Activation of a CH bond in polypyridine systems by acetyl hypofluorite made from F2

Article abstract of DOI:10.1039/c2ob06799d

Activation of the relatively inactive polypyridine backbone with strong electrophilic fluorine, originating from acetyl hypofluorite (AcOF) enables attack of the acetoxy moiety at the α position to the heteroatom. Derivatives of bipyridine, phenanthroline and terpyridine systems have been acetoxylated or oxygenated within a few minutes usually in very good yields.

Full text of DOI:10.1039/c2ob06799d

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PAPER
Activation of a CH bond in polypyridine systems by acetyl hypofluorite made
from F2
†
Julia Gatenyo, Youlia Hagooly, Inna Vints and Shlomo Rozen*
Received 26th October 2011, Accepted 5th December 2011
DOI: 10.1039/c2ob06799d
Activation of the relatively inactive polypyridine backbone with strong electrophilic fluorine, originating
from acetyl hypofluorite (AcOF) enables attack of the acetoxy moiety at the α position to the heteroatom.
Derivatives of bipyridine, phenanthroline and terpyridine systems have been acetoxylated or oxygenated
within a few minutes usually in very good yields.
Introduction
Solutions of this reagent, stable for a few hours at 0 to +20 °C,
are easily prepared by passing commercial nitrogen-diluted
Bipyridine (bpy), phenanthroline (phen) and terpyridine (tpy)
derivatives are important building blocks for the preparation of
coordinating compounds and metallo-supramolecular ensembles.
It can be asserted that, over the last five decades, one of most
extensively investigated family of complexes is that of the metal-
fluorine through a suspension of sodium acetate, solvated with
acetic acid in CFCl or acetonitrile. Although this hypofluorite
3
13
has been utilized for various fluorination reactions, surprisingly
it was also employed for activation of certain simple pyridine
14
derivatives. We describe in this work a general oxygenation
method for the much less reactive polypyridine systems such as
bpy, phen and tpy at the α-position to the nitrogen using this
reagent.
1
polypyridines. The great interest generated by this class of com-
plexes arises in part from their potential application in solar
2
3
energy conversion, photo-catalysis, photo-induced charge sep-
4
aration and for their use as light-driven molecular machines.
They have also found uses in DNA and proteins studies, as
well as in small molecules recognition.
5,6
7
Results and discussion
Only a few synthetic routes leading to oxygen substituted
polypyridines at the α position to the heteroatom were devel-
oped. A common one constitutes of a cross coupling reactions
utilizing pre-functionalized pyridine rings. Such strategy requires
synthesis of suitable building blocks and is frequently a multi-
step procedure. Another notable pathway is hydroxylation
Reacting 2,2′-bipyridine (1) with cold (0 °C) 2 mole-equivalent
of AcOF for just a few minutes, resulted in 85% yield of 2-
15
pyridyl-6-acetoxypyridine (2). In general, achieving diacetoxy-
lation requires larger excess of the reagent and indeed when 1
and 5,5′-dimethyl-2,2′-bipyridyl (4) were treated with 5 mole-
16
equivalent of AcOF, 6,6′-diacetoxy-2,2′-bipyridine (3) and
6,6′-diacetoxy-5,5′-dimethyl-2,2′-bipyridyl (5) were obtained in
through a rearrangement of an appropriate N-oxide with SbCl , a
5
8
route usually suitable for simple pyridine derivatives. In any
9
0% and 95% yields respectively. The 4,4′-bipyridine (6) isomer
event, there is no direct and efficient regiospecific substitution of
the hydrogen α-to the nitrogen atom of the pyridine nucleus by
an oxygenated moiety. Despite the fact that oxygenated bpy and
phen ligands are important in organic heterocyclic and coordi-
nation chemistry, very few synthetic methods leading to their
was also treated with AcOF in the same manner and was acet-
oxylated to form 2,2′-diacetoxy-4,4′-bibyridyl (7) in 95% yield
(Scheme 1).
