Stereoselective synthesis of benzofulvenes via a palladium-catalyzed cyclization of 1,3-dienes derived from Morita-Baylis-Hillman adducts

Article abstract of DOI:10.1016/j.tetlet.2013.08.053

A facile synthesis of benzofulvenes was carried out starting from the Morita-Baylis-Hillman adducts of 2-bromobenzaldehyde. The synthesis was carried out via the sequential bromination, Wittig reaction with aldehyde, and Pd-catalyzed intramolecular Mizoroki-Heck reaction. The stereochemistry of benzofulvenes was dependent on the reaction condition, especially on the kinds of base and reaction time, and the substituent of starting materials.

Full text of DOI:10.1016/j.tetlet.2013.08.053

Tetrahedron Letters 54 (2013) 5808–5813
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Tetrahedron Letters
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Stereoselective synthesis of benzofulvenes via a palladium-catalyzed
cyclization of 1,3-dienes derived from Morita–Baylis–Hillman
adducts
⇑
Cheol Hee Lim, Ko Hoon Kim, Jin Woo Lim, 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 facile synthesis of benzofulvenes was carried out starting from the Morita–Baylis–Hillman adducts of
2-bromobenzaldehyde. The synthesis was carried out via the sequential bromination, Wittig reaction
with aldehyde, and Pd-catalyzed intramolecular Mizoroki–Heck reaction. The stereochemistry of benzo-
fulvenes was dependent on the reaction condition, especially on the kinds of base and reaction time, and
the substituent of starting materials.
Received 12 July 2013
Revised 8 August 2013
Accepted 16 August 2013
Available online 26 August 2013
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
Benzofulvenes
Morita–Baylis–Hillman adducts
Palladium
1,3-Dienes
Fulvene, benzofulvene, and related derivatives have been used
as building blocks for the preparation of metallocene catalysts,1a–d
starting materials of polymers,1e–h discotic liquid crystals,1i and
biologically interesting compounds.2 There have been reported
numerous synthetic methods of fulvene derivatives including the
radical cyclization of enediynes,3a–c photochemical cyclization of
enyne-allenes,3d,e Pt-catalyzed diene-yne cyclization,3f Cu(I)-cata-
lyzed reaction between vinylidene cyclopropanes and iminophe-
nyliodinane,3g Au-catalyzed isomerization of cyclopropenes,3h
dium-catalyzed Mizoroki–Heck reaction of (E,E)-1,3-diene 1a, pre-
pared from the MBH bromide via
a Wittig reaction with
benzaldehyde,6 would produce 2a-Z as a major product via a typi-
cal 5-exo carbopalladation to form the benzylpalladium intermedi-
ate I, rotation around the C-C single bond, and a following b-H
elimination process, as shown in Scheme 1.
The Pd-catalyzed Mizoroki-Heck reaction of 1a was carried out
in the presence of Pd(OAc)2, PPh3, and Et3N in refluxing CH3CN for
1 h. To our delight, 2a-Z was obtained as a major product (55%);
however, 2a-E was also isolated in low yield (25%), as shown in
Table 1 (entry 1). The reaction at 50 °C was very sluggish (entry
2), and 2a (Z + E) was isolated in only 15% combined yield. When
the reaction was performed for a long time (12 h) the yield of 2a
increased to 44%; however, 2a-E was the major product (entry 3).
The best yield of 2a-Z (61%) was obtained by using Et3N
(1.1 equiv) in refluxing CH3CN for 1 h (entry 4).7 When we let
the reaction mixture for a long time, most of 2a-Z was converted
to 2a-E (entry 5), as also observed in entry 3. The reaction with
5 mol % of Pd(OAc)2 showed sluggish reactivity (entry 6). The
use of i-Pr2NEt instead of Et3N showed a similar result (entry
7). It is interesting to note that 2a-E was obtained in high yield
(80%) in the presence of Cs2CO3 even in short time (entry 8).
The reactions in the presence of pyridine (entry 9) and K2CO3 in
toluene (entry 10) were not effective. In addition, the use of KOAc
(entry 11) or CsOAc (entry 12) showed a similar result to that of
K2CO3 (entry 10).
and Nazarov-type cyclization of
a
-hydroxyallene,3i and other
methods.3j–n Palladium-catalyzed synthesis of fulvene derivatives
from [3]cumulene,4a butadiyne,4b 1,2-dialkynylbenzene,4c and a
tandem reaction of 1-(2,2-dibromovinyl)-2-alkynylbenzene4d–f or
ortho-(2-chlorovinyl)alkynylbenzene4g with arylboronic acid have
also been reported.
