Synthesis of a triaza analogue of crushed-fullerene by intramolecular palladium-catalyzed arylation

Article abstract of DOI:10.1021/ol048760s

(Equation Presented) Alkylation and intramolecular palladium-catalyzed arylation allows for the ready synthesis of C₅₇H₃₃N ₃ from symmetrical triindole, a triaza analogue of truxene.

Full text of DOI:10.1021/ol048760s

ORGANIC
LETTERS
2004
Vol. 6, No. 17
2993-2996
Synthesis of a Triaza Analogue of
Crushed-Fullerene by Intramolecular
Palladium-Catalyzed Arylation
,†
,‡
Berta Go´mez-Lor* and Antonio M. Echavarren*
Instituto de Ciencia de Materiales de Madrid, CSIC, Departamento de Qu´ımica
Orga´nica, UniVersidad Auto´noma de Madrid (UAM), Cantoblanco,
28049 Madrid, and Institute of Chemical Research of Catalonia (ICIQ),
43007 Tarragona, Spain
bgl@icmm.csic.es; aechaVarren@iciq.es
Received June 30, 2004
ABSTRACT
Alkylation and intramolecular palladium-catalyzed arylation allows for the ready synthesis of C H N from symmetrical triindole, a triaza
57 33
3
analogue of truxene.
Azafullerenes have attracted much interest.1 Theoretical
studies have predicted several stable C60-2nN2n structures,2
whose detection has been reported under different condi-
tions.3,4 Wudl and Hirsch attempted independently the
synthesis of azafullerene C59N starting from different azide
adducts of C60.5,6 The substitution of one carbon atom of
the fullerene framework with nitrogen leads to a reactive
C59N radical that has been detected in MS experiments and
that can only be isolated as the dimer (C59N)2.6,7 The
corresponding cation, C59N+, has been detected by fragmen-
tation of suitable precursors.6,8 Salts of the cation9,10 and the
anion5,11 have been isolated. Several monomeric substituted
azafullerenes have also been obtained.12 However, no
azafullerene has yet been synthesized from a nonfullerene
† Instituto de Ciencia de Materiales de Madrid.
‡ Institute of Chemical Research of Catalonia (ICIQ) and UAM.
(1) Hummelen, J. C.; Bellavia-Lund, C.; Wudl, F. Top. Curr. Chem. 1999,
199, 93-134.
(6) (a) Lamparth, I.; Nuber, B.; Schick, G.; Skiebe, A.; Gro¨sser, T.;
Hirsch, A. Angew. Chem., Int. Ed. Engl. 1995, 34, 2257-2259. (b) Nuber,
B.; Hirsch, A. Chem. Commun. 1996, 1421-1422.
(7) Lee, K. H.; Park, S. S.; Suh, Y.; Yamabe, T.; Osawa, E.; Luthi, H.
P.; Gutta, P.; Lee, C. J. Am. Chem. Soc. 2001, 123, 11085-11086.
(8) Clipston, N. L.; Brown, T.; Vasil’ev, Y. Y.; Barrow, M. P.;
Herzschuh, R.; Reuther, U.; Hirsch, A.; Drewello, T. J. Phys. Chem. A
2000, 104, 9171-9179.
(9) Kim, K.-C.; Hauke, F.; Hirsch, A.; Boyd, P. D. W.; Carter, E.;
Armstrong, R. S.; Lay, P. A.; Reed, C. A. J. Am. Chem. Soc. 2003, 125,
4024-4025.
(10) Vougioukalakis, G. C.; Chronakis, N.; Orfanopoulos, M. Org. Lett.
2003, 5, 4603-4606.
(2) (a) Stafstro¨m, S.; Hultman, L.; Hellgren, N. Chem. Phys. Lett. 2001,
340, 227-231. (b) Manaa, M. R.; Sprenh, D. W.; Ichord, H. A. J. Am.
Chem. Soc. 2002, 124, 13990-13991.
(3) Hultman, L.; Stafstro¨m, S.; Cziga´ny, Z.; Neidhardt, J.; Hellgren, N.
M.; Brunell, I. F.; Suenaga, K.; Colliex, C. Phys. ReV. Lett. 2001, 87,
225503.
(4) Glenis, S.; Cooke, S.; Chen, X.; Labes, M. N. Chem. Mater. 1994,
6, 1850-1853.
(5) Hummelen, J. C.; Knight, B.; Pavlovich, J.; Gonza´lez, R.; Wudl, F.
Science 1995, 269, 1554-1556.
10.1021/ol048760s CCC: $27.50 © 2004 American Chemical Society
Published on Web 07/24/2004

