Palladium-catalyzed arylation of methyl 2-(acetoxymethyl)acrylate: A convenient synthesis of rearranged Morita-Baylis-Hillman acetates

Article abstract of DOI:10.1016/j.tetlet.2012.11.026

Palladium-catalyzed arylation of methyl 2-(acetoxymethyl)acrylate with aryl iodides afforded the primary acetates of Morita-Baylis-Hillman adducts in good yields with high stereoselectivity under mild conditions (50°C).

Full text of DOI:10.1016/j.tetlet.2012.11.026

Tetrahedron Letters 54 (2013) 419–423
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Tetrahedron Letters
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Palladium-catalyzed arylation of methyl 2-(acetoxymethyl)acrylate: a
convenient synthesis of rearranged Morita–Baylis–Hillman acetates
⇑
Ko Hoon Kim, Jin Woo Lim, 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:
Palladium-catalyzed arylation of methyl 2-(acetoxymethyl)acrylate with aryl iodides afforded the pri-
mary acetates of Morita–Baylis–Hillman adducts in good yields with high stereoselectivity under mild
conditions (50 °C).
Received 3 October 2012
Revised 30 October 2012
Accepted 7 November 2012
Available online 14 November 2012
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Palladium
Morita–Baylis–Hillman acetates
Methyl 2-(acetoxymethyl)acrylate
Arylation
Chelation
Very recently, a palladium-catalyzed chelation-assisted aryla-
tion of allyl acetate has been examined extensively to provide cin-
namyl acetate via the selective b-H elimination process1,2 instead
of b-acetoxy elimination.3 As shown in Scheme 1, many research
groups have reported the arylation of allyl acetate with various
arene sources;1,2 however, there is no precedent reports on the
arylation of allyl acetate bearing an ester group at the 2-position
via the selective b-H elimination process, to the best of our knowl-
edge.3e–g
During the studies on the palladium-catalyzed oxidative aryla-
tion of alkenes with arenes,4 we presumed that the primary acetate
of Morita–Baylis–Hillman (MBH) adduct 2a could be synthesized
efficiently via a Pd-catalyzed chelation-assisted arylation of methyl
2-(acetoxymethyl)acrylate (1a),5,6 as shown in Scheme 1. The pri-
mary acetate 2a has been prepared most frequently via the rear-
rangement of an acetoxy group from the corresponding
secondary MBH acetate,7 and this compound has been widely used
in organic synthesis.7i–k
of 1a and benzene in the presence of Pd(TFA)2/AgOAc (2.5 equiv)/
PivOH (entry 3).4a–e The yield of 2a increased dramatically to
87%. Under the condition, a diphenyl compound 3a was not formed
even in the presence of an excess amount of AgOAc (6.0 equiv)
after 48 h. Although compound 2a was produced as an E/Z mixture
(12:1), we examined the reaction with other arenes such as
p-xylene, o-dichlorobenzene, m-dichlorobenzene, and m-xylene.
The reaction of 1a and p-xylene (entry 4) afforded 2b in high yield
(89%). However, a regioisomeric problem was observed when we
used o-dichlorobenzene and m-dichlorobenzene (entries 5 and 6),
although the combined yields of products were high (90–92%).
When we used m-xylene (entry 7), an inseparable regioisomeric
mixture was obtained in moderate yield (62%). The problematic
regioselectivity in combination with unsatisfactory stereoselectiv-
ity reduced the synthetic applicability of this method.
Thus, we decided to examine the reaction of 1a and iodoben-
zene, and the results of optimization of reaction conditions are
summarized in Table 2. When we examined the conditions of Jiao
employing an excess amount (2.0 equiv) of allyl acetate,2a com-
pound 2a was obtained in 80% (entry 1) with a similar stereoselec-
tivity (E/Z = 10:1). However, compound 1a is a valuable starting
material as compared to simple allyl acetate, thus we examined
the reaction with an equimolar amount of 1a in the presence of
2.0 equiv of iodobenzene (entry 2). Then, the yield of 2a decreased
to 35%, and the results stated that both compound 1a and allyl ace-
tate might be destroyed to some extent under the reaction condi-
tions. The yield of 2a was not improved by using an excess amount
of Ag2CO3 (entry 3). In these respects, we have to consider other
reaction conditions. Literature survey suggested that the condition
The starting material 1a was prepared by the acetylation of the
MBH adduct between formaldehyde and methyl acrylate as re-
ported.5 At the outset of our experiment, we examined the reaction
of 1a and benzene under the conditions of Jiao1b and Liu.1a How-
ever, the results of both conditions were disappointing. Compound
2a was obtained in very low yields, 20% and 9% respectively, as
shown in Table 1 (entries 1 and 2). Thus, we examined the reaction
⇑
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.2012.11.026

420
K. H. Kim et al. / Tetrahedron Letters 54 (2013) 419–423
X = H (Jiao, Liu)
X = I (Jiao)
OAc
X
OAc
+
+
X = B(OH)2 (Jiao)
X = N2BF4 (Correia)
COOMe
OAc
COOMe
and/or
OAc
X
This work
COOMe
1a
OAc
2a
(primary MBH acetate)
X = H or I
3a
Scheme 1.
