Highly efficient Pauson-Khand reaction with C60: Regioselective synthesis of unprecedented cis-1 biscycloadducts

Article abstract of DOI:10.1039/b402616k

Fullerenes undergo regioselectively and highly efficiently the intramolecular Pauson-Khand reaction to afford a new type of unprecedented structure with three fused pentagonal rings on the same fullerene six-membered ring.

Full text of DOI:10.1039/b402616k

Highly efficient Pauson–Khand reaction with C60: regioselective synthesis
of unprecedented cis-1 biscycloadducts†
Nazario Martín,* Margarita Altable, Salvatore Filippone and Ángel Martín-Domenech
Departamento de Química Orgánica, Facultad de Química, Universidad Complutense, E-28040 Madrid,
Spain. E-mail: nazmar@quim.ucm.es; Fax: 0034 913944103; Tel: 0034 913944227
Received (in Cambridge, UK) 20th February 2004, Accepted 2nd April 2004
First published as an Advance Article on the web 4th May 2004
Fullerenes undergo regioselectively and highly efficiently the
intramolecular Pauson–Khand reaction to afford a new type of
unprecedented structure with three fused pentagonal rings on
the same fullerene six-membered ring.
a strong impact on the d values of the pyrrolidine hydrogen atoms
which are significantly shifted to a lower field [3a (323 K): dCH
=
6.4 (br t, 1H); dCH = 5.71 (d, 2J = 12 Hz, 1H); dCH = 5.55 (d, 2J
= 12 Hz, 1H)] in comparison with fulleropyrrolidine22 [dCH = 4.87
2
(dd, 3J = 7.8, 3J = 4.8 Hz, 1H); dCH = 4.99 (d, 2J = 11.3 Hz, 1H);
The chemistry of fullerenes has undergone a rapid development due
to the pioneering work of several synthetic groups during the last
decade.1 However, sizeable challenging synthetic work remains to
be done. Thus, a variety of important modern organic reactions,
available in the arsenal of alkenes chemistry involving transition
metal catalysts, have never been explored in the related full-
erenes.
Among the most significant reactions involving an alkene in
organic synthesis, the Pauson–Khand (PK) reaction plays an
important role. This formal [2+2+1] metal (mostly cobalt) mediated
carbonylative cycloaddition of an alkene and an alkyne represents
the most versatile method for the preparation of cyclopentenones,
including the asymmetric version leading to enantiopure substi-
tuted cyclopentenones and fulfilling the principle of atom econ-
omy.2
dCH = 4.77 (d, 2J = 11.3 Hz, 1H)2].
2
Compounds 3a–d were further reacted with Co2(CO)8 using
stoichiometric amounts in toluene at 60 °C and in the presence of
molecular sieves (4 Å) previously activated.6 The reaction leads
directly to the formation of the PK products (5a–d) as stable brown
solids in excellent yields (95–98%) without isolation of the
intermediate dicobalt carbonyl clusters (4a–d).7 Further purifica-
tion of compounds 5a–d was accomplished by flash chromatog-
raphy in neutral alumina or neutral silica-gel in order to prevent the
hydrolysis of the amido group.
The intramolecular PK reaction from 3a–d leads regioselectively
to the formation of the respective cis-1 biscycloadducts (5a–d),
thus affording a highly rigid system containing three fused
pentagonal rings.
The structure of the novel compounds was unambiguously
1
Alkenes bearing electron-withdrawing groups are not appro-
priate substrates in PK reactions due to their low reactivity and high
