Synthesis of 4-aryl-substituted butenolides and pentenolides by copper-catalyzed hydroarylation

Article abstract of DOI:10.3987/COM-09-S(S)8

We have investigated the effect of the type of protecting group used and the tether length of 4- and 5-hydroxy-substituted 2-alkynoates on the yields and selectivity of the product of hydroarylation. The use of methyl, methoxymethyl, and tert-butyldimethy

Full text of DOI:10.3987/COM-09-S(S)8

HETEROCYCLES, Vol. 80, No. 1, 2010
269
HETEROCYCLES, Vol. 80, No. 1, 2010, pp. 269 - 279. © The Japan Institute of Heterocyclic Chemistry
Received, 2nd February, 2009, Accepted, 5th March, 2009, Published online, 9th March, 2009
DOI: 10.3987/COM-09-S(S)8
SYNTHESIS OF 4-ARYL-SUBSTITUTED BUTENOLIDES AND
PENTENOLIDES BY COPPER-CATALYZED HYDROARYLATION‡
Yoshihiko Yamamoto*† and Naohiro Kirai
Department of Applied Chemistry, Graduate School of Science and Engineering,
Tokyo Institute of Technology, Ookayama, Meguro-ku, Tokyo 152-8552, Japan;
E-mail: omyy@apc.titech.ac.jp
Abstract – We have investigated the effect of the type of protecting group used
and the tether length of 4- and 5-hydroxy-substituted 2-alkynoates on the yields
and selectivity of the product of hydroarylation. The use of methyl,
methoxymethyl, and tert-butyldimethylsilyl (TBS) as protecting groups increased
the total yield of the products. While the protected 4-hydroxy-2-butynoates
afforded products formed from two or more alkyne substrates,
5-hydroxy-2-pentynoate derivatives exclusively yielded 1:1 adducts. These facts
suggest that the product selectivity depends on the distance of the alkoxy group
from the alkyne moiety rather than the type of the protecting group. Among the
protecting groups used in this study, the TBS group was found to produce
butenolides and pentenolides in good total yields via the one-pot
hydroarylation/lactonization.
INTRODUCTION
Furan-2(5H)-one (butenolide) is a privileged oxygen heterocycle, which is widely distributed in nature,
and its naturally occurring derivatives exhibit interesting biological activities. Therefore, a considerable
number of studies have been devoted to the development of an efficient and versatile method to
synthesize butenolides.1 In contrast, 5,6-dihydro-2H-pyran-2-one (pentenolide), which is homologous to
butenolide, has not received significant attention, even though this structural motif found in natural
products is also exhibit bioactivity.2
‡ This paper is dedicated to Prof. Akira Suzuki on the occasion of his 80th birthday.
† Current Address: Department of Applied Chemistry, Graduate School of Engineering, Nagoya
University, Chikusa-ku, Nagoya 464-8603, Japan; E-mail: yamamoto@apchem.nagoya-u.ac.jp

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Recently, we have reported that the Cu-catalyzed hydroarylation of alkynoates with arylboronic acids
stereoselectively produced trisubstituted cinnamate derivatives in good yields.3 On the basis of the
success of the above study, we envisaged that by applying this method to alkynoate substrates with a
hydroxy terminal, we can obtain unsaturated lactones via concomitant cyclization between the hydroxy
and ester carbonylꢀgroups. In fact, we obtained 4-phenylbutenolide (3a), albeit in a moderate yield of
61%, when methyl 4-hydroxy-2-butynoate (1a) reacted with phenylboronic acid (2a) under our optimal
conditions (Scheme 1). As an extension of this sequential hydroarylation/lactonization process, we also
developed the synthetic method for 4-arylcoumarins, which constitute a subgroup of flavonoids
(neoflavones), using phenol-derived propiolates as substrates.4 During this study, we found that the
