Approaches to open fullerenes: Synthesis and kinetic stability of Diels-Alder adducts of substituted isobenzofurans and C60

Article abstract of DOI:10.1021/jo061986j

(Chemical Equation Presented) We have examined the reactions of 1,3-disubstituted isobenzofurans with the fullerene C₆₀ in the context of an approach to open a large orifice on the fullerene framework. A variety of substituted isobenzofurans (6a-h), generated from the reaction of 1,4-substituted 1,4-epoxynaphthalenes 3a-h with 3,6-bis(2-pyridyl)-1,2,4,5- tetrazine (4a) or 1,2,4,5-tetrazine (4b), were added to C₆₀ to afford the Diels-Alder adducts 7a-h. The thermal stability of these adducts toward retro-Diels-Alder fragmentation differs greatly in solution from that in the solid state. In solution, the relatively facile retro-Diels-Alder fragmentation of monoadducts 7a and 7c, to give C₆₀ and the free isobenzofurans 6a and 6c, have rate constants (and activation barriers) of k = 9.29 × 10^-5 s^-1 at 70°C (E_a = 32.6 kcal mol ^-1) and k = 1.36 × 10^-4 s^-1 at 40°C (E_a = 33.7 kcal mol^-1), respectively, indicating that the addition of isobenzofurans to C₆₀ is readily reversible at those temperatures. In the solid state, thermogravimetric analysis of adduct 7a indicates that its decomposition occurs only within the temperature range of 220-300°C. As a result, these compounds can be stored at room temperature in the solid state for several weeks without significant decomposition but have to be handled within several hours in solution.

Full text of DOI:10.1021/jo061986j

Approaches to Open Fullerenes: Synthesis and Kinetic Stability of
Diels-Alder Adducts of Substituted Isobenzofurans and C60
Shih-Ching Chuang, Michael Sander, Thibaut Jarrosson, Scott James, Eugene Rozumov,
Saeed I. Khan, and Yves Rubin*
Department of Chemistry and Biochemistry, UniVersity of California, Los Angeles, California 90095-1569
rubin@chem.ucla.edu
ReceiVed September 27, 2006
We have examined the reactions of 1,3-disubstituted isobenzofurans with the fullerene C60 in the context
of an approach to open a large orifice on the fullerene framework. A variety of substituted isobenzofurans
(6a-h), generated from the reaction of 1,4-substituted 1,4-epoxynaphthalenes 3a-h with 3,6-bis(2-
pyridyl)-1,2,4,5-tetrazine (4a) or 1,2,4,5-tetrazine (4b), were added to C60 to afford the Diels-Alder
adducts 7a-h. The thermal stability of these adducts toward retro-Diels-Alder fragmentation differs
greatly in solution from that in the solid state. In solution, the relatively facile retro-Diels-Alder
fragmentation of monoadducts 7a and 7c, to give C60 and the free isobenzofurans 6a and 6c, have rate
-
5
-1
-1
constants (and activation barriers) of k ) 9.29 × 10
s
at 70 °C (E
) 33.7 kcal mol ), respectively, indicating that the addition of isobenzofurans
to C60 is readily reversible at those temperatures. In the solid state, thermogravimetric analysis of adduct
a indicates that its decomposition occurs only within the temperature range of 220-300 °C. As a result,
a
) 32.6 kcal mol ) and k ) 1.36
-
4
-1
-1
×
10
s
at 40 °C (E
a
7
these compounds can be stored at room temperature in the solid state for several weeks without significant
decomposition but have to be handled within several hours in solution.
Introduction
Because of the very limited availability of adducts of type B,6,7
this type of opening mechanism remains untested. Nevertheless,
several precedents involving highly strained cyclohexanes have
Because of their unusual and novel properties, endohedral
metallofullerenes have remained attractive targets ever since the
initial discovery of the fullerenes.1 Access to endohedral
fullerenes is limited, however, because conventional preparation
methods generally provide very low yields, often involving
tedious purification. Thus, alternative, synthetic approaches to
endohedral fullerenes, e.g., by creating an opening on the
fullerene sphere, inserting a guest entity, closing the cage, and
removing any remaining functionality (“molecular surgery”),
8
been described; the concept should be transferable to fullerenes
thanks to the inherently strained 1,2,3,4,5,6-hexaaddition pattern.
One advantage of this approach is that hexasubstituted adducts
of type B could be isoenergetic or slightly higher in energy
with respect to either open forms C(5o) and C(6o), such that
the closed fullerene framework could be in equilibrium with
the open one. Ideally, the added functional groups should be
removable after insertion of the guest entity to provide pristine
endohedral fullerenes (M@C2n) as recently demonstrated by
2
-4
have attracted increasing attention during the past few years.
These methods should eventually provide access to a wider array
of elements trapped inside fullerene cages than those currently
3
b
Komatsu et al.
5
available.
These considerations motivated us to prepare various preor-
ganized multifunctional reagents containing linked diene and/
or dipolar subunits, for addition to C60 (Chart 1). The three
possible opening strategies outlined in Chart 1 all involve the
One strategy toward opening an orifice within the carbon
framework of a fullerene involves saturating three adjacent
double bonds within one of its six-membered rings (Figure 1).
5
10.1021/jo061986j CCC: $37.00 © 2007 American Chemical Society
2
716
J. Org. Chem. 2007, 72, 2716-2723
Published on Web 03/17/2007

Open Fullerenes: Adducts of Substituted Isobenzofurans and C60
be invoked if the CdC bond to be saturated is reactive enough.
Not surprisingly and as our recent results have shown,6
saturating the last bond turns out to be the most challenging
aspect of this project.
The tethered stepwise cycloadditions depicted in Chart 1
necessitate a good degree of preorganization imparted by tethers
9
of appropriate length and rigidity. Side reactions of the
functional groups with undesired double bonds of C60 need to
be restrained by favoring the best transition state geometries.
Our first published opening approach described the reaction of
a diene-bisazide to effect a tandem series of 1,3-dipolar/Diels-
Alder/1,3-dipolar cycloadditions on C60, conceptually following
2
a
the YY-XX-YY format of Strategy 3. We found that the
open bislactam 1 was formed instead through a complex set of
rearrangements involving the loss of two nitrogen molecules
and the addition of molecular oxygen, due to the high lability
(1) (a) Kroto, H. W.; Heath, J. R.; O’Brien, S. C.; Curl, R. F.; Smalley,
R. E. Nature 1985, 318, 162-163. (b) Kr a¨ tschmer, W.; Lamb, L. D.;
Fostiropoulos, K.; Huffmann, D. R. Nature 1990, 347, 354-356. (c) Chai,
Y.; Guo, T.; Jin, C. M.; Haufler, R. E.; Chibante, L. P. F.; Fure, J.; Wang,
L. H.; Alford, J. M.; Smalley, R. E. J. Phys. Chem. 1991, 95, 7564-7568.
FIGURE 1. A generic strategy to open an orifice on the surface of
fullerene C60 by a two-step saturation of three adjacent CdC bonds of
a single six-membered ring: (a) Addition of four saturating groups
from a tethered reagent. (b) Addition of two saturating groups through
a reactive intermediate on substituents R,R. (c) [2 + 2 + 2] Ring
opening of the 1,2,3,4,5,6-hexaadduct at either the [5,6] or [6,6] ring
junctions.
(
d) Johnson, R. D.; Devries, M. S.; Salem, J.; Bethune, D. S.; Yannoni, C.
