Facile synthesis of benzofulvene derivatives from Baylis-Hillman adducts: In-mediated Barbier reaction combined with Pd(0)-catalyzed intramolecular Heck-elimination cascade

Article abstract of DOI:10.1016/j.tetlet.2010.04.110

A facile synthesis of benzofulvene derivatives was carried out starting from the Baylis-Hillman adducts of 2-bromobenzaldehyde via the sequential bromination, In-mediated Barbier reaction with aldehyde, acetylation, Pd-catalyzed intramolecular Heck reaction, and the elimination of AcOH.

Full text of DOI:10.1016/j.tetlet.2010.04.110

Tetrahedron Letters 51 (2010) 3368–3371
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Facile synthesis of benzofulvene derivatives from Baylis–Hillman adducts:
In-mediated Barbier reaction combined with Pd(0)-catalyzed
intramolecular Heck-elimination cascade
*
Ko Hoon Kim, Sung Hwan Kim, Bo Ram Park, 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 benzofulvene derivatives was carried out starting from the Baylis–Hillman adducts of
2-bromobenzaldehyde via the sequential bromination, In-mediated Barbier reaction with aldehyde, acet-
ylation, Pd-catalyzed intramolecular Heck reaction, and the elimination of AcOH.
Ó 2010 Elsevier Ltd. All rights reserved.
Received 19 March 2010
Revised 19 April 2010
Accepted 19 April 2010
Available online 29 April 2010
Keywords:
Benzofulvenes
Baylis–Hillman adducts
Indium
Palladium
1,4-Elimination
Fulvene and related compounds have been used as building
blocks for the preparation of metallocene catalysts,1a–c starting
materials of polymers,1d,e and biologically interesting compounds.2
Fulvene skeleton could be constructed via the radical cyclization of
enediynes,3a–c photochemical cyclization of enyne-allenes,3d,i Pt-
catalyzed diene-yne cyclization,3e Cu(I)-catalyzed reaction be-
tween vinylidene cyclopropanes and iminophenyliodinane,3f Au-
catalyzed isomerization of cyclopropenes,3g and Nazarov-type
The starting material 4a was prepared from the Baylis–Hill-
man adduct of 2-bromobenzaldehyde via a three-step procedure,
that is, a sequential bromination to 1a,7,8 In-mediated Barbier
reaction with benzaldehyde (2a) to form 3a,7,9 and the following
acetylation (Scheme 2). The reaction of 4a under the influence of
Pd(OAc)2 (10 mol %)/PPh3 (20 mol %) and Et3N (2.0 equiv) in
refluxing CH3CN (condition C in Table 1, vide infra) showed
the best results, and benzofulvene 6a was isolated in 95% yield.10
In the reaction, E and Z isomers were formed together. Two iso-
mers could be separated easily (6a-E 85%, 6a-Z 10%) and identi-
fied by comparison with the reported spectroscopic data of
cyclization of a
-hydroxyallene.3h Pd-catalyzed synthesis of fulvene
derivatives from [3]cumulene,4a butadiyne,4b 1,2-dialkynylben-
zene,4c and a tandem reaction of 1-(2,2-dibromovinyl)-2-alkynyl-
benzene with arylboronic acid4d,e has also been reported.
Recently, Baylis–Hillman adducts have been used extensively
for the synthesis of various important compounds.5–7 Among the
numerous chemical transformations of the Baylis–Hillman adducts
Pd-catalyzed reactions have received a special attention,6,7 includ-
ing inter- and intramolecular Heck type reactions.6e–g Recently, we
reported a Pd-catalyzed domino reaction of acrylate derivative A,
prepared from Baylis–Hillman adduct, to form a tetracyclic com-
pound via a 5-exo-carbopalladation and aryl C–H activation cas-
cade (Scheme 1).7 We imagined that a benzofulvene derivative
could be synthesized via the tandem intramolecular Heck reaction
and the following elimination of AcOH by using B (compound 4a,
vide infra).