Recently, we also reported the synthesis of benzofulvene deriv-
atives from the Morita–Baylis–Hillman (MBH) bromide via a
sequential indium-mediated Barbier reaction with benzaldehyde,
acetylation to make a homoallylic acetate, and a Pd-catalyzed
cyclization.5 The formation of benzofulvene involved a Pd-cata-
lyzed Mizoroki–Heck reaction to form an indene and a following
1,4-elimination of AcOH via a
p-allylpalladium intermediate. In
the reaction, thermodynamically more stable benzofulvene 2a-E
was obtained as a major product (85%) along with 2a-Z (10%) as
minor product, as shown in Scheme 1.5 We presumed that a palla-
Based on the experimental results, we found that the use of a
carbonate base (entries 8 and 10) and/or long reaction time
⇑
Corresponding author.
E-mail address: kimjn@chonnam.ac.kr (J.N. Kim).
0040-4039/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2013.08.053

C. H. Lim et al. / Tetrahedron Letters 54 (2013) 5808–5813
5809
Ph
Ph
COOMe
2a-Z (10%)
AcO
Ph
(i) In, PHCHO
(ii) Ac2O
Pd0
COOMe
+
COOMe
Ref. 5
(E)
COOMe
Br
Br
homoallylic acetate
2a-E (85%)
Br
(i) PPh3
(i) rotation
(ii) - HPdBr
COOMe
Pd0
MBH bromide
(ii) K2CO3, PhCHO
COOMe
PdBr
2a-Z
(E)
This work
H
Ph
I
Br
Ph
1,3-diene 1a
Scheme 1.
Table 1
Optimization of reaction conditions for the conversion of 1a to 2a-Z
b
Entry
Conditions
2a-Za (%)
2a-Ea (%)
1a (%)
1
2
Pd(OAc)2 (10 mol %), PPh3 (20 mol%), Et3N (2.0 equiv), CH3CN, reflux, 1 h
Pd(OAc)2 (10 mol %), PPh3 (20 mol%), Et3N (2.0 equiv), CH3CN, 50 °C, 1 h
55
11
<2
61
8
40
53
5
<2
36
42
28
25
4
0
74
36
0
0
35
0
0
84
0
11
0
3
Pd(OAc)2 (10 mol %), PPh3 (20 mol %), Et3N (2.0 equiv), CH3CN, 50 °C, 12 h
Pd(OAc)2 (10 mol %), PPh3 (20 mol %), Et3N (1.1 equiv), CH3CN, reflux, 1 h
Pd(OAc)2 (10 mol %), PPh3 (20 mol %), Et3N (1.1 equiv), CH3CN, reflux, 12 h
Pd(OAc)2 (5 mol %), PPh3 (10 mol %), Et3N (1.0 equiv), CH3CN, reflux, 1 h
Pd(OAc)2 (10 mol %), PPh3 (20 mol %), i-Pr2NEt (1.1 equiv), CH3CN, reflux, 1 h
Pd(OAc)2 (10 mol %), PPh3 (20 mol %), Cs2CO3 (2.0 equiv), CH3CN, reflux, 1 h
Pd(OAc)2 (10 mol %), PPh3 (20 mol %), pyridine (1.1 equiv), CH3CN, reflux, 12 h
Pd(OAc)2 (10 mol %), PPh3 (20 mol %), K2CO3 (1.1 equiv), toluene, reflux, 1 h
Pd(OAc)2 (10 mol %), PPh3 (20 mol %), KOAc (1.1 equiv), CH3CN, reflux, 1 h
Pd(OAc)2 (10 mol %), PPh3 (20 mol %), CsOAc (1.1 equiv), CH3CN, reflux, 1 h
42
28
71
18
25
80
8
47
34
51
4c
5
6
7
8d
9
10
11
12
a
b
c
Isolated yield.
Recovered 1a.
Selected as Condition A.
Selected as Condition B.
