C-alkynylation of chromones by sonogashira reaction

Article abstract of DOI:10.1071/CH13006

Sonogashira reaction of bromochromones and-flavones with a bromine atom on their benzene or heterocyclic ring with various terminal alkynes gave the desired products with nearly the same efficiency as the previously used iodine derivatives. The coupling reactions were performed in the presence of [tetrakis(triphenylphosphine)palladium(0)], copper(i) co-catalyst, and triethylamine, resulting in the formation of numerous hitherto unknown alkynylated oxygen heterocycles, and provide further proof for the applicability of this reaction for these O-heterocycles. Chromones with ethynyl functionality were prepared by removal of the trimethylsilyl protecting group and used as terminal alkynes in a second cross-coupling reaction.

Full text of DOI:10.1071/CH13006

CSIRO PUBLISHING
Aust. J. Chem. 2013, 66, 646–654
Full Paper
http://dx.doi.org/10.1071/CH13006
C-Alkynylation of Chromones by Sonogashira Reaction
A C
,
A
A B
,
´
Istva´n Pazurik, and Anita Abraha´m
Tama´s Patonay,
A
Department of Organic Chemistry, University of Debrecen, Egyetem te´r 1,
H-4032 Debrecen, Hungary.
B
Research Group of Homogeneous Catalysis HAS-UD, Egyetem te´r 1,
H-4032 Debrecen, Hungary.
C
Corresponding author. Email: patonay.tamas@science.unideb.hu
Sonogashira reaction of bromochromones and -flavones with a bromine atom on their benzene or heterocyclic ring with
various terminal alkynes gave the desired products with nearly the same efficiency as the previously used iodine
derivatives. The coupling reactions were performed in the presence of [tetrakis(triphenylphosphine)palladium(0)],
copper(I) co-catalyst, and triethylamine, resulting in the formation of numerous hitherto unknown alkynylated oxygen
heterocycles, and provide further proof for the applicability of this reaction for these O-heterocycles. Chromones with
ethynyl functionality were prepared by removal of the trimethylsilyl protecting group and used as terminal alkynes in a
second cross-coupling reaction.
Manuscript received: 10 January 2013.
Manuscript accepted: 7 February 2013.
Published online: 24 April 2013.
further equivalent of alkyne and CuI co-catalyst.[6b] Reaction of
3-iodochromones and 3-iodo-1-thiochromones with various
alkynes under copper-free conditions led to the formation of
benzannulated double adducts.[6c] 3-Iodo-40-methoxyflavone
was alkynylated with a paramagnetic alkyne compound under
very similar conditions.[7] 6-, 7-, and 40-Iodoflavones were
alkynylated with 3-hydroxy-3-methylbut-1-yne and 3-methyl-
but-3-en-1-yne. The products were tested for antimicrobial and
cytotoxic activities but no marked effect was found.[8] Larock
and his coworkers reported the synthesis of 3-iodochromones
and flavones and their thio analogues from the corresponding
aryl alkynyl ketones in the presence of ICl, their transformation
into 3-iodochromones and flavones, and the ring-closure of the
2-alkynyl ketone fragment into a furan ring accompanied by
incorporation of an alkoxy group from the solvent in the pres-
ence of a gold(III) catalyst.[9] A similar ring-closure leading to
furans in the presence of copper(I) salts was also reported by
Yamamoto and his coworkers.[10] 3-Iodochromone was coupled
with phenylacetylene and its 4-substituted derivatives in the
presence of Pd(PPh3)2Cl2, CuI, and PPh3 ligand to give deri-
vatives with interesting electrogenerated chemiluminesce
(ECL) properties; X-ray structures and density functional theory
calculations were also presented.[11] 4-Hydroxycoumarin was
tosylated with 4-toluenesulfonyl chloride, and the intermediate,
after replacement of the solvent and without isolation, was
reacted with phenylacetylene and various aliphatic alkynes
under copper-free conditions in the presence of PdII-acetate and
PPh3 to give the expected 4-alkynylcoumarins in moderate to
good yield.[12]
Introduction
The palladium-catalyzed coupling of terminal alkynes with aryl
and vinyl halides (Sonogashira coupling) is an important and
widely used reaction for carbon–carbon bond formation.[1]
These reactions are often used in the field of N-heterocycles, but
relatively little has been published in the field of O-heterocycles.
In 1998, Tsukayama and his coworkers reported the coupling
of 5,7,40-tribenzyloxy-8-iodoisoflavone with 2-methyl-3-butyn-
2-ol in the presence of PdCl2 and CuI to give the expected
Sonogashira product.[2a] The same protocol was also success-
fully used for 6-iodoisoflavones to give various naturally
occurring derivatives.[2b–2e] In 1999, Johnson, Chandraratna,
and their coworkers reported on the coupling of 6-bromo-1-
thiochromanone, 2,2-dimethyl-6-triflyloxy-1-thiochromanone,
and 6-bromo-2,2-dimethylchromanone with various alkynes.
Some of the prepared compounds showed high affinity for
retinoid acid receptors.[3] In 2001, the Sonogashira–Hagihara
cross-coupling of 3-bromocoumarin and phenylacetylene in
excellent yield was reported.[4] In 2002, Cho and his coworkers
coupled 3,5-dibromo-2-pyrone with various alkynes in the
presence of triethylamine as base and dioxane or DMF as
solvent, using Pd(PPh3)2Cl2 as ligand, to give rise to the corre-
sponding 3-alkynyl-5-bromo-2-pyrones with good-to-excellent
yield and regioselectivity; the bromo substituent adjacent to the
lactone group showed higher reactivity.[5] One year later, Pal,
Yeleswarapu, and their coworkers reported the coupling of
3-iodoflavones with four different terminal alkynes in the
presence of Pd(PPh3)2Cl2 as catalyst, CuI as co-catalyst, and
(S)-prolinol as base to give 3-(substituted)alkynylflavones
in 52–81 % yields.[6a,b] In addition,
i.e. 3-enynyl derivatives were obtained as major products when
3-iodoflavones were treated with a terminal alkyne in the
absence of CuI (Heck conditions) followed by the addition of a
a
double adduct,
Recently, we published our results on the palladium-
catalyzed cross-coupling (Heck–Mizoroki reaction) of bromo-
chromones and bromoflavones with various terminal alkenes
and pointed out that this methodology offers a new route to the
Journal compilation Ó CSIRO 2013
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Alkynylation of Chromones
647
C-alkenylation of these oxygen heterocycles including various
naturally occurring systems.[13] The usefulness of Suzuki–
Miyaura cross-couplings for the arylation of (triflyloxy)
coumarins and -flavones has also been demonstrated.[14]
Cross-coupling of similar substrates with terminal alkynes is
also a promising approach; C-alkynylation in the presence of a
neighbouring XH functionality followed by a subsequent ring-
closure may lead to tricyclic systems such furochromones
and pyranochromones frequently isolated from natural sources.
In this contribution, we present our results of the Sonogashira
reaction of simple bromochromones and -flavones with various
terminal alkynes and some transformation of the resulting
products.
period (Table 1, entry 6). As 3-bromochromone (1) is a base-
sensitive substrate, the moderate yield seemed acceptable and we
applied these conditions to further cross-coupling experiments.
Then, we tested the cross-coupling reaction with 3-
bromochromone (1) and other substrates such as bromo-
chromones 9a–d, which have the halo substituent in their ring
A and bromoflavones 10, 11. In addition to the model reactant
phenylacetylene used previously, trimethylsilylacetylene and 3-
methyl-1-butyn-3-ol were used as terminal alkynes because in
both cases the coupled products have a removable end-group,
giving the corresponding ethynyl derivatives after cleavage.
Moreover, 3-hydroxy-3-methylbutynylated chromones and
flavones with an ortho-hydroxy function are reasonable inter-
mediates for naturally occurring tricyclic oxygen heterocycles
with a 2,2-dimethylpyran motif after diastereoselective reduc-
tion and subsequent ring-closure. The results of the C–C
couplings are shown in Table 2. With only one exception, the
desired alkynylated chromones 4, 5, 11a–d, 12a–d, and 13a–d,
and flavones 6–8 and 14–16 were obtained. Surprisingly, no
cross-coupled product 11a but only the Glaser–Hay[16] product
17 was obtained in the reaction of 5-bromochromone (9a) and
phenylacetylene. This by-product was not indentified in the
other reactions. The yields varied over a wide range (23–92 %)
but typically, moderate to good yields were obtained (Table 2).
