Stereoelectronic effects in diastereoselective formation of fulleroids

Article abstract of DOI:10.1021/ol701789u

The substituent effects on diastereoselective formation of fulleroids in the reactions of C₆₀ with various unsymmetrical diazoalkanes were investigated. The steric demand on the stereochemical course of reactions dominated the diastereoselectiv

Full text of DOI:10.1021/ol701789u

ORGANIC
LETTERS
2007
Vol. 9, No. 20
4045-4048
Stereoelectronic Effects in
Diastereoselective Formation of
Fulleroids
Hiroshi Kitamura, Ken Kokubo, and Takumi Oshima*
Department of Applied Chemistry Graduate School of Engineering, Osaka UniVersity,
Yamada-oka, Suita, Osaka 565-0871, Japan
oshima@chem.eng.osaka-u.ac.jp
Received July 26, 2007
ABSTRACT
The substituent effects on diastereoselective formation of fulleroids in the reactions of C60 with various unsymmetrical diazoalkanes were
investigated. The steric demand on the stereochemical course of reactions dominated the diastereoselectivity for diazoalkanes bearing aliphatic
as well as monosubstituted
π-resonating groups, whereas the stereoelectronic effects of coexisting π-resonating aromatic and cyclopropyl
groups played a crucial role in the ring closure of the radical intermediates, overriding the steric demand.
It is well-known that C60 easily undergoes a variety of
addition reactions due to the low-lying LUMO level.1 In
particular, 1,3-dipolar cycloadditions of C60 with diazoalkanes
have been extensively studied since the pioneering work by
Wudl et al. in 1991.2 The reactions of unsymmetrical
diazoalkanes (1, R1R2CN2, R1 * R2) produce two diastereo-
isomers of [6,5]open fulleroids (2 and 3) and the [6,6]closed
methanofullerenes 4 via a nitrogen extrusion of intermediate
[6,6]closed pyrazolinofullerenes,3 depending on the identities
of diazoalkanes. In general, these reactions preferentially
yield fulleroids in which the bulky group is located above
the five-membered ring (pentagon) of the bridged fullerene
subunit.4 In the case of monoaryldiazoalkanes, it was also
found that fulleroids bearing an aryl group above the
pentagon were predominantly obtained.5 Such a diastereo-
selectivity was rationalized by Hirsch et al. on the basis of
(3) Suzuki, T.; Li, Q.; Khemani, K. C.; Wudl, F. J. Am. Chem. Soc.
1992, 114, 7301-7302.
(4) (a) Isaacs, L.; Wehrsig, A.; Diederich, F. HelV. Chim. Acta 1993,
76, 1231-1250. (b) Skiebe, A.; Hirsch, A. J. Chem. Soc., Chem. Commun.
1994, 335-336. (c) Schick, G.; Hirsch, A. Tetrahedron 1998, 54, 4283-
4296. (d) Nakamura, Y.; Inamura, K.; Oomuro, R.; Laurenco, R.; Tidwell,
T. T.; Nishimura, J. Org. Biomol. Chem. 2005, 3, 3032-3038.
(5) (a) Prato, M.; Lucchini, V.; Maggini, M.; Stimpfl, E.; Scorrano, G.;
Eiermann, M.; Suzuki, T.; Wudl, F. J. Am. Chem. Soc. 1993, 115, 8479-
8480. (b) Hummelen, J. C.; Knight, B. W.; LePeq, F.; Wudl, F. J. Org.
Chem. 1995, 60, 532-538. (c) Martin, N.; Sanchez, L.; Guldi, D. M. Chem.
Commun. 2000, 113-114. (d) Hall, M. H.; Lu, H.; Shevlin, P. B. J. Am.
Chem. Soc. 2001, 123, 1349-1354. (e) Hall, M. H.; Shevlin, P.; Lu, H.;
Gichuhi, A.; Shannon, C. J. Org. Chem. 2006, 71, 3357-3363.
(1) (a) Hirsch, A. Top. Curr. Chem. 1999, 199, 1-65. (b) Wilson, S.
R.; Schuster, D. I.; Nuber, B; Meier, M. S.; Maggini, M.; Prato, M.; Taylor,
R. Fullerene, Chemistry, Physics and Technology; John Wiley & Sons
Inc.: New York, 2000; pp 91-176. (c) Nakamura, Y.; O-Kawa, K.;
Nishimura, J. Bull. Chem. Soc. Jpn. 2003, 76, 865-882. (d) Hirsch, A.;
Brettreich, M. Fullerenes, Chemistry and Reactions; Wiley-VCH: Wein-
heim, Germany, 2005; Chapter 4, pp 101-172.
(2) Suzuki, T.; Li, Q.; Khemani, K. C.; Wudl, F.; Almarsson, O. Science
1991, 254, 1186-1188.
10.1021/ol701789u CCC: $37.00
© 2007 American Chemical Society
Published on Web 08/30/2007

