Iron(III) chloride/diorganyl diselenides-promoted regioselective cyclization of alkynyl aryl ketones: Synthesis of 3-organoselenyl chromenones under ambient atmosphere

Article abstract of DOI:10.1002/adsc.201100189

An efficient and environmentally benign synthesis of 3- organoselenylchromenones was accomplished via iron(III) chloride/diorganyl diselenides-promoted intramolecular 6-endo-dig cyclization of alkynyl aryl ketone derivatives. The cyclization reactions pro

Full text of DOI:10.1002/adsc.201100189

FULL PAPERS
DOI: 10.1002/adsc.201100189
Iron(III) Chloride/Diorganyl Diselenides-Promoted
G
Regioselective Cyclization of Alkynyl Aryl Ketones: Synthesis of
3-Organoselenyl Chromenones under Ambient Atmosphere
Benhur Godoi,a Adriane SperanÅa,a Cesar A. Bruning,a Davi F. Back,b
Paulo Henrique Menezes,c Cristina W. Nogueira,a and Gilson Zenia,*
a
Laboratꢀrio de Sꢁntese, Reatividade, Avaliażo Farmacolꢀgica e Toxicolꢀgica de OrganocalcogÞnios, CCNE, UFSM,
Santa Maria, Rio Grande do Sul, Brazil 97105-900
Fax : (+55)-55-3220 8978; phone: (+55)-55-3220-9611; e-mail: gzeni@pq.cnpq.br
Laboratꢀrio de Materiais Inorgꢂnicos, CCNE, UFSM, Santa Maria, Rio Grande do Sul, Brazil 97105-900
Universidade Federal de Pernambuco, Departamento Quꢁmica Fundamental, Recife, Pernambuco, Brazil 50670-901
b
c
Received: March 15, 2011; Revised: April 25, 2011; Published online: August 10, 2011
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adcs.201100189.
Abstract: An efficient and environmentally benign six-membered regioisomers and was carried out
synthesis of 3-organoselenylchromenones was accom- using iron
ACHTUNGTRENUN(NG III) chloride/diorganyl diselenide at room
plished via iron(III) chloride/diorganyl diselenides- temperature and under ambient atmosphere, which
ACHTUNGTRENNUNG
promoted intramolecular 6-endo-dig cyclization of al- could be considered an economic and eco-friendly
kynyl aryl ketone derivatives. The cyclization reac- protocol.
tions proceeded cleanly under mild reaction condi-
tions, and the desired chromenone derivatives were
smoothly isolated in good yields. The methodology Keywords: chalcogenides; chromenones; diselenides;
proved to be highly regioselective, giving only the heterocycles; iron
Introduction
the traditional palladium salts as one of the most em-
ployed transition metals.[7] A straightforward ap-
Heterocycles represent an important class of com- proach for the construction of chromenone deriva-
pounds that have found multiple applications in me- tives is the direct palladium-catalyzed carbonylative
dicinal chemistry by virtue of their broad range of Sonogashira reaction.[8,9,10,11] The innovative use of
pharmacological properties, such as antidepressant, halocyclization reactions of appropriately substituted
antihypertensive and hypoglycemic.[1] In this context,
six-membered oxygenated heterocycles are, probably,
one of the most common structural units present in
natural product structures. In particular, flavone and
chromenone moieties are present in a wide range of
compounds that show important biological and phar-
maceutical applications.[2] For example, flavopiridol
presents anticarcinogenic activity, in particular, in the
treatment of human breast cancer.[3] Quercetin and
nobiletin are known to act as enzymatic inhibitors
(Figure 1).[4]
These rich applications have resulted in the devel-
opment of several strategies for the preparation from
single to more complex heterocycles.[5] Important con-
tributions to that came mainly from the transition
metal-catalyzed cyclization reactions using acyclic
precursors.[6] These approaches include, for example, Figure 1. Biologically active chromenone derivatives.
2042
ꢃ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2011, 353, 2042 – 2050

IronACHTUNGTRENNUNG(III) Chloride/Diorganyl Diselenides-Promoted Regioselective Cyclization of Alkynyl Aryl Ketones
amounts, solvents, reaction temperatures and iron
source in order to improve the yields. Based on these
considerations, we initially investigated the reaction
of alkynyl aryl ketone 1a using CH2Cl2 as solvent,
under an argon atmosphere, at reflux for 15 h. These
reaction conditions gave the desired product 3a in
57% yield (Table 1, entry 1). On changing the temper-
ature to room temperature we observed a significant
improvement in the reaction and the product was
formed in 63% yield (Table 1, entry 2). Moreover, the
use of polar (Table 1, entries 3–7) and apolar aprotic
solvents (Table 1, entry 8) did not improve the reac-
Scheme 1. General scheme.
alkynes is also a fine achievement in the synthesis of tion results, on the contrary lower the reaction yields
chromenone and isochromenone derivatives.[12] The
main advantage of these methodologies is that when
bromine or iodine is used as electrophilic source, the
product has a halogen atom in the final product struc-
tures, which renders the halogenated heterocycles
useful intermediates in many processes, in particular,
palladium-catalyzed cross-coupling reactions.[13]
Table 1. Effect of reaction conditions on the cyclization re-
action.[a}
In recent years, the importance of the development
of enviromentally benign protocols to the preparation
of heterocycles applying green, mild and relatively
cheaper methods has increased significantly.[14] Thus,
iron salts have appeared as a versatile alternative, due
to their low price and low toxicity. Iron trichloride ef-
ficiently promoted the cross-coupling reaction of
Grignard reagents with a variety of organic electro-
philes.[15] The use of catalytic amounts of iron salts
Entry
[Fe]
(equiv.)