The reaction commence with the attack of the electrophilic
9
fluorine of the acetyl hypofluorite on the basic electrons of the
nitrogen atom of the pyridine system thus activating the α pos-
ition to the nitrogen atom toward nucleophilic attack. Since the
acetoxy residue is in the vicinity, the ion pair collapses rapidly
followed by HF elimination and aromatic restoration, both very
strong driving forces. In the case of bpy from the two possible
resonance structures, A is clearly the dominant one because of
the extended conjugation (Scheme 2). A somewhat similar
mechanism could be found in Shreeve’s work dealing with N,N-
preparation could be found in the literature. Probably the best of
these routes is the dihydroxylation using certain copper salts
under solvothermal conditions (180 °C, 80 h, yields below
10
5
0%).
From the several reagents we have developed using elemental
11
12
fluorine, acetyl hypofluorite was found to be very useful.
School of Chemistry, Tel-Aviv University, Tel-Aviv, 69978, Israel. E-mail:
rozens@post.tau.ac.il; Fax: 972-3-6409293; Tel: 972-3-6408378
17
difluoro-bipyridinium salts treated with base.
There is a substantial difference, however, between com-
pounds containing one pyridine nucleus and derivatives
†
1
Electronic supplementary information (ESI) available. See DOI:
0.1039/c2ob06799d
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Scheme 1 Oxygenation of bipyridines with AcOF.
Scheme 3 Oxygenation of phenanthrolines with AcOF.
The described oxygenating reaction is also operable with phe-
nanthrolines. Treating 5,6-dimethyl-1,10-phenanthroline (10)
and 1,7-phenanthroline (13) with acetyl hypofluorite produced
the 2-acetoxy derivatives 11 and 14 (not purified) in 90% yield.
4
,7-Phenanthroline (16) could, however, form the diacetoxy
derivative 17. These compounds as well as other acetoxy pyri-
dine derivatives could be quantitatively hydrolyzed to the corre-
sponding 4,7-dimethyl-1,10-phenanthrolin-2-one (12), 1,7-
18
phenanthrolin-8-one (15)
and 4,7-phenanthroline-3,8-dione
(
18), either spontaneously or in the aqueous acidic reaction
Scheme 2 Reaction mechanism of the acetoxylation of polypyridines.
mixture at 50 °C in nearly quantitative yield (Scheme 3).
Although mono oxygenation of 1,7-phenanthroline (13)
resulted after hydrolysis in a single compound, two potential pro-
ducts 15 and 15a could, at least in theory, be formed
(Scheme 3). In order to determine which nitrogen (N-1 or N-7)
is attacked by AcOF, we preformed some NOE experiments.
Strong NOE was observed between H-4 to H-3 and H-5 as well
as between H-5 to H-4 and H-6. The vinyl proton H-9, however,
displayed an NOE only to H-10 thereby establishing that electro-
philic fluorine in AcOF attacks at N-7 generating 15 only as
shown in Scheme 3.
An interesting issue is the fact that 16 could be doubly oxyge-
nated in the vicinity of both nitrogen atoms forming eventually
the diamide 18. This is in contrast to compounds 10 and 13
which could be oxygenated only once producing, after hydroly-
sis, the amides 12 and 15, no matter how large excess of the
reagent was used. This could be explained by examining the pro-
ducts after the first oxygenation. While in the cases of 10 and 13
we could expect a full conjugation between the oxygen function
containing polypyridine rings. In the case of the former group
the carbocation developed α to the heteroatom is less destabi-
lized by the electronegative fluorine atom compared to polypyri-
dine systems. This fact enabled a relatively long life-time of the
carbocation in simple pyridines to the extent that nucleophilic
elements from the solvents could compete with the acetate anion
14
resulting eventually in α-chloro, bromo or alkoxy derivatives.
In the case of polypyridines the second electron withdrawing
ring further deactivates the first one that bears the positive
charge, resulting in much shorter lifetimes of the respective car-
bocation, counting for the fact that there is a total absence of any
elements originating from the solvent when one is used. This
could be further demonstrated by compounds such as 6,7-
dimethyl-2,3-di(2-pyridyl)quinoxaline (8) and tetra-2-pyridinyl-
pyrazine (9) where the relevant pyridine rings were so electron
depleted that no reaction between them and AcOF could take
place.
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Table 1 Mulliken charge on the nitrogen atom
a
Compound
N
1
1
0 R = H, −0.1319
11 R = OAc, −0.1241
1
1
3 R = H, −0.1690
4 R = OAc, −0.1675
1
6 R = H, −0.2002
R = OAc, −0.2038
a
Atomic units.
