complexes
Eiji Shirakawa,* Takafumi Yamagami, Takahiro Kimura, Shigeru Yamaguchi, and Tamio Hayashi*
Department of Chemistry, Graduate School of Science, Kyoto UniVersity, Sakyo, Kyoto 606-8502, Japan
Received June 25, 2005; E-mail: shirakawa@kuchem.kyoto-u.ac.jp; thayashi@kuchem.kyoto-u.ac.jp
Table 1. Arylmagnesiation of 4-Octyne Followed by Hydrolysisa
Carbometalation of alkynes is one of the most useful methods
for olefin synthesis, since the resulting alkenylmetals can be
transformed to various multisubstituted ethenes in a stereoselective
1
manner. Although heteroatom-containing alkynes undergo carbo-
metalation with diverse organometallic compounds in the presence
2
or absence of a transition metal catalyst, unfunctionalized alkynes
are poor substrates, in particular for the addition of arylmetals.
Here we report that iron4-8 and copper9 complexes cooperatively
3
amount (mol %)
conv
(%)
yield
(%)
b
c
d
entry
Ar
Fe(acac)3
CuBr
E:Z
catalyze the arylmagnesiation of alkynes including dialkylacetylenes
that do not contain a heteroatom. This presents a rare example of
efficient cooperative catalysis.10 It is also remarkable that the metals
1
2
3
4
5
6
3,5-Me C H (1a)
5
0
5
5
0
5
10
10
0
10
10
0
>99
<1
57
>99
<1
14
74
0
26
91
95:5
-
2
6
3
3
87:13
98:2
-
2-Me-1-Nap (1b)
(Fe, Cu, and Mg) used in the present catalytic reaction are all
0
inexpensive.
2d
>99:1
The reaction of 3,5-dimethylphenylmagnesium bromide (1a) with
a
The reaction was carried out in THF (1.7 mL) at 60 °C for 24 h under
4
-octyne (2a) in the presence of Fe(acac)
mol %), and PBu (40 mol %) in THF at 60 °C for 24 h followed
by hydrolysis gave 74% yield of 4-(3,5-dimethylphenyl)-4-octene
3a), where the ratio of E/Z isomers is 95/5 (entry 1 in Table 1).11-13
3
(5 mol %), CuBr (10
a nitrogen atmosphere using an arylmagnesium bromide (0.90 mmol),
3
4
-octyne (0.45 mmol) and PBu3 (0.18 mmol) in the presence of Fe(acac)3
(22 µmol) and/or CuBr (45 µmol). b Determined by GC. c Isolated yield
based on the alkyne. d Determined by GC, GC-MS and H NMR.
1
(
The E geometry indicates that arylmagnesiation took place with
syn-selectivity. The presence of both iron and copper catalysts is
essential for the high yield of arylmagnesiation. Thus, the reaction
Table 2. Hydroarylation of Alkynes Catalyzed by Iron-Coppera
3
without Fe(acac) did not give 3a at all, with all the alkyne (2a)
remaining (entry 2), and the yield of 3a was much lower (26%) in
the reaction without CuBr (entry 3). The cooperative catalysis by
the iron and copper is more obvious in the addition of 2-methyl-
entry
Ar
R1
R2
time (h)
yield (%)b
E:Zc
1-naphthylmagnesium bromide (1b) to 2a (entries 4-6). The yield
1
2
3
4
5
6
7
8
9
Ph
Pr
Pr
Pr
Pr
Pr
Pr
Pr
24
43
24
48
24
24
24
24
24
24
24
62
66
70
61
56
40
67
76
90
36
56
97:3
97:3
95:5
93:7
97:3
95:5
96:4
94:5(:1)
99:1
of arylation product 3b was 91% in the presence of both Fe(acac)
3
4-MeC6H4
3-MeC6H4
2-MeC6H4
3-MeOC6H4
4-FC6H4
Pr
Pr
Pr
Pr
Pr
Bu
Hex Ph
Me
H
and CuBr catalysts, whereas the yield was very low (0% or 2%) in
the absence of either iron or copper catalyst.
Table 2 illustrates the scope of the present arylmagnesiation of
alkynes catalyzed by the iron/copper cooperation. Various aryl-
magnesium bromides added to aliphatic and aromatic unfunction-
alized alkynes in stereoselectivities higher than 90% except for the
addition to 1-(trimethylsilyl)propyne (entry 11). Regioselectivities
over 95% were observed in the reaction of unsymmetrical aryl-
and silylacetylenes (entries 8-11).14 A terminal acetylene, though
in a low yield, participated in the reaction despite the intrinsic
reactivity of its acidic methyne proton toward basic 1a (entry 10).