It is noteworthy that the position of the halogen atom had no
Results and Discussion
As indicated in the Introduction, most Sonogashira couplings
in the field of oxygen heterocycles were performed by starting
from iodo derivatives up to now. However, the synthesis of
iodochromones and -flavones other than the 3-iodo substrates is
laborious, less efficient, and costly. Therefore, we wanted to
investigate the reactivity and usefulness of bromochromones
and -flavones in the preparation of various alkynylated com-
pounds. The starting material bromochromones 1, 9a–d and
bromoflavones 2, 10 were prepared according to previously
published methods.[13a,c,15]
First, we tried to find optimal conditions for the Sonogashira
coupling using 3-bromochromone (1) as substrate and phenyl-
acetylene as the terminal alkyne (Scheme 1). In our attempts, the
classical combination of the tetrakis(triphenylphosphine)palla-
dium(0) [Pd(PPh3)4] catalyst, copper(I) iodide co-catalyst,[1b]
and triphenylphosphine ligand was studied; representative
results are shown in Table 1.
Table 1. Optimization oftheSonogashirareaction of3-bromochromone
(1) and phenylacetylene
DABCO, diazabicyclo[2.2.2]octane; TEA, triethylamine
Entry Solvent Base
Temperature
Reaction
time [h]
Yield
[%]A
[8C]
Triethylamine (TEA) as base and tetrahydrofuran (THF) as
solvent at elevated temperature gave a moderate yield (Table 1,
entry 2); no reaction was observed at room temperature (Table 1,
entry 1). Other bases such as pyrrolidine or diazabicyclo[2.2.2]
octane (DABCO) in THF resulted in much worse yields, if any
(Table 1, entries 3, 4). In N,N-dimethylformamide (DMF), only a
marginal yield was achieved (Table 1, entry 5) but the use of
TEA as base and solvent gave a better result in a shorter reaction
1
2
3
4
5
6
THF
THF
THF
THF
DMF
TEA
RT
60
70
70
70
70
72
7
0
42
0
TEA
Pyrrolidine
DABCO
TEA
6
7
19
9
7
TEA
2
46
AYields refer to isolated pure products.
1, 3–5 2, 6–8
O
R
O
R
R
H
Ph
R1
(i) or (ii)
3, 6 4, 7
5, 8
CMe2OH
Br
R1
R1
SiMe3
Ph
O
O
3–8
1, 2
8
5
O
R
R
O
R1
(i) or (ii)
7
6
R1
Br
Ph
Ph
17
O
O
11–16
9, 10
9a, 11a–13a 9b, 11b–13b 9c, 11c–13c 9d, 11d–13d 10, 14–16
11, 14 12, 15
R1 Ph
13, 16
CMe2OH
H
5
H
6
H
7
H
8
Ph
6
SiMe3
R
position
Scheme 1. Synthesis of ethynylchromones 3 8 and 11 16. Reagents and conditions: (i) alkyne/CuI/Pd(PPh ) /PPh /triethylamine (TEA)/
]
]
60–908C; (ii) alkyne/Pd-C/PPh3/TEA/80–908C.
3 4
3

´
T. Patonay, I. Pazurik, and A. Abraha´m
648
marked effect on the reaction conditions or the yields of the
Sonogashira couplings, which is in sharp contrast with
the Heck–Mizoroki reactions of bromochromones, where the
7-bromo derivative has considerably higher reactivity in com-
parison with the 6-bromo analogue.[13a] Similarly, we demon-
strated the greater reactivity of position 7 in the Suzuki coupling
of 5,7- and 7,8-bis(trifluoromethanesulfonyloxy)flavones. The
difference in the reactivities allowed the regioselective mono-
arylation of these substrates.[14c,e]
Since 1990, it has been known that Pd/C can be used as a
palladium source in Sonogashira cross-coupling;[17a] in 2002,
German researchers reported the successful application of Pd/C
as catalyst in Heck–Mizoroki, Suzuki–Miyaura, and Sonogashira
reactions.[17b] Therefore, we also tested this possibility. As shown
in Table 2 (entries 3, 6, 12, 22), alkynylation using Pd/C instead
of the more expensive tetrakis(triphenylphosphine)palladium(0)
led to the expected products in all cases but the yields were lower,
with the exception of trimethylsilylacetylene (see entry 2 versus
entry 3). However, these conditions could be considered if
scaling up of these coupling reactions was necessary.
Next, we investigated the removal of the end-group from
3-hydroxy-3-methylbutynylated derivatives in the form of ace-
tone, which could lead to an ethynylchromone derivative. This
type of cleavage is usually performed under basic conditions
such as sodium hydroxide in refluxing toluene,[18] sodium
hydride in refluxing toluene,[19] or potassium hydroxide in hot
diisopropyl amine.[19] Some of these reactions have also been
applied in tandem or domino couplings.[19,20] In our case, the
attempted deprotection of 6-(3-hydroxy-3-methyl-1-butynyl)
chromone (13b) failed to give any desired product with either
sodium hydroxide or sodium hydride in hot toluene; no reaction
was observed.
When compound 13b was reacted with 5 M aqueous sodium
hydroxide in the presence of 10 mol-% tetrabutylammo-
nium iodide (TBAI) in toluene at 808C,[21] no cleavage of the
end-group but opening of the chromone ring followed by a retro-
Claisen reaction took place and 20-hydroxy-50-(3-hydroxy-3-
methyl-1-butynyl)acetophenone (18) was obtained in moderate
yield (Scheme 2).
The products were characterized on the basis of their IR, 1H,
and 13C NMR spectra. The only special and noteable spectral
feature observed in the IR spectra of the (trimethylsilyl)ethynyl
derivatives 4, 7, 12a–d, and 15 was the intensive CꢀC stretch
observed between 2140 and 2170 cmꢁ1. In the case of the other
alkyne derivatives, this band was much weaker.
OH
O
(i)
CH3
O
O
OH
OH
13b
18
We can conclude that the results summarized in Tables 1
and 2 clearly show the generality and the synthetic value of the
Sonogashira cross-coupling in the field of benzopyranoids.
Scheme 2. Attempted deprotection of ethynylchromone 13b. Reagents
and conditions: (i) 3 equiv. 5M aqueous NaOH/tetrabutylammonium iodide
(10 mol-%)/PhMe/808C.
Table 2. Sonogashira reaction of bromochromones and -flavones 1, 2, 9a d, 10 and various alkynes
]
Conditions A: alkyne/CuI/Pd(PPh3)4/PPh3/triethylamine (TEA)/708C; Conditions B: alkyne/Pd-C/PPh3/TEA/708C
Entry
Starting material
R
R1
Conditions
Reaction time [h]
Product
Yield [%]A
1
1
1
H
Ph
A
A
B
A
A
B
A
A
A
A
A
B
A
A
A
A
A
A
A
A
A
B
A
A
A
2
3
4
46
63
79
48
85
64
23B
80C
0D
72
89
53
64
36
76
48
62
50
48
54
73
61
28
90
92
2
H
SiMe3
SiMe3
CMe2OH
Ph
3
3
1
H
4
4
4
1
H
3
5
5
2
Ph
Ph
Ph
Ph
H
3
6
6
2
Ph
4
6
7
2
SiMe3
CMe2OH
Ph
5
7
8
2
4
8
9
9a
9b
9c
9c
9d
9a
9b
9c
9d
9a
9b
9c
9d
9d
10
10
10
3
11a
11b
11c
11c
11d
12a
12b
12c
12d
13a
13b
13c
13d
13d
14
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
H
Ph
4.5
3.75
4
H
Ph
H
Ph
H
Ph
2.5
1
H
SiMe3
SiMe3
SiMe3
SiMe3
CMe2OH
CMe2OH
CMe2OH
CMe2OH
CMe2OH
Ph
H
0.5
0.5
2
H
H
H
2
H
1.5
0.5
4
H
H
H
4
Ph
Ph
Ph
3
SiMe3
CMe2OH
1.5
3
15
16
AYields refer to isolated pure products.
BReaction performed at 908C.
CReaction performed at 808C.
DOnly homo-coupled product 17 was obtained (35 %).

Alkynylation of Chromones
649
O
R
R
O
(i)
(i)
4, 19
7, 20
R
H
Ph
O
SiMe3
R
O
4, 7
19, 20
O
O
O
R
TMS
O
12a–d, 15
21a–d, 22
12a, 21a 12b, 21ab 12c, 21c 12d, 21d 15, 22
H
5
H
6
H
7
H
8
Ph
6
R
position
Scheme 3. Deprotection of (trimethylsilyl)ethynylchromones 4, 7, 12a–d and 15. Reagents and conditions: (i) TBAF/THF,
room temperature.
8Ј
O
2Ј
O
O
O
1
(i)
O
O
5Љ
8Љ
3Ј
ϩ
4Љ
4Ј
O
5Ј
3Љ
2Љ
Br
2
O
1
21b
23
Scheme 4. Synthesis of ethynyl-bridged bis-chromone 23.
Then, we studied the removal of the trimethylsilyl group
from derivatives 4, 7, 12, and 15. Several methods have
been published in the literature. 6-[(2-Trimethylsilyl)ethynyl]
thiochromanones have been deprotected by potassium carbonate
in methanol[3] but this approach seemed risky because of the
sensitivity of the chromone ring towards bases (see above).