Table 1
Pd-catalyzed oxidative arylation of compound 1aa
Entry Conditions
Productb (%)
1
Pd(OAc)2 (5 mol%), Ag2CO3 (0.6 equiv), CH3(CH2)3COOH (16 equiv) BQ (2.0 equiv), benzene
(100 equiv), reflux, 36 h
2a (20)
2
3
Pd(OAc)2 (10 mol %), AgOAc (2.0 equiv), DMSO (3.0 equiv) benzene (60 equiv), reflux, 12 h
Pd(TFA)2 (5 mol %), AgOAc (2.5 equiv), PivOH (6.0 equiv) benzene (60 equiv), reflux, 12 h
2a (9)
2a (87)c
COOMe
OAc
4
5
Pd(TFA)2 (5 mol %), AgOAc (2.5 equiv), PivOH (6.0 equiv) p-xylene (60 equiv), 110 °C, 12 h
Pd(TFA)2 (5 mol %), AgOAc (2.5 equiv), PivOH (6.0 equiv) o-dichlorobenzene (60 equiv), 110 °C, 12 h
2b (89)d
Cl
Cl
Cl
COOMe
OAc
Cl
Cl
COOMe
OAc
2c-ortho (40)e
e
2c
-meta (52)
Cl
COOMe
OAc
2d-ortho (17)e
Cl
COOMe
OAc
Pd(TFA)2 (5 mol %), AgOAc (2.5 equiv), PivOH (6.0 equiv) m-dichlorobenzene (60 equiv), 110 °C,
12 h
6
7
Cl
e
2d
-meta (73)
COOMe
OAc
COOMe
OAc
Pd(TFA)2 (5 mol %), AgOAc (2.5 equiv), PivOH (6.0 equiv) m-xylene (60 equiv), 110 °C, 12 h
2e-metae,f
2e-orthoe,f
a
b
c
d
e
f
Substrate 1a (0.5 mmol).
Isolated yield.
E/Z ratio = 12:1.
E/Z ratio = 11:1.
Variable amount of Z isomer (ca. 5–10%) was contaminated.
An inseparable mixture of 2e-meta and 2e-ortho (1:1) was obtained in 62% yield.
Table 2
Optimization of Pd-catalyzed arylation of 1a with iodobenzene
Entry
Conditions
Product (%)
1
2
3
4
1a (2.0 equiv), PhI (1.0 equiv), Pd(OAc)2 (5 mol %) Ag2CO3 (0.6 equiv), benzene, O2 balloon, reflux, 10 h
1a (1.0 equiv), PhI (2.0 equiv), Pd(OAc)2 (5 mol %) Ag2CO3 (0.6 equiv), benzene, O2 balloon, reflux, 12 h
1a (1.0 equiv), PhI (2.0 equiv), Pd(OAc)2 (5 mol %) Ag2CO3 (3.0 equiv), benzene, O2 balloon, reflux, 12 h
1a (1.0 equiv), PhI (1.1 equiv), Pd(OAc)2 (5 mol %) AgOAc (1.1 equiv), AcOH (50 equiv), reflux, 1 h
1a (1.0 equiv), PhI (2.1 equiv), Pd(OAc)2 (5 mol %) AgOAc (3.0 equiv), AcOH (50 equiv), reflux, 3 h
1a (1.0 equiv), PhI (1.1 equiv), Pd(OAc)2 (5 mol %) AgOAc (1.1 equiv), AcOH (50 equiv), 50 °C, 5 h
1a (1.0 equiv), PhI (1.1 equiv), Pd(OAc)2 (5 mol %) AgOAc (1.1 equiv), AcOH (50 equiv), 25 °C, 6 h
2a (80) + 3a (0)
2a (35) + 3a (0)
2a (23) + 3a (20)
2a (82)a + 3a (9)
2a (<5) + 3a (81)
2a (86)d + 3a (0)
2a (68)d + 3a (0)
5b
6c
7
a
b
c
E/Z = 13:1 (based on 1H NMR spectrum).