d
Table 2
Selective synthesis of Z- and E-benzofulvene derivatives
a
Entry
1,3-Diene
Benzofulvene (%)
COOMe
COOMe
Br
1
COOMe
COOMe
1a
1b
A: 2a-Z (61)
B: 2a-Z (5)
A: 2a-E (28)
B: 2a-E (80)
Me
Me
Br
2
COOMe
COOMe
Me
A: 2b-Z (56)
B: 2b-Z (5)
A: 2b-E (29)
B: 2b-E (83)
COOMe
Me
Me
Br
3
COOMe
COOMe
1c
Me
A: 2c-Z (58)
B: 2c-Z (4)
A: 2c-E (29)
B: 2c-E (85)
(continued on next page)

5810
C. H. Lim et al. / Tetrahedron Letters 54 (2013) 5808–5813
Table 2 (continued)
a
Entry
1,3-Diene
Benzofulvene (%)
COOMe
MeO
OMe
Br
Br
OMe
4
COOMe
COOMe
1d
1e
A: 2d-Z (60)
B: 2d-Z (3)
A: 2d-E (31)
B: 2d-E (87)
COOMe
MeO
OMe
5
COOMe
COOMe
OMe
A: 2e-Z (59)
B: 2e-Z (5)
A: 2e-E (31)
B: 2e-E (84)
a
Condition A: 1,3-diene (0.5 mmol), Pd(OAc)2 (10 mol %), PPh3 (20 mol %), Et3N (1.1 equiv), CH3CN, reflux, 1 h; Condition B: 1,3-diene (0.5 mmol), Pd(OAc)2 (10 mol %), PPh3
(20 mol %), Cs2CO3 (2.0 equiv), CH3CN, reflux, 1 h.
COOMe
COOMe
COOMe
PdBr
- HPdBr
+ HPdBr
H
Ph
I
Ph
Ph
PdBr
II
2a-Z (less stable)
- HPdBr
COOMe
- HPdBr
PdBr
COOMe
Pd0
COOMe
2a-Z
2a-E
H
H
PdBr
Ph
2a-E (more stable)
III'
III
Scheme 2.
a: R = Ph (74%)
(i) PPh3 (1.0 equiv)
CH3CN, rt, 1 h
b: R = 4-MePh (73%)
c: R = 3-MePh (71%)
d: R = 2-MeOPh (60%)
e: R = 4-MeOPh (59%)
f: R = 2-naphthyl (77%)
g: R = 4-NO2Ph (83%)
h: R = 2-furyl (75%)
COOMe
(E)
COOMe
(ii) K2CO3 (1.1 equiv)
R-CHO (1.1 equiv)
CH3CN, rt, 20 h
Br
Br Br
R
MBH bromide
1a-h
Scheme 3.
(entries 3 and 5) could convert 2a-Z into more stable 2a–E.3a,5
Benzofulvene 2a-E could be generated from 2a-Z via the addition/
elimination of HPdBr species,8 as shown in Scheme 2. When the
reaction was carried out in the presence of an inorganic carbonate
base, which is less soluble than Et3N, HPdBr species could survive
for a longer time and cause the isomerization to 2a-E.8c Another
plausible route for the formation of 2a-E could be a stereomutation
With these 1,3-dienes, a palladium-catalyzed synthesis of benzo-
fulvenes was carried out under the optimized conditions (Conditions
A and B), and the results are summarized in Tables 2 and 3. The reac-
tions of 1,3-dienes 1b–e (entries 2–5) under the conditions employ-
ing Et3N as a base (Condition A) afforded (Z)-2b–e as major products
(56–60%)along with(E)-2b–e as minorproducts (29–31%), as shown
in Table 2. In a sharp contrast, the reactions in the presence of Cs2CO3
(Condition B), (E)-2b–e were obtained selectively in good yields (83–
87%) along with a low yield of (Z)-2b–e (3–5%).
process of I via the corresponding g
3-benzylpalladium intermedi-
ate III and its enantiomeric III0 (vide infra).9
Encouraged by the successful synthesis of both 2a-Z (entry 4,
selected as Condition A) and 2a-E (entry 8, selected as Condition
B) in a stereoselective manner, we prepared 1,3-diene derivatives
1b–h by the Wittig reaction between various aldehydes and the
phosphonium salt of MBH bromide, as shown in Scheme 3.6 During
the Wittig reaction, E isomers were produced as major products in
all cases in reasonable yields (59–83%).
However, the reaction of naphthalene derivative 1f showed
somewhat different result, as shown in Table 3 (entry 1). The E-iso-
mer 2f-E was produced as a major product (76%) along with low
yield of 2f-Z (10%) even under the influence of Et3N (Condition A).
Similarly, E-benzofulvenes 2g–i were obtained as the sole products
in high yields (86–92%) in the reactions of p-nitrophenyl, 2-furyl,
and acetyl derivatives 1g–i (entries 2–4). In these cases, the

C. H. Lim et al. / Tetrahedron Letters 54 (2013) 5808–5813
5811
Table 3
Selective synthesis of E-benzofulvene derivatives
a
Entry
1,3-Diene
Benzofulvene (%)
COOMe
COOMe
Br
1
COOMe
2f-Z (10)
COOMe
1f
2f-E (76)
O2N
NO2
Br
2
COOMe
1g
COOMe
COOMe
NO2
2g-Z (0)
2h-Z (0)
2g-E (92)
COOMe
O
O
Br
Br
3
4
COOMe
O
1h
2h-E (86)
2i-E (87)
COMe
COMe
COMe
1ib
2i-Z (0)
2j (48)d
COOMe
Br
5
COOMe
1jc
a
Condition A: 1,3-diene (0.5 mmol), Pd(OAc)2 (10 mol %), PPh3 (20 mol %), Et3N (1.1 equiv), CH3CN, reflux, 1 h.
