Folding-induced selective hydrogenation of helical 9,10-anthraquinone analogues

Article abstract of DOI:10.1021/ol802241h

(Figure Presented) The first selective catalytic hydrogenation induced by the artificial helix based on oligo(phenanthroline dicarboxamide)s containing a 9,10-anthraquinone subunit is described. Due to the steric hindrance within the helically folded oligomers, the selective reductions of the anthraquinone units were completely different from those of model substrates, which subsequently mimicked the enzyme catalysis for preventing some reactions from occurring.

Full text of DOI:10.1021/ol802241h

ORGANIC
LETTERS
2008
Vol. 10, No. 21
5035-5038
Folding-Induced Selective
Hydrogenation of Helical
9,10-Anthraquinone Analogues
Hai-Yu Hu,†,‡ Jun-Feng Xiang,† Jing Cao,†,‡ and Chuan-Feng Chen*,†
Beijing National Laboratory for Molecular Sciences, Center for Chemical Biology,
Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China, and
Graduate School, Chinese Academy of Sciences, Beijing 100049, China
cchen@iccas.ac.cn
Received September 26, 2008
ABSTRACT
The first selective catalytic hydrogenation induced by the artificial helix based on oligo(phenanthroline dicarboxamide)s containing a 9,10-
anthraquinone subunit is described. Due to the steric hindrance within the helically folded oligomers, the selective reductions of the anthraquinone
units were completely different from those of model substrates, which subsequently mimicked the enzyme catalysis for preventing some
reactions from occurring.
In the past decade, synthetic helical foldamers1 have attracted
great attention for mimicking the structures and functions
of biological macromolecules and showing potential applica-
tions in material sciences and supramolecular chemistry.
Consequently, numerous helical foldamers have been de-
signed and synthesized by different strategies.1,2 The specific
chemical environments provided by foldamers not only
mimic the catalytic behavior of biological systems for
reactions3 but also prevent some reactions from occurring.4
However, studies of foldamer reactivity are still fewer in
number. One particular study carried out by Moore’s group
involved the methylation of a dimethylaminopyridine unit
placed in the backbone of mPE foldamers using a methy-
lating agent, which acted as a “reactive sieve” for different
sizes and different shapes of guest substrates.5 Another
special example reported by Huc’s group6 is about the
pyridine N-oxidation of the helical oligopyridine dicarboxa-
† Institute of Chemistry.
‡ Graduate School.
(4) (a) Conn, M. M.; Rebek, J., Jr. Chem. ReV. 1997, 97, 1647–1668.
(b) Breslow, R.; Dong, S. D. Chem. ReV. 1998, 98, 1997–2011. (c)
Vriezema, D. M.; Aragone`s, M. C.; Elemans, J. A. A. W.; Cornelissen,
J. J. L. M.; Rowan, A. E.; Nolte, R. J. M. Chem. ReV. 2005, 105, 1445–
1489. (d) Breslow, R. Acc. Chem. Res. 1995, 28, 146–153.
(5) (a) Heemstra, J. M.; Moore, J. S. J. Am. Chem. Soc. 2004, 126,
1648–1649. (b) Heemstra, J. M.; Moore, J. S. J. Org. Chem. 2004, 69,
9234–9237. (c) Smaldone, R. A.; Moore, J. S. J. Am. Chem. Soc. 2007,
129, 5444–5450. (d) Smaldone, R. A.; Moore, J. S. Chem. Commun. 2008,
1011–1013.
(1) (a) Hecht, S. M.; Huc, I. Foldamers: Structure, Properties and
Applications; Wiley-VCH: Weinheim, Germany, 2007. (b) Gellman, S. H.
Acc. Chem. Res. 1998, 31, 173–180. (c) Hill, D. J.; Prince, R. B.; Hughes,
T. S.; Moore, J. S. Chem. ReV. 2001, 101, 3893–4011.
(2) Some recent reviews see: (a) Huc, I. Eur. J. Org. Chem. 2004, 1,
17–29. (b) Gong, B.; Sanford, A. R.; Ferguson, J. S. AdV. Polym. Sci. 2007,
206, 1–29. (c) Li, Z.-T.; Hou, J.-L.; Li, C.; Yi, H.-P. Chem. Asian J. 2006,
1, 766–778. (d) Davis, J. M.; Tsou, L. K.; Hamilton, A. D. Chem. Soc.
ReV. 2007, 36, 326–334
(3) (a) Breslow, R. Acc. Chem. Res. 1980, 13, 170–177. (b) Smaldone,
R. A.; Moore, J. S. Chem.-Eur. J. 2008, 14, 2650–2657
.
(6) Dolain, C.; Zhan, C.; Le´ger, J. M.; Daniels, L.; Huc, I. J. Am. Chem.
Soc. 2005, 127, 2400–2401.
.
10.1021/ol802241h CCC: $40.75
Published on Web 10/10/2008
2008 American Chemical Society

