Iron(III) chloride/diorganyl diselenides: A tool for intramolecular cyclization of alkynone O-methyloximes

Article abstract of DOI:10.1021/jo302770g

This report describes the synthesis of 4-organoselenylisoxazoles via FeCl₃/RSeSeR-mediated intramolecular cyclization of alkynone O-methyloximes. The optimized conditions allowed the cyclization to proceed at room temperature under ambient atmo

Full text of DOI:10.1021/jo302770g

Article
pubs.acs.org/joc
Iron(III) Chloride/Diorganyl Diselenides: A Tool for Intramolecular
Cyclization of Alkynone O‑Methyloximes
Adriane Speranca,† Benhur Godoi,‡ and Gilson Zeni†,*
̧
†Laborator
Rio Grande do Sul, 97105-900 Brazil
́ ́ ́ ̂
io de Síntese, Reatividade, Avaliaca̧ o Farmacologica e Toxicologica de Organocalcogenios, CCNE, UFSM, Santa Maria -
̃
‡Universidade Federal da Fronteira Sul, Cerro Largo, Rio Grande do Sul 97900-000, Brazil
S
* Supporting Information
ABSTRACT: This report describes the synthesis of 4-organoselenylisoxazoles via
FeCl3/RSeSeR-mediated intramolecular cyclization of alkynone O-methyloximes.
The optimized conditions allowed the cyclization to proceed at room temperature
under ambient atmosphere, and the reaction requires a short time to be
completed. The reaction conditions tolerated neutral, electron-donating and
electron-withdrawing groups present in both substrates, alkynone O-methyloximes
and diorganyl diselenides. Treatment of 4-organoselenylisoxazoles with n-
butyllithium, followed by trapping with electrophiles, furnished the functionalized
isoxazoles in good yields. The obtained products also proved to be suitable
substrates for the preparation of 4-bromoisoxazoles via Br/Se exchange reaction.
in many synthetic processes, such as palladium-catalyzed
Sonogashira, Suzuki, and Heck cross coupling as well as
carbonylative reactions.9
INTRODUCTION
■
Compounds containing one or more heterocyclic rings in their
structures are widely studied principally in view of their
important biological activities.1 In particular, isoxazoles
represent an interesting class of heterocycles that display a
range of biological properties, such as anti-inflammatory,2
antimicrobial,3 anticancer,4 and antinociceptive (Figure1).5 In
In recent years, environmental concerns have directly
influenced the development of new methodologies with high
synthetic efficiency, atom economy, and employing mild
reaction conditions. In this sense, iron species have emerged
as a promising alternative, since most of them present low
toxicity and have a small contribution to environmental
pollution. Iron-based protocols have been employed for the
synthesis of different organic compounds by forming carbon−
carbon and carbon−heteroatom bonds.10 In particular, iron-
promoted cyclization reactions of alkyne derivatives consist of
an important synthetic tool for the preparation of different
heterocyclic units employing stoichiometric or catalytic
amounts of the metal reagent.11 Moreover, organic substances
containing an organochalcogen group in their structures have
drawn attention because a large number of them have
pharmacological activities12 and are quite useful as the reactive
site in several different transformations.13 Concerning the bad
reputation related to the smell, toxicity, or instability of
organoselenium compounds, recent studies about the pharma-
cological and toxicological aspects point out these compounds
as promising pharmacological agents in view of their unique
properties.14,15 Regarding the use of organoselenium com-
pounds in organic synthesis, recently others16 and we17 have
described FeCl3/RYYR (Y = S, Se or Te) as an efficient
cyclization promoter of alkenyl and alkynyl substrates. This
Figure 1. Biologically active isoxazole derivative.
this way, the interest of the synthetic organic chemists in the
development of alternative strategies to preparation of isoxazole
derivatives is constant. Consequently, many synthetic ap-
proaches have been related to the construction of isoxazole
moieties. Usually, these compounds have been prepared via
reactions of hydroxylamine with α,β-unsaturated nitriles,
carbonyl compounds, and 1,3-dicarbonyl substrates.6 However,
these classical protocols require the use of expensive transition-
metal catalysts, strong acidic or base conditions, and sometimes
high reaction temperatures. Alternatively, the electrophilic
cyclization7 of 2-alkynone O-methyloximes using different
electrophilic sources was employed to synthesize highly
substituted 4-halo-isoxazoles.8 This method has some advan-
tages when compared with classical methodologies, principally
because 4-bromo- and 4-iodoisoxazoles are versatile precursors
Received: December 20, 2012
Published: January 27, 2013
© 2013 American Chemical Society
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iron/dichalcogenide association is an alternative and useful tool
for the synthesis of functionalized carbo- and heterocycles, such
as cyclobutanes, benzo[b]furans, chromenones, isochrome-
nones, selenophenes, and tellurophenes. Based on these
previous aspects and considering that there is no protocol
reporting the FeCl3/RSeSeR-promoted synthesis of isoxazole
heterocyclic units, in the present study we reported the
synthesis of highly substituted 4-organoselenylisoxazoles 2 via
intramolecular cyclization of alkynone O-methyloximes 1 using
FeCl3/RSeSeR as the promoter system by employing mild and
environmentally benign reaction conditions (Scheme 1).
