The newly modified McMurry reaction toward the improved synthesis of cyclic paraphenylacetylenes

Article abstract of DOI:10.1016/S0040-4039(01)00862-0

Treatment of stilbenedialdehyde derivatives with low-valent titanium generated in a mixed solvent of DME and toluene favored reductive cyclo-oligomerization to give macrocyclic cyclophanepolyenes in relatively good yields leading to improved or new synthesis of a series of cyclic paraphenylacetylenes ([6] to [9]CPPAs).

Full text of DOI:10.1016/S0040-4039(01)00862-0

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 5509–5511
The newly modified McMurry reaction toward the improved
synthesis of cyclic paraphenylacetylenes
Takeshi Kawase, Noriko Ueda, Kenji Tanaka, Yohko Seirai and Masaji Oda*
Department of Chemistry, Graduate School of Science, Osaka University, Toyonaka 560-0043, Japan
Received 21 March 2001; revised 17 May 2001; accepted 18 May 2001
Abstract—Treatment of stilbenedialdehyde derivatives with low-valent titanium generated in a mixed solvent of DME and toluene
favored reductive cyclo-oligomerization to give macrocyclic cyclophanepolyenes in relatively good yields leading to improved or
new synthesis of a series of cyclic paraphenylacetylenes ([6] to [9]CPPAs). © 2001 Elsevier Science Ltd. All rights reserved.
Phenylacetylene macrocycles (PAMs) having well-
defined shapes with rigid cavities are intriguing
molecules from both physicochemical and supramole-
cular points of view.1 In this context, we have recently
reported the synthesis of two members of cyclic para-
phenylacetylenes, [6]CPPA 1a and [8]CPPA 1c2
(Scheme 1), and more recently found that [6]CPPA 1a
we report an effective synthesis of 2a and related com-
pounds by a newly modified McMurry reaction,7 which
has led to the synthesis of previously unknown [7]- and
[9]CPPAs, 1b and 1d. The properties of a series of [6]-
to [9]CPPA thus obtained are also reported for
comparison.
,
having a smooth belt-shaped structure with a 13.2 A
Wennerstro¨m and co-workers reported that treatment
of 1,4-bis(4-formyl-(Z)-styryl)benzene (Z,Z)-3 with
low-valent titanium, generated from TiCl4 and zinc in
THF, afforded [2.2.2]paracyclophanetriene 2e in 50%
yield, but the formation of cyclic oligomers was not
mentioned.8 In order to improve the yield of cyclodimer
2a, we investigated the McMurry reaction of 3 under
several conditions (Scheme 2 and Table 1), and found
that the use of a mixed solvent of DME/toluene (1:1)
gives an isomeric mixture of 2a in 53% yield with a
small amount of 2e (entry 5 in Table 1). Notably, the
known isomer (Z,Z,E)2-2a was formed predominantly.
Variation of the ratio between toluene and DME (2:1
to 1:9) resulted in little change of the yields (entries
diameter forms inclusion complexes with fullerenes
(C60 and C70) and hexamethylbenzene.3,4 To understand
the novel supramolecular properties of CPPAs more
deeply, development of practical synthesis of them
has become an important problem of the study. We
have prepared 1a and 1c from the corresponding
cyclophanepolyenes 2a and 2c, which are usually mix-
tures of geometric isomers, through bromination–de-
hydrobromination in good yields.2 However, the
availability of the cyclophanepolyenes has been unsatis-
factory, because the synthesis of them using the Wittig
or McMurry reaction suffered from low yields and
difficulty in purification.5,6 Therefore, improvement of
the synthesis of cyclophanepolyenes 2 was desired. Here
m
1) Br2 / CDCl3
2) t-BuOK / ether
n
2a (m = 4), b (m = 5),
c (m = 6), d (m = 7)
1a (n = 1), b (n = 2),
c (n = 3), d (n = 4)
Scheme 1.
Keywords: modified McMurry reaction; cyclodimerization; solvent effects; new cyclic paraphenylacetylenes.
* Corresponding author. E-mail: moda@chem.sci.osaka-u.ac.jp
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)00862-0

