Increased activity of in situ catalysts for alkyne metathesis

Article abstract of DOI:10.1021/ol026118x

(figure presented) Reaction of an enyne (1,1-diphenyl-pent-1-ene-3-yne) with a preheated mixture of Mo(CO)₆/4-chlorophenol/3-hexyne at 130 °C furnished 1,1,6,6-tetraphenylhex-1,5-diene-3-yne in an 80% yield. If the starting material was heated

Full text of DOI:10.1021/ol026118x

ORGANIC
LETTERS
2002
Vol. 4, No. 17
2829-2831
Increased Activity of in Situ Catalysts
for Alkyne Metathesis
Glen Brizius and Uwe H. F. Bunz*
Department of Chemistry and Biochemistry, The UniVersity of South Carolina,
Columbia, South Carolina 29208
bunz@mail.chem.sc.edu
Received May 1, 2002
ABSTRACT
Reaction of an enyne (1,1-diphenyl-pent-1-ene-3-yne) with a preheated mixture of Mo(CO)6/4-chlorophenol/3-hexyne at 130 °C furnished 1,1,6,6-
tetraphenylhex-1,5-diene-3-yne in an 80% yield. If the starting material was heated with a mixture of Mo(CO)6 and 4-chlorophenol under identical
conditions, no reaction was observed.
We have developed an efficient protocol to perform alkyne
metathesis utilizing simple catalyst systems formed from Mo-
(CO)6 and 4-chlorophenol at elevated temperatures (130-
150 °C).1 Propynylated alkylbenzenes, styrenes, and stilbenes
all undergo metathesis or ADIMET polymerization smoothly
and afford the desired products in high yield and purity.
However, the in situ catalysts fail if propynylated alkenes
(enynes) or ortho-alkoxy-substituted benzene derivatives are
treated under these conditions.1 Starting materials were
always reisolated in quantitative yield, and none of the
desired products formed. To access oligomers that at least
incorporate the enediyne motif, we prepared the monomer
1, which we subjected to standard alkyne metathesis condi-
tions in the expectation to obtain its dimer (Scheme 1).
Workup showed that a series of compounds, inseparable by
standard chromatographic techniques, had formed. The mass
spectrometric analysis of the reaction mixture suggested that
random metathesis had occurred, and the compounds shown
in Scheme 1 were identified by their molecular ions.
the correct experimental conditions. It seems that once the
system is activated, productive alkyne metathesis of other-
wise sluggishly reacting substrates commences, albeit at the
(unacceptable) price of the formation of all cross dimers. If
the catalyst system could be independently “preactivated”,
it should be feasible to perform alkyne metathesis of enynes.
Consequently, the catalytic mixture of Mo(CO)6 and 4-chlo-
rophenol in o-DCB (o-dichlorobenzene) was placed in a high-
pressure tube, an excess of 3-hexyne (bp 81 °C) added to
Scheme 1. Mass Spectroscopic Analysis of Alkyne Metathesis
of 1
The significance of the experiment lies in the unexpected
detection of the “excised” dimer 2 that suggests that “in situ”
alkyne metathesis of propynylated olefins is possible under
(1) (a) Kloppenburg, L.; Song, D.; Bunz, U. H. F. J. Am. Chem. Soc.
1998, 120, 7973. (b) Bunz, U. H. F.; Kloppenburg, L. Angew. Chem. 1999,
38, 478. (c) Pschirer, N. G.; Bunz, U. H. F. Tetrahedron Lett. 1999, 40,
2481. (d) Brizius, G.; Pschirer, N. G.; Steffen, W.; Stitzer, K.; zur Loye,
H. C.; Bunz U. H. F. J. Am. Chem. Soc. 2000, 122, 12435. (e) Bunz, U. H.
F. Acc. Chem. Res. 2001, 34, 998.
10.1021/ol026118x CCC: $22.00 © 2002 American Chemical Society
Published on Web 08/02/2002