Selected as condition B.
Selected as condition A.
d
E/Z >32:1 (based on 1H NMR spectrum).
of Chen could be a choice.8,4a According to Chen’s condition, the
reaction of 1a and iodobenzene was examined in the presence of
Pd(OAc)2/AgOAc/AcOH (entry 4), and compound 2a was obtained
in good yield (82%). It is interesting to note that diaryl compound
3a could be synthesized in high yield (81%) by increasing the
amount of iodobenzene and AgOAc (entry 5).9,10 However, the
moderate stereoselectivity (E/Z = 13:1) was still
a problem,
although we could increase the yield of 2a up to 82% (entry 4).

K. H. Kim et al. / Tetrahedron Letters 54 (2013) 419–423
421
PdL
H
COOMe
OAc
Ph
Ph
H
AcO
COOMe
Ph
PdL
Ph
H
II (more favorable)
syn β-H elim.
PhPdL
2a-E (major)
rotation
1a
H
AcO
syn-carbopalladation
COOMe
PdL
H
OAc
COOMe
2a-Z (minor)
I
Ph
AcO
COOMe
H
III (less favorable)
Scheme 2.
Table 3
Pd-catalyzed mono- and diarylation of 1a
Entry
Iodoarene
Conditionsa/time (h)
Products (%)
I
A/5
B/3
2a (86) b + 3a (0)
2a (<5) + 3a (81)
1
COOMe
A/12
B/5
COOMe
OAc
I
2
OAc
(0)
2f
3f
b
2f
2f
3f
+
(85)
3f
(6) + (82)
COOMe
OAc
I
COOMe
OAc
A/12
B/10
3
2g
3g
2g (82)b + 3g (0)
2g (38) + 3g (0)
COOEt
I
COOMe
OAc
A/12
B/6
4
COOMe
EtOOC
EtOOC
2h
2h (83)b + 3h (0)
(5) +
EtOOC
OAc
3h
2h
3h
(79)
OMe
I
COOMe
OAc
A/9
B/4
5
COOMe
OAc
MeO
MeO
2i
MeO
3i
2i (75)b + 3i (7)
2i (4) + 3i (72)
a
Condition A: substrate 1a (0.5 mmol), iodoarene (1.1 equiv), Pd(OAc)2 (5 mol %), AgOAc (1.1 equiv), AcOH (50 equiv), 50 °C; Condition B: substrate 1a (0.5 mmol),
iodoarene (2.1 equiv), Pd(OAc)2 (5 mol %), AgOAc (3.0 equiv), AcOH (50 equiv), reflux.
b
Compounds 2a and 2f–i have their stereoisomers in small amounts, respectively, and the E/Z ratio was determined based on 1H NMR spectrum (2a and 2f–h: >32:1; 2i:
12:1).
The stereoselectivity has to be improved in order to be practically
useful. Thus we examined the reaction at lower temperature (en-
tries 6 and 7). To our delight, the reaction proceeded at 50 °C (entry
6) to give 2a in high yield (86%), and the E/Z selectivity increased to
>32:1 at the temperature.10 To our surprise, the reaction produced
2a even at room temperature (25 °C); however, the yield was mod-
erate (68%) as shown in entry 7.
The E/Z selectivity might be originated from the relative energy
difference between the two conformers II and III, as shown in
Scheme 2. The formation of 2a-E as a major product could be ex-
plained as follows. Syn-carbopalladation of a phenylpalladium spe-
cies onto the C@C double bond of 1a to form the alkylpalladium
intermediate I. A subsequent rotation around the C–C single bond
and syn b-H elimination would produce 2a. The conformer III is
less favorable than II due to the presence of a steric hindrance be-
tween the phenyl group and COOMe. In order to check the size ef-
fect of acetoxymethyl group of 1a on the stereoselectivity, we
examined the reaction of 2-(benzoyloxymethyl)acrylate and iodo-
benzene under the optimized conditions (vide supra, 50 °C, 4 h).
However, the stereoselectivity (E/Z = 24:1, 81%) of the correspond-
ing product decreased a little as compared to that of 1a (E/Z >32:1).
Encouraged by the results, we carried out the arylation of 1a
with various iodoarenes, and the results are summarized in Table 3.