Br
TBSO
Pd(0)
Ref. 7
H
TBSO
COOMe
COOMe
A
indeno[2,1-a]indane
AcO
Pd(0)
COOMe
this work
COOMe
Br
B (4a)
benzofulvene (6a)
* Corresponding author. Tel.: +82 62 530 3381; fax: +82 62 530 3389.
E-mail address: kimjn@chonnam.ac.kr (J.N. Kim).
Scheme 1.
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.04.110

K. H. Kim et al. / Tetrahedron Letters 51 (2010) 3368–3371
3369
HO
Ph
Pd(OAc)2, PPh3
conditions A-C
COOMe
decomposition
Br
3a (syn)
Ph
Pd(OAc)2, PPh3
Et3N, CH3CN, reflux
COOMe
PhCHO (2a)
In, aq THF
for 4a
RO
Ph
6a (95%)
E/Z = 85:10
COOMe
COOMe
(i) TBAF (decomp.)
(ii) MsCl, Et3N
Ph
OTBS
COOMe
7a (88%)
Br Br
Br
4a: R = Ac
Pd(OAc)2, PPh3
Et3N, CH3CN, reflux
1a (Z)
5a: R = TBS
for 5a
HBr
B-H adduct
Scheme 2.
Ph
AcO
AcO
Ph
H
- Pd(0)
- HBr
Ph
COOMe
Pd(0)
PdOAc
Pd(0)
- AcOH
- Pd(0)
4a
6a
PdBr
COOMe
COOMe
H
H
H
H
(I)
(II)
Scheme 3.
similar compounds3e and via the NOE experiments with 6e-E
(vide infra). When the reaction was carried out under condition
A (Cs2CO3, DMF, 110 °C) or condition B (Et3N, DMF, 90 °C), the
yield of 6a was somewhat lower (55–61%), as shown in entry
1 in Table 1 (vide infra).
tion temperature (see the footnote in Table 1). Conditions B and/
or C were better than condition A in most cases (entries 1, 2, 5,
and 7). Arylidene derivatives 6a–d (entries 1–4) were synthesized
in good yields (79–95%) while ethylidene derivative 6e (entry 5)
was isolated in moderate yield (57%). As described above, NOE
experiments with compound 6e showed the stereochemistry of
the major compound was found to be E. Methylene derivative 6f
(entry 6) was isolated in low yield (13%), and 6f was very unstable.
Nitrile derivatives 4g (entry 7) and 4h (entry 8) also produced the
corresponding benzofulvenes 6g and 6h in moderate yields (60–
63%); however, the ratio of E/Z (ca. 3:2) was different from those
of esters 6a–e (E/Z = ca. 9:1).
During the studies we observed the isomerization of prepared
benzofulvenes, E to Z and vice versa. Spectroscopically pure prod-
ucts could be obtained by rapid column chromatographic separa-
tion. No severe isomerization and/or decomposition was
observed when the compound was kept in the dark at low temper-
ature; however, isomerization occurred somewhat rapidly under
the influence of sunlight.2c,3d,12 As an example, pure 6a-E was con-
verted to a E/Z mixture (E/Z = 58:42) when kept in the shelf for 24 h
in NMR tube (CDCl3) without prohibiting the exposure to sunlight.
After 7 days the ratio was changed to E/Z = 40:60 and was not
changed further. Similarly, 6a-Z was isomerized to a mixture (E/
Z = 38:62) after 1 day, and the ratio was finally changed to E/
Z = 41:59 after 7 days. Based on the 1H NMR monitoring results,
the final ratio of E/Z (after 7 days) was found to be E/Z = 2:3. Sim-
ilarly, photoisomerization was also observed for the nitrile deriva-
tives. As an example, pure 6g-E was changed to an E/Z mixture (E/
Z = 7:3) after 7 days.