Prepared from MBH bromide of methyl vinyl ketone in 77% yield.
b
c Prepared from MBH acetate of 2-bromobenzaldehyde in two steps: (i) 2-nitropropane (2.0 equiv), K2CO3 (3.0 equiv), DMF, rt, 4 h (63%), (ii) DBU (2.5 equiv), DMF, 110 °C,
48 h (44%).
d
No stereochemistry.
1f
1h
1a
and
g
3-furylmethylpalladium V9b,10 intermediates, as shown in
Figure 1, because the resonance energies of one of the benzene of
naphthalene and furan are small relative to that of benzene.9a,9h,10c
The reason for the selective formation of more stable E-iso-
mers in other cases (2g-E and 2i-E) is not clear at this stage.11
As a last entry, the reaction of alkyl-substituted 1,3-diene 1j
was examined (entry 5). Although the reaction produced some
intractable side products, benzofulvene 2j could be isolated in a
reasonable yield (48%).
In summary, we disclosed a facile synthesis of benzofulvene
derivatives from the Morita–Baylis–Hillman adducts of 2-bromo-
benzaldehyde. The synthesis was carried out via the sequential
bromination, Wittig reaction with aldehyde, and Pd-catalyzed
intramolecular Mizoroki–Heck reaction. The stereochemistry of
benzofulvenes was dependent on the reaction condition, especially
on the kinds of base and reaction time, and the substituent of start-
ing materials.
COOMe
COOMe
COOMe
H
H
H
O
PdBr
PdBr
PdBr
η3-benzylpalladium
intermediate III
(not easy)
η3-furylmethylpalladium
intermediate V (easy)
η3-naphthylmethylpalladium
intermediate IV (easy)
2h-E
2f-E
2a-E
Figure 1.
formations of the corresponding Z-isomers were not observed even
at the early stage of the reactions.
Acknowledgments
For the reactions of 1f and 1h, more stable E-isomers (2f-E and
2h-E) might be formed more readily than the phenyl derivative (1a
to 2a-E) via the corresponding
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
g
3-naphthylmethylpalladium IV9

5812
C. H. Lim et al. / Tetrahedron Letters 54 (2013) 5808–5813
1.8 Hz, 1H), 7.79 (s, 1H); 13C NMR (CDCl3, 75 MHz) d 21.30, 51.22, 119.50,
122.68, 127.30, 127.31, 127.82, 128.06, 129.18, 130.93, 131.57, 132.38, 136.24,
137.16, 137.74, 138.71, 138.86, 140.99, 166.83; ESIMS m/z 277 [M+H]+. Anal.
Calcd for C19H16O2: C, 82.58; H, 5.84. Found: C, 82.77; H, 5.98.
(2012R1A1B3000541). Spectroscopic data were obtained from the
Korea Basic Science Institute, Gwangju branch.
Compound 2c-E: yellow oil; IR (film) 2933, 1710, 1603, 1512, 1259, 1177 cmꢁ1
;
References and notes
1H NMR (CDCl3, 300 MHz) d 2.39 (s, 3H), 3.88 (s, 3H), 7.07 (td, J = 7.8 and 1.2 Hz,
1H), 7.20–7.26 (m, 2H), 7.31–7.34 (m, 3H), 7.40–7.45 (m, 2H), 7.72 (s, 1H), 8.46
(s, 1H); 13C NMR (CDCl3, 75 MHz) d 21.36, 51.45, 123.11, 123.84, 126.23,
127.62, 127.94, 128.34, 129.14, 129.75, 129.93, 136.46, 136.80, 136.88, 138.09,
138.45, 140.34, 140.37, 165.09; ESIMS m/z 277 [M+H]+. Anal. Calcd for
1. For the synthesis of fulvenes and their applications to organometallic and
materials chemistry, see: (a) Rogers, J. S.; Lachicotte, R. J.; Bazan, G. C.
Organometallics 1999, 18, 3976–3980; (b) Gorl, C.; Alt, H. G. J. Organometal.