the mixture, and the closed pressure tube heated to 130 °C
for 1 h. After the pressure cap was removed, it was replaced
with a septum and purged for 1 h with nitrogen at 130 °C to
remove any excess of hexyne. After that time the monomer
3 was added to the reaction mixture and stirred under N2
for another 24 h at 130 °C. Workup furnished the title
compound 2 in 80% yield as a colorless crystalline material.
Single-crystal analysis (Figure 1) assured that metathesis had
succeeded.
Scheme 3. Synthesis of 5, 7, and 9 by Alkyne Metathesis
The pretreated catalyst system was used to make a
dihexoxy-PPE 9 in high yields (95%) and with a degree of
polymerization (Pn) of 140 repeating units.1a,c This polymer
was obtained after a metathesis time of 16 h. Gel permeation
chromatography (GPC) of aliquots taken during the reaction
show a greatly enhanced activity over the traditional Mo-
(CO)6/4-chlorophenol system. The increased activity of the
catalyst system led us to try the dimerization of the TMS-
substituted alkyne 6. Here, the corresponding dimer 7 was
isolated in 36% yield after successful but somewhat more
sluggish reaction. The decreased reactivity must be due to
the significantly increased steric hindrance that the TMS
group imparts upon the monomer. The only other compound
that could be isolated from the reaction mixture was
unreacted starting material, and increasing the temperature/
duration did not improve the yield of the reaction.
Ring-closing alkyne metathesis is a fascinating and
important reaction that has found applications both in the
synthesis of novel natural products as well as in the
preparation of cyclophane- and dehydroannulene-type rings.4
With the successful dimerization of 4 into 5, a series of
dipropynyls 11a-c was prepared (Scheme 4) and their
metathesis reaction was investigated. Subjecting either 11a
or 11c to the conditions of alkyne metathesis furnished (after
multiple chromatographies) the cycles 12a,c but in relatively
disappointing yields (Scheme 4). In the case of 11c, a dimeric
cycle, 13c, is isolated, but in lower yield. If the bispropyne
Figure 1. ORTEP representation of 2.
With this method available we turned our attention to the
problem of the dimerization of ortho-methoxypropynylben-
zene 4 with the in situ catalysts. While this type of ether-
containing substrate is easily metathesized with the Fu¨rstner-
type Mo catalysts2 and probably as well with the Schrock-
type tungsten carbynes,3 the simple in situ approach did not
work well, despite the one example of a low molecular
weight dialkoxy-substituted poly(para-phenyleneethynylene)
formed by in situ ADIMET.1a With the pretreated catalyst
system (Scheme 3), dimerization of 4 occurs at 130 °C in 3
h to give the alkyne 5 in almost quantitative yield after
workup.1c It was possible to lower the reaction temperature
to 75 °C after an initial pretreatment at 130 °C, but then the
yield of the dimer 5 dropped from 98 to 36% after a reaction
time of 24 h.
Scheme 2. Synthesis of 2 from 3
(2) (a) Fu¨rstner, A.; Mathes, C.; Lehmann, C. W. Chem.-Eur. J. 2001,
7, 5299. Fu¨rstner, A.; Mathes, C.; Lehmann, C. W. J. Am. Chem. Soc. 1999,
121, 9453. (b) Tsai, Y.-C.; Diaconescu, P. L.; Cummins, C. C. Organo-
metallics 2000, 19, 5260.
(3) Schrock, R. R. J. Chem. Soc. 2001, 2541. Krouse, S. A.; Schrock,
R. R. Macromolecules 1989, 22, 2569. Zhang, X. P.; Bazan, G. C.
Macromolecules 1994, 27, 4627. Weiss, K.; Michel, A.; Auth, E. M.; Bunz,
U. H. F.; Mangel, T.; Mu¨llen, K. Angew. Chem. 1997, 36, 506. Fu¨rstner,
A.; Guth, O.; Rumbo, A.; Seidel, G. J. Am. Chem. Soc. 1999, 121, 11108.
(4) (a) Pschirer, N. G.; Fu, W.; Adams, R. D.; Bunz, U. H. F. Chem.
Commun. 2000, 87. Ge, P. H.; Fu, W.; Herrmann, W. A.; Herdtweck, E.;
Campana, C.; Adams, R. D.; Bunz, U. H. F. Angew. Chem. 2000, 39, 3607.
(b) Fu¨rstner, A.; Grela, K. Angew. Chem. 2000, 39, 1234. Fu¨rstner, A.;
Seidel, G. Angew. Chem. 1998, 37, 1734.
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Org. Lett., Vol. 4, No. 17, 2002