As also shown in Scheme 2, the reaction of alcohol 3a showed se-
vere decomposition under the conditions A–C. The reaction of TBS
derivative 5a produced indene derivative 7a (88%), and the synthe-
sis of benzofulvene 6a from 7a failed. The formation of many intrac-
table side products was observed during removal of a TBS group
with TBAF, unexpectedly. The mechanism for the formation of 6a
could be postulated as shown in Scheme 3 involving a Pd(0)-cata-
lyzed Heck reaction to form (I) and the following 1,4-elimination
of acetic acid via the p
-allylpalladium intermediate (II).11
Encouraged by the successful results, we prepared various ace-
tates 4b–h and examined the synthesis of benzofulvene derivatives.
Cinnamyl bromides 1a-Z (Scheme 2) and 1b-E (2-bromomethyl-3-
phenylacrylonitrile) were prepared stereoselectively from the cor-
responding Baylis–Hillman adducts, as reported.7,8 In-mediated
Barbier reactions of 1 and various aldehydes, benzaldehyde (2a),
p-tolualdehyde (2b), 2-naphthaldehyde (2c), N-acetyl-indole-3-
carboxaldehyde (2d), acetaldehyde (2e), and formaldehyde (2f)
were carried out in aqueous THF at room temperature for 1 h.7,9a
Syn-isomers were produced as the major products for the ester
derivatives 3a–e while anti-isomers for the nitrile derivatives 3g
and 3h, as reported.7,9 Separation of the major component by col-
umn chromatography afforded syn-isomers for 3a–e in high yields
(76–92%) and anti-isomers for 3g and 3h in 65–69%. Acetylation of
3a–h (Ac2O, pyridine, cat. DMAP, CH2Cl2, rt, 1 h) was carried out and
the acetates 4a–h were obtained in good yields (87–99%). With
these compounds 4b–h in our hands, the next Pd-catalyzed cycliza-
tion reactions to benzofulvenes 6b–h were carried out, and the re-
sults are summarized in Table 1.
In summary, we disclosed a facile synthesis of benzofulvene
derivatives from the Baylis–Hillman adducts of 2-bromobenzalde-
hyde. The synthesis was carried out via the sequential bromina-
tion, In-mediated Barbier reaction with aldehyde, acetylation, Pd-
catalyzed intramolecular Heck reaction, and the 1,4-elimination
of AcOH.
As shown in Table 1, the yields of benzofulvenes were depen-
dent on the reaction conditions including solvent, base, and reac-

3370
K. H. Kim et al. / Tetrahedron Letters 51 (2010) 3368–3371
Table 1
Preparation of starting material 4a–h and Pd-catalyzed synthesis of benzofulvene derivatives 6a–h
Entry
Substrates
Alcohola (%)
Acetatea (%)
Conditionsb
Products (%)
RO
Ar
Ph
COOMe
Ph
A
B
C
COOMe
1
1a + 2a
3a (R = H, 92)
4a (R = OAc, 95)
6a-E (55), 6a-Z (trace)
6a-E (61), 6a-Z (trace)
6a-E (85), 6a-Z (10)
RO
Ar
Ar1
COOMe
Ar1
A
B
2c
1a + 2b
COOMe
3b (R = H, 90)
6b-E (52), 6b-Z (trace)
6b-E (74), 6b-Z (7)
4b (R = OAc, 87)
RO
Ar
Ar2
COOMe
Ar2
3d
1a + 2c
B
C
COOMe
3c (R = H, 85)
4c (R = OAc, 99)
6c-E (71), 6c-Z (8)
RO
Ar3
Ar3
COOMe
Ar
4e
1a + 2d
COOMe
3d (R = H, 87)
4d (R = OAc, 99)
6d-E (73), 6d-Z (16)
RO
Ar
Me
nOe
nOe
Me
H
H
COOMe
A
B
5
6
7
1a + 2e
1a + 2f
1b + 2a
COOMe
3e (R = H, 76)
4e (R = OAc, 99)
decomposition
6e-E (57), 6e-Z (-)
RO
COOMe
Ar
COOMe
B
C
decomposition
6f (13)
Ph
3f (R = H, 90)
4f (R = OAc, 95)
RO
Ph
CN
Ar
A
B
CN
3g (R = H, 69)
4g (R = OAc, 91)
decomposition
6g-E (36), 6g-Z (27)
RO
Ar
Me
CN
Me
CN
8
1b + 2e
B
3h (R = H, 65)
4h (R = OAc, 91)
6h-E/6h-Z (60)
3:2 mixture
a
Ar in 2-bromophenyl and the stereochemistry of 3a–e and 4a–e is syn and 3g–h and 4g–h is anti, as shown.