Chem. 2007, 692, 5727–5753; (c) Gaede, P. E. J. Organometal. Chem. 2000, 616,
29–36; (d) Zhang, Y.; Ma, H.; Huang, J. J. Mol. Catal. A: Chem. 2013, 373, 85–95;
(e) Nakano, T.; Takewaki, K.; Yade, T.; Okamoto, Y. J. Am. Chem. Soc. 2001, 123,
9182–9183; (f) Cappelli, A.; Mohr, G. P.; Anzini, M.; Vomero, S.; Donati, A.;
Casolaro, M.; Mendichi, R.; Giorgi, G.; Makovec, F. J. Org. Chem. 2003, 68, 9473–
9476; (g) Kosaka, Y.; Kitazawa, K.; Inomata, S.; Ishizone, T. ACS Macro Lett.
2013, 2, 164–167; (h) Cappelli, A.; Grisci, G.; Paolino, M.; Castriconi, F.; Giuliani,
G.; Donati, A.; Lamponi, S.; Mendichi, R.; Boccia, A. C.; Samperi, F.; Battiato, S.;
Paccagnini, E.; Gentile, M.; Licciardi, M.; Giammona, G.; Vomero, S. Chem. Eur. J.
2013, 19, 9710–9721. and further references cited therein; (i) Basurto, S.;
Garcia, S.; Neo, A. G.; Torroba, T.; Marcos, C. F.; Miguel, D.; Barbera, J.; Ros, M.
B.; de la Fuente, M. R. Chem. Eur. J. 2005, 11, 5362–5376.
2. For the synthesis of fulvenes and their applications to medicinal chemistry, see:
(a) Alcalde, E.; Mesquida, N.; Frigola, J.; Lopez-Perez, S.; Merce, R. Org. Biomol.
Chem. 2008, 6, 3795–3810; (b) Jeffrey, J. L.; Sarpong, R. Tetrahedron Lett. 2009,
50, 1969–1972; variety of benzofulvene derivatives has been developed as a
nonsteroidal anti-inflammatory drug (NSAID) including sulindac and sulindac
sulfone. These compounds were generally prepared via the Knoevenagel
condensation between aldehydes and indene derivatives, see: (c) Walters, M. J.;
Blobaum, A. L.; Kingsley, P. J.; Felts, A. S.; Sulikowski, G. A.; Marnett, L. J. Bioorg.
Med. Chem. Lett. 2009, 19, 3271–3274; (d) Felts, A. S.; Siegel, B. S.; Young, S. M.;
Moth, C. W.; Lybrand, T. P.; Dannenberg, A. J.; Marnett, L. J.; Subbaramaiah, K. J.
Med. Chem. 2008, 51, 4911–4919.
3. For the synthesis of fulvenes, see: (a) Vavilala, C.; Byrne, N.; Kraml, C. M.; Ho, D.
M., ; Pascal, R. A., Jr. J. Am. Chem. Soc. 2008, 130, 13549–13551; (b) Peabody, S.
W.; Breiner, B.; Kovalenko, S. V.; Patil, S.; Alabugin, I. V. Org. Biomol. Chem. 2005,
3, 218–221; (c) Kovalenko, S. V.; Peabody, S.; Manoharan, M.; Clark, R. J.;
Alabugin, I. V. Org. Lett. 2004, 6, 2457–2460; (d) Bucher, G.; Mahajan, A. A.;
Schmittel, M. J. Org. Chem. 2008, 73, 8815–8828; (e) Schmittel, M.; Vavilala, C. J.
Org. Chem. 2005, 70, 4865–4868; (f) Watanabe, M.; Shiine, K.; Ideta, K.;
Matsumoto, T.; Thiemann, T. J. Chem. Res. 2008, 669–678; (g) Lu, J.-M.; Zhu, Z.-
B.; Shi, M. Chem. Eur. J. 2009, 15, 963–971; (h) Li, C.; Zeng, Y.; Wang, J.
Tetrahedron Lett. 2009, 50, 2956–2959; (i) Cordier, P.; Aubert, C.; Malacria, M.;
Lacote, E.; Gandon, V. Angew. Chem., Int. Ed. 2009, 48, 8757–8760; (j)
Chinnagolla, R. K.; Jeganmohan, M. Eur. J. Org. Chem. 2012, 417–423; (k)
Tsuchikama, K.; Kasagawa, M.; Endo, K.; Shibata, T. Synlett 2010, 97–100; (l)
Alvarez, E.; Miguel, D.; Garcia-Garcia, P.; Fernandez-Rodriguez, M. A.;
Rodriguez, F.; Sanz, R. Synthesis 2012, 44, 1874–1884; (m) Hashmi, A. S. K.;
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Asakawa, T.; Iinuma, M.; Fujii, S.; Tanaka, K.; Kan, T. Chem. Commun. 2006,
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C
19H16O2: C, 82.58; H, 5.84. Found: C, 82.52; H, 6.06.