undesired 4-methoxycoumarin is produced in a significant yield along with the formation of
4-phenylcoumarin, by carrying out the reaction between 2a and methyl 3-(2-hydroxyphenyl)propiolate
(Scheme 1). In contrast, when substrates protected with an easily removable methoxymethyl (MOM)
group were used, the desired 4-arylcoumarins were selectively produced in high yields after the acidic
deprotection of the MOM group in one pot. This result indicated the importance of the protection of the
hydroxy moiety in the substrates. In this paper, we report the results of the synthesis of 4-aryl-substituted
butenolides and pentenolides by Cu-catalyzed hydroarylation, with the emphasis on the effect of
protecting groups on the yields and selectivity of the products.5,6
Ph
R
2 mol % CuOAc
+ PhB(OH)2
CO2Me
MeOH, 28 ˚C
HO
R
O
2a 3 equiv
O
1a R = H
1b R = Ph
3a 2 h, 61%
3b 24 h, 59%
O
O
+
O
O
OH
2 mol % CuOAc
MeOH, 28 ˚C, 12 h
+ PhB(OH)2
CO2Me
2a 3 equiv
Ph
OMe
54% / 37%
Scheme 1. Hydroarylation/lactonization of 4-hydroxy-2-butynoates 1 and methyl
3-(2-hydroxyphenyl)-2-propiolate
RESULTS AND DISCUSSION
At the outset of this study, we revisited the Cu-catalyzed hydroarylation of alkynoates with a terminal
hydroxy group. As mentioned above, the hydroarylation of the alkyne triple bond in 1a and the
subsequent lactonization of the resultant adduct resulted in the formation of 3a in 61% yield. We then
carried out this reaction using phenyl-substituted butynoate 1b as the substrate to obtain the
corresponding 4,5-diphenylbutenolide 3b in a yield of 59%, which is comparable to the above reaction

HETEROCYCLES, Vol. 80, No. 1, 2010
271
(Scheme 1). In order to examine the effect of the tether length between the alkyne and hydroxy moieties
on the reaction, we carried out the Cu-catalyzed hydroarylation of 5-hydroxy-2-pentynoate 1c and
obtained 4-phenylpentenolide 4a in 55% yield as the sole product (Scheme 2). In contrast to the result
obtained from 3-(2-hydroxyphenyl)propiolate with the same tether length (Scheme 1), the corresponding
4-methoxypentenolide was not formed from 1c.
Ph
CO2Me
2 mol % CuOAc
+ PhB(OH)2
O
MeOH, 28 ˚C, 2 h
OH
2a 3 equiv
1c
O
4a 55%
Scheme 2. Hydroarylation/lactonization of 5-hydroxy-2-butynoate 1c
We then studied the hydroarylation of substrates with protected hydroxy groups with the aim of
improving the product yields. First, we carried out the hydroarylation of 4-methoxy-2-butynoate 5a with
3 equivalents of phenylboronic acid 2a (Scheme 3). After stirring the reaction mixture for 1 h, the
products were purified by column chromatography on silica gel to afford the desired 1:1 adduct 6a along
with an unexpected 2:1 adduct 7a in yields of 57% and 32%, respectively.7 The total yield of 89%
obtained by this method is much higher than that of 3a (61%) obtained by using the unprotected substrate
1a (Scheme 1). Therefore, the protection of the terminal hydroxy moiety enhances the product yield. The
unexpected formation of 7a is ascribed to the strong bidentate coordination of 5a to a presumed vinyl
copper intermediate (Scheme 4). As a result, the second molecule of 5a was incorporated into the C–Cu
bond prior to methanolysis of the vinyl copper species. We believed that if this were the case, then by
using cyclic boronate 2a’, the rate of methanolysis must be lowered, resulting in an increase in the yield
of 7a. Therefore, to verify the above speculation, we repeated the reaction with 1 equivalent of 2a’ with
stirring for 3 h and obtained 7a as a major product in 59% yield along with 6a in ca. 20% yield. Moreover,
it is worth noting that the geometries of both the alkene moieties in 7a have been demonstrated to be
controlled perfectly via syn carbocupration.