Table 1. Effect of Different Reaction Parameters on the Iron-
Mediated Cyclization of 1a
a
b
entry
[Fe] (equiv)
(PhSe)2 (equiv)
solvent
yield (%)
c
1
2
FeCl3(1.5)
FeCl3(1.5)
FeCl3(1.5)
FeCl3(1.5)
FeCl3(1.5)
0.5
1.0
0.5
1.0
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
MeCN
MeNO2
EtOH
78
c
45
3
76
66
0
4
5
Scheme 1
6
1.0
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0
7
FeCl3(0.2)
FeCl3(0.5)
FeCl3(1)
7
8
39
54
74
50
64
0
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
FeCl3(2)
FeCl3(1.5)
FeCl3(1.5)
FeCl3(1.5)
FeCl3(1.5)
FeCl3(1.5)
FeCl3(1.5)
FeCl3(1.5)
FeCl3(1.5)
FeCl3·6H2O(1.5)
FeCl2·4H2O(1.5)
Fe(acac)3(1.5)
Fe0(1.5)
DCE
68
0
RESULTS AND DISCUSSION
■
THF
The alkynone Z-O-methyloxime derivatives 1 were prepared by
reacting the corresponding alkynyl ketones with methoxyl-
amine hydrochloride in the presence of pyridine and Na2SO4,
using methanol as solvent at room temperature.18 Since the
alkynyl ketones have a bulky group directly bonded to the
carbonyl function only the required Z-O-methyloxime deriva-
tives were obtained.8,9 In order to determine a general
condition for the cyclization reaction of alkynone O-
methyloximes 1, the 1,3-diphenylprop-2-yn-1-one O-methylox-
ime 1a was submitted to cyclization conditions in the presence
of diphenyl diselenide by varying reaction parameters, such as
solvent, temperature, reaction stoichiometry, and iron species,
and the results are summarized in Table 1. In the first test, the
alkynone O-methyloxime 1a (0.25 mmol) was added to a
solution of diphenyl diselenide (0.5 equiv) and FeCl3 (1.5
equiv) in CH2Cl2 (2.5 mL), under argon atmosphere at room
temperature. Under these conditions, the reaction delivered the
3,5-diphenyl-4-(phenylselenyl)isoxazole 2a in 78% yield (Table
1, entry 1). Since these results, using 0.5 equiv of diphenyl
diselenide, gave the cyclized product 2a in higher than 50%
yield, we concluded that both portions of phenylselenium
(PhSe) from diphenyl diselenide (PhSeSePh) were incorpo-
rated in the final product. In fact, it represents the first
advantage of this cyclization method in view of the atom
economy, which is in agreement with the green chemistry
concept. When the amount of diphenyl diselenide was
increased from 0.5 to 1.0 equiv, a significant decrease in the
reaction efficiency was observed, and the isoxazole 2a was
obtained in only 45% yield (Table 1, entry 2). With the goal of
making our cyclization methodology more attractive, the
FeCl3/(PhSe)2-mediated cyclization reaction of the oxime 1a
was carried out under ambient atmosphere (open to air) and
the reaction system shown to be similarly effective giving the
cyclized product 2a in 76% yield (Table 1, entry 3). This is the
second advantage of our methodology from a practical and
economical standpoint. We observed that the amount of FeCl3
affected the reaction behavior. By varying from catalytic (0.2
equiv) to equimolar ratio of FeCl3, a decrease in the reaction
yields was observed (Table 1, entries 7−9). The fact that the
reactions do not take place by using a catalytic amount of iron
salt suggests that FeCl3 should be required not only to activate
toluene
hexane
DMF
40
7
0
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
39
12
0
0
Fe(SCN)2(1.5)
FeCl3(1.5)
Cu2O
10
d
72
c
0
a
The reaction was performed in the presence of 1a (0.25 mmol) under
b
c
ambient atmosphere for 12 h. Yields by GC analysis. The reaction
was carried out under argon atmosphere. The reaction was performed
d
at reflux temperature.
the triple bond to promote the cyclization but also as a
nucleophile source (Cl−) to remove the alkyl group directly
bonded to the oxygen atom (see the mechanism discussion in
Scheme 2). When the amount of FeCl3 was increased from 1.5
Scheme 2
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to 2.0 equiv, the desired isoxazole 2a was obtained in
comparable good yield (Table 1, entry 10). We have screened
different experiments in order to verify the influence of solvent
nature in the cyclization reaction. The use of polar aprotic
solvents, such as MeCN, MeNO2, and DCE, afforded a
decrease in the reaction yields (Table 1, entries 11, 12, and 14).
When EtOH, THF, and DMF were used, the PhSeSePh/FeCl3
system was inefficient for the formation of 2a (Table 1, entries
13, 15, and 18). We believe that affinity between solvents
(Lewis bases) and FeCl3 (Lewis acid) leads to an inactivation of
the iron salt. Nonpolar solvents, such as toluene and hexane,
furnished poor yields for the expected product because of the
low solubility of the starting materials in these solvents (Table
1, entries 16 and 17). In addition, the yield could not be
improved by using CH2Cl2 at reflux temperature (Table, entry
24). The iron source was also found to be important to the
cyclization process. The hydrous iron species FeCl3·6H2O and
FeCl2·4H2O proved to be somewhat effective for the formation
of the cyclized product (Table 1, entries 19 and 20). These
results suggest that chlorine atoms seem to play a key role in
the cyclization process. This effect becomes more noticeable
since iron reagents, such as Fe(acac)3, Fe(SCN)2, and Fe0, were
demonstrated to be ineffective as the cyclizing agent (Table 1,
entries 21−23). We can infer that chlorine should act as a
nucleophilic species in a substitution reaction to remove the
methyl group bonded to the oxygen atom as detailed in the
mechanism discussion (Scheme 2). According to Bolm and co-
workers, in the metal-catalyzed/promoted transformations the
trace metal impurities should work as the catalytic species.19 In
particular, FeCl3 is known to present traces of Cu2O.20 In order
to eliminate the possibility of a copper contaminant to be
directly involved in the cyclization process, the alkynone O-
methyloxime 1a was submitted to reaction conditions using
Cu2O in absence of FeCl3, and no trace of cyclized product was
observed. These findings suggest that the iron salt is the active
species in this transformation (Table 1, entry 25). Finally,
monitoring the progress of a reaction by TLC, we observed that
all alkynone O-methyloxime 1 was consumed after 5 min, and
the increase of the reaction time to 30 min did not improve the
yields. Based on these results, we concluded that the best
reaction conditions to this cyclization approach were the use of
the proper alkynone O-methyloxime 1 (0.25 mmol), FeCl3 (1.5
equiv), and diorganyl diselenide (0.5 equiv), using CH2Cl2 as
solvent, at room temperature, for 5 min under ambient
atmosphere.
Considering that the chemistry involving iron salts and
diorganyl dichalcogenides is recent, it must be accepted that
knowledge of the mechanistic pathways of the transformations
promoted by these systems is still limited.21 In this context, we
have worked to propose a possible mechanism to these
reactions; however, at this moment to draw a mechanistic
picture would be a speculative exercise. However, the following
experimental data obtained in this study can contribute to the
best understanding of the reaction mechanisms. During our
studies, it became clear that a typical electrophilic cyclization
mechanism, which could involve the PhSeCl22 as electrophilic
source, is improbable. This hypothesis is supported by the fact
that when FeCl3 and diphenyl diselenide reacted, under the
optimized cyclization conditions, in the absence of the alkynone
O-methyloxime 1, no PhSeCl was detected by GC/MS analysis
of the crude reaction mixture (Scheme 2, eq 1). However, the
in situ formation of the PhSeCl cannot be totally discarded.
