Cu-catalyzed synthesis of symmetric group 6 (Fischer) bis-carbene complexes

Article abstract of DOI:10.1021/ol702464r

The efficient copper oxidative homocoupling (CuCl/TMEDA/O₂) of alkynyl Fischer carbene complexes yields bis-carbene complexes having π-tethers. The bimetallic complexes are exceptional templates to prepare diverse organic symmetric structures c

Full text of DOI:10.1021/ol702464r

ORGANIC
LETTERS
2008
Vol. 10, No. 3
365-368
Cu-Catalyzed Synthesis of Symmetric
Group 6 (Fischer) Bis-carbene
Complexes
Mar´ıa P. Lo´pez-Alberca, Mar´ıa J. Manchen˜o,* Israel Ferna´ndez,
Mar Go´mez-Gallego, and Miguel A. Sierra*
Departamento de Qu´ımica Orga´nica, Facultad de Qu´ımica, UniVersidad Complutense,
28040 Madrid, Spain
mjmreal@quim.ucm.es; sierraor@quim.ucm.es
Received October 10, 2007
ABSTRACT
The efficient copper oxidative homocoupling (CuCl/TMEDA/O2) of alkynyl Fischer carbene complexes yields bis-carbene complexes having
-tethers. The bimetallic complexes are exceptional templates to prepare diverse organic symmetric structures connected by -extended
π
π
fragments.
The chemistry of Fischer-type carbene complexes has
steadily developed during the last 40 years.1 However, to
date, most of the synthetic applications of Fischer carbenes
in organic synthesis have been restricted to monocarbene
complexes.2 The first examples of the use of polymetallic
carbene complexes were reported just 15 years ago,3 and
even after the recognition of the usefulness of bi- and
polymetallic reagents as catalysts for organic synthesis, the
full potential of these complexes is yet to be discovered. The
drawback with respect to monocarbene complexes originates
in the difficulties to access and elaborate bi- and polymetallic
carbene structures. Most synthetic routes to these bis-carbene
complexes use the original method of Fischer,4 consisting
of the addition of organollithium compounds to M(CO)6 (M
) Cr or W) and subsequent capture of the intermediate
acylate complex with powerful electrophile agents.5 Other
approaches to these compounds are the double Aumann
reaction between a dialdehyde and a monocarbene complex
(1) Selected reviews on different aspects of metal carbene chemistry:
(a) Do¨tz, K. H.; Fischer, H.; Hofmann, P.; Kreissel, R.; Schubert, U.; Weiss,
K. Transition Metal Carbene Complexes; Verlag Chemie: Deerfield Beach,
FL, 1983. (b) Wulff, W. D. In ComprehensiVe Organic Synthesis; Trost,
B. M., Fleming, I., Eds.; Pergamon: Oxford, 1991; Vol. 5, p 1065. (c)
Wulff, W. D. In ComprehensiVe Organometallic Chemistry II; Abel, E.
W., Stone, F. G. A., Wilkinson, G., Eds.; Pergamon: Oxford, 1995; Vol.
12, p 470. (d) Harvey, D. F.; Sigano, D. M. Chem. ReV. 1996, 96, 271. (e)
Aumann, R.; Nienaber, H. AdV. Organomet. Chem. 1997, 41, 163. (f) de
Meijere, A.; Schirmer, H.; Duetsch, M. Angew. Chem., Int. Ed. 2000, 39,
3964. (g) Barluenga, J.; Flo´rez, J.; Fan˜ana´s, F. J. J. Organomet. Chem.
2001, 624, 5.
(2) For recent examples of some natural products synthesized using
Fischer carbenes, see: (a) Huang, J.; Wu, C.; Wulff, W. D. J. Am. Chem.