N
Solvent
Yield
[%][b]
E
1
2
3
4
FeCl3 (1)
FeCl3 (1)
FeCl3 (1)
FeCl3 (1)
CH2Cl2
CH2Cl2
dioxane
dioxane
DMF
57
63[c]
46
18[d]
15
5
FeCl3 (1)
showed to be effective to promote the C-heteroatom
6
7
8
9
FeCl3 (1)
FeCl3 (1)
FeCl3 (1)
FeCl3·6H2O (1)
FeCl2·4H2O (1)
1
1
1
1
1
1
1
1
1
1
1
2
1.5
0.5
1
0.5
0.5
0.5
0.5
–
THF
13
13
14
40
13
0
0
18
[16]
À
À
À
DMSO
hexane
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
(C N, C O, C S) bond formation.
Iron reagents
also appear as a useful alternative to promote cycliza-
tion-type reactions using catalytic as well as stoichio-
metric quantities.[17]
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
Fe
N
Besides, the incorporation of an organoselenium or
organotellurium group in the structure of molecules
has attracted much attention because of their applica-
tions in several different reactions[18] as well as their
wide biological properties.[19]
Fe(0) (1)
FeCl3 (0.2)
FeCl3 (1.5)
FeCl3 (2)
FeCl3 (3)
FeCl3 (2)
FeCl3 (1)
FeCl3 (1)
FeCl3 (1)
FeCl3 (1)
FeCl3 (1.5)
FeCl3 (2)
–
40
52
52
Our findings on FeCl3/RSeSeR,[20] as an alternative
system to IPy2BF4,[21] halogens,[22] NXS,[23] trichloroiso-
65[e]
71[e]
61
cyanuric acid (TCCA),[24] (coll)2PF6/BF3·3OEt2,[25] or-
IAHCUTNGERNNUG
53[c,f]
67[c,f]
87[c,f]
80[c,f]
n.r[c,f,g]
n.r.[c,f,h]
ganoselenium[26] and organotellurium electrophiles[27]
to promote the cyclization of functionalized alkynes,
associated with the fact that currently there are no re-
ports concerning the use of FeCl3/RSeSeR to prepare
chromenone derivatives, encouraged us to examine if
3-organoselenylchromenones 3 would be generated
from alkynyl aryl ketones 1[28] via intramolecular cy-
FeCl3(1)
[a]
The reaction was performed in the presence of 1a
(0.25 mmol), under an argon atmosphere, at reflux tem-
perature for 15 h.
Yields by GC analysis.
The reaction performed at room temperature.
The reaction performed at 508C.
ACHTUNGTRENNUNGclization reactions using FeCl3/RSeSeR as the cycliz-
ing agent (Scheme 1).
[b]
[c]
[d]
[e]
[f]
Results and Discussion
Yields for isolated products.
The reaction was carried out under ambient atmosphere.
1a and PhSeSePh were recovered quantitatively.
1a was recovered quantitatively.
[g]
[h]
During the course of our study, we have screened
many different combinations of FeCl3/ACTHNUTRGEN(UNG PhSe)2
Adv. Synth. Catal. 2011, 353, 2042 – 2050
ꢃ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
2043

Benhur Godoi et al.
FULL PAPERS
were obtained. This indicates that, considering the green chemistry philosophy. In order to make our
solvents tested, the reaction can proceed effectively methodology more attractive from an economic
only in CH2Cl2. To better understand if the activity of standpoint, we tested the reaction in the absence of
the iron system is due to the different ligand partner an inert atmosphere. For these purposes, the reactions
type on the iron complex or to the effect of a dry iron were carried out using different amounts of iron tri-
salt, some experiments were also carried out using chloride and diphenyl diselenide in an open tube
FeCl3·6H2O, FeCl2·4H2O, FeACTHUNTRGNEU(GN acac)3 and Fe powder (Table 1, entries 20–24). Gratifyingly, using this
and a very sluggish reactivity was observed in each system with FeCl3 (1.5 equiv.) and PhSeSePh
case (Table 1, entries 9–12). Next, the amount of (0.5 equiv.) the product was obtained in 87% yield
FeCl3 was investigated by varying it from a catalytic (Table 1, entry 22). It is important to point out that
ratio of 0.2 to 3 equivalents, however, this did not the unique product obtained during the course of the
offer any improvement in the yields (Table 1, en- optimization was the chromenone derivative with an
tries 13–16). We observed that the amount of PhSe- organyl chalcogenide group at the 3-position. Any
SePh affected the reaction result. In particular, de- chloro- or hydrogen-cyclized products were observed
creasing the amount of PhSeSePh from 2.0 to by GC/MS. In accordance with these results, we con-
0.5 equiv. did not modify the reaction behavior and cluded that the optimum set of conditions for our cyc-
the product was obtained in a similar yield (Table 1, lization reaction was the use of the appropriate alkyn-
entry 19). This result is significant since it suggests yl aryl ketone 1 (0.25 mmol), FeCl3 (1.5 equiv.), dio-
that the two portions of diphenyl diselenide (PhSe) rganyl dichalcogenide (0.5 equiv.) in CH2Cl2, at room
were incorporated in the final product and indicates temperature under ambient atmosphere.
