An expedient synthesis of 3-arylmethylbutenolides from α-methylene- γ-butyrolactones: A useful synthetic application of palladium-catalyzed chelation-controlled oxidative arylation protocol

Article abstract of DOI:10.1016/j.tetlet.2012.11.040

A palladium-catalyzed chelation-controlled oxidative arylation of α-methylene-γ-butyrolactones with arenes provided 3-arylmethylbutenolides as major products along with a low yield of α-arylidene-γ-butyrolactones. The selectivity might be due to a chelation between the palladium center and a directing group at the γ-position of α-methylene-γ-butyrolactones.

Full text of DOI:10.1016/j.tetlet.2012.11.040

Tetrahedron Letters 54 (2013) 329–334
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An expedient synthesis of 3-arylmethylbutenolides from
a-methylene-c-butyrolactones: a useful synthetic application of
palladium-catalyzed chelation-controlled oxidative arylation protocol
⇑
Se Hee Kim, Ko Hoon Kim, Hyun Ju Lee, Jae Nyoung Kim
Department of Chemistry and Institute of Basic Science, Chonnam National University, Gwangju 500-757, Republic of Korea
a r t i c l e i n f o
a b s t r a c t
Article history:
A palladium-catalyzed chelation-controlled oxidative arylation of
arenes provided 3-arylmethylbutenolides as major products along with a low yield of
a
-methylene-
c
-butyrolactones with
-arylidene-
butyrolactones. The selectivity might be due to a chelation between the palladium center and a directing
group at the -position of -methylene- -butyrolactones.
Received 3 October 2012
Revised 3 November 2012
Accepted 9 November 2012
Available online 23 November 2012
a
c-
c
a
c
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
3-Arylmethylbutenolides
Oxidative arylation
Chelation
Palladium
Morita–Baylis–Hillman bromides
A palladium-catalyzed chelation-controlled arylation of olefins
has been studied extensively for the purpose of stereo- and regio-
control, and multiple arylations.1,2 Various functional groups such
as ester, ketone, amide, imide, and amines have been known to
act as a directing group (DG), which stabilizes the palladium inter-
mediate by chelation.1,2 Most of the arylation reactions involved the
use of aryl halides, arylboronic acids, and arenediazonium salts as
an aryl source.2 Recently, Pd-catalyzed oxidative Heck reactions of
allyl esters have been reported with arenes and heteroarenes.1 Very
recently, we also reported an efficient palladium-catalyzed oxida-
butenolide B to date. Based on the recent publications on
palladium-catalyzed chelation-controlled arylations of olefins,1,2
we presumed that such a chelation-controlled oxidative arylation
protocol could be applied efficiently for the synthesis of
3-arylmethylbutenolides from
a-methylene-c-butyrolactones
bearing a directing group (DG) such as an ester or ketone at the
c-position, as shown in Scheme 1.
As a starting material we selected
a-methylene-c-butyrolac-
tone 1a, which could be prepared readily by an indium-mediated
Barbier type reaction between the Morita–Baylis–Hillman (MBH)
bromide and methyl pyruvate.7a With this lactone 1a, we exam-
ined the phenylation in the presence of Pd(OAc)2, AgOAc, and piva-
lic acid in benzene,1f,8a–c as shown in Scheme 2. Carbopalladation
of the C@C double bond of 1a to an initially formed phenylpalla-
dium species PhPd(OPiv) might generate an intermediate I. The
carbopalladation might proceed stereoselectively to the same side
of a directing group (–COOMe) due to a chelation-assisted stabil-
ization effect of the intermediate I. In addition, the proton at the
4-position of the lactone ring is positioned in a syn-relationship
with the palladium center, and a subsequent b-H elimination pro-
ceeded in this direction to produce 3-benzylbutenolide 2a as a ma-
jor product (77%).9 A low yield (19%) of benzylidene lactone 3a was
formed by b-H elimination with the hydrogen at the benzyl moi-
ety. The stereochemistry of a benzylidene moiety of 3a would be
tive Heck type arylation of a
-substituted methyl cinnamates.1f
Diversely substituted butenolides have been found in numer-
ous natural products3 and used for the synthesis of many biolog-
ically important compounds.3–5 Thus, the synthesis of butenolides
from
the important approaches to these compounds. Arcadi et al. re-
ported a Pd-catalyzed arylation of -methylene- -butyrolactones
a-methylene-c-butyrolactones has been known as one of
a
c
with aryl iodides; however, they obtained a mixture of arylidene
lactone A and butenolide B, as shown in Scheme 1.6a,b The
selectivity between A and B was dependent both on the reaction
conditions and aryl iodides. Later, Colby and co-workers reported
a selective synthesis of arylidene lactone derivative A, and they
confirmed the stereochemistry of the arylidene moiety as E-form
by chemical shift of the vinyl proton and X-ray crystal structure.6c
However, there is no method for the selective synthesis of
E-form based on the chemical shift of
a
vinyl proton
(d = 7.77 ppm).6c Compound 3a could be converted quantitatively
into 2a by treatment with DBU (0.3 equiv) in refluxing toluene
(3 h), whereas the reaction of 3a and AgOAc (1.0 equiv) in benzene
⇑
Corresponding author. Tel.: +82 62 530 3381; fax: +82 62 530 3389.