Soc. 2007, 129, 13366. (b) Eastham, S. A.; Ingham, S. P.; Hallet, M. R.;
Herbert, J.; Quayle, P.; Raftery, J. Tetrahedron Lett. 2006, 47, 2299. (c)
Camacho-Da´vila, A.; Herndorn, J. W. J. Org. Chem. 2006, 71, 6682. (d)
Minatti, A.; Do¨tz, K. H. J. Org. Chem. 2005, 70, 3745. (e) Gupta, A.; Sen,
S.; Harmata, M. J. Org. Chem. 2005, 70, 7422. See, also (f) Barluenga, J.;
Santamar´ıa, J.; Toma´s, M. Chem. ReV. 2004, 104, 2259.
(3) For a review in the synthesis and synthetic applications of bi- and
polymetallic carbenes, see: Sierra, M. A. Chem. ReV. 2000, 100, 3591.
(4) Fischer, E. O.; Maasbol, A. Angew. Chem., Int. Ed. 1964, 3, 580.
(5) Examples: (a) Fischer, E. O.; Ro¨ll, W.; Huy, N. H. T.; Ackermann,
K. Chem. Ber. 1982, 115, 2951. (b) Huy, N. H. T.; Lefloch, P.; Robert, F.;
Jeannin, Y. J. Organomet. Chem. 1987, 327, 211. (c) Do¨tz, K. H.;
Tomuschat, P.; Nieger, M. Chem. Ber. 1997, 130, 1605. (d) Albrecht, T.;
Sauer, J.; No¨th, H. Tetrahedron Lett. 1994, 35, 561. (e) Neidlein, R.; Gu¨rtler,
S.; Krieger, C. HelV. Chim. Acta 1994, 77, 2303. (f) Anderson, D. M.;
Bristow, G. S.; Hitchcock, P. B.; Jasim, H. A.; Lappert, M. F.; Skelton, B.
W. J. Chem. Soc., Dalton Trans. 1987, 2843. (g) Berke, H.; Ha¨rter, P.;
Huttner, G.; v. Seyerl, J. J. Organomet. Chem. 1981, 219, 317.
10.1021/ol702464r CCC: $40.75
© 2008 American Chemical Society
Published on Web 01/10/2008

having R-hydrogens,6 the alkylation of alkyl dihalides with
monocarbene anions,7 the reaction of highly reduced pen-
tacarbonylmetalates with bis-amides,8 and the reductive
coupling of alkenyl carbenes.9 All of these methods usually
lead to low yields of the desired complex or are even unable
to produce it.
Scheme 1
Modification of a mononuclear metal-carbene complex
by using a transition-metal-catalyzed reaction would be a
simple answer to obtain elaborated bi- and polymetallic
structures. Nevertheless, the use of transition-metal catalysts
to effect transformations in group 6 metal carbene complexes
is often hampered by the transmetalation reaction of the metal
carbene to the catalysts.10 Our ongoing project directed to
prepare new macrocyclic structures based on a bi- and
polymetallic macrocyclic Fischer carbene scaffolds11 required
an easy and efficient route to alkynyl tethered bis-carbene
complexes. The oxidative coupling of terminal acetylenes
was an attractive way to access these structures. However,
the reactivity of the catalyst in the alkyne coupling had to
be preferred to the transmetalation reaction. For this reason
and based on our experience with catalytic reactions of
Fischer carbene complexes,10 the Hay12 modification of the
original Glaser coupling reaction was chosen. Reported
herein is the successful implementation of this idea to obtain
new bis-carbene complexes as building blocks for the design
of new polymetallic structures and the application of these
scaffolds to the preparation of bis-uracils and bis-imidazoles
as examples of the versatility of these structures in organic
synthesis.
Therefore, no systematic differences were observed between
isostructural chromium and tungsten complexes toward this
process.
This coupling reaction was extended to other alkynylcar-
bene complexes. Thus, dialkynes 3 were obtained in good
yields by Sonogashira coupling of dibromo derivatives 4 with
trimethylsilylacetylene and further desilylation in the pres-
ence of base. The dialkynes 3 were monolithiated with
n-BuLi and reacted with Cr(CO)6, and finally, the “ate”
complex thus formed was reacted with Et3OBF4 to give
monocarbene complexes 1c,d in 35% and 20% yield,
respectively (Scheme 2).