This idea could be supported by the fact that when the oxime
1a was submitted to the electrophilic cyclization, by using
PhSeCl as a cyclization agent, the isoxazole 2a was obtained in
67% yield after 17 h (Scheme 2, eq 2). This expected result is in
agreement with those obtained by the Larock’s previous
cyclization protocol, in which PhSeBr is employed as the
electrophilic reagent.8 When the oxime 1a was submitted to
FeCl3-mediated reaction in the absence of diphenyl diselenide,
and likewise when the same substrate reacted with diphenyl
diselenide in the absence of FeCl3, no cyclized product was
obtained in both reactions (Table 1, entries 5 and 6). The
analysis of these results indicates a dependence of the
cyclization process to simultaneous presence of FeCl3 and
diphenyl diselenide into the reaction mixture. Based on these
experimental data, we supposed that the formation of a mixed
iron/diselenide complex is the species responsible for the
cyclization process. In addition, the result shown in Table 1,
entry 5, also suggests that the cyclization promoted by FeCl3
and a subsequent replacement of the Csp2−Fe bond by the
electrophilic organoselenyl motif could not occur (Scheme 2,
eq 3). Finally, when the reaction was carried out using the
alkynone O-benzyloxime 1m as substrate, we obtained a
mixture of desired isoxazole 2a and benzyl chloride (Scheme 2,
eq 4). This implies that the chlorine anion is acting as a
nucleophile in a SN2 reaction to remove the alkyl group directly
bonded to the oxygen atom.
Based on the above experiments, we believe that a plausible
mechanism for this cyclization reaction could involve two
concomitant mechanistic routes, as demonstrated in Scheme 3.
Scheme 3
First, the mixture of FeCl3 and diorganyl diselenide (R3Se)2
would furnish the reactive species R3SeFeCl2 and R3SeCl. The
reaction of the carbon−carbon triple bond with the electro-
philic R3SeCl leads to the selenonium intermediate a, and a
subsequent nucleophilic anti attack from the oxygen atom into
the activated Csp affords the cationic species b, which gives the
desired product 2 with the elimination of methyl chloride
(route A). Conversely, the coordination of the carbon−carbon
triple bond and the iron(III) specie (R3SeFeCl2) affords the
intermediate c; a nucleophilic anti attack of the oxygen lone
pair into the activated triple bond furnishes the isoxazolyliron
species d, which suffers a reductive elimination process to
generate the desired isoxazole 2 with simultaneous formation of
methyl chloride. These two concomitant pathways could
explain the incorporation of the two portions of R3Se in the
final product.
Once determined the ideal reaction parameters, we examined
the generality of our cyclization methodology (Table 2).
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a
Table 2. Scope and Generality of the Cyclization Reaction
a
Reaction performed in the presence of 1 (0.25 mmol), diorganyl diselenide (0.5 equiv), and FeCl3 (1.5 equiv) using CH2Cl2 (2.5 mL) as solvent,
under ambient atmosphere, at room temperature for 5 min.
Notably, the cyclization reaction was shown to be tolerant to
several different substituents. Different diaryl diselenides
bearing neutral, electron-withdrawing, and electron-donating
groups in the aromatic rings afforded the expected products in
moderate to good yields (Table 2, entries 1−6). Gratifyingly,
the reaction also worked well by using dialkyl diselenides giving
the corresponding 4-butylselenylisoxazole 2g and 4-ethyl-
selenylisoxazole 2h in 55 and 56% yields, respectively (Table
2, entries 7 and 8). These results are significant since the alkyl
group directly bonded to the selenium atom could undergo β-
selenoxide elimination giving the isoxazole without the
selenium group incorporated in the structure. Next, we tested
the influence of steric and electronic effects of different
substituents in the aromatic rings directly bonded to the triple
bond of the alkynone O-methyloximes 1 (Table 2, entries 9−
15). The experiments showed that the cyclization reaction was
not influenced by electronic effects since electron-poor and
electron-rich groups furnished the expected products in similar
yields (Table 2, entries 9−13). It is worth noting that the
protocol was tolerant to the presence of a sterically hindered
naphthalene as well as an alkyl group into the triple bond,
providing the products 2n and 2o in reasonable yields (Table 2,
entries 14 and 15). In addition, the presence of electron-
withdrawing, -donating, and bulky naphthyl groups in the R1
position proved it does not have significant influence in the
reaction behavior. Using the same reaction conditions, the
cyclization of oximes 1i−k led to the formation of the expected
products 2p−r in moderate yields (Table 2, entries 16−18).
Finally, when the optimized conditions were extended to
diorganyl disulfides and ditellurides only traces of the expected
cyclized products were obtained.
Recently, Larock and co-workers reported a competitive
cyclization using halogen and selenium electrophiles on a wide
variety of functionally substituted alkynes. The results indicated
that the nucleophilicity of the competing functional groups is
one of the most important factors in determining the outcome
of these reactions.23 In this context, aiming to study the
regioselectivity of this method to the synthesis of isoxazoles, the
compound 1l was submitted to the cyclization conditions. This
substrate could give both benzo[b]furan 2s′ and isoxazole
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derivative 2s; however, by using our cyclization conditions, 5-
(4-methoxyphenyl)-3-phenyl-4-(phenylselenyl)isoxazole 2s was
obtained as the unique regioisomer (Scheme 4). This result is
in agreement with those obtained by the Larock’s competitive
cyclization, in which the electronic factors play a crucial role in
these reactions.
Scheme 5
Scheme 4
The chalcogen−lithium exchange consists of a useful
synthetic tool since the corresponding organolithium species24
are able to react with a number of different electrophiles
providing grossly functionalized organic molecules.25 Further,
as a PhSe group is a good precursor for the selenium−lithium
exchange reaction, we have carried out this reaction employing
the isoxazole 2a with n-butyllithium. In the first experiment, the
generation of the organolithium intermediate A from selenide
2a was attempted by the addition of n-butyllithium (1.1 equiv)
to a solution of 3,5-diphenyl-4-(phenylselenyl)isoxazole 2a (0.5
mmol) in THF (4 mL) at −78 °C. The resulting solution was
stirred for 15 min at this temperature and quenched in H2O.
Under these conditions, the corresponding 4-hydrogenated
product 3a was isolated in 80% yield (Scheme 4). After this
result, we extended this method by trapping the corresponding
lithium intermediate A with different electrophilic sources, such
as aldehyde, benzoyl chloride, ketone, and trimethylsilyl
chloride. Through this method, the 4-organoselenylisoxazoles
synthesized proved to be convenient precursors for the
preparation of isoxazole derivatives bearing different functional
groups, furnishing the target compounds in moderate to good
yields (Scheme 5).