steric demand in the nitrogen evolution step of pyrazoline
intermediate.4c
chemical shifts of the diagnostic methyl and methine protons
as well as the aryl o-protons,7 since the functional groups
above pentagon and hexagon were much affected by the
strong paramagnetic and the weak diamagnetic currents,
respectively.8 For instance, as shown in Figure 1, the methine
proton of the cyclopropyl group of 2f and 3f resonates at δ
1.0 and 3.9, whereas their aromatic protons resonate at δ
7.2-7.8 and 7.0, respectively. Here, the fulleroids with larger
R1 substituent above pentagon and hexagon are referred to
as 2 and 3, respectively.
A survey of Table 1 indicates the following points: (1)
aliphatic diazoalkanes 1a-c raised the diastereoselectivity
(i.e., 2/3 ratio ) 2 to 18) with increasing the bulkiness of
R1 in conformity with the steric demand (entries 1-3); (2)
p-tolyl-substituted 1d and 1e also attained the high 2/3 ratios
as the above aliphatic diazoalkanes (entries 4 and 5); (3)
surprisingly, however, the replacement of the R2 ) iPr group
of 1e by a smaller cyclopropyl group reversed the 2/3 ratio
()0.6) as found for 1f (entry 6); (4) but cyclopropyl
diazomethane 1g and diazoethane 1h obeyed the usual steric
demand (entries 7 and 8); (5) also of interest is that the
diaryldiazomethanes 1i and 1j exhibited the notable diaste-
reoselectivity where the more electron-donating aromatic
nucleus tended to locate above the hexagon (entries 9 and
10); (6) in addition, the aromatic diazoalkanes, 1d-f, 1i, and
1j provided rather a considerable amount of methano-
fullerenes 4 (10-31%).
However, a detailed study of the steric and electronic
effects governing the diastereoselectivity has not been
hitherto carried out. Hence, in the present work on the
reactions of C60 with various unsymmetrical diazoalkanes,
we have investigated the substituent effects on the diaste-
reoselective formation of fulleroids to provide more insight
into the mechanism and the stereochemical course of these
reactions. Here, we wish to report the decisive electronic
effects of coexisting aryl and cyclopropyl substituents which
reverse the diastereoselectivity deduced from only the steric
demand in the fulleroid formation.
The reactions of C60 with various diazoalkanes 1a-j were
carried out under conditions at ambient temperature as
depicted in Table 1. The unstable diazoalkanes 1a-c and
Table 1. Product Distributions of the Reaction of C60 with
Various Diazoalkanes
Mechanistically, the N2-extrusion of pyrazoline intermedi-
ates is generally argued to proceed via a concerted orbital
controlled [π2s + 2s + 2s + 2a] rearrangement (path a)9
π
σ
σ
or a stepwise biradical pathway (path b),4c,10 with both paths
initially generating the transient [6,5]closed methano-
fullerenes capable of undergoing a facile valence tautom-
erisation (V.T.) into [6,5]open fulleroids 2 and 3 (Scheme
1).
Here, it should be noted that the methanofullerenes 4 are
only formed in the latter radical mechanism. However, the
diazenyl diradical process is needed so as to involve the
protruding azenyl radical terminus for the diastereoselective
formation of fulleroids since the prior N2-extrusion would
result in the loss of steric discrimination on the radical
coupling step (vide infra).
product ratioa [%]
total
entry
1
R1
R2
2
3
4
yieldb [%]
1
2
1a Et
1b iPr
1c tBu
Me
Me
Me
Me
iPr
65
91
35
9
31
23
19
23
42
35
9
36
37
33
3
91
5
4
4
1d p-tolyl
80
10
c
43
c
44
46
60
10
17
31
5
1e p-tolyl
83
6
1f p-tolyl
cyclopropyl
H
26
7
1g cyclopropyl
>99
48
8
1h cyclopropyl Me
8
27
25
9
1i p-tolyl
1j p-anisyl
Ph
Ph
27
15
10
a Determined by H NMR. b Based on used C60. c Trace.
1
Since the 1a-c provided the high 2/3 ratios with a
negligible amount of radical product 4, the reactions of 1a-c
are expected to proceed mainly via the concerted mechanism.
Therefore, the lager substituent (RL) tends to locate in the
quasi-equatorial position of the enveloped pyrazoline ring
in conformer A rather than in the axial position in conformer
1g,h were generated in situ from the corresponding hydra-
zones with silver oxide to just undergo rapidly 1,3-dipolar
cycloaddition with C60 in o-dichrolobenzene solution. The
reactions of relatively stable aryl-substituted diazoalkanes
were performed by adding their toluene solution of 1d-f
and 1i,j (<1 equiv), which were prepared by oxidation of
hydrazones, into the stirred o-dichlorobenzene solution of
C60. Purification of the reaction mixtures was made by HPLC
on a Buckeyprep column to give a mixture of monoadducts
of 2, 3, and 4.6
(6) Further recycle HPLC treatment provided the pure 4 for diazoalkanes
1d-f, 1h-j and also brought about the enrichment of isomer 2 or 3 for
diazoalkanes 1a, 1f, and 1h.
(7) Smith, A. B., III; Strongin, R. M.; Brard, L.; Furst, G. T.; Romanow,
W. J.; Owens, K. G.; Goldschmidt, R. J.; King, R. C. J. Am. Chem. Soc.
1995, 117, 5492-5502.
(8) (a) Pasquarello, A.; Schluter, M.; Haddon, R. C. Science 1992, 257,
1660-1661. (b) Prato, M.; Suzuki, T.; Wudl, F.; Lucchini, V.; Maggini,
M. J. Am. Chem. Soc. 1993, 115, 7876-7877.
The fulleroids and the methanofullerenes were identified
1
by the measurements of UV-vis, H NMR, and 13C NMR
(9) Wallenborn, E.-U.; Haldimann, R. F.; Kla¨rner, F.-G.; Diederich, F.
Chem. Eur. J. 1998, 4, 2258-2265.
spectra. The two diastereomers of fulleroids 2 and 3 both
with Cs symmetry were assigned on the basis of the 1H NMR
(10) (a) Cases, M.; Duran, M.; Mestres, J.; Martin, N.; Sola´, M. J. Org.
Chem. 2001, 66, 433-442. (b) Engel, P. S. Chem. ReV. 1980, 80, 99-150.
4046
Org. Lett., Vol. 9, No. 20, 2007