an atom economy which is an important concept of
Table 2. Scope and generality of the cyclization reaction.[a]
Entry
1
Substrate
G
Product (yield [%])[b]/time
1a R1 =H; R2 =Ph
2
3
4
5
6
1a
1a
1a
1a
1a
(p-F-C6H4Se)2
(p-Cl-C6H4Se)2
(m-CF3-C6H4Se)2
(p-Me-C6H4Se)2
(o-Me-C6H4Se)2
2044
asc.wiley-vch.de
ꢃ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2011, 353, 2042 – 2050

IronACHTUNGTRENNUNG(III) Chloride/Diorganyl Diselenides-Promoted Regioselective Cyclization of Alkynyl Aryl Ketones
Table 2. (Continued)
Entry
Substrate
G
Product (yield [%])[b]/time
7
8
9
1a
(1-naphthylSe)2
1a
1a
ACHTUNGTNER(NUNG n-BuSe)2
AHCTUNGERTG(NNUN EtSe)2
10
11
1b R1 =H; R2 =p-Me-C6H4
1c R1 =H; R2 =m-Me-C6H4
ACHTUNGERTN(NUNG PhSe)2
AHCTUNGERTG(NNUN PhSe)2
12
13
1d R1 =H; R2 =o-Me-C6H4
1e R1 =H; R2 =p-MeO-C6H4
ACHTUNGERTN(NUNG PhSe)2
AHCTUNGERTG(NNUN PhSe)2
14
1f R1 =H; R2 =o-MeO-C6H4
ACHTUNGERTN(NUNG PhSe)2
15
16
1g R1 =H; R2 =p-Cl-C6H4
1h R1 =H; R2 =p-F-C6H4
ACHTUNGERTN(NUNG PhSe)2
AHCTUNGERTG(NNUN PhSe)2
17
1i R1 =H; R2 =1-naphthyl
ACHTUNGERTN(NUNG PhSe)2
Adv. Synth. Catal. 2011, 353, 2042 – 2050
ꢃ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
2045

Benhur Godoi et al.
FULL PAPERS
Table 2. (Continued)
Entry
Substrate
G
Product (yield [%])[b]/time
18
1j R1 =H; R2 =1-phenanthryl
ACHTUNGERTN(NUNG PhSe)2
19
20
21
22
23
24
25
1k R1 =H; R2 =n-Bu
ACHTUNGERTN(NUNG PhSe)2
1l R1 =H; R2 =C6H13
ACHTUNGERTN(NUNG PhSe)2
1j
(p-F-C6H4Se)2
1j
(p-Me-C6H4Se)2
1l R1 =Cl; R2 =Ph
ACHTUNGERTN(NUNG PhSe)2
1l
1l
(p-Me-C6H4Se)2
(p-F-C6H4Se)2
26
1m R1 =Cl; R2 =1-naphthyl
ACHTUNGERTN(NUNG PhSe)2
27
1m R1 =Cl; R2 =n-Bu
ACHTUNGERTN(NUNG PhSe)2
[a]
The reaction was performed in the presence of 1 (0.25 mmol), diorganyl diselenide (0.5 equiv.), FeCl3 (1.5 equiv.), using
CH2Cl2 (5 mL) as solvent, under ambient atmosphere, at room temperature.
Yields for isolated products.
[b]
2046
asc.wiley-vch.de
ꢃ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2011, 353, 2042 – 2050

IronACHTUNGTRENNUNG(III) Chloride/Diorganyl Diselenides-Promoted Regioselective Cyclization of Alkynyl Aryl Ketones
With these optimized conditions in hand we ex- negative effects (Table 2, entry 7). Similarly, dialkyl
plored the substrate scope and limitation of the cycli- diselenides underwent the cyclization to give chrome-
zation method. First, functional groups in the aromat- nones 3h and 3i in 65% and 77% yields, respectively
ic ring of diaryl diselenides were investigated by re- (Table 2, entries 8 and 9). The reaction of each of the
acting various substituted diselenides with FeCl3 and aryl ketones 1b–j with diphenyl diselenide gave the
alkynyl aryl ketone 1a (Table 2). On the one hand, corresponding chromenones 3j–r in approximately
the reaction yield does not seem to be strongly influ- equal amounts indicating that there are no significant
enced by the electronic effect of the substituent since steric interactions or electronic effects in these cases
different diaryl diselenides bearing neutral, electron- (Table 2, entries 10–18). The effect of changing aryl to
withdrawing and electron-donating groups in the aro- alkyl substituents directly bonded to the triple bond
matic rings were compatible with the reaction condi- of the aryl ketones was not significant as in the previ-
tions and yielded the corresponding chromenones ous cases (Table 2, entries 19–22). It is worth noting
without any major by-products and in very similar that the presence of a chlorine atom directly bonded
yields (Table 2, entries 1–6). On the other hand, the in the aromatic ring containing the nucleophilic me-
results in Table 2 show that only a trace amount of thoxy group had no significant influence in the reac-
product was obtained for the cyclization between bis- tion behavior. To the best of our knowledge, the aryl
ACHTUNGTRENNUNG(naphthyl) diselenide and FeCl3, where the steric hin- halogen could undergo a coupling reaction in the
drance of the naphthyl group may exert significant presence of iron salts to afford biaryl products.[15,16] In
our case, the halogen substituent was not affected and
the cyclization process was carried out clean and
smoothly, using the same reaction conditions, leading
to the formation of the expected products in moder-
ate to good yields (Table 2, entries 23–27).