The reactions were carried out under the condition A (entry 6 in

422
K. H. Kim et al. / Tetrahedron Letters 54 (2013) 419–423
COOMe
OAc
COOMe
OAc
4-iodo-m-xylene
COOMe
OAc
5-iodo-m-xylene
COOMe
OAc
1a
Condition A (12 h)
Condition B (6 h)
Condition A (9 h)
Condition B (10 h)
2e-meta
3e-meta
2e-ortho
3e-ortho
Condition A: 2e-meta (82) + 3e-meta (0)
Condition B: 2e-meta (4) + 3e-meta (77)
Condition A: 2e-ortho (79) + 3e-ortho (0)
Condition B: 2e-ortho (84) + 3e-ortho (0)
Scheme 3.
OMe
β
OMe
Ph
OAc
Ph
Pd(OAc)2 (5 mol%)
AgOAc (1.1 equiv)
γ
β
I
OAc Ph
+
Ph
OAc
AcOH (50 equiv)
γ
MeO
MeO
OAc
Ph
OAc
OMe
(1.1 equiv)
4
4
5
5
-Z
-E
-Z
-E
3
3
7
7
1
1
110 °C, 1 h: 80%
50 °C, 12 h: 66%
12
30
Scheme 4.
Table 2) and the condition B (entry 5 in Table 2) with some repre-
sentative iodoarenes. As shown in Table 3, rearranged MBH ace-
tates 2f–i were obtained in good yields (75–85%) under the
condition A. The stereochemistry of the MBH acetates 2f–h was
exclusively E (E/Z >32:1). For the p-methoxy derivative 2i, the ste-
reoselectivity was somewhat low (E/Z = 12:1) than other entries. It
is interesting to note that the diaryl derivative 3i was formed even
at 50 °C, albeit in low yield (7%). In contrast, diarylated MBH ace-
tates 3f, 3h, and 3i were produced as major products (72–82%) un-
der the condition B. However, compound 3g was not formed
presumably due to the steric hindrance between ortho-tolyl moie-
ties.2b,4d,i,8a,9a In order to examine the feasibility for the synthesis of
a differently-substituted diarylated product, we carried out the
reaction of 2f and p-methoxyiodobenzene (condition B, reflux,
7 h). The second arylation proceeded to give the corresponding
diarylated product in good yield (70%); however, an inseparable
mixture of E/Z (1:1) was produced presumably due to epimeriza-
tion of the alkylpalladium intermediate.
yields with high stereoselectivity (E/Z = 33:1) under the condition
A. Diarylated compound 3e-meta was obtained in good yield
(77%) under the condition B, whereas the reaction of 4-iodo-m-xy-
lene did not produce 3e-ortho due to steric reason as in the case of
2-iodotoluene (entry 3 in Table 3).
Nobody has reported the arylation of simple cinnamyl acetate,
although there have been reported numerous papers on the aryla-
tion of allyl acetate.1,2 Thus, we examined the reaction of cinnamyl
acetate and p-methoxyiodobenzene, as shown in Scheme 4. The
reaction provided four compounds. Both
c-aryl compounds (4-Z
and 4-E) and b-aryl compounds (5-Z and 5-E) were formed to-
gether and isolated as a mixture.11 At 110 °C, the ratio between
c-aryl and b-aryl was 3:4 while 19:31 at 50 °C. It is interesting to
note that the Z/E ratio increased a little by lowering the reaction
temperature.
As a next experiment, we examined the phenylation of nitrile
derivative 1b, as shown in Scheme 5. Although the phenylation
reaction proceeded similarly to afford 67a,g in moderate yield
(75%); however, the stereochemistry was not controlled even at
50 °C (6 h). The reason might be the small energy difference be-
tween the corresponding alkylpalladium intermediates II and III
(vide supra, Scheme 2).
In order to show the feasibility for the synthesis of 2e-meta and
2e-ortho (vide supra, entry 7 in Table 1), the reactions of 1a and the
corresponding iodoarenes were examined, as shown in Scheme 3.
Both compounds 2e-ortho and 2e-meta were obtained in high
The reaction of phenyl allyl ether 1c under the same reaction
conditions afforded an inseparable mixture of phenylated com-
pounds 7,12 as shown in Scheme 6. As compared to the regioselec-
tive b-H elimination in the case of 1a to form 2a via the
intermediate II that was stabilized by chelation,13 the correspond-
ing b-H elimination of intermediate IV can happen with either Ha
or Hb.
iodobenzene (1.1 equiv)
CN
Pd(OAc)2 (5 mol%)
Ph
OAc
OAc
AgOAc (1.1 equiv)
AcOH (50 equiv)
50 °C, 6 h
CN
6 (75%, E:Z = 2:1)
1b
Scheme 5.
iodobenzene (1.1 equiv)
- HaPdL or
- HbPdL
MeOOC PdL
Ph
COOMe
OPh
COOMe
OPh
COOMe
Pd(OAc)2 (5 mol%)
Ph
OPh
Hb
Ph
PhO
+
AgOAc (1.1 equiv)
AcOH (50 equiv)
50 °C, 12 h
Ha
HaHb
1c
IV
7 (72%, 2:1)
L
Pd
MeOOC
Ar
ArPdL
- HaPdL
O
2a
1a
O
Me
Ha Ha
II
Scheme 6.