3,5-Me2C6H3
3,5-Me2C6H3
2-Me-1-Nap
3,5-Me C H
Bu
Ph
Ph
SiMe3
10
11
2
6
3
91:5(:4)
72:26(:2)
3,5-Me2C6H3
Me
a
The reaction was carried out in THF (1.7 mL) at 60 °C under a nitrogen
atmosphere using an arylmagnesium bromide (0.90 mmol) and an alkyne
(
0.45 mmol) in the presence of Fe(acac)3 (22 µmol), CuBr (45 µmol) and
PBu3 (0.18 mmol).1 Isolated yield based on the alkyne. c Determined by
GC, GC-MS and H NMR. The values in parentheses shows the ratio of
a regioisomer to (E)- and (Z)-3.
b
2
Addition of D O to the reaction mixture resulting from addition
of 1b to 2a gave arylalkene 3b that is deuterated at its olefinic
methyne, indicating that the arylmagnesiation forming alkenylmag-
nesium actually took place (Scheme 1). Synthetic utility of the
arylmagnesiation products was demonstrated by their further
transformation through one-pot reactions with an electrophile. Thus,
the reaction mixture of the arylmagnesiation of 2a with 1b was
treated with benzaldehyde or benzyl bromide to give allylic alcohol
was treated with 4-octyne (2a) (1.0 equiv to Fe) at 60 °C for 20
min. Hydrolysis of the reaction mixture gave hydroarylation product
3b in 85% yield (Scheme 2). It follows that the addition of an
aryliron to the alkyne forming an alkenyliron took place with high
selectivity. Considering that the reaction of 1b with 2a in the
presence of a catalytic amount (5 mol %) of iron gave only a low
yield (2%) of 3b (entry 6 in Table 1), the alkenyliron species
generated by the arylironation of the alkyne is not reactive toward
further transformations such as transmetalation or polymerization,
keeping its alkenyliron structure under the reaction conditions
15
4
or tetrasubstituted ethene 5, respectively.
Reactions examined with a stoichiometric amount of Fe(acac)
or CuBr gave us significant insight into the reaction mechanism.
Thus, an aryliron species,16 generated from Fe(acac)
, PBu , and
an excess amount (4.0 equiv to Fe) of Grignard reagent 1b in THF,
3
3
3
17164
9
J. AM. CHEM. SOC. 2005, 127, 17164-17165
10.1021/ja0542136 CCC: $30.25 © 2005 American Chemical Society

C O M M U N I C A T I O N S
Scheme 1
Science and Technology, Japan (21 COE on Kyoto University
Alliance for Chemistry).
Supporting Information Available: Experimental procedures and
spectral analyses of all reaction products. This material is available
free of charge via the Internet at http://pubs.acs.org.
References
(
(
(
1) Knochel, P. In ComprehensiVe Organic Synthesis; Trost, B. M., Fleming,
I., Semmelhack, M. F., Eds.; Pergamon Press: New York, 1991; Vol. 4,
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2) For a recent review on carbometalation of heteroatom-containing alkynes
and alkenes, see: Fallis, A. G.; Forgione, P. Tetrahedron 2001, 57, 5899-
Scheme 2
5913.
3) Unfunctionalized alkynes used for the arylmetalation are all aryl-substituted
acetylenes. For examples, see: (a) Eisch, J. J.; Kaska, W. C. J. Am. Chem.
Soc. 1966, 88, 2976-2983. (b) Eisch, J. J.; Amtmann, R.; Foxton, M. W.
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J.; Okada, K.; Shinokubo, H.; Oshima, K. Chem. Lett. 1998, 11-12.
4) In the study on the iron-catalyzed alkyllithiation of heteroatom-containing
alkynes, the corresponding alkyl- and allylmagnesiations have been
conducted for comparison: Hojo, M.; Murakami, Y.; Aihara, H.; Sakuragi,
R.; Baba, Y.; Hosomi, A. Angew. Chem., Int. Ed. 2001, 40, 621-623.
5) The iron-catalyzed carbometalation of alkynes is likely involved in the
regioselective reaction of propargyl epoxides with Grignard reagents. (a)
F u¨ rstner, A.; M e´ ndez, M. Angew. Chem., Int. Ed. 2003, 42, 5355-5357.
(
(
Scheme 3
(
b) Lepage, O.; Kattnig, E.; F u¨ rstner, A. J. Am. Chem. Soc. 2004, 126,
15970-15971.
(
6) For examples of the iron-catalyzed carbometalations of alkynes using
organometallic compounds other than Grignard reagents, see: (a) Ca-
porusso, A. M.; Lardicci, L.; Giacomelli, G. Tetrahedron Lett. 1977, 18,
4
351-4354. (b) Caporusso, A. M.; Giacomelli, G.; Lardicci, L. J. Chem.
Soc., Perkin Trans. 1 1979, 3139-3145.
(
(
(
7) The iron-catalyzed carbometalation of an alkene, a cyclopropenone acetal,
using Grignard reagents including arylmagnesium bromide has been
reported. Nakamura, M.; Hirai, A.; Nakamura, E. J. Am. Chem. Soc. 2000,
122, 978-979.
8) For recent reviews on the iron-catalyzed reactions including carbometa-
lation of carbon-carbon unsaturated bonds, see: (a) Bolm, C.; Legros,
J.; Le Paih, J.; Zani, L. Chem. ReV. 2004, 104, 6217-6254. (b) F u¨ rstner,
A.; Martin, R. Chem. Lett. 2005, 34, 624-629.