E-mail address: kimjn@chonnam.ac.kr (J.N. Kim).
0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2012.11.040

330
S. H. Kim et al. / Tetrahedron Letters 54 (2013) 329–334
ArI, Pd(OAc)2, KOAc, DMF
O
R1
R1
O
O
O
R1
O
O
A/B mixture (Arcadi)
+
+
R2
ArI, Pd(OAc)2, Et3N, DMF
R2
Ar
R2
Ar
A as a major (Colby)
A
B
DG
R1
DG
R1
O
O
DG
R1
O
ArH, Pd(OAc)2, AgOAc, PivOH
O
O
O
B as a major (This work)
R2
R2
Ar
R2
DG = directing group
Ar
B
A
Scheme 1.
O
O
O
benzene (60 equiv)
MeO
Me
Ph
Pd(OAc)2 (5 mol%)
MeO
Me
Ph
MeO
Me
Ph
O
O
O
O
O
O
+
AgOAc (3.0 equiv)
PivOH (6.0 equiv)
reflux, 24 h
Ph
Ph
3a (19%)
1a
PhPd(OPiv)
2a (77%)
β-H elim.
O
PdL
O
MeO
Me
Ph
H
O
Ph
I
(i) workup
same as above
2a + 3a
2a (91%) + no 3a
1a
(ii) DBU (0.3 equiv)
toluene, reflux, 2 h
Scheme 2.
(reflux, 48 h) did not produce 2a at all. In addition, the ratio be-
tween 2a and 3a (ca. 4:1) was not changed much when the palla-
dium-catalyzed phenylation of 1a was carried out for a long time
(48 h). The results stated that 2a must be formed directly by the
Pd-catalyzed phenylation of 1a. Actually, benzylbutenolide 2a
could be prepared in high yield (91%) by treatment of the crude
reaction mixture of 2a and 3a with DBU, after a simple aqueous
workup, as also shown in Scheme 2.
p-xylene, produced butenolide derivatives 2i and 2j, respectively,
in good yields (entries 4 and 5). The corresponding lactone deriva-
tives 3i and 3j were not observed.
Table 1
Pd-catalyzed arylation of 1a
Entry Conditionsa
Products (%)
Encouraged by the successful results we examined arylations of
1a with various arenes, and the results are summarized in Ta-
ble 1.10 The reactions of 1a with o-xylene, p-xylene, m-xylene,
and o-dichlorobenzene produced similar results (entries 2–5). In
all entries, 3-arylmethylbutenolides 2b–e were formed as major
products (51–73%) along with arylidene lactones 3b–e as minor
products (16–22%). No regioisomeric products were observed
when we used o-xylene and o-dichlorobenzene. When we used
m-xylene (entry 4), meta and ortho-isomers were formed together
(vide infra). Actually, the regioisomers could not be separated, and
compounds 2d (meta-2d/ortho-2d = 4:1) and 3d (meta-3d/ortho-
3d = 2:1) were isolated in 73% and 20%, respectively, as their regio-
isomeric mixtures.
O
O
MeO
MeO
MeO
O
O
O
O
O
O
Me
Ph
Me
Benzene
1
reflux, 24 h
Ph
2a (77)
O
3a (19)
O
MeO
O
O
Me
Ph
Me
o-Xylene
2
Ph
100 °C, 24 h
2b (70)
3b (21)
In order to confirm the generality, similar lactone derivatives
1b–d were prepared according to the reported methods7a,b and
examined the oxidative arylation, as shown in Table 2. The reac-
tions of acetyl derivative 1b with benzene or p-xylene showed sim-
ilar results (entries 1 and 2) with that of the ester derivative 1a.
The reaction of 4-unsubstituted lactone 1c produced 2h in moder-
ate yield (45%). However, isolation of the corresponding benzyli-
dene lactone 3h failed due to the presence of some side product
near the spot on TLC (entry 3). The reactions of a pentacyclic lac-
tone 1d,7b under the same reaction conditions with benzene or
O
O
MeO
MeO
O
O
O
O
Me
Ph
Me
Ph
p-Xylene
3
100 °C, 24 h
2c (64)
3c (22)

S. H. Kim et al. / Tetrahedron Letters 54 (2013) 329–334
331
(2.0 equiv) decreased the yield of 4, while the yield increased to
63% by using an excess amount of AgOAc. The result using Pd(TFA)2
was similar to that of Pd(OAc)2.
