Stereoselective coupling reaction of dimethylzinc and alkyne toward nickelacycles

Article abstract of DOI:10.1021/ol2005352

Chemical equations presented. Ni catalyst promotes the three-component coupling reaction of vinyloxacyclopropane, alkyne, and dimethylzinc to provide 2,5-heptadienyl alcohol in high yields. Vinylcyclopropane also participates in a similar three-component

Full text of DOI:10.1021/ol2005352

ORGANIC
LETTERS
2011
Vol. 13, No. 9
2266–2269
Stereoselective Coupling Reaction of
Dimethylzinc and Alkyne toward
Nickelacycles
Takamichi Mori,‡ Toshiyuki Nakamura,† and Masanari Kimura*,†
Graduate School of Science and Technology and Department of Applied Chemistry,
Nagasaki University, 1-14 Bunkyo, Nagasaki 852-8521, Japan
masanari@nagasaki-u.ac.jp
Received February 27, 2011
ABSTRACT
Ni catalyst promotes the three-component coupling reaction of vinyloxacyclopropane, alkyne, and dimethylzinc to provide 2,5-heptadienyl
alcohol in high yields. Vinylcyclopropane also participates in a similar three-component coupling reaction to afford dimethyl
(R-heptadienyl)malonate with excellent E-stereoselectivity.
Metallacycles are attractive and convenient key inter-
mediates for CꢀC bond formation and CꢀC bond clea-
vage reactions.1 Within this decade, examples of Ni-
catalyzed ring-expansion2 and CꢀC bond-cleavage
reactions3 have been extensively developed as efficient
functional transformations. We previously reported the
Ni(0) catalyst accelerated oxidative cyclization of alde-
hydes and conjugated dienes in the presence of Et3B4 and
Et2Zn,5 with subsequent reductive coupling, to provide
bis-homoallyl alcohols with excellent regio- and stereose-
lectivities through key oxanickelacycle intermediates.
Furthermore, we demonstrated that similar catalytic sys-
tems promoted the multicomponent coupling reaction of
Me2Zn, alkyne, conjugated diene, and aldehyde, in this
order, to provide 3,6-octadienyl alcohols with excellent
regio- and stereoselectivities (Scheme 1).6
† Department of Applied Chemistry.
‡ Graduate School of Science and Technology.
(1) (a) Negishi, E.; Holmes, S. J.; Tour, J. M.; Miller, J. A.; Ceder-
baum, F. E.; Swanson, D. R.; Takahashi, T. J. Am. Chem. Soc. 1989,
111, 3336. (b) Kablaoui, N. M.; Buchwald, S. L. J. Am. Chem. Soc. 1995,
117, 6785. (c) Crowe, W. E.; Rachita, M. J. J. Am. Chem. Soc. 1995, 117,
6787. (d) Jun, C.-H. Chem. Soc. Rev. 2004, 33, 610. (e) Kimura, M.;
Tamaru, Y. Top. Curr. Chem. 2007, 279, 173. (f) Saito, N.; Sugimura, Y.;
Sato, Y. Org. Lett. 2010, 12, 3494. (g) Fukushima, M.; Takushima, D.;
Kimura, M. J. Am. Chem. Soc. 2010, 132, 16346.
(2) (a) Suginome, M.; Matsuda, T.; Yoshimoto, T.; Ito, Y. Organo-
metallics 2002, 21, 1537. (b) Zuo, G.; Louie, J. Angew. Chem., Int. Ed.
2004, 43, 2277. (c) Zuo, G.; Louie, J. J. Am. Chem. Soc. 2005, 127, 5798.
(d) Liu, L.; Montgomery, J. J. Am. Chem. Soc. 2006, 128, 5348. (e)
Ogoshi, S.; Nagata, M.; Kurosawa, H. J. Am. Chem. Soc. 2006, 128,
5350. (f) Bowman, R. K.; Jonson, J. S. Org. Lett. 2006, 8, 573.
