Synthesis of 4,4′-spirobi[pentacyclo[5.4.0.02,6.03,10.05,9]undecane]

Article abstract of DOI:10.1016/j.tetlet.2015.10.050

4,4′-Spirobi[pentacyclo[5.4.0.0^2,6.0^3,10.0^5,9]undecane] (10) is first successfully prepared by a nine step synthetic scheme starting from the key intermediate (cyclopentadiene derivate, 2). This synthetic scheme avoids using the hardly obtainable spiro[4.4]nonatetraene (18) as the starting material. In the structure of 10, two polycyclic cages share one spiro-carbon so that it has high density (1.2663 g/cm³) and high volumetric heat of combustion (53.353 MJ/L).

Full text of DOI:10.1016/j.tetlet.2015.10.050

Tetrahedron Letters xxx (2015) xxx–xxx
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
0
2,6 3,10 5,9
Synthesis of 4,4 -spirobi[pentacyclo[5.4.0.0 .0
.0 ]undecane]
⇑
Yijun Shi, Jingyang Jiang , Jianzhi Wang, Yanhua Wang
State Key Laboratory of Fine Chemicals, Faculty of Chemical Environmental and Biological Science and Technology, Dalian University of Technology, Dalian 116024, China
a r t i c l e i n f o
a b s t r a c t
4,4 -Spirobi[pentacyclo[5.4.0.02,6.03,10.05,9]undecane] (10) is first successfully prepared by a nine step
synthetic scheme starting from the key intermediate (cyclopentadiene derivate, 2). This synthetic scheme
0
Article history:
Received 26 August 2015
Revised 12 October 2015
Accepted 15 October 2015
Available online xxxx
avoids using the hardly obtainable spiro[4.4]nonatetraene (18) as the starting material. In the structure of
3
1
0, two polycyclic cages share one spiro-carbon so that it has high density (1.2663 g/cm ) and high vol-
umetric heat of combustion (53.353 MJ/L).
Ó 2015 Elsevier Ltd. All rights reserved.
Keywords:
4
,4 -Spirobi[pentacyclo[5.4.0.02,6.03,10.05,9
0
]
undecane]
Cyclopentadiene derivate
Polycyclic cages
Spiro-carbon
Polycyclic cage compounds have been intriguing many che-
mists since cubane was first synthesized in 1964 especially in
the areas of medicinal chemistry and high-energy-density hydro-
carbon fuels. In the area of medicinal chemistry,1 polycyclic cage
compounds have been reported as an important class in drug dis-
covery research, demonstrating a variety of activities and provid-
ing an excellent scaffold for the design of active therapeutic
–4
5
–19
agents.
In the area of high-energy-density hydrocarbon fuels,
many polycyclic cage hydrocarbons were selected because of their
inherent advantages such as high density, additional strain energy,
2
0–30
and great stability.
adamantane, cubanes,
Typical polycyclic cage hydrocarbons are
Scheme 1. Marchand’s synthesis of 12.
3
1
homocubanes, bishomocubanes, and
The trishomocubane pentacyclo
5.4.0.0 .0 .0 ]undecane (12, PCUD) was first synthesized in
3
2,33
trishomocubanes.
2
,6 3,10 5,9
[
34
1
4% overall yield by Stedman and co-workers, and then it was
reported to be obtained in 47% overall yield by Marchand
3
5,36
3
(Scheme 1).
It has high density (1.23 g/cm ), moderate strain
energy (389.0 kJ/mol), and good stability. But one problem atten-
dant with the use of these polycyclic cage monomers was their
high volatility which prompted them to sublime readily at ambient
2
7,30
temperature.
In an effort to minimize the volatility of these
24 alkenes (14, 15, 16,
7) by McMurry coupling of the monoketone 13 (Scheme 2). These
monomers, Marchand reported the C22
H
1
3
C
22
H24 alkenes are of high densities (1.2–1.3 g/cm ) and relatively
2
1,27,28,37
Scheme 2. Reagents and conditions: (a) HOCH
LiAlH , Et O, reflux, rt; (c) aq HCl, rt; (d) hydrazine monohydrate, diethylene glycol,
KOH, 135–200 °C, rt; (e) NaBH , CH Cl , rt; (f) Zn, TiCl , THF, Py, N , reflux, rt.
