Thermo-cage opening of 4-iodo-1-vinylcubane to a novel styrene derivative

Article abstract of DOI:10.1016/j.tetlet.2008.02.161

Cubane (1) and its derivatives have been cited for exhibiting unusual properties, including explosive and antiviral activity. An additional characteristic of these compounds is their tendency to undergo cage opening under certain conditions. In our attempt to polymerize 4-iodo-1-vinylcubane (4), 4-vinyl-trans-β-iodostyrene (10) was formed quantitatively. By examining both the thermolytic and Lewis acid-assisted rates, a possible mechanism for the rearrangement of 4→10 has been proposed.

Full text of DOI:10.1016/j.tetlet.2008.02.161

Available online at www.sciencedirect.com
Tetrahedron Letters 49 (2008) 2677–2680
Thermo-cage opening of 4-iodo-1-vinylcubane
to a novel styrene derivative
Vincent M. Carroll a, David N. Harpp b, Ronny Priefer a,b,
*
a Department of Chemistry, Biochemistry, and Physics, Niagara University, Niagara University, NY 14109, USA
b Department of Chemistry, McGill University, Montre´al, Que´bec, Canada H3A 2K6
Received 14 January 2008; revised 14 February 2008; accepted 29 February 2008
Available online 4 March 2008
Abstract
Cubane (1) and its derivatives have been cited for exhibiting unusual properties, including explosive and antiviral activity. An
additional characteristic of these compounds is their tendency to undergo cage opening under certain conditions. In our attempt to
polymerize 4-iodo-1-vinylcubane (4), 4-vinyl-trans-b-iodostyrene (10) was formed quantitatively. By examining both the thermolytic
and Lewis acid-assisted rates, a possible mechanism for the rearrangement of 4?10 has been proposed.
Ó 2008 Elsevier Ltd. All rights reserved.
Since the initial synthesis of cubane (1) by Eaton and
Ag(I)
Rh(I)
Cole1 in 1964, numerous publications dealing with the spe-
cial qualities of its derivatives have been reported. Octoni-
trocubane has been classified as the most powerful non-
nuclear explosive.2 In a quite different area, cubylamines
have been reported to be antiviral.3 Cubanes also have a
tendency to behave as quasi-aromatic molecules, partici-
pating in reactions that are typically associated with ben-
zene.4–7 Cubane derivatives have been studied as to their
tendency to undergo cage-opening under certain condi-
tions; for example cubanol will spontaneously open to
form vinylcyclobutenylketene.8,9 Ring opening has also
been observed with cubylamines10,11 and cubanethiol.
Cubane has been reported to rearrange in the presence
of certain metals (Fig. 1).9,12 When cubane (1) was treated
with silver(I) ions, it rearranged to form cuneane (2).13 In
the presence of rhodium(I), syn-tricyclooctadiene (3) was
formed.14 In our quest to synthesize a tethered, cubane-
based polymer, a vinylcubane monomer was initial pre-
pared. Although the polymerization of a tethered cubane
was successfully accomplished via an alternate route,15
2
1
3
Fig. 1. Reactivity of cubane (1) with silver and rhodium.
the use of vinylcubane monomers under various polymeri-
zation techniques yielded no polymers. In many cases a 4-
vinylstyrene derivative was produced. This directed us to
explore this cage opening/rearrangement more closely,
and the results are reported herein.
In our work, we specifically chose 4-iodo-1-vinylcubane
(4) as our monomer due to the additional functionality,
which could facilitate further transformations in post-poly-
mer functionalization reactions.15 The synthesis of 4 was
accomplished in a five-step pathway (Scheme 1). Commer-
cially available dimethyl-1,4-cubane dicarboxylate (5)
underwent partial base hydrolysis to form the 4-methoxy-
carbonyl cubane carboxylic acid (6). This was followed
by a Moriarty reaction, then an additional base hydrolysis
yielding the 4-iodocubanecarboxylic acid (7). Borane
reduction16 of 7 followed by Swern oxidation of 8,12,17 pro-
vided aldehyde, 9. A Wittig reaction afforded 4-iodo-1-
vinylcubane (4)18 in an overall 66% yield from 5.
*
Corresponding author. Tel.: +1 716 286 8261; fax: +1 716 286 8254.
E-mail address: rpriefer@niagara.edu (R. Priefer).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.02.161