The transition-metal-catalyzed cross-coupling reaction using
4-haloisoxazoles as substrate is a desirable transformation for
the construction of new carbon−carbon bonds.26 For this
reason, we decided to examine the selenium−halogen exchange
reaction of 4-phenylselenylisoxazole 2a in an attempt to directly
access the 4-bromoisoxazole. In this way, the reaction of 2a
with molecular bromine in CHCl3, for 1 h, at room temperature
afforded the expected halogenated isoxazole 3f in 85% yield
(Scheme 6).
Scheme 6
atmosphere and had atom economy (the two PhSe groups from
PhSeSePh are incorporated into the isoxazole ring). To our
knowledge, this is the first example of FeCl3/RSeSeR-mediated
isoxazole synthesis. In addition, the 4-organoselenylisoxazole
obtained in the course of this work proved to be convenient as
substrate for the preparation of more functionalized isoxazole
derivatives, becoming a promising alternative to the con-
struction of heterocycle libraries.
EXPERIMENTAL SECTION
■
General Procedure for the FeCl3/(R3Se)2 Cyclization. In a
Schlenk flask, under ambient atmosphere, containing CH2Cl2 (1.5
mL) were added FeCl3 (0.061 g, 1.5 equiv) and the appropriate
diorganyl diselenide (0.5 equiv). The reaction mixture was stirred for
20 min at room temperature. After this time, the corresponding
alkynone O-methyloxime (0.25 mmol) was added, diluted in CH2Cl2
(1 mL), and the reaction was stirred at room temperature for 5 min.
After that, the reaction mixture was diluted with dichloromethane (20
mL) and washed with a saturated aqueous solution of NH4Cl (3 × 10
mL). The organic phase was separated, dried over MgSO4, and
concentrated under vacuum. The residue was purified by flash
chromatography, using hexane/acetate (95:5) as eluent. 3,5-Diphenyl-
4-(phenylselenyl)isoxazole (2a). Obtained as a pale yellow solid. Mp =
1
CONCLUSION
86−87 °C. Yield: 0.066 g (70%). H NMR (CDCl3, 200 MHz): δ
■
8.13−8.05 (m, 2H), 7.79−7.69 (m, 2H), 7.48−7.31 (m, 6H), 7.20−
7.07 (m, 5H). 13C NMR (CDCl3, 100 MHz): δ 172.3, 165.7, 131.5,
130.7, 129.7, 129.4, 128.8, 128.7, 128.6, 128.5, 128.3, 127.8, 127.3,
126.5, 96.3. MS (relative intensity) m/z: 377 (11), 207 (4), 169 (33),
105 (100), 77 (59), 51 (12). FTIR (neat) 4060, 3406, 3032, 2956,
2929, 2854, 2370, 1550, 1373, 1070, 690, 667 cm−1. Anal. Calcd for
C21H15NOSe: C, 67.03; H, 4.02; N, 3.72. Found: C, 67.30; H, 4.09; N,
3.80.
In conclusion, we have developed an alternative and efficient
approach to 4-organoselenylisoxazoles from alkynone O-
methyloximes via FeCl3-mediated intramolecular cyclization
in the presence of substituted diorganyl diselenides. The
cyclization protocol is straightforward and allows for the
construction of highly functionalized isoxazole derivatives in
moderate to good yields. We consider that there are three main
advantages of our methodology; a short reaction time was
required, and the reactions were carried out under ambient
4-(4-Fluorophenylselenyl)-3,5-diphenylisoxazole (2b). Obtained
as a pale yellow solid. Mp = 114−115 °C. Yield: 0.064 g (65%). H
1
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NMR (CDCl3, 200 MHz): δ 8.15−8.05 (m, 2H), 7.77−7.70 (m, 2H),
7.54−7.36 (m, 6H), 7.18−7.05 (m, 2H), 6.93−6.80 (m, 2H). 13C
NMR (CDCl3, 100 MHz): δ 172.1, 165.5, 162.0 (d, 1JCF = 251.0 Hz),
131.4 (d, 3JCF = 8.0 Hz), 130.8, 129.8, 128.8, 128.7, 128.6, 128.4, 127.9,
127.4, 125.7 (d, JCF = 2.9 Hz), 116.6 (d, JCF = 21.9 Hz), 97.2. MS
(relative intensity) m/z: 395 (4), 187 (7), 105 (100), 77 (80), 51 (14).
HRMS: calcd for C21H14FNOSe [ESI, M + H+] 396.0304, found
396.0311. FTIR (neat): 3059, 1884, 1556, 1485, 1377, 1219, 821, 761,
692, 570 cm−1.
1226, 767, 690, 574 cm−1. Anal. Calcd for C17H15NOSe: C, 62.20; H,
4.61; N, 4.27. Found: C, 62.41; H, 4.82; N, 4.31.
3-phenyl-4-(phenylselenyl)-5-(p-tolyl)isoxazole (2i). Obtained as a
white solid. Mp = 112−113 °C. Yield: 0.057 g (59%). 1H NMR
(CDCl3, 200 MHz): δ 8.00 (d, J = 8.1 Hz, 2H), 7.78−7.71 (m, 2H),
7.44−7.35 (m, 3H), 7.26 (d, J = 7.4 Hz, 2H), 7.19−7.13 (m, 5H), 2.39
(s, 3H). 13C NMR (CDCl3, 100 MHz): δ 172.6, 165.7, 141.1, 131.7,
129.7, 129.4, 129.3, 129.0, 128.9, 128.8, 128.3, 127.8, 126.5, 124.8,
95.9, 21.4. MS (relative intensity) m/z: 391 (7), 207 (7), 169 (14),
119 (100), 91 (46), 65 (13). FTIR (neat): 3055, 2920, 2854, 2173,
1570, 1554, 1375, 827, 727, 694, 561, 480 cm−1. Anal. Calcd for
C22H17NOSe: C, 67.69; H, 4.39; N, 3.59. Found: C, 67.81; H, 4.75; N,
3.62.
4
2
4-(4-Chlorophenylselenyl)-3,5-diphenylisoxazole (2c). Obtained
1
as a pale yellow solid. Mp = 124−125 °C. Yield: 0.072 g (70%). H
NMR (CDCl3, 200 MHz): δ 8.12−8.03 (m, 2H), 7.76−7.68 (m, 2H),
7.53−7.35 (m, 6H), 7.18−7.04 (m, 4H). 13C NMR (CDCl3, 100
MHz): δ 172.4, 165.5, 132.8, 130.9, 130.2, 129.9, 129.7, 129.6, 128.7,
128.5, 128.4, 127.8, 127.2, 96.2. MS (relative intensity) m/z: 411 (4),
281 (4), 207 (11), 165 (4), 105 (100), 77 (48), 51 (10). FTIR (neat):
3061, 2926, 1558, 1473, 1442, 1373, 1087, 810, 688, 482 cm−1. Anal.