Copper(I) and silver(I) ions could also cleave the trimethyl-
silyl functionality[20,22,23] but in the case of the copper(I) ion,
dimerization into the corresponding butadiynes has been
observed.[20,23] We decided to apply the ‘classical’ fluoride
ion-promoted cleavage.[24] To our delight, the treatment of
chromone and flavone derivatives 4, 7, 12, and 15 with tetra-
butylammonium fluoride (TBAF) in THF solution smoothly
gave the desired deprotected compounds 19–22, in good to
excellent yields (61–92 %) (Scheme 3). The only exception
was the base-sensitive 3-[2-(trimethylsilyl)ethynyl]chromone
(4), which gave the deprotected product only in 27 % yield.
Chromones 4 and 12 gave the corresponding products in a short
(10–20 min) reaction period; flavones 7 and 15 required longer
treatment.
The successful deprotection was proved by the appearance of
the signal belonging to the terminal alkyne hydrogens in the
1
range d 3.0–3.5 ppm of their H NMR spectra. These ethynyl-
chromone derivatives are useful building blocks. For instance,
they can act as substrates in ‘Click’ reactions to afford
1,4-disubstituted-1,2,3-triazoles of complex structure.[25]
Another application is shown in Scheme 4, the reaction of
6-ethynylchromone (21) with 3-bromochromone (1) in a Sono-
gashira coupling resulting in the ethynyl-bridged bis-chromone
23 in moderate yield (Scheme 4).
allows the synthesis of a wide range of hitherto unknown oxygen
heterocycles including the useful building blocks ethynylchro-
mones as secondary products. Extension of the coupling to
ortho-substituted starting materials can open the way to various
naturally occurring products such as tricyclic systems. Such
exploitation of the coupling will be presented soon.
Experimental
Thin-layer chromatography was carried out on Kieselgel 60 F254
(0.25-mm layer thickness, Merck). Chromatographic separa-
tions were performed using silica gel (Merck, 70–230 mesh);
eluting mixtures are shown. Melting points were determined on
a Boetius hot-stage apparatus and are uncorrected. 1H and 13
C
NMR spectra were recorded with a Bruker AM 360 (360 MHz
for 1H, 90 MHz for 13C nuclei) spectrometer (internal standard
1
TMS, d 0 ppm, or residual CHCl3 peaks (d 7.26 ppm) for H
NMR and (d 77.00 ppm) for 13C NMR)). 13C NMR assignments
were supported by the J-echo technique. IR spectra were
recorded with Perkin–Elmer 16 PC-FT-IR (Fourier-transform
IR) or Jasco FT-IR 4100A instruments with KBr discs. The mass
spectra were recorded on an AutoSpecEQ EIþ spectrometer.
Elemental analyses were performed in-house with Carlo
Erba 1106 EA and Elementar Vario MicroCube instruments.
Triethylamine was distilled from lithium aluminium hydride.
Bromochromones (1, 9a–d) were prepared as previously
reported.[13a] 3-Bromoflavone (2) was prepared according to a
literature procedure[15] by heating flavone with 1.67 equiv. of
N-bromosuccinimide (NBS) and 0.25 equiv. of pyridine in dry
carbon tetrachloride in 77 % yield. (CAUTION: because of the
adverse health effects of the solvent, reaction and workup should
be performed in a well-ventilated hood!). The product was
In conclusion, we have demonstrated that Sonogashira cross-
coupling reaction of bromochromones with various alkynes

´
T. Patonay, I. Pazurik, and A. Abraha´m
650
8
5
2
O
O
R
72.2 (Ca), 101.1 (Cb), 111.0 (C-3), 118.5 (C-8), 123.5 (C-4a),
126.1, 126.4 (C-5, C-6), 134.4 (C-7), 156.2 (C-8a), 158.2 (C-2),
176.3 (C-4). (Found: C 73.55, H 5.41. C14H12O3 requires:
C 73.67, H 5.30 %).
α
β
R1
3
6
3-(2-Phenylethynyl)flavone 6
Chart 1.
Yield: 85 % (Conditions A, reaction period: 3 h); 64 %
(Conditions B, reaction period: 4 h), mp 161–1638C. nmax
(KBr)/cmꢁ1 3058, 1645 (C¼O), 1615 (C¼C), 1554, 1464,
1396 (flavone skeleton), 1306, 1120, 753, 705. dH ([D6]DMSO)
7.44 (br s, 5H, Ar–H), 7.57 (m, 1H, 6-H), 7.67 (br s, 3H, Ar–H),
7.79 (d, J 8.4, 1H, 8-H), 7.89 (m, 1H, 7-H), 8.13 (d, J 7.9, 1H,
5-H), 8.23 (m, 2H, 20,60-H). dH ([D6]DMSO) 82.0 (Ca), 96.1
(Cb), 105.6 (C-3), 118.1 (C-8), 121.0, 121.8 (C-4a, C-10), 122.0
(C-6), 124.7, 125.6 (C-40, C-400), 128.0, 128.3, 128.4, 130.5
(C-20,60, C-30,50, C-200,600, C-300,500), 130.1 (C-10), 131.4 (C-5),
134.3 (C-7), 154.6 (C-8a), 174.8 (C-4). (Found: C 85.61, H 4.48.
C23H14O2 requires: C 85.70, H 4.38 %).
identified by its literature mp[25,26] and its 1H NMR spectrum.
6-Bromoflavone (10) was synthetized by our methodology
(iodine-catalyzed dehydrogenation in hot DMSO solution)[27]
in 53 % yield and was identified by its literature mp[28] and its
1H NMR spectrum.
For numbering of the products, see Chart 1.
General Procedure for the Synthesis of (2-Substituted
Ethynyl)chromones
Conditions A: A mixture of bromochromone 1, 9a–d or
bromoflavone 2, 10 (2.5 mmol), 1-alkyne (3.75 mmol), tetrakis
(triphenylphosphine)palladium(0) (71.9 mg, 0.0622 mmol),
triphenylphosphine (16.3 mg, 0.0622 mmol), and copper(I)
iodide (6.0 mg, 0.0315 mmol) in triethylamine (15 mL) was
heated at 708C under a nitrogen atmosphere. When the starting
material had disappeared (TLC monitoring; for details see
Tables 1 and 2), the solvent was removed under reduced pres-
sure, and the residue was subjected to column chromatography
(eluent: hexane/acetone 4 : 1 v/v unless otherwise stated).
Conditions B: The reaction was performed and worked up as
given in Conditions A but 72 mg 10 % palladium-on-charcoal
catalyst was used as the palladium source.
3-(2-(Trimethylsilyl)ethynyl)flavone 7
Yield: 23 % (Conditions A, reaction period: 5 h, reaction
temperature: 908C), mp 58–598C. nmax (KBr)/cmꢁ1 2959, 2153
(CꢀC), 1651 (C¼O), 1614 (C¼C), 1465, 1381 (flavone skele-
ton), 1250, 1183, 1140, 895, 859. dH (CDCl3) 0.27 (s, 9H, Me3),
7.44 (m,1H, 6-H), 7.54–7.58 (m, 4H, 8-H, 30,50-H, 40-H), 7.70
(m, 1H, 7-H), 8.22–8.29 (overlapping dd, 3H, 5-H, 20,60-H). dC
(CDCl3) 0.2 (Me3), 94.6 (Ca), 104.9 (Cb), 118.1 (C-8), 119.0
(C-3), 123.9 (C-4a), 125.1, 126.1 (C-5, C-6), 127.1 (C-20,60),
128.2 (C-30,50), 130.1 (C-40), 132.8 (C-10), 134.2 (C-7), 157.0
(C-8a), 158.9 (C-2), 178.5 (C-4). (Found: C 75.40, H 5.58.
C20H18O2Si requires: C 75.43, H 5.70 %).
3-(2-Phenylethynyl)chromone 3
3-(3-Hydroxy-3-methyl-1-butynyl)flavone 8
Yield: 46 % (Conditions A, reaction period: 2 h), mp 174.5–
1788C (lit.[9a] 179–1818C). nmax (KBr)/cmꢁ1 3074 (CH), 1650
(C¼O), 1616 (C¼C), 1464, 1380, 1302, 1216, 754. dH (CDCl3)
7.35 (m, 3H, 30,50-H, 40-H), 7.42–7.50 (m, 2H, 6-H, 8-H), 7.60
(m, 2H, 20,60-H), 7.70 (m, 1H, 7-H), 8.24 (s, 1H, 2-H), 8.29 (dd, J
7.9, 1.6, 1H, 5-H). dC (CDCl3) 79.5 (Ca), 95.0 (Cb), 111.4 (C-3),
118.2 (C-8), 122.6, 123.5 (C-4a, C-10), 125.7, 126.2 (C-6, C-40),
128.2, 128.6 (C-5, C-30,50), 131.8 (C-20,60), 133.9 (C-7), 155.9
(C-8a), 157.8 (C-2), 175.3 (C-4). (Found: C 83.04, H 3.99.