Condition A: Pd(OAc)2 (10 mol %), PPh3 (20 mol %), Cs2CO2 (2.0 equiv), DMF, 110 °C, 60 min; condition B: Pd(OAc)2 (10 mol %), PPh3 (20 mol %), Et3N (2.0 equiv), DMF,
b
90 °C, 3 h; condition C: Pd(OAc)2 (10 mol %), PPh3 (20 mol %), Et3N (2.0 equiv), CH3CN, reflux, 60 min.
c
Ar1 is p-tolyl.
d
Ar2 is 2-naphthyl.
e
Ar3 is N-acetyl-3-indolyl.
Acknowledgments
References and notes
1. For the synthesis of fulvene derivatives 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.
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2000, 616, 29–36; (d) Nakano, T.; Takewaki, K.; Yade, T.; Okamoto, Y. J. Am.
Chem. Soc. 2001, 123, 9182–9183; (e) Cappelli, A.; Mohr, G. P.; Anzini, M.;
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 (2009-
0070633). Spectroscopic data were obtained from the Korea Basic
Science Institute, Gwangju branch.

K. H. Kim et al. / Tetrahedron Letters 51 (2010) 3368–3371
3371
Vomero, S.; Donati, A.; Casolaro, M.; Mendichi, R.; Giorgi, G.; Makovec, F. J. Org.
Chem. 2003, 68, 9473–9476; (f) 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.
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6.28 (d, J = 0.9 Hz, 1H), 7.07–7.13 (m, 1H), 7.25–7.35 (m, 6H), 7.54 (dd, J = 8.1
and 1.5 Hz, 1H), 7.69 (dd, J = 8.1 and 1.8 Hz, 1H); 13C NMR (CDCl3, 75 MHz) d
51.86, 52.61, 75.54, 126.86, 126.91, 127.20, 127.88, 128.26 (2C), 128.39,
129.91, 133.22, 138.15, 139.98, 141.73, 166.66. Anal. Calcd for C18H17BrO3: C,
59.85; H, 4.74. Found: C, 60.11; H, 4.98.
2. For the synthesis of fulvene derivatives 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; A variety of benzofulvene derivatives
Compound 3g (anti): 69%; colorless oil; IR (film) 3448, 3063, 2223, 1471 cmÀ1 1H
;
NMR (CDCl3, 300 MHz) d 2.34 (br s, 1H), 4.60 (d, J = 9.0 Hz, 1H), 5.26 (d, J = 9.0 Hz,
1H), 6.04 (s, 1H), 6.10 (s, 1H), 7.03 (ddd, J = 9.3, 7.5 and 1.8 Hz, 1H), 7.16–7.31 (m,
6H), 7.42 (dd, J = 8.1 and 1.2 Hz, 1H), 7.60 (dd, J = 7.8 and 1.5 Hz, 1H); 13C NMR
(CDCl3, 75 MHz) d 55.00, 75.18, 117.99, 122.86, 124.79, 126.80, 127.80, 128.28,
128.39, 128.98, 129.14, 133.22, 133.75, 136.81, 140.57. Anal. Calcd for
C17H14BrNO: C, 62.21; H, 4.30; N, 4.27. Found: C, 62.56; H, 4.67; N, 4.13.