Figure 1. 1H NMR spectrum of a mixture of 2f, 3f, and 4f.
B (Figure 2a). Hence, the larger equatorial RL rotates toward
the pentagon to give rise to the fulleroid 2. In contrast, the
reactions of 1d-f with a π-resonating tolyl group apparently
involve a large extent of radical N2-extrusion in view of the
significant formation of 4 (10-31%). In this possible radical
process, as shown in C, the bulky tolyl group (RL) would
rotate away from the azenyl terminus to preferably afford
the expected isomer 2 (Figure 2b). However, only the 1f
bearing R2 ) cyclopropyl substituent did give rise to the
reverse diastereoselectivity (2/3 ) 0.6), although the com-
parable 1e bearing the slightly larger R2 ) iPr group
exclusively gave the usually expected isomer 2e. To clarify
the peculiar properties of the cyclopropane ring, we carried
out the reactions of cyclopropyl-substituted diazomethane
1g and diazoethane 1h. However, the observed diastereo-
selectivity can be explained by the usual steric demand, i.e.,
cyclopropyl > Me > H, irrespective of whether the N2-
extrusion is concerted or stepwise.
A question is raised on how the cyclopropyl group
provided the torque of bringing the coexisting bulky tolyl
Scheme 1. Possible Mechanism of N2 Extrusion of
Pyrazolinofullerene
Figure 2. (a) Equilibrated conformers A and B of a concerted
transition state: RL, larger substituent; RS, smaller substituent;
superscripts a and e represent axial and equatorial, respectively.
(b) Radical intermediate C.
Org. Lett., Vol. 9, No. 20, 2007
4047