Scheme 2
First, assays to achieve the dimerization reaction were
effected on monocarbene 1a, which was prepared from 1,3-
diethynylbenzene following our previously reported proce-
dure.11,13 Reaction of complex 1a with an excess of CuCl-
TMEDA/air in acetone yielded after 90 min bis-carbene 2a
in good yield (60%).14 The same process with the tungsten
carbene 1b was also efficient. The reaction was completed
within 1 h, yielding carbene 2b in 55% yield (Scheme 1).
Monocarbenes 1c and 1d were reacted under standard Hay
conditions leading to the corresponding homocoupling
products 2c and 2d, which were isolated in 40% and 63%
yield, respectively (Scheme 3). The lower yield of carbene
2c is due to partial decomposition of the product during the
isolation procedure.
All of the coupling reactions tested yielded the desired
bis-carbenes exclusively. Products derived from transmeta-
lation to the metal carbene moiety process were not observed.
We have recently shown10b that transmetalation from chro-
(6) Aumann, R. Eur. J. Org. Chem. 2000, 17.
(7) (a) Macomber, D. W.; Madhukar, P. J. Organomet. Chem. 1992, 433,
279. (b) Macomber, D. W.; Hung, M.-H.; Verma, A. G.; Rogers, R. D.
Organometallics 1988, 7, 2072. (c) Macomber, D. W.; Hung, M.-H.;
Madhukar, P.; Liang, M.; Rogers, R. D. Organometallics 1991, 10, 737.
(d) Macomber, D. W.; Madhukar, P.; Rogers, R. D. Organometallics 1991,
10, 2121.
(8) (a) Wynn, T.; Hegedus, L. S. J. Am. Chem. Soc. 2000, 122, 5034.
(b) Puntener, K.; Hellman, M. D.; Kuester, E.; Hegedus, L. S. J. Org. Chem.
2000, 65, 8301. (c) Kuester, E.; Hegedus, L. S. Organometallics 1999, 18,
5318. (d) Dumas, S.; Lastra, E.; Hegedus, L. S. J. Am. Chem. Soc. 1995,
117, 3368. (e) Hsiao, Y.; Hegedus, L. S. J. Org. Chem. 1997, 62, 3586.
(9) (a) Ram´ırez-Lo´pez, P.; Go´mez-Gallego, M.; Sierra, M. A.; Lejon,
T.; Manchen˜o, M. J. Angew. Chem., Int. Ed. 2002, 41, 3442. (b) Sierra, M.
A.; Mart´ınez-AÄ lvarez, R.; Go´mez-Gallego, M. Chem. Eur. J. 2007, 13, 736
and pertinent references therein.
(10) (a) Go´mez-Gallego, M.; Manchen˜o, M. J.; Sierra, M. A. Acc. Chem.
Res. 2005, 38, 44. (b) Lo´pez-Alberca, M. P.; Manchen˜o, M. J.; Ferna´ndez,
I.; Go´mez-Gallego, M.; Sierra, M. A.; Torres, R. Org. Lett. 2007, 9, 1757.
(11) (a) Ferna´ndez, I.; Manchen˜o, M. J.; Go´mez-Gallego, M.; Sierra,
M. A. Org. Lett. 2003, 5, 1237. (b) Ferna´ndez, I.; Sierra, M. A.; Manchen˜o,
M. J.; Go´mez-Gallego, M.; Ricart, S. Organometallics 2001, 20, 4304.
(12) Hay, A. S. J. Org. Chem. 1962, 27, 3320.
(13) (a) Llordes, A.; Sierra, M. A.; Lo´pez-Alberca, M. P.; Molins, E.;
Ricart, S. J. Organomet. Chem. 2005, 690, 6096. (b) Della Sala, G.; Artillo,
A.; Ricart, S.; Spinella, A. J. Organomet. Chem. 2007, 692, 1623. (c) Artillo,
A.; Della Salla, G.; De Santis, M.; Llordes, A.; Ricart, S.; Spinella, A. J.
Organomet. Chem. 2007, 692, 1277.