Typical synthetic procedure of 4a: A solution of 3a (361 mg, 1.0 mmol), acetic
anhydride (153 mg, 1.5 mmol), pyridine (158 mg, 2.0 mmol), and DMAP
(12 mg, 0.1 mmol) in CH2Cl2 (4 mL) was stirred at room temperature for 1 h.
After the usual aqueous extractive workup and column chromatographic
purification process (hexanes/EtOAc, 15:1) compound 4a was obtained as
colorless oil, 383 mg (95%). Other compounds 4b–h were prepared similarly
and the selected spectroscopic data of 4a and 4g are as follows.
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 fulvene derivatives, 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) Watanabe,
M.; Shiine, K.; Ideta, K.; Matsumoto, T.; Thiemann, T. J. Chem. Res. 2008, 669–
678; (f) Lu, J.-M.; Zhu, Z.-B.; Shi, M. Chem. Eur. J. 2009, 15, 963–971; (g) Li, C.;
Zeng, Y.; Wang, J. Tetrahedron Lett. 2009, 50, 2956–2959; (h) Cordier, P.; Aubert,
C.; Malacria, M.; Lacote, E.; Gandon, V. Angew. Chem., Int. Ed. 2009, 48, 8757–
8760; (i) Schmittel, M.; Vavilala, C. J. Org. Chem. 2005, 70, 4865–4868.
4. For the other synthesis of fulvene derivatives, see: (a) Furuta, T.; Asakawa, T.;
Iinuma, M.; Fujii, S.; Tanaka, K.; Kan, T. Chem. Commun. 2006, 3648–3650; (b)
Dyker, G.; Borowski, S.; Henkel, G.; Kellner, A.; Dix, I.; Jones, P. G. Tetrahedron Lett.
2000, 41, 8259–8262; (c) Lee, C.-Y.; Wu, M.-J. Eur. J. Org. Chem. 2007, 3463–3467;
(d) Ye, S.; Yang, X.; Wu, J. Chem. Commun. 2010, 2950–2952; (e) Ye, S.; Gao, K.;
Zhou, H.; Yang, X.; Wu, J. Chem. Commun. 2009, 5406–5408; (f) Rahman, S. M. A.;
Sonoda, M.; Itahashi, K.; Tobe, Y. Org. Lett. 2003, 5, 3411–3414.
5. 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) Ciganek, E.. In Organic Reactions;
Paquette, L. A., Ed.; John Wiley & Sons: New York, 1997; Vol. 51, pp 201–
350; (d) Basavaiah, D.; Rao, P. D.; Hyma, R. S. Tetrahedron 1996, 52, 8001–8062;
(e) Drewes, S. E.; Roos, G. H. P. Tetrahedron 1988, 44, 4653–4670; (f) Kim, J. N.;
Lee, K. Y. Curr. Org. Chem. 2002, 6, 627–645; (g) Lee, K. Y.; Gowrisankar, S.; Kim,
J. N. Bull. Korean Chem. Soc. 2005, 26, 1481–1490; (h) Langer, P. Angew. Chem.,
Int. Ed. 2000, 39, 3049–3052; (i) Radha Krishna, P.; Sachwani, R.; Reddy, P. S.
Synlett 2008, 2897–2912; (j) Declerck, V.; Martinez, J.; Lamaty, F. Chem. Rev.
2009, 109, 1–48.
