All-(Z)-cyclooctadeca-1,4,7,10,13,16-hexaene: Structure and first preparation via an intramolecular Wittig reaction

Article abstract of DOI:10.1016/S0040-4039(02)01951-2

The first synthesis of all-(Z)-cyclooctadeca-1,4,7,10,13,16-hexaene was achieved using an intramolecular Wittig reaction as a key step. The structure was firmly established by X-ray analysis.

Full text of DOI:10.1016/S0040-4039(02)01951-2

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 8099–8101
All-(Z)-cyclooctadeca-1,4,7,10,13,16-hexaene: structure and first
preparation via an intramolecular Wittig reaction
Sophie Guiard, Maurice Santelli and Jean-Luc Parrain*
Laboratoire de Synth e` se Organique, UMR CNRS 6009, Facult e´ des Sciences de Saint J e´ r oˆ me, 13397 Marseille, France
Received 22 July 2002; accepted 9 September 2002
Abstract—The first synthesis of all-(Z)-cyclooctadeca-1,4,7,10,13,16-hexaene was achieved using an intramolecular Wittig reaction
as a key step. The structure was firmly established by X-ray analysis. © 2002 Elsevier Science Ltd. All rights reserved.
1
The concept of homoconjugation enounced by Win-
stein attracts continuing attention because of the theo-
retical challenges, unique structures, and organic
synthesis of macrocyclic polyolefins with a higher
degree of insaturation. Bestmann has described the first
synthesis of cycloolefin via auto-oxidation of bisphos-
2
6
materials with interesting properties. The term homo-
conjugation is used if the p-fragments are held in close
proximity by one or two sp centres. In this context, a
wide range of cyclic compounds containing double or
triple bonds have been described in the literature. For
example, two compounds having a cyclic Z-skipped
polyolefin skeleton that are ‘homoconjugated’ ana-
logues of benzene and cyclooctatetraene have been3
synthesised: the all-(Z)-cyclonona-1,4,7-triene (CNT)
and the all-(Z)-cyclododeca-1,4,7,10-tetraene (CDT)
Fig. 1). To the best of our knowledge, larger macro-
cyclic Z-skipped polyolefins possessing more than 12
carbon atoms have never been prepared.
phorane. However by this methodology, the formation
of strain cycles is defavourable and the reaction led to
3
6,7
oligomers. Based on this observation, we thought
that the bisphosphorane 6 would be the appropriate
precursor to cyclooctadeca-1,4,7,10,13,16-hexaene 1
(
Scheme 1).
In this communication, we report that cyclooctadeca-
,4,7,10,13,16-hexaene can effectively be prepared via
1
4
an intramolecular Wittig reaction. Our investigation
began with the preparation of the non-stabilised phos-
phorane aldehyde 2 under the conditions previously
(
8
defined by Bestmann. This compound was easily pre-
pared via the corresponding bisphosphorane 6. The
preparation of bisphosphorane 6 is summarised in
Scheme 2.
Recently, we have described a new synthetic approach5
towards CDT via an intramolecular Wittig reaction.
So, we have planned to extend this methodology to the
After protection of commercially available but-3-yn-1-
ol 3 with dihydropyran in the presence of a catalytic
amount of PPTS, protected butynol was metalled with
n-butyllithium in THF then condensed on
paraformaldehyde to give the corresponding propargyl
9
alcohol (60% yield over two steps). Reaction of alcohol
and tosylchloride in the presence of potassium hydrox-
10
ide in diethylether, at rt, furnished the corresponding
tosylate 4 in a quantitative yield. Reaction of 4 and
but-3-yn-1-ol in the presence of potassium carbonate,
Figure 1.
*
0
Corresponding author.
Scheme 1.
040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)01951-2