Thus a plausible reaction mechanism could be suggested, as
shown in Figure 1, with 1a as a typical example. An arylpalladium
intermediate could be generated from arene and Pd(OPiv)2 most
likely via an electrophilic palladation (SEAr) process.8b,11a–e The
regioselective formations of 2b–e, 2g, and 2j suggested the
involvement of an electrophilic palladation process. However, a
Table 1 (continued)
Entry Conditionsa
Products (%)
O
O
MeO
MeO
O
O
O
O
O
O
Me
Ph
Me
m-Xylene
4
Ph
100 °C, 24 h
2d (73)b
3d (20)c
partial contribution of
a concerted metalation-deprotonation
(CMD) process cannot be ruled out completely at this stage.8a,i,11f,g
As described above, a subsequent carbopalladation of 1a to form
the intermediate I, and the following b-H elimination produced
2a–e as major products. The reduced Pd0 was oxidized to PdII by
AgOAc, and the PdII carries out the catalytic cycle.
O
O
MeO
Me
Ph
MeO
O
O
Cl
Me
o-
5
Dichlorobenzene
100 °C, 24 h
Cl
Ph
In order to compare the reactivity, the reaction of 1a was exam-
ined with iodobenzene instead of benzene, as shown in Scheme 4.
Literature survey suggested two plausible reaction conditions for
the arylation of 1a with aryl iodides. Chen and co-workers carried
out the Pd-catalyzed arylation of cinnamates under the influence of
AgOAc in acetic acid.12 Fabrizi and co-workers performed the ary-
lation of b-arylacrylamides in the presence of Et3N.13 The reaction
in the presence of Pd(OAc)2 and AgOAc in AcOH (Chen’s condition)
afforded the products 2a and 3a in high yield (93%) in short time
(2 h). However, compounds 2a (47%) and 3a (46%) were isolated
in almost equal amounts.14 Interestingly, a mixture of products
was formed when the reaction of 1a was carried out under Fabrizi’s
condition employing excess amounts of Et3N.13 The compounds 2a
and 5 were isolated as a mixture in low yield (30%), along with a
mixture of double bond-isomerized compounds 6 and 7 (34% as
a 1:1 mixture). Compounds 5 and 7 might be produced by in-situ
generated triethylamine hydroiodide-mediated demethoxycarb-
onylation of 2a and 6, respectively.15
2e (51)
3e (16)
Cl
Cl
a
Conditions: Substrate 1a (0.5 mmol), Pd(OAc)2 (5 mol %), AgOAc (3.0 equiv),
PivOH (6.0 equiv), arene (60 equiv).
b
meta (3,5-Dimethylphenyl)/ortho (2,4-dimethylphenyl) = 4:1.
meta (3,5-Dimethylphenyl)/ortho (2,4-dimethylphenyl) = 2:1.
c
In order to clarify the chelation effect on the selective formation
of butenolides in the reactions of 1a–d, we examined the reaction
of 4,5-diphenyl lactone 1e.5a The lactone 1e has no suitable direct-
ing group, and we expected that the ratio between butenolide and
benzylidene lactone might be changed. Actually, the reaction of 1e
produced three compounds, 2k, 3k, and 4, as shown in Scheme 3.
As expected, butenolide 2k was produced as a minor product
(17%) under the typical reaction conditions, while the yield of a
benzylidene lactone 3k increased to 32%. Without a directing
group the carbopalladation of 1e proceeded non-stereoselectively,
as also shown in Scheme 3, and produced a mixture of 2k and 3k. It
is interesting to note that a diarylated lactone 4 was obtained to-
gether in 37% in the reaction. The second phenylation of 3k to 4
might occur because the benzylidene moiety of 3k is sterically less
crowded than that of 3a. Reducing the amount of AgOAc
In summary, a palladium-catalyzed chelation-controlled oxi-
dative arylation of
a-methylene-c-butyrolactones with arenes
was carried out to obtain 3-arylmethylbutenolides as major
products. The selective formation of a butenolide might be the
result of a chelation between the palladium center and a direct-
ing group.