2a 3 equiv
6a 57% + 7a 32% (64:36)
1 h
MeO
Ph
CO2Me
Ph
2 mol % CuOAc
MeOH, 28 ˚C
CO2Me
+
MeO
MeO
CO2Me
5a
MeO
CO2Me
6a
6a 21% (NMR) + 7a 59% (26:74)
2a' 1 equiv
7a
3 h
O
PhB
O
Scheme 3. Hydroarylation of 4-methoxy-2-butynoate 5a

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HETEROCYCLES, Vol. 80, No. 1, 2010
MeO
Ph
CO2Me
Cu
MeO
Cu
Ph
7a
CO2Me
MeO
O
MeO
CO2Me
MeO
Scheme 4. Proposed pathway to 2:1 adduct 7a
With the aim of obtaining the corresponding butenolides, we examined the use of different easily
removable protecting groups. First, MOM-protected 5b was allowed to react with 1 equivalent of
phenylboronate 2a’ for 2 h by following the same procedure as above to obtain a 2:1 adduct 7b as the
major product along with a 1:1 adduct 6b in yields of 63% and 12%, respectively (Scheme 5). In this case,
a 3:1 adduct 8b was also obtained in 15% yield, suggesting that the two oxygen atoms of the MOM
protecting group enhance the coordination ability of 5b and hence facilitate its incorporation into the
C–Cu bond. We then attempted to carry out lactonization of the obtained products by the removal of
MOM groups under acidic conditions (6 M HCl in MeOH). However, the reaction was sluggish at
ambient temperature and led to a low total yield of less than 25%. The deprotection reaction at elevated
temperature, on the other hand, resulted in the decomposition of products.
OMOM
E
OMOM
E
E
2 mol %
CuOAc
Ph
MOMO
5b
Ph
Ph
+
+
+
E
O
PhB
O
MeOH
28 ˚C, 2 h
OMOM
E
E
E
2a' 1 equiv
OMOM
OMOM OMOM
6b 12%
7b 63%
8b 15%
Scheme 5. Hydroarylation of 4-(methoxymethoxy)-2-butynoate 5b (E = CO2Me)
The use of tert-butyldimethylsilyl (TBS) instead of MOM as the protecting group proved to be
advantageous (Scheme 6). The hydroarylation of 4-siloxy-2-butynoate 5c with 3 equivalents of 2a was
carried out by stirring for 6 h under optimal conditions to produce 1:1 and 2:1 adducts, which were
detected by TLC analysis. When the reaction mixture was treated with 6 M HCl in the same reaction
vessel, the deprotection effectively took place even at ambient temperature for 1 h, and butenolide 3a was
obtained as the major product in 56% yield along with bis(butenolide) 9 in 31% yield.8 In contrast, when
this reaction was carried out using 1 equivalent of phenylboronate 2a’ instead of 2a with stirring for 24 h,
9 was obtained as the major product in 58% yield along with 3a in 21% yield (Scheme 6).
Finally, we investigated the use of this one-pot Cu-catalyzed hydroarylation/lactonization method for the
synthesis of 4-arylpentenolides 4 from 5-silyloxy-2-pentynoate 5d (Scheme 7 and Table 1). In the
presence of 2 mol % CuOAc, 5d was treated with 3 equivalents of phenylboronic acid 2a in MeOH at 28

HETEROCYCLES, Vol. 80, No. 1, 2010
273
O
CO2Me
O
Ph
TBSO
1) 2 mol % CuOAc
5c
Ph
+
+
MeOH, 28 ˚C
2) 6 M HCl, rt, 1 h
O
2a
3 equiv
2a'
1 equiv
O
or
O
3a
9
O
From 2a (6 h): 3a 56% + 9 31%
From 2a' (24 h): 3a 21% + 9 58%
Scheme 6. Hydroarylation/lactonization of 4-(tert-butyldimethylsilyloxy)-2-butynoate 5c
˚C for 3 h and subsequent acidic removal of the TBS group at room temperature for 1 h afforded the
desired product 4-phenylpentenolide 4a in a high yield of 86% (Table 1, entry 1). In the case of the
homopropargyl system 5d, it was found that only 1:1 coupling of the alkyne and arylboronic acid
occurred, indicating that the ease of the insertion of the second alkyne molecule is influenced by the
tether length between the alkyne and silyloxy moieties rather than the protecting groups used. In fact,