8
100
S. Guiard et al. / Tetrahedron Letters 43 (2002) 8099–8101
Scheme 2. Reagents and conditions: (a) DHP, PPTS, CH Cl
2
2,
(
(
99%); (b) i. n-BuLi, THF, −78°C; ii. Paraformaldehyde
60%); (c) TsCl, KOH, Et O, rt; (97%); (d) But-3-yn-1-ol,
2
CuI, NaI, K CO , DMF, 35°C, (82%); (e) P-2 nickel, ethylene
2
3
diamine, H , EtOH, (80%); (f) HCl 1 M, MeOH (99%); (g) I ,
2
2
PPh , imidazole, THF, −10°C, then rt (81%); (h) PPh ,
3
3
CH CN, reflux (95%); (i) NaHMDS (2 M in THF), THF, −78
3
to 0°C, then O (35%).
2
sodium iodide and copper(I) iodide gave the monopro-
11
tected diynol 5 in 82% yield. Semihydrogenation over
Brown P-2 Ni catalyst in the presence of ethylene
diamine afforded the corresponding all-(Z)-dienol in
1
2
80% yield.
After deprotection of hydroxy group with 1 M HCl in
methanol, the dienediol was iodinated with the couple
triphenylphosphine/iodine in the presence of imida-
1
3
zole. The sensitive diiodiene in the presence of
triphenylphosphine yielded the bistriphenylphospho-
nium salt 6 which was purified by crystallisation (77%
yield over three steps).
Figure 2. ORTEP drawing of 1.
Although 1 shows two magnetically different hydrogen
atoms in the solid state (Fig. 2), 1 shows a conforma-
tional change very rapidly in solution as seen on the H
The key step of the synthesis was realised via an
intramolecular Wittig reaction. The diphosphorane was
generated by treatment of THF insoluble bisphospho-
nium salt 6 (0.025 M), at −78°C, with 2.2 equiv. of
NaHMDS. As expected, oxidation reaction of phos-
phorane with a stream of oxygen did not furnish the
all-(Z)-cyclonona-1,4,7-triene but the cyclooctadeca-
1
NMR spectrum recorded in CDCl at 25°C.
3
The side view of 1 shows the unplaness of the molecule
that ‘S-like’-conformation with eight central carbons in
the same plan.
1
,4,7,10,13,16-hexaene 1 in fair yield (35% isolated), as
major product with a total control of the stereochem-
istry of the two double bonds formed. Oligomers (15%)
were also detected but easily separated by column
chromatography. The cyclooctadeca-1,4,7,10,13,16-hex-
1
4
ane 1 possesses a NMR analysis similar to all-(Z)-
cyclododeca-1,4,7,10-tetrane (CDT). After crystalli-
sation in a mixture of cyclohexane and acetone (4/1),
the structure of 1 has been confirmed by X-ray
1
5
analysis and MS analysis.
At the solid state, a crown conformation was found for
1
6
17
the all-(Z)-cyclononatriene and the all-(Z)-CDT. On
the contrary, the cyclooctadeca-1,4,7,10,13,16-hexaene
1
presents an ‘S-like’-conformation with a C3v symme-
try. The ORTEP drawing shows that all the double
bonds exhibit a Z configuration demonstrating that the
Wittig reaction proceeded with total stereocontrol. At
the methylenic positions, it can be noted that one of the
hydrogen atoms is pointing towards the molecule centre
while the other hydrogen atoms are alternatively below
and above the medium plan of the molecule. Finally,
Another interesting feature of this compound is based
on its stacking-up, which is very regular. Each molecule
of cyclooctadeca-1,4,7,10,13,16-hexaene 1 is stacked up
with each axial hydrogen (H and H ) on C and C
10
the core of 1 exhibits a diameter of 3.46 A.
,
1
10
1