Calcd for C21H14ClNOSe: C, 61.41; H, 3.44; N, 3.41. Found: C,
61.27; H, 3.19; N, 3.38.
3-Phenyl-4-(phenylselenyl)-5-(m-tolyl)isoxazole (2j). Obtained as
1
a pale orange solid. Mp = 59−60 °C. Yield: 0.063 g (65%). H NMR
(CDCl3, 200 MHz): δ 7.92−7.85 (m, 2H), 7.77−7.72 (m, 2H), 7.45−
7.22 (m, 6H), 7.21−7.12 (m, 5H), 2.37 (s, 3H). 13C NMR (CDCl3,
100 MHz): δ 172.5, 165.6, 138.7, 131.7, 131.4, 129.7, 129.4, 129.2,
128.9, 128.8, 128.5, 128.3, 127.4, 126.6, 125.1, 96.6, 21.3. MS (relative
intensity) m/z: 391 (7), 207 (19), 169 (17), 119 (100), 91 (57), 73
(24), 51 (6). FTIR (neat): 3410, 3051, 2924, 1573, 1548, 1436, 1381,
1018, 920, 794, 738, 696, 453 cm−1. Anal. Calcd for C22H17NOSe: C,
67.69; H, 4.39; N, 3.59. Found: C, 67.81; H, 4.42; N, 3.62.
3,5-Diphenyl-4-(3-trifluoromethyl)phenylselenyl)isoxazole (2d).
Obtained as a white solid. Mp = 70−71 °C. Yield: 0.055g (50%).
1H NMR (CDCl3, 200 MHz): δ 8.12−7.82 (m, 2H), 7.73−7.60 (m,
2H), 7.52−7.15 (m, 10H). 13C NMR (CDCl3, 100 MHz): δ 172.5,
165.5, 132.4, 132.2 (J = 1.4 Hz), 131.7 (J = 32.2 Hz), 130.9, 129.9,
129.7, 128.8, 128.7, 128.4, 127.8, 127.1, 126.8, 125.9 (J = 3.6 Hz),
125.8 (J = 272.9 Hz), 123.5 (J = 3.6 Hz), 95.9. MS (relative intensity)
m/z: 445 (4), 281 (11), 207 (30), 105 (100), 77 (37), 51 (9). HRMS:
calcd for C22H14 F3NOSe [ESI, M + Na+] 468.0097, found 468.0108.
FTIR (neat): 3061, 2924, 1556, 1487, 1413, 1325, 1176, 1122, 1068,
769, 690, 570 cm−1.
3-Phenyl-4-(phenylselenyl)-5-(o-tolyl)isoxazole (2k). Obtained as
1
an orange oil. Yield: 0.058 g (60%). H NMR (CDCl3, 200 MHz): δ
7.93−7.84 (m, 2H), 7.43−7.20 (m, 7H), 7.17−7.07 (m, 5H), 2.33 (s,
3H). 13C NMR (CDCl3, 100 MHz): δ 175.4, 164.1, 138.0, 131.3,
130.6, 130.5, 130.4, 129.8, 129.5, 129.2, 128.7, 128.5, 128.4, 127.0,
126.6, 125.5, 99.3, 20.1. MS (relative intensity) m/z: 391 (11), 207
(13), 179 (9), 169 (18), 119 (100), 103 (11), 91 (70), 65 (18), 51
(10). FTIR (neat): 3057, 2926, 1606, 1577, 1477, 1375, 1255, 1118,
939, 773, 731, 690, 503 cm−1. Anal. Calcd for C22H17NOSe: C, 67.69;
H, 4.39; N, 3.59. Found: C, 67.85; H, 4.43; N, 3.61.
3-Phenyl-4-(phenylselenyl)-5-(p-tolyl)isoxazole (2e). Obtained as
1
a white solid. Mp = 112−113 °C. Yield: 0.057 g (59%). H NMR
(CDCl3, 200 MHz): δ 8.00 (d, J = 8.1 Hz, 2H), 7.78−7.71 (m, 2H),
7.44−7.35 (m, 3H), 7.26 (d, J = 7.4 Hz, 2H), 7.19−7.13 (m, 5H), 2.39
(s, 3H). 13C NMR (CDCl3, 100 MHz): δ 172.6, 165.7, 141.1, 131.7,
129.7, 129.4, 129.3, 129.0, 128.9, 128.8, 128.3, 127.8, 126.5, 124.8,
95.9, 21.4. MS (relative intensity) m/z: 391 (7), 207 (7), 169 (14),
119 (100), 91 (46), 65 (13). FTIR (neat): 3059, 2941, 1554, 1487,
1444, 1377, 1114, 937, 798, 765, 692, 569, 482 cm−1. Anal. Calcd for
C22H17NOSe: C, 67.69; H, 4.39; N, 3.59. Found: C, 67.81; H, 4.75; N,
3.62.
5-(4-Methoxyphenyl)-3-phenyl-4-(phenylselenyl)isoxazole (2l).
Obtained as a pale yellow solid. Mp = 130−131 °C. Yield: 0.056 g
1
(55%). H NMR (CDCl3, 200 MHz): δ 8.12−8.05 (m, 2H), 7.77−
7.69 (m, 2H), 7.44−7.36 (m, 3H), 7.21−7.13 (m,5H), 7.00−6.93 (m,
2H), 3.85 (s, 3H). 13C NMR (CDCl3, 100 MHz): δ 172.4, 165.8,
161.5, 131.8, 129.7, 129.5, 129.4, 128.9, 128.8, 128.7, 128.3, 126.5,
120.1, 114.1, 100.0, 55.3. MS (relative intensity) m/z: 407 (3), 327
(7), 281 (21), 253 (13), 207 (68), 191 (15), 135 (100), 103 (30), 73
(43). HRMS: calcd for C22H17NO2Se [ESI, M + H+] 408.0504, found
408.0516. FTIR (neat): 2956, 2926, 2837, 1734, 1604, 1496, 1375,
1249, 1024, 831, 734, 688, 559 cm−1.