S. Nature 1992, 355, 239-240. (e) Shinohara, H.; Sato, H.; Saito, Y.;
Ohkohchi, M.; Ando, Y. J. Phys. Chem. 1992, 96, 3571-3573. (f) Gillan,
E. G.; Yeretzian, C.; Min, K. S.; Alvarez, M. M.; Whetten, R. L.; Kaner,
R. B. J. Phys. Chem. 1992, 96, 6869-6871. (g) Shinohara, H. Rep. Prog.
Phys. 2000, 63, 843-892. (h) Sidorov, L. N.; Boltalina, O. V. Russ. Chem.
ReV. 2002, 71, 535-561. (i) Akasaka, T.; Nagase, S. Endofullerenes: A
New Family of Carbon Clusters; Kluwer Academic Publishers: Dordrecht,
CHART 1. Three Conceptual Strategies for the Stepwise
Addition Of Tethered Reactive Units to Three Adjacent
CdC Bonds of a Single Six-Membered Ring of C60
2002. (j) Ge, Z.; Duchamp, J. C.; Cai, T.; Gibson, H. W.; Dorn, H. C. J.
Am. Chem. Soc. 2005, 127, 16292-16298. (k) Feng, L.; Nakahodo, T.;
Wakahara, T.; Tsuchiya, T.; Maeda, Y.; Akasaka, T.; Kato, T.; Horn, E.;
Yoza, K.; Mizorogi, N.; Nagase, S. J. Am. Chem. Soc. 2005, 127, 17136-
17137. (l) Shi, Z.-Q.; Wu, X.; Wang, C.-R.; Lu, X.; Shinohara, H. Angew.
Chem., Int. Ed. 2006, 45, 2107-2111. (m) Feng, L.; Tsuchiya, T.; Wakahara,
T.; Nakahodo, T.; Piao, Q.; Maeda, Y.; Akasaka, T.; Kato, T.; Yoza, K.;
Horn, E.; Mizorogi, N.; Nagase, S. J. Am. Chem. Soc. 2006, 128, 5990-
5
991. (n) Cardona, C. M.; Elliott, B.; Echegoyen, L. J. Am. Chem. Soc.
2006, 128, 6480-6485. (o) Wang, X.; Zuo, T.; Olmstead, M. M.; Duchamp,
J. C.; Glass, T. E.; Cromer, F.; Balch, A. L.; Dorn, H. C. J. Am. Chem.
Soc. 2006, 128, 8884-8889. (p) Wakahara, T.; Iiduka, Y.; Ikenaga, O.;
Nakahodo, T.; Sakuraba, A.; Tsuchiya, T.; Maeda, Y.; Kako, M.; Akasaka,
T.; Yoza, K.; Horn, E.; Mizorogi, N.; Nagase, S. J. Am. Chem. Soc. 2006,
1
28, 9919-9925. (q) Beavers, C. M.; Zuo, T.; Duchamp, J. C.; Harich, K.;
Dorn, H. C.; Olmstead, M. M.; Balch, A. L. J. Am. Chem. Soc. 2006, 128,
1
1352-11353. (r) Yamada, M.; Nakahodo, T.; Wakahara, T.; Tsuchiya,
T.; Maeda, Y.; Akasaka, T.; Kako, M.; Yoza, K.; Horn, E.; Mizorogi, N.;
Kobayashi, K.; Nagase, S. J. Am. Chem. Soc. 2005, 127, 14570-14571.
(
2) (a) Schick, G.; Jarrosson, T.; Rubin, Y. Angew. Chem., Int. Ed. 1999,
3
8, 2360-2363. (b) Rubin, Y.; Jarrosson, T.; Wang, G.-W.; Bartberger,
M. D.; Houk, K. N.; Schick, G.; Saunders, M.; Cross, R. J. Angew. Chem.,
Int. Ed. 2001, 40, 1543-1546. (c) Carravetta, M.; Murata, Y.; Murata, M.;
Heinmaa, I.; Stern, R.; Tontcheva, A.; Samoson, A.; Rubin, Y.; Komatsu,
K.; Levitt, M. H. J. Am. Chem. Soc. 2004, 126, 4092-4093.
(
3) (a) Murata, Y.; Murata, M.; Komatsu, K. Chem. Eur. J. 2003, 9,
1
2
(
600-1609. (b) Komatsu, K.; Murata, M.; Murata, Y. Science 2005, 307,
38-240. (c) Komatsu, K.; Murata, Y. Chem. Lett. 2005, 34, 886-891.
d) Murata, M.; Murata, Y.; Komatsu, K. J. Am. Chem. Soc. 2006, 128,
8
024-8033.
(
4) (a) Iwamatsu, S.-I.; Uozaki, T.; Kobayashi, K.; Re, S.; Nagase, S.;
Murata, S. J. Am. Chem. Soc. 2004, 126, 2668-2669. (b) Iwamatsu, S.;
Murata, S.; Andoh, Y.; Minoura, M.; Kobayashi, K.; Mizorogi, N.; Nagase,
S. J. Org. Chem. 2005, 70, 4820-4825. (c) Iwamatsu, S.; Murata, S. Synlett
challenging eventual full saturation of one of the fullerene six-
membered rings followed by a [2 + 2 + 2] ring opening. These
strategies differ only in the number of CdC bonds that are
saturated during the first step(s); the functional groups must be
well-chosen and separated by suitable linkers. Strategies 2 and
2
005, 14, 2117-2129. (d) Iwamatsu, S.; Murata, S.; Stanisky, C. M.; Cross,
R. J.; Saunders, M.; Mizorogi, N.; Nagase, S.; Murata, S. Angew. Chem.,
Int. Ed. 2006, 45, 5337-5340.
(5) (a) Arce, M.-J.; Viado, A. L.; An, Y.-Z.; Khan, S. I.; Rubin, Y. J.
Am. Chem. Soc. 1996, 118, 3775-3776. (b) Rubin, Y. Chem. Eur. J. 1997,
3
, 1009-1016. (c) Rubin, Y. Chimia 1998, 52, 118-126. (d) Rubin, Y.
3
involve more than one step; reactive moieties, such as alkoxyl
Top. Curr. Chem. 1999, 199, 67-91.
(6) Chuang, S.-C.; Clemente, F. R.; Khan, S. I.; Houk, K. N.; Rubin, Y.
Org. Lett. 2006, 8, 4525-4528.
radicals, carbon radicals, nitrenes, or carbenes, must be formed
from their initial intermediates to further saturate the remaining
CdC bonds. Alternatively, less reactive groups such as dienes
or 1,3-dipoles (azides, azomethine ylides, nitrilimines, etc.) may
(7) A C3V-tris-epoxide C60O3 has been isolated and partially characterized.
From its UV-vis absorption features, it is likely the assigned structure;
see: Tajima, Y.; Takeuchi, K. J. Org. Chem. 2002, 67, 1696-1698.