2 2
CH OH, TsOH, PhMe, reflux, rt; (b)
nonvolatile.
From the structure point of view, these com-
4
2
pounds are two polycyclic cages connected by a C@C double bond
in their structures and this connection style is like two balls con-
4
2
2
4
2
nected by a bar. In an idea to design a structure having two balls
fused together to get higher density and higher volumetric heat
⇑
Corresponding author.
E-mail address: jyjiang@dlut.edu.cn (J. Jiang).
http://dx.doi.org/10.1016/j.tetlet.2015.10.050
040-4039/Ó 2015 Elsevier Ltd. All rights reserved.
0
Please cite this article in press as: Shi, Y.; et al. Tetrahedron Lett. (2015), http://dx.doi.org/10.1016/j.tetlet.2015.10.050

2
Y. Shi et al. / Tetrahedron Letters xxx (2015) xxx–xxx
quinone with 2 in 75.8% yield and the intramolecular [2+2] photo-
cyclization of 3 formed 4 in 80.1% yield. 4 was converted to 5 in
9.5% yield by Wolff–Kishner reduction and 5 was converted to
6
the dixanthate 7 through a two step reaction in 48.3% overall yield.
The pyrolysis of 7 afforded the key diene intermediate 1 in 51%
Figure 1. The structure of 10.
yield and 1 was reacted with p-benzoquinone in CH
10 °C to form 8 as a yellow solid in 94% yield. The intramolecular
2+2] photocyclization of 8 gave 9 in 90% yield and 9 was converted
2 2
Cl at
ꢀ
[
of combustion polycyclic cage hydrocarbon, a spirobi(polycyclic
cage) compound 10 (Fig. 1) was designed. Here in this Letter the
synthesis of 10 is presented.
to polycyclic cage hydrocarbon 10 as the goal compound in 63%
yield by Wolff–Kishner reduction. For compounds 14 which was
prepared by known method and 10, their densities and volumetric
heat of combustions were measured. From the date shown in
Table 1, we found that 10 had higher density and higher volumetric
heat of combustion.
It is known that spiro[4.4]nonatetraene (18) has been synthe-
sized and it can act as diene to react with dienophile such as
dimethyl azodicarboxylate in Diels–Alder reaction.3
8–40
For the
synthesis of 10, 18 seems to be an ideal starting material following
a three step synthetic route (Scheme 3). But 18 was difficult to be
obtained, highly reactive toward oxidation and polymerization,
and easy to decompose within a few days even stored neat at
In summary, polycyclic cage hydrocarbon 10 was successfully
synthesized and it has two PCUDs sharing one spiro-carbon in its
3
structure. Compound 10 had high density (1.2663 g/cm ) and high
39
volumetric heat of combustion (53.353 MJ/L). In our future work,
the synthesis of new spirobi(polycyclic cage) hydrocarbon such
as spirobi(homocubane) will be tried. In addition, many intermedi-
ates in Scheme 4 may be valuable in the field of medicinal
chemistry.
ꢀ
30 °C. So Scheme 3 was not chosen as the synthetic route of 10.
On considering new synthetic route, an inspiration from the
publication of Semmelhack3
8,39
was drawn and a synthetic route
using 2 as starting material was designed (Scheme 4). Following
this route, 3 was prepared by the Diels–Alder reaction of p-benzo-
Scheme 3.
Scheme 4. Reagents and conditions: (a) CH
O, CH OH, 90 °C, rt, 100%; (e) NaH, THF, CH
monohydrate, diethylene glycol, KOH, 135–200 °C, rt, 63%.
