Stereoselective cyclotrimerization of enantiopure iodonorbornenes catalyzed by Pd nanoclusters for C 3 or C 3 v symmetric syntris(norborneno)benzenes

Article abstract of DOI:10.1021/jo100710h

(Figure presented) C₃ or C_3v symmetric enantiopure syn-tris(norborneno)benzenes with various functional groups were synthesized through Pd-catalyzed cyclotrimerization of enantiopure iodonorbornenes. The generality of Pd-catalyzed cyclotrimerization for syn-tris(norborneno)benzenes were well-demonstrated.

Full text of DOI:10.1021/jo100710h

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SCHEME 1. Pd-Catalyzed Cyclotrimerization of Enantiopure
Iodonorbornenes
Stereoselective Cyclotrimerization of Enantiopure
Iodonorbornenes Catalyzed by Pd Nanoclusters for
C3 or C3v Symmetric syn-Tris(norborneno)benzenes
Shuhei Higashibayashi,† A. F. G. Masud Reza,† and
Hidehiro Sakurai*,†,‡
†Research Center for Molecular Scale Nanoscience, Institute
for Molecular Science, 5-1 Higashiyama, Myodaiji, Okazaki
444-8787, Japan, and ‡PRESTO, Japan Science and
Technology Agency, Tokyo 102-0075, Japan
hsakurai@ims.ac.jp
Received April 13, 2010
through cyclotrimerization of norbornene derivatives, where
both desired syn- and undesired anti-isomers are generally
obtained.3,4 In most of the reported examples such as
Cu-mediated or Pd-catalyzed cyclotrimerization, undesired
anti-isomers were obtained as a major product. Given such
background, one of the important issues in this area is the
development of a general method for selective formation of syn-
tris(norborneno)benzenes. We have recently reported Pd-cata-
lyzed cyclotrimerization of enantiopure iodonorbornenes to
prepare C3 symmetric enantiopure syn-tris(norborneno)ben-
zenes under Pd-nanocluster conditions (Scheme 1).5 In this
paper, we report the applicability of this Pd-catalyzed cyclotri-
merization reaction to prepare C3 or C3v symmetric syn-tris-
(norborneno)benzenes with various functional groups.
C3 or C3v symmetric enantiopure syn-tris(norborneno)ben-
zenes with various functional groups were synthesized
through Pd-catalyzed cyclotrimerization of enantiopure
iodonorbornenes. The generality of Pd-catalyzed cyclotri-
merization for syn-tris(norborneno)benzenes were well-
demonstrated.
Standard reaction conditions for Pd-catalyzed cyclotri-
merization of enantiopure iodonorbornenes are shown
in Scheme 1. 5 mol % of Pd(OAc)2, 10 mol % of PPh3,
1000 mol % of Bu4NOAc, 1000 mol % of Na2CO3, and
molecular sieves 4 A were suspended in 1,4-dioxane. The
(3) (a) Gasman, P. G.; Gennick, I. J. Am. Chem. Soc. 1980, 102, 6864.
(b) Durr, R.; De Lucchi, O.; Cossu, S.; Lucchini, V. Chem. Commun. 1996, 2447.
(c) Paulon, A.; Cossu, S.; De Lucchi, O.; Zonta, C. Chem. Commun. 2000,
1837. (d) Yan, Z.; McCracken, T.; Xia, S.; Maslak, V.; Gallucci, J.; Hadad,
C. M.; Badjic, J. D. J. Org. Chem. 2008, 73, 355. Cu-mediated cyclotrimer-
ization: (e) Sergio, R. D.; Lucchini, C. V.; De Lucchi, O. Angew. Chem., Int.
Ed. 1997, 36, 2805. (f) Zonta, C.; Cossu, S.; Peluso, P.; De Lucchi, O.
Tetrahedron Lett. 1999, 40, 8185. (g) Cossu, S.; Cimenti, C.; Peluso, P.;
Paulon, A.; De Lucchi, O. Angew. Chem., Int. Ed. 2001, 40, 4086. (h) Borsato,
G.; De Lucchi, O.; Fabris, F.; Groppo, L.; Lucchini, V.; Zambon, A. J. Org.