C17H10O2 requires: C 82.91, H 4.09 %).
Yield: 80 % (Conditions A, reaction period: 4 h, reaction
temperature: 808C, column chromatography: toluene/ethyl
acetate, 4 : 1 v/v), mp 138.5–1418C. nmax (KBr)/cmꢁ1 3437
(C–OH), 2982, 1630 (C¼O), 1615 (C¼C), 1466, 1386 (flavone
skeleton), 1239, 1135, 953, 760. dH (CDCl3) 1.60 (s, 6H, Me2),
7.43 (m, 1H, 6-H), 7.47–7.56 (m, 4H, 8-H, 30,50-H, 40-H), 7.71
(m, 1H, 7-H), 8.18 (dd, J 8.0, 2.1,1H, 8-H), 8.25 (dd, 1H, J 8.2,
1.9, 5-H). dC (CDCl3) 32.6 (Me2), 64.9 (CMe2OH), 85.6 (Ca),
111.1, 112.1 (C-3, Cb), 117.9 (C-8), 124.6 (C-6), 125.5, 125.7
(C-4a, C-5), 127.3 (C-20,60), 128. 6 (C-30,50), 130.4 (C-40), 132.9
(C-10), 135.5 (C-7), 156.8, 157.3 (C-2, C-8a), 179.6 (C-4).
(Found: C 79.08, H 5.28. C20H16O3 requires: C 78.93, H 5.30 %).
3-(2-(Trimethylsilyl)ethynyl)chromone 4
Yield: 63 % (Conditions A, reaction period: 3 h); 79 %
(Conditions B, reaction period: 4 h), mp 95–968C. nmax (KBr)/
cmꢁ1 2956, 2164 (CꢀC), 1648 (C¼O), 1614 (C¼C), 1464,
1218, 1188, 860, 842, 762. dH (CDCl3) 0.27 (s, 9H, Me3), 7.38–
7.49 (m, 2H, 6-H, 8-H), 7.68 (m, 1H, 7-H), 8.18 (s, 1H, 2-H),
8.24 (dd, 1H, J 8.6, 1.4, 5-H). dC (CDCl3) 0.2 (Me3), 94.9 (Ca),
101.3 (Cb), 111.5 (C-3), 118.5 (C-8), 123.8 (C-4a), 126.1, 126.5
(C-5, C-6), 134.3 (C-7), 156.1 (C-8a), 159.1 (C-2), 175.6 (C-4).
(Found: C 69.12, H 5.65. C14H14O2Si requires: C 69.38, H
5.82 %).
6-(2-Phenylethynyl)chromone 11b
Yield: 72 % (Conditions A, reaction period: 4.5 h), mp 116–
1178C. nmax (KBr)/cmꢁ1 3066, 1648 (C¼C), 1610 (C¼C), 1492,
1440, 1318, 836, 754. dH (CDCl3) 6.34 (d, J 6.4, 1H, 3-H), 7.29–
7.39 (m, 3H, 30,50-H, 40-H), 7.43 (d, J 8.4, 1H, 8-H), 7.52 (m, 2H,
20,60-H), 7.77 (dd, J 8.4, 2.1, 1H, 7-H), 7.84 (d, J 6.4, 1H, 2-H),
8.36 (d, J 2.1, 1H, 5-H). dC (CDCl3) 88.0, 90.8 (Ca, Cb), 113.4
(C-3), 118.9 (C-8), 121.1 (C-6), 123.0, 125.1 (C-4a, C-10), 128.7
(C-30,50), 129.0, 129.4 (C-5, C-40), 132.0 (C-20,60), 136.8 (C-7),
155.6 (C-2), 156.2 (C-8a), 177.1 (C-4). (Found: C 82.88, H 3.91.
C17H10O2 requires: C 82.91, H 4.09 %).
3-(3-Hydroxy-3-methyl-1-butynyl)chromone 5
Yield: 48 % (Conditions A, reaction period: 3 h), mp 109–
1118C. nmax (KBr)/cmꢁ1 3416 (C–OH), 3072 (C–H), 1652
(C¼O), 1614 (C¼C), 1466, 1284, 1232, 1166 (C–O), 768. dH
(CDCl3) 1.64 (s, 6H, Me2), 3.60–3.80 (br s, 1H, OH), 7.36–7.50
(m, 2H, 6-H, 8-H), 7.69 (m, 1H, 7-H), 8.14 (s, 1H, 2-H), 8.22 (dd,
J 7.1, 1.4, 1H, 5-H). dC (CDCl3) 31.5 (Me2), 65.4 (CMe2OH),
7-(2-Phenylethynyl)chromone 11c
Yield: 89 % (Conditions A, reaction period: 3.75 h), 53 %
(Conditions B, reaction period: 4 h), mp 129–1308C. nmax (KBr)/
cmꢁ1 3064, 2204 (CꢀC), 1648 (C¼O), 1616 (C¼C), 1422,

Alkynylation of Chromones
651
1348, 1308, 1028, 828. dH (CDCl3) 6.34 (d, J 6.0, 1H, 3-H), 7.38,
7.49–7.60 (m, 7H, Ar-H), 7.84 (d, J 6.0, 1H, 2-H), 8.17 (d, J 8.4,
1H, 5-H). dC (CDCl3) 87.7 (Ca), 93.3 (Cb), 113.2 (C-3), 120.8
(C-8), 122.2, 124.1 (C-4a, C-10), 125.8 (C-6), 128.3 (C-40),
128.4 (s, C-30,50), 129.0 (C-7), 129.0 (C-5), 131.8 (C-20,60),
155.3 (C-2), 156.1 (C-8a), 177.0 (C-4). (Found: C 83.04, H 3.99.
C17H10O2 requires: C 82.91, H 4.09 %).
1H, 7-H), 7.94 (d, J 6.5, 1H, 2-H), 8.16 (dd, J 7.5, 1.4, 1H, 5-H).
dC (CDCl3) 0.2 (Me3), 98.2 (Cb), 102.5 (Ca), 113.5 (C-3), 114.3
(C-8), 125.0 (C-6), 125.3 (C-4a), 126.4 (C-5), 138.2 (C-7), 155.7
(C-2), 156.7 (C-8a), 177.5 (C-4). (Found: C 69.47, H 5.84.
C14H14O2Si requires: C 69.38, H 5.82 %).
5-(3-Hydroxy-3-methyl-1-butynyl)chromone 13a
Yield: 50 % (Conditions A, reaction period: 2 h, column
chromatography: hexane/acetone 8 : 1 v/v), mp 101.5–
103.58C. nmax (KBr)/cmꢁ1 3404 (OH), 2980, 1653 (C¼O),
1594, 1474, 1400, 1388, 1344, 1171 (C–O), 954, 845, 768. dH
(CDCl3) 1.72 (s, 6H, Me2), 2.94 (s, 1H, OH), 6.29 (d, J 5.8, 1H,
3-H), 7.39 (d, J 7.8, 1H, 8-H), 7.45 (d, J 7.4, 1H, 6-H), 7.56 (m,
1H, 7-H), 7.77 (d, J 5.8, 1H, 2-H). dH ([D6]DMSO) 1.55 (s, 6H,
Me2), 5.66 (s, 1H, OH), 6.44 (d, J 6.0, 1H, 3-H), 7.48 (m, 1H,
7-H), 7.87 (d, J 6.6, 1H, 8-H), 8.03 (d, J 7.4, 1H, 6-H), 8.41 (d,
J 6.0, 1H, 2-H). dC ([D6]DMSO) 31.0 (Me2), 63.3 (CMe2OH),
73.7 (Ca), 102.4 (Cb), 112.1 (C-3), 112.9 (C-4a), 124.0 (C-5),
124.5, 124.7 (C-6, C-8), 136.9 (C-7), 155.9 (C-8a), 156.5 (C-2),
175.6 (C-4). (Found: C 73.79, H 5.22. C14H12O3 requires:
C 73.67, H 5.30 %).
8-(2-Phenylethynyl)chromone 11d
Yield: 64 % (Conditions A, reaction period: 2.5 h), mp 94–
968C. nmax (KBr)/cmꢁ1 3066, 3070, 1658 (C¼O), 1588, 1574,
1476, 1432, 1406, 1334, 1246, 800, 760. dH (CDCl3) 6.39 (d,
J 6.4, 1H, 3-H), 7.33–7.45 (m, 4H, 6-H, 30,50-H, 40-H), 7.53–7.66
(m, 2H, 20,60-H), 7.85 (dd, J 6.4, 1.4, 1H, 7-H), 7.95 (d, J 6.4, 1H,
2-H), 8.17 (dd, J 7.6, 1.4, 1H, 5-H). dC (CDCl3) 82.7 (Ca), 96.1
(Cb), 113.2 (C-3), 114.2 (C-8), 122.5 (C-10), 124.8, 125.0 (C-4a,
C-6), 125.8 (C-40), 128.4 (C-30,50), 128. 9 (C-5), 131.7 (C-20,60),
137.2 (C-7), 155.4 (C-2), 156.1 (C-8a), 177.2 (C-4). (Found:
C 82.97, H 3.91. C17H10O2 requires: C 82.91, H 4.09 %).
