Chemo- and regioselective dimerization of terminal alkynes promoted by methylaluminoxane

Article abstract of DOI:10.1021/ol9903584

(figure presented) Methylalumoxane (MAO) was found to be an active catalytic precursor for the chemo- and regioselective dimerization of a wide range of aryl-and alkyl-substituted terminal alkynes yielding the corresponding geminal dimers A. For an olefin

Full text of DOI:10.1021/ol9903584

ORGANIC
LETTERS
2000
Vol. 2, No. 6
737-740
Chemo- and Regioselective Dimerization
of Terminal Alkynes Promoted by
Methylaluminoxane
Aswini K. Dash and Moris S. Eisen*
Department of Chemistry and Institute of Catalysis Science and Technology,
Technion-Israel Institute of Technology, Haifa 32000 Israel
chmoris@techunix.technion.ac.il
Received November 15, 1999
ABSTRACT
Methylalumoxane (MAO) was found to be an active catalytic precursor for the chemo- and regioselective dimerization of a wide range of aryl-
and alkyl-substituted terminal alkynes yielding the corresponding geminal dimers A. For an olefin-functionalized terminal alkyne (RCtCH, R
) MeCdCH ), the geminal dimer undergoes an intermolecular [4 + 2] cycloaddition forming compound B.
2
The metal-catalyzed dimerization/oligomerization of terminal
alkynes attracts major research attention because it provides
a facile entry into the chemistry of conjugated enynes, a
versatile building block for the synthesis of natural products1
and organic conducting polymers.2 Enynes are the simplest
coupling product of alkynes in the metal-based oligomer-
ization cycle. The catalytic dimerization cycle is believed
to proceed by the activation of the alkyne C-H bond by a
metal complex producing the metal acetylide LnMCtCR
(Ln ) ancillary ligands) compound. Insertion of the alkyne
carbon-carbon triple bond into the acetylide moiety yields
an alkenyl intermediate LnMCHdCRCtCR, which may
followed by a σ-bond metathesis with another alkyne C-H
bond, allowing the dimer formation and regenerating the
LnMCtCR species. The factors that govern the regio- and
stereoselectivity strongly depend on the electronic and steric
hindrance of the alkyne substituents and the coordination
sphere of the active metal center.3 The use of stoichiometric
amounts of organoaluminum reagents in organic synthesis
is well documented in the literature.4 Regarding the catalytic
use of organoaluminum compounds, they have been utilized
in processes such as hydrosilylation reactions,5 epoxide ring
6
opening to carbonyl compounds
and recently in the
polymerization of R-olefins.7 Regarding alkynes, a bis-
(benzamidinate) aluminum hydride complex8 and, recently,
a cationic aminotroponiminate aluminum complex9 have been
t
found to promoted the selective dimerization of BuCtCH
(3) (a) Horton, A. D. J. Chem. Soc. Chem. Commun. 1992, 185. (b)
Horton, A. D.; Orpen, A. G. Angew. Chem., Int. Ed. Engl. 1992, 31, 876.
(4) (a) Eisch, J. J. In ComprehensiVe Organic Synthesis; Trost, B. M.,
Fleming, I., Eds.; Pergamon Press: Oxford, U.K., 1991; Vol. 8, p 733. (b)
Eisch, J. J. In ComprehensiVe Organometallic Chemistry, 2nd ed.; McKillop,
A., Ed.; Pergamon: New York, 1995; Vol. 11, pp 222-311. (c) Zietz, J.
R., Jr.; Robinson, G. C.; Lindsay, K. L. In ComprehensiVe Organometallic
Chemistry; Wilkinson, G., Stone, F. G. A., Abel, E. W., Eds.; Pergamon
Press: Oxford, U.K., 1982; Vol. 7, p 365.
(1) (a) Miller, S. J.; Kim, S.-H.; Chen, Z. R.; Grubbs, R. H. J. Am. Chem.
Soc. 1995, 117, 2108. (b) Grissom, J. W.; Gunawardena, G. U.; Klingberg,
D. Tetrahedron 1996, 52, 6453.
(2) (a) Parshall, G. W.; Ittle, S. D. Homogeneous Catalysis, 2nd ed; John
Wiley & Sons: New York, 1992. (b) Materials for Nonlinear Optics:
Chemical Perspectives; Stucky, G. D., Marder, S. R., Sohn, J., Eds; ACS
Symposium Series 455; American Chemical Society: Washington, DC,
1991.