J. Org. Chem, Vol. 72, No. 8, 2007 2717

Chuang et al.
of intermediate triazoline rings formed by 1,3-dipolar cycload-
for large-scale synthesis, and perhaps more importantly, their
ease of removal through retro-Diels-Alder reactions. The
physical stability of the isobenzofuran-C60 adducts is also
important: if they are too labile, the Diels-Alder adducts may
be difficult to handle; if they are too stable, the addends may
be difficult to remove at a later stage. As seen in the
ditions between azide and fullerene systems. The open fullerene
a,10
1
, with its first effectiVe orifice,2 gave us the opportunity to
study the introduction of small gases such as helium and
molecular hydrogen (H2) inside it.2b It became clear, however,
that much larger openings on fullerene surfaces would be needed
to provide endohedral access to larger species, especially for
the transition metals, which have much greater potential to
exhibit unusual and novel properties.1 The approach presented
in Figure 1 should provide access to appropriately large
openings, since the addends impart sufficient strain to push apart
the three CdC double bonds formed through [2 + 2 + 2] ring
opening.5
1
2
accompanying paper, a variety of cis-1 bisadducts of C60 can
be prepared through double Diels-Alder cycloadditions of bis-
isobenzofurans following the methodology described in the
present paper; their unusual thermal stability gave us the
opportunity to examine different strategies for saturating
the remaining double bond by reactions of convergent functional
-4
,8m
6
groups at both ends of the addend framework.
The Diels-Alder reaction of the parent isobenzofuran with
1
3
C60 was initially reported by Wudl. However, the addition of
substituted isobenzofurans to C60 has not been adequately
explored; we wanted to optimize these reactions to apply them
to the preparation of open C60 adducts. For example, the addition
of the commercially available 1,3-diphenylisobenzofuran to C60
has been reported to provide an isolable monoadduct,14 but we
were unable to reproduce this result, possibly because of the
high propensity for reversibility of the adduct.
We have developed a general approach for the preparation
of mono- and bis-substituted isobenzofurans using an optimiza-
1
5
The judicious selection of the adding groups is key to the
success of this synthetic project. Hence, we became interested
in the reactivity of substituted isobenzofurans (IBFs)11 and their
potential for undergoing multiple additions with C60 thanks to
the ease of substitution of their furan precursors, the possibilities
tion of the methodology of Warrener. The isobenzofuran
precursors 3a-h were readily available in up to 50 g quantity
through the reaction of benzyne with furans 2a-h, respectively.
The reactive isobenzofurans were generated in situ through the
cycloaddition of the bicyclic adducts 3a-h with 3,6-bipyridyl-
1
,2,4,5-tetrazine (4a) or with the much more reactive parent
(
8) (a) Schwesinger, R.; Prinzbach, H. Angew. Chem., Int. Ed. Engl. 1972,
1,2,4,5-tetrazine (4b). Since all of the monoadducts 7a-h
showed a propensity for cycloreversion, we examined the kinetic
stability of two representative systems (7a and 7c) toward retro-
Diels-Alder fragmentation in solution by H NMR spectroscopy
and in the solid state by thermogravimetric analysis (TGA).
1
0, 942-943. (b) Vogel, E.; Altenbach, H.-J.; Sommerfeld, C.-D. Angew.
Chem., Int. Ed. Engl. 1972, 10, 939-940. (c) Vogel, E.; Altenbach, H.-J.;
Schmidbauer, E. Angew. Chem., Int. Ed. Engl. 1973, 10, 838-840. (d)
Vogel, E.; Altenbach, H.-J. Angew. Chem., Int. Ed. Engl. 1973, 10, 937-
1
9
39. (e) de Meijere, A.; Kaufmann, D.; Schallner, O. Angew. Chem., Int.
Ed. Engl. 1971, 6, 417-418. (f) Howard, W.; Whitlock, Jr.; Schatz, P. F.
J. Am. Chem. Soc. 1971, 93, 3837-3839. (g) Braschwitz, W.-D.; Otten,
T.; R u¨ cker, C.; Fritz, H.; Prinzbach, H. Angew. Chem., Int. Ed. Engl. 1989,
Results and Discussion
2
8, 1348-1350. (h) Prinzbach, H.; Schwesinger, R. Angew. Chem., Int.
Ed. Engl. 1972, 11, 940-942. (i) R u¨ cker, C.; Fritz, H.; Prinzbach, H.
Tetrahedron Lett. 1983, 24, 4099-4102. (j) Handreck, D.-R.; Hunkler, D.;
Prinzbach, H. Angew. Chem., Int. Ed. Engl. 1989, 28, 1351-1353. (k)
Mohler, D. L.; Vollhardt, K. P. C.; Wolff, S. Angew. Chem., Int. Ed. 1990,
Formation of the Isobenzofuran Monoadducts. The 1,4-
disubstituted 1,4-epoxynaphthalenes 3a-h were prepared by in
situ generation of benzyne in the presence of the respective
substituted furans 2a-h (Table 1). Although benzyne can be
prepared by a number of methods, we found that it was most
readily obtained from the thermal decomposition of benzene-
2
9, 1151-1154. (l) Spanget-Larsen, J.; Gleiter, R. Angew. Chem., Int. Ed.
Engl. 1978, 17, 441-442. (m) Irle, S.; Rubin, Y.; Morokuma, K. J. Phys.
Chem. A. 2002, 106, 680-688. (n) Sawicka, D.; Wilsey, S.; Houk, K. N.
J. Am. Chem. Soc. 1999, 121, 864-865.
1
6
(9) (a) Diederich, F.; G o´ mez-L o´ pez, M. Chem. Soc. ReV. 1999, 28, 263-
2
77. (b) Diederich, F.; Kessinger, R. Acc. Chem. Res. 1999, 32, 537-545.
(c) Qian, W.; Rubin, Y. Angew. Chem., Int. Ed. 2000, 39, 3133-3137. (d)
(12) See the following article in this issue: Sander, M.; Jarrosson, T.;
Chuang, S.-C.; Khan, S. I.; Rubin Y. J. Org. Chem. 2007, 72, 2724-2731.
(13) Prato, M.; Suzuki, T.; Foroudian, H.; Li, Q.; Khemani, K.; Wudl,
F.; Leonetti, J.; Little, R. D.; White, T. J. Am. Chem. Soc. 1993, 115, 1594-
1595.
(14) (a) Bidell, W.; Douthwaite, R. E.; Green, M. L. H.; Stephens, A.
H. H.; Turner, J. F. C. J. Chem. Soc., Chem. Commun. 1994, 1641-1642.
(b) Chernega, A. N.; Green, M. L. H.; Haggitt, J.; Stephens, A. H. H. J.
Chem. Soc., Dalton Trans. 1998, 755-767.
(15) (a) Warrener, R. N. J. Am. Chem. Soc. 1971, 93, 2346-2348. (b)
Friedrichsen, W. AdV. Heterocycl. Chem. 1980, 26, 135-241. (c) Rodrigo,
R. Tetrahedron 1988, 44, 2093-2135. (d) Rickborn, B. AdVances in
Theoretically Interesting Molecules; JAI Press: Greenwich, 1989; Vol. 1,
pp 1-134. (e) Bird, C. W. Prog. Heterocycl. Chem. 1990, 2, 87-101. (f)
Peters, O.; Friedrichsen, W. Trends Heterocycl. Chem. 1995, 4, 217-259.
(16) (a) Hoffmann, R. W. Dehydrobenzene and Cycloalkynes; Academic
Press: New York, 1967. (b) Hart, H. In The Chemistry of Triple-Bonded
Functional Groups, Supplement C2; Patai, S., Ed; Wiley: Chichester, 1994;
Chapter 18. (c) Himeshima, Y.; Sonoda, T.; Kobayashi, H. Chem. Lett.
1983, 1211-1214. (d) Kitamura, T.; Yamane, M.; Inoue, K.; Tokada, M.;
Fukatsu, N.; Meng, Z.; Fujiwara, Y. J. Am. Chem. Soc. 1999, 121, 11674-
11679.