(3) (a) Ikeda, S.; Miyashita, H.; Taniguchi, M.; Kondo, H.; Okano,
M.; Sato, Y.; Odashima, K. J. Am. Chem. Soc. 2002, 124, 12060. (b)
Necas, D.; Tursky, M.; Kotora, M. J. Am. Chem. Soc. 2004, 126, 10222.
(c) Ikeda, S.; Sanuki, R.; Miyachi, H.; Miyashita, H.; Taniguchi, M.;
Odashima, K. J. Am. Chem. Soc. 2004, 126, 10331. (d) Saito, S.; Masuda,
M.; Komagawa, S. J. Am. Chem. Soc. 2004, 126, 10540. (e) Murakami,
M.; Ashida, S.; Matsuda, T. J. Am. Chem. Soc. 2005, 127, 6932. (f)
Murakami, M.; Ashida, S.; Matsuda, T. J. Am. Chem. Soc. 2006, 128,
2166.
Scheme 1. Ni-Catalyzed Multicomponent Coupling Reaction
with Alkyne, Diene, Aldehyde, and Me2Zn
(4) (a) Kimura, M.; Ezoe, A.; Shibata, K.; Tamaru, Y. J. Am. Chem.
Soc. 1998, 120, 4033. (b) Kimura, M.; Ezoe, A.; Tanaka, S.; Tamaru, Y.
Angew. Chem., Int. Ed. 2001, 40, 3600. (c) Kimura, M.; Ezoe, A.; Mori,
M.; Iwata, K.; Tamaru, Y. J. Am. Chem. Soc. 2006, 128, 8559.
(d) Tamaru, Y.; Kimura, M. Organic Syntheses 2006, 83, 88.
Ikeda et al. revealed the Ni-catalyzed coupling reaction
of allyl chloride, an alkyne, and Me2Zn in the presence of
Ni catalyst via the syn stereoselective addition of a
r
10.1021/ol2005352
Published on Web 03/30/2011
2011 American Chemical Society

π-allylnickel species followed by methyl group transfer to
the alkyne to produce 1,4-pentadiene.7 Furthermore, the
Ni(0) metal-catalyzed coupling reaction of alkyne-teth-
ered vinylcyclopropanes with allyl chloride has been
reported.8 In this case, the addition of the π-allylnickel
species to the alkyne moiety proceeds with β-syn elim-
ination of the cyclopropyl CꢀC bond giving the (E)-1,
3-diene with excellent regio- and stereoselectivities.
Encouraged by these multicomponent coupling reac-
tions involving π-allylnickel species by Ikeda’s protocols
and our previous strategies utilizing oxanickelacycles
with alkynes and organozinc reagents, we were pro-
mpted to develop stereodefined functionalizations using
allylating agents and alkynes based on the structural
variety of oxanickelacycles.
Table 1. Ni-Catalyzed Three-Component Connection Reaction
of Alkyne, Vinyloxacyclopropane and Me2Zna
entry
ligand
solvent
conditions
yield of 1a (%) [E/Z]
1
2
none
none
none
none
none
none
Ph3P
n-Bu3P
dppf
THF
rt, 24 h
50 °C, 24 h
rt, 24 h
rt, 24 h
rt, 24 h
rt, 24 h
rt, 48 h
rt, 48 h
rt, 48 h
rt, 24 h
92 [3:1]
89 [3:1]
84 [3:1]
81 [3:1]
59 [3:1]
20 [3:1]
71 [3:1]
no reaction
no reaction
81 [1:1]
THF
3
ether
toluene
CH2Cl2
dioxane
THF
Herein, we would like to report the regio- and stereo-
controlled three-component coupling reaction of alkynes,
Me2Zn, and vinyloxacyclopropane and vinylcyclopropane
through nickelacycle intermediates to provide dienyl
homoallylalcohols and R-dienyl malonates.
