[4 + 2] Cycloadditions of rigid s-cis dienes to C60. A synchronous Diels-Alder reaction

Article abstract of DOI:10.1021/ol0003735

(Matrix presented) The Diels-Alder reaction of rigid s-cis dienes with C₆₀ occurs by a concerted mechanism, via a symmetrical transition state.

Full text of DOI:10.1021/ol0003735

ORGANIC
LETTERS
2001
Vol. 3, No. 4
545-548
[4 + 2] Cycloadditions of Rigid s-cis
Dienes to C . A Synchronous
60
Diels−Alder Reaction
Nikos Chronakis and Michael Orfanopoulos*
Department of Chemistry, UniVersity of Crete, 71409 Iraklion, Crete, Greece
orfanop@chemistry.uch.gr
Received December 4, 2000
ABSTRACT
The Diels−Alder reaction of rigid s-cis dienes with C60 occurs by a concerted mechanism, via a symmetrical transition state.
Among the functionalizations of C60, the Diels-Alder
reactions with rigid s-cis dienes are particularly useful, since
they usually provide thermally stable adducts.1 However, the
mechanism of this reaction still remains unexplored.2
Following our recent studies on the [2 + 2]3 and the ene4
reactions of [60]fullerene, we present here a mechanistic
study of the [4 + 2] cycloaddition reaction of rigid s-cis
dienes to C60. For this purpose, R-secondary kinetic isotope
effects (KIEs) were used in order to determine whether the
mechanism is concerted or stepwise. 2,3-Dimethylene-7-
oxabicyclo[2.2.1]heptane (1-d0) and its deuterated analogues
1-d2 and 1-d4 were chosen as the appropriate reactive
substrates. The synthesis of compounds 1-d0, 1-d2, and 1-d4
is shown in Scheme 1.
A 10-fold molar excess of the conjugated diene 1-d0
reacted smoothly with C60 at 80 °C, in a toluene solution.
No multiadducts were detected by HPLC, and the Diels-
Alder adduct 2-d0 was remarkably stable at the reaction
temperature. The isolated adduct 2-d0 was stable even after
prolonged heating in toluene, at 80 °C. Under these condi-
tions not even traces of retro Diels-Alder products were
detected by HPLC and H NMR spectroscopy. In the H
NMR spectrum of the adduct 2-d0 at 298 K (Figure 1), the
diastereotopic methylene hydrogens Ha and Hb of the
cyclohexene ring absorb at 4.15 ppm and appear as a sharp
AB system. In addition, the methine hydrogens Hc appear
as a singlet absorption at 5.20 ppm and the four methylene
hydrogens Hd and He are represented by two multiplet
absorptions at 2.06 and 1.77 ppm, respectively.
1
1
(1) (a) Diederich, F.; Jonas, U.; Gramlich, V.; Hermann, A.; Ringsdorf,
H.; Thilgen, C. HelV. Chim. Acta 1993, 76, 2445. (b) Paquette, L. A.; Trego,
W. E. Chem. Commun. 1996, 419. (c) Herrera, A.; Martinez, R.; Gonzalez,
B.; Illescas, B.; Martin, N.; Seoane, C. Tetrahedron Lett. 1997, 38, 4873.
(d) Torres-Garcia, G.; Luftmann, H.; Wolff, C.; Mattay, J. J. Org. Chem.
1997, 62, 2752. (e) Tome, A. C.; Enes, R. F.; Cavaleiro, J. A. S.; Elguero,
J. Tetrahedron Lett. 1997, 38, 2557.
(2) The mechanism of the Diels-Alder reaction of Danishefsky’s dienes
with C60 has been recently reported. Mikami, K.; Matsumoto, S.; Okubo,
Y.; Fujitsuka, M.; Ito, O.; Suenobu, T.; Fukuzumi, S. J. Am. Chem. Soc.
2000, 122, 2236.
The cyclohexene ring of 2-d0 can adopt two nondegenerate
boat conformations, namely, a folded one and an extended
one. To verify the stability of the two conformers, we used
ab initio calculations. The two geometries were fully
optimized at the HF/3-21G level of theory, and the local
minima were found to be almost isoenergetic. In particular,
(5) Frisch, M. J., et al. Gaussian 94, Revision D.4, Gaussian, Inc.,
Pittsburgh, PA, 1995.
(6) (a) Rubin, Y.; Khan, S.; Freedberg, D. I.; Yeretzian, C. J. Am.
Chem. Soc. 1993, 115, 344. (b) Zhang, X.; Foote, C. S. J. Org. Chem.
1994, 59, 5235. (c) Illescas, B.; Martin, N.; Seoane, C.; Orti, E.; Viruela,
P. M.; Viruela, R.; de la Hoz, A. J. Org. Chem. 1997, 62, 7585.
(3) (a) Vassilikogiannakis, G.; Orfanopoulos, M. J. Am. Chem. Soc. 1997,
119, 7394. (b) Vassilikogiannakis, G.; Chronakis, N.; Orfanopoulos, M. J.
Am. Chem. Soc. 1998, 120, 9911. (c) Vassilikogiannakis, G.; Orfanopoulos,
M. J. Org. Chem. 1999, 64, 3392.
(4) Chronakis, N.; Orfanopoulos, M. Org. Lett. 1999, 1, 1909.
10.1021/ol0003735 CCC: $20.00 © 2001 American Chemical Society
Published on Web 01/23/2001