precursor where more than one carbon atom is replaced by
nitrogen atoms. An attempt toward a rational synthesis of
diazafullerene has been reported by Tobe. In this approach,
a pyridinophane was synthesized as a precursor to C58N2,
whose anion C58N2 was detected in a LD-TOF mass
experiment.13
We report the ready synthesis of 3 (C57H33N3), the neutral
precursor of 1, by a triple palladium-catalyzed intramolecular
arylation, as well as lower analogues. We also address the
issue of the regioselectivity of this reaction, which could shed
light on the mechanism of this palladium-catalyzed C-H
functionalization process.17
-
Scheme 1
Figure 1.
We have previously found that the arylation reaction on
nitrofluorene 4 gives a 2:1 ratio of nitrofluorenes 5a,b
(Scheme 2).18 This low selectivity is difficult to reconcile
with a palladation proceeding by an electrophilic aromatic
substitution and was alternatively interpreted as due to the
Scheme 2
We have previously completed a synthesis of tribenzol:
l′:l′′benzo1,2-e:3,4-e′:5,6-e′′triacephenanthrylene (C60H30) by
using a palladium-catalyzed intramolecular arylation reaction
in the key step;14 C60H30 suffers by multiple intramolecular
cyclodehydrogenation reactions in LDI-TOF-MS.15 We
decided to apply the palladium-catalyzed intramolecular
arylation approach16 to the synthesis of a tricationic 1. This
3+
cationic species could form triazafullerene C57N3 (2)
(triaza60fulleronium) by pyrolysis or under the conditions
of LDI-TOF-MS by formal 15-fold H2 losses (Scheme 1).
(11) Prassides, K.; Keshavarz-K., M.; Hummelen, J. C.; Andreoni, W.;
Giannozzi, P.; Beer, E.; Bellavia, C.; Cristofolini, L.; Gonza´lez, R.; Lappas,
A.; Murata, Y.; Malecki, M.; Srdanov, V.; Wudl, F. Science 1996, 271,
1833-1835.
(12) Hauke, F.; Hirsch, A. Tetrahedron 2001, 57, 3697-3708.
(13) Tobe, Y.; Nakanishi, H.; Sonoda, M.; Tomonari, W.; Achiba, Y.
Chem. Commun. 1999, 1625-1626.
(14) (a) Go´mez-Lor, B.; de Frutos, OÄ .; Echavarren. A. M. Chem.
Commun. 1999, 2431-2432. (b) Go´mez-Lor, B.; Gonza´lez-Cantalapiedra,
E.; Ruiz, M.; de Frutos, OÄ .; Ca´rdenas, D. J.; Santos, A.; Echavarren, A. M.
Chem. Eur. J. 2004, 10, 2601-2608.
(15) (a) Go´mez-Lor, B.; Koper, C.; Fokkens, R. H.; Vlietstra, E. J.; Cleij,
T. J.; Jenneskens, L. W.; Nibbering N. M. M.; Echavarren, A. M. Chem.
Commun. 2002, 370-371. (b) Boorum, M. M.; Vasil′ev, Y. V.; Drewello,
T.; Scott, L. T. Science 2001, 294, 828-831.
(16) Echavarren, A. M.; Go´mez-Lor, B.; Gonza´lez, J. J.; de Frutos, OÄ .
Synlett 2003, 585-597.
2994
Org. Lett., Vol. 6, No. 17, 2004

Scheme 3
steric effect of the nitro group. We decided to try the
conditions, whereas 9-[(2-bromophenyl)methyl]fluorene gives
fully aromatic benzo[e]acephenanthrylene in the palladium-
catalyzed intramolecular arylation.18
intramolecular arylation on carbazole 8,19 a more appropriate
substrate for the analysis of the effect of the nitro group.
First, the arylation reaction was assayed on simple N-[(2-
bromophenyl)methyl]carbazole (6). Reaction of 6 with
Pd(OAc)2 (15 mol %) as the catalyst in DMF, in the presence
of K2CO3 as the base and BnMe3NBr as a bromide source,
gave 9H-indolo(3,2,1-de)phenanthridine (8H-7b-aza-benzo-
[e]acephenanthrylene) 720 in quantitative yield. It is interest-
ing to note that no benzylic oxidation of 7 occurs under these
Under conditions similar to those used in the cyclization
of 6, carbazole 8 gave a mixture of two arylated derivatives
along with the corresponding lactames resulting from ben-
zylic oxidation. To quantify the regioisomeric mixture, the
crude product was directly treated with MnO2 in CH2Cl2 at
room temperature to give a 1.2:1 mixture of 9H-indolo[3,2,1-
de]phenanthridin-9-ones 9a,b in 68% overall yield. Although
the major regiosiomer is the one resulting from arylation at
the unsubstituted arene ring,21 a substantial amount of product
(17) In this context, the term “C-H functionalization” is preferred to
“C-H activation”: Sezen, B.; Sames, D. J. Am. Chem. Soc. 2003, 125,
10580-10585.
(18) Gonza´lez, J. J.; Garc´ıa, N.; Go´mez-Lor, B.; Echavarren, A. M. J.
Org. Chem. 1997, 62, 1286-1291.
(20) Gosh, S.; Data, D. B.; Data, I.; Das, T. K. Tetrahedron 1989, 45,
3775-3787.
(19) Derivative 8 was prepared by N-alkylation of 4-nitro-9H-carbazole
with 1-bromo-2-(bromomethyl)benzene. Synthesis of 4-nitro-9H-carbazole:
(a) Moslakev, N.; Barbasiewicz, M.; Makosza, M. Tetrahedron 2004, 60,
347-358. (b) Barclay, B. M.; Campbell, N. J. Chem. Soc. 1945, 530-533.
(21) The regiochemical assignment for 9a and 9b is supported by COSY
and HMBC spectra of 9a and by comparison of the 1H NMR spectra with
that of unsubstituted 9H-indolo[3,2,1-de]phenanthridin-9-one. See Support-
ing Information for details.
Org. Lett., Vol. 6, No. 17, 2004
2995