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V. M. Carroll et al. / Tetrahedron Letters 49 (2008) 2677–2680
CO2Me
CO2Me
-
BCl3
+
i
BCl3
6
5
HO2C
MeO2C
11
4
I
I
ii
CH2OH
CO2H
-
-
BCl3
BCl3
iii
8
+
+
7
I
I
12
I
I
iv
BCl3
CHO
v
9
4
I
I
Scheme 1. Reagents and conditions: (i) (a) 1 equiv NaOH/MeOH/THF,
(b) HCl, 92%; (ii) (a) IBDA, I2, benzene, D, 6 h, (b) NaOH/MeOH, (c)
HCl, 92%; (iii) (a) BH3ÁSMe2/THF, 0 °C, (b) HCl, 95%; (iv) DMSO,
(COCl)2, Et3N, CH2Cl2, 93%; (v) Ph3PCH3Br, n-BuLi, THF, 88%.
13
I
I
13
Attempted polymerization of 4 via cationic, anionic, and
free-radical techniques were all unsuccessful.12 However,
with cationic and free-radical procedures where elevated
temperatures are employed, an aromatic product was
detected, which was ultimately determined to be 4-vinyl-
trans-b-iodostyrene (10).19 In these instances, complete
conversion was observed after 2 and 3 days, respectively.
When 4 was refluxed in toluene with or without the
presence of a UV-light source, complete conversion was
accomplished in 3 days. This indicated to us that the reac-
tion was not a radical process. The decrease in reaction
time with the addition of 10% of a Lewis acid (AlBr3,
AlCl3, BCl3, or BF3) suggested that the reaction may be
acid-catalyzed. A similar cubane conversion had been pre-
viously reported; however this required the addition of
[Ru(COD)Cl]2 for the initial opening to the cyclooctate-
traene intermediate.20
In our case we postulate that the initial alkene attack on
the Lewis acid did occur, as would be expected for poly-
merization (Scheme 2). However, the subsequent attack
on the carbocation product 11 by an additional alkene, 4,
did not take place. Instead, the cage opened to form the less
strained derivative, 12 which would further open to form
the tricyclooctadiene derivative, 13 and ultimately cyclo-
octatetraene, 14. Tricyclooctadienes have been reported
to open to give the cyclooctatetraene derivatives in the
presence of Rh(I).14
14
I
10
I
Scheme 2. Proposed mechanism of the conversion of 4-iodo-1-vinylcu-
bane (4) to the rearrangement product, 4-vinyl-trans-b-iodo-styrene (10).
(>80 °C) to give trans-b-halostyrene.21 In order to deter-
mine whether the reaction was indeed being accelerated
by the presence of a Lewis acid, different equivalences
of BCl3 were added and the reaction was monitored by
GC. When 4 was heated in refluxing toluene, complete
conversion to 10 was accomplished in 72 h. Samples
were taken every 12 h and analyzed by GC. It was
necessary to lower the injection temperature to 150 °C
in order to observe the starting material, 4. When
employing a higher injection temperature, the intensity
of the peak at 13.3 min increased.22 It is reasonable to
postulate that this signal corresponds to cyclooctatetra-
ene, 14 (starting 4-iodo-1-vinylcubane (4) is detected at
12.4 min, Fig. 2).
In addition, it has been reported that halogenated
cyclooctatetraene derivatives rearrange upon heating
Vinyl cubane 4, had completely disappeared after 36 h;
the final 36 h was needed to convert the remaining cyclo-