Compound 4a (syn): 95%; colorless oil; IR (film) 2951, 1735, 1724, 1232 cmÀ1
;
1H NMR (CDCl3, 300 MHz) d 1.83 (s, 3H), 3.58 (s, 3H), 5.13 (d, J = 9.9 Hz, 1H),
5.63 (s, 1H), 6.28 (s, 1H), 6.41 (d, J = 9.9 Hz, 1H), 7.06–7.12 (m, 1H), 7.24–7.34
(m, 4H), 7.38–7.42 (m, 2H), 7.51 (dd, J = 7.8 and 1.5 Hz, 1H), 7.56 (dd, J = 8.1
and 1.2 Hz, 1H); 13C NMR (CDCl3, 75 MHz) d 20.81, 50.15, 51.93, 76.28, 126.46,
127.26, 127.71, 128.29, 128.35, 128.37, 128.43, 129.30, 133.06, 138.15, 138.25,
138.96, 166.28, 169.78.
Compound 4g (anti): 91%; pale yellow solid; mp 99–101 °C; IR (film) 3063,
3034, 2223, 1743, 1226 cmÀ1 1H NMR (CDCl3, 300 MHz) d 2.10 (s, 3H), 4.79 (d,
;
J = 9.9 Hz, 1H), 6.00 (d, J = 0.9 Hz, 1H), 6.04 (s, 1H), 6.30 (d, J = 9.9 Hz, 1H), 7.04
(ddd, J = 7.5, 7.5 and 1.8 Hz, 1H), 7.16–7.31 (m, 6H), 7.44 (dd, J = 8.1 and 1.2 Hz,
1H), 7.52 (dd, J = 8.1 and 1.8 Hz, 1H); 13C NMR (CDCl3, 75 MHz) d 20.97, 52.86,
75.79, 117.62, 122.40, 124.95, 127.41, 127.85, 128.33, 128.50, 129.26, 129.30,
133.33, 133.67, 135.61, 136.94, 169.59; ESIMS m/z 392 [M+Na]+, 394
[M+2+Na]+.
Typical synthetic procedure of 6a (condition C): A stirred solution of 4a (202 mg,
0.5 mmol), Pd(OAc)2 (11 mg, 0.05 mmol), PPh3 (26 mg, 0.1 mmol), and TEA
(101 mg, 1.0 mmol) in CH3CN (4 mL) was heated to reflux for 1 h under
nitrogen atmosphere. The reaction mixture was allowed to cool to room
temperature, the reaction was quenched with water (10 mL), and the reaction
mixture was extracted with diethyl ether (30 mL Â 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/EtOAc, 20:1) to afford compounds 6a-E (111 mg,
85%), and 6a-Z (13 mg, 10%). Other compounds 6b–h were prepared similarly
and the selected spectroscopic data of compounds 6a, 6e, and 6g are as follows.
Compound 6a-E: 85%; pale yellow solid; mp 35–36 °C; IR (film) 3056, 2948,
6. For the Pd-catalyzed chemical transformations of Baylis–Hillman adducts, see:
(a) Gowrisankar, S.; Lee, H. S.; Kim, S. H.; Lee, K. Y.; Kim, J. N. Tetrahedron 2009,
65, 8769–8780. and further references cited therein; (b) Kim, K. H.; Kim, E. S.;
Kim, J. N. Tetrahedron Lett. 2009, 50, 5322–5325; (c) Kim, H. S.; Lee, H. S.; Kim, S.
H.; Kim, J. N. Tetrahedron Lett. 2009, 50, 3154–3157; (d) Kim, J. M.; Kim, S. H.;
Lee, H. S.; Kim, J. N. Tetrahedron Lett. 2009, 50, 1734–1737; (e) Park, J. B.; Ko, S.
H.; Hong, W. P.; Lee, K.-J. Bull. Korean Chem. Soc. 2004, 25, 927–930; (f)
Vasudevan, A.; Tseng, P.-S.; Djuric, S. W. Tetrahedron Lett. 2006, 47, 8591–8593;
(g) Kim, J. M.; Kim, K. H.; Kim, T. H.; Kim, J. N. Tetrahedron Lett. 2008, 49, 3248–
3251. and further references cited therein.
