Synthesis of chromones via palladium-catalyzed ligand-free cyclocarbonylation of o-iodophenols with terminal acetylenes in phosphonium salt ionic liquids

Article abstract of DOI:10.1021/jo902210p

(Chemical Equation Presented) The highly efficient and selective palladium-catalyzed ligand-free cyclocarbonylation reaction of o-iodophenols with terminal acetylenes and CO in the phosphonium salt ionic liquid,C ₁₄H₂₉(C₆H₁₃)₃P ⁺Br^-, affords diversified chromones in good to excellent yields under atmospheric CO pressure. The ionic liquid, as the reactionmedium, enhances the efficiency of the cyclocarbonylation reaction.

Full text of DOI:10.1021/jo902210p

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ever, most of the methods suffer from harsh reaction condi-
Synthesis of Chromones via Palladium-Catalyzed
Ligand-Free Cyclocarbonylation of o-Iodophenols with
Terminal Acetylenes in Phosphonium Salt Ionic Liquids
tions, poor substituent tolerance, and low to moderate yields.
During the past two decades, the palladium-catalyzed carbo-
nylation of o-iodophenols with terminal acetylenes has become
an attractive method to synthesize chromones.4 In some
situations, this reaction produces a mixture of six-membered
chromones 1 and five-membered aurones 2 (Scheme 1).5
Qian Yang and Howard Alper*
Centre for Catalysis Research and Innovation, Department of
Chemistry, University of Ottawa, 10 Marie Curie, Ottawa,
Ontario K1N 6N5, Canada
SCHEME 1. Pd-Catalyzed Cyclocarbonylation of o-Iodo-
phenols and Terminal Acetylenes
howard.alper@uottawa.ca
Received October 16, 2009
Ionic liquids (ILs), because of their low volatility, non-
flammability, capability to dissolve various organic and in-
organic compounds, and potentially recyclable properties,
have attracted considerable attention as environmentally
friendly reaction media. Many transition metal-catalyzed reac-
tions in task-specific ionic liquids (TSILs) have established
some highly effective and easily separable catalytic systems.6
Imidazolium-based ionic liquids are most commonly used as
these alternative solvents.7 In recent years, phosphonium
salt ionic liquids (PSILs) have been the subject of some
The highly efficient and selective palladium-catalyzed
ligand-free cyclocarbonylation reaction of o-iodophenols
with terminal acetylenes and CO in the phosphonium salt
ionic liquid, C14H29(C6H13)3PþBr-, affords diversified chro-
mones in good to excellent yields under atmospheric CO
pressure. The ionic liquid, as the reaction medium, enhances
the efficiency of the cyclocarbonylation reaction.
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948 J. Org. Chem. 2010, 75, 948–950
Published on Web 01/12/2010
DOI: 10.1021/jo902210p
r
2010 American Chemical Society