4
5
6
7
8
THF
9b
10c
THF
The reaction was readily conducted by exposing Me2Zn
to a mixture of vinyloxacyclopropane and alkynes at room
temperature under nitrogen atmosphere. The results
using various kinds of ligands and solvents are shown in
Table 1.9 It was clear that THF was the most effective
solvent (entries 1ꢀ6, Table 1). In all cases, the alkynes
tended to attack on the terminal carbon atom of the vinylic
group to afford heptadienyl alcohol 1a via methyl group
transfer from Me2Zn in a 3:1 ratio of E and Z isomers with
respect to the C-2 olefin geometry. Although various kinds
of ligands such as monodentate, bidentate phosphine, and
NHC ligands were employed in the reaction (entries 7ꢀ10,
Table 1), it was the absence of ligand at room temperature
that provided the best result in the formation of 1a (entry 1,
Table 1).
Next, we conducted the multicomponent coupling reac-
tion of substituted vinyloxacyclopropane, various alkynes,
and Me2Zn under the optimized conditions of Table 1.
Although diphenylacetylene participated in the coupling
reaction in good yield to afford a mixture of E and Z
isomers (entry 1, Table 2), bis(trimethylsilyl)acetylene and
an electron-deficient alkyne did not provide the desired
results (entries 2 and 3, Table 2). An unsymmetrical alkyne
took part in the reaction in high yield to give regio- and
stereoisomers as an inseparable mixture (entry 4, Table 2).
NHC
THF
a The reaction was undertaken in the presence of vinyloxacyclopro-
pane (1 mmol), Ni(acac)2 (0.1 mmol), ligand (0.2 mmol), and dimethyl-
zinc (1.2 mmol; 1 M hexane solution) in solvent (3 mL) under nitrogen
atmosphere. b dppf: diphenylphosphinoferrocene (0.1 mmol) was used.
c NHC ligand was prepared from 1,3-bis(2,6-diisopropylphenyl)-
imidazolium chloride with 0.2 mmol of t-BuOK.
Terminal alkynes also provided the expected products 1e
and 1f in moderate to good yields, along with the branched
regioisomers 1e0 and 1f0 (entries 5 and 6, Table 2).
2-Methyl-2-vinyloxacyclopropane underwent a similar
Table 2. Ni-Catalyzed Coupling Reaction of Various Alkyne,
Substituted Vinyloxacyclopropane, and Me2Zna
entry epoxide R alkyne R0
R00
time (h) yield (%) [E:Z ratio]
1
2
3
4
5
6
7
8
9
H
Ph
Ph
TMS
24
24
24
24
24
24
24
24
24
1b: 84 [2:1]
(5) (a) Kimura, M.; Fujimatsu, H.; Ezoe, A.; Shibata, K.; Shimizu,
M.; Matsumoto, S.; Tamaru, Y. Angew. Chem. Int Ed. 1999, 38, 397.
(b) Kimura, M.; Miyachi, A.; Kojima, K.; Tanaka, S.; Tamaru, Y.
J. Am. Chem. Soc. 2004, 126, 14360.
(6) (a) Kimura, M.; Ezoe, A.; Mori, M.; Tamaru, Y. J. Am. Chem.
Soc. 2005, 127, 201. (b) Kimura, M.; Kojima, K.; Tatsuyama, Y.; M.;
Tamaru, Y. J. Am. Chem. Soc. 2006, 128, 6332. (c) Kimura, M.;
Tatsuyama, Y.; Kojima, K.; Tamaru, Y. Org. Lett. 2007, 9, 1871.
(d) Kimura, M.; Togawa, M.; Tatsuyama, Y.; Matsufuji, K., Y. Tetra-
hedron Lett. 2009, 50, 3982.
(7) (a) Ikeda, S.; Cui, D.-M.; Sato, Y. J. Org. Chem. 1994, 59, 6877.
(b) Cui, D.-M.; Tsuzuki, T.; Miyake, K.; Ikeda, S.; Sato, Y. Tetrahedron
1998, 54, 1063. (c) Ikeda, S.; Miyashita, H.; Sato, Y. Organometallics
1998, 17, 4316.
(8) Ikeda, S.; Obara, H.; Tsuchida, E.; Shirai, N.; Odashima, K.