K. H. Kim et al. / Tetrahedron Letters 54 (2013) 419–423
423
8. For the selected examples on Pd-catalyzed Heck reaction with aryl iodide
under the influence of AgOAc/AcOH, see: (a) Xu, D.; Lu, C.; Chen, W. Tetrahedron
2012, 68, 1466–1474; (b) Guo, H.-M.; Rao, W.-H.; Niu, H.-Y.; Jiang, L.-L.; Liang,
L.; Zhang, Y.; Qu, G.-R. RSC Adv. 2011, 1, 961–963.
9. For the synthesis of tetrasubstituted allylic alcohols and their synthetic
applications, see: (a) He, Z.; Kirchberg, S.; Frohlich, R.; Studer, A. Angew.
Chem., Int. Ed. 2012, 51, 3699–3702; (b) Xie, M.; Lin, G.; Zhang, J.; Li, M.; Feng, C.
J. Organomet. Chem. 2010, 695, 882–886; (c) Yang, Y.; Zhu, S.-F.; Zhou, C.-Y.;
Zhou, Q.-L. J. Am. Chem. Soc. 2008, 130, 14052–14053; (d) Zhang, D.-H.; Dai, L.-
Z.; Shi, M. Eur. J. Org. Chem. 2010, 5454–5459; (e) Novoa, A.; Pellegrini-Moise,
N.; Bourg, S.; Thoret, S.; Dubois, J.; Aubert, G.; Cresteil, T.; Chapleur, Y. Eur. J.
Med. Chem. 2011, 46, 3570–3580; (f) Aoki, M.; Izumi, S.; Kaneko, M.; Ukai, K.;
Takaya, J.; Iwasawa, N. Org. Lett. 2007, 9, 1251–1253.
In summary, the primary acetates of Morita–Baylis–Hillman ad-
ducts were synthesized via a palladium-catalyzed arylation of
methyl 2-(acetoxymethyl)acrylate with aryl iodides in good yield
in a highly stereoselective manner under mild conditions (50 °C).
Acknowledgments
This research was supported by Basic Science Research Program
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.
10. Typical procedure for the synthesis of 2a: A mixture of 1a (79 mg, 0.5 mmol),
iodobenzene (112 mg, 1.1 equiv), Pd(OAc)2 (6 mg, 5 mol%), AgOAc (92 mg,
1.1 equiv), and AcOH (1.5 g, 50 equiv) was heated to 50 °C for 5 h. After the
aqueous extractive workup and column chromatographic purification process
(hexanes/Et2O, 20:1), the product 2a was isolated as a colorless oil, 101 mg
(86%). Other compounds were synthesized similarly, and the selected
spectroscopic data of unknown compounds 2b, 2e-meta, 2e-ortho, 2h, 3a, 3e-
meta, 3f, and 3i are as follows.
References and notes
1. For the palladium-catalyzed chelation-assisted arylation of allyl esters with
arenes, see: (a) Shang, X.; Xiong, Y.; Zhang, Y.; Zhang, L.; Liu, Z.-Q. Synlett 2012,
259–262; (b) Pan, D.; Yu, M.; Chen, W.; Jiao, N. Chem. Asian J. 2010, 5, 1090–
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1577–1588. and further references cited therein.
2. For the palladium-catalyzed chelation-assisted arylation of allyl esters with
aryl halides, arylboronic acids, and arenediazonium salts, see: (a) Pan, D.; Chen,
A.; Su, Y.; Zhou, W.; Li, S.; Jia, W.; Xiao, J.; Liu, Q.; Zhang, L.; Jiao, N. Angew.
Chem., Int. Ed. 2008, 47, 4729–4732; (b) Su, Y.; Jiao, Ning Org. Lett. 2009, 11,
2980–2983; (c) Moro, A. V.; Cardoso, F. S. P.; Correia, C. R. D. Org. Lett. 2009, 11,
3642–3645.