4-(2-Methoxyphenylselenyl)-3,5-diphenylisoxazole (2f). Obtained
as a pale yellow solid. Mp = 89−90 °C. Yield: 0.068 g (70%). 1H NMR
(CDCl3, 200 MHz): δ 8.09−8.01 (m, 2H), 7.75−7.67 (m, 2H), 7.50−
7.32 (m, 6H), 7.16−6.93 (m, 4H), 2.34 (s, 3H). 13C NMR (CDCl3,
100 MHz): δ 173.0, 165.9, 136.6, 132.3, 130.7, 130.3, 129.7, 128.8,
128.7, 128.6, 128.3, 128.0, 127.8, 127.4, 127.1, 126.4, 99.9, 21.2. MS
(relative intensity) m/z: 391 (5), 207 (5), 183 (12), 105 (100), 77
(48), 51 (8). HRMS: calcd for C22H17NOSe [ESI, M + H+] 392.0554,
found 392.0568. FTIR (neat): 3053, 1554, 1444, 1373, 935, 918, 750,
692, 56 cm−19.
5-(4-Chlorophenyl)-3-phenyl-4-(phenylselenyl)isoxazole (2m).
Obtained as a pale yellow solid. Mp = 113−114 °C. Yield: 0.068 g
1
(66%). H NMR (CDCl3, 200 MHz): δ 8.12−8.02 (m, 2H), 7.77−
7.68 (m, 2H), 7.47−7.34 (m, 5H), 7.20−7.10 (m, 5H). 13C NMR
(CDCl3, 100 MHz): δ 171.1, 165.8, 136.9, 131.2, 129.9, 129.5, 129.1,
129.0, 128.8, 128.7, 128.4, 128.3, 126.7, 125.7, 96.7. MS (relative
intensity) m/z: 411 (14), 402 (28), 326 (15), 298 (15), 207 (9), 180
(9), 105 (100), 77 (54), 51 (6). FTIR (neat): 3446, 2924, 1600, 1575,
1544, 1475, 1253, 1016, 935, 831, 729, 698 cm−1. Anal. Calcd for
C21H14ClNOSe: C, 61.41; H, 3.44; N, 3.41. Found: C, 61.62; H, 3.50;
N, 3.46.
4-(Butylselenyl)-3,5-diphenylisoxazole (2g). Obtained as a yellow
1
oil. Yield: 0.049 g (55%). H NMR (CDCl3, 200 MHz): δ 8.20−8.14
(m, 2H), 7.95−7.88 (m, 2H), 7.56−7.43 (m, 6H), 2.45 (t, J = 7.2 Hz,
2H), 1.33 (quint, J = 7.3 Hz), 1.13 (sext, J = 7.2 Hz, 2H), 0.66 (t, J =
7.2 Hz, 3H). 13C NMR (CDCl3, 100 MHz): δ 170.5, 165.2, 130.3,
129.6, 129.2, 128.8, 128.5, 128.3, 127.9, 127.8, 96.8, 31.5, 28.9, 22.3,
13.2. MS (relative intensity) m/z: 357 (1), 207 (8), 169 (3), 105
(100), 77 (38), 51 (8). HRMS: calcd for C19H19NOSe [ESI, M + H+]:
358.0711, found 358.0714. FTIR (neat): 3059, 2956, 2927, 2860,
1554, 1489, 1444, 1375, 1257, 937, 773, 692, 487 cm−1.
5-(Naphthalen-1-yl)-3-phenyl-4-(phenylselenyl)isoxazole (2n).
Obtained as a pale orange solid. Mp = 106−107 °C. Yield: 0.071 g
1
(67%). H NMR (CDCl3, 200 MHz): δ 8.00−7.86 (m, 5H), 7.62−
7.40 (m, 7H), 7.10−7.03 (m, 5H). 13C NMR (CDCl3, 100 MHz): δ
174.5, 164.4, 133.5, 131.5, 131.2, 131.1, 129.9, 129.8, 129.2, 129.1,
128.8, 128.6, 128.5, 128.4, 127.1, 126.6, 126.4, 125.3, 124.8, 124.7,
100.7. MS (relative intensity) m/z: 427 (11), 230 (9), 215 (12), 167
(29), 155 (94), 127 (100), 105 (9), 89 (12), 77 (21), 51 (8). FTIR
(neat): 3064, 1573, 1490, 1436, 1371, 1062, 1018, 800, 731, 729, 698.
cm−1 Anal. Calcd for C25H17NOSe: C, 70.42; H, 4.02; N, 3.29. Found:
C, 70.66; H, 4.08; N, 3.37.
4-(Ethylselenyl)-3,5-diphenylisoxazole (2h). Obtained as a pale
yellow solid. Mp = 56−57 °C. Yield: 0.046 g (56%). 1H NMR (CDCl3,
200 MHz): δ 8.24−8.14 (m, 2H), 7.96−7.88 (m, 2H), 7.52−7.44 (m,
6H), 2.48 (quart, J = 7.3 Hz, 2H), 1.11 (t, J = 7.5 Hz, 3H). 13C NMR
(CDCl3, 100 MHz): δ 170.7, 165.3, 130.3, 129.7, 129.3, 128.8, 128.5,
128.4, 127.8, 126.5, 99.9, 22.6, 14.9. MS (relative intensity) m/z: 329
(10), 327 (7), 281 (6), 207 (17), 135 (4), 117 (11), 105 (100), 77
(54), 51 (12). FTIR (neat): 3055, 2958, 2926, 1560, 1485, 1442, 1373,
5-Butyl-3-phenyl-4-(phenylselenyl)isoxazole (2o). Obtained as a
1
yellow oil. Yield: 0.051 g (57%). H NMR (CDCl3, 200 MHz): δ
7.84−7.77 (m, 2H), 7.44−7.32 (m, 3H), 7.22−7.12 (m, 5H), 2.93 (t, J
= 7.8 Hz, 2H), 1.69 (quint, J = 7.6 Hz, 2H), 1.35 (sext, J = 7.6 Hz,
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2H), 0.89 (t, J = 7.2 Hz, 3H). 13C NMR (CDCl3, 100 MHz): δ 178.6,
163.8, 131.8, 129.6, 129.4, 129.3, 129.2, 128.5, 128.3, 126.5, 97.4, 29.6,
26.4, 22.2, 13.4. MS (relative intensity) m/z: 357 (44), 193 (38), 169
(100), 144 (28), 116 (54), 89 (46), 77 (68), 57 (45), 51 (28). HRMS:
calcd for C19H19NOSe [ESI, M + H+] 358.0705, found 358.0657.
FTIR (neat): 3059, 2929, 2870, 1577, 1477, 1382, 1022, 734, 690, 491
cm−1.
3,5-Diphenyl-4-(trimethylsilyl)isoxazole (3b). Purified by flash
chromatography using hexane as eluent. Obtained as a white solid.