when the methoxy analogue of 5d, i.e., 5e, was subjected to hydroarylation with 2a, it afforded a 1:1
adduct 10 in a moderate yield (Scheme 8); this result supports the above inference. We have previously
reported that a bishomo congener such as methyl 6-methoxy-2-hexynoate also exclusively yields a 1:1
adduct on hydroarylation.3
R
CO2Me
1) cat. CuOAc
+
R
B(OH)2
2a–e 3 equiv
MeOH, 28 ˚C
2) 6 M HCl, rt, 1 h
OTBS
5d
O
4a–e
O
Scheme 7. Hydroarylation/lactonization of 5-(tert-butyldimethylsilyloxy)-2-pentynoate 5d
Ph
2 mol % CuOAc
CO2Me
+ PhB(OH)2
CO2Me
10 64%
MeOH, 28 ˚C, 24 h
OMe
5e
2a 3 equiv
MeO
Scheme 8. Hydroarylation of 5-(methoxy)-2-pentynoate 5e
In order to demonstrate the feasibility of this method, the performance of different substituted arylboronic
acids was also examined, and the results are summarized in Table 1. p-Tolylboronic acid 2b underwent
hydroarylation to afford 4b in a high yield comparable to that obtained in the case of 2a; however, a
longer reaction time of 6 h was required (Table 1, entry 2). The hydroarylation using sterically demanding
o-tolylboronic acid did not proceed to completion for 24 h, even though an increased amount of catalyst
was employed (6 mol %). It was found that this one-pot hydroarylation/lactonization method gave good

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HETEROCYCLES, Vol. 80, No. 1, 2010
results with arylboronic acids that possess both electron-donating and electron-withdrawing substituents
such as 2c–e (entries 3–5); although in the cases of electron-deficient arylboronic acids 2d and 2e, an
increased amount of copper catalyst was required.
Table 1. Synthesis of 4-arylpentenolides 4a–e from 5d
Entry
R
ArB(OH)2
Cat. [mol %]
Hydroarylation [h]
Products, yield [%]
4a, 86
1
2
3
4
5
H
2a
2b
2c
2d
2e
2
2
2
4
4
3
6
2
4
4
Me
OMe
Cl
4b, 88
4c, 86
4d, 78
CHO
4e, 61
In conclusion, we have demonstrated that the use of protecting groups such as methyl, MOM, and TBS
increased the yields of hydroarylation, and the product selectivity mainly depends on the distance
between the alkoxy group and the alkyne moiety rather than the type of protecting group. Among the
protecting groups used in this study, the TBS group was found to produce butenolides and pentenolides in
high total yields by the proposed one-pot hydroarylation/lactonization method.
EXPERIMENTAL
Column chromatography was performed on silica gel (Cica silica gel 60N) with mixed solvents [hexane /
AcOEt]. 1H and 13C NMR spectra were obtained on a Varian Gemini 2000 NMR spectrometer for samples in
1
CDCl3 solutions at 25 ˚C. H NMR chemical shifts are reported in terms of chemical shift (ꢀ, ppm)
relative to the singlet at 7.26 ppm for chloroform. Splitting patterns are designated as follows: s, singlet; d,
doublet; t, triplet; q, quartet; quint, quintet; sext, sextet; sept, septet; m, multiplet. Coupling constants are
13
reported in Hz. C NMR spectra were fully decoupled and are reported in terms of chemical shift (ꢀ,
ppm) relative to the triplet at 77.0 ppm for CDCl3. EI mass measurements were performed with a
Shimadzu GCMS-QP2010 plus mass spectrometer. ESI mass spectra were recorded on a JEOL
JMS-T100CS mass spectrometer as a MeOH solution. Elemental analyses were performed at Center for
Advanced Materials Analysis of Tokyo Institute of Technology. Melting points were obtained in capillary
tubes. All solvents and CuOAc were purchased and used as received. Alkynoates 1bꢀꢁꢂꢀ1c,9b 5a,9c 5b,9c
5c,9b 5d,9d and 5e9e were prepared according to the procedures reported in the literatures. Products 3a,10a
3b,10b and 4a10c are known compounds.