10.1021/ol9903584 CCC: $19.00 © 2000 American Chemical Society
Published on Web 02/19/2000

toward the corresponding geminal dimer. For other group
13 metal compounds, the linear trimerization of silylacetylene
has been observed, using GaCl3 in the presence of Grignard
reagents.10 In this paper, we report the catalytic activity of
methylaluminoxane (MAO), the well-known cocatalyst in
the polymerization of R-olefins, for the regio- and chemo-
selective head-to-tail dimerization of terminal alkynes. In
addition, we present a simple kinetic competition between
two different alkynes allowing the formation of cross dimers.
Moreover, we show that the head-to-tail dimer obtained
from the dimerization of the vinyl substituted alkyne HCt
C-C(Me)dCH2, undergoes either an intermolecular Diels-
Alder cycloaddition, or reacts with the polar alkyne HCt
CCO2Et to form the corresponding Diels-Alder cross adduct.
Reaction of an excess of iPrCtCH with catalytic amounts
of methylaluminoxane (MAO), in nonpolar solvents (C6H6,
toluene, cyclohexane), results in the exclusive multigram
formation of the chemo- and regioselective head-to-tail dimer
2,4-diisopropyl-1-butene-3-yne (1), without formation of
other dimer or higher oligomers. To explore the scope of
the catalytic reaction, the dimerization reactions on a range
of substrates (alkyl- and aryl-substituted terminal alkynes)
were studied under similar reaction conditions producing,
in all cases, exclusively the corresponding regioselective
head-to-tail dimer as shown in eq 1 (Table 1).
yield (> 99%), whereas for other less bulky substituted
terminal alkynes the time varies from 20 h up to 48 h. In
contrast, when the reaction was carried out at higher
temperature (78 °C), 99.5% yield was obtained for almost
all alkynes in about 1 h (Table 1).
The activation parameters for the MAO-dimerization of
iPrCtCH were measured and are characterized by a rather
small enthalpy of activation (11.6(3) kcal mol-1) and a large
negative (even for an intermolecular reaction) entropy of
activation (-40.4(5) eu; ∆Gq ) 24(1) kcal mol-1 at 298 K).
These parameters suggest a highly ordered transition state
with considerable bond making to compensate to bond
breaking. Thus, it seems plausible that a four-center transition
state is operative for aluminum complexes in analogy to other
early transition-metal/lanthanide/actinide complexes, were no
oxidative addition or reductive elimination operative exhibit-
11
ing a large negative entropy of activation (Figure 1).
Figure 1. Plausible mode of insertion for organoaluminum
complexes.
In contrast to the alkyl- and aryl-substituted alkynes, the
dimerization reaction of TMSCtCH was found to proceed
without selectivity. The catalytic reaction with MAO is
operative only at high temperatures producing a mixture of
the three expected dimers (the number in parentheses are
the isolated yields with a conversion of 100%) (eq 2).12,13
The dimerization of terminal alkynes was found to be slow
at room temperature depending on the nature of the alkyne
substituents. For example, for BuCtCH, 10 days are
t
necessary at room temperature to complete a 100% conver-
sion into the corresponding geminal dimer in quantitatively
Table 1. Activity Data for the Catalytic Dimerization of
Teminal Alkynes (RCtCH) Promoted by Methylaluminoxanea
gem-H2CdC(R)CtC(R) Nt,
entry
R
solventb
C6H6
C6H6
C6H6
C6H6
C6H6
C6H6
(isolated yield, %)
h-1 c
1
2
3
iPr
99.3
99.2
99.7
99.4
97.4
99.1
99.2
44e
5.1
4.8
0.4
3.7
0.1
3.3
2.4
0.1
4.4
1.5
The solvent effect was also studied in the MAO-catalyzed
dimerization of PrCtCH. For aromatic solvents like C6H6
nBu
tBu
Ph
i
4
5
6
7
8
9
or toluene, no major difference is exhibited in the kinetics
of the reaction. In cyclohexane, the reaction is slower by a
factor of 3 possibly because of the low miscibility of MAO
in nonpolar aliphatic solvents. However, no reaction was
observed in polar solvents (ether, THF), presumably due to
Me
p-tBu-Ph
H2CdC(Me) C6H6
Me3Sid
iPr
C6H6
toluene
cyclohexane
THF
diethyl ether
no solvent
98.9
99
10
11
12
13
iPr
iPrf
iPrf
iPr
(5) (a) Asao, N.; Sudo, T.; Yamamoto, Y. J. Org. Chem. 1996, 61, 7654.