mide strands. The same group recently also reported an
interesting selective bromination of helically folded oligo-
amides by N-bromosuccinimide.7
Recently, we reported a new class of phenanthroline-
derived oligoamide helical foldamers.8 Due to their small
helical hollows and extremely compact structures, we
envisioned that the active group inside the helical cavity
could be well-protected against some reactions from occur-
ring. Consequently, we designed and synthesized the oligo-
mers 1∼3 (Scheme 1), in which the reactive 9,10-anthraquino-
Scheme 1
.
Synthesis and Selective Catalytic Hydrogenations of
Oligomers 1∼3
Figure 1
.
UV-vis spectra of the molecular strands 1∼4 (solid line)
and 1a∼4a (dash line) in CHCl3 (c ) 1.0 × 10-5 M).
hypochromic effect with an increasing number of phenan-
throline rings was observed, indicating the formation of the
helical ordering and π-π* stacking of the phenanthroline
units (λmax ) ∼330 nm) in 1∼3.9,10
A single crystal of oligomer 2 suitable for X-ray diffraction
was obtained by slow evaporation of a solution of CH2Cl2/
EtOH.11 The crystal structure showed that oligomer 2 adopts
a regular helical secondary structure, and the two carbonyl
groups of the 9,10-anthraquinone unit position inside and
outside the helical hollow, respectively (Figure 2), which
ne unit was positioned at the midpoint of the helical
foldamer’s backbone. Herein, we report the folding-induced
selective hydrogenation of the helical anthraquinone ana-
logues to give the new helical foldamers 1a∼3a. To our
knowledge, this is the first selective reduction of the single
artificial helix, which shows completely different catalytic
hydrogenation from the mode reaction of diacetamide
anthraquinone.
Figure 2. Side view (a) and top view (b) of the crystal structure of
2. Solvent molecules and hydrogen atoms have been omitted for
The oligomers 1∼3 were synthesized by the reaction of
the appropriate monoacid8a with 1,8-diaminoanthracene-9,10-
dione in dichloromethane in the presence of dicyclohexyl-
carbodiimide and 1-hydroxybenzotriazole (Scheme 1). Simi-
lar to the oligo(phenanthroline dicarboxamide)s previously
clarity.
implies the two carbonyls can show different catalytic
hydrogenation activities.12
The catalytic hydrogenations were performed under a
hydrogen atmosphere in acetic acid in the presence of 10%
Pd/C. We first tested the hydrogenation of diacetamide
8
1
reported, the H NMR and 2D NOESY studies clearly
supported formation of the helical secondary structures of
oligoamides 1∼3 in solution.9 The UV/vis absorption spectra
further confirmed the intramolecular interactions of the
helical foldamers (Figure 1, solid line). As expected, a
(10) Nelson, J. C.; Saven, J. G.; Moore, J. S.; Wolynes, P. G. Science
1997, 277, 1793–1796
.
(7) Srinivas, K.; Kauffmann, B.; Dolain, C.; Le´ger, J. M.; Ghosez, L.;
Huc, I. J. Am. Chem. Soc. 2008, 130, 13210–13211.
(8) (a) Hu, Z.-Q.; Hu, H.-Y.; Chen, C.-F. J. Org. Chem. 2006, 71, 1131–
1138. (b) Hu, H.-Y.; Xiang, J.-F.; Yang, Y.; Chen, C.-F. Org. Lett. 2008,
10, 69–72. (c) Hu, H.-Y.; Xiang, J.-F.; Yang, Y.; Chen, C.-F. Org. Lett.
2008, 10, 1275–1278.
(11) Crystal data for 2·6(C2H5OH)·2(H2O): C138H160N16O26; Mw )
2458.82; triclinic; space group P-1; a ) 16.062(4) Å, b ) 20.088(5) Å, c
) 22.642(6) Å; R ) 84.27(3)°, ꢀ ) 70.17(2)°, γ ) 67.43(3)°; V ) 6342(3)
Å3; Z ) 2; T ) 112(2) K; R1 )0.2082; wR2 ) 0.4190 (all data); R1
0.1533, wR2 ) 0.3804 [I > 2σ(I)].
)
(12) Maurizot, V.; Dolain, C.; Leydet, Y.; Le´ger, J. M.; Guionneau, P.;
(9) See Supporting Information.
Huc, I. J. Am. Chem. Soc. 2004, 126, 10049–10052.
5036
Org. Lett., Vol. 10, No. 21, 2008