V. M. Carroll et al. / Tetrahedron Letters 49 (2008) 2677–2680
2679
0.35
0.3
Rearrangement with 0.25 equivalence of boron trichloride
100
90
80
70
60
50
40
30
20
10
0
0.25
0.2
10
4
I
I
0.15
0.1
I
14
0.05
0
4
14
10
12
12.5
13
13.5
14
14.5
15
15.5
-0.05
Retention Time (mins)
0
2
4
6
8
10
12
Fig. 2. Time profile rearrangement of 4-iodo-1-vinylcubane (4) to 4-vinyl-
trans-b-iodostyrene (10) shown at time zero (yellow), 12 h (pink), and 72 h
(blue) heating in toluene.
Time (hours)
Fig. 4. Time profile rearrangement of 4-iodo-1-vinylcubane (4) to 4-vinyl-
trans-b-iodostyrene (10) using 0.25 equiv BCl3.
Rearrangement with No Lewis Acid
100
Rearrangement with 0.75 equivalence of boron trichloride
90
80
70
60
50
100
90
80
70
60
50
40
40
30
4
14
10
20
10
0
4
30
20
10
0
14
10
0
12
24
36
48
60
72
Time (hours)
0
2
4
6
8
Fig. 3. Time profile rearrangement of 4-iodo-1-vinylcubane (4) to 4-vinyl-
trans-b-iodostyrene (10).
Time (hours)
Fig. 5. Time profile rearrangement of 4-iodo-1-vinylcubane (4) to 4-vinyl-
trans-b- iodostyrene (10) using 0.75 equiv BCl3.
octatetraene, 14, into 10. (Fig. 3) (4-vinyl-trans-b-iodo-
styrene (10) appears at 15.1 min).
The addition of 25% and 75% of the Lewis acid BCl3,
dramatically increased the rate of the reaction for complete
conversion after only 12 (Fig. 4) and 8 h (Fig. 5), respec-
tively. The reactions were monitored every 2 hours and it
was observed that there was no significant amount of 14
at any time interval. Cope reported the use of acids to
accelerate the conversion of halogenated cyclooctatetraene
to trans-b-halostyrene however, in their study the acid
sources were carboxylic acids only.21 They noted a positive
relationship between acid strength and rearrangement;21 it
was theorized that the ionization step forming 15 (Scheme
3) would be accelerated in the presence of an acid.
Scheme 3 illustrates a proposed mechanism using 14 as
the model cyclooctatetraene. The coordination of iodine
with a Lewis acid should increase the rate of formation
of 15 and ultimately the overall rate of the reaction. In
all the three cases the rate was first order with respect to
the disappearance of 4-iodo-1-vinylcubane (4).
the Lewis acid. The reverse reaction (14?4) is not possible
and the non-Lewis acid assisted reaction requires 36 h for
complete disappearance of 4 (Fig. 3); thus any reaction
proceed at a more rapid rate must therefore be catalyzing
the first step as well. Upon addition of a Lewis acid, the
reaction was completed in less than 36 h, thus the acid must
play two roles: initially, to assist in the ring opening
(Scheme 2) as well as with the cyclooctatetraene rearrange-
ment (Scheme 3).
This is the first reported example of a cubane derivative
undergoing cage-opening to a cyclooctatetraene derivative
without the assistance of rhodium(I). The initial product
continued to rearrange to the much more stable styrene
derivative. Work is currently underway to examine the
use of other Lewis acids as well as the incorporation of dif-
ferent halides on the cube backbone. In addition, we are
attempting to isolate cyclooctatetraene, 14, in order to deter-
mine the kinetic nature of both steps in the cage-opening/
rearrangement pathway.
What remained unknown was whether the initial con-
version of 4?14 was also being accelerated by the use of

