A novel one-pot synthesis of ferrocenyl-substituted 1,2,4-oxadiazoles

Article abstract of DOI:10.1016/j.jorganchem.2014.02.018

One-pot synthesis of 5-ferrocenyl-1,2,4-oxadiazoles via the reaction between 3-ferrocenylpropynal and amidoximes is described. 3-Ferrocenylpropynal reacts with a variety of amidoximes in the presence of KOH in refluxing dioxane to afford a broad range of

Full text of DOI:10.1016/j.jorganchem.2014.02.018

Journal of Organometallic Chemistry 759 (2014) 67e73
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Journal of Organometallic Chemistry
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A novel one-pot synthesis of ferrocenyl-substituted 1,2,4-oxadiazoles
*
Metin Zora , Arif Kivrak, Yilmaz Kelgokmen
Department of Chemistry, Middle East Technical University, 06800 Ankara, Turkey
a r t i c l e i n f o
a b s t r a c t
Article history:
One-pot synthesis of 5-ferrocenyl-1,2,4-oxadiazoles via the reaction between 3-ferrocenylpropynal and
amidoximes is described. 3-Ferrocenylpropynal reacts with a variety of amidoximes in the presence of
KOH in refluxing dioxane to afford a broad range of 5-ferrocenyl-1,2,4-oxadiazole derivatives. The re-
action first produces the corresponding conjugate addition product which, upon cyclization and rear-
rangement, yields the targeted 1,2,4-oxadiazole. The reaction appears to be general for a diversity of
amidoximes and tolerates the presence of aryl groups with electron-withdrawing and electron-donating
substituents.
Received 6 January 2014
Received in revised form
20 February 2014
Accepted 25 February 2014
Keywords:
1,2,4-Oxadiazole
Amidoxime
Ó 2014 Elsevier B.V. All rights reserved.
Ferrocene
3-Ferrocenylpropynal
Conjugate addition
Cyclization
Introduction
amidoximes 2, afford 1,2,4-oxadiazoles 4 and isoxazoles 5 when
treated with bases and acids, respectively (Scheme 1) [22]. 1,2,4-
1,2,4-Oxadiazoles are prominent targets for synthetic chemists
primarily because of their diverse and potent biological properties
[1]. In fact, 1,2,4-oxadiazoles have been reported to exhibit a wide
range of biological properties, including analgesic [2], anti-
asthmatic [3], anti-diabetic [4], anthelmintic [5], diuretic [6], anti-
inflammatory [7], antimicrobial [8], antiparasitic [9], anti-HIV
[10], and antitumor [11] activities. They have also been used
frequently as bioisosteres of esters and amides [12], and as dipep-
tide mimetics [13] in a number of pharmacologically important
compounds. In addition,1,2,4-oxadiazoles are present in a variety of
biologically important molecules, such as muscarinic agonists [14],
serotoninergic (5-HT3) antagonists [15], benzodiazepine receptor
agonists [16], growth hormone secretagogous [17], and dopamine
ligands [18]. The biological activity of substituted 1,2,4-oxadiazoles
has made them a focus of medicinal chemistry over the years.
1,2,4-Oxadiazoles are commonly synthesized by the 1,3-dipolar
cycloaddition of nitrile oxides to nitriles [19], and the reaction of
amidoximes with carboxylic acids or their derivatives [20]. In fact
over the years, many methods have been developed for the syn-
thesis of 1,2,4-oxadiazoles [21], and new variants continue to
appear since they are prized as potential drug candidates and
biological probes. Recently, we have shown that conjugate addition
Oxadiazoles 4 can also be synthesized directly from amidoximes
2 and -alkynic aldehydes 1 in one-pot manner under basic
a,b
conditions [22]. It is noteworthy to mention that ferrocenyl-
substituted oxadiazoles have great potential for biological and
medicinal studies since, according to recent studies, the combina-
tion of ferrocenyl group with biologically active molecules may
enhance their current biological activities or create new medicinal
properties [23,24]. Therefore, we investigated the synthesis of
ferrocenyl-substituted 1,2,4-oxadiazoles as well. Unfortunately, the
reaction between 3-ferrocenylpropynal (6) and benzamidoxime
(2a) did not yield the expected conjugate addition product. How-
ever, when the same reaction was carried out in the presence of
KOH, it afforded the expected 5-ferrocenyl-3-phenyl-1,2,4-
oxadiazole (10a) in high yield. Accordingly, we explored one-pot
synthesis of 5-ferrocenyl-1,2,4-oxadiazole derivatives by employ-
ing the reaction of 3-ferrocenylpropynal (6) with a variety of ami-
doximes 2. Herein we report the results of this study.
Results and discussion
Initially, the starting materials were prepared. 3-
Ferrocenylpropynal (6) was synthesized from ethynylferrocene
(7) by a modified formylation reaction (Scheme 2) [25]. The lith-
iation of ethynylferrocene (7) with n-BuLi, followed by the treat-
ment with DMF and subsequently quenching with phosphate
buffer, afforded 3-ferrocenylpropynal (6) in 89% yield. Note that a
products 3, obtained from
a,b-alkynic aldehydes/ketones 1 and
* Corresponding author. Tel.: þ90 312 2103213; fax: þ90 312 2103200.
E-mail address: zora@metu.edu.tr (M. Zora).
http://dx.doi.org/10.1016/j.jorganchem.2014.02.018
0022-328X/Ó 2014 Elsevier B.V. All rights reserved.

68
M. Zora et al. / Journal of Organometallic Chemistry 759 (2014) 67e73
R3
KOH
N
R1
N
O
KOH
O
R1
O
R2
OH
65 oC
4
O
or NaH
N
R1
+
NH2
R3
R2
R3
NH2
HCl
N
R2
2
1
3
R1
N
O
5
Scheme 1.
reverse quench into a phosphate buffer has been shown to be
responsible for a high yielding formylation reaction [26]. Amidox-
imes 2 were synthesized by the reaction of hydroxylamine hydro-
chloride with nitriles 8 in the presence of triethylamine in refluxing
ethanol (Scheme 2) [22,27], most of which were obtained in good
yields. The lowest yield (15%) was observed for the ferrocenyl
amidoxime 2k, consistent with the findings of earlier researchers
obtaining a 19% yield [28]. This low yield can be attributed to that
as 0.5e3 h, and the longer reaction times diminished the yields of
5-ferrocenyl-1,2,4-oxadiazoles 10 (Table 1, Entries and 5).
1
Apparently, at high temperatures such as 100 ꢀC, oxadiazoles
started to be decomposed gradually. For this reason, the reactions
were followed by the frequent TLC analysis for the completion of
the reaction. In most cases, oxadiazoles 10 were obtained in good to
high yields. However, oxadiazole derivative 10k bearing two fer-
rocenyl groups at 3 and 5 positions was isolated in low yield (22%)
(Table 1, Entry 11). As seen in Table 1, the reaction is general for a
diversity of amidoximes 2 and tolerates the presence of aryl groups
with electron-donating and electron-withdrawing moieties.