Scheme 1. Synthesis of the Rigid s-cis Dienes 1-d0, 1-d2, and
1-d4
Figure 1. Diels-Alder reaction of 1-d0 with C60.
system at 4.16 ppm) and the signal of the methine hydrogens
Hc and Hc′ at 5.21 ppm (Figure 2). The average value of
the intermolecular R-deuterium isotope effect was found to
be kH/kD(4D) ) 0.61 ( 0.03 [kH/kD(4D) ) 0.88 ( 0.03 per D
atom].
The origin of R-secondary isotope effects is due to changes
in the force constants upon going from reactants to the
transition state at the rate-determining step. In a concerted
mechanism, the force constants7 for the bonds CR-H(D) are
greater in the transition state than in the reactant, because
the out-of-plane bending vibrations increase upon conversion
of the reaction centers from sp2 to sp3. Thus, the isotope
effect is expected to be inverse. The large inverse value of
the R-secondary isotope effect that was measured here
strongly supports a one-step mechanism (Scheme 2, case B
or C) for the Diels-Alder reaction. In the case of a stepwise
mechanism (Scheme 2, case A) the R-secondary isotope
effect should have been close to one.8 These effects (inverse
R-secondary isotope effects) are comparable to previously
calculated8 or measured9 isotope effects for other Diels-
Alder reactions, which were interpreted as supporting a
concerted mechanism.
It is interesting to note here that for the [4 + 2]
cycloadditions substantial differences between calculated
isotope effects for the “inside” and “outside” hydrogens on
the diene terminal double bonds have been also reported.10
These isotope effect patterns were attributed to steric and
electronic interactions for the concerted Diels-Alder reac-
tions and provide a sensitive probe of the transition state
geometry.
the folded conformation is more stable than the extended
one by 0.5 kcal/mol. All the computations were performed
with the GAUSSIAN 94 program package.5
The dynamic behavior of cycloadduct 2-d0 was investi-
1
gated by using variable-temperature H NMR experiments.
No change of the sharp AB system at 4.15 ppm was observed
at different temperatures, ranging from -40 to +74.3 °C.
This indicates that the boat-to-boat inversion of the cyclo-
hexene ring connecting the C60 cage to the organic addend
has a high activation energy. The fast flipping motion of
the cyclohexene ring has already been reported for other
organofullerenes.6
Along with the M+ ion of C60 at 720, the MALDI-TOF
MS of 2-d0 gave the M - 28 ion at 814, which indicates the
loss of a -CH2-CH2- fragment under the spectrometric
conditions.
To determine the intermolecular R-secondary isotope effect
kH/kD(4D), a mixture of C60 and a 10-fold excess of an
equimolar mixture of 1-d0/1-d4 was dissolved in deoxygen-
ated toluene and heated at 80 °C. The reaction was followed
by HPLC equipped with a Cosmosil 5C18-MS reversed
phase column. A 45% yield of the Diels-Alder monoadducts
was obtained after 4 h, based on the recovered C60. The
fullerene cycloadducts 2-d0 and 2-d4 (Figure 2) were purified
by flash column chromatography (SiO2, C60: hexane/CH2-
Cl2 ) 1/1; 2-d0, 2-d4: hexane/CH2Cl2 ) 1/3) and character-
ized by 1H NMR spectroscopy and MALDI-TOF mass
spectrometry [2-d0: m/z (M - 28) 814; 2-d4: m/z (M -
28) 818]. The isotope effect kH/kD(4D) is proportional to the
ratio of the 2-d0/2-d4 adducts and was measured by the
integration of the signals of the methylene hydrogens (AB
In the present study, the averaged secondary kinetic isotope
effects of the “inside” and “outside” terminal double bond
hydrogens of the diene were measured experimentally.
Furthermore, by using “Thornton analysis” 11 a better inside
of the transition state geometry was obtained. For example,
in the concerted Diels-Alder reaction of rigid s-cis dienes
with C60, the transition state may be either symmetricals
both bonds formed to the same extentsor unsymmetricals
546
Org. Lett., Vol. 3, No. 4, 2001