Organometallics 2008, 27, 1645.
(9) See the Supporting Information.
H
TMS
1c: 35 [2:1]
H
CO2Me CO2Me
no reaction
H
Et
Ph
1d: 93 [8:5:2:1]
1e: 81 [2:1], 10e: 15
1f: 64 [2:1], 10f: 33
1g: 100 [1:2]
1h: 75 [1:3]
H
H
Ph
H
H
TMS
Et
Me
Me
Me
Et
Ph
TMS
Ph
TMS
1i: 61 [1:1]
a The reaction was undertaken in the presence of vinyloxacyclopro-
pane (1 mmol), Ni(acac)2 (0.1 mmol), and dimethylzinc (1.2 mmol; 1 M
hexane solution) in THF (3 mL) at room temperature under nitrogen
atmosphere.
Org. Lett., Vol. 13, No. 9, 2011
2267

coupling reaction with good to excellent yields, and em-
ployment of 3-hexyne led to the formation of the desired
product 1g in quantitative yield in a 1:2 ratio of E and Z
isomers (entry 7, Table 2). Diphenylacetylene and bis-
(trimethylsilyl)acetylene also showed similar reactivities
and selectivities in moderate to good yields (entries 8 and 9,
Table 2).
smoothly at room temperature within several hours
and the coupling products were obtained with excellent
E-stereoselectivities (entries 1 and 2, Table 3). The tri-
methylsilyl group also took part in efficient coupling to
give the corresponding desired product 2c in moderate
yield with E-stereoselectivity (entry 3, Table 3). Unsymme-
trical internal alkynes participated in the coupling reaction
giving rise to a mixture of regioisomers with exclusive E-
stereoselectivities (entries 4 and 5, Table 3). In all cases, the
stereochemistry with respect to the Me group and the
olefinic main chain is the Z-form, as in the reaction of
vinylcyclopropane. The reaction using terminal alkynes
such as trimethylsilylacetylene and phenylacetylene was
changed dramatically, and the desired products 2 were not
obtained at all. Instead, the dienynes 3f and 3g, involving
dimerization of the terminal alkynes, were produced as
major products (entries 6 and 7, Table 3).
A plausible reaction mechanism for the multicomponent
coupling reaction of vinyloxacyclopropane, alkyne, and
dimethylzinc is displayed in Scheme 2. Low stereoselectiv-
ities for the coupling reactions usingvinyloxacyclopropane
might originate from the formation of the π-allyloxanick-
elacycle intermediate I in equilibrium with the 6-membered
oxanickelacycle II. It is known that vinyloxacyclopropane
readily undergoes oxidative addition toward Ni(0) metal
species coordinated by alkynes to form four- or six-mem-
bered oxanickelacycles. This is followed by methyl group
transferfrom theZnatom to theNimetal center, leading to
CꢀC bond formation and a mixture of E and Z isomers.
Terminal carbons of phenylacetylene and trimethylsilyla-
cetylene attack on the allylic position of vinyloxacyclo-
propane to afford the branched regiosomers 10 owing to
less steric repulsion between the H atom of the terminal
alkyne and the allylic moiety of intermediate III
(Scheme 2).
Table 3. Ni-Catalyzed Three-component Connection Reaction
of Various Alkyne, Vinylcyclopropane, and Me2Zna
Scheme 2. Reaction Mechanism for Coupling Reaction of Vi-
nyloxacyclopropane, Alkyne, and Me2Zn
entry
R0
Et
R00
Et
time (h)
yield (%) [E:Z]
2a: 84 [8:1]
1
2
3
4
5
6
7
1
3
Ph
TMS
Et
Ph
2b: 73 [E only]
2c: 63 [E only]
2d: 92 [E only]b
2e:83 [E only]
TMS
Ph
3
6
Me
H
TMS
Ph
1
24
6
3f: 71 [E only]
3g: 56 [E only], 20g: 24
H
TMS
a The reaction was undertaken in the presence of vinylcyclopropane
(1 mmol), Ni(acac)2 (0.1 mmol), alkyne (1 mmol), and diethylzinc (1.2
mmol; 1 M hexane solution) in THF (3 mL) at room temperature under
nitrogen atmosphere. b Product 2d was obtained as a mixture of regioi-
somer in a 3:1 ratio.
