Tandem reductive ring opening-retro-Bingel reactions of bismethano[60]fullerenes to give 1,2-dihydro[60]fullerylglycines

Article abstract of DOI:10.1039/b100655j

Bismethano[60]fullerene derivatives 1 and 3 give 1,2-dihydro[60]fullerylglycines 2 and 4 respectively by a novel tandem reductive ring opening-retro-Bingel reaction.

Full text of DOI:10.1039/b100655j

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Tandem reductive ring opening-retro-Bingel reactions of
bismethano[60]fullerenes to give 1,2-dihydro[60]fullerylglycines
Glenn A. Burley,a Paul A. Keller,*a Stephen G. Pyne*a and Graham E. Ballb
a Department of Chemistry, University of Wollongong, Wollongong, New South Wales, 2522, Australia.
E-mail: Stephen_Pyne@uow.edu.au; Paul_Keller@uow.edu.au
b NMR Spectroscopy Unit, University of New South Wales, Sydney, New South Wales, 2052, Australia
Received (in Cambridge) 17th January 2001, Accepted 12th February 2001
First published as an Advance Article on the web 6th March 2001
Bismethano[60]fullerene derivatives 1 and 3 give 1,2-dihy-
dro[60]fullerylglycines 2 and 4 respectively by a novel
tandem reductive ring opening-retro-Bingel reaction.
a mixture of the 1,2-dihydro[60]fullerylglycine 2 and C60.
Separation of this mixture by column chromatography on silica
gel gave pure samples of 2 and C60 in yields of 42 and 12%,
respectively (Scheme 1).12 These fullerene compounds arise
formally from a tandem reductive ring opening-retro-Bingel
reaction and a double retro-Bingel reaction, respectively.