Chem. 2002, 67, 7894. (i) Borsato, G.; De Lucchi, O.; Fabris, F.; Lucchini, V.;
Pasqualotti, M.; Zambon, A. Tetrahedron Lett. 2003, 44, 561. (j) Fabris, F.;
Zambrini, L.; Rosso, E.; De Lucchi, O. Eur. J. Org. Chem. 2004, 3313. (k) De
Lucchi, O.; Dastan, A.; Fabris, F.; Balci, M. Helv. Chim. Acta 2004, 87, 2364.
(l) Dastan, A.; Uzundumlu, E.; Balci, M.; Fabris, F.; De Lucchi, O. Eur. J.
Org. Chem. 2004, 183. (m) Zonta, C.; Fabris, F.; De Lucchi, O. Org. Lett.
2005, 7, 1003. (n) Borsato, G.; Brussolo, S.; Crisma, M.; De Lucchi, O.;
Lucchini, V.; Zambon, A. Synlett 2005, 1125. (o) Fabris, F.; Pellizzaro, L.;
Zonta, C.; De Lucchi, O. Eur. J. Org. Chem. 2007, 283. (p) Rieth, S.; Yan, Z.;
Xia, S.; Gardlik, M.; Chow, A.; Fraenkel, G.; Hadad, C. M.; Badjic, J. D.
syn-Tris(norborneno)benzenes have been recently utilized
as synthetic intermediates for syntheses of C3 or C3v symmetric
buckybowls1 or as cup- or basket-shaped host molecules to
encapsulate guest molecules.2 According to these recent appli-
cations, syn-tris(norborneno)benzenes with a variety of func-
tional groups are recognized as molecules for new materials or
their precursors. syn-Tris(norborneno)benzenes are prepared
(1) (a) Sakurai, H.; Daiko, T.; Hirao, T. Science 2003, 301, 1878.
(b) Higashibayashi, S.; Sakurai, H. J. Am. Chem. Soc. 2008, 130, 8592.
(2) (a) Zonta, C.; Cossu, S.; De Lucchi, O. Eur. J. Org. Chem. 2000, 1965.
(b) Maslak, V.; Yan, Z.; Xia, S.; Gallucci, J.; Hadad, C. H.; Badjic, J. D.
J. Am. Chem. Soc. 2006, 128, 5887. (c) Fabris, F.; Pellizzaro, L.; Zonta, C.;
De Lucchi, O. Eur. J. Org. Chem. 2007, 283. (d) Scarso, A.; Pellizzaro, L.;
De Lucchi, O.; Linden, A.; Fabris, F. Angew. Chem., Int. Ed. 2007, 46, 4972.
(e) Yan, Z.; Xia, S.; Gardlik, M.; Seo, W.; Maslak, V.; Gallucci, J.; Hadad,
C. M.; Badjic, J. D. Org. Lett. 2007, 9, 2301. (f) Rieth, S.; Yan, Z.; Xia, S.;
Gardlik, M.; Chow, A.; Fraenkel, G.; Hadad, C. M.; Badjic, J. D. J. Org.
Chem. 2008, 73, 5100. (g) Wang, B.-Y.; Bao, X.; Yan, Z.; Maslak, V.; Hadad,
C. M.; Badjic, J. D. J. Am. Chem. Soc. 2008, 130, 15127. (h) Wang, B.-Y.;
Bao, X.; Stojanovic, S.; Hadad, C. M.; Badjic, J. D. Org. Lett. 2008, 10, 5361.
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De Lucchi, O. Org. Lett. 2009, 11, 3926.
€
J. Org. Chem. 2008, 73, 5100. (q) Dalkꢀılꢀıc-, E.; Guney, M.; Dastan, A.;
Saracoglu, N.; De Lucchi, O.; Fabris, F. Tetrahedron Lett. 2009, 50, 1989.
See also ref 1a.
(4) Pd-catalyzed cyclotrimerization of halonorbornenes: (a) Cossu, S.;
De Lucchi, O.; Paulon, A.; Peluso, P.; Zonta, C. Tetrahedron Lett. 2001, 42,
3515. (b) Zambrini, L.; Fabris, F.; De Lucchi, O.; Gardenal, G.; Visentin, F.;
Canovese, L. Tetrahedron 2001, 57, 8719.