3. For the palladium-catalyzed arylation of allylic esters involving b-OAc
elimination, see: (a) Liu, Y.; Yao, B.; Deng, C.-L.; Tang, R.-Y.; Zhang, X.-G.; Li, J.-
H. Org. Lett. 2011, 13, 1126–1129; (b) Yao, B.; Liu, Y.; Wang, M.-K.; Li, J.-H.; Tang,
R.-Y.; Zhang, X.-G.; Deng, C.-L. Adv. Synth. Catal. 2012, 354, 1069–1076; (c) Mino,
T.; Koizumi, T.; Suzuki, S.; Hirai, K.; Kajiwara, K.; Sakamoto, M.; Fujita, T. Eur. J.
Org. Chem. 2012, 678–680; (d) Yuan, F.-Q.; Sun, F.-Y.; Han, F.-S. Tetrahedron
2012, 68, 6837–6842; (e) Mariampillai, B.; Herse, C.; Lautens, M. Org. Lett. 2005,
7, 4745–4747; Ma and co-workers have also reported the palladium-catalyzed
reaction of indole and methyl 2-(acetoxymethyl)acrylate involving a b-OAc
elimination, see: (f) Ma, S.; Yu, S. Tetrahedron Lett. 2004, 45, 8419–8422; (g) Ma,
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4. For our recent contributions on the palladium-catalyzed arylation with arenes,
see: (a) Lee, H. S.; Kim, K. H.; Kim, S. H.; Kim, J. N. Adv. Synth. Catal. 2012, 354,
2419–2426; (b) Kim, K. H.; Lee, S.; Kim, S. H.; Lim, C. H.; Kim, J. N. Tetrahedron Lett.
2012, 53, 5088–5093; (c) Kim, K. H.; Lee, H. S.; Kim, J. N. Tetrahedron Lett. 2011,
52, 6228–6233; (d) Kim, K. H.; Lee, H. S.; Kim, S. H.; Kim, J. N. Tetrahedron Lett.
2012, 53, 2761–2764; (e) 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: (f) Lafrance, M.;
Fagnou, K. J. Am. Chem. Soc. 2006, 128, 16496–16497; (g) Stuart, D. R.; Fagnou, K.
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Compound 2b: 89%; colorless oil; IR (film) 1741, 1721, 1234 cmÀ1 1H NMR
;
(CDCl3, 300 MHz) d 2.06 (s, 3H), 2.25 (s, 3H), 2.30 (s, 3H), 3.85 (s, 3H), 4.84 (s,
2H), 6.98 (s, 1H), 7.01–7.14 (m, 2H), 8.04 (s, 1H); 13C NMR (CDCl3, 75 MHz) d
19.33, 20.79, 20.91, 52.13, 59.42, 127.17, 129.20, 129.95, 130.01, 133.31,
133.80, 135.21, 144.92, 167.05, 170.46; ESIMS m/z 285 [M+Na]+. Anal. Calcd for
C
15H18O4: C, 68.68; H, 6.92. Found: C, 68.53; H, 7.03.
Compound 2e-meta: 82%; colorless oil; IR (film) 1742, 1718, 1234 cmÀ1
;
1H
NMR (CDCl3, 300 MHz) d 2.03 (s, 3H), 2.25 (s, 6H), 3.76 (s, 3H), 4.88 (s, 2H), 6.91
(s, 2H), 6.94 (s, 1H), 7.86 (s, 1H); 13C NMR (CDCl3, 75 MHz) d 20.83, 21.20,
52.15, 59.37, 126.13, 127.17, 131.23, 134.03, 138.13, 145.86, 167.35, 170.60;
ESIMS m/z 285 [M+Na]+. Anal. Calcd for C15H18O4: C, 68.68; H, 6.92. Found: C,
68.85; H, 6.97.
Compound 2e-ortho: 79%; colorless oil; IR (film) 1742, 1720, 1240 cmÀ1 1H
;
NMR (CDCl3, 300 MHz) d 2.00 (s, 3H), 2.20 (s, 3H), 2.25 (s, 3H), 3.77 (s, 3H), 4.77
(s, 2H), 6.94 (d, J = 7.8 Hz, 1H), 6.96 (s, 1H), 7.01 (d, J = 7.8 Hz, 1H), 7.97 (s, 1H);
13C NMR (CDCl3, 75 MHz) d 19.18, 20.87, 21.16, 52.13, 59.53, 126.60, 126.71,
128.66, 130.55, 131.02, 137.04, 139.48, 144.71, 167.20, 170.59; ESIMS m/z 285
[M+Na]+. Anal. Calcd for C15H18O4: C, 68.68; H, 6.92. Found: C, 68.59; H, 6.77.