benzene
O
O
Ph
Ph
Ph
Ph
O
O
Ph
Ph
O
O
Ph
Ph
O
(60 equiv)
O
+
+
reflux
Ph
Ph
Ph
Ph
1e
2k
3k
4
Conditions
2k
17
18
3k
32
60
4
Pd(OAc)2 (5 mol%), AgOAc (3.0 equiv), PivOH (6.0 equiv), 24 h
Pd(OAc)2 (5 mol%), AgOAc (2.0 equiv), PivOH (6.0 equiv), 24 h
37
10
Pd(OAc)2 (10 mol%), AgOAc (6.0 equiv), PivOH (6.0 equiv), 24 h
Pd(TFA)2 (5 mol%), AgOAc (2.0 equiv), PivOH (6.0 equiv), 10 h
13
23
0
63
15
43
O
O
O
Ph
H
PdL
O
Ph
H
O
O
MeO
Me
Ph
H
O
PdL
+
Ph
Ph
Ph
PdL
H
H
Ph
Ph
stereoselective carbopalladation of 1a
leading to selective formation of 2a
(Scheme 2)
non-stereoselective carbopalladation of 1e
leading to a mixture of 2k and 3k
Scheme 3.

332
S. H. Kim et al. / Tetrahedron Letters 54 (2013) 329–334
Table 2
Pd-catalyzed arylation of 1b–d
Entry
Substrate/conditionsa
Products (%)
O
O
O
Me
Me
Me
Me
Ph
O
O
O
O
O
O
O
Me
Me
Ph
Me
1
Ph
Ph
1b
benzene
reflux, 24 h
2f (75)
3f (16)
O
O
Me
O
O
O
1b
Me
Ph
Me
2
3
p-Xylene
100 °C, 24 h
Ph
2g (52)
3g (18)
O
O
O
Ph
Ph
O
O
O
O
O
O
O
Ph
Ph
Ph
1c
benzene
reflux, 24 h
2h (45)
3hb
O
O
O
O
O
O
O
O
4
Ph
Ph
Ph
Ph
1d
3ic
benzene
reflux, 24 h
2i (95)
O
O
O
O
O
O
1d
5
p-Xylene
100 °C, 24 h
Ph
3jc
2j (80)
a
Conditions: Substrate 1 (0.5 mmol), Pd(OAc)2 (5 mol %), AgOAc (3.0 equiv), PivOH (6.0 equiv), arene (60 equiv).
Observed in a trace amount on TLC, but failed to isolate.
Not formed.
b
c
Pd(OAc)2
PivOH
ArH
2 Ag0
2 AcOH
Pd(OPiv)2
2 AgOAc
2 PivOH
PivOH
Pd0
ArPd(OPiv)
1a
O
Pd(OPiv)
O
2a-e (major)
3a-e (minor)
PivOH
MeO
Me
Ph
H
O
Ar
I
Figure 1. A plausible catalytic cycle.

S. H. Kim et al. / Tetrahedron Letters 54 (2013) 329–334
333
iodobenzene (1.1 equiv), Pd(OAc)2 (1 mol%)
AgOAc (1.1 equiv), AcOH, 110 oC, 2 h
1a
1a
2a (47%) + 3a (46%)
O
H
H
O
iodobenzene (2.0 equiv), Pd(OAc)2 (5 mol%)
Et3N (10 equiv), 100 oC, 24 h
MeO
Me
Ph
Me
O
Me
O
O
O
O
2a
+
+
+
Ph
Me
Ph
Ph
Me
5
6
7
30% (2a:5 = 4:1)
Scheme 4.
34% (6:7 = 1:1)
Kim, J. N. Bull. Korean Chem. Soc. 2009, 30, 1012–1020; (b) Park, B. R.; Kim, K. H.;
Lim, J. W.; Kim, J. N. Tetrahedron Lett. 2012, 53, 36–40; (c) Lim, J. W.; Kim, K. H.;
Kim, S. H.; Kim, J. N. Bull. Korean Chem. Soc. 2012, 33, 1781–1784.
Acknowledgments
This research was supported by the Basic Science Research Pro-
gram through the National Research Foundation of Korea (NRF)
funded by the Ministry of Education, Science and Technology
(2012R1A1B3000541). Spectroscopic data were obtained from
the Korea Basic Science Institute, Gwangju branch.
6. For the Pd-catalyzed arylation of
a-methylene-c-butyrolactones, see: (a)
Arcadi, A.; Chiarini, M.; Marinelli, F.; Berente, Z.; Kollar, L. Org. Lett. 2000, 2,
69–72; (b) Arcadi, A.; Chiarini, M.; Marinelli, F.; Berente, Z.; Kollar, L. Eur. J. Org.
Chem. 2001, 3165–3173; (c) Han, C.; Barrios, F. J.; Riofski, M. V.; Colby, D. A. J.
Org. Chem. 2009, 74, 7176–7179; (d) Elford, T. G.; Ulaczyk-Lesanko, A.; De
Pascale, G.; Wright, G. D.; Hall, D. G. J. Comb. Chem. 2009, 11, 155–168; (e)
Belovodskii, A. V.; Shults, E. E.; Shakirov, M. M.; Bagryanskaya, I. Y.; Gatilov, Y.