1
Mp = 156−157 °C. Yield: 0.102 g (70%). H NMR (CDCl3, 400
MHz): δ 7.65−7.63 (m, 2H), 7.60−7.57 (m, 2H), 7.53−7.47 (m, 6H),
−0.03 (s, 9H). 13C NMR (CDCl3, 100 MHz): δ 176.0, 168.2, 131.6,
130.1, 129.7, 129.2, 129.1, 129.0, 128.3, 108.4, 0.27. MS (relative
intensity) m/z: 293 (43), 278 (100), 204 (74), 135 (72), 105 (22), 77
(72), 51 (11). HRMS: calcd for C18H19NOSi [ESI, M]: 293.1236.
Found: 293.1240. FTIR (neat): 3462, 3055, 2935, 1552, 1454, 1369,
1249, 1139, 1070, 761, 634 cm−1.
3-(2-Chlorophenyl)-5-phenyl-4-(phenylselenyl)isoxazole (2p).
Obtained as a pale yellow solid. Mp = 87−88 °C. Yield: 0.057 g
1
(56%). H NMR (CDCl3, 200 MHz): δ 8.22−8.13 (m, 2H), 7.50−
7.22 (m, 7H), 7.14−7.03 (m, 5H). 13C NMR (CDCl3, 100 MHz): δ
170.8, 165.8, 134.1, 131.6, 130.8, 130.7, 130.6, 130.0, 129.6, 129.2,
128.7, 128.3, 127.6, 127.2, 126.8, 126.4, 99.1. MS (relative intensity)
m/z: 411 (5), 281 (10), 207 (25), 169 (22), 105 (100), 77 (60), 51
(13). FTIR (neat): 3446, 3064, 1575, 1558, 1475, 1373, 1022, 756,
729, 686, 453 cm−1. Anal. Calcd for C21H14ClNOSe: C, 61.41; H, 3.44;
N, 3.41. Found: C, 61.55; H, 3.48; N, 3.49.
(3,5-Diphenylisoxazol-4-yl)phenylmethanone (3c). Purified by
flash chromatography using ethyl acetate/hexane (5:95) as eluent.
Obtained as a pale yellow solid. Mp = 116−117 °C. Yield: 0.036g
1
(45%). H NMR (CDCl3, 400 MHz): δ 7.81−7.78 (m, 2H), 7.71−
7.67 (m, 2H), 7.60−7.57 (m, 2H), 7.45−7.24 (m, 9H). 13C NMR
(CDCl3, 100 MHz): δ 190.8, 169.0, 162.2, 136.8, 133.9, 130.8, 129.8,
129.7, 128.8, 128.7, 128.6, 128.2, 128.1, 127.5, 126.6, 114.1. MS
(relative intensity) m/z: 325 (29), 296 (7), 180 (16), 105 (100), 77
(74), 51 (13). FTIR (neat): 3061, 1593, 1492, 1404, 1325, 1242, 1136,
902, 742, 688 cm−1. Anal. Calcd for C22H15NO2 C, 81.21; H, 4.65; N,
4.30. Found: C, 81.40; H, 4.71; N, 4.37.
3-(4-tert-Butylphenyl)-5-phenyl-4-(phenylselenyl)isoxazole (2q).
Obtained as a pale orange solid. Mp = 124−125 °C. Yield: 0.045 g
(51%) 1H NMR (CDCl3, 200 MHz): δ 8.11−8.05 (m, 2H), 7.75−7.66
(m, 2H), 7.48−7.37 (m, 5H), 7.22−7.13 (m, 5H), 1.32 (s, 9H). 13C
NMR (CDCl3, 100 MHz): δ 172.4, 165.5, 153.0, 131.8, 130.7, 129.5,
128.7, 128.6, 128.4, 127.4, 126.5, 125.7, 125.3, 96.1, 34.7, 31.2. MS
(relative intensity) m/z: 433 (7), 281 (5), 207 (15), 169 (49), 144 (7),
105 (100), 89 (13), 77 (57), 51 (5). FTIR (neat): 3446, 3055, 2929,
2866, 1575, 1475, 1375, 837, 734, 688, 586 cm−1. Anal. Calcd for
C25H23NOSe: C, 69.44; H, 5.36; N, 3.24. Found: C, 69.62; H, 5.41; N,
3.30.
(3,5-Diphenylisoxazol-4-yl)-p-tolylmethanol (3d). Purified by flash
chromatography using ethyl acetate/hexane (20:80) as eluent.
Obtained as a white solid. Mp = 135−136 °C. Yield: 0.128 g (75%).
1H NMR (CDCl3, 200 MHz): δ 7.75−7.63 (m, 2H), 7.50−7.23 (m,
8H), 7.18 (d, J = 7.9 Hz, 2H), 7.05 (d, J = 8.0 Hz, 2H), 6.00 (s, 1H),
2.62 (s, 1H), 2.29 (s, 3H). 13C NMR (CDCl3, 100 MHz): δ 167.9,
163.4, 138.7, 137.2, 130.1, 129.4, 129.3, 129.1, 129.0, 128.6, 128.4,
128.2, 127.8, 126.1, 116.0, 67.0, 20.9. MS (relative intensity) m/z: 341
(26), 248 (16), 220 (11), 119 (29), 105 (100), 91 (25), 77 (73), 51
(12). FTIR (neat): 3307, 1593, 1566, 1450, 1276, 1159, 1060, 781,
686 cm−1. Anal. Calcd for C23H19NO2: C, 80.92; H, 5.61; N, 4.10.
Found: C, 81.22; H, 5.69; N, 4.15.
(3,5-Diphenylisoxazol-4-yl)diphenylmethanol (3e). Purified by
flash chromatography using ethyl acetate/hexane (20:80) as eluent.
Obtained as a white solid. Mp = 148−149 °C. Yield: 0.113 g (56%).
1H NMR (CDCl3, 200 MHz): δ 7.25−7.03 (m, 20H), 2.79 (s, 1H).
13C NMR (CDCl3, 100 MHz): δ 167.8, 163.3, 144.9, 130.1, 129.2,
3-(Naphthalen-2-yl)-5-phenyl-4-(phenylselenyl)isoxazole (2r).
Obtained as a pale orange solid. Mp = 106−108 °C. Yield: 0.066 g
1
(62%). H NMR (CDCl3, 200 MHz): δ 8.27 (s, 1H), 8.18−8.10 (m,
2H), 7.88−7.72 (m, 4H), 7.55−7.43 (m, 5H), 7.26−7.13 (m, 5H). 13C
NMR (CDCl3, 100 MHz): δ 172.6, 165.6, 133.7, 132.8, 131.6, 130.8,
129.5, 128.9, 128.8, 128.7, 128.6, 128.0, 127.9, 127.6, 127.3, 126.9,
126.6, 126.3, 126.0, 125.7, 96.5. MS (relative intensity) m/z: 427 (11),
322 (4), 230 (5), 169 (17), 153 (7), 127 (8), 105 (100), 77 (50), 51
(7). FTIR (neat): 3051, 1575, 1546, 1494, 1438, 1382, 860, 819, 686,
466 cm−1. Anal. Calcd for C25H17NOSe: C, 70.42; H, 4.02; N, 3.29.