The stereochemistry of the products was unequivocally
determined on the basis of NOE experiments. The results
ofirradiation attheboldprotons areillustrated inFigure1.
According to the NOE results, irrespective of the kinds of
regioisomers derived from the symmetrical and unsymme-
trical alkynes, it was apparent that methyl group transfer
from Me2Zn to the acetylenic triple bond proceeded in a
syn manner to deliver Z-stereochemistry withrespect to the
C5olefinic geometryand E-stereochemistry with respect to
the C2 position by the ring expanding reaction processes of
the vinyl cyclopropyl groups.
Next, we investigated the coupling reaction of alkynes,
Me2Zn, and vinylcyclopropane derived from dimethyl
malonate and 1,4-dichloro-2-butene under similar catalytic
conditions (Table 3). In most cases, the reaction proceeded
2268
Org. Lett., Vol. 13, No. 9, 2011

Scheme 3. Reaction Mechanism for Coupling Reaction of Vi-
nylcyclopropane, Alkyne, and Me2Zn
Figure 1. NOE data for the irradiation at the bold methylene
protons.
A reaction mechanism for the coupling reaction of
alkyne, vinylcyclopropane, and Me2Zn is displayed in
Scheme 3. The exclusive E-stereochemistry might stem
from the stability of the produced nickelacycles. Forma-
tion of allylnickel species IV would predominate over that
of 8-membered ring species V owing to the entropy effect
for the ring-closing reaction. This is followed by insertion
of the alkyne to the allylic terminus of the allylnickel
species to provide (E)-2 isomer exclusively. As in the case
of using terminal alkyne, zinc acetylide derived from
dimethylzinc and terminal alkyne might preferentially
participate in the coupling reaction via transmetalation
withallylnickel species IV0 togiverise todieneꢀyne 3 asthe
major products.10
In summary, we have developed a Ni-catalyzed three-
component coupling reaction of Me2Zn, alkynes, and
vinyloxacyclopropanes and vinylcyclopropanes to af-
ford dienyl alcohols and R-heptadieneyl dimethyl mal-
onates in excellent yields with high stereoselectivities.
The application and scope of this method for the
synthesis of complicated molecules, such as terpenes
and physiologically active molecules, are currently
under investigation.
Acknowledgment. Financial support from the Min-
istry of Education, Culture, Sports, Science, and
Technology, Japanese Government (Grant-in Aid
for Scientific Research (B) 21350055) is gratefully
acknowledged. This work was supported by the Asahi
Glass Foundation.
(10) Since Ni(0) catalysts tend to promote a head-to-tail dimerization
of terminal alkynes in the presence of organozinc reagents to give the
enyne framework, the aleternative coupling reaction involving dimer-
ization of terminal alkyne followed by carbonickelation toward vinyl-
cyclopropane to provide dieneꢀyne 3 might be probable. (a) Giacomelli,
G.; Marcacci, F.; Caporusso, A. M.; Lardicci, L. Tetrahedron Lett. 1979,
20, 3217. (b) Ogoshi, S.; Ueta, M.; Oka, M.; Kurosawa, H. Chem.
Commun. 2004, 2732. (c) Nakao, Y.; Shirakawa, E.; Tsuchimoto, T.;
Hiyama, T. J. Organomet. Chem. 2004, 689, 3701. (d) Takahashi, G.;
Shirakawa, E.; Tsuchimoto, T.; Kawakami, Y. Adv. Synth. Catal. 2006,
348, 837.
Supporting Information Available. Experimental pro-
cedures and NMR spectra for all products. This material
is available free of charge via the Internet at http://pubs.
acs.org.
Org. Lett., Vol. 13, No. 9, 2011
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