(14) The synthesis of complex 2a is representative: The Hay catalyst
was prepared according to the literature (see ref 12). To the resulting catalyst
was added dropwise a solution of the monocarbene in dry acetone. The
mixture was stirred until the disappearance of monocarbene (checked by
TLC). The reaction was quenched with water and filtered to eliminate the
salts formed. The filtrate was extracted with diethyl ether. The combined
organic phases were washed with HCl (5%) and water, dried over MgSO4,
and filtered. The solvent was eliminated and purification by column
chromatography on silica gel afforded pure compound: 1H NMR (CDCl3)
δ ) 7.71-7.43 (m, 8H), 4.77 (q, J ) 7.1 Hz, 4H), 1.60 (t, J ) 7.1 Hz,
6H); 13C NMR (CDCl3) δ ) 313.7, 225.7, 216.1, 135.8, 135.0, 133.2, 129.2,
122.6, 121.7, 91.4, 80.5, 76.0, 75.0, 15.0; IR (CHCl3) ν 2062, 1954, 1217,
775 cm-1. Anal. Calcd for C36H18O12Cr2: C, 57.92; H, 2.43. Found: C,
57.78; H, 2.21.
366
Org. Lett., Vol. 10, No. 3, 2008

serve as scaffolds to prepare diverse organic structures, taking
advantage of the reactivity of Fischer carbene complexes.
The versatility of these compounds was checked against two
well-known reactions of simple Fischer carbene complexes.
Thus, compound 2a was reacted with tosylhydrazine yielding
the symmetric bis-pyrazole 717 in 75% yield, and the
bimetallic bis-uracyl 8 was prepared by reacting complex
2a with N,N′-dimethylurea at rt in 69% yield.13 Oxidation
of complex 8 gives metal free bis-uracyl 9 in excellent yield
(85%)18 (Scheme 5).
Scheme 3
Scheme 5
mium or tungsten carbene complexes to Pd catalysts occurs
preferably with Pd(II) salts, while Pd(0) species show a bias
for oxidative addition instead of transmetalation. The results
reported above are consistent with this behavior. The use of
the bidentate ligand N,N,N′,N′-tetramethylene diamine com-
plex (TMEDA)-Cu(I) should enhance the oxidative coupling
at the expense of the Cu-Cr or Cu-W transmetalation.
Aminocarbene 5 is also susceptible to coupling. Complex
5 was prepared following Wulff’s procedure15 and submitted
to standard CuCl/TMEDA/O2 coupling conditions. The
reaction was instantaneously completed, and product 6 was
isolated in 30% yield (Scheme 4). The yield was moderate,
Scheme 4
In conclusion, a new method to prepare (poly)alkyne-
tethered bis-carbene complexes is reported. The procedure
is based on a copper oxidative coupling that is compatible
with the metallic fragment of the starting carbene. Under
the conditions employed (TMEDA)-Cu(I), Cr or W to Cu
transmetalation does not occur. The procedure allows the
design of new Fischer carbenes as building blocks for the
synthesis of new π-extended polymetallic and organic
compounds. Two examples of the use of these new scaffolds
but the method constitutes a straightforward synthesis
compared to the procedure developed by Fischer for the
preparation of analogous complexes.16
The carbene complexes isolated throughout this work were
relatively stable and could be purified by SiO2 chromatog-
raphy. All of them present similar spectroscopic features.
Thus, the 13C NMR spectra of chromium complexes 1c, 1d,
2a, 2c, and 2d exhibit a signal in the range of 313.7-312.6
ppm characteristic of an alkoxy carbene moiety. In the same
way, tungsten carbene 2b shows the corresponding signal
at 285.9 ppm. All of them also present the signals assignable
to the C-C triple bond in the range 92.6-73.9 ppm.
The synthesis of the compounds 2a-d and 6 is a simple
entry to new oligoenyne structures. These compounds may
(17) Aumann, R.; Jasper, B.; Fro¨lich, R. Organometallics 1995, 14, 2447.