Qian, W.; Rubin, Y. J. Am. Chem. Soc. 2000, 122, 9564-9565. (e) Qian,
W.; Rubin, Y. Angew. Chem., Int. Ed. 1999, 38, 2356-2360. Herzog, A.;
Hirsch, A.; Vostrowsky, O. Eur. J. Org. Chem. 2000, 171-180. (f) Djojo,
F.; Hirsch, A.; Grimme, S. Eur. J. Org. Chem. 1999, 3027-3039. (g)
Echegoyen, L. E.; Djojo, F. D.; Hirsch, A.; Echegoyen, L. J. Org. Chem.
2
000, 65, 4994-5000. (h) Reuther, U.; Brandm u¨ ller, T.; Donaubauer, W.;
Hampel, F.; Hirsch, A. Chem. Eur. J. 2002, 8, 2261-2273. (l) Thilgen, C.;
Diederich, F. C. R. Acad. Sci, Ser. IIc: Chim, 2006, 9, 868-880.
(10) For fullerene derivatives having smaller or fully blocked openings,
see: (a) Hummelen, J. C.; Prato, M.; Wudl, F. J. Am. Chem. Soc. 1995,
17, 7003-7004. (b) Birkett, P. R.; Avent, A. G.; Darwish, A. D.; Kroto,
H. W.; Taylor, R.; Walton, D. R. M. Chem. Commun. 1995, 1869-1870.
c) Arce, M. J.; Viado, A. L.; An, Y.-Z.; Khan, S. I.; Rubin, Y. J. Am.
1
(
Chem. Soc. 1996, 118, 3775-3776. (d) Schick, G.; Hirsch, A.; Mauser,
H.; Clark, T. Chem. Eur. J. 1996, 2, 935-943.
(
11) (a) Naito, K.; Rickborn, B. J. Org. Chem. 1980, 45, 4061-4062.
(b) Dodge, J. A.; Bain, J. D.; Chamberlin, A. R. J. Org. Chem. 1990, 55,
4
190-4198. (c) Sasaki, T.; Kanematsu, K.; Hayakawa, K.; Sugiura, M. J.
Am. Chem. Soc. 1975, 97, 355-360. (d) Binger, P.; Wedemann, P.; Goddard,
R.; Brinker, U. H. J. Org. Chem. 1996, 61, 6462-6464. (e) Luo, Y.;
Herndon, J. W. Organometallics 2005, 24, 3099-3103.
2718 J. Org. Chem., Vol. 72, No. 8, 2007

Open Fullerenes: Adducts of Substituted Isobenzofurans and C60
TABLE 1. Formation of Reactive Isobenzofurans and Their [4 +
SCHEME 1
2
] Cycloaddition with C60
reotopic SiMe2), and 0.93 ppm (Sit-Bu). The Cs-symmetry of
1
3
this compound is revealed also in the C NMR spectrum: a
3
single oxa-bridge sp carbon is found at 80.46 ppm, while the
3
two directly connected sp carbons on the fullerene appears at
9
5.08 ppm. The related Cs-symmetric compounds 7d, 7e, and
7
g show similar features, while the C1-symmetric compounds
yield (%)a
7a-c and 7h have doubled signals in the substituent patterns.
Satisfactory mass spectral data for most of these adducts was
very difficult to obtain in most instances due to their thermally
labile nature.
substrate
R1
R2
(4a, 45 °C) (4b, 25 °C)
7
7
7
7
7
7
7
7
a
b
c
d
e
f
H
H
H
Me
H
58 (66)
31 (48)
43 (57)
85 (89)
18 (52)
b
62 (72)
40 (56)
51 (60)
78 (86)
39 (62)
44 (76)
32 (50)
33 (55)
CH2OAc
CO2Me
Me
Substituent Effects. The steric effects that various substit-
uents on isobenzofurans 6a-h have on the rates of cycloaddition
with C60 and on the thermal stability of the corresponding
adducts 7a-h can be extrapolated from their yields. For the
parent system, the formation of adduct 7a is readily achieved
in 58% yield (66% based on recovered C60) through the reaction
of C60 and 3,6-bipyridyl-1,2,4,5-tetrazine (4a) at room temper-
ature for 16 h. With the isobenzofuran precursor 3d having
methyl groups at the 1,3-positions, formation of the correspond-
ing adduct 7d was considerably more difficult. It was necessary
to increase the reaction temperature to 40-45 °C to facilitate
the formation of 1,3-dimethyl isobenzofuran (6d) as seen by
(CH2)3COCH3 (CH2)3COCH3
CH2OTBS
CH2OH
H
CH2OTBS
CH2OH
CH2OH
g
h
b
15 (47)
a
Yields in parenthesis are based on recovered C60. b Pyrazoline side-
products 9a or 9b obtained instead.
diazonium-2-carboxylate,17 which we prepared freshly and used
immediately under appropriately safe conditions. A small
amount of propylene oxide was added to remove any acidic
contaminants. Good yields (60-80%) of adducts 3a-h were
obtained after heating a slurry of benzenediazonium-2-carboxy-
late under reflux in the presence of the respective furan (2a-
h) in dry THF.
1
the slow buildup in concentration of product 7d by H NMR.
This shows that steric factors intervene in the reaction between
3d and tetrazine 4a at the onset of the series of cycloadditions
before the formation of isobenzofuran 6d, which reacts quickly
with C60 (Vide infra). Although increasing the reaction temper-
ature generally overcame the steric factors, a further slight
increase in temperature (to ca. 50 °C) resulted in a remarkable
acceleration of the competing reaction of tetrazines 4a and 4b
with C60 to give the unexpected side products 9a and 9b,
Warrener’s methodology15 was subsequently applied to
bicyclic adducts 3a-h to generate the isobenzofurans 6a-h in
situ through reactions with either 3,6-bipyridyl-1,2,4,5-tetrazine
4a) or 1,2,4,5-tetrazine (4b). Most of the isobenzofuran
precursors 3a-h underwent facile inverse-electron-demand [4
2] cycloaddition with 3,6-bipyridyl-1,2,4,5-tetrazine (4a) to
(
1
8
+
respectively.
form the intermediate adducts 5a-h after the initial extrusion
of N2, although the more sterically hindered precursors
3
e-g were slow to react with 3,6-bipyridyl-1,2,4,5-tetrazine (4a)
and suffered competing addition of the tetrazine moiety to
18
C60. Subsequent [2 + 2 + 2] retrocycloaddition generated the
reactive isobenzofurans 6a-h, with pyridazines 8a or 8b as side
products. The corresponding cycloadducts 7a-h were obtained
in overall good yields (47-89%, based on recovered C60).
The characterization of monoadducts 7a-h is based on their
1H, C, and MS spectral data. For example, compound 7f
displays two sets of doublets at 5.03 and 5.15 ppm (J )
13
1
1.8 Hz) for the diastereotopic methylene protons of the CH2O
To further understand the effects of various substituents at
the 1 and 3 positions of isobenzofuran, we studied the reactions
of the remaining isobenzofuran precursors 3b-h (Table 1). We
found that the rates of isobenzofuran formation in reactions with
1
group in the H NMR spectrum, in addition to the expected
multiplet centered at 7.5 ppm for the ortho-substituted phenyl
ring and the signals of the TBS group at 0.16, 0.19 (diaste-
3
,6-bis(2-pyridyl)tetrazine (4a) were substantially slower when
(
(
17) Stiles, M.; Miller, R. G. J. Am. Chem. Soc. 1960, 82, 3802.
