Synthesis of dihydroindenofuran scaffold via a Pd-catalyzed 5-endo-trig cyclization/enolate O-alkylation cascade

Article abstract of DOI:10.1016/j.tetlet.2010.06.127

An efficient synthesis of dihydroindenofurans was carried out starting from the Baylis-Hillman adducts via a Pd-catalyzed 5-endo-trig-carbopalladation and enolate O-alkylation cascade as a key step. This is the first example of enolate O-alkylation with a C(sp³)-bound palladium intermediate.

Full text of DOI:10.1016/j.tetlet.2010.06.127

Tetrahedron Letters 51 (2010) 4648–4652
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Tetrahedron Letters
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Synthesis of dihydroindenofuran scaffold via a Pd-catalyzed 5-endo-trig
cyclization/enolate O-alkylation cascade
Eun Sun Kim a, Ko Hoon Kim a, Sunhong Park b, Jae Nyoung Kim a,
*
a Department of Chemistry and Institute of Basic Science, Chonnam National University, Gwangju 500-757, Republic of Korea
b Department of Chemistry and Research Institute of Natural Science, Gyeongsang National University, Jinju 660-701, Republic of Korea
a r t i c l e i n f o
a b s t r a c t
Article history:
An efficient synthesis of dihydroindenofurans was carried out starting from the Baylis–Hillman adducts
via a Pd-catalyzed 5-endo-trig-carbopalladation and enolate O-alkylation cascade as a key step. This is the
first example of enolate O-alkylation with a C(sp3)-bound palladium intermediate.
Ó 2010 Elsevier Ltd. All rights reserved.
Received 26 May 2010
Revised 23 June 2010
Accepted 28 June 2010
Available online 3 July 2010
Keywords:
Palladium
Enolate O-alkylation
Dihydroindenofurans
Baylis–Hillman adducts
The palladium-catalyzed C-arylation reaction of a ketone eno-
late with haloarenes is a powerful method for the construction of
a
5-endo-trig-carbopalladation and enolate O-alkylation cascade, as
shown in Scheme 1. Numerous dihydrofuran moiety-containing
tri- and6 polycyclic7 compounds were found in biologically impor-
tant natural products, and the construction of these scaffolds has
received much attention.6,7 Pd-catalyzed O-arylations between
arylpalladium intermediates and enolates have been reported as
described above;3 however, an intramolecular O-alkylation
between alkylpalladium intermediate and an enolate has not been
reported, to the best of our knowledge.3h,i
Two cinnamyl bromides, 1a and 1b, were prepared from the
corresponding Baylis–Hillman adducts with HBr according to the
reported method.8,9 The starting materials 3a–j were prepared by
the reactions of 1a and 1b with active methylene compounds
2a–f, as shown in Table 1. Introduction of 2a–f at the secondary po-
sition of the cinnamyl bromides was carried out in CH3CN in the
presence of DABCO and additional base such as NaOH or K2CO3
depending on the substrates, as reported.9,10 When we used 2a
and 2c–e, the corresponding products were formed as a syn/anti
mixture, and the separation was somewhat difficult. However,
the stereochemistry of 3 would not affect the Pd-catalyzed cycliza-
tion because the reaction would involve an enolate intermediate as
shown in Scheme 1, thus we used a syn/anti mixture for the Pd-cat-
alyzed reaction without separation.11
-aryl ketones that has demonstrated excellent substrate scope.1
The reactions with the enolates of ester and malonate have also
been reported.2 However, all the reactions provided C-arylated
products. Intramolecular O-arylation could be realized when the
enolate and aryl halide are present together in the same molecule
and when the competitive C-arylation is difficult at the same time.