5-(2-(Trimethylsilyl)ethynyl)chromone 12a
Yield: 36 % (Conditions A, reaction period: 1 h), mp 76–
778C. nmax (KBr)/cmꢁ1 2959, 2142 (CꢀC), 1661, 1645 (C¼O),
1592, 1470, 1400, 1343, 1250, 985, 842, 760. dH (CDCl3) 0.37
(s, 9H, Me3), 6.30 (d, J 5.6, 1H, 3-H), 7.38 (m, 1H, 7-H), 7.55 (m,
2H, 6-H, 8-H), 7.75 (d, J 5.6, 1H, 2-H). dC (CDCl3) 0.2 (Me3),
102.5, 102.6 (Ca, Cb), 112.8 (C-3), 119.0 (C-8), 123.8 (C-4a),
126.8 (C-6), 126.9 (C-5), 133.2 (C-7), 155.1 (C-8a), 157.1 (C-2),
176.0 (C-4). (Found: C 69.49, H 5.72. C14H14O2Si requires:
C 69.38, H 5.82 %).
6-(3-Hydroxy-3-methyl-1-butynyl)chromone 13b
Yield: 48 % (Conditions A, reaction period: 1.5 h, column
chromatography: toluene/ethyl acetate, 4 : 1 v/v), mp 127.5–
128.58C. nmax (KBr)/cmꢁ1 3378 (OH), 2980, 1632 (C¼O),
1608, (C¼C), 1600, 1478, 1442, 1228, 1166 (C–O), 928, 846,
826. dH (CDCl3) 1.64 (s, 6H, Me2), 2.96 (s, 1H, OH), 6.36 (d,
J 6.0, 1H, 3-H), 7.38 (d, J 9.1, 1H, 8-H), 7.65 (dd, J 9.1, 2.0, 1H,
7-H), 7.86 (d, J 6.0, 1H, 2-H), 8.23 (d, J 2.0, 1H, 5-H). dC
(CDCl3) 32.0 (Me2), 66.1 (CMe2OH), 81.0 (Ca), 95.8 (Cb),
113.7 (C-3), 119.0 (C-8), 121.0 (C-6), 125.2 (C-4a), 129.8 (C-5),
137.2 (C-7), 156.1 (C-2), 156.4 (C-8a), 177.6 (C-4). (Found:
C 73.72, H 5.21. C14H12O3 requires: C 73.67, H 5.30 %).
6-(2-(Trimethylsilyl)ethynyl)chromone 12b
Yield: 76 % (Conditions A, reaction period: 0.5 h, column
chromatography: hexane/acetone, 8 : 1 v/v), mp 98–1008C. nmax
(KBr)/cmꢁ1 2959, 2142, 2166 (CꢀC), 1650 (C¼O), 1614
(C¼C), 1474, 1438, 1246, 914, 834. dH (CDCl3) 0.28 (s, 9H,
Me3), 6.33 (d, J 6.0, 1H, 3-H), 7.46 (d, J 8.7, 1H, 8-H), 7.72 (dd,
J 8.7, 2.1, 1H, 7-H), 7.84 (d, J 6.0, 1H, 2-H), 8.31 (d, J 2.1, 1H,
5-H). dC (CDCl3) 0.5 (Me3), 96.5 (Cb), 103.8 (Ca), 113.8 (C-3),
119.1 (C-8), 121.3 (C-6), 125.3 (C-4a), 130.4 (C-5), 137.4 (C-7),
156.0 (C-2), 156.4 (C-8a), 177.4 (C-4). (Found: C 69.29, H 5.69.
C14H14O2Si requires: C 69.38, H 5.82 %).
7-(3-Hydroxy-3-methyl-1-butynyl)chromone 13c
Yield: 54 % (Conditions A, reaction period: 0.5 h, column
chromatography: toluene/ethyl acetate, 4 : 1 v/v), mp 121–
1228C. nmax (KBr)/cmꢁ1 3436 (OH), 2976, 1654, 1632
(C¼O), 1618 (C¼C), 1590, 1428, 1352, 1274, 1162 (C–O),
1146, 856, 824. dH (CDCl3) 1.65 (s, 6H, Me2), 3.06 (s, 1H, OH),
6.35 (d, J 6.4, 1H, 3-H), 7.35 (d, J 8.9, 1H, 6-H), 7.42 (br s, 1H, 8-
H), 7.84 (d, J 6.4, 1H, 2-H), 8.10 (d, J 8.9, 1H, 5-H). dC (CDCl3)
31.9 (Me2), 66.1 (CMe2OH), 81.0 (Ca), 98.9 (Cb), 113.8 (C-3),
121.6 (C-8), 124.8 (C-4a), 126.4 (C-6), 129.1 (C-5), 129.4 (C-7),
156.2 (C-2), 156.7 (C-8a), 177.8 (C-4). (Found: C 73.71, H 5.19.
C14H12O3 requires: C 73.67, H 5.30 %).
7-(2-(Trimethylsilyl)ethynyl)chromone 12c
Yield: 48 % (Conditions A, reaction period: 0.5 h, column
chromatography: hexane/acetone, 8 : 1 v/v), mp 156–1598C.
n
max (KBr)/cmꢁ1 3068, 2964, 2902 (C–H), 2160 (CꢀC), 1648
(C¼O), 1618 (C¼C), 1424, 1250, 936, 874, 844, 822. dH
(CDCl3) 0.28 (s, 9H, Me3), 6.33 (d, J 6.0, 1H, 3-H), 7.46 (d,
J 8.7, 1H, 6-H), 7.57 (br s, 1H, 8-H), 7.85 (d, J 6.0, 1H, 2-H), 8.17
(d, J 8.7, 1H, 5-H). dC (CDCl3) 0.4 (Me3), 99.7 (Cb), 103.6 (Ca),
113.9 (C-3), 122.0 (C-8), 125.1 (C-4a), 126.4 (C-6), 129.3 (C-5),
129.4 (C-7), 156.1 (C-2), 156.7 (C-8a), 177.6 (C-4). (Found:
C 69.33, H 5.71. C14H14O2Si requires: C 69.38, H 5.82 %).
8-(3-Hydroxy-3-methyl-1-butynyl)chromone 13d
Yield: 73 % (Conditions A, reaction period: 4 h, column
chromatography: toluene/ethyl acetate, 4 : 1 v/v); 51 % (Condi-
tions B, reaction period: 4 h), mp 131–1328C. nmax (KBr)/cmꢁ1
3380 (OH), 2980, 1636 (C¼O), 1586, 1410, 1332, 1242, 1174
(C-O), 808, 756. dH (CDCl3) 1.68 (s, 6H, Me2), 3.03 (s, 1H, OH),
6.38 (d, J 5.8, 1H, 3-H), 7.31 (m, J 7.3, 1H, 6-H), 7.69 (dd, J 7.3,
1.4, 1H, 7-H), 7.87 (d, J 5.8, 1H, 2-H), 8.14 (dd, J 7.3, 1.4, 1H, 5-
H). dC (CDCl3) 31.6 (Me2), 65.8 (CMe2OH), 75.6 (Ca), 101.4
(Cb), 113.4 (C-3), 114.0 (C-8), 125.0, 126.1 (C-5, C-6), 125.1
(C-4a), 137.7 (C-7), 155.7 (C-2), 156.4 (C-8a), 177.8 (C-4).
(Found: C 73.55, H 5.45. C14H12O3 requires: C 73.67,
H 5.30 %).
8-(2-(Trimethylsilyl)ethynyl)chromone 12d
Yield: 62 % (Conditions A, reaction period: 2 h, column
chromatography: hexane/acetone, 8 : 1 v/v), mp 96–988C. nmax
(KBr)/cmꢁ1 2152 (CꢀC), 1660 (C¼O), 1572, 1476, 1432, 1402,
1326, 1242, 1030, 844, 808, 754. dH (CDCl3) 0.31 (s, 9H, Me3),
6.37 (d, J 6.5, 1H, 3-H), 7.35 (m, 1H, 6-H), 7.81 (dd, J 7.5, 1.4,

´
T. Patonay, I. Pazurik, and A. Abraha´m
652
6-(2-Phenylethynyl)flavone 14
2.64 (s, 3H, COMe), 6.93 (d, J 8.6, 1H, 30-H), 7.50 (dd, J 8.6, 1.9,
1H, 40-H), 7.81 (d, J 1.9, 1H, 60-H), 12.34 (s, 1H, 20-OH). dC
(CDCl3) 29.2 (C-2), 32.5 (Me2), 64.6 (CMe2OH), 78.2 (Ca),
93.0 (Cb), 115.9 (C-30), 119.0 (C-50), 126.7 (C-10), 129.8 (C-60),
137.6 (C-40), 160.2 (C-20), 188.2 (C-1). (Found: C 71.39, H 6.42.