3
OH, ꢀ10 °C, rt, 75.8%; (b) hv, EtOAc, rt, 80.1%; (c) hydrazine monohydrate, diethylene glycol, KOH, 135–200 °C, rt, 69.5%; (d) HCl,
H
2
3
3
I, CS , 35 °C, rt, 48.3%; (f) 200 °C, rt, 51%; (g) p-benzoquinone, CH Cl , ꢀ10 °C, rt, 94%; (h) hv, EtOAc, rt, 90%; (i) hydrazine
2
2
2
Please cite this article in press as: Shi, Y.; et al. Tetrahedron Lett. (2015), http://dx.doi.org/10.1016/j.tetlet.2015.10.050

Y. Shi et al. / Tetrahedron Letters xxx (2015) xxx–xxx
3
Table 1
12. Sklyarova, A. S.; Rodionov, V. N.; Parsons, C. G.; Quack, G.; Schreiner, P. R.;
Densities and volumetric heat of combustions of compounds 14 and 10
Fokin, A. A. Med. Chem. Res. 2012, 22, 360–366.
3. Joubert, J.; Sharma, R.; Onani, M.; Malan, S. F. Tetrahedron Lett. 2013, 54, 6923–
1
Compound
Densitya (g/cm3)
Volumetric heat
6927.
of combustionb (MJ/L)
14. Beinat, C.; Banister, S. D.; Hoban, J.; Tsanaktsidis, J.; Metaxas, A.; Windhorst, A.
D.; Kassiou, M. Bioorg. Med. Chem. Lett. 2014, 24, 828–830.
15. Joubert, J.; Samsodien, H.; Baber, Q. R.; Cruickshank, D. L.; Caira, M. R.; Malan, S.
F. J. Chem. Crystallogr. 2014, 44, 194–204.
1
1
.2436
.2663
50.536
53.353
16. Wilkinson, S. M.; Gunosewoyo, H.; Barron, M. L.; Boucher, A.; McDonnell, M.;
Turner, P.; Morrison, D. E.; Bennett, M. R.; McGregor, I. S.; Rendina, L. M.;
Kassiou, M. ACS Chem. Neurosci. 2014, 5, 335–339.
7. Wlochal, J.; Davies, R. D.; Burton, J. Org. Lett. 2014, 16, 4094–4097.
8. Zindo, F. T.; Barber, Q. R.; Joubert, J.; Bergh, J. J.; Petzer, J. P.; Malan, S. F. Eur. J.
Med. Chem. 2014, 80, 122–134.
1
1
1
9. Geldenhuys, W. J.; Malan, S. F.; Murugesan, T.; Van der Schyf, C. J.; Bloomquist,
J. R. Bioorg. Med. Chem. 2004, 12, 1799–1806.
2
2
2
0. Segal, C.; Pethe, S.; Williams, K. R. Combust. Sci. Tech. 2001, 163, 229–244.
1. Segal, C.; Shyy, W. Trans. ASME 1996, 118, 180–186.
2. Marchand, A. P.; Sorokin, Viktor D.; Watson, W. H.; Carlson, T. F.; Krawiec, M.
Struct. Chem. 1994, 5, 367–373.
a
From gas pycnometer.
Recorded by calorimeter.
b
23. Marchand, A. P.; Zope, A.; Zaragoza, P.; Bott, S. G. Tetrahedron 1994, 50, 1687–
1698.
Supplementary data
2
4. Marchand, A. P.; Vidyasagar, V. J. Org. Chem. 1991, 56, 282–286.
5. Marchand, A. P.; Reddy, G. M.; Deshpande, M. N.; Watson, W. H.; Nagl, A.; Lee,
O. S.; Osawa, E. J. Am. Chem. Soc. 1990, 112, 3521–3529.
2
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2015.10.
2
2
2
2
3
3
6. Marchand, A. P.; Jin, Pei-Wen; Alsenoy, Christian Van J. Mol. Struct. (Theochem)
1990, 204, 209–218.
0
50.
7. Marchand, A. P.; Deshpande, M. N.; Reddy, G. Madhusudhan Am. Chem. Soc. Div.
Fuel Chem. 1989, 34, 946–954.
8. Flippen-Anderson, J.; Gilardi, Richard; George, Clifford; Marchand, A. P. Acta
Cryst. 1988, C44, 1617–1619.
9. de Meijere, A.; Redlich, S.; Frank, D.; Magull, J.; Hofmeister, A.; Menzel, H.;
Konig, B.; Svoboda, J. Angew. Chem. 2007, 46, 4574–4576.