Recently, a Pd-catalyzed intramolecular O-arylation has been
applied for the synthesis of many interesting compounds including
benzofurans and isocoumarins.3
The Baylis–Hillman reaction, which involves the coupling of
activated vinylic compounds with electrophiles under the catalytic
influence of a tertiary amine, gives rise to adducts, so called Baylis–
Hillman adducts, with a new stereocenter and has proven to be a
very useful carbon–carbon bond-forming method in the synthesis
of highly functionalized molecules.4 The chemical transformations
of Baylis–Hillman adducts provided many interesting compounds
and are well documented in many review articles.4 The Baylis–Hill-
man adducts could also supply various substrates that can be used
in the Pd-catalyzed reaction to furnish valuable compounds.4g,5 As
an example, a Pd-catalyzed domino reaction with modified Baylis–
Hillman adducts has been used for the synthesis of tetracyclic but-
terfly-like scaffold.5a
Initially, we examined the Pd-catalyzed reaction of 3a, as a
representative example, under various conditions, as shown in
Table 2. The use of Et3N in DMF was totally ineffective either at
70–80 °C or at higher temperature (entries 1 and 2). The use of
Cs2CO3 in toluene afforded 4a in 57% isolated yield (entry 3).10
The use of TBAB/K2CO3 both in DMF and CH3CN produced 4a in
During the studies5 we reasoned out that dihydroindenofuran
scaffold could be constructed in a one-pot via the intramolecular
* 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 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.06.127

E. S. Kim et al. / Tetrahedron Letters 51 (2010) 4648–4652
Ph
4649
Ph
Ph
H
OH
Ph
Ph
Ph
EWG
O
EWG
O
Pd(0)
O
EWG
Br
EWG
2nd bond formation
(enolate O-alkylation)
Br
Br
1st bond formation
B-H adducts
(5-endo-carbopalladation)
Scheme 1.
Table 1
Preparation of starting materials 3a–j
COOMe
Br
R2
OH
R1
Br
deoxybenzoin (2a)
acetophenone (2b)
desoxyanisoin (2c)
ethyl benzoylacetate (2d)
methyl acetoacetate (2e)
acetylacetone (2f)
(i) DABCO (1.1 equiv)
CH3CN, rt, 30 min
EWG1
O
EWG
1a (92%)
Ref. 8
(ii) 2a-f (1.2 equiv)
base (1.2 equiv)
rt, 5-48 h
Br
Br
Br
CN
Br
3a-j
1b (86%)
Entry
Substrates
1a + 2a
R1/R2/EWG
Base/Time (h)
Productsa (%)
1
2
3
4
5
6
7
8
9
10
Ph/Ph/COOMe
H/Ph/COOMe
Ph/Ph/CN
p-MeOPh/p-MeOPh/CN
COOEt/Ph/COOMe
COOEt/Ph/CN
COOMe/Me/COOMe
COOMe/Me/CN
COOMe/Me/COOMe
COOMe/Me/CN
NaOH/48
NaOH/48
NaOH/48
NaOH/24
K2CO3/5
K2CO3/24
K2CO3/24
K2CO3/24
K2CO3/24
K2CO3/24
3a (85, 2/1)
3b (56)
1a + 2bb
1b + 2a
1b + 2c
1a + 2d
1b + 2d
1a + 2e
1b + 2e
1a + 2f
1b + 2f
3c (89, 3/2)
3d (83, 3/2)
3e (83, 3/2)
3f (90, 3/2)
3g (68, 1/1)
3h (85, 1/1)
3i (83)
3j (88)
a
Isolated yield and the ratio of syn/anti in the parenthesis was based on 1H NMR.
Excess amounts (3.0 equiv) of 2b was used. Otherwise the yield of a bis alkylation product was increased.
b
endo-trig-carbopalladation12 to form the palladium intermediate
(II), and the following coupling with enolate to produce
dihydroindenofuran 4a. The structure of 4a was confirmed to be
dihydroindenofuran (exactly, 3a,8-dihydro-1-oxacyclopenta[a] in-
dene) by its HMBC and NOE data, as shown in Figure 1. The struc-
ture of dihydroindenofuran and the cis-ring junction (cis around
3a- and 8a-positions) was confirmed unequivocally by the X-ray
crystal structure of 4g (vide infra),13 as shown in Figure 2.