Interestingly, none of the double reductive ring-opened bisful-
lerylglycine adduct {C60H2[C(NHCHPh2)(CO2R)]2} was iso-
lated. The structure of 2 was clearly evident from NMR
spectroscopy. The UV-vis spectrum of 2 in DCM showed
distinct absorbances at 430, 640 and 705 nm, similar to that
found in the derivative C60H[C(NHCHPh2)(CO2But)].10 The
1H NMR spectrum of 2 revealed a one proton singlet at d 6.84
that corresponded to the single fullerene proton (Hc). An upfield
shift of the aromatic protons of the benzhydryl moiety was
consistent with the chemical transformation of the imine to the
secondary amino functionality. The addend region of 2 revealed
two doublets at d 5.41 and 5.24 (J = 11.9 Hz) corresponding to
the diastereotopic benzyl protons (Hd/HdA). The other benzylic
protons (He) resonated as a two proton singlet at d 5.08, whereas
the two proton singlet at d 3.40 was identified as corresponding
to the methylene protons (Hf). A singlet one proton resonance
at d 4.84 corresponded to the benzhydryl resonance (Hg). A
three proton coupled spin system was identified as Ha (d 4.97,
d, J 12.3 Hz), Hb (d 5.24, d, J 2.5 Hz) and NH (d 3.67, dd, J 12.3,
2.5 Hz).
The addition of a single bis(ethoxycarbonyl)methylene unit
[C(CO2Et)2] to [60]fullerene is readily achieved by treatment of
C60 with diethyl bromomalonate under Bingel reaction condi-
tions.1 Sequential Bingel additions have been used to prepare
the corresponding bis- and tris-adducts as mixtures of regio-
isomers.2 The regiochemistry of these reactions however,
improves as the fullerene becomes more substituted, as
exemplified by the regioselective synthesis of C60[C(CO2Et)2]6
with the all-e addition pattern starting from e-e-e-
C60[C(CO2Et)2]3.3 The regioselective formation of bis- through
to hexakis-adducts can now be realized using tethered-directed
remote functionalization.4 Anthracene and 9,10-dimethylan-
thracene have been employed as reversible covalent templates
to regioselectively prepare tetrakis- and hexakis-derivatives
(C60[C(CO2Et)2]n
n
=
4,6).5 Non-tethered bis-adducts
(C60[C(CO2Et)2]2) can be isomerised under carefully controlled
electrochemical conditions to afford predominantly a thermo-
dynamically favoured mixture of bis-adducts (‘walk-on-the-
sphere rearrangements’).6 While one or more of the methano
groups of higher adducts can be removed under reductive
conditions (retro-Bingel reaction), either electrochemically7 or
chemically,8,9 to give less substituted methano[60]fullerenes or
C60 itself. The potential of using a malonate addend as a
reversible directing group or a protecting group of more reactive
double bonds on the fullerene sphere for the synthesis of
functionalised fullerenes has been recently demonstrated.7d,8
Earlier we reported a method for preparing the protected
The 13C NMR spectrum of the fulleryl sp2 region of 2, like
that of C60H[C(NHCHPh2)(CO2But)], revealed a structure
lacking a plane of symmetry due to the newly formed
stereogenic centre at C61. This centre gives rise to diastereo-
topic pairs of fulleryl sp2 carbons that lie either side of the plane
bisecting C1 and C2 of the fullerene sphere. A single set of
fulleryl sp3 resonances at Cc (d 58.9), and Cw (d 67.3) were
observed in addition to resonances corresponding to the addend
Ca (d 70.4), Cb (d 66.3) Cd (d 67.8), Ce (d 66.2), Cf (d 47.5) and
Cg (d 66.5). These carbons were readily assigned from HSQC
and HMBC experiments.
In principle, the product 2 could arise from the anionic
intermediates A or B. The driving force for mono-elimination of
the tether from A or B might be the relief of ring strain upon
expulsion of one arm of the tether. In the case of A, a further
driving force may be the conversion of a fulleryl dianion
intermediate to a thermodynamic more stable fulleryl mono-
anionic system. Clearly the rate of mono-elimination of the
cyclopropane
amino
acid
fullerene
derivative
C60[C(NNCPh2)(CO2 But)] from the reaction C60 and tert-butyl
N-diphenylmethyleneglycinate under Bingel reaction condi-
tions.10 Treatment of this methano[60]fullerene derivative with
sodium cyanoborohydride under protic conditions resulted in
reduction of the C61 imino group and concomitant ring opening
of the cyclopropane ring to give, after a further reduction step
and protonolysis, the novel 1,2-dihydro[60]fullerylglycine
derivative, C60H[C(NHCHPh2)(CO2But)].10 More recently we
have extended this study to the synthesis of the corresponding
tethered trans-4 bismethano[60]fullerene derivative 1.11 Inter-
estingly, the regiochemistry of this tethered reaction was
different to that found using the analogous tethered bismalonate
system. We report here our study on the reductive ring opening
reactions of the bis-adduct 1 and that of its corresponding
untethered diethyl ester analogue 3.
Treatment of a solution of 1 in THF–MeOH at pH 4 with
sodium cyanoborohydride at ambient temperature, as described
by us previously,10 resulted in only recovered starting material.
However, after much experimentation, we discovered that
treatment of a solution of 1 in DCM with 5 equiv. of boron
trifluoride–diethyl ether, initially at 0 °C with warming to rt
over 30 min (presumably to activate the imine by complexation
to the imine nitrogen), followed by the addition of acetonitrile
and 10 equiv. of sodium cyanoborohydride gave, after 90 min,
Scheme 1
DOI: 10.1039/b100655j
Chem. Commun., 2001, 563–564
This journal is © The Royal Society of Chemistry 2001
563

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addend is much faster than the rate of elimination of the entire
addend as indicated by the relative isolated yields of 2 and
C60.
The application of this chemistry to prepare more highly
functionalised fullerenes is in progress. In principle, bis-
cyclopropane imino esters can also function as directing and
protecting groups for the synthesis of more highly function-
alised fullerenes. For example, after the addition of further
addends to the fullerene surface of 1 or 3 the bis-cyclopropane
imino ester group could be then converted, under relatively mild
conditions that would be compatible with a variety of other
functional groups, to the mono-fullerylglycine moiety to give a
variety of novel multifunctionalised fullerenes.