0. Qiu, L. M.; Ye, D. Y.; Wei, W.; Chen, K. H.; Hou, J. X.; Zheng, J.; Gong, X. D.; Xiao,
H. M. J. Mol. Struct. (Thoechem) 2008, 866, 63–74.
1. Biegasiewicz, K. F.; Griffiths, J. R.; Savage, G. P.; Tsanaktsidis, J.; Priefer, R. Chem.
Rev. 2015, 115, 6719–6745.
References and notes
1
.
Marchand, A. P.; Geldenhuys, W. J.; Malan, S. F.; Bloomquist, J. R.; Schyf, C. J. V.
d. Med. Res. Rev. 2005, 25, 21–48.
2
3
.
.
Oliver, D. W.; Malan, S. F. Med. Chem. Res. 2007, 17, 137–151.
Joubert, J.; Geldenhuys, W. J.; Van der Schyf, C. J.; Oliver, D. W.; Kruger, H. G.;
Govender, T.; Malan, S. F. ChemMedChem 2012, 7, 375–384.
Schyf, C. J. V. d.; Geldenhuys, W. J. Neurotherapeutics 2009, 6, 175–186.
Mdzinarishvili, A.; Geldenhuys, W. J.; Abbruscato, T. J.; Bickel, U.; Klein, J.; Van
der Schyf, C. J. Neurosci. Lett. 2005, 383, 49–53.
4
5
.
.
3
3
3
2. Griffin, Gary W. Chem. Rev. 1989, 89, 997–1010.
3. Marchand, A. P. Chem. Rev. 1989, 89, 1011–1033.
4. Stedman, R. John; Miller, L. S.; Davis, L. D.; Hoover, J. R. E. J. Org. Chem. 1970, 35,
6.
7.
8.
9.
Gunosewoyo, H.; Guo, J. L.; Bennett, M. R.; Coster, M. J.; Kassiou, M. Bioorg. Med.
Chem. Lett. 2008, 18, 3720–3723.
Hao, J.; Mdzinarishvili, A.; Abbruscato, T. J.; Klein, J.; Geldenhuys, W. J.; Van der
Schyf, C. J.; Bickel, U. Brain Res. 2008, 1196, 113–120.
4169–4175.
3
3
3
5. Marchand, A. P.; Allen, R. W. J. Org. Chem. 1974, 39, 1596.
6. Kenwright, A. M.; Sellars, J. D. Magn. Reson. Chem.: MRC 2012, 50, 803–808.
7. Segal, C.; Friedauer, M. J.; Udaykumar, H. S.; Shyy, W.; Marchand, A. P. J. Propul.
Power 1997, 13, 246–249.
Geldenhuys, W. J.; Bezuidenhout, L.-M.; Dluzen, D. E. Eur. J. Pharmacol. 2009,
6
19, 38–43.
Joubert, J.; van Dyk, S.; Green, I. R.; Malan, S. F. Eur. J. Med. Chem. 2011, 46,
010–5120.
3
3
4
8. Semmelhack, M. F.; Foos, J. S.; Katz, S. J. Am. Chem. Soc. 1972, 94, 8637–8638.
9. Semmelhack, M. F.; Foos, J. S.; Katz, S. J. Am. Chem. Soc. 1973, 95, 7325–7336.
0. Haumann, T.; Benet-Buchholz, J.; Boese, R. J. Mol. Struct. (Thoechem) 1996, 374,
5
1
0. Wang, J.; Ma, C.; Balannik, V.; Pinto, L. H.; Lamb, R. A.; Degrado, W. F. ACS Med.
Chem. Lett. 2011, 2, 307–312.
299–304.
1
1. Lockman, J. A.; Geldenhuys, W. J.; Jones-Higgins, M. R.; Patrick, J. D.; Allen, D.
D.; Van der Schyf, C. J. Brain Res. 2012, 1489, 133–139.
Please cite this article in press as: Shi, Y.; et al. Tetrahedron Lett. (2015), http://dx.doi.org/10.1016/j.tetlet.2015.10.050