Yang and Alper
JOCNote
TABLE 1. Palladium-Catalyzed Cyclocarbonylation of o-Iodophenol
TABLE 2. Palladium-Catalyzed Cyclocarbonylation of o-Iodophenols
with Phenyl Acetylenea
with Terminal Acetylenesa
temp
(°C)
yieldb
of 5a
entry
1
cat.
base
CO
200
psi
sol.
Pd(PPh3)2Cl2 Et3N
110
PSIL102
95
2c
Pd(PPh3)4
K2CO3 200
psi
110
PSIL102
ND
3
4
5
6
Pd(PPh3)2Cl2 Et3N
Pd(PPh3)2Cl2 Et3N
1 atm 110
1 atm rt
1 atm 110
1 atm 110
PSIL102
PSIL102
PSIL102
PSIL102
PSIL102
PSIL101
PSIL110
PSIL109
74
trace
91
95
Pd(OAc)2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
Et3N
Et3N
Et2NH 1 atm 110
Et3N
Et3N
Et3N
Et3N
Et3N
7
58
8d
9e
10f
11
1 atm 110
1 atm 110
1 atm 110
1 atm 110
1 atm 110
50
41h
43i
[BMIM]NTf2 35j
12g PdCl2
Et3N
28k
aReaction conditions: o-iodophenol (1 mmol), phenyl acetylene (2
mmol), Pd cat. (5 mol %), Et3N or Et2NH (3 mmol) or K2CO3 (4 mmol),
PSIL or [BMIM]NTf2 (1.5 g). bIsolated yield. cNeither product 5a nor
5b was detected. The only detected product was 2-(2-phenylethynyl)-
aReaction conditions: o-iodophenols (1 mmol), terminal acetylenes (2
mmol), PdCl2 (5 mol %), Et3N (3 mmol), C14H29(C6H13)3PþBr- (1.5 g),
110 °C, 24 h. bIsolated yield. cUse of [BMIM]NTf2 as reaction medium
under identical reaction conditions afforded 41% of 19a and 26% of 2-
heptylidenebenzofuran-3(2H)-one. Methyl 3-hydroxy-4-iodobenzoate
was used as the substrate.
e
-
phenol. dPSIL101: C14H29(C6H13)3-PþCl-. PSIL110: C14H29Pþ PF6
.
d
fPSIL109: C14H29(C6H13)3PþNTf2
.
gReaction was run in 3 mL of
j
Et3N. h15% 5b was obtained. 28% 5b was obtained. 23% 5b was
i
obtained. k35% 5b was obtained.
further investigations. When the CO pressure was reduced
from 200 psi to 1 atm, the yield decreased from 95% to 74%
(Table 1, entry 3). Running the reaction at room temperature
instead of 110 °C afforded trace quantities of the product
(Table 1, entry 4). To our surprise, without any phosphine
ligand, both Pd(OAc)2 and PdCl2 catalyzed the reaction very
efficiently with PSIL102 as the reaction medium and 5a was
obtained in 91% and 95% yields, respectively (Table 1,
entries 5 and 6). A reaction carried out under similar condi-
tions but with conventional solvent did not give any of the
desired product.4f When the reaction was carried out with
Et2NH as the base instead of Et3N, the isolated yield was
reduced from 95% to 58% (Table 1, entry 7). From the above
results, PdCl2 was chosen as the optimal catalyst and Et3N as
the base. Other ionic liquids were also investigated for the
cyclocarbonylation reaction (Table 1). When the reaction
was carried out in PSIL101, C14H29(C6H13)3PþCl-, the iso-
lated yield of 5a was only 50% (Table 1, entry 8). Running the
reaction in other ionic liquids gave the expected product and
its isomer in low selectivity (Table 1, entries 9, 10, and 11).
With Et3N as the base and solvent, two isomers were isolated
in 63% total yield (Table 1, entry 12). Hence, a pronounced
counteranion effect was observed showing the increase in
publications. They have higher thermal stability than the nitro-
gen-based analogues. McNulty and co-workers, as well as several
other groups, described several different reactions in PSILs
affording products in good to excellent yields.8 Recently, we
reported several palladium-catalyzed reactions in PSILs.9
Kalini and Torii et al. reported the syntheses of chromones
via palladium-catalyzed cyclocarbonylation of o-iodophe-
nols with terminal acetylenes, the yields of the products were
based on rather unreliable TLC and UV spectroscopy yields.
Several of the chromones were isolated in quite low yields
(45-63%).4f,h These results encouraged us to investigate the
utility of PSILs for the cyclocarbonylation of o-iodophenols
with terminal acetylenes to give 2-substituted chromones.
We now report that the ionic liquid, PSIL102, C14H29-
(C6H13)3PþBr-, can be employed as a very efficient re-
action medium for the selective synthesis of chromones by
palladium-catalyzed cyclocarbonylation of o-iodophenols
with terminal acetylenes. The reaction affords high yields
of the desired products.
Initially, the cyclocarbonylation of o-iodophenol with
phenyl acetylene was chosen as the model reaction. The
results are presented in Table 1.
selectivity and yield of 5a when moving from bistriflamide
-
The results in Table 1 show that cyclocarbonylation of
o-iodophenol with phenyl acetylene can be performed in
PSIL102, C14H29(C6H13)3PþBr-, affording 5a in 95% iso-
lated yield when Pd(PPh3)2Cl2 was used as the catalyst and
Et3N as the base under 200 psi of CO pressure and 110 °C
(Table 1, entry 1). In contrast, when Pd(PPh3)4 was used as
the catalyst and K2CO3 as the base, neither 5a nor 5b was
formed (Table 1, entry 2). So Pd(PPh3)2Cl2 was used for
to bromide: Br- >Cl- > NTf2
.
The optimal reaction conditions for the cyclocarbonyla-
tion reaction in PSIL102 were then applied to a variety of
aromatic and aliphatic terminal acetylenes. The results are
summarized in Table 2.
The results in Table 2 show that by the use of simple PdCl2
as catalyst, Et3N as base, and PSIL102 as the ionic liquid, the
cyclocarbonylation of o-iodophenol with both aromatic and
aliphatic terminal acetylenes proceeded well, affording pro-
ducts in good to excellent yields. Acetylenes containing
methyl or electron-withdrawing substituents on the aromatic
(9) (a) Cao, H.; McNamee, L.; Alper, H. Org. Lett. 2008, 10, 5281.
(b) Yang, Q.; Robertson, A.; Alper, H. Org. Lett. 2008, 10, 5079. (c) Cao,
H.; McNamee, L.; Alper, H. J. Org. Chem. 2008, 73, 3530.
J. Org. Chem. Vol. 75, No. 3, 2010 949