Found: C, 70.61; H, 4.09; N, 3.35.
129.0, 128.9, 128.8, 128.5, 128.1, 127.9, 127.8, 127.7, 127.6, 120.9,
77.8. MS (relative intensity) m/z: 403 (14), 402 (28), 326 (15), 298
(15), 207 (9), 180 (9), 105 (100), 77 (54), 51 (6). HRMS: calcd for
C28H21NO2 [ESI, M] 403.1572, found 403.1579. FTIR (neat): 3460,
1570, 1490, 1448, 1334, 1161, 875, 694 cm−1.
5-(2-Methoxyphenyl)-3-phenyl-4-(phenylselenyl)isoxazole (2s).
Obtained as a pale yellow solid. Mp = 95−96 °C. Yield: 0.058 g
1
(57%). H NMR (CDCl3, 200 MHz): δ 7.85−7.79 (m, 2H), 7.50−
7.31 (m, 5H), 7.15−6.94 (m, 7H), 3.73 (s, 3H). 13C NMR (CDCl3,
100 MHz): δ 172.7, 164.1, 157.5, 132.2, 131.7, 131.2, 129.6, 129.4,
129.0, 128.9, 128.5, 128.3, 126.2, 120.3, 116.7, 111.3, 99.9, 55.3. MS
(relative intensity) m/z: 407 (9), 207 (8), 169 (8), 135 (100), 105 (9),
92 (12), 77 (36), 51 (7). HRMS: calcd for C22H17NO2Se [ESI, M]
407.0425, found 407.0429. FTIR (neat): 3412, 2929, 1614, 1575,
1373, 1282, 1093, 914, 754, 677, 532 cm−1.
General Procedure for the Preparation of the 4-Bromo-3,5-
diphenylisoxazole. A solution of bromine (0.32 g, 2 mmol) in
CHCl3 (2 mL) was added dropwise to a solution of 3,5-diphenyl-4-
(phenylselenyl)-isoxazole 2a (0.188 g, 0.5 mmol) in CHCl3 (10 mL)
at 25 °C. After complete addition, the reaction was stirred under reflux
for 3 h. After this time, the reaction mixture was diluted in CH2Cl2 (10
mL) and washed with brine solution (3 × 10 mL). The organic phase
was separated, dried over MgSO4, and concentrated under vacuum.
The residue was purified by chromatography on silica gel using hexane
as eluent. 4-Bromo-3,5-diphenylisoxazole (3f). Obtained as a pale yellow
solid. Mp = 128−129 °C. Yield: 0.127 g (85%). 1H NMR (CDCl3, 200
MHz): δ 8.13−8.05 (m, 2H), 7.89−7.81 (m, 2H), 7.57−7.48 (m, 6H).
13C NMR (CDCl3, 100 MHz): δ 165.7, 162.1, 130.6, 130.1, 128.8,
General Procedure for the Reaction of (3,5-Diphenylisox-
azol-4-yl)lithium Intermediate with Different Electrophiles. To
a two-necked round-bottomed flask, under argon, containing a
solution of 2a (0.5 mmol) in THF (4 mL) at −78 °C was added
dropwise n-BuLi (0.55 mmol, of a 2.5 M solution in hexane). The
reaction mixture was stirred for 15 min and then was gradually added a
solution of the appropriate electrophilic specie (0.55 mmol) in THF
(2 mL), at −78 °C. The reaction mixture was allowed to stir at 25 °C
for 1 h. After this time, the mixture was diluted in ethyl acetate (20
mL) and washed with a saturated aqueous solution of NH4Cl (3 × 10
mL). The organic phase was separated, dried over MgSO4, and
concentrated under vacuum. 3,5-Diphenylisoxazole (3a). Obtained as a
white solid. Mp = 138−139 °C. Yield: 0.088 g (80%). 1H NMR
(CDCl3, 200 MHz): δ 7.89−7.78 (m, 4H), 7.55−7.40 (m, 6H), 6.83
(s, 1H). 13C NMR (CDCl3, 100 MHz): δ 170.4, 162.9, 130.1, 129.9,
129.3, 128.9, 128.8, 127.6, 126.8, 125.8, 108.4, 97.4. MS (relative
intensity) m/z: 221 (36), 193 (8), 165 (6), 144 (14), 105 (100), 89
(12), 77 (61), 51 (20). FTIR (neat): 3113, 3047, 1570, 1462, 1400,
819, 763, 690 cm−1. Anal. Calcd for C15H11NO: C, 81.43; H, 5.01; N,
6,33. Found: C, 81.71; H, 5.12; N, 6.40.
128.6, 128.5, 127.8, 127.0, 126.7, 89.5. MS (relative intensity) m/z:
299 (12), 220 (17), 180 (14), 105 (100), 77 (60), 51 (17). HRMS:
calcd for C15H10BrNO [ESI, M + H+] 300.0019, found 299.9979.
FTIR (neat): 3446, 3055, 1489, 1446, 1388, 1072, 927, 765, 705 cm−1.
ASSOCIATED CONTENT
■
S
* Supporting Information
Experimental procedures, additional experimental details for
1
the preparation of all compounds, and H and 13C NMR
spectra for all products. This material is available free of charge
via the Internet at http://pubs.acs.org.
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Article
C.; Green, K. N.; Klotz, L. O.; Sies, H.; Jacob, C. Org. Biomol. Chem.
2003, 1, 4317.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: gzeni@ufsm.br.
(13) (a) Santi, C.; Santoro, S.; Battistelli, B. Curr. Org. Chem. 2012,
14, 2442. (b) Santi, C.; Battistelli, B.; Testaferri, L.; Tiecco, M. Green
Chem. 2012, 14, 1277. (c) Yu, L.; Huang, X. Synlett 2007, 1371.
(d) Murai, T.; Nonoyama, T. Tetrahedron 2012, 68, 10489.
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Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We are grateful to FAPERGS (PRONEX-10/0005-1), CAPES,
and CNPq (CNPq/INCT-catalise) for financial support. CNPq
is also acknowledged for the fellowships.
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Chem. 2011, 696, 2228.
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H.; Nogueira, C. W.; Zeni, G. Adv. Synth. Catal. 2011, 353, 2042.
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