Scheme 4 Oxygenation of terpyridines with AcOF.
and the remote nitrogen atom which considerably reduces its
basicity, in the case of 16 there is a cross conjugation diminish-
ing the electron withdrawing effect of the oxygen on the far
away nitrogen atom which still remains quite basic and thus
allows an additional molecule of AcOF to attack it.
DFT calculations (B3LYP/6-31+G(d)) support the above
reasoning. We focused on the Mulliken charge distribution each
nitrogen atom bears before and after oxygenation of the men-
tioned above phenanthroline skeletons. Although the differences
are not striking, the trend is clear. From Table 1 we could see
that only the mono oxidized 16 retain enough negative charge on
the second nitrogen atom allowing an additional amide for-
mation. The reduced basicity of the second nitrogen in 10 and
Working with it is not as complicated as one may think. Techni-
cal commercial fluorine can be diluted on the spot or premixed
fluorine/nitrogen mixtures could be purchased.
21
Experimental section
1
H NMR spectra were recorded using a 400 MHz spectrometer
with CDCl as a solvent and Me Si as an internal standard. The
3
4
13
proton broadband decoupled C NMR spectra were recorded at
either 50.2 MHz or at 100.5 MHz. Here too, CDCl served as a
3
solvent and Me Si as an internal standard. MS was measured
4
under CI, ESI or APPI conditions.
1
3, however, causes the reaction to be terminated after mono
oxygenation. These conclusions are in line with the experimental
outcome mentioned above.
General fluorination procedure
Fluorine is a strong oxidant and corrosive material. In organic
chemistry, it is mostly used after dilution with nitrogen or
helium. Such dilution can be achieved by using either an appro-
priate copper or monel vacuum line constructed in a well-venti-
lated area or simply purchasing prediluted fluorine. A detailed
description for simple setup had appeared in the past. The reac-
tions themselves are carried out in regular glassware. If elemen-
tary precautions are taken, work with F is simple and we have
Terpyridines produced similar results. Due to the extended
aromaticity, these molecules display enhanced chemical stability
and as a result any modification reaction on the polypyridine
skeleton is somewhat more difficult. Indeed, these derivatives
required much larger excess of acetyl hypofluorite to achieve the
desired oxygenation, but the electronic structures enabled both
nitrogen atoms to be attacked by the electrophilic fluorine.
Around 10 mole-equivalent of AcOF were used in order to trans-
fer 2,2′:6′,2′′-terpyridine (19) to pyridine-2,6-dipyridone 21, via
its respective diacetate 20, in 85% overall yield. It should be
noted that 21 is a known compound prepared in the past by a
21
2
had no bad experience working with it.
Preparation of AcOF and its reaction with polypyridines
1
9
total synthesis in less than 25% yield. Similarly 4′-(4-chloro-
phenyl)-2,2′:6′,2′′-terpyridine (22) was acetoxylated to 23 in
A mixture of 10–15% F2 in N2 was bubbled into a cold
(
1
−45 °C) suspension of 2 g of AcONa·AcOH dispersed in
00 mL of CH CN and 10 mL of AcOH all placed in a standard
8
0% yield (Scheme 4).
3
glass vessel. The solvated salt could be made by leaving anhy-
drous AcONa over AcOH in a closed desiccator for at least 24 h.
The amount of the AcOF thus obtained could be easily deter-
mined by reacting aliquots of the reaction mixture with aqueous
KI solution and titrating the liberated iodine. After the desired
concentration of AcOF is achieved (usually 0.1–0.15 M), the
oxidizing solution was added in portions of 10–20 ml each to
the desired solid polypyridine derivative. The reactions were
carried out on scales of 1–5 mmol using 2.5–10 fold excess of
AcOF, with conversions higher than 95%. They were usually
Conclusion
It has been demonstrated that acetyl hypofluorite can serve as a
powerful regioselective oxygenating agent for various polypyri-
dine derivatives, a task very difficult to achieve by any other
means. The fact that it is made from diluted fluorine should not
deter chemists from working with it. Thus, for example, fluorine
2
0
is less toxic than chlorine, and in concentrations of 10–20% in
N is also much less corrosive than both chlorine and bromine.