(18) Compound 8. A solution of 21 mg (0.24 mmol) of N,N′-
dimethylurea in 20 mL of THF was added by syringe pump into a solution
of 60 mg (0.08 mmol) of bis-carbene 2a in 80 mL of THF for 12 h. Then,
the mixture was stirred for an additional 24 h at room temperature. The
solvent was removed in vacuo, and the residue was purified by column
chromatography on silica gel affording 46 mg (69 %) of compound 8: 1H
NMR (CDCl3) δ 7.67-7.66 (m, 2H), 7.51-7.46 (m, 4H), 7.31-7.30 (m,
2H), 7.21 (s, 2H), 4.19 (s, 6H), 3.28 (s, 6H); 13C NMR (CDCl3) δ 261.4,
223.7, 217.3, 149.4, 141.2, 134.7, 132.3, 129.7, 128.9, 124.5, 123.0, 102.8,
80.6, 75.5, 45.9, 35.7; IR (CHCl3) ν 2053, 1910, 1696, 1660 cm-1. Anal.
Calcd for C38H22Cr2N4O12: C, 54.95; H, 2.67. Found: C, 55.22;H, 2.40.
Compound 9. A solution of 50 mg (0.06 mmol) of bis-carbene 8 was
stirred in a mixture of hexane/ethyl acetate 1:1 for 8 h under sunlight. The
solvent was removed in vacuo and the residue dissolved in ethyl acetate
and filtered through a short pad of Celite. Further chromatography on silica
gel afforded 16 mg (85%) of 9: 1H NMR (CDCl3) δ 7.61-7.57 (m, 2H),
7.47-7.39 (m, 4H), 7.29-7.28 (m, 2H), 5.62 (s, 2H), 3.33 (s, 6H), 3.14 (s,
6H); 13C NMR (CDCl3) δ 162.2, 153.2, 152.5, 134.1, 133.9, 131.5, 129.3,
(15) Rahm, A.; Wulff, W. D.; Rheingold, A. L. Organometallics 1993,
12, 597.
(16) (a) Hartbaum, C.; Mauz, E.; Roth, G.; Weissenbach, K.; Fischer,
H. Organometallics 1999, 18, 2619. (b) Hartbaum, C.; Roth, G.; Fischer,
H. Chem. Ber. 1997, 130, 479. (c) Hartbaum, C.; Fischer, H. Chem. Ber.
1997, 130, 1063. (d) Hartbaum, C.; Roth, G.; Fischer, H. Eur. J. Inorg.
Chem. 1998, 191. (e) Hartbaum, C.; Fischer, H. J. Organomet. Chem. 1999,
578, 186. (f) For coupling reactions in allenylidene complexes, see: Szesni,
N.; Drexler, M.; Maurer, J.; Winter, R. F.; de Montigny, F.; Lapinte, C.;
Steffeus, S.; Heck, J.; Weibert, B.; Fischer, H. Organometallics 2006, 25,
5774.
128.5, 122.7, 102.9, 80.7, 75.1, 34.5, 28.1; IR (CHCl3) ν 1704, 1659 cm-1
.
Anal. Calcd for C28H22N4O4: C, 70.18; H, 4.63. Found: C 70. 32; H, 4.
80.
Org. Lett., Vol. 10, No. 3, 2008
367

to access to symmetric organic bis-pyrazole and bis-uracyl
derivatives are reported. Efforts to explore the versatility of
this method to access to other metallic complexes and organic
structures are underway in our laboratories.
is gratefully acknowledged. M.P.L.A. thanks the Ministerio
de Educacio´n y Ciencia (Spain) for a predoctoral (FPU)
grant.
Supporting Information Available: Full experimental
and characterization data for all the compounds prepared
through this work. This material is available free of charge
via the Internet at http://pubs.acs.org.
Acknowledgment. Support for this work under Grant No.
CTQ2004-06250-C02-01/BQU from the Ministerio de Cien-
cia y Tecnolog´ıa (Spain) and the CAM (CAM-UCM-910762)
OL702464R
368
Org. Lett., Vol. 10, No. 3, 2008