18) (a) Murata, Y.; Suzuki, M.; Rubin, Y.; Komatsu, K. Bull. Chem.
spatially demanding substituents were present at either one or
both of the oxabicyclic bridgehead carbon atoms of the
isobenzofuran precursors 3b-e and 3h, as evidenced by the
Soc. Jpn. 2003, 76, 1669-1672. (b) Miller, G. P.; Tetreau, M. C.; Olmstead,
M. M.; Lord, P. A.; Balch, A. L. Chem. Commun. 2001, 1758-1759.
J. Org. Chem, Vol. 72, No. 8, 2007 2719

Chuang et al.
FIGURE 2. (a) Crystal structure of the mono(isobenzofuran)-C60
adduct 7a, with two CS molecules of crystallization omitted for clarity.
b) Packing structure of adduct 7a; red ) oxygen, yellow ) sulfur.
2
(
moderate-to-low yields of 7b-e and 7h and the requirement
for higher reaction temperatures. For instance, the reaction of
diketone 3e with tetrazine 4a and C60 had to be performed at a
temperature of 45 °C or higher, or otherwise no isobenzofuran-
C60 adduct 7e was observed.
Interestingly, we found that the parent tetrazine 4b was much
more reactive and the reaction could be performed at room
temperature, with yields of the isobenzofuran-C60 adducts
increasing substantially.19 Although the relative reactivities of
these two tetrazines in inverse-electronic-demand Diels-Alder
reactions with isobenzofuran precursors has yet to be quanti-
1
FIGURE 3. Real-time H NMR observation of the concentrations of
products in the reaction between 3,6-bis(2-pyridyl)-1,2,4,5-tetrazine (4a)
and C60. The observed intermediates or products are 1,4-dihydro-1,4-
epoxynaphthalene (3a), the C60-isobenzofuran adduct 7a, intermediate
adduct 5a, and 4,5-bis(2-pyridyl)-pyridazine (8a); see Table 1 for
structures. Y-axis: intensity of each species relative to the integration
intensity of 3,6-bis(2-pyridyl)-1,2,4,5-tetrazine (4a) at time zero.
2
0
fied, it appears that steric hindrance between the C1/C4
substituents of 3a-h and the C3/C6 substituents of tetrazine
4
a is the main factor influencing the rates of these cycloaddi-
tions.
The lower yields for adducts 7f-h in the reaction with the
monofunctionalized C60 derivatives.22 This C(sp )-C(sp ) bond
is particularly longer, by ca. 0.50 Å, than the corresponding
bond lengths of the 2,3-dihydro-1,4-epoxynaphthalene-chro-
3
3
parent tetrazine 4b are due to the appearance of byproduct 9b
as well as the secondary reversible addition of the hydroxyl
group of compound 7h to form the cis-1 bisadduct 7h′ that
occurs before and during the purification of compound 7h
2
3
mium complex or the 2-mono- or 2,3-disubstituted-1,4-
2
4,25
epoxynaphthalenes,
reflecting a relief of bond strain in the
functionalized CdC bond of C60 as is usually observed. The
ease with which we obtained such large crystals may arise from
the rigid, polar structure of 7a coincidentally favoring packing
interactions in the crystal, together with the presence of the
highly polarizable solvent molecules of CS2 which maintains
many fullerene derivatives in solution at relatively high con-
centrations and far better than aromatic solvents. The crystal
packing structure contains two molecules of CS2 in the unusually
long crystallographic cell (b-axis, 31.615 (10) Å).
(
Scheme 1). 3,6-Dihydro-1,2,4,5-tetrazine (4b) was prepared
19
following the method described by Sauer et al. Unfortunately,
this synthesis usually provides the tetrazine in an overall yield
below 10% and as a CH2Cl2 solution. Despite the added
complication of preparing the parent tetrazine 4b, its use has
the great advantage of facilitating the reaction rates and
improving yields, both of which were critical to the success of
this project and the subsequent formation of Diels-Alder
bisadducts.6
2
6
Real-Time Observation of the Reaction Course. We used
H NMR spectroscopy to monitor the reaction course of the
,12
1
Crystal Structure of Monoadduct 7a. The single-crystal
X-ray structure of the isobenzofuran monoadduct 7a has not
been described. Slow evaporation of a CS2 solution of 7a yielded
cycloaddition of 3,6-bis(2-pyridyl)-1,2,4,5-tetrazine (4a) with
isobenzofuran precursor 3a and the subsequent formation of the
isobenzofuran-C60 adduct 7a (Figure 3). This experiment also
permitted us to observe intermediate 5a and its decomposition
prior to the formation of the C60-adduct 7a, showing that it is
the rate-limiting step in the series of cycloadditions (Table 1).
2
1
unusually large black prisms (up to ca. 2- to 3-mm crystals).
The structural information provided by this isobenzofuran-C60
3
3
adduct is interesting (Figure 2). The only C(sp )-C(sp ) single
bond in this C60 derivative has a length of 1.603 Å, which is
3
3
very close to those of the C(sp )-C(sp ) bonds of other
(22) (a) Diederich, F.; Isaacs, L.; Philp, D. J. Chem. Soc., Perkin Trans.
1
1
994, 2, 391-394. (b) Nuber, B.; Hampel, F.; Hirsch, A. Chem. Commun.
996, 1799-1780.
(
19) (a) Sauer, J. In ComprehensiVe Heterocyclic Chemistry 2; Pergamon
(23) Nirchio, P. C.; Wink, D. J. Organometallics 1991, 10, 2499-2505.
(24) (a) Ernet, T.; Maulitz, A. H.; W u¨ rthwein, E.-U.; Haufe, G. J. Chem.
Press: Oxford, 1996; Vol. 6, p 901-957. (b) Sauer, J.; Heldmann, D. K.;
Hetzenegger, J.; Krauthan, J.; Sichert, H.; Schuster, J. Eur. J. Org. Chem.
So., Perkin Trans. 2001, 1, 1929-1938. (b) Taylor, N. J.; Keay, B. A.;
Rodrigo, R. Can. J. Chem. 1984, 62, 1099-1102.
(25) (a) Kohnke, F. H.; Stoddart, J. F.; Slawin, A. M. Z.; Williams, D.
J. Acta Crystallogr., Sect. C 1988, 44, 742-745. (b) Schlemper, E. O.;
Shinmyozu, T.; McCormick, J. P. Acta. Crystallogr., Sect. B 1982, 38,
2981-2983.
(26) (a) Rubin, Y.; Khan, S.; Freedberg, D. I.; Yeretzian, C. J. Am. Chem.
Soc. 1993, 115, 344-345. (b) Khan, S. I.; Oliver, A. M.; Paddon-Row, M.
N.; Rubin, Y. J. Am. Chem. Soc. 1993, 115, 4919-4920. (c) An, Y.-Z.;
Anderson, J. L.; Rubin, Y. J. Org. Chem. 1993, 58, 4799-4801.
1
998, 2885-2896.
20) The reactivities of these tetrazines with other alkenes and alkynes
(
have been reported. For examples, see: (a) Balcar, J.; Chrisam, G.; Huber,
F. X.; Sauer, J. Tetrahedron Lett. 1983, 24, 1481-1484. (b) Thalhammer,
F.; Wallfahrer, U.; Sauer, J. Tetrahedron Lett. 1990, 31, 6851-6854.