Scheme 4. Ring-Closing Metathesis of the Dipropynylarenes 11a-c
11b is submitted to the conditions of the alkyne metathesis,
In conclusion, we have developed an improved version
of the instant catalysts formed from molybdenum hexacar-
bonyl and phenols first reported by Mortreux,5 used by Mori,6
and optimized by us.1 The latest generation of the in situ
catalyst described herein is capable of dimerizing enyne
substrates as well as ortho-alkoxy-substituted propynylben-
zenes unreactive under the regular in situ conditions. We
have used the expanded scope of this reaction to make a
series of novel bridged tolane cyclophanes.7 In the future,
we will investigate the use of this catalytic system for the
synthesis of enyne-containing oligomers and cycles.
See ref 8 for experimental details for the synthesis of
compounds 2 and 12b.
the cycle 12b is isolated in 79% yield, indicating a correlation
between linker chain length and yield of obtained cycles.
Here as well, some of the dimer 13b forms, but only in low
yield. While the NMR spectra of monomeric and dimeric
cycles are very similar, the molecular ion peaks in the mass
spectra ensure that the assignment was correct.
(5) (a) Mortreux, A.; Blanchard, M. Chem. Commun. 1974, 786. (b) See
also: Villemin, D.; Heroux, M.; Blot, V. Tetrahedron Lett. 2001, 42, 3701.
(6) Kaneta, N.; Hirai, T.; Mori, M. Chem. Lett. 1995, 1055. Nishida,
M.; Shiga, H.; Mori, M. J. Org. Chem. 1998, 63, 8606.
(7) Crisp, G. T.; Bubner, T. P. Tetrahedron 1997, 53, 11881. Crisp, G.
T.; Bubner, T. P. Tetrahedron 1997, 53, 11899.
(8) Synthesis of Compound 2. A 30 mL cylindrical high-pressure glass
tube (Ace Glass, Inc.; dried overnight) was charged under N2 with Mo-
(CO)6, (30.0 mg, 0.114 mmol) freshly distilled 4-chlorophenol (147 mg,
1.14 mmol), and o-DCB (3 mL, dried over molecular sieves). 3-Hexyne
(100 mg, 1.22 mmol) was added, and the tube was sealed with a Teflon
cap. After the mixture was heated to 130 °C for 2 h, the cap was removed
and replaced with an upside-down rubber septum, which was secured with
copper wire. A 20 gauge syringe needle was placed in the septum to serve
as a gas outlet, and a slow stream of N2 was introduced via cannula. This
mixture was heated at 130 °C for 1 h. Compound 3 (250 mg, 1.15 mmol,
dissolved in 0.5 mL o-DCB) was added via syringe. Heating at 130 °C
with continued N2 purge gave a dark brown solution after 24 h. The mixture
was cooled and diluted with CHCl3. Washing with 10% NaOH, 10% HCl,
and H2O followed by removal of solvent in vacuo gave a mixture of 2 and
3. Column chromatography (5% EtOAc/hexanes) followed by recrystalli-
zation (hexanes) gave 2 as a mildly fluorescent white solid (175 mg, 80%).
1H NMR: δ 7.23-7.35 (m, 20H), 6.12 (s, 2H). 13C NMR: δ 151.81, 141.62,
139.08, 129.94, 128.20, 128.14, 128.06, 127.85, 107.56, 93.26. IR (thin
film, cm-1): 3057, 3020, 2916, 2849, 2731, 2212, 1952, 1885, 1812, 1738,
1656, 1597, 1493, 1441, 1367, 1263, 1182, 1078, 1026, 915, 856, 767,
693, 633. MS: M+ calcd, 382.1722; found, 382.1734. Mp: 129 °C.
Synthesis of Compound 12b. A 250 mL cylindrical high-pressure glass
tube (Ace Glass, Inc.; dried overnight) was charged under N2 with Mo-
(CO)6, (235 mg, 0.890 mmol) freshly distilled 4-chlorophenol (1.16 g, 9.02
mmol), and o-DCB (50 mL, dried over molecular sieves). 3-Hexyne (1.00
g, 12.2 mmol) was added, and the tube was sealed with a Teflon cap. After
the mixture was heated to 130 °C for 2 h, the cap was removed and replaced
Acknowledgment. We thank the Petroleum Research
Funds and the National Science Foundation for support (NSF
CHE 0138-659). U.B. is a Camille Dreyfus Teacher Scholar.
Supporting Information Available: Detailed descrip-
tions of experimental procedures and characterization of all
new compounds and syntheses of the metathesis substrates.
This material is available free of charge via the Internet at
http://pubs.acs.org.
OL026118X
with an upside-down rubber septum, which was secured with copper wire.
A mild nitrogen purge was introduced as described above, and compound
11b (3.00 g, 9.04 mmol) was added. Heating overnight at 130 °C followed
by standard workup (as described above) yielded, after flash chromatography
1
(10% EtOAc/hexanes), cycle 12b as a colorless solid (1.98 g, 78.7%). H
NMR: δ 7.51-7.52 (m, 2H), 7.24-7.27 (m, 2H), 6.93-6.99 (m, 4H),
4.14-4.17 (t, 4H), 1.92 (m, 6H). 13C NMR: δ 160.26, 132.15, 129.33,
121.09, 114.69, 114.49, 90.14, 69.52, 27.50, 21.93. IR (thin film, cm-1):
3064, 3020, 2931, 2863, 2745, 2553, 2204, 1901, 1775, 1693, 1589, 1478,
1441, 1382, 1278, 1234, 1151, 1093, 1041, 982, 945, 829, 752. MS: M+
calcd, 556.2614; found, 556.2604. MP: 82 °C. UV-vis (CHCl3): 280 nm,
312 nm (λmax). Fluorescence (CHCl3): 358 nm (broad).
Org. Lett., Vol. 4, No. 17, 2002
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