is formed by reaction at the position para to a nitro group.
This low sensitivity to the effect of such a strong electron-
withdrawing group raises additional doubts on the proposal
of a conventional electrophilic aromatic substitution mech-
anism for this reaction.
compounds 3, 7, and 13 suffer oxidation by oxygen at the
methylenes to give the corresponding lactames and must be
kept under Ar.
Taking advantage of the presence of six bromo substituents
in 10, palladium-catalyzed functionalization could provide
a variety of hexasubstituted derivatives with C3h symmetry.
Thus, for example,24 N-benzylation of 11 in (DMF, rt, 16 h)
provided 15 in 91% yield, which was coupled with phenyl-
boronic acid to give 16 (74%), displaying nine phenyl groups
surrounding a triindole nucleus.
The synthesis of 13, a lower analogue of 3, was carried
out from known symmetrical hexabromotriindole 10, which
is readily available by reaction of indole with Br222 (Scheme
3). Reductive debromination of 10 with triethylammonium
formate and Pd/C yielded 11 (95%). This preparation of
symmetrical triindole 11 is more convenient than that
previously reported based on the acid-catalyzed reaction
between indole and 3-bromoindole, which furnishes a
complex mixture of indole dimers and trimers from which
11 could be only obtained in low yield.23 N-Alkylation with
1-bromo-2-(bromomethyl)benzene gave 12 (93%), which
under the conditions of the palladium-catalyzed intra-
molecular arylation gave 13 in 73% yield as a white powder
insoluble in all NMR solvents. When the reaction was
performed in N,N-dimethylacetamide with Cs2CO3 as base,
partially oxidized 13 was obtained. On the other hand,
palladium-catalyzed reaction of the triamide analogue of 12,
prepared by reaction of 11 with o-bromobenzoyl chloride in
44% yield, failed to provide the desired arylation derivative.
The synthesis of 3 (C57N3H33) was similarly carried out
in two steps from triindole 11 (Scheme 3). Alkylation of 11
with 1-bromo-2-bromomethylnaphthalene gave 14 (92%),
which underwent a triple palladium-catalyzed arylation under
the standard conditions to give 3 in 64% yield as a yellow
powder. In contrast with 13, 3 is soluble in CDCl3 and
acetone-d6, although a well-resolved 1H NMR spectrum was
best obtained in 1,1,2,2-tetrachloroethane-d2 at 100 °C. Solid
In summary, we have shown that now readily available
symmetrical triindole 11 can be used for the ready construc-
tion of large triazapolyarenes such as 3 based on the
intramolecular palladium-catalyzed arylation reaction. Tri-
indole 11 is a triaza analogue of truxene, a useful scaffold
for the synthesis of complex polyarenes.14,16 The nonselective
arylation on carbazole 8 is not consistent with an electrophilic
aromatic substitution reaction for this process. Substitution
at the periphery of triindole 11 can also be carried out by
palladium-catalyzed coupling reactions. Work along these
lines is underway for the synthesis of related systems.
Acknowledgment. This work was supported by the
MCyT (BQU2001-0193), the CAM (Projects 07N/0047/2002
and 07N/0085/2002), and the ICIQ Foundation. We also
acknowledge Johnson Matthey PLC for a loan of Pd salts.
Supporting Information Available: Experimental pro-
cedures and characterization data. This material is available
free of charge via the Internet at http://pubs.acs.org.
OL048760S
(22) Robertson, N.; Parsons, S.; MacLean, E. J.; Coxall, R. A.; Mount,
A. R. J. Mater. Chem. 2000, 10, 2043-2047.
(23) Bocchi, V.; Palla, G. Tetrahedron 1986, 42, 5019-5024.
(24) Reductive deuteriodebromination of hexabromotriindole 11 with
formic acid-d2 and Et3N afforded 11-d6 in 88% yield.
2996
Org. Lett., Vol. 6, No. 17, 2004