Encouraged by the results, we carried out the synthesis of var-
ious dihydroindenofurans with 3b–j under the optimized condi-
tions (entry 3 in Table 2), and the results are summarized in
Table 3. As shown in Table 3, the yields of products were highly
dependent on the substrates. The reaction of deoxybenzoin deriv-
ative 3c (entry 3) showed a similar result with that of 3a, while the
reaction of acetophenone derivative 3b produced 4b in low yield
(entry 2) presumably due to low enolate content of the acetophe-
none moiety. Desoxyanisoin derivative 3d also showed a low yield
of 4d due to a similar reason, and the reaction required a long reac-
tion time (entry 4). As expected from the results of entries 1–4,
Table 2
Optimization of reaction conditions for the synthesis of 4a
Entry Conditionsa
Yield (%)
1
2
PPh3 (20 mol %), Et3N (2.0 equiv), DMF, 70–80 °C, 2 h
PPh3 (20 mol %), Et3N (2.0 equiv), DMF, 110–120 °C,
30 min
Sluggish
Decompose
3
4
5
PPh3 (20 mol %), Cs2CO3 (2.0 equiv), toluene, reflux, 1 h 57
TBAB (1.0 equiv), K2CO3 (2.0 equiv), DMF, 70–80 °C, 2 h 27
TBAB (1.0 equiv), K2CO3 (2.0 equiv), CH3CN, reflux, 18 h 20
a
Pd(OAc)2 (10 mol %) is common.
low yield (20–27%) along with many intractable side products (en-
tries 4 and 5). As is often the case in the Pd-catalyzed coupling
reactions of aryl bromide and a ketone enolate,3a–d the use of
Cs2CO3 in toluene showed the best results.
The mechanism for the formation of 4a could be postulated as
shown in Scheme 2. Oxidative addition of Pd(0) to form (I), 5-
Ph
Ph
Ph
Ph
Ph
3
Ph
O
Pd(OAc)2/PPh3
H
O
4
7
- Pd(0)
- HBr
3a
8a
COOMe
3a
O1
COOMe
Cs2CO3
toluene, reflux
PdBr
COOMe
PdBr
(I)
8
4a
(II)
Scheme 2.

4650
E. S. Kim et al. / Tetrahedron Letters 51 (2010) 4648–4652
Table 3
Pd-catalyzed synthesis of dihydroindenofurans 4a
δ=7.25-7.34
H
Entry
3
Time (h)
Product 4 (%)
δ=6.72 (d)
H
H
Ph
H
O
Ph
4a (57)
4b (42)
1
3a
1
COOMe
O
H
H
H
δ=3.75 (AB quartet)
COOMe
δ=7.25-7.34
H
Ph
Figure 1. Selected HMBC (C?H) and NOE (H?H) correlations for 4a.
H
2
3b
3c
3d
3e
3f
12
22
22
1
O
COOMe
Ph
H
Ph
4c (62)
3
O
CN
Ar
H
Ar
4b
4d (31)
O
CN
EtOOC
H
Ph
4e (80)
5
O
COOMe
EtOOC
H
Ph
4f (41)
6
12
1
O
CN
MeOOC
H
Me
4g (74)
7
3g
3h
3i
O
COOMe
MeOOC
H
Me
Figure 2. ORTEP drawing of compound 4g.
4h (28)
8
2
O
higher yields of dihydroindenofurans were expected for the sub-
strates 3e–j that has higher enol contents. The expectation was
found to be correct, and the yields of dihydroindenofurans were
good (74–81%) for the ester derivatives 3e, 3g, and 3i (entries 5,
7 and 9); however, the yields of dihydroindenofurans having a ni-
trile group (4f, 4h and 4j) were very low (26–41%), as shown in en-
tries 6, 8, and 10. The formation of many intractable side products
was observed, but the reason is not clear at this stage.
As a next entry, we examined the synthesis of a dihydrofuran
moiety-containing pentacyclic compound 4k using 1a and a-tetra-
lone (2g), as shown in Scheme 3. The starting material 3k was pre-
pared in 68% yield using the procedure in Table 1. The next Pd-
catalyzed cyclization of 3k under the same conditions afforded
4k in a reasonable yield (35%).
CN
MeOC
H
Me
4i (81)
9
1
O
COOMe
MeOC
H
Me
4j (26)
10
3j
1
O
CN
a
Conditions: compound 3 (1.0 mmol), Pd(OAc)2 (10 mol %), PPh3 (20 mol %),
Cs2CO3 (2.0 equiv), toluene, reflux, 22 h.
b
Ar is p-methoxyphenyl.
O
(i) DABCO (1.1 equiv)
CH3CN, rt, 30 min
O
same conditions
2 h
1a
+
(ii) 2g (3.0 equiv)
NaOH (1.2 equiv)
rt, 48 h
COOMe
O
COOMe
2g
Br
4k (35%)
3k (68%, 3/1)
Scheme 3.