2680
V. M. Carroll et al. / Tetrahedron Letters 49 (2008) 2677–2680
2. Zhang, M.-X.; Eaton, P. E.; Gilardi, R. Angew. Chem., Int. Ed. 2000,
I
I
39, 401.
3. Bashir-Hashemi, A. In NASA Conference Publication, 1994; p 127.
4. Geschwend, H. W.; Rodriguez, H. R. Org. React. NY 1979, 26, 1.
5. Beak, P.; Snieckus, V. Acc. Chem. Res. 1982, 15, 306.
6. Eaton, P. E.; Castaldi, G. J. Am. Chem. Soc. 1985, 107, 724.
7. Della, E. W.; Hine, P. T.; Patney, H. K. J. Org. Chem. 1977, 42, 2940.
8. Cole, T. W. Jr. Ph.D. Dissertation, University of Chicago, 1966.
9. Hormann, R. E. Ph.D. Dissertation, University of Chicago, 1987.
10. Bashir-Hashemi, A. Angew. Chem. 1993, 105, 585; Angew. Chem., Int.
Ed. Engl. 1993, 32, 612.
11. Bashir-Hashemi, A.; Li, J.; Gelber, N.; Ammon, H. J. Org. Chem.
1995, 60, 698.
12. Priefer, R. Ph.D. Dissertation, McGill University, 2003.
13. Cassar, L.; Eaton, P. E.; Halpern, J. J. Am. Chem. Soc. 1970, 92,
6366.
H
14
+
I
I
H
H
15
I
14. Cassar, L.; Eaton, P. E.; Halpern, J. J. Am. Chem. Soc. 1970, 92,
3515.
15. Priefer, R.; Nguyen, S.; Farrell, P. G.; Harpp, D. N. Macromolecules
2003, 36, 5435.
H
I
16. Priefer, R.; Farrell, P. G.; Harpp, D. N. Synthesis 2002, 18, 2671.
17. Eaton, P. E.; Galoppini, E.; Gilardi, R. J. Am. Chem. Soc. 1994, 116,
7588.
18. 4-Iodo-1-vinylcubane (4). Yield 88%. White solid with mp 77–79 °C.
1H NMR (400 MHz, CDCl3): d 4.09 (m, 3H), 4.19 (m, 3H), 4.92 (dd,
1H, J = 1.95, 17.10 Hz), 5.06 (dd, 1H, J = 1.95, 10.60 Hz), 6.05 (dd,
1H, 10.60, 17.10 Hz); 13C NMR (75.5 MHz, CDCl3): d 39.18, 50.49,
54.31, 60.34, 113.15, 136.66. Elemental Anal. Calcd C10H9I: C, 46.90;
H, 3.54, Found: C, 47.22; H, 3.45.
H
10
Scheme 3. Proposed mechanism of cyclooctratetraene, 14, to 4-vinyl-
trans-b-iodo-styrene (10).
19. 4-Vinyl-trans-b-iodostyrene (10). White solid with mp 101–102 °C. 1H
NMR (400 MHz, CDCl3): d 5.27 (dd, 1H, J = 0.60, 10.80 Hz), 5.75
(dd, 1H, J = 0.60, 17.10 Hz), 6.67 (dd, 1H, 10.80, 17.10 Hz), 6.81 (d,
1H, 14.70 Hz), 7.24 (d, 2H, 8.40 Hz), 7.35 (d, 2H, 8.40 Hz), 7.39 (d,
1H, 14.70 Hz); 13C NMR (75.5 MHz, CDCl3): d 114.28, 126.03,
126.43, 136.09, 136.87, 137.40, 144.36, 149.69. Elemental Anal. Calcd
Acknowledgements
We thank the Natural Sciences and Engineering
Research Council of Canada (NSERC) for financial
support. R.P. thanks Niagara University Academic Center
for Integrated Science for additional financial support.
C
10H9I: C; 46.90; H, 3.54. Found: C, 47.04; H 3.22.
20. Eaton, P. E.; Sto¨ssel, D. J. Org. Chem. 1991, 56, 5138.
21. Cope, A. C.; Burg, M. J. Org. Chem. 1952, 71, 168.
22. Injection volume: 5 lL; injection rate: 5 lL/s; injection temperature:
150 °C; column flow; 1.0 mL/min; column temperature: 40–290 °C at
10 °C/min; FID detector temperature: 290 °C.
References and notes
1. Eaton, P. E.; Cole, T. W., Jr. J. Am. Chem. Soc. 1964, 86, 962. 3157.