Cross-coupling reactions with acetylenic dithiafulvenes

Article abstract of DOI:10.1055/s-2004-835641

The scope of acetylenic dithiafulvenes in palladium-catalyzed cross-coupling reactions is reported. From such reactions we have obtained a selection of new extended tetrathiafulvalenes (TTFs), based on p-diethynylbenzene, tri-, and tetraethynylethene core

Full text of DOI:10.1055/s-2004-835641

2818
LETTER
Cross-Coupling Reactions with Acetylenic Dithiafulvenes
C
ross-CouplingR
a
eactions wi
t
th
A
cet
r
ylenic
D
i
ithiaful
n
venes e Qvortrup,a,b Asbjørn Sune Andersson,a Jan-Philipp Mayer,b Anne Sofie Jepsen,b Mogens Brøndsted Nielsen*a
a
Department of Chemistry, University of Copenhagen, Universitetsparken 5, 2100 Copenhagen Ø, Denmark
Fax +4535320212; E-mail: mbn@kiku.dk
b
Department of Chemistry, University of Southern Denmark, Campusvej 55, 5230 Odense M, Denmark
Received 29 July 2004
tolerance of acetylenic coupling reactions.5 We now focus
on the ability of acetylenic dithiafulvenes to undergo
Sonogashira–Hagihara cross-couplings6 with different
aryl and vinyl halides. Until now only one such example
has been reported, namely the coupling with 2,5-diiodo-
thiophene which provided the extended TTF 4.1b
Abstract: The scope of acetylenic dithiafulvenes in palladium-cat-
alyzed cross-coupling reactions is reported. From such reactions we
have obtained a selection of new extended tetrathiafulvalenes
(TTFs), based on p-diethynylbenzene, tri-, and tetraethynylethene
cores.
Key words: alkynes, conjugation, cross-coupling, enynes, hetero-
cycles
The proton affinity of the acetylide of 2 is close to that of
phenylacetylide. Thus, we find from calculations, em-
ploying the Gaussian 03 program package,7 values of 364
and 369 kcal mol–1, respectively (at 0 K).8 In other words,
the acidities of 2 and phenylacetylene are assumed to be
similar if solvent effects are neglected.
The development of new acetylenic building blocks based
on the dithiafulvene unit has allowed ready access to
alkyne-extended derivatives of the p-donor tetrathiaful-
valene (TTF).1 Compound 1 (Figure 1) presents one such
building block that was recently reported by Diederich,
Nielsen, and co-workers.1a,b Thus, subjecting 1, after de-
silylation (2), to an oxidative Hay homo-coupling2 affords
the butadiyne-extended TTF 3. Owing to their redox and
chromophoric properties, such molecules are interesting
in both materials and supramolecular chemistry.1b,f,3 Mo-
lecular construction from acetylenic building blocks4 ben-
efits from the versatility and high functional group
The Sonogashira coupling between 2 and a simple aryl
halide was first investigated. Compound 1 was desilylated
by K2CO3 in MeOH–THF according to a standard proce-
dure.1b The resulting product 2 was then treated with 1,4-
diiodobenzene (5) and the Pd(PPh3)2Cl2–CuI catalyst sys-
tem, which gave the p-diethynylbenzene-extended TTF 6
in good yield (Scheme 1).9
R
R
CO2Me
S
S
S
S
S
S
2, i
I
I
MeO2C
S
5
TTF
S
S
R
CO2Me
S
S
6 (R = CO2Me)
1 (R = SiMe3), 2 (R = H)
R
MeO2C
R
S
R
R
R
R
S
S
S
S
S
3
S
Br
Br
CO2Me
R2
2
R1
MeO2C
ii or iii
R1
S
Me3Si
SiMe3
7
S
Me3Si
SiMe3
S
8 (R = CO2Me)
S
S
Scheme 1 Palladium-catalyzed cross-couplings with 2. Reagents
and conditions: i. Pd(PPh3)2Cl2, CuI, Et3N, THF, r.t., 2.5 h, 78%; ii.
Pd(PhCN)2Cl2, P(t-Bu)3, CuI, (i-Pr)2NH, THF, toluene, microwave
heating, 60 °C, 6 min, 38%; iii. Pd(PhCN)2Cl2, P(t-Bu)3, CuI, (i-
Pr)2NH, THF, toluene, ultrasonification, 30 °C, 4 h; 84%.
R1
R2
4 (R1 = CO2Me, R2 = Si(i-Pr)3)
R1
Figure 1 Acetylenic derivatives of tetrathiafulvalene (TTF).
Geminally functionalized Tetraethynylethenes (TEEs) are
conviniently constructed from the vinylic dibromide 7
(Scheme 1) and arylacetylenes, which contain either
electron-donating (e.g. NMe2) or withdrawing (e.g. NO2)
SYNLETT 2004, No. 15, pp 2818–2820
Advanced online publication: 08.11.2004
DOI: 10.1055/s-2004-835641; Art ID: D21504ST
© Georg Thieme Verlag Stuttgart · New York
0
7
.1
2
.2
0
0
4