As already known, the cyclizations of alkynes or
their derivatives giving a mixture of five- and six-
membered heterocycles in the presence of transition
metals have been reported.[29] The results have shown
that the regiochemical effect of the reaction is strong-
ly dependent on the electronic (relative nucleophilici-
ty of the functional groups, polarization of the
carbon-carbon triple bond, and cationic nature of the
intermediate) and steric effects (hindrance and geo-
metrical alignment of the functional groups), as well
as the nature of the transition metals source. In this
context, in view of the high activation of the triple
bond by the carbonyl group, our cyclization method-
ology showed to be regioselective, providing the de-
sired chromenones 3, via a 6-endo-dig cyclization pro-
cess, as the unique regioisomers, which was confirmed
by X-ray diffraction analysis (Figure 2). The forma-
tion of five-membered ring products, via a 5-exo-dig
process, was not observed in any case (Scheme 2).
Figure 2. ORTEP view of the compound 3a.[30]
Scheme 2. Regioselectivity of the cyclization reaction.
Adv. Synth. Catal. 2011, 353, 2042 – 2050
ꢃ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
2047

Benhur Godoi et al.
FULL PAPERS
Conclusions
8.0 Hz, J=1.5 Hz, 1H), 7.72–7.59 (m, 3H), 7.56–7.38 (m,
5H), 7.38–7.24 (m, 2H), 6.90–6.75 (m, 2H); 13C NMR
1
(CDCl3, 50 MHz): d=175.8, 167.3, 162.0 (d, JC,F
=
In summary, we have developed an alternative and ef-
ficient method for the synthesis of 3-organoselenyl-
chromenone derivatives via the intramolecular 6-
endo-dig cyclization of alkynyl aryl ketones. The
methodology proved to be highly regioselective,
giving only the six-membered regioisomers and was
carried out using FeCl3/RSeSeR at room temperature
and under ambient atmosphere which is considered to
constitute an economic and eco-friendly protocol. To
the best of our knowledge, this is the first example of
chromenone synthesis using FeCl3/RSeSeR and the
present method would be very valuable for the prepa-
ration of heterocycles possessing 3-organoseleno
units. We believe that this approach to 3-organochalc-
ogen-chromenones should prove quite useful in syn-
thesis, particularly when one considers that there are
many ways to transform the resulting selenium func-
tionalities into other substituents. Concerning the bad
reputation related to the bad smell, toxicity or insta-
bility of selenium compounds, we observed that all
compounds prepared in this manuscript, are solids or
oil, completely odorless, very stable which can be pu-
rified and stored in the lab, in a simple flask, for more
than one month. Studies related to biological activity
(pharmacology and toxicology) of the chromenone
derivatives are in progress in our laboratory.
3
246.6 Hz), 155.7, 133.9, 133.7 (d, JC,F =8.0 Hz), 130.6, 129.1,
127.9, 126.4, 125.5, 125.3 (d, 4JC,F =3.3 Hz), 122.2, 117.7,
2
115.9 (d, JC,F =21.6 Hz), 114.5, 114.4; MS (EI, 70 eV): m/z
(relative intensity)=395 (48), 377 (5), 315 (67), 301 (9), 196
(100), 165 (54), 105 (89), 77 (25); anal. (%) calcd. for
C21H13FO2Se: C 63.81, H 3.31; found: C 63.90, H 3.30.
3-(Butylselenyl)-2-phenyl-4H-chromen-4-one (3h): Ob-
tained as a red oil; yield: 0.056 (65%). 1H NMR (CDCl3,
200 MHz): d=8.25 (dd, J=7.9 Hz, J=1.6 Hz, 1H), 7.77–
7.60 (m, 3H), 7.57–7.32 (m, 5H), 2.84 (t, J=7.3 Hz, 2H),
1.49 (quint, J=7.6 Hz, 2H), 1.24 (sext, J=7.2 Hz, 2H), 0.79
(t, J=7.2 Hz, 3H); 13C NMR (CDCl3, 100 MHz): d=176.5,
165.6, 155.8, 134.3, 133.6, 130.5, 129.3, 127.9, 126.2, 125.3,
121.9, 117.7, 112.6, 31.9, 26.9, 22.6, 13.4; MS (EI, 70 eV):
m/z (relative intensity)=357 (4), 301 (100), 221 (27), 165
(42), 121 (10), 89 (31), 77 (15); HR-MS: m/z=353.0392,
calcd. for C19H18O2Se [M+Na]: 381.0369.