(
21) Black prism, approximate dimensions 0.40 × 0.20 × 0.10 mm, space
group P2(1)/n, Z ) 4, a ) 9.927(3) Å, b ) 31.615(10) Å, c ) 12.614(4)
3
Å, â ) 108.654(6)°, V ) 3751(2) Å , temp ) 100(2) K, R1 ) 0.059, Rw
)
0.1089, GoF ) 1.039.
2720 J. Org. Chem., Vol. 72, No. 8, 2007

Open Fullerenes: Adducts of Substituted Isobenzofurans and C60
SCHEME 2. Retro-Diels-Alder Reaction of Isobenzofuran
Adducts 7a and 7c in the Presence of Excess
N-Methylmaleimide
FIGURE 4. Thermogravimetric (TGA) analysis of the isobenzofuran-
C60 adduct 7a.
The reaction of 3,6-bis(2-pyridyl)-1,2,4,5-tetrazine (4a) with
isobenzofuran precursor 3a was complete within just 40 min at
2
6
5 °C; the observed rates of disappearance of 3a and 4a were
-4
-4 -1
.61 × 10 and 6.53 × 10 s , respectively. The concentra-
may occur along the lines of the solid state anthracene transfer
reaction reported by Kr a¨ utler et al.
-
3
-1
29
tion of intermediate 5a (kobs ) 1.85 × 10 s ) reached its
maximum value within 40 min, and then the isobenzofuran 6a
began to form slowly. Upon its formation, 6a reacted with C60
instantly to provide the isobenzofuran-C60 adduct 7a (kobs )
9
6
mediate 5a was complete within 12 h (kobs ) 6.98 × 10 s ),
which is consistent with the time necessary for the reaction to
reach completion when performed on larger scales. Thus, this
single NMR spectroscopy experiment provided the full kinetic
scope for the one-pot synthesis of the isobenzofuran-C60 adduct
In solution, the 1,3-dimethylisobenzofuran monoadduct 7d
underwent cycloreversion to give C60 upon treatment with
maleic anhydride (10 equiv) in toluene under reflux; ca. 90%
of free C60 was recovered within 25 min. The least-stable
monoadduct 7c decomposed slowly in solution, even at room
temperature, as a result of both electronic and steric effects
imparted by the ester groups. In the gas phase, as monitored
through mass spectrometry, we could not obtain signals for the
molecular ions of any of the mono(isobenzofuran)-C60 adducts
7a-h when using MALDI-FT-ICR, MALDI-TOF, or FAB
ionization methods, once again reflecting the labile nature of
these adducts. In general, each of these isobenzofuran monoad-
ducts was stable in the solid state but gradually decomposed in
solution at higher than room temperature.
-
5
-1
.47 × 10 s ); accordingly, it was not possible to observe
a directly in the NMR spectra. The decomposition of inter-
-
5 -1
7
a. The maximum yield of this reaction, as evidenced from the
integral intensities, was ca. 60-70%, which is a value consistent
with the yield calculated from the weight of the isolated
compound.
Kinetics of Isobenzofuran-C60 Adduct Formation. The
varying degrees of thermal stability of the isobenzofuran-C60
adducts 7a-h with their different substituents prompted us to
use NMR spectroscopy to determine the activation energies for
the cycloreversion (retro-Diels-Alder reaction) of two repre-
sentative compounds, 7a and 7c. We quantified these rates of
decomposition by observing the decrease in integral intensity
Practical Considerations on the Thermal Stability of
Isobenzofuran-C60 Adducts. The flash chromatographically
purified isobenzofuran-C60 monoadducts 7a-h were all stable
in the solid state at room temperature for long periods of time,
but their stability in solution was only moderate because they
tended to undergo slow to moderately fast [4 + 2]cycloreversion
at temperatures from 20 to 80 °C. For example, the adduct 7a
was fairly stable at room temperature but began to decompose
gradually at 45 °C in solution. The retro-Diels-Alder reactions
of all of the synthesized adducts 7a-h were quite fast in solution
at temperatures above 80 °C.27
1
for the oxa-bridge methine protons in the H NMR spectra
recorded in C2D2Cl4 and CDCl3 at fixed temperatures. The
liberated isobenzofurans 6a and 6c were trapped by their reaction
with a large excess (100×) of N-methylmaleimide to form stable
isobenzofuran-maleimide adducts that do not undergo retro-
In the solid state, thermogravimetric (TGA) analysis showed
that 7a decomposes at temperatures between 220 and 300 °C,
undergoing a weight loss of 17% (theoretical weight loss 14%)
corresponding to the loss of the isobenzofuran moiety with an
Diels-Alder reaction under the experimental conditions (Scheme
30
2
). Spectra were acquired at fixed time intervals over a range
of temperatures that were appropriate for observing the decom-
position within a practical time scale. For both 7a and 7c, the
kinetics of decomposition fit well to exponential decays within
the studied range of temperatures. Table 2 displays the rate
constants calculated for the decompositions of the adducts 7a
onset at 200 °C. Further heating to 840 °C caused the complete
loss of C60 through sublimation (Figure 4).1
a,28
Long-term
storage (>2 years) of 7a at room temperature led to the
appearance of C60 and some species that were more polar than
31
and 7c at different temperatures; it is quite evident that adduct
7
a, as monitored by TLC (SiO2; toluene/hexanes, 1:1; Rf ) 0.2-
7
a is more stable than adduct 7c.
0
.4). One of the more polar compounds, a brown-colored
Arrhenius plots (ln k vs 1/T) for the decompositions of the
C60-isobenzofuran adducts 7a and 7c exhibited excellent linear
species, was possibly a mixture of regioisomeric bis(isobenzo-
furan)-C60 adducts formed through slow isobenzofuran transfer
to a neighboring molecule in the solid state. This phenomenon
(29) Schwenninger, R.; M u¨ ller, T.; Kr a¨ utler, B. J. Am. Chem. Soc. 1997,
1
19, 9317-9318.
(30) Tobia, D.; Harrison, R.; Phillips, B.; White, T. L.; DiMare, M.;
(
27) An, Y.-Z.; Ellis, G. A.; Viado, A. L.; Rubin, Y. J. Org. Chem. 1995,
0, 6353-6361.
28) Rausch, H.; Braun, T. Chem. Phys. Lett. 2001, 350, 15-18.
Rickborn, B. J. Org. Chem. 1993, 58, 6701-6706.
(31) Lonhienne, T.; Gerday, C.; Feller, G. Biochim. Biophys. Acta 2000,
1543, 1-10.
6
(
J. Org. Chem, Vol. 72, No. 8, 2007 2721

Chuang et al.
1
TABLE 2. Rate Constants and Activation Parameters Calculated from Time-Resolved H NMR Spectroscopy Data on Adducts 7a (in
C2D2Cl4) and 7c (in CDCl3)
q
q
q
q
q
∆
H ) Ea - RT
∆G ) RT(23.76 + ln T - ln k)
∆S ) (∆H - ∆G )/T
adduct
T (K)
k (s-
1 a
)
(kcal mol
-1
)
(kcal mol
-1
)
(cal mol
-1 -1
K )
-
-
-
-
-
-
5
4
4
4
3
3
7a
343
9.29 × 10
1.74 × 10
3.69 × 10
7.56 × 10
1.34 × 10
2.16 × 10
31.8
31.8
31.8
31.8
31.8
31.8
26.6
26.6
26.4
26.3
26.3
26.3
15.2
3
3
3
3
3
48
53
58
63
68
15.0
15.2
15.3
15.2
14.9
-
-
-
-
-
4
4
4
3
3
7c
313
1.36 × 10
2.41 × 10
6.63 × 10
1.67 × 10
2.98 × 10
33.2
33.2
33.2
33.2
33.2
24.0
24.0
23.8
23.5
23.5
29.5
28.9
29.2
29.4
29.0
3
3
3
3
18
23
28
33
a
The kinetics of fragmentation were measured in tetrachloroethane-d2 (7a) and chloroform-d (7c).
reactive isobenzofurans in the presence of C60. This approach
allows adducts to be prepared from isobenzofuran precursors
featuring various functional groups at the 1 and 3 positions. In
general, these isobenzofuran-C60 adducts were stable in the solid
state but slowly decomposed in solution at temperatures above
2
5 °C. Thus, isobenzofurans could be used as reagents for
blocking reactive CdC bonds of C60, i.e., their function may
be similar to that of 9,10-dimethylanthracene (DMA) but at
35,36
higher temperature.