C13H14O3 requires: C 71.54, H 6.47 %).
Yield: 28 % (Conditions A, reaction period: 3 h), mp 178–
1818C. nmax (KBr)/cmꢁ1 3061, 1657 (C¼O), 1614 (C¼C), 1567,
1497, 1449, 1356 (flavone skeleton), 842, 769, 759. dH (CDCl3)
6.84 (s, 1H, 3-H), 7.37 (m, 3H, 8-H, 40-H, 40-H), 7.56 (m, 6H,
30,50-H, 20,60-H, 30,50-H), 7.83 (dd, J 8.1, 1.9, 1H, 7-H), 7.94 (dd,
J 8.0, 2.0, 2H, 20,60-H), 8.39 (d, J 1.9, 1H, 5-H). dC (CDCl3) 87.8,
90.6 (Ca, Cb), 107.8 (C-3), 118.6 (C-8), 120.9, 122.9, 124.1
(C-4a, C-6, C-100), 126.4 (C-300,500), 128.7 (C-30,50), 128.8, 129.1
(C-40, C-400), 129.2 (C-20,60), 131.7 (C-10), 131.8 (C-20,60), 131.9
(C-5), 136.6 (C-7), 155.8 (C-8a), 163.6 (C-2), 177.8 (C-4).
(Found: C 85.56, H 4.41. C23H14O2 requires: C 85.70, H 4.38 %).
General Procedure for the Synthesis of Ethynylchromones
and -Flavones by Removal of the Trimethylsilyl End-group
To a solution of trimethylsilyl derivatives 4, 7, 12a–d, or
15 (0.4545 mmol) in THF (5 mL) was added 1 M tetra-
butylammonium fluoride in THF (0.15 mL); the mixture was
stirred under nitrogen at room temperature and the reaction was
monitored by thin-layer chromatography. After completion, the
solvent was removed under reduced pressure and the residue
was separated by column chromatography (eluent: hexane/
acetone 2 : 1 v/v).
6-(2-(Trimethylsilyl)ethynyl)flavone 15
Yield: 90 % (Conditions A, reaction period: 1.5 h, reaction
temperature: 808C, column chromatography: toluene/ethyl
acetate, 4 : 1 v/v)), mp 158–1608C. nmax (KBr)/cmꢁ1 3066,
2957, 2166 (CꢀC), 1640 (C¼O), 1612 (C¼C), 1566, 1477,
1452, 1433, 1360 (flavone skeleton), 832, 776. dH (CDCl3) 0.33
(s, 9H, Me3), 6.84 (s, 1H, 3-H), 7.54 (m, 4H, 8-H, 30,50-H, 40-H),
7.75 (dd, J 8.3, 2.1, 1H, 7-H), 7.91 (dd, J 8.6, 1.9, 2H, 20,60-H),
8.34 (d, J 1.8, 1H, 5-H). dC (CDCl3) ꢁ0.2 (Me3), 95.6 (Ca),
103.2 (Cb), 107.5 (C-3), 118.2 (C-8), 120.5 (C-6), 123.6 (C-4a),
126.2 (C-30,50), 129.0 (C-20,60), 129.5 (C-40), 131.5 (C-10),
131.7 (C-5), 136.6 (C-7), 155.0 (C-8a), 163.3 (C-2), 177.4
(C-4). (Found: C 75.59, H 5.61. C20H18O2Si requires:
C 75.43, H 5.70 %).
3-Ethynylchromone 19
Yield: 27 %, reaction period: 20 min, mp 126–1298C. nmax
(KBr)/cmꢁ1 3245 (ꢀCH), 1639 (C¼O), 1614 (C¼C), 1464,
1378, 1346, 1166, 850, 757. dH (CDCl3) 3.28 (s, 1H, ꢀCH),
7.36–7.50 (m, 2H, 6-H, 8-H), 7.70 (m, 1H, 7-H), 8.19 (s, 1H,
2-H), 8.26 (1H, dd, J 7.8, 1.8, 5-H). dC (CDCl3) 74.0 (Cb), 83.6
(Ca), 110.7 (C-3), 118.5 (C-8), 123.8 (C-4a), 126.2, 126.6 (C-5,
C-6), 134.5 (C-7), 155.3 (C-8a), 159.2 (C-2), 175.5 (C-4).
(Found: C 77.47, H 3.67. C11H6O2 requires: C 77.64, H 3.55 %).
3-Ethynylflavone 20
6-(3-Hydroxy-3-methyl-1-butynyl)flavone 16
Yield: 72 %, reaction period: 45 min, mp 165–1678C. nmax
(KBr)/cmꢁ1 3205 (ꢀCH), 2094 (CꢀC), 1631 (C¼O), 1614
(C¼C), 1546, 1468, 1373 (flavone skeleton), 758. dH (CDCl3)
3.44 (s, 1H, ꢀCH), 7.44 (m, 1H, 6-H), 7.56 (m, 4H, 8-H, 30,50-H,
40-H), 7.70 (m, 1H, 7-H), 8.18 (dd, J 8.4, 1.9, 8-H), 8.29 (dd,
J 7.9, 1.7, 1H, 5-H). dC (CDCl3) 75.9 (Cb), 86.5 (Ca), 106.3
(C-3), 118.1 (C-8), 122.1 (C-4a), 125.8, 126.2 (C-5, C-6), 128.4,
129.0 (C-20,60, C-30,50), 131.8 (C-5), 132.1 (C-10), 134.3 (C-7),
155.5 (C-8a), 167.1 (C-2), 176.8 (C-4). (Found: C 83.07, H 3.98.
C17H10O2 requires: C 82.91, H 4.09 %).
Yield: 92 % (Conditions A, reaction period: 3 h, reaction
temperature: 808C), mp 129–1328C. nmax (KBr)/cmꢁ1 3458
(OH), 2978, 1643 (C¼O), 1613 (C¼C), 1565, 1450, 1434,
1358 (flavone skeleton), 1214 (C–OH), 1170, 843. dH ([D6]
DMSO) 1.53 (s, 6H, Me2), 5.60 (s, 1H, OH), 7.06 (s, 1H, 3-H),
7.60 (m, 5H, Ph), 7.79 (m, 2H, 6-H, 7-H), 7.98 (s, 1H, 5-H), 8.10
(d, J 6.9, 2H, 20,60-H). dC ([D6]DMSO) 38.5 (Me2), 63.1
(CMe2OH), 78.5 (Ca), 96.5 (Cb), 106.5 (C-3), 118.8 (C-8),
119.3 (C-6), 122.8 (C-4a), 125.9 (C-30,50), 126.9 (C-40), 128.6
(C-20,60), 130.4 (C-10), 131.4 (C-5), 135.9 (C-7), 154.5 (C-8a),
162.2 (C-2), 175.8 (C-4). (Found: C 78.79, H 5.42. C20H16O3
requires: C 78.93, H 5.30 %).
5-Ethynylchromone 21a
This compound has been reported previously[8] without
melting point or any spectral data.
Yield: 79 %, reaction period: 15 min, mp 122–1248C. nmax
(KBr)/cmꢁ1 3236 (ꢀCH), 2095 (CꢀC), 1639 (C¼O), 1593,
1472, 1401, 1347, 1291, 1210, 966, 833, 763, 715. dH (CDCl3)
3.54 (s, 1H, ꢀCH), 7.33 (d, J 6.0, 1H, 3-H), 7.42 (m 1H, 7-H),
7.58 (m, 2H, 6-H, 8-H), 7.77 (d, J 6.0, 1H, 2-H). dC (CDCl3)
82.0, 83.3 (Ca, Cb), 113.8 (C-3), 118.9 (C-8), 121.0 (C-4a),
125.3 (C-5), 132.4, 132.6 (C-6, C-7), 154.1 (C-2), 156.9 (C-8a),
172.2 (C-4). (Found: C 77.71, H 3.52. C11H6O2 requires:
C 77.64, H 3.55 %).