V.; Tolstikov, G. A. Russ. J. Org. Chem. 2010, 46, 1719–1734.
References and notes
7. For the synthesis of starting materials, see: (a) Lee, K. Y.; Park, D. Y.; Kim, J. N.
Bull. Korean Chem. Soc. 2006, 27, 1489–1492. and further references cited
therein on the chemical transformations of the Morita–Baylis–Hillman
adducts; (b) Park, B. R.; Kim, S. H.; Kim, Y. M.; Kim, J. N. Tetrahedron Lett.
2011, 52, 1700–1704.
1. For the palladium-catalyzed chelation-assisted arylations with arenes, see: (a)
Li, Z.; Zhang, Y.; Liu, Z.-Q. Org. Lett. 2012, 14, 74–77; (b) Zhang, Y.; Li, Z.; Liu, Z.-
Q. Org. Lett. 2012, 14, 226–229; (c) Shang, X.; Xiong, Y.; Zhang, Y.; Zhang, L.; Liu,
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2010, 5, 1090–1093; (e) Pan, D.; Jiao, N. Synlett 2010, 1577–1588. and further
references cited therein; Very recently, we reported an efficient synthesis of
8. For our recent contributions on the palladium-catalyzed arylation with arenes,
see: (a) Kim, K. H.; Lee, H. S.; Kim, J. N. Tetrahedron Lett. 2011, 52, 6228–6233;
(b) Kim, K. H.; Lee, H. S.; Kim, S. H.; Kim, J. N. Tetrahedron Lett. 2012, 53, 2761–
2764; (c) Kim, K. H.; Lee, H. S.; Kim, S. H.; Kim, J. N. Tetrahedron Lett. 2012, 53,
1323–1327; The condition employing PivOH as a proton shuttle during the aryl
C–H bond activation was originally developed by Fagnou and applied
extensively for the C–H bond activation of arenes, see: (d) Lafrance, M.;
Fagnou, K. J. Am. Chem. Soc. 2006, 128, 16496–16497; (e) Stuart, D. R.;
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9. Typical procedure for the synthesis of 2a and 3a: A stirred mixture of 1a (123 mg,
0.5 mmol), Pd(OAc)2 (5.7 mg, 5 mol %), AgOAc (251 mg, 1.5 mmol), and PivOH
(307 mg, 3.0 mmol) in benzene (235 mg, 30 mmol) was heated to reflux under
nitrogen atmosphere for 24 h. After cooling to room temperature, the reaction
mixture was filtered over a pad of Celite and washed with CH2Cl2 (100 mL). The
filtrates were washed with a saturated solution of NaHCO3 (20 mL Â 3), and the
organic layer was dried over MgSO4. After removal of solvent and column
chromatographic purification process (hexanes/CH2Cl2, 1:1) 2a was isolated as
a white solid (124 mg, 77%) along with 3a as a white solid (31 mg, 19%). Other
compounds were synthesized similarly, and the selected spectroscopic data of
2a, 2b, 2f, 2i, 2j, 3a, 3b and 3f are as follows.
fully-substituted cinnamates via
oxidative arylations with arenes, see: (f) Lee, H. S.; Kim, K. H.; Kim, S. H.;
Kim, J. N. Adv. Synth. Catal. 2012, 354, 2419–2426.
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1291–1293; (k) Buezo, N. D.; Alonso, I.; Carretero, J. C. J. Am. Chem. Soc. 1998,
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3. For the biologically important natural and non-natural butenolides, see: (a)
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Puranik, V. G.; Argade, N. P. Org. Biomol. Chem. 2011, 9, 6312–6322; (c) Schulz,
D.; Ohlendorf, B.; Zinecker, H.; Schmaljohann, R.; Imhoff, J. F. J. Nat. Prod. 2011,
74, 99–101; (d) Hwang, S.; Kim, J. H.; Kim, H. S.; Kim, S. Eur. J. Org. Chem. 2011,
7414–7418; (e) Zhang, M.; Iinuma, M.; Wang, J.-S.; Oyama, M.; Ito, T.; Kong, L.-
Y. J. Nat. Prod. 2012, 75, 694–698; (f) Wu, T.-Y.; Yang, I.-H.; Tsai, Y.-T.; Wang, J.-
Y.; Shiurba, R.; Hsieh, T.-J.; Chang, F.-R.; Chang, W.-C. J. Nat. Prod. 2012, 75, 572–
576; (g) Trost, B. M.; Burns, A. C.; Bartlett, M. J.; Tautz, T.; Weiss, A. H. J. Am.