1
Figure 2. Determination of the intermolecular R-secondary isotope effect in the Diels-Alder reaction of 1-d0/1-d4 with C60 by H NMR
spectroscopy.
one bond stronger than the others(Scheme 2, cases B and
C correspondingly).
in deoxygenated toluene and heated at 80 °C. The fullerene
cycloadducts 2-d0 and 2-d2 were purified by flash column
chromatography and characterized by 1H NMR spectroscopy
and MALDI-TOF MS [2-d0: m/z (M - 28) 814; 2-d2: m/z
(M - 28) 816]. The value of the R-secondary isotope effect
kH/kD(2D) is proportional to the adduct ratio 2-d0/2-d2 and
The transition-state structure was subjected to the “Thorn-
ton analysis”, which provides a general method to visualize
the symmetry of the transition state. For this purpose, the
magnitude of the secondary deuterium isotope effect kH/kD(2D)
between 1-d0 and 1-d2 with C60 was measured and compared
with that derived from the intermolecular competition
between 1-d0 vs 1-d4 and C60. It should be noted that kH,
kD(2D), and kD(4D) are the rate constants for the formation of
Diels-Alder cycloadducts between 1-d0, 1-d2, 1-d4, and C60,
respectively.
1
was measured by H NMR integration of the appropriate
signals.
It is interesting to note that hydrogen atoms Ha and Ha′ as
1
well as Hb and Hb′ have different chemical shifts in the H
NMR spectrum (CS2/C6D6 as solvent). As a result, these
protons appear as two AB quartets, separated by 0.013 ppm
(Figure 3). Apparently, the homoallylic location of the
methylene deuterium atoms in adduct 2-d2 affects the
chemical shift of Ha′ and Hb′ to an extent sufficient to
distinguish them from Ha and Hb.
The R-secondary isotope effect was measured by integra-
tion of the absorption of the methylene hydrogens at 4.17
ppm [4kH + 2kD(2D)] and the absorption of the methine
hydrogens Hc, Hc′ at 5.21 ppm [2kH + 2kD(2D)]. The average
value of the intermolecular R-deuterium isotope effect was
found to be kH/kD(2D) ) 0.78 ( 0.03 [kH/kD(2D) ) 0.88 ( 0.03
per D atom]. The results are summarized in Table 1.
The measured kH/kD(4D) and kH/kD(2D) values shown in Table
As a typical procedure, a mixture of C60 and a 10-fold
excess of an equimolar mixture of 1-d0/1-d2 was dissolved
Scheme 2. Energy versus Reaction Coordinate Diagrams for
the Concerted and Stepwise Mechanisms of the Diels-Alder
Reaction
Table 1. R-Secondary Isotope Effects for the Diels-Alder
Cycloaddition Reaction of 2,3-Dimethylene-7-oxabicyclo[2.2.1]-
heptane with C60
t
convn
T
substr
solvent (h) (%)a (°C) kH/kD (av)b kH/kD (per D)
1-d 0/1-d 4 toluene
1-d 0/1-d 2 toluene
4
4
45
45
80 0.61 ( 0.03 0.88 ( 0.03
80 0.78 ( 0.03 0.88 ( 0.03
1
a On the basis of recovered C60. b Determined by H NMR integration
of the appropriate signals. The error was ( 4%.
Org. Lett., Vol. 3, No. 4, 2001
547