tendency to afford 1,3-dienes by a competitive elimination reaction.
However, during recent years a wide variety of examples of inter-
and intramolecular PK reactions involving electron-withdrawing
substituted alkenes have been reported.3
established by spectroscopic techniques (UV-vis, FTIR, H, 13C
1
NMR, MS). Thus, as a diagnostic signal, the H NMR spectra of
compounds 5a–d show a proton corresponding to the enone moiety
at d ~ 6.8 ppm. The 13C NMR spectra of compounds 5a–d showed
their lack of symmetry as well as the presence of the carbonyl group
at around 202 ppm. The structure of compounds 5a–d was further
and unambiguously confirmed as the cis-1 biscycloadduct, based
on the above spectroscopic data, as well as by HMQC and HMBC
experiments, comparison with UV-vis spectra8 and high resolution
mass spectroscopy (see supporting information).
Formation of compounds 5a–d reveals that fullerene double
bonds are reactive enough to undergo the highly versatile PK
reaction.
In order to compare the reactivity of the fullerene moiety with
that of an olefinic double bond, we have carried out the synthesis of
compound 6 endowed simultaneously with reactive alkynyl and
In this communication we describe the first PK reaction on the
C
60 molecule affording regioselectively unprecedented cis-1 biscy-
cloadducts. Our first attempts of intermolecular PK reaction with
the parent [60]fullerene and different alkynes in the presence of
Co2(CO)8 were unsuccessful. Therefore, we carried out the design
of novel fullerene derivatives (3a–d, 6) endowed with a 1,6-enyne
moiety involving a fullerene double bond as suitable candidates to
undergo the PK reaction. A further advantage of the fullerene core
is the absence of hydrogen atoms on the C60 surface, thus
preventing the competitive b-hydride elimination process.
The synthesis of the C60-based enyne 2 was carried out by
1,3-cycloaddition reaction of the azomethyne ylide, generated in
situ from DL-propargylglycine 1 and formaldehyde, to C60 in
refluxing o-dichlorobenzene by following Prato’s procedure
(Scheme 1).4 Compound 2 is endowed with a pyrrolidine amino
group able to undergo acylation reactions with acyl chlorides to
form more soluble N-acylfulleropyrrolidines (3a–d) which were
obtained in excellent yields (90–95%, see supplementary in-
formation).
Compounds 2 and 3a–d showed in the 1H NMR spectra the
expected alkynyl protons at around 2.2 and 2.4 ppm, respectively.
However, while fulleropyrrolidine 2 showed a well-resolved set of
signals for the pyrrolidine protons, non-resolved broad signals were
observed for N-acylfulleropyrrolidines 3a–d at room temperature.
1H NMR experiments at different temperatures showed that a good
resolution of 3a was observed when increasing the temperature at
323 K (see supporting information). This dynamic behaviour can be
accounted for by the rotational barrier of the acyl group linked to
the nitrogen atom.5 Furthermore, the presence of the acyl group has
† Electronic supplementary information (ESI) available: experimental
section. See http://www.rsc.org/suppdata/cc/b4/b402616k/
Scheme 1
1338
C h e m . C o m m u n . , 2 0 0 4 , 1 3 3 8 – 1 3 3 9
T h i s j o u r n a l i s © T h e R o y a l S o c i e t y o f C h e m i s t r y 2 0 0 4