5510
T. Kawase et al. / Tetrahedron Letters 42 (2001) 5509–5511
TiCl4-Zn(Cu)
+
solvent
CHO
OHC
(Z,Z)-3
2e
(Z,Z,E)2-2a
Scheme 2.
Table 1. Yields of 2a and 2e in various solventsa
formylstyryl)stilbene 410 under the present conditions in
37% yield together with [2.2.2.2]paracyclophanetetraene
(21%), the intramolecular cyclization product. The
yields of 2a and 2c were thus significantly improved as
compared with those in the previous procedures, and
the corresponding CPPAs were readily obtained in
almost pure forms simply by chromatographic filtration
through alumina gel. The present improvement allowed
the synthesis of [7]CPPA 1b11 by [3+4] coupling
approach and [9]CPPA 1d11 by cyclotrimerization of 3:
the sequential treatments converted a mixture of 3 and
4 (1:1) into a mixture of 1a, 1b and 1c (ca. 1:2:1), and
a mixture of the Z,Z- and E,Z-isomer10 of 3 (ca. 3:1)
into a mixture of 1a and 1d (ca. 10:1). Gel permea-
tion chromatography of the mixtures afforded 1b and
1d in 20 and 4% yield, respectively, as fine yellow
needles. The cyclotrimerization of 3 occurred only when
a mixture of (Z,Z)-3 and (E,Z)-3 was used as a sub-
strate.
Entry
Solvent
Yields (%)
2e
2a
1b
2
3
4
5
THF
DME
THF–toluene (1:1)
DME–toluene (9:1)
DME–toluene (1:1)
DME–toluene (1:2)
50
34
18
4
–
12
16
40
53
41
3
6
Trace
a Conditions: A suspension of TiCl4–Zn in the solvent system was
heated at reflux for 2 h, then a solution of the dialdehyde 3 in the
solvent was added dropwise to the suspension over 30 min at rt, and
the reaction mixture was stirred at rt for 12 h, then heated at reflux
for 5 h.
b Ref. 8.
4–6). The reaction in DME only or THF/toluene (1:1)9
gave 2e as a major product together with a stereoiso-
meric mixture of 2a (entries 2 and 3). In toluene only,
the reduction of TiCl4 with ZnꢀCu did not proceed
smoothly. The McMurry couplings in ethereal solvents
generally afford a mixture of geometric isomers proba-
bly due to isomerization through an electron transfer
process.7 Actually, 2a was obtained as a messy mixture
of the geometric isomers when the coupling was carried
out in DME only. Therefore, E-selective double bond
formation under the present modified McMurry reac-
tion seems to play a key role for the cyclooligomeriza-
tion. The strong solvent effects suggest that the reactive
intermediate generated in DME/toluene would be dif-
ferent from those generated in solvents without toluene.
Although the elucidation of the reactive intermediate
has been unsatisfactory, the present modified reaction
would be promising for the preparation of macrocyclic
compounds of physicochemical interest.
The selected spectral data of 1a–d together with those
of an acyclic oligomer 52 are shown in Table 2. The
averaged values of the inner phenylacetylene part of 5 is
taken as reference for comparison. The simple NMR
spectra of 1b and 1d clearly indicate that the molecules
have a belt-shaped structure similar to 1a and 1c. While
the aromatic protons move slightly up-field, the sp
carbons move appreciably down-field (more sp2-like
due to bending) as the ring-size becomes smaller (higher
1
strain). Thus, the H NMR spectra exhibit no alternate
changes associated with a peripheral conjugation. Simi-
lar to the case of acyclic oligomers,12 no significant
bathochromic shift of the longest UV–vis absorptions
are observed for 1a to 1d. The emission spectra, how-
ever, exhibit broadening and bathochromic shift with
decrease of the ring-size, probably due to the increase
of strain and rigidity of the molecules.
A stereoisomeric mixture of 2c, the precursor for
[8]CPPA 1c, was also obtained from (Z,Z,Z)-4,4%-bis(4-
In conclusion, the newly modified McMurry reactions
allowed the improved or new synthesis of cyclic para-
tBu
tBu
tBu
tBu
5
CHO
OHC
5
4