It should be mentioned that these reactions also produce acet-
aldehyde along with oxadiazoles 10. As we reported previously
[22], the isolation of acetaldehyde from such reactions was not
attempted due to its low boiling point (21 ꢀC), but its formation was
ferrocenyl group is very effective at stabilizing an
a radical or car-
bocation [24,29], which significantly decreases the electrophilicity
of cyanoferrocene (ferrocenylnitrile) (8k). Note that cyanoferrocene
(8k) was synthesized from ferrocenecarboxaldehyde (9) in one-pot
manner through the dehydration of in situ formed oxime with KI
and ZnO in refluxing acetonitrile (Scheme 2) [30]. As summarized
in Table 1, a variety of amidoximes 2 were employed in this study.
Subsequently, we investigated the feasibility of one-pot syn-
thesis of 5-ferrocenyl-1,2,4-oxadiazoles 10 directly from amidox-
imes 2 and 3-ferrocenylpropynal (6). As concluded from our
previous study [22], the reactions were performed in the presence
of KOH in dioxane at 100 ꢀC. The results from a systematic study are
shown in Table 1. Initially, the reaction between 3-
ferrocenylpropynal (6) and benzamidoxime (2a) was carried out,
which afforded 5-ferrocenyl-substituted 1,2,4-oxadiazole 10a in
84% yield (Table 1, Entry 1). Then, as seen in Table 1, a variety of 5-
ferrocenyl-1,2,4-oxadiazoles 10 were synthesized under the same
conditions. The reactions went to completion in short times, such
proved by a control experiment. We anticipated that if an
a,b-
alkynic ketone such as 1,3-diphenylpropynone is employed, the
reaction would produce the isolable acetophenone instead of
acetaldehyde. As expected, the reaction between 1,3-
diphenylpropynone and benzamidoxime (2a) yielded 3,5-
diphenyl-1,2,4-oxadiazole and acetophenone [22], the formation
of latter clearly proves the occurrence of acetaldehyde in these
reactions. Noticeably, the formation of such side products is
important for the elucidation of the reaction mechanism as it will
be shown below.
The proposed mechanism for the formation of 5-ferrocenyl-
1,2,4-oxadiazoles 10 is depicted in Scheme 3. First, conjugate
addition of amidoxime 2 to 3-ferrocenylpropynal (6) produces
compound 11, in which hydrogen abstraction from primary amine
yields compound 12. Then intramolecular conjugate addition takes
place to give five-membered compound 13. Subsequently,
hydrogen exchange produces compound 14, which yields com-
pound 15 upon keto-enol tautomerization. Finally, compound 15
undergoes a rearrangement to afford 5-ferrocenyl-1,2,4-oxadiazole
10 and enolate 16, the hydrolysis of the latter gives acetaldehyde
(Scheme 3).
1. n-BuLi, THF, -40 oC
O
2. DMF, -40 to 0 oC
H
H
Fe
Fe
3. 10% aq. KH2PO4, 5 oC
7
6
OH
NH2OH.HCl
N
R
CN
R
NH2
NEt3, EtOH
78 oC
Conclusion
8
2
In summary, we have developed a new method for the synthesis
of 5-ferrocenyl-1,2,4-oxadiazoles by utilizing the reactions between
3-ferrocenylpropynal and amidoximes. Amidoximes were prepared
by the reaction of hydroxylamine hydrochloride with nitriles. The
reaction of 3-ferrocenylpropynal with a wide range of amidoximes
in the presence of KOH in dioxane at 100 ꢀC yielded the corre-
sponding 5-ferrocenyl-1,2,4-oxadiazoles along with acetaldehyde.
In many cases, 1,2,4-oxadiazoles were obtained from these re-
actions in good to high yields. The reaction was surprisingly general
O
NH2OH.HCl
CN
H
Fe
Fe
KI, ZnO
CH3CN, 82 oC
9
8k
Scheme 2.

M. Zora et al. / Journal of Organometallic Chemistry 759 (2014) 67e73
Table 1 (continued )
69
Table 1
One-pot synthesis of 5-ferrocenyl-1,2,4-oxadiazoles in the presence of KOH.
Entry
Amidoxime
Time (h)
1,2,4-Oxadiazole
% Yielda
7
0.5
78
Entry
Amidoxime
Time (h)
1,2,4-Oxadiazole
% Yielda
1b
2
84
8
0.5
54
2
3
4
3
95
85
61
9
0.5
82
0.5
10
0.5
44
11
0.5
22
0.5
a
Isolated yield.
b
The same reaction carried out for 4 and 8 h produced oxadiazole 10a in 70 and
61% yields, respectively.
c
The same reaction carried out for 4 h produced oxadiazole 10e in 69% yield.
for a diversity of amidoximes and allowed the presence of aryl
groups with electron-withdrawing and electron-donating sub-
stituents. In conclusion, the chemistry developed here represents a
rapid entry into 5-ferrocenyl-1,2,4-oxadiazole derivatives. In addi-
tion, the synthesized ferrocenyl heterocycles have potential as new
pharmacophores and scaffolds in medicinal chemistry.
5c
1
90
Experimental section
General information
6
2
79
1H and 13C NMR spectra were recorded at 400 and 100 MHz,
respectively. Chemical shifts are reported in parts per million (ppm)
downfield from an internal TMS (trimethylsilane) reference.
Coupling constants (J) are reported in Hertz (Hz), and spin

70
M. Zora et al. / Journal of Organometallic Chemistry 759 (2014) 67e73
Fc
O
OH
O
H
O
N
KOH
-H2O
N
+
Fc
H
NH2
R
NH2
6
2
R
Fc = ferrocenyl
11
Fc
Fc
Fc
~H+
O
H
H
H
O
O
O
N
N
N
NH O-K+
N- OH
K+
N-K+
H
R
R
13
14
R
12
Fc
H
O
H2O
O
Fc
O
H
N
N
+
N-
O
N
O-K+
H3C
K+
H
-KOH
R
R
10
16
15
Scheme 3.
multiplicities are presented by the following symbols: s (singlet), br
s (broad singlet), d (doublet), t (triplet), q (quartet), m (multiplet).
DEPT 13C NMR information is given in parentheses as C, CH, CH2 and
CH3. Infrared spectra (IR) were recorded by using attenuated total
reflection (ATR). Band positions are reported in reciprocal centi-
meters (cmꢁ1). Mass spectra (MS) and high resolution mass spectra
(HRMS) were obtained by using Electrospray Ionization (ESI) with
Micro-Tof; m/z values are reported (For each measurement, the mass
scale was recalibrated with sodium formate clusters, and samples
were dissolved and measured in MeOH). Flash chromatography was
performed using thick-walled glass columns and “flash grade” silica
(230e400 mesh). Thin layer chromatography (TLC) was performed
by using commercially prepared 0.25 mm silica gel plates and
visualization was effected with short wavelength UV lamp (254 nm).