Representative Procedure for Cu-catalyzed Hydroarylation of Alkynoates with Phenyloronic Acid:
Synthesis of Butenolide 3b from Alkynoate 1b and Phenylboronic acid 2a. To a solution of 1b (95

HETEROCYCLES, Vol. 80, No. 1, 2010
275
mg, 0.5 mmol) and 2a (183 mg, 1.5 mmol) in MeOH (1.0 mL) was added CuOAc (1.23 mg, 0.01 mmol).
The reaction mixture was degassed at –78 ˚C, and then stirred at 28 ˚C under Ar atmosphere for 24 h.
After filtration through a pad of celite to remove insoluble materials, the filtrate was concentrated in
vacuo. The residue was purified by silica gel flash column chromatography (hexane/AcOEt 10:1–5:1) to
give 4,5-diphenyl-2(5H)-furanone (3b) (70 mg, 59%) as colorless solids (mp 154–157 ˚C, lit.,10b mp
147.5–150 ˚C): 1H NMR (300 MHz, CDCl3): ꢀ 6.33 (d, J = 1.6 Hz, 1 H), 6.55 (d, J = 1.6 Hz, 1 H),
7.30–7.43 (m, 10 H); 13C NMR (75 MHz, CDCl3): ꢀ 84.1, 114.4, 127.4, 127.7, 128.8, 129.0, 129.4,
129.5, 131.1, 134.8, 165.7, 172.4.
4-Phenyl-5,6-dihydro-2H-pyran-2-one (4a): colorless solid (mp 55–57 ˚C, lit.,10c mp 56–58 ˚C); 1H
NMR (300 MHz, CDCl3): ꢀ 2.87 (dt, J = 6.0, 0.9 Hz, 2 H), 4.54 (t, J = 6.0 Hz, 2 H), 6.38 (t, J = 0.9 Hz, 1
H), 7.44–7.48 (m, 3 H), 7.53–7.57 (m, 2 H); 13C NMR (75 MHz, CDCl3): ꢀ 26.2, 65.9, 114.9, 125.9,
128.9, 130.6, 135.9, 155.2, 164.8.
Methyl 4-methoxy-3-phenylbut-2-enoate (6a): colorless oil; 1H NMR (300 MHz, CDCl3): ꢀ 3.33 (s, 3
H), 3.77 (s, 3 H), 4.94 (d, J = 0.9 Hz, 2 H), 6.21 (d, J = 0.9 Hz, 1 H), 7.35–7.41 (m, 3 H), 7.49–7.53 (m, 2
H); 13C NMR (75 MHz, CDCl3): ꢀ 51.2, 58.0, 67.9, 119.4, 127.0, 128.3, 129.0, 138.7, 154.9, 166.2;
MS (EI): m/z (%): 206 (87) [M+], 191 (23) [M+ – CH3], 174 (36) [M+ – CH3OH], 159 (100) [M+ – CH3OH
– CH3]; Anal. Calcd (%) for C12H14O3 (206.09): C 69.88; H 6.84. Found: C 69.83; H 6.83.
Dimethyl 4-(2-methoxy-1-phenylethylidene)-3-(methoxymethyl)pent-2-enedioate (7a): colorless oil;
1H NMR (300 MHz, CDCl3): ꢀ 3.31 (s, 3 H), 3.33 (s, 3 H), 3.57 (s, 3 H), 3.79 (s, 3 H), 4.41 (d, J = 2.1 Hz,
2 H), 4.55 (s, 2 H), 5.50 (t, J = 2.1 Hz, 1 H), 7.21–7.34 (m, 5 H); 13C NMR (75 MHz, CDCl3): ꢀ 51.0,
51.9, 58.1, 58.8, 71.3, 72.5, 120.8, 127.9, 128.0, 128.2, 132.5, 138.8, 148.0, 155.4, 165.7, 167.0; MS
(ESI): calcd for C18H22O6 (334.14): found m/z 357.05 [M + Na]+; Anal. Calcd (%) for C18H22O6
(334.36): C 64.66; H 6.63. Found: C 64.66; H 6.71.
