Khlebnikov et al.
JOCArticle
SCHEME 1. Cycloaddition of Ylides 2a-c to DMAD
cycloaddition to CdC dipolarophiles to form dibenzo[b,f ]-
pyrrolo[1,2-d][1,4]oxazepine derivatives containing a pyrrolidine
moiety. Cycloaddition of the ylides to CtC dipolarophiles can
provide access to the corresponding pyrroline and pyrrole deri-
vatives. 1,3-Dipolar cycloaddition of azomethine ylides across the
[6,6] ring juncture in C60 is widely used to functionalize
fullerenes.6 This method led to an important class of fullerene
derivatives, pyrrolidino[30,40:1,2][60]fullerenes, having useful ap-
plications in materials science and medicinal chemistry.6,7 The
approach generally involves in situ generation of azomethine
ylides from aldehydes and amines followed by their cycloaddition
to fullerenes.6-8 Cycloaddition of azomethine ylides generated by
ring-opening of aziridines to C60 is much less studied,9 but this
method can be expected to provide a stereoselective route to
fulleropyrrolidine derivatives.
In this note, we report the cycloaddition of azomethine
ylides generated from 1-aryl-1,11b-dihydroazirino[1,2-d ]di-
benz[b, f ][1,4]oxazepines to CtC dipolarophiles and to full-
erene C60. Heating aziridines 1a-c in the presence of acet-
ylenes leads to products formed by 1,3-dipolar cycloaddition
of the corresponding iminium ylides 2a-c to the triple bond.
Thus, from aziridines 1a-c in refluxing toluene, in the
presence of dimethyl acetylenedicarboxylate (DMAD) as a
dipolar trap, cycloadducts 3a-c were obtained in high yields
(Scheme 1). Compounds 3a-c can be easily dehydrogenated
with active MnO2 for 30 min at rt to give compounds 4a-c in
94-97% yield.
FIGURE 1. Energy profiles for conformational transformations of
adducts 3a,b and 4a,b. Relative free energies [kcal mol-1, 298 K]
3
computed at the B3LYP/6-31G(d) level. Hydrogen atoms on aro-
matic rings and methyl groups are omitted for clarity.
exists in both solution and the solid state as a single conforma-
tional isomer, while the corresponding dehydrogenated com-
pound 4b is present as a mixture of atropoisomers 4b and 40b
(ratio at 25 °C in CDCl3 0.6:0.4, in DMSO-d6 0.7:0.3, in crystal
ca. 0.8:0.2). The ratios of atropoisomers in solutions were
unchanged after keeping the solutions for 3 days at rt. The ob-
servation of a sole set of signals in the NMR spectra of
pyrroline 3b can be explained by either the low rotation barrier
of the aryl group or the high free energy difference of rotatio-
nal isomers. According to DFT B3LYP/6-31G(d) calculations
(Figure 1), the degenerate rotation barrier (ΔGq) of thePh-ring
in 3a equals 7.7 kcal mol-1. Once the hydrogen in the ortho-
3
position of the phenyl ring is substituted by a bromine the
barrier to rotation rises to 15.2 kcal mol-1. This is not enough
to prevent interconversion of rotamers at rt. On the other
hand, the free energy difference between atropoisomers 3b and
3
30b is sufficiently large (ΔΔG = 5.6 kcal mol-1) for only one,
the most stable isomer 3b, to be observed in the NMR spectra
and in the solid state.
3
Dehydrogenation of pyrroline 3a to pyrrole 4a changes the
molecular shape, resulting in an increase of the rotational barrier
to degenerate rotation of the Ph ring from 7.7 to 12.6 kcal
The NMR spectra demonstrated different conformational
behavior of o-Br-phenyl-substituted pyrroline 3b and pyrrole
4b. Pyrroline 3b, according to 1H NMR and X-ray analysis,
3
mol-1. In pyrrole 4a, in contrast to pyrroline 3a, one more
topomerization process can be observed, namely oxazepine ring
inversion (ΔGq = 18.5 kcal mol-1). Substitution of the hydro-
gen in the ortho-position of the phenyl ring with a bromine
causes a sharp increase of the barrier of rotation of the aryl
(6) (a) Hirsch, A.; Brettreich, M.; Wudl, F. Fullerenes: Chemistry and
Reactions; Wiley-VCH: Weinhem, Germany, 2005. (b) Langa, F.;
Nierengarten, J.-F., Eds. Fullerenes: Principles and Applications; Royal
Society of Chemistry: Cambridge, U.K., 2007. (c) Abrasonis, G.; Amer,
M. S.; Blanco, R.; Zhe, C. Fullerene Research Advances; Kramer, C. N., Ed.;
Nova Science: New York, 2007.
(7) Kharisov, B. I.; Kharissova, O. V.; Gomez, M. J.; Mendez, U. O. Ind.
Eng. Chem. Res. 2009, 48, 545.
(8) (a) Maggini, M.; Scorrano, G.; Prato, M. J. Am. Chem. Soc. 1993, 115,
9798. (b) Prato, M. Acc. Chem. Res. 1998, 31, 519. (c) Tagmatarchis, N.;
Prato, M. Pure Appl. Chem. 2005, 77, 1675.
(9) (a) Bianco, A.; Gasparrini, F.; Maggini, M.; Misiti, D.; Polese, A.;
Prato, M.; Scorrano, G.; Toniolo, C.; Villani, C. J. Am. Chem. Soc. 1997, 119,
7550. (b) Thomas, K. G.; Biju, V.; George, M. V.; Guldi, D. M.; Kamat, P. V.
J. Phys. Chem. A 1998, 102, 5341. (c) Schergna, S.; Ros, T. D.; Linda, P.;
Ebert, C.; Gardossi, L.; Prato, M. Tetrahedron Lett. 1998, 39, 7791. (d)
Gasparrini, F.; Misiti, D.; Negra, F. D.; Maggini, M.; Scorrano, G.; Villani,
C. Tetrahedron. 2001, 57, 6997. (e) Bianco, A.; Maggini, M.; Nogarole, M.;
Scorrano, G. Eur. J. Org. Chem. 2006, 2934. (f) Brunetti, F. G.; Herrero,
3
group from 12.6 (4a) to 26.5 (4b) kcal mol-1, whereas the
barrier to inversion of the oxazepine ring changes only slightly
3
from 18.5 to 19.6 kcal mol-1. The free energy difference bet-
3
ween atropoisomers 4b and 40b, in contrast to compounds 3b
and 30b, is only 0.86 kcal mol-1, and this leads to the detection
3
of both atropoisomers in the crystal (see the Supporting In-
formation (SI)) and solutions. The equilibrium in solution is
established fast enough, probably via inversion of the oxazepine
ring, which has a lower activation barrier than aryl rotation.
Heating aziridine 1a with unsymmetrical acetylenes 5a-c
leads to mixtures of the regioisomeric cycloadducts 6a-c and
7a-c in 73-93% overall yields (Scheme 2). The major
isomers 7a,c and 6b were isolated pure and their structure
ꢀ
M. A.; de M. Munoz, J.; Giordani, S.; Dıaz-Ortiz, A.; Filippone, S.; Ruaro,
´
G.; Meneghetti, M.; Prato, M.; Vazquez, E. J. Am. Chem. Soc. 2007, 129,
ꢁ
14580.
5212 J. Org. Chem. Vol. 75, No. 15, 2010