The relative proportions of solvents in chromatography solvent
mixtures refer to the volume:volume ratio. All commercially avail-
able reagents were used directly without purification unless other-
wise stated. All the solvents used in reactions distilled for purity. The
inert atmosphere was created by slight positive pressure (ca. 0.1 psi)
of argon. All glassware was dried in oven prior to use. Note that we
reported the synthesis of amidoximes 2aej in a previous study [22].
In the preparation of amidoximes, commercially available nitriles
were employed, except that cyanoferrocene (8k) was prepared ac-
cording to a recent protocol [30].
and removed on a rotary evaporator. Purification of the crude
product by flash chromatography on silica gel using hexane/ethyl
acetate (1:2) as the eluent afforded 74 mg (15%) of the indicated
product. 1H NMR (400 MHz, CDCl3):
d
4.69 (br s, 2H), 4.47 (s, 2H),
4.21 (s, 2H), 4.15 (s, 5H) (OH peak was not observed due to H/D
exchange); 13C NMR (100 MHz, CDCl3):
171.9 (C), 73.4 (C), 69.7
d
(CH), 68.8 (CH), 67.7 (CH). The spectral data were in agreement with
those reported previously for this compound [28].
3-Ferrocenylpropynal (6)
Ethynylferrocene (7) (840 mg, 4.00 mmol) was dissolved in dry
THF (10 mL) under argon and the solution was cooled to ꢁ40 ꢀC. n-
BuLi (1.6 M in hexane, 2.5 mL, 4.00 mmol) was then added drop-
wise over 5 min maintaining the temperature between ꢁ35
and ꢁ40 ꢀC. After completion of the addition, anhydrous DMF
(0.6 mL, 8.00 mmol) was added in one portion and the cooling bath
was removed. The resulting reaction mixture was allowed to warm
to room temperature and stirred for 30 min. The reaction mixture
was then poured into a vigorously stirred biphasic solution, pre-
pared from a 10% aqueous solution of KH2PO4 (50 mL, 40.00 mmol)
and diethyl ether (50 mL), cooled over ice to 5 ꢀC. After layers were
separated, organic phase was washed with water (2 ꢂ 40 mL). Then
the resulting organic layer was dried over MgSO4 and removed on a
rotary evaporator. Purification of the crude product by flash chro-
matography on silica gel using hexane/ethyl acetate (9:1) as the
eluent afforded 847 mg (89%) of the indicated product. 1H NMR
Ferrocenecarboxamide oxime (2k)
(400 MHz, CDCl3):
d
9.27 (s, 1H), 4.60 (s, 2H), 4.41 (s, 2H), 4.25 (s,
176.2 (C), 99.5 (C), 87.7 (C), 73.3
To
a stirred solution of cyanoferrocene (8k) (422 mg,
5H); 13C NMR (100 MHz, CDCl3):
d
2.00 mmol) and NEt3 (364 mg, 3.60 mmol) in absolute EtOH
(10 mL) was slowly added hydroxylamine hydrochloride (208 mg,
3.00 mmol) and the resulting solution was heated under reflux
until nitrile was over (The progress of the reaction was monitored
by routine TLC for the disappearance of nitrile). After the solvent
was removed on a rotary evaporator to nearly dryness, ethyl acetate
(20 mL) and water (20 mL) were added. After the layers were
separated, the aqueous layer was extracted with ethyl acetate
(3 ꢂ 20 mL). The combined organic layers were dried over MgSO4
(CH), 71.3 (CH), 70.6 (CH), 59.2 (C). The spectral data were in
agreement with those reported previously for this compound [25].
General procedure for the one-pot synthesis of 5-ferrocenyl-1,2,4-
oxadiazoles (10) in the presence of KOH (Table 1)
To a stirred solution of 3-ferrocenylpropynal (6) (0.25 mmol) in
dioxane (7.5 mL) under argon was added the proper amidoxime 2

M. Zora et al. / Journal of Organometallic Chemistry 759 (2014) 67e73
71
(0.32 mmol) and KOH (0.25 mmol) and the resulting mixture was
3-(4-Chlorophenyl)-5-ferrocenyl-1,2,4-oxadiazole (10e) (Table 1,
heated under reflux for appropriate time. The progress of the re-
action was monitored by routine TLC for the disappearance of 3-
ferrocenylpropynal (6). After the reaction was over, the mixture
was allowed to cool to room temperature and filtrated to remove
undissolved KOH. Organic solvent was then removed on a rotary
evaporator to give the crude product, which was purified by flash
column chromatography on silica gel using hexane/ethyl acetate
(9:1) as the eluent to afford the corresponding 5-ferrocenyl-1,2,4-
oxadiazole derivative 10.
entry 5)
3-Ferrocenylpropynal (6) (50 mg, 0.21 mmol), 4-chloro-N0-
hydroxybenzimidamide (2e) (46 mg, 0.27 mmol) and KOH (12 mg,
0.21 mmol) were employed to afford 69 mg (90%) of the indicated
product. 1H NMR (400 MHz, CDCl3):
d
8.08 (d, J ¼ 8.2 Hz, 2H), 7.47
(d, J ¼ 8.2 Hz, 2H), 5.05 (s, 2H), 4.55 (s, 2H), 4.20 (s, 5H); 13C NMR
(100 MHz, CDCl3):
d 179.6 (C), 167.9 (C), 137.1 (C), 129.1 (CH), 128.9
(CH), 125.7 (C), 71.7 (CH), 70.2 (CH), 69.1 (CH), 65.9 (C); IR (neat):
1591, 1571, 1473, 1404, 1348, 1278, 1143, 1080, 1004, 910, 823,
761 cmꢁ1; MS (ESI, m/z): 364.01 [M]þ; HRMS (ESI): calcd. for
C
18H13ClFeN2O: 364.0066 [M]þ, found: 364.0061.