3-(Phenylselenyl)-2-p-tolyl-4H-chromen-4-one (3j): Ob-
tained as a yellow solid; mp 99–1008C; yield: 0.074 g (78%).
1H NMR (CDCl3, 200 MHz): d=8.26 (dd, J=7.9 Hz, J=
1.7 Hz, 1H), 7.72–5.53 (m, 3H), 7.50–7.38 (m, 2H), 7.37–
7.18 (m, 4H), 7.17–7.08 (m, 3H), 2.41 (s, 3H); 13C NMR
(CDCl3, 100 MHz): d=175.8, 167.9, 155.8, 141.1, 133.7,
131.4, 131.3, 130.7, 129.1, 128.9, 128.5, 126.6, 126.5, 125.4,
122.3, 117.7, 113.5, 21.4; MS (EI, 70 eV): m/z (relative inten-
sity)=391 (45), 377 (33), 311 (72), 191 (48), 165 (21), 119
(100), 91 (12), 77 (13); anal. (%) calcd. for C22H16O2Se: C
67.52, H 4.12; found: C 67.78, H 4.20.
2-Butyl-3-(phenylselenyl)-4H-chromen-4-one (3s): Ob-
tained as a yellow oil; yield: 0.072 g (84%). 1H NMR
(CDCl3, 200 MHz): d=8.20 (dd, J=7.6 Hz, J=1.6 Hz, 1H),
7.70–7.57 (m, 1H), 7.48–7.31 (m, 4H), 7.25–7.08 (m, 3H),
3.15 (t, J=7.6 Hz, 2H), 1.70 (quint, J=7.6 Hz, 2H), 1.40
(sext, J=7.5 Hz, 2H), 0.92 (t, J=7.2 Hz, 3H); 13C NMR
(CDCl3, 100 MHz): d=175.3, 173.6, 155.6, 133.5, 131.1,
130.5, 129.0, 126.5, 126.4, 125.2, 122.4, 117.5, 113.4, 35.5,
29.7, 22.3, 13.6; MS (EI, 70 eV): m/z (relative intensity)=
358 (100), 357 (12), 329 (38), 316 (22), 301 (32), 251 (59),
171 (49), 115 (82), 102 (31), 91 (34), 77 (71); anal. (%)
calcd. for C19H18O2Se: C 63.87, H 5.08; found: C 64.10, H
5.12.
Experimental Section
General Procedure for the FeCl3/ACTHNUTRGNEUNG
(R3Se)2 Cyclization
To a Schlenck tube, under ambient atmosphere, containing
CH2Cl2 (4 mL) were added FeCl3 (0.061 g, 1.5 equiv.) and di-
organyl dichalcogenide (0.5 equiv.) and the reaction mixture
was stirred for 20 min at room temperature. After this time,
the apropriate alkynyl aryl ketone (0.25 mmol) in CH2Cl2
(1 mL) was added and the reaction mixture stirred for deter-
mined time. After this, the mixture was diluted with
6-Chloro-2-phenyl-3-(phenylselenyl)-4H-chromen-4-one
(3w): Obtained as a yellow solid; mp 129–1308C; yield:
dichloroACHTUNGTRENNUNGmethane (20 mL) and washed with a saturated solu-
1
tion of NH4Cl (20 mL). The organic phase was separated,
dried over MgSO4, and concentrated under vacuum. The
residue was purified by flash chromatography and eluted
with hexane/acetate (95:5).
0.087 g (87%). H NMR (CDCl3, 400 MHz): d=8.19 (d, J=
2.7 Hz, 1H), 7.66–7.62 (m, 2H), 7.59 (dd, J=8.8 Hz, J=
2.4 Hz, 1H), 7.50–7.39 (m, 4H), 7.33–7.27 (m, 2H), 7.14–
7.09 (m, 3H); 13C NMR (CDCl3, 100 MHz): d=174.8, 167.6,
154.3, 134.0, 133.9, 131.5, 131.4, 131.0, 130.8, 129.2, 129.0,
128.0, 126.9, 126.0, 123.4, 119.6, 114.5; MS (EI, 70 eV): m/z
(relative intensity)=412 (71), 411 (45), 331 (43), 258 (20),
178 (100), 163 (25), 105 (55), 89 (21), 77 (26); anal. (%)
calcd. for C21H13ClO2Se: C 61.26, H 3.18; found: C 61.39, H
3.22.