Compound 2h: 83%; colorless oil; IR (film) 1742, 1721, 1243 cmÀ1 1H NMR
;
(CDCl3, 300 MHz) d 1.40 (t, J = 7.2 Hz, 3H), 2.10 (s, 3H), 3.86 (s, 3H), 4.39 (q,
J = 7.2 Hz, 2H), 4.92 (s, 2H), 7.44 (d, J = 8.4 Hz, 2H), 7.99 (s, 1H), 8.08 (d,
J = 8.4 Hz, 2H); 13C NMR (CDCl3, 75 MHz) d 14.25, 20.85, 52.41, 59.00, 61.19,
128.42, 129.18, 129.80, 131.11, 138.41, 144.08, 165.86, 166.88, 170.50; ESIMS
m/z 329 [M+Na]+. Anal. Calcd for C16H18O6: C, 62.74; H, 5.92. Found: C, 62.92;
H, 5.69.
Compound 3a: 81%; colorless oil; IR (film) 1741, 1720, 1231 cmÀ1 1H NMR
;
(CDCl3, 300 MHz) d 2.09 (s, 3H), 3.51 (s, 3H), 4.82 (s, 2H), 7.11–7.16 (m, 2H),
7.17–7.23 (m, 2H), 7.27–7.31 (m, 3H), 7.32–7.37 (m, 3H); 13C NMR (CDCl3,
75 MHz) d 20.88, 51.77, 64.11, 126.54, 128.01, 128.30, 128.36, 128.56, 128.70,
129.30, 139.49, 141.27, 153.27, 169.39, 170.56; ESIMS m/z 333 [M+Na]+. Anal.
Calcd for C19H18O4: C, 73.53; H, 5.85. Found: C, 73.32; H, 5.96.
Compound 3e-meta: 77%; colorless oil; IR (film) 1742, 1717, 1230 cmÀ1 1H
;
NMR (CDCl3, 300 MHz) d 2.01 (s, 3H), 2.19 (s, 6H), 2.20 (s, 6H), 3.44 (s, 3H), 4.70
(s, 2H), 6.68 (s, 2H), 6.73 (s, 2H), 6.86 (s, 1H), 6.89 (s, 1H); 13C NMR (CDCl3,
75 MHz) d 20.90, 21.18, 21.24, 51.71, 64.26, 125.95, 126.24, 126.94, 130.07,
130.27, 137.38, 137.67, 139.44, 141.18, 154.12, 169.73, 170.54; ESIMS m/z 389
[M+Na]+. Anal. Calcd for C23H26O4: C, 75.38; H, 7.15. Found: C, 75.16; H, 7.18.
5. For
the
synthesis
and
synthetic
applications
of
methyl
2-
(acetoxymethyl)acrylate, see: (a) Du, Y.; Feng, J.; Lu, X. Org. Lett. 2005, 7,
1987–1989; (b) Mandal, S. K.; Paira, M.; Roy, S. C. J. Org. Chem. 2008, 73, 3823–
3827; (c) Zhuang, Z.; Pan, F.; Fu, J.-G.; Chen, J.-M.; Liao, W.-W. Org. Lett. 2011,
13, 6164–6167; (d) Pan, F.; Chen, J.-M.; Zhuang, Z.; Fang, Y.-Z.; Zhang, S. X.-A.;
Liao, W.-W. Org. Biomol. Chem. 2012, 10, 2214–2217; (e) Adak, L.; Bhadra, S.;
Chattopadhyay, K.; Ranu, B. C. New J. Chem. 2011, 35, 430–437; (f) Dey, R.;
Chattopadhyay, K.; Ranu, B. C. J. Org. Chem. 2008, 73, 9461–9464; (g) Adak, L.;
Chattopadhyay, K.; Ranu, B. C. J. Org. Chem. 2009, 74, 3982–3985; (h) Qi, J.;
Porco, J. A., Jr. J. Am. Chem. Soc. 2007, 129, 12682–12683; (i) Kazmaier, U.;
Schmidt, C. Synthesis 2009, 2435–2439.
Compound 3f: 82%; pale yellow oil; IR (film) 1742, 1718, 1231 cmÀ1 1H NMR
;
(CDCl3, 300 MHz) d 2.01 (s, 3H), 2.26 (s, 3H), 2.27 (s, 3H), 3.46 (s, 3H), 4.74 (s,
2H), 6.89–6.95 (m, 2H), 6.96–7.10 (m, 6H); 13C NMR (CDCl3, 75 MHz) d 20.91,
21.20, 21.23, 51.73, 64.48, 125.40, 128.66, 128.68, 128.92, 129.38, 136.89,
138.29, 138.57, 138.70, 153.78, 169.69, 170.61; ESIMS m/z 361 [M+Na]+. Anal.