We thank the Australian Research Council for financial
support and for a PhD scholarship to G. A. B.
Notes and references
1 C. Bingel, Chem. Ber., 1993, 126, 1957.
2 A. Hirsch, I. Lamparth and H. R. Karfunkel, Angew. Chem., Int. Ed.
Engl., 1994, 33, 437.
3 A. Hirsch, I. Lamparth and T. Grösser, J. Am. Chem. Soc., 1994, 116,
9385.
To examine the influence of the tether on this ring opening-
retro-Bingel reaction, the diethyl ester 3 was prepared from the
base-catalysed trans-esterification of 1 with ethanol–THF–
sodium carbonate as shown in Scheme 2. Treatment of 3 under
similar reduction conditions to those described for 1 above also
resulted in formation of a ring opened-retro-Bingel product, the
ethyl ester 4. This compound was obtained pure in 51% yield
after column chromatography. A smaller amount of C60 (10%)
was also isolated (Scheme 2). Compound 4 exhibited 1H NMR
and 13C NMR resonances that were almost identical to those of
C60H[C(NHCHPh2)(CO2But)]10 and 2, except for those reso-
nances associated with the different ester groups. The mono-
ester 4 was also prepared in 58% yield from reductive ring
opening of the methano[60]fullerene 5 (Scheme 3). In this case
C60 (12%) and the reduced addend 6 (8%) were also isolated.
The isolation of 6 supports our earlier proposed mechanism for
these ring-opening reactions.10,13
4 F. Diederich and R. Kesinger, Acc. Chem. Res., 1999, 32, 537.
5 (a) I. Lamparth, C. Maichle-Mössmer and A. Hirsch, Angew. Chem., Int.
Ed. Engl., 1995, 34, 1607; (b) R. Schwenninger, T. Müller and B.
Kräutler, J. Am. Chem. Soc., 1997, 119, 9317; (c) X. Camps and A.
Hirsch, J. Chem. Soc., Perkin Trans. 1, 1997, 1595.
6 (a) R. Kessinger, M. Gómez-López, C. Boudon, J.-P. Gisselbrecht, M.
Gross, L. Echegoyen and F. Diederich, J. Am. Chem. Soc., 1998, 120,
8545; (b) L. E. Echegoyen, F. D. Djojo, A. Hirsch and L. Echegoyen,
J. Org. Chem., 2000, 65, 4994.
7 (a) M. Keshavarz-K., B. Knight, R. C. Haddon and F. Wudl,
Tetrahedron, 1996, 52, 5149; (b) R. Kessinger, J. Crassous, A. Herman,
M. Ruttimann, L. Echegoyen and F. Diederich, Angew. Chem., Int. Ed.,
1998, 37, 1919; (c) N. S. Fender, B. Nuber, D. I. Schuster, S. R. Wilson
and L. Echegoyen, J. Chem. Soc., Perkin Trans. 2, 2000, 1924; (d) R.
Kessinger, N. S. Fender, L. E. Echegoyen, C. Thilgen, L. Echegoyen
and F. Diederich, Chem. Eur. J., 2000, 6, 2184.
8 N. N. P. Moonen, C. Thilgen, L. Echegoyen and F. Diederich, Chem.
Commun., 2000, 335.
9 For a related study on other methano[60]fullerenes see: M. W. J. Beulen,
L. Echegoyen, J. A. Rivera, M. A. Herranz, A. Martin-Domenech and N.
Martin, Chem. Commun., 2000, 917.
10 G. A. Burley, P. A. Keller, S. G. Pyne and G. E. Ball, Chem. Commun.,
1998, 2539.
11 G. A. Burley, P. A. Keller, S. G. Pyne and G. E. Ball, Chem. Commun.,
2000, 1717.