E. S. Kim et al. / Tetrahedron Letters 51 (2010) 4648–4652
4651
9. For the introduction of nucleophiles at the secondary position of Baylis–
Hillman adducts, see Kim, E. S.; Kim, K. H.; Kim, S. H.; Kim, J. N. Tetrahedron Lett.
2009, 50, 5098–5101. and further references cited therein.
In summary, we disclosed an efficient synthesis of dihydroinde-
nofu rans starting from the Baylis–Hillman adducts via the Pd-cat-
alyzed 5-endo-trig-carbopalladation and enolate O-alkylation
cascade as a key step. This is the first example of enolate O-alkyl-
ation with a C(sp3)-bound palladium intermediate.
10. Typical procedure for the synthesis of 3a: To a solution of 1a (668 mg, 2.0 mmol)
in CH3CN (5 mL) was added DABCO (246 mg, 2.2 mmol) and the reaction
mixture was stirred at room temperature for 30 min. Deoxybenzoin (2a,
470 mg, 2.4 mmol) and NaOH (96 mg, 2.4 mmol) were added to the solution
and the reaction mixture was stirred at room temperature for 48 h. After the
usual aqueous workup and column chromatographic purification process
(hexanes/CH2Cl2/diethyl ether, 15:1:1) 3a was isolated as a syn/anti (2:1)
mixture, 763 mg, (85%). Other starting materials 3b–k were prepared similarly,
and compounds 3c–h and 3k were isolated as syn/anti mixtures. Selected
spectroscopic data of 3a, 3b, and 3i are as follows. Analytically pure samples of
major-3a and minor-3a were obtained by careful column chromatography, and
the stereochemistry was not confirmed.
Acknowledgments
This work was supported by the National Research Foundation
of Korea Grant funded by the Korean Government (2010-0015675).
Spectroscopic data were obtained from the Korea Basic Science
Institute, Gwangju branch.
Compound 3a (major): white solid, mp 157–159 °C; IR (KBr) 1722, 1680,
1268 cmÀ1 1H NMR (CDCl3, 300 MHz) d 3.64 (s, 3H), 5.40–5.49 (m, 2H), 5.78 (s,
;
1H), 6.28 (s, 1H), 6.91 (t, J = 7.8 Hz, 1H), 7.04–7.09 (m, 3H), 7.11–7.21 (m, 3H),
7.28 (d, J = 7.8 Hz, 1H), 7.37–7.43 (m, 3H), 7.47–7.52 (m, 1H), 7.98–8.01 (m,
2H); 13C NMR (CDCl3, 75 MHz) d 48.16, 51.77, 57.11, 125.44, 126.02, 126.94,
127.22, 127.93, 128.23, 128.49, 128.58, 129.23, 129.56, 132.93, 133.01, 135.12,
136.64, 138.84, 141.43, 166.63, 197.81; ESIMS m/z 449 (M++1), 451 (M++3).
Anal. Calcd for C25H21BrO3: C, 66.82; H, 4.71. Found: C, 67.03; H, 4.82.
Compound 3a (minor): white solid, mp 127–129 °C; IR (KBr) 1717, 1682,
References and notes
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Hamann, B. C.; Hartwig, J. F. J. Am. Chem. Soc. 1997, 119, 12382–12383; (b)
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2. For the Pd-catalyzed intermolecular C-arylation of ester enolate or malonate,
see: (a) Moradi, W. A.; Buchwald, S. L. J. Am. Chem. Soc. 2001, 123, 7996–8002;
(b) Lee, S.; Beare, N. A.; Hartwig, J. F. J. Am. Chem. Soc. 2001, 123, 8410–8411; (c)
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Tetrahedron Lett. 2002, 43, 2847–2849.
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C.; Taylor, D.; Gillmore, A. T. Org. Lett. 2004, 6, 4755–4757; (b) Willis, M. C.;
Taylor, D.; Gillmore, A. T. Tetrahedron 2006, 62, 11513–11520; (c) Churruca, F.;
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Whitwood, A. C.; Taylor, R. J. K. Eur. J. Org. Chem. 2009, 2947–2952;
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Commun. 2009, 6744–6746; (i) Negishi, E.-I.; Liou, S.-Y.; Xu, C.; Shimoyama, I.;
Makabe, H. J. Mol. Catal. A: Chem. 1999, 143, 279–286.