group above the unexpected hexagon. As a consequence, we
may rationalize the reverse diastereoselectivity by resorting
to the cooperative π-resonating effects of tolyl and cyclo-
propyl groups. Ideally, the most enhanced radical stabilization
will be attained in the coplanar conformation for the tolyl
group and the bisected one for cyclopropyl group with respect
to the spin-centered sp2-hyblidized plane as shown in
intermediate D (Figure 3).11 In such a biradical intermediate,
p-anisyl substituents, the preferential location of tolyl and
anisyl groups above the hexagon can be explained on the
basis of the more enhanced radical stabilization by these
electron-donating aromatic nuclei. As shown in the equilib-
rium between F and G (Figure 4), tolyl and anisyl groups
Figure 4. The stereoelectronic effects in diastereoselective ring
closure of diazenyl diradical intermediates.
are likely to adopt the favorable coplanar conformation with
respect to the central sp2-hybridized plane in order to
optimally stabilize the spin center. Hence, the more favored
conformer F would provide 3 due to the steric congestion
between the less π-resonating phenyl group and the azenyl
moiety.
In summary, we found that the steric demand dominates
the diastereoselectivity of fulleroid formation for diazo-
alkanes bearing an aliphatic as well as a monosubstituted
π-resonating group, whereas the stereoelectronic effects of
coexisting π-resonating groups play an important role in the
ring closure of the azenyl radical intermediates, reversing
the diastereoselectivity. These findings provide very useful
insight into the mechanistic understanding of diazoalkanes-
fullerene reactions.
Figure 3. The stereoelectronic effects in diastereoselective ring
closure of diazenyl diradical intermediates.
the bisected cyclopropane ring will necessarily suffer from
the more steric repulsion with the azenyl moiety as compared
with the facing tolyl plane. Accordingly, the cyclopropyl
group is apt to rotate toward the pentagon. In contrast, the
iPr group can approach the azenyl moiety by directing the
less hindered methine as denoted in the less congested E
(Figure 3).
Supporting Information Available: General procedure
for the reaction of diazoalkanes with C60, 1H and 13C NMR
spectra of 2, 3, and 4, HPLC charts of the reaction mixtures,
1H NMR spectra for the determination of product ratios, and
1H-1H decoupling spectra of the mixture of 2i, 3i and 2j,
3j. This material is available free of charge via the Internet
at http://pubs.acs.org.
Considering the efficient π-resonating stabilization of the
carbon-centered radical, we can regard the reverse diaste-
reoselectivity of diaryl-substituted 1i and 1j as strong
evidence for the involvement of an electronic effect in the
present radical ring-closure.12 In view of the identical steric
bulk of the aromatic portion of the phenyl, p-tolyl, and
OL701789U
(11) (a) de Meijere, A. Angew. Chem., Int. Ed. Engl. 1979, 18, 809-
886. (b) Engel, P. S.; Nalepa, C. J.; Horsey, D. W.; Keys, D. E.; Grow, R.
T. J. Am. Chem. Soc. 1983, 105, 7102-7107.
(12) Shevlin et al. carried out the similar reaction of diazoalkane 1j with
C60 and obtained the mixture of corresponding fulleroids and methano-
fullerene; see ref 5d.
4048
Org. Lett., Vol. 9, No. 20, 2007