2
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1
8
monitored by TLC or NMR and in most cases were completed
within a few minutes. The reaction was terminated by pouring
it into NaHCO3 solution followed by water until neutral,
1,7-Phenanthrolin-8-one (15) was prepared from 1,7-phe-
nanthroline (13) (0.6 g, 3.3 mmol) as described above, using 2
equiv of the oxidizing solution. After hydrolysis, a beige product
(0.58 g, 90% yield) was obtained: mp > 300 °C (decomposition);
drying the organic layer over MgSO and evaporation of the
4
1
solvent. The crude product was usually purified by vacuum
flash chromatography (Merck silica gel 60H) with petroleum
ether/ethyl acetate serving as eluent or by recrystallization.
Several of the products are known and referenced, but frequently
not adequately described. In such cases their properties are given
below.
H NMR (DMSO-d ) 8.98–8.96 (2 H, m), 8.39 (1 H, dd, J =
8.0, J = 1.6 Hz), 8.07 (1 H, d, J = 8.9 Hz), 7.58–7.54 (2 H,
m), 6.68 ppm (1 H, d, J = 9.7 Hz); C NMR (DMSO-d6)
162.34, 150.81, 144.28, 140.26, 136.59, 135.84, 130.84, 123.27,
121.47, 120.72, 116.99, 113.99 ppm; HRMS (ESI) m/z calcd for
C H N O 197.0715 (M + H) , found 197.0719.
4,7-Phenanthroline-3,8(4H,7H)-dione (18) was prepared
from 4,7-phenanthroline (16) (0.6 g, 3.3 mmol) as described
above, using 5 equiv of the oxidizing solution. A beige
product (0.67 g, 95% yield) was obtained: mp > 300 °C
6
1
2
1
13
1
+
12 8 2
1
5
2
-Pyridyl-6-acetoxypyridine (2) was prepared from 2,2′-
bipyridine (1) (0.4 g, 2.6 mmol) as described above, using 2.5
equiv of the oxidizing solution. A white solid (0.46 g, 85%
1
yield) was obtained: mp 73–74 °C; H NMR (CDCl ) 8.68–8.66
3
1
(1 H, m), 8.35–8.32 (2 H, m), 7.92 (1 H, t, J = 7.9 Hz), 7.80 (1
(decomposition); H NMR (DMSO-d ) 8.54 (2 H, d, J = 9.6
Hz), 7.50 (2 H, s), 6.64 ppm (2 H, d, J = 9.6 Hz); C NMR
6
1
13
H, td, J = 7.7, J = 1.8 Hz), 7.31 (1 H, ddd, J = 7.5, J = 4.8,
1
2
1
2
1
J = 1.1 Hz), 7.10 (1 H, dd, J = 8.0, J = 0.7 Hz), 2.39 ppm (3
(DMSO-d6) 161.26, 135.05, 134.72, 122.90, 119.07,
114.08 ppm; HRMS (ESI) m/z calcd for C H N O 213.0664
3
1
2
13
H, s); C NMR (CDCl ) 169.26, 157.44, 155.82, 155.13,
3
12
8
2
2
+
1
2
49.38, 140.44, 137.09, 124.19, 121.58, 119.36, 116.45,
(M + H) , found 213.0667.
+
19
1.51 ppm; MS (CI) m/z 215.1 (M + H) .
6,6-(Pyridine-2,6-diyl)dipyridin-2(1H)-one (21) was pre-
pared from 2,2′:6′,2′′-terpyridine (19) (0.5 g, 2.1 mmol) as
described above, using 10 equiv of the oxidizing solution. After
hydrolysis, a white product (0.48 g, 85% yield) was obtained
with physical properties matching those in the literature.
1
6
6
,6′-Diacetoxy-2,2′-bipyridine (3) was prepared from 2,2′-
bipyridine (1) (0.4 g, 2.6 mmol) as described above, using 5
equiv of the oxidizing solution. A white solid (0.62 g, 90%
yield) was obtained with physical constants in accordance to the
ones in the literature.