4. For the general review on Baylis–Hillman reaction, see: (a) Basavaiah, D.; Rao,
A. J.; Satyanarayana, T. Chem. Rev. 2003, 103, 811–891; (b) Singh, V.; Batra, S.
Tetrahedron 2008, 64, 4511–4574; (c) Kim, J. N.; Lee, K. Y. Curr. Org. Chem. 2002,
6, 627–645; (d) Lee, K. Y.; Gowrisankar, S.; Kim, J. N. Bull. Korean Chem. Soc.
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Hillman adducts, see: (a) Kim, K. H.; Lee, H. S.; Kim, S. H.; Kim, S. H.; Kim, J. N.
Chem. Eur. J. 2010, 16, 2375–2380; (b) Lee, H. S.; Kim, S. H.; Kim, T. H.; Kim, J. N.
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Lee, K. Y.; Lee, J.-E.; Kim, J. N. Tetrahedron Lett. 2007, 48, 8619–8622; (e) Lee, H.
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3858–3861; (g) Kim, H. S.; Lee, H. S.; Kim, S. H.; Kim, J. N. Tetrahedron Lett. 2009,
50, 3154–3157.
6. For the synthesis of dihydrofuran moiety-containing tricyclic natural products,
see: (a) Malona, J. A.; Cariou, K.; Frontier, A. J. J. Am. Chem. Soc. 2009, 131, 7560–
7561; (b) Giese, M. W.; Moser, W. H. Org. Lett. 2008, 10, 4215–4218; (c) Li, H.;
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Scammells, P. J.; Rizzacasa, M. A. Angew. Chem., Int. Ed. 2007, 46, 7835–7838; (e)
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2676.
1438 cmÀ1 1H NMR (CDCl3, 300 MHz) d 3.55 (s, 3H), 5.18 (d, J = 11.7 Hz, 1H),
;
5.61 (s, 1H), 5.91 (d, J = 11.7 Hz, 1H), 6.03 (s, 1H), 6.98 (t, J = 7.8 Hz, 1H), 7.11 (t,
J = 7.8 Hz, 1H), 7.16–7.22 (m, 1H), 7.25–7.48 (m, 7H), 7.52–7.60 (m, 2H), 7.92–
7.95 (m, 2H); 13C NMR (CDCl3, 75 MHz) d 51.06, 51.51, 55.72, 125.91, 127.17,
127.49, 128.04, 128.50 (2C), 128.55, 128.83, 129.16, 129.74, 132.90, 133.48,
136.65, 136.73, 138.77, 139.67, 166.67, 197.71; ESIMS m/z 449 (M++1), 451
(M++3).
Compound 3b: 56%; colorless oil; IR (film) 1720, 1686, 1438 cmÀ1 1H NMR
;
(CDCl3, 300 MHz) d 3.43 (dd, J = 17.4 and 7.5 Hz, 1H), 3.60 (dd, J = 17.4 and
7.5 Hz, 1H), 3.70 (s, 3H), 5.12 (t, J = 7.5 Hz, 1H), 5.51 (s, 1H), 6.39 (s, 1H), 7.05–
7.10 (m, 1H), 7.21–7.27 (m, 2H), 7.42–7.48 (m, 2H), 7.53–7.59 (m, 2H), 7.93–
7.99 (m, 2H); 13C NMR (CDCl3, 75 MHz) d 41.41, 42.35, 51.99, 124.93, 126.06,
127.43, 128.06, 128.22, 128.34, 128.61, 133.19, 133.39, 136.57, 140.83, 141.18,
166.75, 197.03; ESIMS m/z 373 (M++1), 375 (M++3).