1,4-Diphenyl-1,3-butadiyne 17
Yield: 35 % (Conditions A, reaction period: 3 h), mp
81–838C (lit.[29] 87–888C). The 1H NMR spectrum was identical
to that reported.[30]
20-Hydroxy-50-(3-hydroxy-3-methyl-1-butynyl)
acetophenone 18
6-Ethynylchromone 21b
A mixture of 6-(3-hydroxy-3-methyl-1-butynyl)chromone
(13b) (250 mg, 1.095 mmol), TBAI (40 mg, 0.1083 mmol),
5 M sodium hydroxyde solution (0.66 mL, 3.300 mmol), and
toluene (15 mL) was heated at 808C for 30 min, then the solvent
was removed under reduced pressure and the residue was
separated by column chromatography (eluent: hexane/acetone
4 : 1 v/v) to give 94 mg (39 %) of acetophenone 18, mp:
56.5–57.58C. nmax (KBr)/cmꢁ1 3629 (OH), 2986, 1648
(C¼O), 1566, 1478, 1364, 1321, 1302, 1235, 1194, 1152, 968,
930, 817. dC (CDCl3) 1.63 (s, 6H, Me2), 2.04 (s, 1H, CMe2OH),
Yield: 66 %, reaction period: 15 min, mp 182–1858C. nmax
(KBr)/cmꢁ1 3216 (ꢀCH), 2104 (CꢀC), 1647 (C¼O), 1615
(C¼C), 1474, 1437, 1313, 1196, 832. dH ([D6]DMSO) 4.36
(s, 1H, ꢀCH), 6.40 (d, J 6.5, 1H, 3-H), 7.69 (d, J 8.9, 1H, 8-H),
7.87 (d, J 8.9, 1H, 7-H), 8.05 (brs, 1H, 5-H), 8.33 (d, J 6.5, 1H,
2-H). dC ([D6]DMSO) 78.5, 80.5 (Ca, Cb), 111.5 (C-3), 117.6
(C-8), 118.0 (C-6), 123.2 (C-4a), 127.7 (C-5), 135.4 (C-7), 154.7
(C-8a), 154.8 (C-2), 174.4 (C-4). (Found: C 77.59, H 3.61.
C11H6O2 requires: C 77.64, H 3.55 %).

Alkynylation of Chromones
653
7-Ethynylchromone 21c
References
[1] (a) J. A. Marsden, M. M. Haley, In Metal-catalyzed Cross-Coupling
Reactions (Eds A. de Meijere, F. Diederich) 2004, Vol. 1, p. 317
(Wiley-VCH: Weinheim).
Yield: 68 %, reaction period: 10 min, mp 161.5–162.58C.
nmax (KBr)/cmꢁ1 3244 (ꢀCH), 2106 (CꢀC), 1665, 1643
(C¼O), 1599, 1428, 1343, 1298, 1212, 876, 820. dH (CDCl3)
3.30 (s, 1H, ꢀCH), 6.34 (d, J 6.0, 1H, 3-H), 7.49 (d, J 8.6, 1H,
6-H), 7.58 (br s, 1H, 8-H), 7.85 (d, J 6.0, 1H, 2-H), 8.15 (d, J 8.6,
1H, 5-H). dC (CDCl3) 81.0, 82.3 (Ca, Cb), 113.2 (C-3), 121.7
(C-8), 125.5 (C-4a), 125.9 (C-8), 127.7 (C-7), 128.6 (C-5), 155.4
(C-2), 156.0 (C-8a), 180.8 (C-4). (Found: C 77.52, H 3.49.
C11H6O2 requires: C 77.64, H 3.55 %).
(b) C. E. Castro, R. D. Stephens, J. Org. Chem. 1963, 28, 2163.
(c) K. Sonogashira, Y. Tohda, N. Hagihara, Tetrahedron Lett. 1975,
16, 4467. doi:10.1016/S0040-4039(00)91094-3
(d) K. Sonogashira, J. Organomet. Chem. 2002, 653, 46. doi:10.1016/
S0022-328X(02)01158-0
(e) H. Doucet, J.-C. Hierso, Angew. Chem. Int. Ed. 2007, 46, 834.
doi:10.1002/ANIE.200602761
[2] (a) M. Tsukayama, H. Li, M. Nishiuchi, M. Takahashi, Y. Kawamura,
J. Chem. Res. (S) 1998, 238; J. Chem. Res. (M) 1998, 1181.
doi:10.1039/A709191E
8-Ethynylchromone 21d
Yield: 61 %, reaction period: 10 min, mp 233–2358C. nmax
(KBr)/cmꢁ1 3217 (ꢀCH), 2106 (CꢀC), 1649 (C¼O), 1589,
1574, 1478, 1434, 1410, 1336, 805, 754. dH (CDCl3) 3.48 (s, 1H,
ꢀCH), 6.38 (d, J 6.1, 1H, 3-H), 7.38 (m, 1H, 6-H), 7.84 (dd,
J 7.9, 1.8, 1H, 7-H), 7.94 (d, J 6.1, 1H, 2-H), 8.20 (dd, J 7.8, 1.8,
5-H). dC (CDCl3) 80.1, 81.1 (Ca, Cb), 110.0 (C-8), 116.0 (C-3),
124.7 (C-4a), 125.5 (C-6), 128.2, 129.1 (C-5, C-7), 155.7 (C-2),
158.0 (C-8a), 179.5 (C-4). (Found: C 77.80, H 3.53. C11H6O2
requires: C 77.64, H 3.55 %).
(b) M. Tsukayama, A. Oda, Y. Kawamura, M. Nishiuchi, K. Yamashita,
Tetrahedron Lett. 2001, 42, 6163. doi:10.1016/S0040-4039(01)01234-5
(c) M. Tsukayama, H. Wada, Y. Kawamura, K. Yamashita, M. Nishiuchi,
Chem. Pharm. Bull. 2004, 52, 1285. doi:10.1248/CPB.52.1285
(d) T. Tokuoka, K. Yamashita, Y. Kawamura, M. Tsukayama,
M. M. Hossain, Synth. Commun. 2006, 36, 1201. doi:10.1080/
00397910500514121
(e) M. M. Hossain, Y. Kawamura, K. Yamashita, M. Tsukayama,
Tetrahedron 2006, 62, 8625. doi:10.1016/J.TET.2006.06.066
[3] A. T. Johnson, L. Wang, A. M. Standeven, M. Escobar, R. A. S.
Chandraratna, Bioorg. Med. Chem. 1999, 7, 1321. doi:10.1016/S0968-
0896(99)00055-3
6-Ethynylflavone 22
[4] M.-S. Schiedel, C. A. Briehn, P. Ba¨uerle, J. Organomet. Chem. 2002,
Yield: 91 %, reaction period: 45 min (column chromatogra-
phy: toluene/ethyl acetate, 4 : 1 v/v), mp 167.5–168.58C. nmax
(KBr)/cmꢁ1 3286 (ꢀCH), 1652 (C¼O), 1603, 1567, 1458, 1435,
1356 (flavone skeleton), 773. dH (CDCl3) 3.15 (s, 1H, ꢀCH),
6.83 (s, 1H, 3-H), 7.53 (m, 4H, 8-H, 30,50-H, 40-H), 7.78 (dd, 1H,
J 8.3, 2.0, 7-H), 7.92 (dd, J 8.0, 1.9, 2H, 20,60-H), 8.37 (d, J 2.0,
1H, 5-H). dC (CDCl3) 78.5, 82.1 (Ca, Cb), 107.8 (C-3), 118.6
(C-8), 119.6 (C-6), 123.9 (C-4a), 126.4 (C-30,50), 129.2
(C-20,60), 129.9 (C-40), 131.5 (C-10), 131.9 (C-5), 137.0 (C-7),
156.0 (C-8a), 163.6 (C-2), 177.5 (C-4). (Found: C 82.81, H 4.20.
C17H10O2 requires: C 82.91, H 4.09 %).
653, 200. doi:10.1016/S0022-328X(02)01153-1
[5] J.-H. Lee, J.-S. Park, C.-G. Cho, Org. Lett. 2002, 4, 1171. doi:10.1021/
OL025613Q
[6] (a) M. Pal, V. Subramanian, K. Parasuraman, K. R. Yeleswarapu,
Tetrahedron 2003, 59, 9563. doi:10.1016/J.TET.2003.10.003
(b) M. Pal, V. Subramanian, K. Parasuraman, K. R. Yeleswarapu,
Tetrahedron Lett. 2004, 45, 2305. doi:10.1016/J.TETLET.
2004.01.113
(c) N. K. Swamy, L. K. Tatini, J. M. Babu, P. Annamalai, M. Pal,
Chem. Commun. 2007, 1035. doi:10.1039/B612770C
+
[7] T. Ka´lai, G. Kulcsa´r, E. Osz, J. Jeko, B. Su¨megi, K. Hideg, ARKIVOC
+
2004, vii, 266.