Methyl 5-methoxy-3-phenylpent-2-enoate (10): colorless oil; 1H NMR (300 MHz, CDCl3): ꢀ 3.30 (s,
3 H), 3.37–3.42 (m, 2 H), 3.48–3.53 (m, 2 H), 3.76 (s, 3 H), 6.12 (s, 1 H), 7.36–7.40 (m, 3 H), 7.45–7.50
(m, 2 H); 13C NMR (75 MHz, CDCl3): ꢀ 31.6, 51.2, 58.4, 71.3, 118.3, 126.7, 128.5, 129.0, 141.1, 157.3,
166.6; MS (EI): m/z (%): 220 (10) [M+], 188 (100) [M+ – CH3OH], 175 (62) [M+ – CH2OCH3], 157 (28)
[M+ – CH3OH – OCH3]; Anal. Calcd (%) for C13H16O3 (220.26): C 70.89; H 7.32. Found: C 70.69; H
7.52.
Representative Procedure for Cu-catalyzed Hydroarylation of Protected Hydroxyalkynoates with
Phenylboronate: Reaction of Alkynoate 5b and Phenylboronate 2a’. To a solution of 5b (633 mg,
4.0 mmol) and 2a’ (760 mg, 4.0 mmol) in MeOH (8.0 mL) was added CuOAc (9.81 mg, 0.08 mmol). The

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HETEROCYCLES, Vol. 80, No. 1, 2010
reaction mixture was degassed at –78 ˚C, and then stirred at 28 ˚C under Ar atmosphere for 2 h. After
filtration through a pad of celite to remove insoluble materials, the filtrate was concentrated in vacuo. The
residue was purified by alumina short column chromatography (hexane/AcOEt 1:2) to remove residual
2a’. The crude products were purified by silica gel flash column chromatography (hexane/AcOEt 20:1) to
give methyl 4-(methoxymethoxy)-3-phenylbut-2-enoate (6b) (113 mg, 12%) as colorless oil: 1H NMR
(300 MHz, CDCl3): ꢀ 3.30 (s, 3 H), 3.77 (s, 3 H), 4.65 (s, 2 H), 5.08 (d, J = 0.3 Hz, 2 H), 6.20 (d, J = 0.3
Hz, 1 H), 7.36–7.42 (m, 3 H) , 7.49–7.54 (m, 2 H); 13C NMR (75 MHz, CDCl3): ꢀ 51.3, 55.4, 63.5, 96.4,
119.4, 127.0, 128.3, 129.0, 138.9, 154.5, 166.1; MS (EI): m/z (%): (no molecular ion peak) 204 (23)
[M+ – CH3OH], 191 (56) [M+ – CH2OCH3], 175 (33) [M+ – OCH2OCH3], 159 (100) [M+ – C6H5]; MS
(ESI): calcd for C13H16O4 (236.10): found m/z 259.06 [M + Na]+; Anal. Calcd (%) for C13H16O4
(236.26): C 66.09; H 6.83. Found: C 66.05; H 6.87.
Further elution (hexane/AcOEt 3:1) gave dimethyl 4-(2-(methoxymethoxy)-1-phenylethylidene)-3-
((methoxymethoxy)methyl)pent-2-enedioate (7b) (497 mg, 63%) as colorless oil: 1H NMR (300 MHz,
CDCl3): ꢀ 3.25 (s, 3 H), 3.36 (s, 3 H), 3.57 (s, 3 H), 3.79 (s, 3 H), 4.60–4.62 (m, 6 H), 4.71 (s, 2 H), 5.49
(t, J = 2.0 Hz, 1 H), 7.25–7.30 (m, 5 H); 13C NMR (75 MHz, CDCl3): ꢀ 51.2, 52.0, 55.3, 55.4, 66.9, 67.6,
96.1, 96.5, 121.5, 128.0, 128.2, 128.3, 132.8, 139.0, 148.3, 154.8, 165.7, 166.8; MS (ESI): calcd for
C20H26O8 (394.16): found m/z 417.07 [M + Na]+; Anal. Calcd (%) for C20H26O8 (394.42): C 60.90; H