6,6′′-Diacetoxy-4′-(4-chlorophenyl)-2,2′:6′,2′′-terpyridine
(23) was prepared from 22 (0.4 g, 1.2 mmol) as described above,
using 10 equiv of the oxidizing solution. A beige product
6
,6′-Diacetoxy-5,5′-dimethyl-2,2′-bipyridine (5) was pre-
pared from 5,5′-dimethyl-2,2′-bipyridyl (4) (0.7 g, 3.8 mmol) as
described above, using 5 equiv of the oxidizing solution. A pale
yellow product (1.08 g, 95% yield) was obtained, mp starting to
1
(0.42 g, 80% yield) was obtained: mp 177–179 °C; H NMR
(CDCl ) 8.59–8.57 (4 H, m), 7.98 (2 H, t, J = 8.0 Hz), 7.79 (2
3
1
1
decompose at 210 °C; H NMR (CDCl ) 8.17 (2 H, d, J = 7.8
H, d, J = 8.5 Hz), 7.49 (2 H, d, J = 8.5 Hz), 7.15 (2 H, d, J =
1 1 1
3
1
13
Hz), 7.68 (2 H, d, J = 7.8 Hz), 2.39 (3 H, s), 2.24 ppm (3 H, s);
8.0), 2.4 ppm (3 H, s); C NMR (CDCl ) 169.30, 157.45,
1
3
1
3
C NMR (CDCl ) 168.95, 156.19, 152.43, 141.50, 125.68,
155.64, 155.14, 149.46, 140.42, 136.94, 135.43, 129.30, 128.84,
3
1
19.93, 21.13, 16.04 ppm; HRMS (ESI) m/z calcd for
119.70, 119.45, 116.77, 29.84 ppm; HRMS (APPI) m/z calcd for
C H N O Cl 460.1064 (M + H) , found 460.1059.
25 18 3 4
+
C H N O 323.1008 (M + Na), found 323.1010. Anal. Calcd.
1
6
16
2
4
for C H N O : C, 63.99; H, 5.37; N, 9.33. Found: C, 63.69;
1
6 16 2 4
H, 5.16; N, 9.22.
,2′-Diacetoxy-4,4′-bipyridyline(7) was prepared from 4,4′-
bipyridine (6) (0.5 g, 3.2 mmol) as described above, using 5
2
Acknowledgements
This work was supported by the USA-Israel Binational Science
Foundation (BSF), and by the Israel Science Foundation. We
wish to express our gratitude to Prof. Y. Kashman from our
school for his help with the NOE experiments. Y. H. thanks the
Israel Ministry of Science and Technology for a scholarship.
equiv of the oxidizing solution. A pale beige product (0.82 g,
1
9
5% yield) was obtained: mp 178–181 °C; H NMR (CDCl )
3
8
.28 (2 H, d, J = 7.7 Hz), 7.90 (2 H, t, J = 7.8 Hz), 7.11 (2 H,
1
1
1
3
d, J = 8.0 Hz), 2.40 ppm (3 H, s); C NMR (CDCl ) 169.20,
1
3
1
57.39, 154.53, 140.47, 119.68, 116.85, 21.48 ppm; HRMS
(
APPI) m/z calcd for C H N O 295.0695 (M + Na), found
1
4 12 2 4
2
1
95.0696. Anal. Calcd. for C H N O : C, 61.76; H, 4.44; N,
14 12 2 4
References
0.29. Found: C, 61.46; H, 4.30; N, 10.36.
,7-Dimethyl-1,10-phenanthrolin-2(1H)-one (12) was pre-
pared from 5,6-dimethyl-1,10-phenanthroline (10) (0.4 g,
.9 mmol) as described above, using 2 equiv of the oxidizing
solution. After hydrolysis, a pale beige product (0.38 g, 90%
4
1
(a) N. Armaroli, Chem. Soc. Rev., 2001, 30, 113; (b) D. R. McMillin and
K. M. McNett, Chem. Rev., 1998, 98, 1201.
2
M. K. Nazeeruddin and M. Grätzel, in Photofunctional Transition Metals
Complexes, Structure and Bonding, ed. V. W. W. Yam, Springer-Verlag,
Berlin, 2007.