Calcd for C21H22O4: C, 74.54; H, 6.55. Found: C, 74.51; H, 6.81.
Compound 3i: 72%; colorless oil; IR (film) 1739, 1716, 1605, 1512, 1249 cmÀ1
;
1H NMR (CDCl3, 300 MHz) d 2.03 (s, 3H), 3.47 (s, 3H), 3.73 (s, 3H), 3.74 (s, 3H),
4.76 (s, 2H), 6.74 (d, J = 9.0 Hz, 2H), 6.78 (d, J = 9.0 Hz, 2H), 6.98 (d, J = 9.0 Hz,
2H), 7.05 (d, J = 9.0 Hz, 2H); 13C NMR (CDCl3, 75 MHz) d 20.97, 51.74, 55.17,
55.24, 64.84, 113.34, 113.58, 124.31, 130.40, 131.17, 132.23, 134.03, 153.50,
159.82, 160.07, 170.01, 170.70; ESIMS m/z 393 [M+Na]+. Anal. Calcd for
6. Very recently, a palladium-catalyzed arylation of methyl 2-(acetoxymethyl)acrylate
with triarylbismuth reagent has been reported involving a b-OAc elimination, see:
Rao, M. L. N.; Giri, S. Eur. J. Org. Chem. 2012, 4580–4589.
C
21H22O6: C, 68.10; H, 5.99. Found: C, 68.42; H, 5.73.
7. For the synthesis of MBH acetates and their synthetic applications, see: (a)
Basavaiah, D.; Muthukumaran, K.; Sreenivasulu, B. Synthesis 2000, 545–548; (b)
Kabalka, G. W.; Venkataiah, B.; Dong, G. Tetrahedron Lett. 2003, 44, 4673–4675;
(c) Liu, Y.; Mao, D.; Qian, J.; Lou, S.; Xu, Z.; Zhang, Y. Synthesis 2009, 1170–1174;
(d) Ollevier, T.; Mwene-Mbeja, T. M. Tetrahedron 2008, 64, 5150–5155; (e) Park,
J. B.; Ko, S. H.; Kim, B. G.; Hong, W. P.; Lee, K.-J. Bull. Korean Chem. Soc. 2004, 25,
27–28; (f) Park, J.; Heo, R.; Kim, J.-Y.; Yoo, B. W.; Yoon, C. M. Bull. Korean Chem.
Soc. 2009, 30, 1195–1197; (g) Shanmugam, P.; Rajasingh, P. Tetrahedron 2004,
60, 9283–9295; (h) Sa, M. M.; Meier, L.; Fernandes, L.; Pergher, S. B. C. Catal.
Commun. 2007, 8, 1625–1629; (i) Lee, M. J.; Lee, K. Y.; Kim, J. N. Bull. Korean
Chem. Soc. 2005, 26, 477–480; (j) Garrido, N. M.; Garcia, M.; Sanchez, M. R.;
Diez, D.; Urones, J. G. Synlett 2010, 387–390; (k) Garrido, N. M.; Garcia, M.; Diez,
D.; Sanchez, M. R.; Sanz, F.; Urones, J. G. Org. Lett. 2008, 10, 1687–1690.
11. The mixture of four acetates was hydrolyzed to the corresponding alcohols
with K2CO3 in aqueous MeOH, and the structures of 4 and 5 were identified by
comparison with the reported data, see: (a) Ebner, C.; Pfaltz, A. Tetrahedron
2011, 67, 10287–10290; (b) Calo, V.; Nacci, A.; Monopoli, A.; Ferola, V. J. Org.
Chem. 2007, 72, 2596–2601.
12. (a) Basavaiah, D.; Bakthadoss, M.; Pandiaraju, S. Chem. Commun. 1998, 1639–
1640; (b) Kim, S. H.; Kim, S. H.; Kim, J. N. Bull. Korean Chem. Soc. 2008, 29, 2039–
2042; (c) Nasiri, F.; Malakutikhah, D. Monatsh. Chem. 2011, 142, 807–812; (d)
Itoh, S.; Araki, T. WO 2009/064031 (Chem. Abstr. 2009, 150, 539329).
13. The b-H elimination with the ring proton is somewhat difficult because syn-
periplanarity between the C–H and C–Pd bonds would be difficult, as noted in
our previous paper.4a