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4626 J. Org. Chem. 2010, 75, 4626–4628
Published on Web 06/10/2010
DOI: 10.1021/jo100710h
r
2010 American Chemical Society

Higashibayashi et al.
JOCNote
the preparation of 11 as previously reported.5b Pure iodonor-
bornene derivatives are prepared by treatment with t-BuOK
from a mixture of gem- diiodonorbornane and iodonorbornene
in other cases (see the Supporting Information). However,
treatment of 6 and 7 by such a strong base causes epimerization
of the R-position of the alkoxycarbonyl group. Direct utility of a
mixture of gem-diiodonorbornane and iodonorbornene for this
cyclotrimerization is advantageous for base-sensitive substrates.
Thus-prepared syn-tris(norborneno)benzenes 10-13 are all C3
symmetric enantiopure compounds.
Use of an enantiopure iodonorbornene is valuable even for
preparation of C3v symmetric syn-tris(norborneno)benzenes
since cyclotrimerization of racemic iodonorbornenes could pre-
fer anti-isomer formation.4a As expected, cyclotrimerization of 8
afforded syn-14 as a major product in 60% yield (syn/anti =
78:22).7 The syn-selectivity of 14 is lower than those of C3
symmetric ones. To check the stereoselectivity, the reaction of
nonsubstituted iodonorbornene 9 was also investigated to give
similar syn/anti = 77:23 ratio in 26% yield.7
FIGURE 1. Enantiopure iodonorbornenes.
Desired syn-isomers were obtained as a major product in
every example as expected. Observed syn/anti selectivity caused
by substituents ranges from 100:0 to 77:23. As a general trend,
higher syn-selectivity is observed for C3 symmetric tris(nor-
borneno)benzenes than C3v symmetric ones. Judging from the
difference on the selectivity between the C3 and C3v symmetric
compounds as well as the substituents effect, symmetrical
palladacycle species, which derive from a dimer of iodonorbor-
nenes, could be generated as the intermediate in the side reaction
pathway for anti-isomers.8 Although the formation of anti-
isomer is undesired, it will help us to elucidate the reaction
mechanism of cyclotrimerization.
As described above, Pd-catalyzed cyclotrimerization of
enantiopure iodonorbornens were generally applied to pre-
paration of C3 or C3v symmetric syn-tris(norborneno)ben-
zenes with various functional groups. The thus-obtained syn-
tris(norborneno)benzenes possess amenable functional groups
to prepare derivatives. They can be applied as synthetic inter-
mediates to the synthesis of C3- or C3v-symmetric buckybowls
as well as cup-shaped molecules.
FIGURE 2. Yield and syn/anti ratio of tris(norborneno)benzenes.
aRatio after conversion to 11. b1H NMR ratio.
mixture was heated at 100 °C for a few minutes, which gene-
rates small size of Pd-nanoclusters (∼3.5 nm).5 An enantiopure
iodonorbornene was added, and the reaction mixture was
stirred at 100 °C for 2-3 h. Cyclotrimerization of enantiopure
iodonorbornenes shown in Figure 1 were examined. The
obtained syn-tris(norborneno)benzenes and their yield (syn/
anti) are summarized in Figure 2. In the case of cyclotrimer-
ization of 1 (PMB = p-methoxybenzyl), syn-isomer 10 was
obtained in 57% yield exclusively without formation of the
anti-isomer. Although cyclotrimerization of 2, 3, 6þ 7, 8, and9
afforded mixtures of syn- and anti-isomers, syn-isomers were
obtained as the major products with high syn-selectivity.