allyl systems. The synthesis of 6 was carried out in moderate yield
from fulleropyrrolidine 2 by alkylation reaction with allyl bromide
under basic conditions (Scheme 2).
cyclization yields, in addition to the chiral center on the
fulleropyrrolidine ring, four new chiral carbons on the fullerene
surface with a well-defined stereochemistry.
Further reaction of 6 under the same conditions [Co2(CO)8,
molecular sieves, toluene, 60 °C] afforded a mixture of compounds
(7 and 8) resulting from the PK reaction on the fullerene double
bond and the allyl group, respectively. The reaction was highly
efficient, leading to compounds 7 and 8 with the same yield (41%),
thus revealing the high reactivity of the fullerene core in the
intramolecular PK reaction.
Compound 7 showed in the 1H NMR spectrum the vinyl proton
of the cyclopentenone ring at d 6.81 ppm. This proton was coupled
with the Csp2 at 126.5 ppm in the HMQC experiment, and with the
Csp2 at 184.1 ppm, the carbonyl carbon at 202.2 ppm and a
fullerene Csp3 at ~ 70 ppm in the HMBC experiments. As
expected, the signals of the olefinic protons of the unreacted allyl
moiety are observed at d 6.15 (m, –CHN), 5.48 (m, NCH2) and 5.36
(m, NCH2). In contrast, these allyl protons are not present in the 1H
NMR spectrum of 8 which shows the vinyl proton of the
cyclopentenone ring as a singlet at d 6.19 ppm. HMQC and HMBC
experiments unambiguously confirmed the proposed structures (see
supporting information).
It is worth mentioning that the competitive PK reaction to form
the analogue to 8 from 3d was not observed. In this case, the
presence of the carbonyl and phenyl groups linked to the double
bond strongly prevent this reaction, thus accounting for the sole
formation of compound 5d.
Cis-1 biscycloadducts 5a–d and 7 are, to the best of our
knowledge, the first example of three fused pentagonal rings on the
same hexagonal ring of the fullerene core. These compounds are
obtained as a mixture of enantiomers provided that the PK
In summary, we report for the first time a new [2+2+1]
cycloaddition reaction on the fullerene core which regioselectively
affords a new type of cis-1 biscycloadducts with three fused
pentagonal rings. This new reaction opens the way for compounds
bearing a larger number of fused rings on the fullerene surface with
interest in fields such as materials science or biological applica-
tions. In addition, this new reactivity of fullerenes should promote
research with other transition metal catalysts affording a new
avenue in the chemistry of fullerenes. This study is currently under
investigation in our laboratory.
Financial support by the MCyT of Spain (Project BQU2002-
00855) is gratefully acknowledged. We thank the CAIs of the UCM
and Dr M. Witt from Bruker Daltonics for the accurate mass
spectra. S. F. thanks CAM for a postdoctoral contract and M. A.
thanks MCyT for a research grant.
Notes and references
1 (a) A. Hirsch, The Chemistry of Fullerenes, Thieme, New York, 1994; (b)
F. Diederich and C. Thilgen, Science, 1996, 271, 317–323; (c) R. Taylor,
Lecture Notes on Fullerene Chemistry. A Handbook for Chemists,
Imperial College Press, London, 1999; (d) A. Hirsch, Ed.; Fullerenes and
Related Structures, Topics in Current Chemistry, Springer, Berlin, 1998,
vol. 199; (e) D. M. Guldi and N. Martín, Eds.; Fullerenes: From Synthesis
to Optoelectronic Properties, Kluwer Academic Publishers, Dordrecht,
2002.
2 For recent reviews on the PK reaction, see: (a) A. J. Fletcher and S. D. R.
Christie, J. Chem. Soc., Perkin Trans. 1, 2000, 1657–1668; (b) K. M.
Brummond and J. L. Kent, Tetrahedron, 2000, 56, 3263–3283; (c) T.
Sugihara, M. Tamaguchi and M. Nishizawa, Chem. Eur. J., 2001, 7,
3315–3318; (d) S. E. Gibson and A. Stevenazzi, Angew. Chem., Int. Ed.,
2003, 42, 1800–1810; (e) J. Blanco-Urgoiti, L. Añorbe, L. Pérez-Serrano,
G. Domínguez and J. Pérez-Castells, Chem. Soc. Rev., 2004, 33,
32–42.
3 For a recent review, see: M. R. Rivero, J. Adrio and J. C. Carretero, Eur.
J. Org. Chem., 2002, 2881–2889.
4 M. Prato and M. Maggini, Acc. Chem. Res., 1998, 31, 519–526.
5 A. Bagno, S. Claeson, M. Maggini, M. L. Martini, M. Prato and G.
Scorrano, Chem. Eur. J., 2002, 8, 1015–1023.
6 (a) L. Pérez-Serrano, L. Casarrubios, G. Domínguez and J. Pérez-
Castells, Org. Lett., 1999, 8, 1187–1188; (b) J. Blanco-Urgoiti, L.
Casarrubios, G. Domínguez and J. Pérez-Castells, Tetrahedron Lett.,
2002, 43, 5763–5765. It is worth mentioning that the PK reaction also
proceeds in the absence of molecular sieves although in a lower yield.
7 Acetylene-linked di-cobalt and tetra-cobalt carbonyl clusters covalently
connected to the C60 have also been reported by S. M. Draper, M.
Delamesiere, E. Champeil, B. Twamley, J. J. Byrne and C. J. Long, J.
Organomet. Chem., 1999, 589, 157–167. It is important to note that
isolation of the intermediate dicobalt carbonyl complexes can be
achieved by carrying out the reaction at room temperature. Thus,
intermediate 4a (FTIR (KBr): n = 2922, 2050, 2017, 1647, 518 cm21
)
was isolated in 75% yield after flash chromatography.
8 (a) K. Kordatos, S. Bosi, T. Da Ros, A. Zambon, V. Lucchini and M.
Prato, J. Org. Chem., 2001, 66, 2802–2808; (b) Y. Nakamura, N. Takano,
T. Nishimura, E. Yashima, M. Sato and T. Kudo, Org. Lett., 2001, 3,
1193–1196.
Scheme 2
C h e m . C o m m u n . , 2 0 0 4 , 1 3 3 8 – 1 3 3 9
1339
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