DMA has been used at room temperature
to reversibly block the addition sites of C60 to allow, for
example, stepwise functionalization toward Oh-symmetric hexak-
isadducts. Because the 9,10-dimethylanthracene adduct of C60
is very labile already at 25 °C, high selectivity cannot be
imparted fully in all of the steps leading to the final hexakisad-
duct; it is possible that this problem may be alleviated through
the use of isobenzofurans. Further investigation into the ap-
plications of isobenzofurans for this goal and for the preparation
of open fullerenes remains ongoing and will be reported in due
time.
Experimental Section
General Procedure A. Preparation of Isobenzofuran Precur-
sors 3a-h. The benzyne precursor was prepared using the following
typical procedure. Generally, ∼1.5 equiv of anthranilic acid was
used with respect to 1 equiv of furan derivative. Isoamyl nitrite
(
5.0 mL, 38 mmol) was added to a solution of anthranilic acid
FIGURE 5. Arrhenius plots for the retro-Diels-Alder fragmentation
of adducts 7a and 7c.
(2.45 g, 17.9 mmol) and trichloroacetic acid (34 mg, 0.21 mmol)
in THF (30 mL) at 0 °C. The resulting solution was stirred
vigorously for a few minutes at 0 °C and then warmed to room
temperature. After stirring for 1 h at room temperature, the color
of the suspension had turned pale yellow. The solid (Caution!
Danger of explosive decomposition! No metal spatula) was
collected by filtration and washed with dry THF into a flask
containing a furan derivative (12.0 mmol). Propylene oxide (2 mL)
and dry THF were added until the total volume was ca. 60 mL.
The resulting mixture was then gradually heated to 60 °C. The
diazonium salt decomposed gradually to generate benzyne. After
fits, giving the corresponding activation energies: 32.6 ( 0.9
-
1
and 33.7 ( 1.9 kcal mol , respectively (Figure 5). These
activation energies are within the range of energies required
32
for typical retro-Diels-Alder reactions, i.e., 31-42 kcal
-
1 33
mol . In contrast, the decomposition of the C60-cyclopenta-
diene adduct occurs with an activation energy of only 26.7 kcal
-
1 34
mol .
1
h, the decomposition of the diazoniumcarboxylate salt was
Conclusion
complete, and the solution was heated under reflux for several
minutes. The solution was then concentrated to a volume of ca.
4
Isobenzofuran monoadducts of C60 are readily available by
optimizing Warrener’s methodology for the generation of
mL and purified by silica gel chromatography using appropriate
37
38
39
40
41
eluents. Compounds 3a, 3b, 3c, 3d, 3e, and 3f were
prepared using this method through the reactions of compounds
(
32) Jurczak, J.; Kawczy n´ ski, A. L.; Koluk, T. J. Org. Chem. 1985, 50,
107-1110.
33) Willcot, M. R.; Cargill, R. L.; Sears, A. B. Prog. Phys. Org. Chem.
972, 9, 25-98.
34) Giovane, L. M.; Barco, J. W.; Yadav, T.; Lafleur, A. L.; Marr, J.
A.; Howard, J. B.; Rotello, V. M. J. Phys. Chem. 1993, 97, 8560-8561.
1
(
(35) Lamparth, I.; Maichle-M o¨ ssmer, C.; Hirsch, A. Angew. Chem., Int.
Ed. Engl. 1995, 34, 1607-1609.
(36) Wang, G.-W.; Saunders, M.; Cross, R. J. J. Am. Chem. Soc. 2001,
123, 256-259.
1
(
2722 J. Org. Chem., Vol. 72, No. 8, 2007

Open Fullerenes: Adducts of Substituted Isobenzofurans and C60
2
3
a, 2b,42 2c, 2d, 2e, and 2f, respectively, with benzyne. Compounds
g and 3h were obtained after deprotection of the TBS group of 3f
144.6, 145.0, 145.2, 145.3, 145.4, 145.57, 145.63, 145.9, 146.0,
146.2, 146.4, 146.7, 147.0, 147.3, 153.4. IR (KBr) ν (cm ) 2951,
2925, 2853, 1460, 1252, 1112, 835, 526.
-
1
(with TBAF) and the acetyl group of 3b (with LiOH), respectively.
See experimental description and spectral data for compounds 3b-e
and 3 g,h in Supporting Information.
Tetrazine Adduct 9b. Compound 9b was observed in the
reaction whenever 4b was used as the tetrazine source. It was also
prepared by treating C60 (72 mg, 0.10 mmol) with tetrazine 4b
1
,8-Bis(tert-butyldimethylsilyloxymethyl)-11-oxatricyclo-
2
,7
[
6,2,1,0 ]undeca-2,4,6,9-tetraene (3f). According to general
(16.4 mg, 0.20 mmol) in toluene (80 mL) at room temperature for
procedure A, the silylated furan 2f (5.35 g, 15 mmol) was converted
to pure adduct 3f (5.70 g, 88%) as a yellow oil. 1H NMR
5 days. The color of the mixture turned from purple to brown. Silica
gel was added, and the whole mixture was stirred for 5 h. The
reaction mixture was then poured onto a silica gel column. Elution
with toluene gave recovered C60. Further elution with toluene/EtOAc
(9:1) gave compound 9b (26 mg, 33%, 64% based on recovered
(500 MHz, CDCl
3
) δ (ppm) 0.12 (s, 12H), 0.92 (s, 18H), 4.26 (d,
J ) 11.0 Hz, 2H), 4.41 (d, J ) 11.0 Hz, 2H), 6.91-6.95 (m, 2H),
7
1
2
4
.21-7.23 (m, 2H). 13C NMR (125.7 MHz, CDCl
) δ (ppm) -5.2,
1
3
-
8.4, 25.8, 61.7, 92.3, 119.5, 124.8, 143.9, 151.1. IR (neat) ν (cm )
955, 2929, 2858, 1472, 1256, 1105, 838. EI-MS m/z (rel. intensity)
1
C ). H NMR 500 MHz (CS /CDCl , 9:1) δ (ppm) 6.13 (d, J )
6
0
2
3
+
31 (70, [M - H] ), 375 (42), 271 (48), 243 (88), 229 (71), 213
2
.0 Hz, 1H), 6.53 (d, J ) 2.0 Hz, 1H), 7.52 (s, 1H), 9.20 (s, 1H).
C NMR 125 MHz (C D Cl ) δ (ppm) 52.0, 54.5, 71.5, 75.5, 135.8,
2 2 4
(62), 145 (57), 115 (100), 90 (87). HRMS (m/z) calcd for C24
39 3
H O -
13
Si
2
, 431.2438, found 431.2429.