1
1
yield) was obtained: mp 202–203 °C; H NMR (CDCl ) 10.73
3
3 K. Szacilowski, W. Macyk, A. Drzewiecka-Matuszek, M. Brindell and
(
7
1 H, br), 8.75 (1 H, d, J = 4.3 Hz), 7.73 (2 H, q, J = 9.3 Hz),
G. Stochel, Chem. Rev., 2005, 105, 2647.
1
1
4
E. Baranoff, F. Barigelletti, S. Bonnet, J. P. Collin, L. Flamigni,
P. Mobian and J. P. Sauvage, in Photofunctional Transition Metals Com-
plexes, Structure and Bonding, ed. V. W. W. Yam, Springer-Verlag,
Berlin, 2007.
5 (a) K. E. Erkkila, D. T. Odom and J. K. Barton, Chem. Rev., 1999, 99,
2777; (b) C. Metcalfe and J. A. Thomas, Chem. Soc. Rev., 2003, 32, 215.
K. K. W. Lo, K. H. K. Tsang, K. S. Sze, C. K. Chung, T. K. M. Lee,
K. Y. Zhang, W. K. Hui, C. K. Li, J. S. Y. Lau, D. C. M. Ng and N. Zhu,
Coord. Chem. Rev., 2007, 251, 2292.
.38 (1 H, d, J = 4.3 Hz), 6.70 (1 H, s), 2.74 (3 H, s), 2.58 ppm
1
13
(3 H, s); C NMR (CDCl ) 161.91, 149.00, 148.74, 144.79,
3
1
1
2
36.55, 135.44, 128.05, 123.97, 122.47, 121.84, 117.80, 116.93,
9.40, 18.91 ppm; HRMS (APPI) m/z calcd for C H N O
1
4 12 2
+
25.1028 (M + H) , found 225.1031. Anal. Calcd. for
6
C H N O: C, 74.98; H, 5.39; N, 12.49. Found: C, 74.68; H,
5
1
4 12 2
.34; N, 12.28.
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7
(a) M. H. Keefe, K. D. Benkstein and J. T. Hupp, Coord. Chem. Rev.,
13 (a) O. Lerman, Y. Tor and S. Rozen, J. Org. Chem., 1981, 46, 4629;
(b) S. Rozen, A. Hagooly and R. Harduf, J. Org. Chem., 2001, 66, 7464;
(c) S. Rozen, Acc. Chem. Res., 1988, 21, 307.
2
000, 205, 201; (b) P. D. Beer and J. Cadman, Coord. Chem. Rev., 2000,
05, 131.
2
8
9
J. Yamamoto, M. Imagawa, S. Yamauchi, O. Nakazawa, M. Umezu and
T. Matsuura, Tetrahedron, 1981, 37, 1871.
X.-M. Zhang, M.-L. Tong and X.-M. Chen, Angew. Chem., Int. Ed.,
14 S. Rozen, D. Hebel and D. Zamir, J. Am. Chem. Soc., 1987, 109, 3789.
15 S. Rozen and D. Hebel, Heterocycles, 1989, 28, 249.
16 T. Umemoto, M. Nagayoshi, K. Adachi and G. Tomizawa, J. Org. Chem.,
1998, 63, 3379.
17 R. P. Singh, G. V. Eggers and J. M. Shreeve, Synthesis, 2003, 1009.
18 P. Karrer and A. Pletscher, Helv. Chim. Acta, 1948, 31, 786.
19 T. J. Donohoe, L. P. Fishlock and P. A. Procopiou, Org. Lett., 2008, 10,
285.
2
002, 41, 1029.
0 J.-P. Zhang, Y.-Y. Lin, Y,-Q. Weng and X.-M. Chen, Inorg. Chim. Acta,
006, 359, 3666.
1 (a) C. Gal and S. Rozen, Tetrahedron Lett., 1984, 25, 449; (b) M. Kol,
S. Rozen and E. Appelman, J. Am. Chem. Soc., 1991, 113, 2648;
c) S. Rozen and D. Zamir, J. Org. Chem., 1990, 55, 3552.
2 S. Rozen, O. Lerman and M. Kol, J. Chem. Soc., Chem. Commun., 1981,
43.
1
2
1
(
20 American Enviromental Group ltd, AEGL (Acute Exposure Guidline
Level) (50), October 2, 2009.
21 S. Dayan, M. Kol and S. Rozen, Synthesis, 1999, 1427.
1
4
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