5-Ferrocenyl-3-phenyl-1,2,4-oxadiazole (10a) (Table 1, entry 1)
3-Ferrocenylpropynal (6) (50 mg, 0.21 mmol), N0-hydrox-
ybenzimidamide (2a) (37 mg, 0.27 mmol) and KOH (12 mg,
0.21 mmol) were employed to afford 58 mg (84%) of the indicated
3-(2-Chlorophenyl)-5-ferrocenyl-1,2,4-oxadiazole (10f) (Table 1,
entry 6)
3-Ferrocenylpropynal (6) (50 mg, 0.21 mmol), 2-chloro-N0-
hydroxybenzimidamide (2f) (46 mg, 0.27 mmol) and KOH (12 mg,
0.21 mmol) were employed to afford 60 mg (79%) of the indicated
product. 1H NMR (400 MHz, CDCl3):
d
8.16 (m, 2H), 7.52 (m, 3H),
5.08 (s, 2H), 4.56 (s, 2H), 4.22 (s, 5H); 13C NMR (100 MHz, CDCl3):
179.3 (C), 168.7 (C), 131.0 (CH), 128.8 (CH), 127.6 (CH), 127.2 (C),
product. 1H NMR (400 MHz, CDCl3):
d
7.95 (dd, J ¼ 7.4 and 1.9 Hz,
1H), 7.56 (dd, J ¼ 7.9 and 1.5 Hz, 1H), 7.43 (m, 2H), 5.09 (s, 2H), 4.57
(s, 2H), 4.23 (s, 5H); 13C NMR (100 MHz, CDCl3):
177.2 (C), 165.7
d
71.5 (CH), 70.1 (CH), 69.1 (CH), 66.2 (C); IR (neat): 1595, 1583, 1477,
1444, 1352, 1274, 1139, 1109, 1024, 999, 904, 881, 819, 752 cmꢁ1; MS
(ESI, m/z): 353.04 [M þ Na]þ; HRMS (ESI): calcd. for C18H14Fe-
N2ONa: 353.0353 [M þ Na]þ, found: 353.0348.
d
(C), 131.7 (C), 129.9 (CH), 129.7 (CH), 128.9 (CH), 125.0 (CH), 124.7
(C), 69.9 (CH), 68.4 (CH), 67.3 (CH), 63.9 (C); IR (neat): 1591, 1566,
1473, 1328, 1274, 1143, 1107, 1026, 1002, 908, 879, 823, 758 cmꢁ1
;
MS (ESI, m/z): 364.01 [M]þ; HRMS (ESI): calcd. for C18H13ClFeN2O:
5-Ferrocenyl-3-(p-tolyl)-1,2,4-oxadiazole (10b) (Table 1, entry 2)
3-Ferrocenylpropynal (6) (50 mg, 0.21 mmol), N0-hydroxy-4-
methylbenzimidamide (2b) (41 mg, 0.27 mmol) and KOH (12 mg,
0.21 mmol) were employed to afford 69 mg (95%) of the indicated
364.0066 [M]þ, found: 364.0061.
5-Ferrocenyl-3-(3-fluorophenyl)-1,2,4-oxadiazole (10g) (Table 1,
entry 7)
product. 1H NMR (400 MHz, CDCl3):
d
8.04 (d, J ¼ 7.9 Hz, 2H), 7.31
(d, J ¼ 7.9 Hz, 2H), 5.07 (s, 2H), 4.54 (s, 2H), 4.21 (s, 5H), 2.34 (s, 3H);
13C NMR (100 MHz, CDCl3):
179.1 (C), 168.7 (C), 141.3 (C), 129.5
3-Ferrocenylpropynal (6) (50 mg, 0.21 mmol), 3-fluoro-N0-
hydroxybenzimidamide (2g) (42 mg, 0.27 mmol) and KOH (12 mg,
0.21 mmol) were employed to afford 57 mg (78%) of the indicated
d
(CH), 127.5 (CH), 124.4 (C), 71.5 (CH), 70.1 (CH), 69.1 (CH), 66.3 (C),
21.6 (CH3); IR (neat): 1595, 1575, 1409, 1346, 1278, 1143, 1103, 1029,
908, 881, 821, 759 cmꢁ1; MS (ESI, m/z): 344.06 [M]þ; HRMS (ESI):
calcd. for C19H16FeN2O: 344.0612 [M]þ, found: 344.0607.
product. 1H NMR (400 MHz, CDCl3):
d
7.94 (pseudo d, J ¼ 6.8 Hz,
1H), 7.86 (pseudo d, J ¼ 8.8 Hz, 1H), 7.48 (pseudo d, J ¼ 6.0 Hz, 1H),
7.29e7.15 (m, 1H), 5.07 (s, 2H), 4.55 (s, 2H), 4.21 (s, 5H); 13C NMR
(100 MHz, CDCl3):
d
179.7 (C), 167.9 (C), 162.9 (d, J ¼ 244.0 Hz, C),
130.5 (d, J ¼ 8.2 Hz, CH), 129.3 (d, J ¼ 8.0 Hz, C), 123.2 (d, J ¼ 2.5 Hz,
CH), 117.9 (d, J ¼ 21.0 Hz, CH), 114.6 (d, J ¼ 23.0 Hz, CH), 71.7 (CH),
70.2 (CH), 69.1 (CH), 65.9 (C); IR (neat): 1600,1585,1523,1488,1415,
1357, 1267, 1201, 1132, 1026, 1001, 877, 858, 821, 798, 763 cmꢁ1; MS
(ESI, m/z): 348.04 [M]þ; HRMS (ESI): calcd. for C18H13FFeN2O:
348.0361 [M]þ, found: 348.0358.
5-Ferrocenyl-3-(4-methoxyphenyl)-1,2,4-oxadiazole (10c) (Table 1,
entry 3)
3-Ferrocenylpropynal (6) (50 mg, 0.21 mmol), N0-hydroxy-4-
methoxybenzimidamide (2c) (45 mg, 0.27 mmol) and KOH
(12 mg, 0.21 mmol) were employed to afford 64 mg (85%) of the
indicated product. 1H NMR (400 MHz, CDCl3):
d
8.09 (d, J ¼ 8.7 Hz,
2H), 7.01 (d, J ¼ 8.7 Hz, 2H), 5.06 (s, 2H), 4.53 (s, 2H), 4.20 (s, 5H),
3.87 (s, 3H); 13C NMR (100 MHz, CDCl3):
178.9 (C), 168.4 (C), 161.9
5-Ferrocenyl-3-(naphthalen-1-yl)-1,2,4-oxadiazole (10h) (Table 1,
entry 8)
d
3-Ferrocenylpropynal (6) (50 mg, 0.21 mmol), N0-hydroxy-1-
naphthimidamide (2h) (50 mg, 0.27 mmol) and KOH (12 mg,
0.21 mmol) were employed to afford 43 mg (54%) of the indicated
(C), 129.0 (CH), 119.7 (C), 114.2 (CH), 71.5 (CH), 70.1 (CH), 69.1 (CH),
66.4 (C), 55.4 (CH3); IR (neat): 1595, 1485, 1417, 1352, 1251, 1172,
1107, 1026, 1002, 900, 877, 817, 765 cmꢁ1; MS (ESI, m/z): 360.06
[M]þ; HRMS (ESI): calcd. for C19H16FeN2O2: 360.0561 [M]þ, found:
360.0558.
