Synthesis of substituted linear Ter- and quaterphenyls via dewar benzenes

Article abstract of DOI:10.1055/s-0030-1259321

Tetramethylcyclobutadiene-AlClcomplex reacted with bisalkynes possessing phenylene and biphenylene spacer giving rise to mono- and bis-Dewar benzenes. The rearrangement of the bis-Dewar benzene derivatives under thermal conditions (150 C) yielded the corr

Full text of DOI:10.1055/s-0030-1259321

396
LETTER
Synthesis of Substituted Linear Ter- and Quaterphenyls via Dewar Benzenes
S
ynthesis of
S
t
ubstitut
ě
e
d
Linear
T
p
er- and Qua
á
terphenyls nka Janková,a Simona Hybelbauerová,b Martin Kotora*a,c
a
Department of Organic and Nuclear Chemistry, Faculty of Science, Charles University in Prague,
Hlavova 8, 128 43 Praha 2, Czech Republic
Fax +420(221)951324; E-mail: kotora@natur.cuni.cz
Department of Teaching and Didactics of Chemistry, Faculty of Science, Charles University in Prague,
Albertov 3, 128 43 Praha 2, Czech Republic
Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic,
v.v.i., Flemingovo nám. 2, 166 10 Praha 6, Czech Republic
b
c
Received 3 November 2010
The starting model bisalkynes 3a and 3b were prepared in
two steps from the corresponding 1,4-diiodoaromatics 1
(Scheme 1) by two pathways. Pathway A started with the
Sonogashira reaction under standard conditions with tri-
Abstract: Tetramethylcyclobutadiene–AlCl3 complex reacted with
bisalkynes possessing phenylene and biphenylene spacer giving rise
to mono- and bis-Dewar benzenes. The rearrangement of the bis-
Dewar benzene derivatives under thermal conditions (150 °C)
yielded the corresponding linear ter- and quaterphenyl compounds methylsilylethyne to give bis(trimethylsilylethynyl)are-
possessing substituted terminal benzene rings. A mixture of an
alkynylbiphenyl and a terphenyl was also obtained by the reaction
of tetramethylzirconacyclopentadiene with bisalkynylbenzene in
which were reacted with chloroformate to yield the
13% combined yield.
nes 2. After isolation and purification, their treatment with
n-BuLi resulted in the formation of lithioderivatives,
corresponding bisalkynylarenes 3. 1,4-Bis(carboxy-
Key words: Dewar benzene, alkynes, cyclobutadiene, polycycles,
methylalkynyl)benzene (3a) and and 1,1¢-bis(carboxyme-
metallacycles
thylakynyl)biphenyl (3b) were isolated in 17% and 25%
yields, respectively. Although both products were formed
in reasonable yields (ca. 50–60%), as judged by the anal-
Substituted Dewar benzenes (DB) and their synthesis1
yses of the reaction mixtures, low isolated yields can be
have been known since 1960s; however, their application
attributed to difficult separation of the products from the
in organic synthesis is rather scarce. Although several
methods for preparation of DB have been developed,
probably the most versatile and simple procedure is based
on the reaction of aluminum trichloride with two equiva-
starting material and intractable side products. A more di-
rect synthesis of 3a and 3b (pathway B) relied on the
Negishi coupling of iodobenzenes 1a or 1b with zinc
acetylides formed in situ from methyl propynoate, zinc
lents of an alkyne (e.g., 2-butyne)2 and an activated
alkyne. The initial step gives rise to a complex compound
that could be formally described as tetramethylcyclobuta-
diene–AlCl3 complex3 that reacts with the activated
alkyne to yield the corresponding DB. This method was
used for the synthesis of DB polymers and permethylated
ladderanes,4 chiral DB,5 phenyl-substituted DB,6 conju-
gates with ferrocene,7 and finally the method could also be
used as a protecting group.8
bromide, and a base.9 This method was shorter and more
successful furnishing the desired target compounds 3a
and 3b in higher isolated yields of 53% and 48%, respec-
tively.
SiMe3
path A
path B
I
I
Pd(PPh3)4
CuI, Et3N
n
1a, n = 1
1b, n = 2
The above-mentioned easy access to substituted Dewar
benzenes and their facile quantitative rearrangement un-
der thermal or photochemical conditions into substituted
benzene rings provided strong impetus to apply this chem-
istry for the synthesis of polyaryl compounds. We envi-
sioned that an alternative and hitherto unexplored
methodology for the synthesis of polyaryls such as p-ter-
and p-quaterphenyls bearing substituted terminal ben-
zenes rings could be based on the use of the corresponding
Dewar benzenes, which in turn could be prepared by the
AlCl3-mediated reaction of internal alkynes with activated
bisalkynylarenes.
Me3Si
SiMe3
PdCl2(PPh3)2
COOMe
LDA, ZnBr2
n
2a, n = 1, 99%
2b, n = 2, 83%
n-BuLi
MeOOC
COOMe
ClCOOMe
n
3a, n = 1, 17% (path A), 53% (path B)
3b, n = 2, 25% (path A), 48% (path B)
Scheme 1 Preparation of bisalkynylarenes 3
In the next step both bisalkynylarenes 3a and 3b reacted
with tetramethylcyclobutadiene–AlCl3 complex under
standard conditions (Scheme 2). In both cases the prod-
ucts were obtained as mixtures of mono- and bis-Dewar
benzenes 4 and 5 that were difficult to separate not only
SYNLETT 2011, No. 3, pp 0396–0398
Advanced online publication: 13.01.2011
DOI: 10.1055/s-0030-1259321; Art ID: G32010ST
© Georg Thieme Verlag Stuttgart · New York
x
x.
x
x.
2
0
1
1