12 Synthesis of 2: Boron trifluoride–diethyl ether (0.104 g, 732.80 mmol)
was added dropwise over 1 min to a solution of 111 (0.095 g, 73.19
mmol) in DCM (100 mL) at 0 °C. The reaction mixture was allowed to
warm to rt over a 30 min period when MeCN (50 mL) was added.
Sodium cyanoborohydride (0.046 g, 732.80 mmol) was added to the
reaction mixture which was stirred for 90 min and then concentrated in
vacuo. The reaction mixture was redissolved in chloroform (100 mL)
and washed with saturated ammonium chloride solution (10 mL),
followed by saturated sodium bicarbonate solution (10 mL). The
organic layer was dried (MgSO4) and concentrated in vacuo. Column
chromatography, eluting with DCM–hexane (90:10) provided [60]full-
erene (0.006 g, 12%) and 2 (0.043 g, 42%) as a brown amorphous solid.
UV/vis (DCM) 330 nm (sh, 15000), 435 nm (3000). 1H NMR (CDCl3
CS2 (80+40), 600 MHz): d 3.37 (s, 2H), 3.66 (dd, 1H, J = 12.3, 2.7 Hz),
4.84 (s, 1H), 4.98 (d, 1H, J = 12.3 Hz), 5.07 (s, 2H), 5.24 (d, 1H, J =
11.9 Hz), 5.28 (d, 1H, J = 2.7 Hz), 5.41 (d, 1H, J = 11.9 Hz), 6.84 (s,
1H), 7.19 (t, 2H, J = 7 Hz), 7.23–7.38 (m, 14H), 7.41 (t, 2H, J = 7.9
Hz), 7.47 (t, 2H, J = 7.6 Hz), 7.64 (d, 2H, J = 7.8 Hz), 7.74 (d, 2H, J
= 7.8 Hz). 13C NMR (CDCl3 CS2 (80+40), 125 MHz): d 172.39,
172.31, 154.03, 152.99, 152.17, 151.05, 147.50, 147.20, 147.07, 146.97,
146.43, 146.43, 146.42, 146.38, 146.33, 146.25, 146.19, 146.18, 146.16,
145.88, 145.75, 145.71, 145.58, 145.44, 145.42, 145.35 (2 3 C),
145.31, 145.22, 144.74, 144.68, 144.38, 144.35, 143.17, 143.13, 143.11,
142.63, 142.58, 142.56, 142.43, 142.23, 142.14, 142.09, 142.06, 142.04,
142.01, 141.72, 141.70, 141.54, 141.49, 141.47, 140.39, 140.37, 139.62,
139.23, 137.34, 136.43, 136.32, 136.14, 135.45, 129.32, 129.12, 129.07,
129.04, 128.91, 128.71, 128.04, 127.68, 127.29, 127.26, 70.38, 67.74,
67.32, 66.56, 66.35, 66.09, 58.87, 49.08. MS(ES): m/z 1327 (M + 23),
720 (C60).
Scheme 2
Thus we have demonstrated a general method for reductive
ring opening of [60]fullerenes having a fused cyclopropane
imino ester moiety. Both bis- and monomethano[60]fullerenes
of this type give 1,2-dihydro[60]fullerylglycines, the latter by a
novel tandem reductive ring opening-retro-Bingel reaction. In
light of these results it can be concluded that the presence of the
tether is not the driving force for the mono-elimination of one of
the addends. While C60 is formed in all of these reactions it is
only a minor component and thus the rate of elimination of one
of these addends from the bismethanofullerene derivatives
appears to be higher than the corresponding elimination of both
addends. These results suggest that a dianion like A may be an
intermediate in the tandem reductive ring opening-retro-Bingel
reactions of 1 and 3.
13 The reduced addend was not isolated from the reactions involving 1 and
3 because of the small scales of these reactions.
Scheme 3
564
Chem. Commun., 2001, 563–564