product. 1H NMR (400 MHz, CDCl3):
d
8.99 (d, J ¼ 8.5 Hz, 1H), 8.34
(d, J ¼ 7.1 Hz,1H), 8.03 (d, J ¼ 8.2 Hz,1H), 7.95 (d, J ¼ 8.1 Hz,1H), 7.62
(m, 3H), 5.14 (s, 2H), 4.57 (s, 2H), 4.25 (s, 5H); 13C NMR (100 MHz,
CDCl3):
d 178.5 (C), 169.1 (C), 133.9 (C), 131.7 (CH), 130.8 (C), 129.3
N,N-Dimethyl-4-(5-ferrocenyl-1,2,4-oxadiazol-3-yl)aniline (10d)
(Table 1, entry 4)
(CH), 128.7 (CH), 127.5 (CH), 126.4 (CH), 126.3 (CH), 125.1 (CH), 124.2
(C), 71.7 (CH), 70.2 (CH), 69.2 (CH), 66.2 (C); IR (neat): 1600, 1595,
3-Ferrocenylpropynal (6) (50 mg, 0.21 mmol), 4-(dimethyla-
mino)-N0-hydroxybenzimidamide (2d) (49 mg, 0.27 mmol) and
KOH (12 mg, 0.21 mmol) were employed to afford 48 mg (61%) of
1577, 1353, 1305, 1261, 1149, 1028, 1002, 904, 879, 808, 777 cmꢁ1
;
MS (ESI, m/z): 403.05 [M þ Na]þ; HRMS (ESI): calcd. for C22H16Fe-
N2ONa: 403.0510 [M þ Na]þ, found: 403.0504.
the indicated product. 1H NMR (400 MHz, CDCl3):
d
8.00
(d, J ¼ 8.8 Hz, 2H), 6.78 (d, J ¼ 8.8 Hz, 2H), 5.06 (s, 2H), 4.53 (s, 2H),
4.21 (s, 5H), 3.05 (s, 6H); 13C NMR (100 MHz, CDCl3):
178.4 (C),
3-(Benzo[d][1,3]dioxol-5-yl)-5-ferrocenyl-1,2,4-oxadiazole (10i)
(Table 1, entry 9)
d
169.8 (C), 152.2 (C), 128.7 (CH), 114.5 (C), 111.8 (CH), 71.3 (CH), 70.1
(CH), 69.0 (CH), 66.7 (C), 40.2 (CH3); IR (neat): 1598, 1564, 1487,
1431, 1355, 1280, 1193, 1145, 1103, 1024, 1001, 890, 877, 819,
765 cmꢁ1; MS (ESI, m/z): 373.09 [M]þ; HRMS (ESI): calcd. for
3-Ferrocenylpropynal (6) (50 mg, 0.21 mmol), N0-hydroxybenzo
[d][1,3]dioxole-5-carboximidamide (2i) (49 mg, 0.27 mmol) and
KOH (12 mg, 0.21 mmol) were employed to afford 65 mg (82%) of
the indicated product. 1H NMR (400 MHz, CDCl3):
d
7.71 (d,
C
20H19FeN3O: 373.0878 [M]þ, found: 373.0872.
J ¼ 8.0 Hz, 1H), 7.59 (s, 1H), 6.93 (d, J ¼ 8.0 Hz, 1H), 6.05 (s, 2H), 5.05

72
M. Zora et al. / Journal of Organometallic Chemistry 759 (2014) 67e73
(s, 2H), 4.55 (s, 2H), 4.21 (s, 5H); 13C NMR (100 MHz, CDCl3):
d 179.0
[4] (a) J. Xu, L. Wei, R. Mathvink, J. He, Y.J. Park, H. He, B. Leiting, K.A. Lyons,
F. Marsilio, R.A. Patel, J.K. Wu, N.A. Thornberry, A.E. Weber, Bioorg. Med.
Chem. Lett. 15 (2005) 2533;
(b) M. Benltifa, S. Vidal, B. Fenet, M. Msaddek, P.G. Goekjian, J.P. Praly,
A. Brunyanszki, T. Docsa, P. Gergely, Eur. J. Org. Chem. (2006) 4242.
[5] R.D. Haugwitz, A.J. Martinez, J. Venslavsky, R.G. Angel, B.V. Maurer,
G.A. Jacobs, V.L. Narayanan, L.R. Cruthers, J. Szanto, J. Med. Chem. 28 (1985)
1234.
[6] J.W.H. Watthey, M. Desai, R. Rutledge, R. Dotson, J. Med. Chem. 23 (1980) 690.
[7] (a) S.E. Dahlgren, T. Dalhamn, Acta Pharmacol. Toxicol. 31 (1972) 193;
(b) P.C. Unangst, G.P. Shrum, D.T. Connor, R.D. Dyer, D.J. Schrier, J. Med. Chem.
35 (1992) 3691;
(C), 168.3 (C), 149.9 (C), 148.1 (C), 122.4 (CH), 121.1 (C), 108.6 (CH),
107.6 (CH), 101.5 (CH2), 71.5 (CH), 70.1 (CH), 69.1 (CH), 66.2 (C); IR
(neat): 1591, 1456, 1325, 1238, 1134, 1103, 1035, 1008, 933, 881, 817,
761 cmꢁ1; MS (ESI, m/z): 397.03 [M þ Na]þ; HRMS (ESI): calcd. for
C
19H14FeN2O3Na: 397.0252 [M þ Na]þ, found: 397.0246.
5-Ferrocenyl-3-(1H-indol-4-yl)-1,2,4-oxadiazole (10j) (Table 1,
entry 10)
3-Ferrocenylpropynal (6) (50 mg, 0.21 mmol), N0-hydroxy-1H-
indole-4-carboximidamide (2j) (47 mg, 0.27 mmol) and KOH
(12 mg, 0.21 mmol) were employed to afford 34 mg (44%) of the
(c) D.N. Nicolaides, K.C. Fylaktakidou, K.E. Litinas, D. Hadjipavlou-Litina, Eur. J.