1
1
1
1
1
1
2
C
36.5, 136.7, 139.3, 140.0, 140.3, 140.4, 142.69, 142.73, 143.1,
43.4, 143.5, 143.8, 143.9, 144.0, 144.1, 144.31, 144.32, 144.34,
44.36, 144.38, 144.45, 144.49, 144.53, 144.6, 144.67, 144.69,
44.8, 144.9, 145.10, 145.13, 145.2, 145.5, 145.9, 146.0, 146.3,
46.6, 146.7, 147.0, 147.18, 147.24, 147.3, 147.40, 147.43, 148.2,
General Procedure B. Isobenzofuran Additions to C60 To
Give Adducts 7a-h. An isobenzofuran precursor (3a-h; 1 equiv
relative to C60) and a tetrazine (4a or 4b;19 1.1 equiv relative to
3
a-h) were added to a solution of C60 in freshly distilled dry
toluene (1-1.5 mg C60/mL toluene) at 20 °C. This reaction mixture
was then stirred under Ar for 16 h at either 45 °C (whenever 4a
was used) or 25 °C (whenever 4b was used). The resulting brown
solution was then subjected to flash chromatography (toluene/
EtOAc, 9:1). The purple fraction containing C60 eluted first,
followed by the fraction containing the desired C60-isobenzofuran
adduct (7a-h), which was then concentrated. The residual brown
-
1
48.7, 148.8, 149.1, 149.5, 149.6, 151.2, 160.8. IR (KBr) ν (cm
)
917, 1673, 1600, 1270. MS-FAB m/z (rel. intensity) 720 (100,
+
+
+
60 ), 793 (53, MH ). HRMS (m/z) calcd for M
62 4 2
C H N O
792.0324, found 792.0335.
Kinetic Experiment Monitoring the Formation of Compound
7a. Real-time observation of the course of the reaction between
solid was redissolved in an appropriate solvent (e.g., CS
2
or CHCl
or 2 mL). This solution was then added to stirred pentane (20-
0 mL) to precipitate the cycloadducts and remove any oily solvent
3
;
C
2
(
60 (7.26 mg, 0.01 mmol), 3,6-bis(2-pyridyl)-1,2,4,5-tetrazine (4a;
.36 mg, 0.01 mmol), and the isobenzofuran precursor 3a
1.44 mg, 0.01 mmol) was conducted in a solution of d -o-
1
3
4
impurities (mostly phthalate plasticizers). Finally, the slurry was
centrifuged, the resulting solid was collected, resuspended in
pentane, and centrifuged again, and the collected solid was dried
under vacuum.
As noted in the text, all of these Diels-Alder monoadducts
decomposed in solution through retro-Diels-Alder reactions, with
rates depending on the temperature. Therefore, purification must
be performed carefully without exceeding a temperature of 40 °C,
particularly during evaporation on the rotary evaporator. In addition,
it was not possible to obtain satisfactory mass spectral data for most
of these adducts. Although some M and MH ions were detected
when using FAB or MALDI-MS, their intensities were not
sufficiently high to allow determination accurate masses. See
experimental description and spectral data for compounds 7b-e
and 7g,h in Supporting Information.
dichlorobenzene and carbon disulfide (1:1; 1 mL) at 25 °C. A total
of 729 FIDs were collected with 30° angle pulses. The acquired
FID data were then transformed into a 2D data set. The peaks of
interest were integrated and exported in ASCII files. The data were
imported into Microsoft Excel and analyzed.
Kinetics of the Decompositions of Adducts 7a and 7c.
N-Methylmaleimide (100 equiv) and mesitylene (0.25 mg, internal
standard) were added to a solution of adduct 7a (2.0 mg) in C
Cl (1 mL). The decomposition of adduct 7a was monitored at 343,
48, 353, 358, 363, and 368 K using H NMR. The corresponding
measurements for compound 7c (3.0 mg) in CDCl (1 mL) were
2 2
D -
+
+
4
1
3
3
conducted at 313, 318, 323, 328, and 333 K. The decompositions
of compounds 7a and 7c were monitored using a method similar
to that described above for conducting the real-time observations.
The resulting ASCII data were imported into Excel. The Excel data
set was then plotted using KaleidaGraph (Synergy Software) to
obtain the rate constants.
9
,10-(1,8-Bis(tert-butyldimethylsilyloxymethyl)-11-oxa-tricyclo-
2,7
[
6.2.1.0 ]undeca-2,4,6-trieno)-1′,2′-buckminsterfullerene (7f). A
mixture of compound 3f (51.8 mg, 0.12 mmol), a solution of
tetrazine 4b in CH Cl (0.37 mmol/mL, 0.4 mmol), and C60
72 mg, 0.1 mmol) in toluene (100 mL) was stirred at 20 °C for
2
2
(
2
4 h. Chromatography on SiO
0.7) gave the pure adduct 7f (49.0 mg, 44%; 76% based on
2
with toluene/cyclohexane 1:1 (R
f
Acknowledgment. We thank the NSF for grants CHE-
0080942 (Y.R.), CHE-9871332 (X-ray), CHE-9974928 (NMR),
and DGE-0114443 (TGA), the Alfred P. Sloan Research
Foundation, and the ACS Petroleum Research Fund for sup-
porting this study. We thank Dr. Jane Strouse for assistance
with the NMR spectroscopy experiments, J e´ r oˆ me Zoidakis of
the Mahdi Abu-Omar group for discussions regarding the kinetic
data, and Dr. Peter Glink (Editchem.com) for a generous
allotment of his editing time.
)
1
recovered C60) as a brown solid. H NMR (500 MHz, CDCl
3
) δ
(
ppm) 0.16 (s, 6H), 0.19 (s, 6H), 0.93 (s, 18H), 5.03 (d, J )
1
7
1
1
1.8 Hz, 2H), 5.15 (d, J ) 11.8 Hz, 2H), 7.49-7.52 (m, 2H), 7.82-
.85 (m, 2H). 13C NMR (125.7 MHz, CDCl
8.5, 26.0, 64.3, 80.5, 95.1, 122.4, 127.8, 137.6, 137.9, 139.2, 139.5,
41.7, 141.8, 142.18, 142.21, 142.25, 142.29, 142.7, 143.1, 144.2,
3
) δ (ppm) -5.3, -5.2,
(37) Cossu, S.; De Lucchi, O. Tetrahedron 1996, 52, 14247-14252.
(38) Linde, H.; Cramer, G. Arch. Pharm. 1988, 321, 237-240.
(39) Best, W. M.; Collins, P. A.; McCulloch, R. K.; Wege, D. Aust. J.
Chem. 1982, 35, 843-848.
40) Newman, M. S.; Dali, H. M.; Hung, W. M. J. Org. Chem. 1975,
0, 262-264.
41) Cattalani, M.; Cossu, S.; Fabris, F.; De Lucchi, O. Synth. Commun.
996, 26, 637-647.
42) Sader-Bakaouni, L.; Charton, O.; Kunesch, N.; Tillequin, F.
Tetrahedron 1998, 54, 1773-1782.
Supporting Information Available: Experimental description
and spectral data for compound 3b-e,g,h and 7b-e,g,h and
crystallographic information files in CIF format. This material is
available free of charge via the Internet at http://pubs.acs.org.
(
4
(
1
(
JO061986J
J. Org. Chem, Vol. 72, No. 8, 2007 2723