(b) Sudo, T.; Asao, N.; Gevorgyan, V.; Yamamoto, Y. J. Org. Chem. 1999,
64, 2494.
(6) (a) Maruoka, K.; Ooi, T.; Nagahara, S.; Yamamoto, H. Tetrahedron
Lett. 1989, 30, 5607. (b) Maruoka, K.; Ooi, T.; Nagahara, S.; Yamamoto,
H. Tetrahedron 1991, 47, 6983.
(7) (a) Coles, M. P.; Jordan, R. F. J. Am. Chem. Soc. 1997, 119, 8125.
(b) Radzewich, C. E.; Coles, M. P.; Jordan, R. F. J. Am. Chem. Soc. 1998,
120, 9384.
99.5
4.7
a The reactions were carried out at the corresponding reflux temperatures.
b Deuterated solvents. c Turnover frequencies. d No reaction was observed
at room temperature. e Other dimers are obtained in the reaction mixture:
trans-(TMS)CHdCHCtC(TMS) (33%) and cis-(TMS)CHdCHCtC(TMS)
(23%). f No reaction was observed at either room or reflux temperatures.
738
Org. Lett., Vol. 2, No. 6, 2000

the coordination of the donor atom of the solvent to the Lewis
acid metal center. This interaction is expected to block the
coordination site at the metal impeding the alkyne to react
with either an Al-Me or an Al-acetylide moiety. The same
lack in reactivity was observed by using substituted terminal
alkynes containing heteroatom functional groups (RCtCH;
R ) CH2NH2, CH2NMe2, CO2Et, CH2CH2CN).
iPrCtCD was studied. Mixing MAO with iPrCtCD at room
temperature in a stoichiometric ratio of 1:2, respectively,
allows the formation of CH3D and the dideuterium geminal
dimer D2CdC(iPr)CtCPri, suggesting the formation of an
aluminum-acetylide bond. The CH3D was characterized by
2
either H NMR (δ ) -1. 43 ppm) or 13C{H} NMR (δ )
14.1, doublet, 2J ) 18.8 Hz). Kinetically, by comparing the
i
i
Although the turnover frequencies for the MAO-catalyzed
dimerization of terminal alkynes are rather small (Table 1),
in the absence of moisture and oxygen, MAO is able to react
continuously producing large turnover numbers (50-100).
reaction of MAO with either PrCtCD or PrCtCH, no
kinetic isotope effect was observed, indicating the rapidity
of the reaction. Moreover, the stoichiometric reaction of
MAO with iPrCtCH (1:2) yielded at room temperature only
the geminal dimer despite the possible formation of 4-methyl-
2-pentene or 2,3-dimethyl-1-butene isomers. This result
corroborates that for MAO, the insertion of the alkyne into
the Al-alkyl bond is not a major competing pathway for
product formation.4b,16
i
Hence, the reaction of MAO with PrCtCH (1:10) was
carried out repeatedly 10 times with the same catalyst, after
vacuum transferring the product, indicating a high thermal
and chemical stability of the active Al complex. Unlike the
heteroatom-substituted terminal alkynes, the olefin function-
alized terminal alkyne undergoes coupling reaction toward
the head-to-tail dimer. Thus, the reaction of MAO in benzene
with an excess of HCtCC(Me)dCH2 results in the quantita-
tive formation of the geminal dimer 10 in 20 or 2 h at either
room temperature or 78 °C, respectively (eq 3).14
To gain some insight into the catalytic reaction and to
understand the role of the aluminum center in MAO (to
ensure that no other metal contamination is the active
catalyst), a similar reaction was carried out utilizing Me3Al
instead of MAO. Thus, in the reaction of Me3Al with
iPrCtCH at room or high temperature no products are
observed. However, the addition of a stoichiometric amount
of triple distilled water (Me3Al/H2O ) 1:1.8) into the same
reaction mixture leads to a quantitative formation of the head-
to-tail dimer 1. This result corroborates with the fact that
MAO is a stronger Lewis acid as compared to Me3Al and is
presumably responsible for such activity.17,18
A plausible pathway for the MAO-catalyzed dimerization
of terminal alkynes is shown in Scheme 1. The proposed
mechanism consists of a sequence of well-established
elementary reactions such as insertion of an alkyne into an
M-carbyl σ-bond and σ-bond metathesis. Thus, the first step
in the catalytic cycle involves the σ-bond metathesis
(12) Stockis and Hoffmann have performed calculations on the polariza-
tion of the π*-orbitals in TMSCtCH. The electronic effects due to the
polarization are believed to be responsible for the difference in regio-
selectivities of the dimerization results. Stockis, A.; Hoffmann, R. J. Am.