Med. Chem. 33 (1998) 715;
(d) L.F.C.C. Leite, M.N. Ramos, J.B.P. Da Silva, A.L.P. Miranda, C.A.M. Fraga,
E.J. Barreiro, Il Farmaco 54 (1999) 747;
(e) R.M. Srivastava, A. De Almeida Lima, O.S. Viana, M.J. Da Costa Silva,
M.T.J.A. Catanho, J.O.F. DeMorais, Bioorg. Med. Chem. 11 (2003) 1821;
(f) N.M.M. Bezerra, S.P. De Oliveira, R.M. Srivastava, J.R. Da Silva, Il Farmaco 60
(2005) 955.
indicated product. 1H NMR (400 MHz, DMSO-d6):
d
11.48 (s, 1H),
7.89 (m, 1H), 7.73e7.45 (m, 2H), 7.37e6.98 (m, 2H), 5.12 (s, 2H), 4.68
(s, 2H), 4.25 (s, 5H); 13C NMR (100 MHz, DMSO-d6):
177.8 (C),
d
[8] (a) A.C.L. Leite, R.F. Vieira, A.R. De Faria, A.G. Wanderley, P. Afiatpour,
E.C.P.A. Ximenes, R.M. Srivastava, C.F. De Oliveira, M.V. Medeiros, E. Antunes,
D.J. Brondani, Il Farmaco 55 (2000) 719;
168.5 (C), 136.4 (C), 127.0 (CH), 124.9 (C), 120.6 (CH), 120.0 (CH),
117.1 (C), 114.7, 102.3 (CH), 71.6 (CH), 69.8 (CH), 68.7 (CH), 65.6 (C);
IR (neat): 3325, 3101, 1591, 1575, 1523, 1487, 1429, 1346, 1313, 1274,
1191, 1029, 1002, 893, 823, 761 cmꢁ1; MS (ESI, m/z): 369.06 [M]þ;
HRMS (ESI): calcd. for C20H15FeN3O: 369.0565 [M]þ, found:
369.0559.
(b) M.H. Gezginci, A.R. Martin, S.G. Franzblau, J. Med. Chem. 44 (2001) 1560;
(c) A.G. Tyrkov, L.T. Sukhenko, Pharm. Chem. J. 38 (2004) 376;
(d) Y.W. Jo, W.B. Im, J.K. Rhee, M.J. Shim, W.B. Kim, E.C. Choi, Bioorg. Med.
Chem. 12 (2004) 5909;
(e) D. Rakesh, R.B. Sun, R.P.L. Tangallapally, R.E. Lee, Eur. J. Med. Chem. 44
(2009) 460.
[9] D.M. Cottrell, J. Capers, M.M. Salem, K. DeLuca-Fradley, S.L. Croft,
K.A. Werbovetz, Bioorg. Med. Chem. 12 (2004) 2815.
3,5-Diferrocenyl-1,2,4-oxadiazole (10k) (Table 1, entry 11)
[10] (a) T. Sakamoto, M.D. Cullen, T.L. Hartman, K.M. Watson, R.W. Buckheit,
C. Pannecouque, E. De Clercq, M. Cushman, J. Med. Chem. 50 (2007) 3314;
(b) K. Liu, H. Lu, L. Hou, Z. Qi, C. Teixeira, F. Barbault, B.T. Fan, S. Liu, S. Jiang,
L. Xie, J. Med. Chem. 51 (2008) 7843.
[11] (a) C.B. Vu, E.G. Corpuz, S.G. Pradeepan, S. Violette, C. Bartlett, T.K. Sawyer,
Bioorg. Med. Chem. Lett. 9 (1999) 3009;
3-Ferrocenylpropynal (6) (50 mg, 0.21 mmol), ferrocene-
carboxamide oxime (2k) (66 mg, 0.27 mmol) and KOH (12 mg,
0.21 mmol) were employed to afford 20 mg (22%) of the indicated
product. 1H NMR (400 MHz, CDCl3):
d
5.07 (pseudo t, J ¼ 1.6 Hz, 2H),
4.98 (pseudo t, J ¼ 2.0 Hz, 2H), 4.55 (pseudo t, J ¼ 1.6 Hz, 2H), 4.45
(b) C.B. Vu, E.G. Corpuz, T.J. Merry, S.G. Pradeepan, C. Bartlett, R.S. Bohacek,
M.C. Botfield, C.J. Eyermann, B.A. Lynch, I.A. MacNeil, M.K. Ram, M.R. van
Schravendijk, S. Violette, T.K. Sawyer, J. Med. Chem. 42 (1999) 4088;
(c) K.A. Jessen, N.M. English, J.Y. Wang, S. Maliartchouk, S.P. Archer, L. Qiu,
R. Brand, J. Kuemmerle, H.Z. Zhang, K. Gehlsen, J. Drewe, B. Tseng, S.X. Cai,
S. Kasibhatla, Mol. Cancer Ther. 4 (2005) 761;
(d) H.Z. Zhang, S. Kasibhatla, J. Kuemmerle, W. Kemnitzer, K. Ollis-Mason,
L. Qiu, C. Crogan-Grundy, B. Tseng, J. Drewe, S.X. Cai, J. Med. Chem. 48 (2005)
5215;
(pseudo t, J ¼ 2.0 Hz, 2H), 4.21 (s, 5H), 4.18 (s, 5H); 13C NMR
(100 MHz, CDCl3):
d 178.4 (C), 170.4 (C), 71.4 (CH), 70.4 (C), 70.2
(CH), 70.1 (CH), 69.8 (CH), 69.1 (CH), 68.4 (CH), 66.4 (C); IR
(neat):1593, 1556, 1458, 1380, 1315, 1276, 1159, 1105, 1024, 999, 881,
813, 769 cmꢁ1; MS (ESI, m/z): 438.01 [M]þ; HRMS (ESI): calcd. for
C
22H18Fe2N2O: 438.0118 [M]þ, found: 438.0113.
(e) M.L. Boys, L.A. Schretzman, N.S. Chandrakumar, M.B. Tollefson, S.B. Mohler,
V.L. Downs, T.D. Penning, M.A. Russell, J.A. Wendt, B.B. Chen, H.G. Stenmark,
H. Wu, D.P. Spangler, M. Clare, B.N. Desai, I.K. Khanna, M.N. Nguyen, T. Duffin,
V.W. Engleman, M.B. Finn, S.K. Freeman, M.L. Hanneke, J.L. Keene, J.A. Klover,
G.A. Nickols, M.A. Nickols, C.N. Steininger, M. Westlin, W. Westlin, Y.X. Yu,
Y. Wang, C.R. Dalton, S.A. Norring, Bioorg. Med. Chem. Lett. 16 (2006) 839;
(f) S. Fujii, K. Ohta, T. Goto, H. Kagechika, Y. Endo, Bioorg. Med. Chem. 17
(2009) 344.
Acknowledgments
We thank the Scientific and Technical Research Council of
Turkey (110T113) and the Research Board of Middle East Technical
University (METU) (BAP-2011-07-02-00-01) for financial support of
this research, and METU Faculty Development Program (ÖYP-
Yüzüncü Yıl University) for a scholarship to A.K.
[12] (a) G.D. Diana, D.L. Volkots, T.J. Nitz, T.R. Baily, M.A. Long, N. Vescio, S. Aldous,
D.C. Pevear, F. Dutko, J. Med. Chem. 37 (1994) 2421;
(b) S. Borg, R.C. Vollinga, M. Labarre, K. Payza, L. Terenius, K. Luthman, J. Med.
Chem. 42 (1999) 4331.
Appendix A. Supplementary data
[13] V.V. Sureshbabu, H.P. Hemantha, S.A. Naik, Tetrahedron Lett. 49 (2008) 5133.