Chem. Soc. 2012, 134, 1474–1477; (h) Florence, G. J.; Morris, J. C.; Murray, R. G.;
Osler, J. D.; Reddy, V. R.; Smith, T. K. Org. Lett. 2011, 13, 514–517; (i) Prasad, K.
R.; Gandi, V. R. Tetrahedron: Asymmetry 2010, 21, 275–276; (j) Griggs, N. D.;
Phillips, A. J. Org. Lett. 2008, 10, 4955–4957; (k) Brown, G. D.; Wong, H.-F.
Tetrahedron 2004, 60, 5439–5451.
4. For the synthesis of various butenolides, see: (a) Billamboz, M.; Legeay, J. C.;
Hapiot, F.; Monflier, E.; Len, C. Synthesis 2012, 137–143; (b) Chen, B.; Ma, S.
Chem. Eur. J. 2011, 17, 754–757; (c) Ghobril, C.; Kister, J.; Baati, R. Eur. J. Org.
Chem. 2011, 3416–3419; (d) Katae, T.; Sugiyama, S.; Satoh, T. Synthesis 2011,
1435–1441; (e) Ramachandran, P. V.; Pratihar, D.; Garner, G.; Raju, B. C.
Tetrahedron Lett. 2011, 52, 4985–4988; (f) Ruan, S.-T.; Luo, J.-M.; Du, Y.; Huang,
P.-Q. Org. Lett. 2011, 13, 4938–4941; (g) Wu, Y.; Singh, R. P.; Deng, L. J. Am.
Chem. Soc. 2011, 133, 12458–12461; (h) Hopkinson, M. N.; Ross, J. E.; Giuffredi,
G. T.; Gee, A. D.; Gouverneur, V. Org. Lett. 2010, 12, 4904–4907; (i) Adrio, J.;
Carretero, J. C. J. Am. Chem. Soc. 2007, 129, 778–779; (j) Miao, R.; Gramani, S. G.;
Lear, M. J. Tetrahedron Lett. 2009, 50, 1731–1733; (k) Duffy, R. J.; Morris, K. A.;
Vallakati, R.; Zhang, W.; Romo, D. J. Org. Chem. 2009, 74, 4772–4781; (l)
Boukouvalas, J.; Loach, R. P. J. Org. Chem. 2008, 73, 8109–8112; (m)
Braukmuller, S.; Bruckner, R. Eur. J. Org. Chem. 2006, 2110–2118.
Compound 2a: 77%; white solid, mp 83–84 °C; IR (KBr) 1769, 1747, 1261, 1127,
1056 cmÀ1 1H NMR (300 MHz, CDCl3) d 1.70 (s, 3H), 3.62 (d, J = 15.0 Hz, 1H),
;
3.73 (d, J = 15.0 Hz, 1H), 3.77 (s, 3H), 7.08–7.28 (m, 7H), 7.36–7.45 (m, 3H); 13
C
NMR (75 MHz, CDCl3) d 20.58, 30.15, 53.29, 86.74, 126.55, 127.59, 128.30,
128.56, 128.84, 128.95, 129.82, 130.28, 137.35, 161.23, 168.70, 172.56; ESIMS
m/z 345 [M+Na]+. Anal. Calcd for C20H18O4: C, 74.52; H, 5.63. Found: C, 74.77;
H, 5.49.
Compound 2b: 70%; colorless oil; IR (film) 1771, 1749, 1262, 1128, 1059 cmÀ1
;
1H NMR (300 MHz, CDCl3) d 1.70 (s, 3H), 2.20 (s, 6H), 3.54 (d, J = 15.0 Hz, 1H),
3.67 (d, J = 15.0 Hz, 1H), 3.78 (s, 3H), 6.84 (d, J = 7.5 Hz, 1H), 6.91 (s, 1H), 7.00 (d,
J = 7.5 Hz, 1H), 7.10–7.14 (m, 2H), 7.39–7.44 (m, 3H); 13C NMR (75 MHz, CDCl3)
d 19.30, 19.78, 20.61, 29.66, 53.28, 86.64, 125.49, 127.64, 128.89, 128.98,
129.64, 129.76, 130.32, 134.59, 134.71, 136.65, 160.89, 168.78, 172.63 (one
carbon was overlapped); ESIMS m/z 351 [M+H]+. Anal. Calcd for C22H22O4: C,
75.41; H, 6.33. Found: C, 75.64; H, 6.58.