Yang and Alper
JOCNote
ring react quite efficiently with o-iodophenol to form the
corresponding chromones in 64-94% yields (Table 2, entries
2-5). The heteroaromatic substituted acetylene 14 could
also give 2-thiophene-substituted chromone in 92% yield
(Table 2, entry 6). All three aliphatic acetylenes reacted with
o-iodophenol affording 2-alkyl-substituted chromones in
good yields (Table 2, entries 7-9). Note that for entry 8,
use of an N-based ionic liquid affords significantly reduced
yield of 19a (41%), as well as the formation of a substantial
amount of 2-heptylidenebenzofuran-3(2H)-one(26%). When
methyl 3-hydroxy-4-iodobenzoate was used as the substrate
for the reaction with phenyl acetylene, the anticipated pro-
duct was obtained in 79% yield (Table 2, entry 10). Thus, our
method can be considered as a valuable alternative to the
existing methods,4a,c as it affords better yields for some of the
2-alkyl-substituted chromones,4c and hetero-aryl-substituted
chromones 5a, 7a, and 15a.4a In addition, our method does
not require the use of phosphine ligand.
cyclocarbonylation of o-iodophenols with terminal acety-
lenes. By using PSIL102 as the ionic liquid, the reaction
proceeds in a highly efficient and selective way to give
various chromones in good to excellent yields under
atmospheric CO pressure and no phosphine ligand is re-
quired.
Experimental Section
General Procedure for the Cyclocarbonylation of o-Iodophe-
nols with Terminal Acetylenes. A mixture of o-iodophenol (1.0
mmol), terminal acetylene (2 mmol), PdCl2 (0.05 or 0.01 mmol),
Et3N (3 mmol), and PSIL102 [trihexyl(tetradecyl)phosphonium
bromide] (1.5 g) was added to the autoclave with magnetic
stirring. The autoclave was closed, purged three times with
CO, and pressurized with CO at room temperature at 15 psi,
and then the autoclave was immersed in an oil bath preheated at
110 °C for 24 h. Excess CO was discharged at room temperature.
The reaction mixture was purified by flash chromatography on
silica gel with hexane/EtOAc (v/v, 10:1) as the eluant to give the
corresponding chromones in 64-96% yields.
2-Phenyl-4H-chromen-4-one (5a). The title compound was
prepared from the cyclocarbonylation of o-iodophenol with
phenyl acetylene according to the general procedure, and the
desired product was obtained in 95% yield after flash chromato-
graphy on silica gel. 1H NMR (400 MHz, CDCl3) δ 8.09 (dd, 1H,
J = 8.0 and 1.6 Hz), 7.76 (d, 1H, J = 1.6 Hz), 7.74 (d, 1H,
J = 2.0 Hz), 7.56-7.52 (m, 1H), 7.41-7.34 (m, 4H), 7.28-7.24
(m, 1H), 6.66 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 177.9,
162.9, 155.8, 133.4, 131.3, 128.7, 125.9, 125.2, 124.8, 123.6,
117.8, 107.1; HRMS (EI) m/z calcd for C15H10O2 (Mþ)
222.0681, found 222.0679.
We have also briefly investigated if the catalyst loading can
be reduced to further improve the efficiency of the reaction.
Thus, exposure of o-iodophenol and phenyl acetylene to our
optimized cyclocarbonylation conditions using 1 mol %
PdCl2 as catalyst led to the desired product 5a in 81%
isolated yield (eq 1). Therefore, the product is isolated in
good yield using this reduced loading of the catalyst.
The recyclability of the reaction mixture containing active
catalyst and PSIL102 in the cyclocarbonylation reaction of
o-iodophenol with 1-octyne (Table 2, entry 8) was also
investigated, and 78% isolated yield of 19a was obtained in
the second run (see experimental details in the Supporting
Information).
Acknowledgment. We are grateful to Cytec Canada, Inc.
and to the Natural Sciences and Engineering Research
Council for support of this work. We benefited from discus-
sions with Dr. A. Robertson on this work.
Supporting Information Available: Detailed experimental
procedures and spectral data for all compounds. This material is
available free of charge via the Internet at http://pubs.acs.org.
In conclusion, PSIL102, C14H29(C6H13)3PþBr-, is a highly
effective reaction medium for the palladium-catalyzed
950 J. Org. Chem. Vol. 75, No. 3, 2010