LETTER
Cross-Coupling Reactions with Acetylenic Dithiafulvenes
2819
substituents, in the presence of the Pd(PPh3)2Cl2 cata- nonlinearities.1b In the quest for new NLO candidates, we
lyst.4,10 Nevertheless, treatment of 7 with 2 under these prepared a donor–acceptor chromophore with a central
conditions failed to provide the TEE-extended TTF 8. triethynylethene (enetriyne) core (Scheme 3). First the al-
Many cross-couplings are enhanced by using bulky, elec- dehyde 1014 was subjected to a Corey–Fuchs dibromo-
tron-rich phosphines.11 Recently, Hundertmark et al.12 olefination,15 which gave the vinylic dibromide 11
developed a versatile catalyst system, Pd(PhCN)2Cl2–P(t- containing a p-nitrophenylacetylene substituent. A cross-
Bu)3, that allows room temperature Sonogashira coupling coupling reaction between 2 and 11 [employing Pd(Ph-
of aryl bromides with a wide variety of terminal acetyl- CN)2Cl2–P(t-Bu)3 with ultrasonification] afforded 12 in a
enes. We therefore turned to this catalyst and at the same yield of 30%. For comparison, 12 is only obtained in a
time subjected the reaction mixture to microwave heating yield of 10% with the Pd(PPh3)2Cl2 catalyst.
at 60 °C for six minutes. Hereby 8 was gratifyingly ob-
Br
Br
tained in a yield of 38%. The yield was improved further
by substituting the microwave heating with ultrasonifica-
tion at 30 °C for four hours.13 The TEE core was under
these conditions constructed in yields as high as 84%. The
reaction also worked at room temperature without micro-
wave or ultrasonification, but it required much longer
reaction time (up to 24 hours), and the yield varied con-
siderably. In contrast, high yields and short reaction times
are easy to reproduce when using ultrasonification. The
beneficial use of ultrasonification is likely a result of the
high viscosity of the reaction mixture since little solvent
is employed (ca. 1 mL per 1 mmol of 2).
CHO
i
O2N
10
O2N
11
R
R
R
R
S
S
S
S
2, ii
TEE 8, containing two silyl-protected acetylene groups, is
an interesting module for further acetylenic scaffolding.
We present here our first efforts. The trimethylsilyl pro-
tecting groups were removed by K2CO3 in THF–MeOH,
and the desilylated compound was hereafter subjected to
an oxidative Hay coupling2 with an excess of phenyl-
acetylene (Scheme 2). This cross-coupling provided the
large conjugated chromophore 9 in 18%. The rather low
yield is partly due to significant decomposition of the
desilylated intermediate. We have experienced similar
stability problems in the deprotection step of related
acetylenic scaffolds, such as diethynylethene-extended
TTFs.1e
12 (R = CO2Me)
O2N
Scheme 3 Synthesis of donor–acceptor chromophore. Reagents and
conditions: i. CBr4, PPh3, Zn, CH2Cl2, r.t., 72%; ii. Pd(PhCN)2Cl2,
P(t-Bu)3, CuI, (i-Pr)2NH, THF, toluene, ultrasonification, 30 °C, 2.5
h, 30%.
In conclusion, we have devised methods for performing
cross-coupling reactions between the acetylenic dithiaful-
vene 2 and a variety of halides, which have allowed the
preparation of several new extended tetrathiafulvalenes
with acetylenic cores. These chromophores are currently
investigated for their linear and nonlinear optical proper-
ties, as well as redox properties.
R
R
R
R
S
S
S
S
i, ii
8
Acknowledgment
The Danish Technical Research Council (STVF, Research project
# 26-01-0033), Carlsbergfondet, and Direktør Ib Henriksens Fond
are gratefully acknowledged for financial support.
References
9 (R = CO2Me)
(1) (a) Nielsen, M. B.; Moonen, N. N. P.; Boudon, C.;
Gisselbrecht, J.-P.; Seiler, P.; Gross, M.; Diederich, F.
Chem. Commun. 2001, 1848. (b) Nielsen, M. B.; Utesch, N.
F.; Moonen, N. N. P.; Boudon, C.; Gisselbrecht, J.-P.;
Concilio, S.; Piotto, S. P.; Seiler, P.; Günter, P.; Gross, M.;
Diederich, F. Chem.–Eur. J. 2002, 8, 3601. (c) Nielsen, M.
B. Synlett 2003, 1423. (d) Kumagai, T.; Tomura, M.;
Nishida, J.-i.; Yamashita, Y. Tetrahedron Lett. 2003, 6845.
(e) Nielsen, M. B.; Gisselbrecht, J.-P.; Thorup, N.; Piotto, S.
P.; Boudon, C.; Gross, M. Tetrahedron Lett. 2003, 44, 6721.
(f) Qvortrup, K.; Jakobsen, M. T.; Gisselbrecht, J.-P.;
Scheme 2 Acetylenic scaffolding with 8. Reagents and conditions:
i. K2CO3, THF, MeOH; ii. phenylacetylene, CuCl, TMEDA, CH2Cl2,
air; 18%. TMEDA = N,N,N¢,N¢-tetramethylethylenediamine.
One way of circumventing the stability issue is to attach
the dithiafulvene units in the final step. In particular, we
target novel donor–acceptor chromophores with good
NLO properties. Recent studies have revealed that acety-
lenic scaffolds containing dithiafulvene donor groups and
p-nitrophenyl acceptor groups exhibit good third-order
Synlett 2004, No. 15, 2818–2820 © Thieme Stuttgart · New York