LETTER
Synthesis of Substituted Linear Ter- and Quaterphenyls
397
from each other but also from the unreacted starting mate-
rial. Their low solubility in various solvents should be
mentioned as well. Pure compounds were obtained only
after tedious chromatography of the reactions mixture by
using preparative TLC. Although conversions were at
least 50%, the difficulties regarding the product separa-
tion resulted in rather low isolated yields. Thus in the case
of the reaction of 3a was isolated mono-DB derivatives 4a
and bis-DB derivative 5a in 17 and 10% yields, respec-
tively. In a similar fashion, workup of the reaction mixture
with 3b furnished mono-DB derivatives 4b and bis-DB
derivative 5b in 28% and 17% yields, respectively.
COOMe
4a
4b
6a, 95%
COOMe
COOMe
COOMe
6b, 97%
7a, 98%
MeOOC
5a
5b
COOMe
COOMe
MeOOC
MeOOC
4a, 17%
7b, 97%
3a
+
COOMe
COOMe
Scheme 3 Rearrangement of DB 4 and 5 into polyaryls 6 and 7
MeOOC
AlCl3
yield any reasonable amounts of 4 or 5, only trace amount
of these compounds were observed by TLC analysis. The
major product was hexamethylbenzene formed by the ho-
mocyclotrimerization of 2-butyne. Partial success was ob-
tained using the stoichiometric process based on the
reaction of tetramethylzirconacyclopentadiene (8), pre-
pared from Cp2ZrBu2 and 2-butyne, with 3a in the pres-
ence of CuCl.11 After two days reaction time, which is
typical for alkynes bearing just one activating group,11b,d
1H NMR analysis indicated that 4a was formed in 21%
and 5a in 28% yields (Scheme 4). Workup of the reaction
mixture furnished 2:3 mixture of 4a and 5a in 13% isolat-
ed yield.
5a, 10%
1.
CH2Cl2, –20 °C
COOMe
2. DMSO
MeOOC
4b, 28%
3b
+
COOMe
MeOOC
5b, 17%
2CuCl
Scheme 2 Synthesis of Dewar benzene derivatives 4 and 5
ZrCp2
+
3a
4a
+
5a
2 d
20 °C
(21%)
(28%)
Next the prepared compounds 4 and 5 were subjected to
thermal rearrangement to the corresponding linear pol-
yarenes. The neat compounds 4 and 5 were heated at
150 °C for six hours (Scheme 3). In all cases the reaction
proceeded uneventfully to give the expected products in
quantitative yields. The rearrangement of mono-BDs 4a
and 4b gave rise the corresponding alkynylbiphenyl 6a
(95%) and alkynylterphenyl 6b (97%). The bis-DB 5a and
5b yielded the corresponding terphenyl 7a (95%)10a and
quaterphenyl 7b (97%).10b As far as physical properties of
these compounds are concerned, low solubility of the
formed compounds in all spectrum of solvents was no-
ticed again.
8
Scheme 4 Reaction of zirconacyclopentadiene 8 with 3a
An interesting issue is the stereochemistry of the prepared
DB 5 and polyarenes 7. It is reasonable to expect 5a and
7a to exist as diastereomers (with axially chirality) due to
the hindered rotation along the C–C bond connecting the
DB and substituted aryl frameworks with the benzene ring
(as observed before11d). On the other hand, free rotation
along the bond connecting the middle benzene rings in 5b
and 7b precludes the formation of any stereoisomers un-
der usual conditions (20 °C). In the case of 5a only one set
of signals was observed in 1H NMR spectrum at 400 MHz.
However, when the spectrum was recorded at higher op-
erational frequency (600 MHz) the measured data indicat-
ed the presence of two stereoisomers (cis and trans with
respect to the position of the methyl ester groups to the
The starting bisalkynes 3a and 3b also constitute an inter-
esting starting material for potential cyclotrimerization
with 2-butyne. In this regard the cyclotrimerization of ei-
ther 3a or 3b with 2-butyne under catalytic conditions in
the presence of Ni(cod)2/2PPh3 or RhCl(PPh3)3 did not
Synlett 2011, No. 3, 396–398 © Thieme Stuttgart · New York