Compound 2d-Z: yellow oil; IR (film) 2954, 2930, 1718, 1510, 1239 cmꢁ1
;
1H
NMR (CDCl3, 300 MHz) d 3.28 (s, 3H), 3.89 (s, 3H), 6.92 (d, J = 8.1 Hz, 1H), 6.97
(d, J = 7.5 Hz, 1H), 7.17 (dd, J = 7.5 and 1.2 Hz, 1H), 7.26–7.36 (m, 3H), 7.40–7.42
(m, 1H), 7.58 (s, 1H), 7.78 (d, J = 7.8 Hz, 1H), 7.89 (s, 1H); 13C NMR (CDCl3,
75 MHz) d 51.14, 55.47, 110.22, 119.73, 120.27, 122.58, 126.51, 127.22, 127.60,
128.46, 130.14, 131.77, 132.46, 136.13, 138.77, 138.90, 140.76, 157.45, 166.63;
ESIMS m/z 293 [M+H]+. Anal. Calcd for C19H16O3: C, 78.06; H, 5.52. Found: C,
77.93; H, 5.84.
Compound 2d-E: yellow oil; IR (film) 2990, 1708, 1519, 1346 cmꢁ1 1H NMR
;
(CDCl3, 300 MHz) d 3.86 (s, 3H), 3.88 (s, 3H), 6.97–6.99 (m, 2H), 7.06–7.10 (m,
1H), 7.22 (t, J = 7.5 Hz, 1H), 7.39–7.42 (m, 2H), 7.50 (d, J = 7.5 Hz, 1H), 7.57 (d,
J = 7.5 Hz, 1H), 7.71 (s, 1H), 8.48 (s, 1H); 13C NMR (CDCl3, 75 MHz) d 51.41,
55.53, 110.72, 120.16, 123.04, 123.69, 125.56, 127.49, 127.78, 130.01, 130.39,
131.20, 134.92, 136.58, 136.61, 139.99, 140.35, 157.68, 165.15; ESIMS m/z 293
[M+H]+.
Compound 2g-E: yellow solid, mp 146–148 °C; IR (KBr) 2949, 1711, 1603, 1463,
1252, 1099 cmꢁ1 1H NMR (CDCl3, 300 MHz) d 3.90 (s, 3H), 7.09 (td, J = 7.5 and
;
1.2 Hz, 1H), 7.21 (d, J = 7.8 Hz, 1H), 7.28 (td, J = 7.8 and 1.2 Hz, 1H), 7.43 (d,
J = 7.8 Hz, 1H), 7.70 (d, J = 9.0 Hz, 2H), 7.76 (s, 1H), 8.31 (d, J = 9.0 Hz, 2H), 8.44
(s, 1H); 13C NMR (CDCl3, 75 MHz) d 51.62, 123.66, 123.68, 123.83, 128.11,
128.89, 129.63, 130.04, 134.45, 135.72, 139.01, 140.60, 141.99, 143.83, 147.47,
164.80; ESIMS m/z 308 [M+H]+. Anal. Calcd for C18H13NO4: C, 70.35; H, 4.26; N,
4.56. Found: C, 70.10; H, 4.43; N, 4.37.
Compound 2h-E: yellow solid, mp 120–122 °C; IR (KBr) 2952, 1714, 1519,
1347, 1238 cmꢁ1 1H NMR (CDCl3, 300 MHz) d 3.87 (s, 3H), 6.60 (dd, J = 3.3 and
;
1.8 Hz, 1H), 6.88 (d, J = 3.3 Hz, 1H), 7.32 (td, J = 7.5 and 1.2 Hz, 1H), 7.38 (td,
J = 7.5 and 1.2 Hz, 1H), 7.44 (d, J = 7.2 Hz, 1H), 7.68 (s, 1H), 7.73 (d, J = 1.8 Hz,
1H), 8.26 (s, 1H), 8.74 (d, J = 8.1 Hz, 1H); 13C NMR (CDCl3, 75 MHz) d 51.40,
112.90, 119.15, 121.41, 123.18, 125.03, 127.86, 127.97, 129.95, 132.80, 135.84,
139.36, 140.11, 144.96, 152.04, 165.36; ESIMS m/z 253 [M+H]+. Anal. Calcd for
C
16H12O3: C, 76.18; H, 4.79. Found: C, 76.49; H, 4.71.