[14] (a) B.S. Orlek, F.E. Blaney, F. Brown, M.S.G. Clark, M.S. Hadley, J. Hatcher,
G.J. Riley, H.E. Rosenberg, H.J. Wadsorth, P. Wyman, J. Med. Chem. 34 (1991)
2726;
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.jorganchem.2014.02.018.
(b) T. Suzuki, H. Uesaka, H. Hamajima, T. Ikami, Chem. Pharm. Bull. 47 (1999)
876.
[15] C.J. Swain, R. Baker, C. Kneen, J. Moseley, J. Saunders, E.M. Seward,
G. Stevenson, M. Beer, J. Stanton, K. Watling, J. Med. Chem. 34 (1991) 140.
[16] (a) F. Watjen, R. Baker, M. Engelstoff, R. Herbert, A. Macleod, A. Knight,
K. Merchant, J. Moseley, J. Saunders, C.J. Swain, E. Wong, J.P. Springer, J. Med.
Chem. 32 (1989) 2282;
(b) J.P. Williams, K. Lavrador, Comb. Chem. High Throughput Screening 3
(2000) 43.
[17] M. Ankersen, B. Peschke, B.S. Hansen, T.K. Hansen, Bioorg. Med. Chem. Lett. 7
(1997) 1293.
[18] F.I. Carroll, J.L. Gray, P. Abraham, M.A. Kuzemko, A.H. Lewin, J.W. Boja,
M.J. Kuhar, J. Med. Chem. 36 (1993) 2886.
[19] (a) M.L. Kuznetsov, V.Y. Kukushkin, M. Haukka, A.J.L. Pombeiro, Inorg. Chim.
Acta 356 (2003) 85;
References
[1] For reviews of 1,2,4-oxadiazoles, see: (a) J.C. Jochims, in: A.R. Katritzky,
C.W. Rees, E.F.V. Scriven, R.C. Storr (Eds.), Comprehensive Heterocyclic
Chemistry II, vol. 4, Pergamon, Oxford, 1996, pp. 179e228 (Chapter 4.04);
(b) K. Hemming, J. Chem. Res. Synop. (2001) 209;
(c) L.A. Kayukova, Pharm. Chem. J. 39 (2005) 539;
(d) K. Hemming, in: A.R. Katritzky, C.A. Ramsden, E.F.V. Scriven, R.J.K. Taylor,
V.V. Zhdankin (Eds.), Comprehensive Heterocyclic Chemistry III, vol. 5, Per-
gamon, Oxford, U.K., 2008, pp. 243e314 (Chapter 5.04);
(e) A. Pace, P. Pierro, Org. Biomol. Chem. 7 (2009) 4337.
[2] (a) R. Antunes, H. Batista, R.M. Srivastava, G. Thomas, C.C. Araujo, Bioorg. Med.
Chem. Lett. 8 (1998) 3071;
(b) K.I. Itoh, H. Sakamaki, C.A. Horiuchib, Synthesis (2005) 1935;
(c) J.K. Augustine, V. Akabote, S.G. Hegde, P. Alagarsamy, J. Org. Chem. 74
(2009) 5640;
(d) N. Nishiwaki, K. Kobiro, S. Hirao, J. Sawayama, K. Saigo, Y. Ise, Y. Okajima,
M. Ariga, Org. Biomol. Chem. 9 (2011) 6750.
(b) R. Antunes, H. Batista, R.M. Srivastava, G. Thomas, C.C. Araujo, R.L. Longo,
H. Magalhaes, M.B.C. Leao, A.C. Pava, J. Mol. Struct. 660 (2003) 1.
[3] (a) J.T. Palmer, R.M. Rydzewski, R.V. Mendonca, D. Sperandio, J.R. Spencer,
B.L. Hirschbein, J. Lohman, J. Beltman, M. Nguyen, L. Liu, Bioorg. Med. Chem.
Lett. 16 (2006) 3434;
[20] (a) C.D. Bedford, R.A. Howd, O.D. Dailey, A. Miller, H.W. Nolen, R.A. Kenley,
J.R. Kern, J.S. Winterle, J. Med. Chem. 29 (1986) 2174;
(b) J. Garfunkle, C. Ezzili, T.J. Rayl, D.G. Hochstatter, I. Hwang, D.L. Boger,
J. Med. Chem. 51 (2008) 4392.
(b) T.L. Deegan, T.J. Nitz, D. Cebzanov, D.E. Pufko, J.A. Porco Jr., Bioorg. Med.

M. Zora et al. / Journal of Organometallic Chemistry 759 (2014) 67e73
73
Chem. Lett. 9 (1999) 209;
[23] (a) C. Biot, G. Glorian, L.A. Maciejewski, J.S. Brocard, J. Med. Chem. 40 (1997)
3715;
(c) C.K. Sams, J. Lau, Tetrahedron Lett. 40 (1999) 9359;
(d) A.R. Gangloff, J. Litvak, E.J. Shelton, D. Sperandio, V.R. Wang, K.D. Rice,
Tetrahedron Lett. 42 (2001) 1441;
(e) R.F. Poulain, A.L. Tartara, B.P. Deprez, Tetrahedron Lett. 42 (2001) 1495;
(f) T. Zhou, Z.C. Chen, Synth. Commun. 32 (2002) 887;
(g) E. Meyer, A.C. Joussef, H. Gallardo, Synthesis (2003) 899;
(h) A. Hamze, J.F. Hernandez, P. Fulcrand, J. Martinez, J. Org. Chem. 68 (2003)
7316;
(i) M.D. Evans, J. Ring, A. Schoen, A. Bell, P. Edwards, D. Berthelot,
R. Nicewongera, C.M. Baldino, Tetrahedron Lett. 44 (2003) 9337;
(j) V.M.L. Braga, S.J. de Melo, R.M. Srivastava, E.P. da S. Falcao, J. Braz. Chem.
Soc. 15 (2004) 603;
(k) V. Santagada, F. Frecentese, E. Perissutti, D. Cirillo, S. Terracciano,
G. Caliendo, Bioorg. Med. Chem. Lett. 14 (2004) 4491;
(l) A.R. Katritzky, A.A. Shestopalov, K. Suzuki, ARKIVOC vii (2005) 36;
(m) S. Buscemi, A. Pace, A.P. Piccionello, N. Vivona, J. Fluorine Chem. 127
(2006) 1601;
(b) O. Domarle, G. Blampain, H. Agnanet, T. Nzadiyabi, J. Lebibi, J. Brocard,
L. Maciejewski, C. Biot, A.J. Georges, P. Millet, Antimicrob. Agents Chemother.
42 (1998) 540;
(c) C. Biot, L. Delhaes, C.M. N’Diaye, L.A. Maciejewski, D. Camus, D. Dive,
J.S. Brocard, Bioorg. Med. Chem. 7 (1999) 2843;
(d) M. Zora, E.U. Gungor, Tetrahedron Lett. 42 (2001) 4733;
(e) M. Zora, B. Yucel, N.B. Peynircioglu, J. Organomet. Chem. 656 (2002) 11;
(f) M. Zora, B. Yucel, S. Acikalin, Tetrahedron Lett. 44 (2003) 2237;
(g) G. Jaouen, S. Top, A. Vessieres, G. Leclercq, M.J. McGlinchey, Curr. Med.