398
Š. Janková et al.
LETTER
(5) (a) Dopper, J. H.; Greijdanus, B.; Wynberg, H. J. Am. Chem.
Soc. 1975, 97, 216. (b) Dopper, J. H.; Greijdanus, B.;
Luxman, D.; Wynberg, H. J. Chem. Soc., Chem. Commun.
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(6) Janková, Š.; Dračínský, M.; Císařová, I.; Kotora, M. Eur. J.
Org. Chem. 2008, 47.
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M. Dalton Trans. 2009, 3137.
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plane of the benzene ring), albeit the difference in shift
values was rather marginal (the ester Me groups appeared
at d = 3.791 and 3.793 ppm, 25 °C, CDCl3). By using dy-
namic NMR spectroscopy the rotation barrier was calcu-
lated (DG# = ca. 70 kJ/mol),12 which is too low for a
potential isomer separation.13
An analogous picture was also observed in the case of the
polyarene 7a: at 400 MHz the measured data indicated the
presence of two diastereomers, albeit the difference in
shift values was rather marginal (the H atoms of the cen-
tral benzene ring appeared at d = 7.076 and 7.085 ppm,
25 °C, DMSO-d6). Using dynamic NMR spectroscopy the
rotational barrier for 7a was calculated to be DG# = ca. 77
kJ/mol.
3, 3847.
(9) Anastasia, L.; Negishi, E. Org. Lett. 2001, 3, 3111.
(10) (a) Dimethyl 3,3¢¢,4,4¢¢,5,5¢¢,6,6¢¢-octamethyl-1,1¢:4¢,1¢¢-
terphenyl-2,2¢¢-dicarboxylate (7a)
1H NMR (600 MHz, CDCl3, Me4Si): d = 2.02 (s, 6 H), 2.25–
2.29 (m, 18 H), 3.43 (s, 3 H), 3.56 (s, 3 H), 7.17–7.18 (m, 4
H). 13C NMR (150 MHz, CDCl3, Me4Si): d = 16.22, 16.25,
16.75, 17.50, 17.53, 17.55, 17.78, 51.38, 51.59, 129.07,
129.13, 129.42, 132.04, 132.10, 132.76, 133.00, 134.59,
134.69, 136.12, 136.32, 136.55, 136.69, 138.79, 138.96,
170.82, 170.91. IR (CHCl3): n = 2962, 2923, 2852, 1725,
1263, 1099, 1018, 801 cm–1. MS (EI): m/z (%) = 459 (12)
[M+], 458 (41), 427 (30), 426 (100), 395 (23), 379 (22), 351
(12), 295 (22). HRMS: m/z calcd for C30H34O4: 458.2457;
found: 458.2439. Rf = 0.65 (hexane–EtOAc = 1:1).
(b) Dimethyl 3,3¢¢,4,4¢¢,5,5¢¢,6,6¢¢-octamethyl-
In conclusion, Dewar benzenes may serve as intermedi-
ates in the preparation of ter- and quaterphenyls with sub-
stituted terminal benzene rings. Namely, the whole
reaction sequence is based on the reaction of tetramethyl-
cyclobutadiene–AlCl3 complex with bisalkynes bearing
ester groups giving rise to bis-Dewar benzenes, thermal
rearrangement of which then yields the corresponding
polyaryl compounds.
1,1¢:4¢,1¢¢:4¢¢,1¢¢¢-quaterphenyl-2,2¢¢-dicarboxylate (7b)
Mp 228–230 °C (CH2Cl2). 1H NMR (600 MHz, CDCl3,
Me4Si): d = 2.07 (s, 3 H), 2.26–2.29 (m, 18 H), 3.47 (s, 6 H),
7.26–7.27 (m, 4 H), 7.64–7.66 (m, 4 H). 13C NMR (150
MHz, CDCl3, Me4Si): d = 16.28, 16.79, 17.59, 17.82, 51.57,
126.28, 129.37, 129.71, 130.07, 132.18, 132.83, 134.71,
136.05, 136.72, 139.08, 139.34. IR (CHCl3): n = 3077, 3029,
2984, 2950, 2222, 1727, 1605, 1434, 1378, 1292, 1201,
1174, 1004, 819, 732 cm–1. MS (EI): m/z (%) = 535 (14)
[M+], 534 (43), 319 (17), 318 (100), 288 (12), 287 (71), 260
(33), 229 (24), 202 (22), 200(11), 149 (13). HRMS: m/z
calcd for C36H38O4: 534.2770; found: 534.2764. Rf = 0.43
(hexane–EtOAc = 1:1).
Acknowledgment
We gratefully acknowledge financial support from the research pro-
jects GAAV (IAA401110805), and Ministry of Education, Youth,
and Sports of the Czech Republic (LC06070, MSM0021620857).
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