9) For examples of the copper-catalyzed carbomagnesiation, see: (a)
Duboudin, J. G.; Jousseaume, B. J. Organomet. Chem. 1979, 168, 1-11.
(b) Xie, M.; Huang, X. Synlett 2003, 477-480.
(
10) One of the earliest and the most effective examples of this type of the
cooperative catalysis is the Sonogashira coupling, where palladium and
copper catalysts activate aryl halides and terminal alkynes, respectively.
(
a) Sonogashira, K.; Tohda, Y.; Hagihara, N. Tetrahedron Lett. 1975, 16,
lacking the copper catalyst. On the other hand, alkyne 2a did not
undergo any reactions with the diarylcuprate17 derived from CuBr
and Grignard reagent 1b (4.0 equiv to Cu), indicating that the copper
does not participate in the step of arylmetalation of the alkyne
forming an alkenylmetal species. It is most likely that the main
role of the copper catalyst is to promote the metal exchange between
the alkenyliron and the aryl Grignard reagent. The catalytic cycle
consistent with the experimental results is shown in Scheme 3.
Addition of aryliron 6 to alkyne 2 forms alkenyliron 7. The alkenyl
group on iron transfers to copper by the transmetalation18 with
diarylcuprate 8 to give alkenyl(aryl)cuprate 9 and to regenerate
aryliron 6. Alkenylmagnesium bromide 10 is released as the
arylmagnesiation product by the transmetalation between alkenyl-
cuprate 9 and aryl Grignard reagent 119 to complete the catalytic
cycle.
In conclusion, we have disclosed the arylmagnesiation of alkynes
effectively catalyzed by a catalyst system consisting of iron and
copper. The most striking feature is that the cooperative catalysis
enables us to conduct otherwise hardly attainable arylmagnesiation
of dialkylacetylenes.
4
467-4470. For an account, see: (b) Sonogashira, K. J. Organomet.
Chem. 2002, 653, 46-49. The cooperative catalysis has recently been
reviewed with an appropriate classification: (c) Lee, J. M.; Na, Y.; Han,
H.; Chang, S. Chem. Soc. ReV. 2004, 33, 302-312. See also the following
reviews: (d) van den Beuken, E. K.; Feringa, B. L. Tetrahedron 1998,
5
1
4, 12985-13011. (e) Chen, E. Y.-X.; Marks, T. J. Chem. ReV. 2000,
00, 1391-1434.
1
(11) Configuration of (E)-3a was determined by NOE experiment in H NMR.
1
The ratio of E to Z was determined by GC, GC-MS and H NMR.
(
3
12) The reaction in the absence of PBu gave less than 3% yield of 3a with
4
(
6% conversion of 2a. The amount of PBu
Fe: 3 mol %; Cu: 6 mol %) without significant loss of the yield (61%,
E:Z ) 91:9). For the experimental conditions, see Supporting Information.
(13) The use of FeCl , CuCl, CuI, and CuBr gave similar results. The yields
3
can be reduced to 10 mol %
3
2
3 2 3
were low with other phosphine ligands (PPh , PhPMe , PCy , and dppp)
and with nitrogen ligands (pyridine and substituted pyridines).
14) High regioselectivities for aryl(alkyl)alkynes were also reported in the
arylmetalations. See refs 3a, d-f.
(
(15) A mixture of two diastereomeric isomers, both of which have (Z)-
configuration, due to the central chirality at the R-carbon of the allylic
alcohol and the axial chirality based on the restricted rotation about the
naphthyl-alkenyl bond.
(
3
16) Organoiron compounds are generated by the reaction of FeCl with
alkylmagnesium bromides. Kauffmann, T.; Laarmann, B.; Menges, D.;
Voss, K.-U.; Wingberm u¨ nster, D. Tetrahedron Lett. 1990, 31, 507-510.
17) Rahman, M. T.; Hoque, A. K. M. M.; Siddique, I.; Chowdhury, D. A.
N.; Nahar, S. K.; Saha, S. L. J. Organomet. Chem. 1980, 188, 293-300.
(
(18) Arylcuprates generated in situ from CuCN‚2LiCl and arylmagnesium
iodides are used effectively in the iron-catalyzed coupling with aryl iodides.
Sapountzis, I.; Lin, W.; Kofink, C. C.; Despotopoulou, C.; Knochel, P.
Angew. Chem., Int. Ed. 2005, 44, 1654-1657.
(
19) Transmetalation between alkenyl(aryl)cuprates and arylmagnesium bro-
mides should be involved in the copper-catalyzed arylmagnesiation of
propargyl alcohols or sulfonylacetylenes. See ref 7.
Acknowledgment. This work has been supported financially
by Grant-in-Aids for Creative Scientific Research (16GS0209) and
for Scientific Research, the Ministry of Education, Culture, Sports,
JA0542136
J. AM. CHEM. SOC.
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