2-Phenyl-3-(phenylselenyl)-4H-chromen-4-one (3a): Ob-
tained as a pale yellow solid; mp 130–1318C; yield: 0.079 g
1
(87%). H NMR (CDCl3, 200 MHz): d=8.25 (dd, J=7.7 Hz,
J=1.3 Hz, 1H), 7.72–7.60 (m, 3H), 7.52–7.24 (m, 7H), 7.18–
7.07 (m, 3H); 13C NMR (CDCl3, 100 MHz): d=175.8, 167.7,
155.8, 134.0, 133.9, 131.2, 130.9, 130.6, 129.1, 128.9, 127.9,
126.6, 126.5, 125.5, 122.3, 117.8, 114.0; MS (EI, 70 eV): m/z
(relative intensity)=378 (100), 377 (56), 361 (13), 297 (67),
178 (84), 165 (38), 105 (62), 77 (19); anal. (%) calcd. for
C21H14O2Se: C 66.85, H 3.74; found: C 67.01, H 3.80.
Acknowledgements
3-(4-Fluorophenylselenyl)-2-phenyl-4H-chromen-4-one
(3b): Obtained as a pale yellow solid; mp 138–1398C; yield:
We are grateful to FAPERGS (PRONEX-10/0005-1),
CAPES (SAUX) and CNPq (CNPq/INCT-catalise) for the fi-
1
0.079 g (83%). H NMR (CDCl3, 200 MHz): d=8.23 (dd, J=
2048
asc.wiley-vch.de
ꢃ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2011, 353, 2042 – 2050

IronACHTUNGTRENNUNG(III) Chloride/Diorganyl Diselenides-Promoted Regioselective Cyclization of Alkynyl Aryl Ketones
nancial support. CNPq is also acknowledged for the fellow-
ships.
Zeni, Synthesis 2009, 4001; c) F. Colobert, A.-S. Casta-
net, O. Abillard, Eur. J. Org. Chem. 2005, 3334; d) B.
Godoi, J. S. S. Neto, A. SperanÅa, C. I. Acker, C. W.
Nogueira, G. Zeni, Tetrahedron Lett. 2009, 50, 5326;
e) A. Arcadi, S. Cacchi, G. Fabrizi, F. Marinelli, L.
Moro, Synlett 1999, 1432; f) T. Yao, D. Yue, R. C.
Larock, J. Org. Chem. 2005, 70, 9985.
References
[1] a) S. Sebille, D. Gall, P. de Tullio, X. Florence, P.
Lebrun, B. Pirotte, J. Med. Chem. 2006, 49, 4690;
b) P. B. Madrid, A. P. Liou, J. L. DeRisi, R. K. Guy, J.
Med. Chem. 2006, 49, 4535; c) T. Heinrich, H. Bçttcher,
K. Schiemann, G. Holzemann, M. Schwarz, G. D. Bar-
toszyk, C. Amsterdam, H. E. Greiner, C. A. Seyfried,
Bioorg. Med. Chem. 2004, 12, 4843; d) L. Tang, J. Yu,
Y. Leng, Y. Feng, Y. Yang, R. Ji, Bioorg. Med. Chem.
Lett. 2003, 13, 3437.
[2] B. H. Havsteen, Pharmacol. Ther. 2002, 96, 67.
[3] a) M. D. Losiewicz, B. A. Carlson, G. Kaur, E. A. Saus-
ville, P. J. Worland, Biochem. Biophys. Res. Commun.
1994, 201, 589; b) W. Filgueira de Azevedo, H.-J. Muel-
ler-Dieckmann, U. Schulze-Gahmen, P. J. Worland, E.
Sausville, S.-H. Kim, Proc. Natl. Acad. Sci. USA 1996,
93, 2735; c) J. Czech, D. Hoffmann, R. Naik, H.-H.
Sedlacek, Int. J. Oncol. 1995, 6, 31; d) G. Kaur, M. Ste-
tler-Stevenson, S. Sebers, P. Worland, H. Sedlacek, C.
Myers, J. Czech, R. Naik, E. Sausville, J. Natl. Cancer
Inst. 1992, 84, 1736.
[4] a) H. Bormann, M. F. Melzig, Pharmazie 2000, 55, 129;
b) A. Minagawa, Y. Otani, T. Kubota, N. Wada, T. Fur-
ukawa, K. Kumai, K. Kameyama, Y. Ojada, M. Fujii,
M. Yano, T. Sato, A. Ito, M. Kitajima, Jpn. J. Cancer
Res. 2001, 92, 1322.
[5] a) G. Zeni, R. C. Larock, Chem. Rev. 2004, 104, 2285;
b) G. Zeni, R. C. Larock, Chem. Rev. 2006, 106, 4644.
[6] a) Y. Yamamoto, I. D. Gridnev, N. T. Patil, T. Jin,
Chem. Commun. 2009, 5075; b) I. Nakamura, Y. Yama-
moto, Chem. Rev. 2004, 104, 2127; c) F. Rodrꢁguez, F. J.
Fananas, in: Targets in Heterocyclic Systems, Vol. 13,
(Eds.: O. A. Attanasi, D. Spinelli), Societa Chimica
Italiana, Rome, 2009, p 273.
[14] a) A. Fꢄrstner, R. Martin, H. Krause, G. Seidel, R.
Goddard, C. W. Lehmann, J. Am. Chem. Soc. 2008,
130, 8773; b) A. Fꢄrstner, B. D. Sherry, Acc. Chem. Res.
2008, 41, 1500; c) A. Fꢄrstner, R. Martin, Chem. Lett.