6.64. Found: C 60.71; H 6.83.
Further elution (hexane/AcOEt 1:1) gave trimethyl 7-(methoxymethoxy)-2,4-bis((methoxymethoxy)-
methyl)-6-phenylhepta-1,3,5-triene-1,3,5-trioate (8b) (113 mg, 15%) as colorless gummy oil: 1H NMR
(300 MHz, CDCl3): ꢀ 3.18 (s, 3 H), 3.25 (s, 3 H), 3.37 (s, 3 H), 3.62 (s, 3 H), 3.70 (s, 3 H), 3.81 (s, 3 H),
4.16 (s, 2 H), 4.51 (s, 2 H), 4.55 (s, 2 H), 4.63 (s, 6 H), 5.80 (br s, 1 H), 7.29–7.31 (m, 5 H); 13C NMR
(75 MHz, CDCl3): ꢀ 51.2, 51.7, 52.0, 55.2, 55.4, 65.9, 67.3, 68.1, 95.8, 96.1, 96.3, 120.8, 128.0, 128.4,
128.5, 130.3, 132.2, 138.3, 144.6, 147.4, 151.7, 165.8, 166.3, 167.3; MS (ESI): calcd for C27H36O12
(552.22): found m/z 575.11 [M + Na]+; Anal. Calcd (%) for C27H36O12 (552.57): C 58.69; H 6.57.
Found: C 58.73; H 6.52.
Representative Procedure for Cu-catalyzed One-pot Hydroarylation/lactonization of
Silyloxyalkynoates: Reaction of 5c with Phenylboronic Acid 2a. To a solution of 5c (114 mg, 0.5
mmol) and 2a (183 mg, 1.5 mmol) in MeOH (1.0 mL) was added CuOAc (1.23 mg, 0.01 mmol). The
reaction mixture was degassed at –78 ˚C, and then stirred at 28 ˚C under Ar atmosphere for 6 h. To this
solution was added MeOH (2 mL) and 6 M HCl (1 mL) in this order, and the reaction mixture was stirred
for 1 h at room temperature. The resultant mixture was extracted with AcOEt (10 mL ꢁ 3). The combined
organic layer was washed with H2O (15 mL) and brine (15 mL), dried over Na2SO4, and concentrated in

HETEROCYCLES, Vol. 80, No. 1, 2010
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vacuo. The residue was purified by silica gel flash column chromatography (hexane/AcOEt 5:1) to give
4-phenylfuran-2(5H)-one (3a) (45 mg, 56%) as colorless solids (mp 92–93 ˚C, lit.,10a mp 91–93 ˚C); 1H
NMR (300 MHz, CDCl3): ꢀ 5.24 (d, J = 1.8 Hz, 2 H), 6.39 (t, J = 1.8 Hz, 1 H), 7.46–7.52 (m, 5 H); 13C
NMR (75 MHz, CDCl3): ꢀ 71.0, 113.0, 126.4, 129.3, 129.6, 131.7, 163.9, 173.8.
Further elution (hexane/AcOEt 3:1) gave 4-phenyl-3,3'-bifuran-2,5'(2'H,5H)-dione (9) (19 mg, 31%) as
pale-yellow solids (mp 115–118 ˚C): 1H NMR (300 MHz, CDCl3): ꢀ 5.01 (d, J = 2.0 Hz, 2 H), 5.13 (s, 2
H), 6.55 (t, J = 2.0 Hz, 1 H), 7.36–7.40 (m, 2 H), 7.50–7.60 (m, 3 H); 13C NMR (75 MHz, CDCl3): ꢀ
71.6, 72.4, 118.3, 119.1, 126.9, 129.7, 130.0, 131.6, 153.1, 164.8, 170.6, 172.8; MS (ESI): calcd for
C14H10O4 (242.06): found m/z 265.00 [M + Na]+; Anal. Calcd (%) for C14H10O4 (242.23): C 69.42; H