T. Kawase et al. / Tetrahedron Letters 42 (2001) 5509–5511
Table 2. Selected spectral data of 1a–1d and 5
1a
7.35
5511
1b
1c
1d
5
1H NMRa
13C NMRa
7.36
7.40
7.43
94.21
123.56
131.33
354 (5.51)
414, 442
7.52c
90.7c
sp Carbon
ipso
97.65
96.14
94.95
123.93
130.87
349 (5.40)
471
123.92
131.07
355 (5.41)
418, 448
123.67
131.21
355 (5.47)
416, 447
Aromatic
Absorption max.
Emission max.b
(log m)b
358 (5.05)
398, 418
a l ppm, in CDCl3.
b In cyclohexane.
c Averaged values of inner phenylacetylene units of the molecule.
phenylacetylenes composed of six to nine phenyl-
acetylene units. The reaction would be applicable to the
preparation of other macrocyclic cyclophanes.13 CPPAs
thus obtained provide no evidence for cyclic conjuga-
tion around the curved periphery. Their spectral prop-
erties vary mainly with decrease of ring-size of the
molecules, which increases the strain of the molecules
due to larger bending of the triple bonds and deeper
boat-form of the benzene rings. Further studies on
CPPAs are in progress from the supramolecular point
of view.
Chem. Rev. 1989, 89, 1513–1524; (b) Fu¨rstner, A.; Bog-
danovie, B. Angew. Chem., Int. Ed. Engl. 1996, 35, 2442–
2469.
8. Tanner, D.; Wennerstro¨m, O.; Norinder, U.; Mu¨llen, K.;
Trinks, R. Tetrahedron 1986, 42, 4499–4502.
9. The authors thank Dr. S. Luff (UK) for valuable infor-
mation that the McMurry reaction proceeds well in a
mixed solvent system of THF and toluene (1:1).
10. 1H NMR data of the new dialdehydes; (E,Z)-3: 1H NMR
(270 MHz, CDCl3): l=6.65 (d, J=12.2 Hz, 1H), 6.74 (d,
J=12.2 Hz, 1H), 7.13 (d, J=16.4 Hz, 1H), 7.19 (d,
J=16.4 Hz, 1H), 7.23–7.25 (m, AA%BB% pattern, JAB=8.1
Hz, 2H), 7.40–7.43 (m, AA%BB% pattern, JAB=8.5 Hz,
2H), 7.42–7.44 (m, AA%BB% pattern, JAB=8.1 Hz, 2H),
7.62–7.64 (m, AA%BB% pattern, JAB=8.2 Hz, 2H), 7.75–
7.77 (m, AA%BB% pattern, JAB=8.2 Hz, 2H), 7.85–7.87
(m, AA%BB% pattern, JAB=8.2 Hz, 2H), 9.97 (s, 1H), 9.99
Acknowledgements
This work was supported by Grant-in-Aid for Scientific
Research (No. 10874087 and 11440189) from Ministry
of Education, Science and Culture (Japan).
1
(s, 1H). (Z,Z,Z)-4: mp 130–131°C, H NMR (270 MHz,
CDCl3): l=6.54 (s, 2H), 6.59 (d, J=12.2 Hz, 1H), 6.70
(d, J=12.2 Hz, 1H), 7.06–7.08 (m, AA%BB% pattern,
J
AB=8.6 Hz, 4H), 7.11–7.13 (m, AA%BB% pattern, JAB=
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