Chem. 11 (2004) 2505;
(h) G. Jaouen, Bioorganometallics, Wiley-VCH, Weinheim, 2006;
(i) M. Zora, C. Acikgoz, M. Odabasoglu, O. Buyukgungor, J. Organomet. Chem.
692 (2006) 1571;
(j) G. Jaouen, P. Dyson, in: R.H. Crabtree, D.M.P. Mingos, D. O’Hare (Eds.),
Comprehensive Organometallic Chemistry III, vol. 12, Elsevier, Oxford, 2007,
pp. 445e464 (Chapter 8);
(n) M. Tamura, Y. Ise, Y. Okajima, N. Nishiwaki, M. Ariga, Synthesis (2006)
3453;
(o) K.K.D. Amarasinghe, M.B. Maier, A. Srivastava, J.L. Gray, Tetrahedron Lett.
47 (2006) 3629;
(p) L. Yan, P. Huo, G. Doherty, L. Toth, J.J. Hale, S.G. Mills, R. Hajdu,
C.A. Keohane, M.J. Rosenbach, J.A. Milligan, G.J. Shei, G. Chrebet, J. Bergstrom,
D. Card, E. Quackenbush, A. Wickhamc, S.M. Mandala, Bioorg. Med. Chem. Lett.
16 (2006) 3679;
(k) D. Dive, C. Biot, ChemMedChem 3 (2008) 383;
(l) M. Zora, O. Velioglu, J. Organomet. Chem. 693 (2008) 2159;
(m) C.G. Hartinger, P.J. Dyson, Chem. Soc. Rev. 38 (2009) 391;
(n) G. Jaouen, N. Metzler-Nolte (Eds.), Medicinal Organometallic Chemistry,
Topics in Organometallic Chemistry, vol. 32, Springer, Berlin, 2010;
(o) M. Gormen, P. Pigeon, S. Top, E.A. Hillard, M. Huche, C.G. Hartinger, F. de
Montigny, M.A. Plamont, A. Vessieres, G. Jaouen, ChemMedChem 5 (2010)
2039;
(q) W. Du, W.K. Hagmann, J.J. Hale, Tetrahedron Lett. 47 (2006) 4271;
(r) X. Yang, Z. Wang, X. Fang, X. Yang, F. Wu, Y. Shen, Synthesis (2007) 1768;
(s) D. Grant, R. Dahl, N.D.P. Cosford, J. Org. Chem. 73 (2008) 7219.
[21] For selected syntheses of 1,2,4-oxadiazoles, see: (a) A.H. Moustafa, Synthesis
(2003) 837;
(p) P. Pigeon, S. Top, A. Vessieres, M. Huche, M. Gormen, M. El Arbi,
M.A. Plamont, M.J. McGlinchey, G. Jaouen, New J. Chem. 35 (2011) 2212.
[24] (a) M. Zora, M. Kokturk, T. Eralp, Tetrahedron 62 (2006) 10344;
(b) M. Zora, T.A. Tumay, O. Buyukgungor, Tetrahedron 63 (2007) 4018.
[25] (a) G. Doisneau, G. Balavoine, T. Fillebeen-Khan, J. Organomet. Chem. 425
(1992) 113;
(b) A. Auffrant, F. Diederich, Helv. Chim. Acta 87 (2004) 3085.
[26] M. Journet, D. Cai, L.M. DiMichele, R.D. Larsen, Tetrahedron Lett. 39 (1998)
6427.
[27] A.G.M. Barrett, S.M. Cramp, R.S. Roberts, F.J. Zecri, Comb. Chem. High
Throughput Screening 3 (2000) 131.
[28] A.D. Ryabov, G.M. Kazankov, I.M. Panyashkina, O.V. Grozovsky,
O.G. Dyachenko, V.A. Polyakov, L.G. Kuz’mina, J. Chem. Soc. Dalton Trans.
(1997) 4385.
(b) T. Suyama, N. Suzuki, M. Nishimura, Y. Saitoh, H. Ohkoshi, J.I. Yamaguchi,
Bull. Chem. Soc. Jpn. 78 (2005) 873;
(c) Y. Wang, R.L. Miller, D.R. Sauer, S.W. Djuric, Org. Lett. 7 (2005) 925;
(d) M. Adib, M. Mahdavi, N. Mahmoodi, H. Pirelahi, H.R. Bijanzadeh, Synlett
(2006) 1765;
(e) W. Du, Q. Truong, H. Qi, Y. Guo, H.R. Chobanian, W.K. Hagmann, J.J. Hale,
Tetrahedron Lett. 48 (2007) 2231;
(f) Q. Zhao, S. Liu, Y. Li, Q. Wang, J. Agric. Food Chem. 57 (2009) 2849;
(g) M. Adib, S. Bagherzadeh, M. Mahdavia, H.R. Bijanzadeh, Mendeleev
Commun. 20 (2010) 50;
[29] (a) T.G. Traylor, J.C. Ware, J. Am. Chem. Soc. 89 (1967) 2304;
(b) W.E. Watts, J. Organomet. Chem. Libr. 7 (1979) 399;
(c) X. Creary, M.E. Mehrsheikh-Mohammadi, S. McDonald, J. Org. Chem. 54
(1989) 2904;
(h) S. Dosa, J. Daniels, M. Gutschow, J. Heterocycl. Chem. 48 (2011) 407;
(i) S.D. Diwakar, R.S. Joshi, C.H. Gill, J. Heterocycl. Chem. 48 (2011) 882;
(j) D. Kumar, G. Patel, L. Vijayakrishnan, S.G. Dastidar, A. Ray, Chem. Biol. Drug
Des. 79 (2012) 810;
(d) X. Creary, Org. Lett. 2 (2000) 2069;
(k) Z. Fu, R. Su, Y. Wang, Y.F. Wang, W. Zeng, N. Xiao, Y. Wu, Z. Zhou, J. Chen,
F.X. Chen, Chem. Eur. J. 18 (2012) 1886;
(e) L.E. Harrington, I. Vargas-Baca, N. Reginato, M.J. McGlinchey, Organome-
tallics 22 (2003) 663.
(l) H.Y. Lin, B.B. Snider, J. Org. Chem. 77 (2012) 4832.
[22] A. Kivrak, M. Zora, Tetrahedron 70 (2014) 817.
[30] A. Kivrak, M. Zora, J. Organomet. Chem. 692 (2007) 2346.