Compound 2f: 75%; colorless oil; IR (film) 1766, 1726, 1054 cmÀ1 1H NMR
;
(300 MHz, CDCl3) d 1.59 (s, 3H), 2.15 (s, 3H), 3.65 (d, J = 14.7 Hz, 1H), 3.71 (d,
J = 14.7 Hz, 1H), 7.04–7.28 (m, 7H), 7.35–7.45 (m, 3H); 13C NMR (75 MHz,
CDCl3) d 19.78, 23.72, 30.33, 92.12, 126.71, 127.60, 128.32, 128.66, 128.94,
129.50, 129.89, 130.13, 137.31, 161.21, 172.97, 202.86; ESIMS m/z 307 [M+H]+.
Anal. Calcd for C20H18O3: C, 78.41; H, 5.92. Found: C, 78.16; H, 6.11.
Compound 2i: 95%; white solid, mp 85–86 °C; IR (KBr) 1769, 1726, 1678, cmÀ1
;
1H NMR (500 MHz, CDCl3) d 3.83 (d, J = 16.0 Hz, 1H), 3.99 (d, J = 16.0 Hz, 1H),
6.83–6.85 (m, 2H), 7.02 (d, J = 8.0 Hz, 1H), 7.20–7.90 (m, 10H), 7.37 (t,
J = 7.5 Hz, 1H), 7.50 (t, J = 8.0 Hz, 1H), 7.61 (d, J = 8.0 Hz, 1H), 7.76 (t,
5. For our recent contributions for the synthesis of butenolides and
a-methylene-
c
-butyrolactones, see: (a) Kim, K. H.; Lee, H. S.; Kim, S. H.; Lee, K. Y.; Lee, J.-E.;

334
S. H. Kim et al. / Tetrahedron Letters 54 (2013) 329–334
J = 7.5 Hz, 1H), 7.81 (d, J = 7.5 Hz, 1H); 13C NMR (125 MHz, CDCl3) d 30.74, ESIMS m/z 307 [M+H]+. Anal. Calcd for C20H18O3: C, 78.41; H, 5.92. Found: C,
63.73, 96.98, 125.01, 125.31, 125.32, 125.52, 126.70, 127.03, 128.01, 128.45,
128.59, 128.69, 128.90, 128.95, 129.33, 130.60, 131.93, 133.47, 136.58, 137.01,
137.36, 151.12, 157.82, 159.33, 174.50, 196.87; ESIMS m/z 441 [M+H]+. Anal.
Calcd for C31H20O3: C, 84.53; H, 4.58. Found: C, 84.74; H, 4.82.
78.73; H, 5.76.
10. The optimization of reaction conditions was briefly examined. The use of
Cu(OAc)2 or K2S2O8 as an oxidant was not effective, whereas Ag2CO3 showed a
similar reactivity to that of AgOAc. The amount of arenes could be reduced to
40 equiv; however, we used 60 equiv of arenes for the convenience of reaction.
The reaction of 1a with commercial Pd(OPiv)2 (benzene/AgOAc/PivOH, reflux,
24 h) showed very similar results (2a: 75%, 3a: 15%). For the preparation of
Pd(OPiv)2 from Pd(OAc)2 and PivOH in toluene, see: Ragaini, F.; Gasperini, M.;
Cenini, S.; Arnera, L.; Caselli, A.; Macchi, P.; Casati, N. Chem. Eur. J. 2009, 15,
8064–8077.
11. For the selected examples on Pd-catalyzed oxidative arylations with arenes,
see: (a) Obora, Y.; Ishii, Y. Molecules 2010, 15, 1487–1500; (b) Miyasaka, M.;
Hirano, K.; Satoh, T.; Miura, M. J. Org. Chem. 2010, 75, 5421–5424; (c) Yokota,
T.; Tani, M.; Sakaguchi, S.; Ishii, Y. J. Am. Chem. Soc. 2003, 125, 1476–1477; (d)
Tani, M.; Sakaguchi, S.; Ishii, Y. J. Org. Chem. 2004, 69, 1221–1226; (e) Jia, C.; Lu,
W.; Kitamura, T.; Fujiwara, Y. Org. Lett. 1999, 1, 2097–2100; (f) Zhang, Y.-H.;
Shi, B.-F.; Yu, J.-Q. J. Am. Chem. Soc. 2009, 131, 5072–5074; (g) Zhang, S.; Shi, L.;
Ding, Y. J. Am. Chem. Soc. 2011, 133, 20218–20229.
12. For the Pd-catalyzed Heck reaction with aryl iodide under the influence of
AgOAc/AcOH, see: Xu, D.; Lu, C.; Chen, W. Tetrahedron 2012, 68, 1466–1474.
13. (a) Bernini, R.; Cacchi, S.; De Salve, I.; Fabrizi, G. Synlett 2006, 2947–2952; (b)
Battistuzzi, G.; Bernini, R.; Cacchi, S.; De Salve, I.; Fabrizi, G. Adv. Synth. Catal.