2005, 34, 624; d) C. Bolm, J. Legros, J. L. Paih, L. Zani,
Chem. Rev. 2004, 104, 6217.
[15] a) A. Fꢄrstner, A. Leitner, M. Mendez, H. Krause, J.
Am. Chem. Soc. 2002, 124, 13856; b) A. Fꢄrstner, A.
Leitner, Angew. Chem. 2002, 114, 632; Angew. Chem.
Int. Ed. 2002, 41, 609; c) G. Seidel, D. Laurich, A.
Fꢄrstner, J. Org. Chem. 2004, 69, 3950; d) A. Fꢄrstner,
A. Schlecker, C. W. Lehmann, Chem. Commun. 2007,
4277.
[16] a) A. Correa, C. Bolm, Angew. Chem. 2007, 119, 9018;
Angew. Chem. Int. Ed. 2007, 46, 8862; b) M. Taillefer,
N. Xia, A. Ouali, Angew. Chem. 2007, 119, 952; Angew.
Chem. Int. Ed. 2007, 46, 934; c) S. L. Buchwald, C.
Bolm, Angew. Chem. 2009, 121, 5694; Angew. Chem.
Int. Ed. 2009, 48, 5586; d) O. Bistri, A. Correa, C.
Bolm, Angew. Chem. 2008, 120, 596; Angew. Chem. Int.
Ed. 2008, 47, 586; e) A. Correa, M. Carril, C. Bolm,
Angew. Chem. 2008, 120, 2922; Angew. Chem. Int. Ed.
2008, 47, 2880.
[17] a) G. Cantagrel, B. C. Carnavalet, C. Meyer, J. Cossy,
Org. Lett. 2009, 11, 4262; b) T. Xu, Z. Yu, L. Wang,
Org. Lett. 2009, 11, 2113; c) K. Cao, F.-M. Zhang, Y.-Q.
Tu, X.-T. Zhuo, C.-A. Fan, Chem. Eur. J. 2009, 15,
6332; d) W.-H. Ji, Y.-M. Pan, S.-Y. Zhao, Z.-P. Zhan,
Synlett 2008, 3046; e) V. Terrasson, J. Michaux, A.
Gaucher, J. Wehbe, S. Marque, D. Prim, J.-M. Cam-
pagne, Eur. J. Org. Chem. 2007, 5332; f) Y. Du, J.
Chang, J. Reiner, K. Zhao, J. Org. Chem. 2008, 73,
2007; g) S. Sabine Laschat, R. Frohlich, B. Wibbeling, J.
Org. Chem. 1996, 61, 2829; h) J. Wang, L. Zhang, Y.
Jing, W. Huang, X. Zhou, Tetrahedron Lett. 2009, 50,
4978; i) J. Bonnamour, C. Bolm, Org. Lett. 2008, 10,
2665; j) A. Mukherjee, K. Pati, R.-S. Liu, J. Org. Chem.
2009, 74, 6311.
[7] J. J. Li, G. W. Gribble, Palladium in Heterocyclic
Chemistry, Pergamon, New York, 2000.
[8] a) B. Liang, M. Huang, Z. You, Z. Xiong, K. Lu, R.
Fathi, J. Chen, Z. Yang, J. Org. Chem. 2005, 70, 6097;
b) H. Miao, Z. Yang, Org. Lett. 2000, 2, 1765.
[9] a) V. N. Kalinin, M. V. Shostakovsky, A. B. Ponamar-
yov, Tetrahedron Lett. 1990, 31, 4073; b) P. G. Ciattini,
E. Morera, G. Ortar, S. S. Rossi, Tetrahedron 1991, 47,
6449; c) S. Torri, H. Okumoto, L.-H. Xu, M. Sadakane,
M. V. Shostakovsky, A. B. Ponomaryov, V. N. Kalinin,
Tetrahedron 1993, 49, 6773; d) H. Miao, Z. Yang, Org.
Lett. 2000, 2, 1765.
[18] a) G. Perin, E. J. Lenard¼o, R. G. Jacob, R. B. Panatieri,
Chem. Rev. 2009, 109, 1277; b) G. Zeni, D. S. Lꢄdtke,
R. B. Panatieri, A. L. Braga, Chem. Rev. 2006, 106,
1032; c) G. Zeni, A. L. Braga, H. A. Stefani, Acc.
Chem. Res. 2003, 36, 731.
[19] a) C. W. Nogueira, G. Zeni, J. B. T. Rocha, Chem. Rev.
2004, 104, 6255; b) C. W. Nogueira, J. B. T. Rocha, J.
Braz. Chem. Soc. 2010, 21, 2055.
[10] P. G. Ciattini, E. Morera, G. Ortar, S. S. Rossi, Tetrahe-
dron 1991, 47, 6449.
[20] R. M. Gay, F. Manarin, C. C. Schneider, D. A. Baran-
celli, M. D. Costa, G. Zeni, J. Org. Chem. 2010, 75,
5701.
[21] a) J. Barluenga, H. Vꢅzquez-Villa, A. Ballesteros, J. M.
Gonzꢅlez, Org. Lett. 2003, 5, 4121; b) J. Barluenga, H.