2820
K. Qvortrup et al.
LETTER
Boudon, C.; Jensen, F.; Nielsen, S. B.; Nielsen, M. B.
J. Mater. Chem. 2004, 14, 1768.
(11) For a recent review on electron-rich phosphines in organic
synthesis, see: Valentine, D. H. Jr.; Hillhouse, J. H. Synthesis
2003, 2437.
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(13) Experimental Procedure for Preparation of 8: Compound
1 (418 mg, 1.27 mmol) was desilylated to form 2 as
previously described (ref.1b). To a mixture of CuI (3.5 mg)
and Pd(PhCN)2Cl2 (20 mg) under argon was added argon-
degassed THF (0.5 mL), toluene (0.5 mL), HN(i-Pr)2 (0.17
mL). Then P(t-Bu)3 (10% in hexane, 0.125 mL) was added
and hereafter dibromide 7 (156 mg, 0.413 mmol), which
resulted in a dark brown mixture. This mixture was
transferred via a syringe to the flask containing solid 2. The
mixture was subjected to ultrasonification at 30 °C for 4 h,
whereupon it was filtered through a plug of silica (eluent:
CH2Cl2). Column chromatography (SiO2, CH2Cl2 →
CH2Cl2–EtOAc 10:1) afforded 8 as a red-brown solid (253
mg, 84%). Mp 143–146 °C (decomp.). UV/Vis (CHCl3): l
(e/M–1cm–1): 294 (15200), 333 (15300), 378 (14500), 454
(39000) nm. 1H NMR (300 MHz, CDCl3): d = 0.23 (s, 18 H),
3.83 (s, 6 H), 3.84 (s, 6 H), 5.65 (s, 2 H) ppm. 13C NMR (75
MHz, CDCl3): d = –0.2, 53.4 (two overlapping), 92.7, 96.1,
97.4, 101.8, 105.2, 112.5, 118.6, 130.6, 132.2, 148.0, 159.3,
159.7 ppm. MALDI-TOF-MS (matrix: 2,5-dihydroxy-
benzoic acid): m/z = 728 [M+]. Anal. Calcd for
(7) Gaussian 03, Revision B.03, Frisch, M. J. et al., Gaussian
Inc., Pittsburg PA, 2003.
(8) The acetylene and acetylide structures were geometry
optimized at the semiempirical PM3 level. Frequencies were
calculated to verify that the calculated structures are local
minima on the potential energy surface and to correct for
zero-point kinetic energies. Single-point energy calculations
were performed on the optimized structures at the B3LYP/6-
311++G(2d,p) level.
C32H32O8S4Si2 (729.03): C, 52.72; H, 4.42. Found: C, 52.96;
H, 4.82.
(14) The aldehyde 10 was prepared according to a literature
procedure: Tretyakov, E. V.; Tkachev, A. V.; Rybalova, T.
V.; Gatilov, Y. V.; Knight, D. W.; Vasilevsky, S. F.
Tetrahedron 2000, 56, 10075.
(9) All new compounds were fully characterized by 1H NMR
and 13C NMR spectroscopy, elemental analysis and/or
HRMS.
(15) Corey, E. J.; Fuchs, P. L. Tetrahedron Lett. 1972, 3769.
(10) Tykwinski, R. R.; Schreiber, M.; Carlón, R. P.; Diederich,
F.; Gramlich, V. Helv. Chim. Acta 1996, 79, 2249.
Synlett 2004, No. 15, 2818–2820 © Thieme Stuttgart · New York