1
Figure 3. Determination of the R-secondary isotope effect in the Diels-Alder reaction of 1-d0/1-d2 with C60 by H NMR spectroscopy.
1 were in good agreement with the mechanistic predictions
of the “Thornton analysis”.
In the case of a symmetrical, concerted mechanism, the
new bonds x1 and x2 (Scheme 3) are formed at the same
effect per deuterium atom and [kH/kD(2D)]2 should be exactly
equal to kH/kD(4D). The measured isotope effect values verify
eq 1 and support a symmetrical transition state.
[kH/kD(2D)]2 ) (0.78)2 ) 0.61 ) kH/kD(4D)
(1)
In conclusion, the measured values of the R-secondary
isotope effects are consistent with a concerted mechanism
of the Diels-Alder reaction of rigid s-cis dienes with C60.
Comparison of the kH/kD(4D) and [kH/kD(2D)]2 values, applying
the “Thornton analysis”, supports a symmetrical transition
state.
Scheme 3. Synchronous Transition State in the Concerted
Diels-Alder Cycloaddition of Rigid s-cis Dienes to C60
Acknowledgment. We thank Greek Secretariat of Re-
search and Technology (ΠENE∆ 1999) for financial support
and for research fellowship to N.C. Professor G. J. Kara-
batsos is also acknowledged for valuable comments and
discussions. We also thank Dr. G. Froudakis for computa-
tional work and Dr. G. Vassilikogiannakis for taking the MS
at Scripps Research Institute.
extent in the transition state, leading to the same extent of
rehybridization (from sp2 to sp3) of the reaction centers C1
and C2. Consequently, deuterium substitution of C1 or C2
carbon atoms would lead to the same R-deuterium isotope
Supporting Information Available: 1H NMR and 13C
NMR spectra and GC MS for 1-d0, 1-d2, and 1-d4; 1H NMR
1
and 13C NMR spectra and MALDI-TOF MS of 2-d0; H
(7) Streitwieser, A.; Jagow, R. H.; Fahey, R. C.; Suzuki, S. J. Am. Chem.
Soc. 1958, 80, 2326.
(8) Houk, K. N.; Gonzalez, J.; Li, Y. Acc. Chem. Res. 1995, 28, 81.
(9) Mattson, O.; Westway, K. C. AdV. Phys. Org. Chem. 1996, 31, 143.
(10) Wiest, O.; Houk, K. N.; Black, K. A.; Tomas, B.; IV J. Am. Chem.
Soc. 1995, 117, 8594.
NMR and MALDI-TOF MS of 2-d0/2-d2 and 2-d0/2-d4; ab
initio theoretical calculations. This material is available free
of charge via the Internet at http://pubs.acs.org.
(11) Taagepera, M.; Thornton, E. R. J. Am. Chem. Soc. 1972, 94, 1168.
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