Compound 3i: 83%; colorless oil; IR (film) 1723, 1700, 1437 cmÀ1 1H NMR
;
(CDCl3, 300 MHz) d 1.95 (s, 3H), 2.24 (s, 3H), 3.68 (s, 3H), 4.92 (d, J = 12.3 Hz,
1H), 5.17 (d, J = 12.3 Hz, 1H), 5.93 (s, 1H), 6.30 (s, 1H), 7.07 (t, J = 7.8 Hz, 1H),
7.25 (t, J = 7.8 Hz, 1H), 7.39 (d, J = 7.8 Hz, 1H), 7.55 (d, J = 7.8 Hz, 1H); 13C NMR
(CDCl3, 75 MHz) d 29.35, 29.76, 46.19, 51.96, 71.92, 125.35, 127.69, 128.80,
128.88, 129.65, 133.76, 137.25, 138.25, 166.28, 202.11, 202.54; ESIMS m/z 353
(M++1), 355 (M++3).
Typical procedure for the synthesis of 4a: A mixture of 3a (450 mg, 1.0 mmol),
Pd(OAc)2 (22 mg, 10 mol %), PPh3 (52 mg, 20 mol %), and Cs2CO3 (652 mg,
2.0 mmol) in toluene (3 mL) was heated to reflux for 1 h. After the usual
aqueous workup and column chromatographic purification process (hexanes/
CH2Cl2/diethyl ether, 5:1:1), 4a was isolated as a white solid, 210 mg (57%).
Other compounds 4b–k were prepared similarly, and the selected
spectroscopic data of 4a–c, 4g, 4i, and 4k are as follows.
Compound 4a: 57%; pale yellow solid, mp 116–118 °C; IR (KBr) 1755, 1737,
1237 cmÀ1 1H NMR (CDCl3, 300 MHz) d 3.64 (d, J = 17.4 Hz, 1H), 3.85 (s, 3H),
;
3.86 (d, J = 17.4 Hz, 1H), 5.21 (s, 1H), 6.72 (d, J = 7.2 Hz, 1H), 7.02 (t, J = 7.2 Hz,
1H), 7.17–7.24 (m, 4H), 7.25–7.34 (m, 6H), 7.37–7.42 (m, 2H); 13C NMR (CDCl3,
75 MHz) d 44.52, 52.87, 63.72, 92.24, 112.77, 124.19, 124.85, 126.88, 126.97,
127.62, 127.67, 127.99, 128.53, 128.57, 129.36, 130.89, 134.09, 139.48, 141.89,
149.42, 173.66; ESIMS m/z 391 (M++Na). Anal. Calcd for C25H20O3: C, 81.50; H,
5.47. Found: C, 81.29; H, 5.61.
Compound 4b: 42%; colorless oil; IR (film) 1735, 1244, 1207 cmÀ1 1H NMR
;
(CDCl3, 300 MHz) d 3.56 (d, J = 17.7 Hz, 1H), 3.82 (s, 3H), 3.86 (d, J = 17.7 Hz,
1H), 4.85 (d, J = 3.3 Hz, 1H), 5.57 (d, J = 3.3 Hz, 1H), 7.20–7.34 (m, 7H), 7.56–
7.59 (m, 2H); 13C NMR (CDCl3, 75 MHz) d 44.56, 52.76, 60.14, 94.06, 97.38,
123.88, 125.14, 125.48, 127.46, 127.50, 128.20, 128.69, 130.24, 139.35, 143.02,
155.98, 173.66; ESIMS m/z 293 (M++1). Anal. Calcd for C19H16O3: C, 78.06; H,
5.52. Found: C, 78.33; H, 5.49.
Compound 4c: 62%; colorless oil; IR (firm) 2239, 1655, 1261 cmÀ1 1H NMR
;
(CDCl3, 300 MHz) d 3.87 (d, J = 17.7 Hz, 1H), 3.94 (d, J = 17.7 Hz, 1H), 5.32 (s,
1H), 6.72 (d, J = 7.8 Hz, 1H), 7.10 (t, J = 7.8 Hz, 1H), 7.21–7.28 (m, 4H), 7.30–7.42
(m, 8H); 13C NMR (CDCl3, 75 MHz) d 45.70, 65.47, 82.29, 113.05, 119.94,
124.19, 124.96, 127.41, 127.58, 127.68, 128.08, 128.29, 128.84, 129.03, 129.45,
129.80, 133.00, 137.53, 140.05, 148.91; ESIMS m/z 336 (M++1). Anal. Calcd for
C
24H17NO: C, 85.94; H, 5.11; N, 4.18. Found: C, 85.67; H, 5.35; N, 4.08.