Chem. Soc. 1980, 102, 2952. The cis isomer will probably be formed by
an isomerization of the trans isomer via an envelope mechanism; see: Wang,
J. Q.; Dash, A. K.; Berthet, J. C.; Ephritikhine, M.; Eisen, M. S.
Organometallics 1999, 18, 2407.
Heating a benzene solution of compound 10 (78 °C for 5
h) leads to the quantitative (yield >99.5%) formation of 11,
which is the [4 + 2] intermolecular Diels-Alder cyclo-
addition product. From the two possible expected stereo-
isomers, only one isomer was exclusively obtained as
established by 2D-NMR spectroscopic measurements.14,15 It
is noteworthy that small or trace amounts of higher cyclo-
addition oligomers where not detected by either NMR or
GC/MS spectrometry.
(13) No allenic compounds were formed in any of the dimerization
reactions. (a) Evans, W. J.; Keyer, R. A.; Ziller, J. W. Organometallics
1993, 12, 2618. (b) St. Claire, M.; Schaefer, W. P.; Bercaw, J. E.
Organometallics 1991, 10, 525. (c) Thomson, M. E.; Baxter, S. M.; Bulls,
A. R.; Burger, B. J.; Nolan, M. C.; Santarsiero, B. D.; Schefer, W. P.;
Bercaw, J. E. J. Am. Chem. Soc. 1987, 109, 203.
To study the fate of the MAO during the reaction, a
stoichiometric reaction between MAO and deuterated alkyne
1
(14) Compound 1-16 were characterized by H NMR, 13C NMR, 2D-
COSY, NOESY, CH correlation, and GC/MS spectroscopy; see the
Supporting Information
(15) The reaction of 10 with HCtCCO2Et for 5 h at 78 °C forms 11
(78%) and the cross Diels Alder cycloaddition product 16 (22%).
(8) Duchateau, R.; Meetsma, A.; Teuben, J. H. J. Chem. Soc., Chem.
Commun. 1996, 223.
(9) Korolev, A. V.; Guzei, I. A.; Jordan, R. F. J. Am. Chem. Soc. 1999,
121, 11605.
(10) Kido, Y.; Yamaguchi, M. J. Org. Chem. 1998, 63, 8086.
(11) (a) Boff, L. S.; Novak, B. M. Macromolecules 1997, 30, 3494. (b)
Evans, W. J.; DeCoster, P. M.; Greaves, J. Macromolecules 1995, 28, 7929.
(c) Heeres, H. J.; Heeres, A.; Teuben, J. H. Organometallics 1990, 9, 1508.
(d) Mitchell, J. P.; Hajela, S.; Brookhart, S. K.; Hardcastle, K. I.; Henling,
L. M.; Bercaw, J. E. J. Am. Chem. Soc. 1996, 118, 1045. (e) Fu, P.-F.;
Marks, T. J. J. Am. Chem. Soc. 1995, 117, 10747 and references therein.
(f) Schaverien, C. J. Organometallics 1994, 13, 69. (g) Heeres, H. J.; Teuben,
J. H. Organometallics 1991, 10, 1980. (h) Straub, T.; Haskel, A.; Eisen,
M. S. J. Am. Chem. Soc. 1995, 117, 6364. (i) Haskel, A.; Straub, T.; Dash,
A. K.; Eisen, M. S. J. Am. Chem. Soc. 1999, 121, 3014.
(16) The insertion reaction of alkynes into Al-R (R) ethyl, isobutyl)
or Al-H producing the corresponding Al-vinyl bond has been reported;
see: Wilke, G. V.; Mu¨ller, H, Liebiegs Ann. Chem. 1960, 629, 222.