Compound 2i-E: yellow oil; IR (film) 2979, 1709, 1603, 1512, 1178 cmꢁ1
;
1H
NMR (CDCl3, 300 MHz) d 2.58 (s, 3H), 7.08 (td, J = 7.8 and 1.2 Hz, 1H), 7.25 (td,
J = 7.8 and 1.2 Hz, 1H), 7.36–7.46 (m, 5H), 7.49–7.54 (m, 2H), 7.66 (s, 1H), 8.62
(s, 1H); 13C NMR (CDCl3, 75 MHz) d 28.49, 123.44, 123.95, 128.05, 128.23,
128.36, 128.43, 129.07, 136.65, 136.84, 136.96, 137.06, 140.31, 140.36, 141.31,
196.69; ESIMS m/z 247 [M+H]+. Anal. Calcd for C18H14O: C, 87.78; H, 5.73.
Found: C, 87.64; H, 5.84.
Compound 2j: pale yellow oil; IR (film) 2948, 1711, 1252, 1180 cmꢁ1 1H NMR
;
(CDCl3, 300 MHz) d 2.27 (s, 3H), 2.48 (s, 3H), 3.86 (s, 3H), 7.23 (td, J = 7.2 and
1.2 Hz, 1H), 7.29 (dd, J = 7.2 and 1.2 Hz, 1H), 7.32 (s, 1H), 7.38–7.40 (m, 1H),
7.75 (d, J = 7.5 Hz, 1H); 13C NMR (CDCl3, 75 MHz) d 25.13, 27.28, 52.02, 122.68,
124.05, 126.27, 127.10, 132.68, 133.65, 136.41, 137.61, 139.57, 147.86, 168.14;
ESIMS m/z 215 [M+H]+. Anal. Calcd for C14H14O2: C, 78.48; H, 6.59. Found: C,
78.72; H, 6.81.
8. For the isomerization of double bond catalyzed by XPdH species, see: (a) Calo,
V.; Nacci, A.; Monopoli, A.; Laera, S.; Cioffi, N. J. Org. Chem. 2003, 68, 2929–
2933; (b) Huang, Q.; Larock, R. C. J. Org. Chem. 2003, 68, 7342–7349; (c)
Nasveschuk, C. G.; Frein, J. D.; Jui, N. T.; Rovis, T. Org. Lett. 2007, 9, 5099–5102;
(d) Narhi, K.; Franzen, J.; Backvall, J.-E. Chem. Eur. J. 2005, 11, 6937–6943; (e)
Yip, K.-T.; Zhu, N.-Y.; Yang, D. Org. Lett. 2009, 11, 1911–1914; (f) Dankwardt, J.
W.; Flippin, L. A. J. Org. Chem. 1995, 60, 2312–2313; We also examined the
reaction of 1a in the presence of AgOAc or Ag2CO3 in order to trap the liberated
HBr irreversibly by forming insoluble silver salts and eventually increase the
selectivity for the formation of 2a-Z. However, the reaction was so sluggish in
refluxing CH3CN. For the use of silver salts to a similar purpose, see: (g)
Abelman, M. M.; Oh, T.; Overman, L. E. J. Org. Chem. 1987, 52, 4130–4133; (h)
Larock, R. C.; Gong, W. H. J. Org. Chem. 1989, 54, 2047–2050; (i) Grigg, R.;
Loganathan, V.; Santhakumar, V.; Sridharan, V.; Teasdale, A. Tetrahedron Lett.
1991, 32, 687–690.
5. For our recent synthesis of benzofulvene derivatives, see: Kim, K. H.; Kim, S. H.;
Park, B. R.; Kim, J. N. Tetrahedron Lett. 2010, 51, 3368–3371. Further references
were cited on the MBH reaction, Pd-catalyzed chemical transformations of
modified MBH adducts, and the synthesis of cinnamyl bromides from MBH
adducts.
6. For the synthesis of 1,3-dienes from MBH adducts and their synthetic
applications, see: (a) Lim, C. H.; Kim, S. H.; Park, K. H.; Lee, J.; Kim, J. N.
Tetrahedron Lett. 2013, 54, 387–391; (b) Lee, C. G.; Lee, K. Y.; Kim, S. J.; Kim, J. N.
Bull. Korean Chem. Soc. 2007, 28, 719–720; (c) Zhou, R.; Wang, C.; Song, H.; He,
Z. Org. Lett. 2010, 12, 976–979; (d) Crist, R. M.; Reddy, P. V.; Borhan, B.
Tetrahedron Lett. 2001, 42, 619–621; (e) Muthiah, C.; Kumar, K. S.; Vittal, J. J.;
Swamy, K. C. K. Synlett 2002, 1787–1790; (f) Palmelund, A.; Myers, E. L.; Tai, L.