4.16. Found: C 69.32; H 4.26.
4-p-Tolyl-5,6-dihydro-2H-pyran-2-one (4b): colorless solid (mp 90–91 ˚C); 1H NMR (300 MHz,
CDCl3): ꢀ 2.40 (s, 3 H), 2.85 (dt, J = 6.0, 1.2 Hz, 2 H), 4.52 (t, J = 6.0 Hz, 2 H), 6.35 (t, J = 1.2 Hz, 1 H),
7.25 (d, J = 8.4 Hz, 2 H), 7.45 (d, J = 8.4 Hz, 2 H); 13C NMR (75 MHz, CDCl3): ꢀ 21.2, 26.1, 65.9,
113.9, 125.8, 129.6, 132.9, 141.1, 155.1, 165.1; MS (EI): m/z (%): 188 (100) [M+], 158 (67) [M+ –
CH2O], 130 (60) [M+ – CH2O – CO]; Anal. Calcd (%) for C12H12O2 (188.22): C 76.57; H 6.43. Found: C
76.45; H 6.36.
4-(4-Methoxyphenyl)-5,6-dihydro-2H-pyran-2-one (4c): colorless solid (mp 97–98 ˚C); 1H NMR (300
MHz, CDCl3): ꢀ 2.84 (t, J = 6.0 Hz, 2 H), 3.86 (s, 3 H), 4.51 (t, J = 6.0 Hz, 2 H), 6.31 (s, 1 H), 6.95 (d, J
= 8.7 Hz, 2 H), 7.52 (d, J = 8.7 Hz, 2 H); 13C NMR (75 MHz, CDCl3): ꢀ 26.0, 55.3, 65.8, 112.6, 114.3,
127.5, 128.0, 154.6, 161.6, 165.3; MS (EI): m/z (%): 204 (100) [M+], 174 (39) [M+ – CH2O], 146 (41)
[M+ – CH2O – CO]; Anal. Calcd (%) for C12H12O3 (204.22): C 70.57; H 5.92. Found: C 70.60; H 5.89.
4-(4-Chlorophenyl)-5,6-dihydro-2H-pyran-2-one (4d): colorless solid (mp 96–98 ˚C); 1H NMR (300
MHz, CDCl3): ꢀ 2.84 (dt, J = 6.0, 1.2 Hz, 2 H), 4.53 (t, J = 6.0 Hz, 2 H), 6.36 (t, J = 1.2 Hz, 1 H), 7.42 (d,
J = 8.7 Hz, 2 H), 7.48 (d, J = 8.7 Hz, 2 H); 13C NMR (75 MHz, CDCl3): ꢀ 26.1, 65.8, 115.3, 127.2,
129.2, 134.3, 136.7, 153.8, 164.6; MS (EI): m/z (%): 208 (100) [M+], 178 (77) [M+ – CH2O], 150 (35)
[M+ – CH2O – CO]; Anal. Calcd (%) for C11H9ClO2 (208.64): C 63.32; H 4.35. Found: C 63.09; H 4.34.
4-(4-Formylphenyl)-5,6-dihydro-2H-pyran-2-one (4e): colorless solid (mp 137–139 ˚C); 1H NMR
(300 MHz, CDCl3): ꢀ 2.91 (dt, J = 6.0, 1.2 Hz, 2 H), 4.57 (t, J = 6.0 Hz, 2 H), 6.46 (t, J = 1.2 Hz, 1 H),
7.70 (d, J = 8.7 Hz, 2 H), 7.96 (d, J = 8.7 Hz, 2 H), 10.07 (s, 1 H); 13C NMR (75 MHz, CDCl3): ꢀ 26.2,
65.9, 117.4, 126.5, 130.02, 137.3, 141.6, 153.7, 164.2, 191.2; MS (EI): m/z (%): 202 (100) [M+], 172 (9)
[M+ – CH2O], 144 (50) [M+ – CH2O – CO]; Anal. Calcd (%) for C12H10O3 (202.21): C 71.28; H 4.98.
Found: C 71.09; H 5.10.

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ACKNOWLEDGEMENTS
This research was partially supported by the MEXT, Grant-in-Aid for Scientific Research (B), 20350045,
Scientific Research on Priority Area "Chemistry on Concerto Catalysis" (20037018). We thank Prof. K.
Tomooka (Kyushu University) for use of a NMR spectrometer and Profs. H. Suzuki, T. Takao, T. Ikariya,
and S. Kuwata (Tokyo Instituted of Technology) for use of mass spectrometers.
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