Org. Lett., Vol. 2, No. 6, 2000
739

i
the regioselective insertion of PrCtCH into the tert-butyl
acetylide complex and from the regioselective insertion of
tBuCtCH into the isopropyl acetylide complex, respectively
(eq 4). The different amounts of 13 and 14 suggest that the
Scheme 1. Plausible Mechanism for the Dimerization of
Terminal Alkynes
i
insertion of PrCtCH into either the isopropyl-acetylide or
t
the butyl-acetylide metal complex is much faster than that
of the bulkier tBuCtCH. To support the insertion hypothesis,
iPrCtCH/tBuCtCH time, h 1 (%) 3 (%) 12 (%) 13 (%) 14 (%)
1:1
1:1
2:1
1:2
12
2
12
34.2 28.9
1.5
28.0
30.6
22.6
43.5
6.5
6.0
4.7
9.2
60.6
64.0
40.9
2.8
8.7
6.5
between the terminal C-H bond of the alkyne and the Al-
Me bond of MAO, yielding the rapid formation of the
acetylide complex AlCtCR (A) and methane, as observed
during the catalytic and stoichiometric reactions. Complex
A undergoes a regioselective 1,2-head-to-tail insertion
(through a four-center transition state), yielding the alkenyl
complex B. The protonolysis of complex B, by another
alkyne, produces the corresponding geminal dimer and
regenerates the catalytic complex A. As no higher oligomers
are observed during the catalytic reaction, the turnover
limiting step for the catalytic dimerization is the insertion
of the alkyne into the Al-acetylide complex.19
0.5
three parallel reactions were carried out. In the first reaction,
the cross dimerization products were followed at regular
intervals during the course of the reaction using equimolar
amounts of the two alkynes, whereas the other two experi-
ments were performed by using nonequimolar ratio between
i
the alkynes. The reaction of equimolar amounts of PrCt
t
CH and BuCtCH with MAO was stopped after 2 h (time
i
to complete the exclusive disappearance of PrCtCH),
producing 1, 13 as the major cross compound, and 14.
Similarly, the dimerization of a 2:1 or 1:2 ratio of iPrCtCH/
tBuCtCH for 12 or 0.5 h, respectively, corroborates for a
faster insertion of the PrCtCH into the metal-acetylide as
compared to BuCtCH (eq 4).
Interestingly, the cross dimerization of a 2:1 ratio of
iPrCtCH and PhCtCH produced nearly the same amounts
of 1 and the cross dimer 15 with a total yield of 94%. The
latter is obtained by the insertion of PrCtCH into the
phenylacetylide-aluminum bond (eq 5).
Since in the dimerization of the terminal alkynes only the
geminal dimers were produced, it was interesting to induce
some kinetic competition to allow the formation of specific
i
t
i
cross dimers. The reaction of equimolar amounts of PrCt
t
CH and BuCtCH with MAO produced, after 12 h, three
homocoupling and two cross-coupling dimers (eq 4). The
obtained homocoupling dimers were the expected 1 and 3
and trace amounts of the unexpected trans isomer 12, which
i
t
is formed by the insertion of BuCtCH into the tert-butyl
acetylide complex when the bulky group of the alkyne is
pointing toward the metal center (Figure 1). The cross dimers
obtained were the two geminal 13 and 14, resulting from
(17) Zirconocene dimethyl will react with MAO yielding the corre-
sponding cationic zirconocene complex, whereas Me3Al is unable to remove
the methyde group (methyl with the pair of electrons) from the metal center.
(18) Attempts to trap any organoaluminium complexes in situ by NMR
spectroscopy were unsuccessful.
(19) In the hydrosilylation of alkynes catalyzed by AlX3 or RAlCl2, the
zwiterionic complex I has been proposed. For MAO, this intermediate can
be ruled out because of the following observations: The hydrosilylation of
terminal alkynes with PhSiH3 by MAO does not occur and a stoichiometric
amount of PhSiH2Me was obtained. No reaction was observed for internal
alkynes, as already observed for complex I.5 No reaction was observed for
terminal alkynes with functional electron-withdrawing groups.
Acknowledgment. This research was supported by The
Israel Science Foundation, administered by The Israel
Academy of Sciences and Humanities under contract 69/
97-1; by the Fund for the Promotion of Research at the
Technion; and by the E. and J. Bishop Research Fund.
A.K.D. thanks the Technion for a postdoctoral fellowship.
Supporting Information Available: Experimental pro-
cedures and ful spectroscopic data for compounds 1-16. This
material is available free of charge via the Internet at
http://pubs.acs.org.
OL9903584
740
Org. Lett., Vol. 2, No. 6, 2000