[8] R. Artali, P. L. Barili, G. Bombieri, P. Da Re, N. Marchini,
F. Meneghetti, P. Valenti, Farmaco 2003, 58, 875. doi:10.1016/
S0014-827X(03)00145-9
1-(4-Oxo-4H-1-benzopyran-3-yl)-2-(4-oxo-4H-1-
benzopyran-6-yl)ethyne 23
A mixture of 3-bromochromone (1) (220 mg, 0.978 mmol),
6-ethynylchromone (21b) (250 mg, 1.470 mmol), tetrakis(tri-
phenylphosphine)palladium(0) (29 mg, 0.0251 mmol), tri-
phenylphosphine (6 mg, 0.0229 mmol), and copper(I)iodide
(3 mg, 0.0158 mmol) in triethylamine (15 mL) was heated at
1108C under a nitrogen atmosphere for 2.5 h; then the solvent
was removed under reduced pressure and the residue was
subjected to column chromatography (eluent: hexane/acetone
2 : 1 v/v) to give 140 mg (46 %) ethyne 23, mp 264–2678C. nmax
(KBr)/cmꢁ1 1666 br (C¼O), 1615 (C¼C), 1481, 1225, 1140,
834, 761. dH ([D6]DMSO) 6.42 (d, J 6.5, 1H, 30-H), 7.57 (m, 1H,
60-H), 7.74 (m, 2H, 80-H, 80-H), 7.85–7.94 (m, 3H, 70-H, 50-H,
70-H), 8.14 (dd, J 7.9, 1.7, 1H, 50-H), 8.34 (d, J 6.5, 1H, 20-H),
8.90 (s, 1H, 20-H). dC ([D6]DMSO) 81.8 (C-1), 92.4 (C-2), 109.4
(C-30), 112.5 (C-30), 118.7, 119.7 (C-80, C-80), 119.3 (C-60),
124.4, 122.1 (C-4a0, C-4a0), 125.3, 126.3 (C-50, C-60), 127.9
(C-50), 134.8, 136.4 (C-70, C-70), 155.5, 155.7 (C-8a0, C-8a0),
174.5 (C-40), 175.6 (C-40). (Found: C 76.29, H 3.31. C20H10O4
requires: C 76.43, H 3.21 %).
[9] (a) T. Yao, X. Zhang, R. C. Larock, J. Am. Chem. Soc. 2004, 126,
11164. doi:10.1021/JA0466964
(b) T. Yao, X. Zhang, R. C. Larock, J. Org. Chem. 2005, 70, 7679.
doi:10.1021/JO0510585
(c) C. Zhou, A. V. Dubrovsky, R. C. Larock, J. Org. Chem. 2006, 71,
1626. doi:10.1021/JO0523722
[10] N. T. Patil, H. Wu, Y. Yamamoto, J. Org. Chem. 2005, 70, 4531.
doi:10.1021/JO050191U
[11] S.-W. Yang, A. Elangovan, T.-I. Ho, Photochem. Photobiol. Sci. 2005,
4, 327. doi:10.1039/B416319B
[12] X. Fu, S. Zhang, J. Yin, D. P. Schumacher, Tetrahedron Lett. 2002, 43,
6673. doi:10.1016/S0040-4039(02)01447-8
[13] (a) T. Patonay, A. Vasas, A. Kiss-Szikszai, A. M. S. Silva, J. A. S.
Cavaleiro, Aust. J. Chem. 2010, 63, 1582. doi:10.1071/CH10295
(b) A. Vasas, T. Patonay, K. Ko´nya, A. M. S. Silva, J. A. S. Cavaleiro,
Aust. J. Chem. 2011, 64, 647.
(c) Sz. Fekete, T. Patonay, A. M. S. Silva, J. A. S. Cavaleiro, ARKIVOC
2012, v, 210.
[14] (a) N. Eleya, Z. Khaddour, T. Patonay, P. Langer, Synlett 2012, 223.
(b) I. Malik, M. Hussain, T. H. Nguyen, A. Villinger, P. Langer, Synlett
2010, 2244.
(c) N. Eleya, I. Malik, S. Reimann, K. Wittler, T. Patonay, A. Villinger,
R. Ludwig, P. Langer, Eur. J. Org. Chem. 2012, 1639. doi:10.1002/
EJOC.201101491
(d) O. Akrawi, G. Z. Nagy, T. Patonay, A. Villinger, P. Langer,
Tetrahedron Lett. 2012, 53, 3206. doi:10.1016/J.TETLET.2012.03.108
(e) Z. Hassan, T. Patonay, P. Langer, Synlett 2013, 24, 412. doi:10.1055/
S-0032-1317944
Acknowledgements
´
´
Financial support of TAMOP-4.2.2–08/1–2008–0014 and TAMOP 4.2.1./
B-09/1/KONV-2010–0007 projects is highly appreciated. The latter project
is implemented through the New Hungary Development Plan, co-financed
by the European Social Fund and the European Regional Development Fund.

´
T. Patonay, I. Pazurik, and A. Abraha´m
654
[15] R. Bogna´r, M. Ra´kosi, G. Litkei, Acta Chir. Acad. Sci. Hung. 1962,
34, 353.
[22] A. Carpita, L. Mannocci, R. Rossi, Eur. J. Org. Chem. 2005, 1859 and
references cited therein. doi:10.1002/EJOC.200400810
[16] (a) C. Glaser, Ber. Dtsch. Chem. Ges. 1869, 2, 422. doi:10.1002/
CBER.186900201183
(b) C. Glaser, Ann. Chem. Pharm. 1870, 154, 137. doi:10.1002/JLAC.
18701540202
(c) A. S. Hay, J. Org. Chem. 1962, 27, 3320. doi:10.1021/
JO01056A511
[17] (a) M. A. De La Rosa, E. Velarde, A. Guzman, Synth. Commun. 1990,
[23] (a) Y. Nishihara, K. Ikegashira, K. Hirabayashi, J.-I. Ando, A. Mori,
T. Hiyama, J. Org. Chem. 2000, 65, 1780. doi:10.1021/JO991686K
(b) Y. Nishihara, M. Takemura, A. Mori, K. Osakada, J. Organomet.
Chem. 2001, 620, 282. doi:10.1016/S0022-328X(00)00794-4
[24] (a) A. Lindstro¨m, L. Ripa, A. Hallberg, Org. Lett. 2000, 2, 2291.
doi:10.1021/OL006056F
(b) A. Gangjee, J. Yu, R. L. Kisliuk, J. Heterocycl. Chem. 2002, 39,
833. doi:10.1002/JHET.5570390433
20, 2059. doi:10.1080/00397919008053137
(b) R. G. Heidenreich, K. Ko¨hler, J. G. E. Krauter, J. Pietsch, Synlett
2002, 1118. doi:10.1055/S-2002-32589
[18] (a) J. G. Rodr´ıguez, J. L. Tejedor, J. Org. Chem. 2002, 67, 7631.
doi:10.1021/JO0203589
(c) A. Arcadi, S. Cacchi, S. Di Giuseppe, G. Fabrizi, F. Marinelli,
Synlett 2002, 453. doi:10.1055/S-2002-20464
´
[25] K. Ko´nya, Sz. Fekete, A. Abraha´m, T. Patonay, Mol. Divers. 2012, 16,
91. doi:10.1007/S11030-012-9360-7
(b) J. G. Rodr´ıguez, J. Esquivias, A. Lafuente, C. D´ıaz, J. Org. Chem.
2003, 68, 8120. doi:10.1021/JO034972B
(c) J. G. Rodr´ıguez, J. Esquivias, Tetrahedron Lett. 2003, 44, 4831.
doi:10.1016/S0040-4039(03)01137-7
[26] H. de Diesbach, H. Kramer, Helv. Chim. Acta 1945, 28, 1399.
doi:10.1002/HLCA.6602801197
[27] T. Patonay, J. A. S. Cavaleiro, A. Le´vai, A. M. S. Silva, Heterocycl.
Commun. 1997, 3, 223. doi:10.1515/HC.1997.3.3.223
[19] Z. Nova´k, P. Nemes, A. Kotschy, Org. Lett. 2004, 6, 4917. doi:10.1021/
OL047983F
[28] N. J. Reddy, M. Bokadia, T. Sharma, J. A. Donelly, J. Org. Chem.
1981, 46, 638. doi:10.1021/JO00316A034
[20] A. Nagy, Z. Nova´k, A. Kotschy, J. Organomet. Chem. 2005, 690,
4453. doi:10.1016/J.JORGANCHEM.2004.12.036
[21] H.-F. Chow, C. W. Wan, K.-H. Low, Y.-Y. Yeung, J. Org. Chem.
2001, 66, 1910. doi:10.1021/JO001538Q
[29] S. R. Landor, P. D. Landor, Z. T. Fomum, G. W. B. Mpango, J. Chem.
Soc., Perkin Trans. 1 1979, 2289. doi:10.1039/P19790002289
[30] N. Kakusawa, K. Yamaguchi, J. Kurita, J. Organomet. Chem. 2005,
690, 2956. doi:10.1016/J.JORGANCHEM.2005.03.021