S. Guiard et al. / Tetrahedron Letters 43 (2002) 8099–8101
8. Bestmann, H. J. Angew. Chem. 1960, 72, 34.
8101
going on the cavity formed, respectively, by C -C -C -
1
7
18
1
C -C and C -C -C -C -C of the following molecule.
9. (a) Roberts, C. D.; Schuetz, R.; Leumann, C. J. Synlett
1999, 6, 819; (b) Cantin, M.; Schuetz, R.; Leumann, C. J.
Tetrahedron Lett. 1997, 38, 4211–4214; (c) Chilot, J.-J.;
Doutheau, A.; Gore, J.; Saroli, A. Tetrahedron Lett.
1986, 27, 849; (d) Dumez, E.; Faure, R.; Dulcere, J.-P.
Eur. J. Org. Chem. 2001, 13, 2577.
2
3
8
9
10
11
12
At the solid state, the stacking of 1 is similar to
columnar structures. Nevertheless, the distance between
the two molecules within the stack amounts to 4.47 A.
,
This result is incompatible with p–p stacking, which
could explain the cohesion in the molecular edifice.
1
0. Brandsma, L.; Verkruijsse, H. D. Synthesis of Acetylenes,
In summary, we have achieved the first synthesis of
all-(Z)-cyclooctadeca-1,4,7,10,13,16-hexaene 1 using an
intramolecular Wittig reaction as a key step. This com-
pound could be an interesting precursor for the synthe-
sis of metabolites of polyunsaturated fatty acid. Further
applications of 1 are in progress and will be reported in
due course.
Allenes and Cumulenes; 1981; p. 223.
11. (a) Jeffery, T.; Gueugnot, S.; Linstrumelle, G. Tetra-
hedron Lett. 1992, 22, 5757; (b) Pivnitsky, K. K.; Vasil-
java, L. L.; Lapitskaya, M. A. Synthesis 1993, 65; (c)
Durand, S.; Parrain, J.-L.; Santelli, M. Synthesis 1998,
1015.
12. Brown, C. A.; Ajruja, V. K. J. Chem. Soc., Chem.
Commun. 1973, 553.
1
3. (a) Corey, E. J.; Shih, C.; Shih, N.-Y.; Shimoji, K.
Tetrahedron Lett. 1984, 25, 5013–5016; (b) Becker, D.;
Cyjon, R.; Cosse, A.; Moore, I.; Kimmel, T.; Wysoki, M.
Tetrahedron Lett. 1990, 31, 4923.
Supplementary material
X-Ray crystal structure data (cif file) for the C18
hexaene 1 is available from the author upon request
14. Procedure for the preparation of cyclooctadeca-
1,4,7,10,13,16-hexaene from bisphosphonium salt 6: To a
suspension of 6 (4.0 g, 4.44 mmol, 1 equiv.) in THF (180
mL) was added at −78°C, a 2 M THF solution of
NaHMDS (6.22 mL, 12.43 mmol, 2.4 equiv.). The ylide
solution was then allowed to warm to 0°C, and stirred for
(
CCDC 194074).
Acknowledgements
1
h. The solution was cooled at −78°C and a flow of
−
1
oxygen (4 mL min ) was bubbled through the solution
for 4 h. After hydrolysis with satd aq. NH Cl, the
aqueous layer was extracted with Et O (3×50 mL). The
organic layers were washed with satd aq. NaCl, dried
over MgSO then concentrated in vacuo. Flash chro-
We thank CNRS and MESR for providing financial
support, the ‘conseil R e´ gional de la R e´ gion PACA’ and
Isotochim chimie fine for awarding a fellowship to one
of us (S.G.).
4
2
4
matography on silica gel (petroleum ether; R =0.37) led
f
1
to 92 mg (35%) of 1 as a white solid (mp 61°C). H NMR
References
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3
) l: 5.36–5.40 (m, 12H); 2.84–2.94 (m,
13
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3
1
2
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(6C). MS (70 eV): 240 (M, 0.1), 131 (16), 129 (14), 119
(10), 117 (30), 115 (12), 106 (11), 105 (24), 104 (11), 93
(18), 92 (21), 91 (100), 81 (9), 80, (31), 79 (28), 77 (62), 67
(38), 66 (19), 65 (31), 55 (9), 54 (9), 53 (21), 52 (9), 51
(14), 41 (73), 39 (46).
3
15. Colourless crystals of 1 (C18H24) were grown from a
solution of 1 in a 4/1 mixture of cyclohexane/acetone.
Data collection was conducted at 298 K on a monoclinic
crystal; a=17.001(10), b=17.001(10); c=4.474(10) A
,
;
3
4
i=90(10)°; V=1119.9(3) A
,
; space group: R3; Z=3;
2
2
o o
2
R=0.045; wR=0.051 (w=1/[| (F )+0.03F ]); GOF=
+
−
−3
1.398; Dz =0.1 and Dz =−0.1 e A .
,
16. Krause, A.; Musso, H.; Boland, W.; Ahlrichs, R.; Gleiter,
R.; Boese, R.; B a¨ r, M. Angew. Chem., Int. Ed. Engl. 1989,
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5
6
7