R.; Tisserand, S.; Butts, C. P.; Aggarwal, V. K. Chem. Commun. 2007, 4128–4130.
7. Typical synthetic procedure of 2a:A stirred solution of 1a (172 mg, 0.5 mmol),
Pd(OAc)2 (11 mg, 10 mol %), PPh3 (26 mg, 20 mol%), and Et3N (56 mg, 1.1 equiv)
in CH3CN (2.0 mL) was heated to reflux for 1 h under nitrogen atmosphere. The
reaction mixture was allowed to cool to room temperature, quenched with
water (10 mL), and extracted with diethyl ether (30 mL ꢀ 3). The combined
organic layers were washed with dilute HCl solution, brine, dried over MgSO4,
and concentrated under vacuum. The residue was purified by column
chromatography (hexanes/ether, 20:1) to afford compounds 2a-Z (80 mg,
61%)5 and 2a-E (37 mg, 28%)5 as yellow oils. Other compounds were prepared
similarly. Compounds 2a-Z, 2a-E, 2b-Z, 2b-E, 2f-Z, and 2f-E are known
compounds,5 and the selected spectroscopic data of unknown compounds
2c-Z, 2c-E, 2d-Z, 2d-E, 2g-E, 2h-E, 2i-E, and 2j are as follows.
9. For the generation and reactions of
g3-benzyl-, g
3-naphthylmethylpalladium
and related intermediates, see: (a) Peng, B.; Zhang, S.; Yu, X.; Feng, X.; Bao, M.
Org. Lett. 2011, 13, 5402–5405; (b) Zhang, S.; Bao, M. Synlett 2012, 2431–2434;
(c) Johns, A. M.; Tye, J. W.; Hartwig, J. F. J. Am. Chem. Soc. 2006, 128, 16010–
16011; (d) Urkalan, K. B.; Sigman, M. S. Angew. Chem., Int. Ed. 2009, 48, 3146–
3149; (e) Kuwano, R.; Kondo, Y. Org. Lett. 2004, 6, 3545–3547; (f) Kuwano, R.;
Kondo, Y.; Matsuyama, Y. J. Am. Chem. Soc. 2003, 125, 12104–12105; (g) Legros,
J.-Y.; Primault, G.; Toffano, M.; Riviere, M.-A.; Fiaud, J.-C. Org. Lett. 2000, 2, 433–
436; (h) Baird, J. M.; Kern, J. R.; Lee, G. R.; Morgans, D. J., Jr.; Sparacino, M. L. J.
Org. Chem. 1991, 56, 1928–1933; (i) Legros, J.-Y.; Toffano, M.; Fiaud, J.-C.
Tetrahedron 1995, 51, 3235–3246; For the g3
benzylpalladium intermediate, see: (j) Kuwano, R. Synthesis 2009, 1049–1061.
10. For the
3-furylmethylpalladium intermediates, see: (a) Shi, Y.; Brenner, P.;
- -
g1 g3 isomerization of
Compound 2c-Z: yellow oil; IR (film) 2977, 1709, 1603, 1512, 1259, 1178 cmꢁ1
;
g
Bertsch, S.; Radacki, K.; Dewhurst, R. D. Organometallics 2012, 31, 5599–
5605; (b) Recio, A., III; Heinzman, J. D.; Tunge, J. A. Chem. Commun. 2012, 142–
1H NMR (CDCl3, 300 MHz) d 2.38 (s, 3H), 3.27 (s, 3H), 7.13–7.19 (m, 3H), 7.25–
7.37 (m, 3H), 7.41–7.44 (m, 1H), 7.58 (d, J = 1.2 Hz, 1H), 7.72 (dd, J = 6.6 and

C. H. Lim et al. / Tetrahedron Letters 54 (2013) 5808–5813
5813
144; (c) Primault, G.; Legros, J.-Y.; Fiaud, J.-C. J. Organometal. Chem. 2003, 687,
353–364.
11. A base-mediated epimerization at the benzylic position of the intermediate I
could be another possible route for the formation of E-isomers. Thus, the
selective formations of more stable E-isomers in the cases of p-nitrophenyl
derivative (2g-E) and acetyl derivative (2i-E) could be explained by the
increased acidity of the benzylic protons of the corresponding benzylpalladium
intermediates. For the stereomutation of similar benzylpalladium
intermediates, see: (a) Grigg, R.; Sridharan, V.; Stevenson, P.; Sukirthalingam,
S.; Worakun, T. Tetrahedron 1990, 46, 4003–4018; (b) Grigg, R.; Fretwell, P.;
Meerholtz, C.; Sridharan, V. Tetrahedron 1994, 50, 359–370.