anthraquinone (4) as the model13 and found the reaction
could be finished in 45 min to give the anthrone 4a in a
quantitative yield (Scheme 2). It was found that compound
attempted to obtain the crystals of the anthrones. Although
we have not succeeded so far, the crystals of a dianthrone
derivative of 4a suitable for X-ray analysis were unexpect-
edly obtained by slow diffusion of ether into a solution of
4a in DMF,16,17 and its crystal structure provided an
accessorial evidence for the structure of 4a (Figure 4).
Scheme 2
.
Selective Catalytic Hydrogenation of Diacetamide
Anthraquinones 4 and 5
4a did not dissolve in CDCl3, and the 1H NMR spectrum in
d6-DMSO showed that 4a could be transformed into anthrol
4b. After 1 day, almost no changes of the spectrum occurred,9
in which the tautomeric constant ([anthrone]/[anthrol]) was
found to be approximately 1/1.8.14 We also synthesized
dibutyramide anthraquinone 5 but found that its hydrogena-
tion product 5a did not dissolve in CDCl3 either.9,15
Figure 4. Side view (a) and top view (b) of the crystal structure of
the dianthrone. Hydrogen atoms have been omitted for clarity.
The first evidence for the hydrogenation of 4 came from
the UV/vis absorption spectrum, in which the characteristic
absorption of the anthraquinone chromophore at ∼440 nm
disappeared (Figure 1, green dash line). The 1H and 13C NMR
and MS spectra were also in agreement with the structure
of anthrone 4a, which was further established by the TOCSY
and NOESY spectra. In the TOCSY spectrum of 4a, no cross
peaks between Ha and the aryl protons Hc-He were ob-
served.9 Meanwhile, the NOESY spectrum of 4a also
exhibited no cross peaks between Ha and the aryl protons
Hc-He but the expected correlation between proton Ha and
the NH proton Hb (Figure 3). These observations indicated
Under the same conditions as above, it was interestingly
found that the catalytic hydrogenations of oligomers 1∼3
selectively occurred on the outer carbonyl group to give the
anthrone analogues 1a∼3a in high yields. It was different
from the model compound 4 that oligomers 1a∼3a did not
dissolve in d6-DMSO, but they were found to be stable in
CDCl3 for more than one month. Compared with oligomers
1∼3, the characteristic absorption band of the anthraquinone
chromophore at ∼440 nm disappeared in the UV-vis
absorption spectra of 1a∼3a (Figure 1, dash line), while the
absorption bands of the phenanthroline rings were still
identical to those of 1∼3, which implied that oligomers
1
1a∼3a were also in helical structures. Moreover, the H
NMR spectra of 1a∼3a showed a new peak for the
methylene proton Ha but no obvious changes for the shifts
of NH zone signals, especially the proton Hh signal (Figure
5). The results not only suggested the formation of the
anthrones but also indicated the maintained helical confor-
mation of the oligomers.
Structures of the oligomers 1a∼3a were further proved
by their TOCSY and NOESY spectra.9 In the NOESY
spectra of 2a, a cross peak between proton Ha and proton
(13) To our surprise, no reductions of diacetamide anthraquinones were
hitherto reported.
(14) McCann, G. M.; McDonnell, C. M.; Magris, L.; O’Ferrall, R. A. M.
J. Chem. Soc., Perkin Trans. 2 2002, 784–795.
(15) We also synthesized di(n-decanamide) anthraquinone (R ) n-C9H19)
but found that its hydrogenation product did not dissolve in either CDCl3
or d6-DMSO.
(16) The reaction mechanism for formation of the dianthrone is not clear,
which might be through a photoreaction under the influence of sunlight
and air. For a similar reaction, see: Scho¨nebrg, A.; Mustafa, A. J. Chem.
Soc. 1945, 657–660. In addition, owing to the poor solubility of the
dianthrone in common solvents, it has not been characterized by NMR and
MS spectra.
Figure 3. Partial NOESY spectrum (600 MHz, d6-DMSO) of 4a.
(17) Crystal data for the dianthrone: C36H30N4O6; Mw ) 614.64;
monoclinic; space group P2(1)/n; a ) 8.0388(16) Å, b ) 11.363(2) Å, c )
16.369(3) Å; R ) 90.00°, ꢀ ) 94.27(3)°, γ ) 90°; V ) 1491.1(5) Å3; Z )
2; T ) 173(2) K; R1 ) 0.0907; wR2 ) 0.1561 (all data); R1) 0.0644, wR2
) 0.1455 [I > 2σ(I)].
that the hydrogenation of 4 selectively occurred on the inside
carbonyl group to give product 4a. Moreover, we have also
Org. Lett., Vol. 10, No. 21, 2008
5037