Cyclotrimerization of 2 with a carbonyl group afforded 11 in
49% yield with a syn/anti = 95:5 ratio.6 Similarly, 12 was
synthesized by cyclotrimerization of 3 with a TBS ether
(TBS=t-BuMe2Si) at the exo position in 53% yield with a
syn/anti = 90:10 ratio.6 On the other hand, cyclotrimerization
of 4 with a TBS ether at the endo position resulted in a complex
mixture without formation of tris(norborneno)benzene. We
have previously reported that iodonobornenes 5do not undergo
cyclotrimerization, either.5b These results suggest that a sub-
stituent at the endo position in norbornene skeleton prevents
cyclotrimerization.5b A mixture of gem-diiodonorbornane 6
and iodonorbornene 7 can be directly subjected to cyclotrimer-
ization to afford 13 in 32% yield (syn/anti = 89:11), similarly to
Experimental Section
Representative Procedure of Pd-Catalyzed Cyclotrimeriza-
tion. A suspension of Pd(OAc)2 (11.3 mg, 0.050 mmol), PPh3
(26.2 mg, 0.10 mmol), Bu4NOAc (3.0 g, 10.0 mmol), Na2CO3
(1.1 g, 10.0 mmol), and molecular sieves 4 A (293 mg) in 1,4-
dioxane (15 mL) was heated at 100 °C for a few minutes under
argon atmosphere. After the color of the solution changed to
black, a solution of 8 (293 mg, 1.00 mmol) in 1,4-dioxane (5 mL)
was quickly added to the solution at 100 °C. After being stirred
for 2 h, the reaction mixture was cooled to ambient temperature.
The reaction mixture was filtered through Celite, and the filter
cake was washed with t-BuOMe/hexane(1:1). After evaporation
of solvent, the residue was dissolved in t-BuOMe/hexane (1:1,
10 mL), and CH3CO2H (1.2 mL) was added. The organic layer
was washed with ethylene glycol/water (1:2, 10 mL ꢀ 3), water
(10 mL ꢀ 3), and brine, dried over Na2SO4, filtered through
Celite, and evaporated. The crude product was purified by silica
gel column chromatography (10-20% EtOAc/hexane) to give a
(7) Synthesis of 14 and 15 by Cu-mediated cyclotrimerization was re-
ported in refs 3h (98%, syn/anti = 1:4) and 3e (100%, syn/anti = 1:3),
respectively.
(8) (a) Catellani, M. Synlett 2003, 298. (b) Catellani, M.; Motti, E.; Della Ca,
N. Acc. Chem. Res. 2008, 41, 1512 and references cited therein.
(6) We have previously reported that only syn-11 or syn-12 was formed by
the cyclotrimerizations (see ref 5). Thorough scrutiny revealed that the minor
anti-isomer was a contaminant in the product.
J. Org. Chem. Vol. 75, No. 13, 2010 4627

Higashibayashi et al.
JOCNote
mixture of syn- and anti-14. The mixture was separated by GPC
(gel permeation chromatography) to give syn-14 (77.1 mg, 47%)
and anti-14 (21.3 mg, 13%). syn-14: IR (KBr) ν 2983, 2917, 1382,
136.2, 112.6, 81.5, 81.3, 45.4, 45.2, 45.1, 42.3, 42.0, 25.9, 24.4, 24.3;
HRMS (EI) m/z calcd for C30H36O6 [Mþ] 492.2512, found
492.2506.
1
1264, 1206, 1162, 1065, 1023, 860 cm-1; H NMR (CDCl3) δ
4.07-4.04 (6H, m), 3.24 (6H, s), 2.22 (3H, d, J = 9.8 Hz), 1.84
(3H, dt, J = 9.8, 1.5 Hz), 1.50 (9H, s), 1.29 (9H, s); 13C NMR
(CDCl3) δ 136.1, 112.6, 81.5, 45.3, 42.6, 25.9, 24.4; HRMS (EI)
m/z calcd for C30H36O6 [Mþ] 492.2512, found 492.2513. anti-14:
IR (KBr) ν 2983, 2936, 1383, 1373, 1263, 1208, 1175, 1164, 1065,
Acknowledgment. This work was supported by MEXT,
JST, and the Sumitomo Foundation. We thank Ms. Sachiko
Nakano for technical support.
1023, 860 cm-1 1H NMR (CDCl3) δ 4.17-4.13 (4H, m),
;
Supporting Information Available: Experimental proce-
dures and characterization data for all new compounds. This
material is available free of charge via the Internet at http://
pubs.acs.org.
4.08-4.04 (2H, m), 3.26-3.20 (6H, m), 2.23 (3H, d, J = 9.5 Hz),
1.80 (2H, ddd, J = 9.5, 1.3, 1.3 Hz), 1.74 (1H, dt, J = 9.5, 1.5 Hz),
1.50 (9H, s), 1.285 (6H, s), 1.278 (3H, s); 13CNMR(CDCl3) δ136.3,
4628 J. Org. Chem. Vol. 75, No. 13, 2010