Compound 4g: 74%; white solid, mp 57–59 °C; IR (KBr) 1742, 1705, 1648 cmÀ1
;
1H NMR (CDCl3, 300 MHz) d 2.22 (s, 3H), 3.47 (d, J = 17.7 Hz, 1H), 3.77 (d,
J = 17.7 Hz, 1H), 3.81 (s, 3H), 3.82 (s, 3H), 4.92 (s, 1H), 7.22–7.26 (m, 3H), 7.52–
7.56 (m, 1H); 13C NMR (CDCl3, 75 MHz) d 14.33, 43.52, 50.96, 52.89, 58.55,
94.47, 105.65, 124.66, 125.26, 127.56, 127.84, 138.70, 142.46, 165.69, 168.33,
172.26; ESIMS m/z 289 (M++1). Anal. Calcd for C16H16O5: C, 66.66; H, 5.59.
Found: C, 66.95; H, 5.77.
Compound 4i:81%;colorlessoil; IR (film)1751, 1625, 1385 cmÀ1;1HNMR (CDCl3,
300 MHz) d 2.26 (s, 3H), 2.35 (s, 3H), 3.47 (d, J = 17.7 Hz, 1H), 3.77 (d, J = 17.7 Hz,
1H), 3.80 (s, 3H), 5.03 (s, 1H), 7.18–7.24 (m, 3H), 7.51–7.54 (m, 1H); 13C NMR
(CDCl3, 75 MHz) d 15.59, 29.44, 43.29, 52.87, 59.21, 93.91, 118.06, 124.49,
125.82, 127.65, 127.75, 138.48, 142.74, 166.87, 172.14, 193.07; ESIMS m/z 273

4652
E. S. Kim et al. / Tetrahedron Letters 51 (2010) 4648–4652
(M++1). Anal. Calcd for C16H16O4: C, 70.57; H, 5.92. Found: C, 70.50; H, 6.13.
Compound 4k: 35%; pale yellow oil; IR (film) 1737, 1437, 1260 cmÀ1 1H NMR
(CDCl3, 300 MHz) d 2.49–2.57 (m, 2H), 2.79–3.01 (m, 2H), 3.55 (d, J = 17.7 Hz,
1H), 3.82 (s, 3H), 3.87 (d, J = 17.7 Hz, 1H), 4.76 (s, 1H), 7.06–7.29 (m, 7H), 7.32–
7.34 (m, 1H); 13C NMR (CDCl3, 75 MHz) d 21.04, 28.44, 44.86, 52.76, 62.11, 94.32,
110.20, 120.85, 123.44, 125.08, 126.27, 127.14, 127.17, 127.49, 127.51, 127.80,
135.89, 139.53, 141.78, 149.35, 173.55; ESIMS m/z 319 (M++1). Anal. Calcd for
12. For the examples of Pd-catalyzed cyclizations involving 5-endo-
;
carbopalladation in Baylis–Hillman chemistry, see: (a) Vasudevan, A.; Tseng,
P.-S.; Djuric, S. W. Tetrahedron Lett. 2006, 47, 8591–8593; (b) Park, J. B.; Ko, S.
H.; Hong, W. P.; Lee, K.-J. Bull. Korean Chem. Soc. 2004, 25,
927–930.
13. Crystal data of compound 4g: solvent of crystal growth (hexane); empirical
formula C16H16O5, Fw = 288.29, crystal dimensions 0.34 Â 0.20 Â 0.09 mm3,
monoclinic, space group P2(1)/n, a = 10.3057(19) Å, b = 10.362(2) Å,
C21H18O3: C, 79.22; H, 5.70. Found: C, 79.56; H, 5.55.
11. We separated the two isomers in the case of 3a,10 and carried out the Pd-
catalyzed cyclization reactions separately. Both isomers produced 4a as the
major product, although the yield with minor isomer was slightly lower (37%)
than the cases of major isomer (59%) and the mixture (57%, entry 1 in Table 2).
c = 13.347(3) Å,
a
= 90°, b = 104.855(10)°,
F000 = 608, MoK
r(I)). The X-ray data has been deposited in CCDC with
c
= 90°, V = 1377.6(5) Å3, Z = 4,
(k = 0.71073 Å), R1 = 0.0898,
Dcalcd = 1.390 mg/m3,
a
wR2 = 0.2598 (I>2
number 777033.