Figure 6. Partial TOCSY spectrum (600 MHz, CDCl3) of oligomer
2a.
the helically folded oligomers, the selective catalytic hydro-
genation of the anthraquinone unit was completely different
from that of model substrates. The results presented here
cannot only mimic the enzyme catalysis for preventing some
reactions from occurring but also provide a convenient
method to synthetic new helical foldamers. Further studies
will attempt to build higher-ordered structures by the
coupling reactions16 of the helical anthrone analogues and
will also focus on the design of reactions in which the
oligomers have potential to act catalytically.
Figure 5.
Partial 1H NMR spectra (600 MHz, CDCl3) of oligomers
1∼3 and 1a∼3a (5.0 mM).
Hb was shown, while no cross peaks between Ha and the
NH protons Hh were observed, which were all in agreement
with the structure of 2a. Moreover, the TOCSY spectrum
of 2a also showed the expected correlations between proton
Ha and protons Hb and Hc (Figure 6), which further provided
unambiguous evidence for the selective hydrogenation of 2
occurring on the outer carbonyl group to give product 2a.
This result is completely different from that of the model
reaction, in which the presence of diacetamide units might
make the adjacent keto groups bind with the catalyst more
stably and subsequently yield the selective reduction products
of anthrones. For oligomers 1∼3, the selective catalytic
hydrogenation is most likely caused by the steric hindrance
within the helically folded oligomers.
Acknowledgment. We thank the National Natural Science
Foundation of China (20625206) and the National Basic
Research Program (2007CB808004, 2008CB617501) for
financial support. We also thank Dr. Hai-Bin Song at Nankai
University for determining the crystal structures.
Supporting Information Available: Synthesis and char-
1
acterization data of new compounds. Copies of H and 13C
NMR spectra. TOCSY, NOESY, and UV-vis spectra of
1∼4 and 1a∼4a. The X-ray crystallographic files (CIF) for
2 and the dianthrone derivative of 4a. This material is
available free of charge via the Internet at http://pubs.acs.org.
In conclusion, we have presented the first selective
reduction induced by a single artificial helix based on
oligo(phenanthroline dicarboxamide)s containing a 9,10-
anthraquinone subunit. Due to the steric hindrance within
OL802241H
5038
Org. Lett., Vol. 10, No. 21, 2008