Vazquez-Villa, I. Merino, A. Ballesteros, J. M. Gonza-
lez, Chem. Eur. J. 2006, 12, 5790; c) J. Barluenga, M.
Trincado, E. Rubio, J. M. Gonzꢅlez, Angew. Chem.
2003, 115, 2508; Angew. Chem. Int. Ed. 2003, 42, 2406;
[11] Q. Yang, H. Alper, J. Org. Chem. 2010, 75, 948.
[12] a) T. Yao, R. C. Larock, J. Org. Chem. 2003, 68, 5936;
b) C. Zhou, A. V. Dubrovsky, R. C. Larock, J. Org.
Chem. 2006, 71, 1626; c) P. R. Likhar, M. S. Subhas, M.
Roy, S. Roy, M. L. Kantam, Helv. Chim. Acta 2008, 91,
259.
[13] a) C.-H. Cho, B. Neuenswander, G. H. Lushington,
R. C. Larock, J. Comb. Chem. 2008, 10, 941; b) F. Man-
arin, J. A. Roehrs, R. Brand¼o, C. W. Nogueira, G.
Adv. Synth. Catal. 2011, 353, 2042 – 2050
ꢃ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
2049

Benhur Godoi et al.
FULL PAPERS
d) J. Barluenga, H. Vꢅzquez-Villa, A. Ballesteros, J. M.
Gonzꢅlez, J. Am. Chem. Soc. 2003, 125, 9028; e) J. Bar-
luenga, M. Trincado, M. Marco-Arias, A. Ballesteros,
E. Rubio, J. M. Gonzꢅlez, Chem. Commun. 2005, 2008.
[22] a) T. Okitsu, K. Sato, A. Wada, Org. Lett. 2010, 12,
3506; b) H. Trabulsi, R. Guillot, G. Rousseau, Eur. J.
Org. Chem. 2010, 5884; c) F. Bellina, F. Colzi, L. Man-
nina, R. Rossi, S. Viel, J. Org. Chem. 2003, 68, 10175.
[23] a) A. Sniady, K. A. Wheeler, R. Dembinski, Org. Lett.
2005, 7, 1769; b) M. S. Rao, N. Esho, C. Sergeant, R.
Dembinski, J. Org. Chem. 2003, 68, 6788; c) Q. Ding, J.
Wu, Adv. Synth. Catal. 2008, 350, 1850; d) H. P. Bi, L.
N. Guo, X. H. Duan, F. R. Gou, S.-H. Huang, X. Y.
Liu, Y. M. Liang, Org. Lett. 2007, 9, 397.
J. Org. Chem. 2003, 68, 5936; c) T. Yao, R. C. Larock,
Tetrahedron Lett. 2002, 43, 7401; d) Z. W. Just, R. C.
Larock, J. Org. Chem. 2008, 73, 2662; e) Y. Chen, C.-H.
Cho, R. C. Larock, Org. Lett. 2009, 11, 173; f) Y. Chen,
C. H. Cho, F. Shi, R. C. Larock, J. Org. Chem. 2009, 74,
6802.
[27] a) D. Alves, M. Prigol, C. W. Nogueira, G. Zeni, Synlett
2008, 914; b) B. Godoi, A. SperanÅa, D. F. Back, R.
Brand¼o, C. W. Nogueira, G. Zeni, J. Org. Chem. 2009,
74, 3469.
[28] Y. Tohda, K. Sonogashira, N. Hagihara, Synthesis 1977,
777.
[29] a) H. Sashida, M. Kaname, A. Nakayama, H. Suzuki,
M. Minoura, Tetrahedron 2010, 66, 5149; b) Y. X.
Zhang, L. Guo, Y. H. Wang, L. L. Zhu, Z. Chen, Tetra-
hedron 2010, 66, 321; c) A. Gimeno, M. Medio-Simꢀn,
C. R. de Arellano, G. Asensio, A. B. Cuenca, Org. Lett.
2010, 12, 1900.
[30] CCDC 788061 contains the supplementary crystallo-
graphic data of 3a for this paper. These data can be ob-
tained free of charge from The Cambridge Crystallo-
graphic Data Centre via www.ccdc.cam.ac.uk/data_re-
quest/cif.
[24] A. Sniady, M. S. Morreale, K. A. Wheeler, R. Dembin-
ski, Eur. J. Org. Chem. 2008, 3449.
[25] a) T. Okitsu, D. Nakazawa, R. Taniguchi, A. Wada,
Org. Lett. 2008, 10, 4967; b) V. Andre, S. Robin, G.
Rousseau, Tetrahedron Lett. 2008, 49, 5059; c) T.
Okitsu, D. Nakazawa, K. Nakagawa, T. Okano, A.
Wada, Chem. Pharm. Bull. 2010, 58, 418; d) G. Rous-
seau, T. Strzalko, M. C. Roux, Tetrahedron Lett. 2004,
45, 4503.
[26] a) S. Roy, B. Neuenswander, D. Hill, R. C. Larock, J.
Comb. Chem. 2009, 11, 1128; b) T. Yao, R. C. Larock,
2050
asc.wiley-vch.de
ꢃ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2011, 353, 2042 – 2050