2007, 349, 297–302.
14. The reason for the disruption of selectivity under Chen’s condition is not clear
at this stage. The compounds 2a and 3a were formed even at lower
temperature (80 °C); however, the ratio between 2a and 3a was almost same
with that of 110 °C.
Compound 2j: 80%; white solid, mp 165–167 °C; IR (KBr) 1768, 1727,
1602 cmÀ1 1H NMR (300 MHz, CDCl3) d 2.19 (s, 3H), 2.29 (s, 3H), 3.75 (d,
;
J = 17.1 Hz, 1H), 3.90 (d, J = 17.1 Hz, 1H), 6.43 (d, J = 7.5 Hz, 1H), 6.87–7.06 (m,
5H), 7.11 (t, J = 7.5 Hz, 1H), 7.22–7.35 (m, 5H), 7.49 (t, J = 7.8 Hz, 1H), 7.57 (d,
J = 7.8 Hz, 1H), 7.73 (t, J = 7.5 Hz, 1H), 7.80 (d, J = 7.5 Hz, 1H); 13C NMR (75 MHz,
CDCl3) d 19.07, 20.93, 29.60, 63.52, 97.17, 124.48, 125.29, 125.46, 125.96,
126.87, 127.69, 128.01, 128.46, 128.74, 129.07, 129.28, 130.17, 130.32, 130.49,
131.66, 133.36, 133.90, 135.17, 135.64, 136.80, 136.96, 150.98, 158.15, 158.74,
174.60, 197.08; ESIMS m/z 469 [M+H]+. Anal. Calcd for C33H24O3: C, 84.59; H,
5.16. Found: C, 84.23; H, 5.37.
Compound 3a: 19%; white solid, mp 84–86 °C; IR (KBr) 1762, 1646, 1450,
1230 cmÀ1 1H NMR (300 MHz, CDCl3) d 1.22 (s, 3H), 3.80 (s, 3H), 4.64 (d,
;
J = 1.8 Hz, 1H), 7.18–7.40 (m, 10H), 7.77 (d, J = 1.8 Hz, 1H); 13C NMR (75 MHz,
CDCl3) d 20.81, 52.44, 53.33, 84.80, 126.84, 128.23, 128.71 (2C), 129.17, 130.26,
130.67, 133.42, 136.63, 139.50, 171.26, 173.12; ESIMS m/z 345 [M+Na]+. Anal.
Calcd for C20H18O4: C, 74.52; H, 5.63. Found: C, 74.75; H, 5.61.
Compound 3b: 21%; white solid, mp 126–127 °C; IR (KBr) 1760, 1644, 1454,
1226 cmÀ1 1H NMR (300 MHz, CDCl3) d 1.22 (s, 3H), 2.12 (s, 3H), 2.20 (s, 3H),
;
3.79 (s, 3H), 4.63 (d, J = 1.8 Hz, 1H), 7.01–7.09 (m, 3H), 7.18–7.39 (m, 5H), 7.72
(d, J = 1.8 Hz, 1H); 13C NMR (75 MHz, CDCl3) d 19.62, 19.75, 20.86, 52.59, 53.31,
84.66, 125.27, 128.13, 128.52, 128.74, 129.10, 130.00, 131.05, 131.95, 136.95,
136.99, 139.74, 139.77, 171.55, 173.27; ESIMS m/z 351 [M+H]+. Anal. Calcd for
C22H22O4: C, 75.41; H, 6.33. Found: C, 75.74; H, 6.55.
Compound 3f: 16%; white solid, mp 112–113 °C; IR (KBr) 1758, 1721, 1644,
15. For an iodide ion-mediated dealkoxycarbonylation, see: (a) Lee, H. S.; Kim, S.
H.; Kim, Y. M.; Kim, J. N. Tetrahedron Lett. 2010, 51, 5071–5075; (b) Lee, M. J.;
Park, D. Y.; Lee, K. Y.; Kim, J. N. Tetrahedron Lett. 2006, 47, 1833–1837; (c)
Krapcho, A. P. ARKIVOC 2007, 1–53; (d) Krapcho, A. P. ARKIVOC 2007, 54–120.
1200 cmÀ1 1H NMR (300 MHz, CDCl3) d 1.08 (s, 3H), 2.34 (s, 3H), 4.82 (d,
;
J = 1.8 Hz, 1H), 7.20–7.36 (m, 10H), 7.76 (d, J = 1.8 Hz, 1H); 13C NMR (75 MHz,
CDCl3) d 21.01, 25.81, 50.38, 90.25, 126.69, 127.97, 128.68, 129.10, 130.42,
130.84, 133.17, 136.90, 140.08, 171.10, 209.63 (one carbon was overlapped);