1710, 1349, 1182 cmÀ1 1H NMR (CDCl3, 300 MHz) d 3.88 (s, 3H), 7.06 (t,
;
J = 8.1 Hz, 1H), 7.23 (t, J = 7.5 Hz, 1H), 7.36–7.47 (m, 5H), 7.52–7.55 (m, 2H),
7.72 (s, 1H), 8.48 (s, 1H); 13C NMR (CDCl3, 75 MHz) d 46.74, 118.43, 119.07,
122.93, 123.31, 123.67, 123.73, 124.43, 125.17, 131.66, 132.15, 132.31, 133.40,
135.65, 135.78, 160.36; ESIMS m/z 285 [M+Na]+. Anal. Calcd for C18H14O2: C,
82.42; H, 5.38. Found: C, 82.33; H, 5.64.
Compound 6a-Z: 10%; pale yellow oil; IR (film) 2945, 1716, 1431, 1244 cmÀ1
;
1H NMR (CDCl3, 300 MHz) d 3.25 (s, 3H), 7.28–7.45 (m, 8H), 7.60 (d, J = 0.9 Hz,
1H), 7.72–7.75 (m, 1H), 7.82 (d, J = 1.2 Hz, 1H); 13C NMR (CDCl3, 75 MHz) d
51.54, 119.84, 123.03, 127.68, 128.20, 128.43, 128.62, 130.42, 131.75, 132.47,
136.70, 137.62, 139.00, 139.16, 141.72, 167.01; ESIMS m/z 285 (M++Na).
7. Kim, K. H.; Lee, H. S.; Kim, S. H.; Kim, S. H.; Kim, J. N. Chem. Eur. J. 2010, 16,
2375–2380.
8. For the synthesis of cinnamyl bromide derivatives in a stereoselective manner
from Baylis–Hillman adducts, see: (a) Gowrisankar, S.; Kim, S. H.; Kim, J. N. Bull.
Korean Chem. Soc. 2009, 30, 726–728. and further references cited therein; (b)
Basavaiah, D.; Reddy, K. R.; Kumaragurubaran, N. Nat. Prot. 2007, 2, 2665–2676;
(c) Das, B.; Banerjee, J.; Ravindranath, N. Tetrahedron 2004, 60, 8357–8361; (d)
Fernandes, L.; Bortoluzzi, A. J.; Sa, M. M. Tetrahedron 2004, 60, 9983–9989; (e)
Sa, M. M.; Ramos, M. D.; Fernandes, L. Tetrahedron 2006, 62, 11652–11656; (f)
Deng, J.; Hu, X.-P.; Huang, J.-D.; Yu, S.-B.; Wang, D.-Y.; Duan, Z.-C.; Zheng, Z. J.
Org. Chem. 2008, 73, 2015–2017; (g) Lee, K. Y.; Lee, Y. J.; Kim, J. N. Bull. Korean
Chem. Soc. 2007, 28, 143–146; (h) Lee, K. Y.; Park, D. Y.; Kim, J. N. Bull. Korean
Chem. Soc. 2006, 27, 1489–1492.
9. For the stereoselective synthesis of Barbier reaction products, see: (a) Kim, K.
H.; Lee, H. S.; Kim, S. H.; Lee, K. Y.; Lee, J.-E.; Kim, J. N. Bull. Korean Chem. Soc.
2009, 30, 1012–1020. and further references cited therein; (b) Paquette, L. A.;
Mendez-Andino, J. Tetrahedron Lett. 1999, 40, 4301–4304; (c) Lee, A. S.-Y.;
Chang, Y.-T.; Wang, S.-H.; Chu, S.-F. Tetrahedron Lett. 2002, 43, 8489–8492; (d)
Kabalka, G. W.; Venkataiah, B.; Chen, C. Tetrahedron Lett. 2006, 47, 4187–4189;
(e) Yu, S. H.; Ferguson, M. J.; McDonald, R.; Hall, D. G. J. Am. Chem. Soc. 2005,
127, 12808–12809.
Compound 6e-E: 57%; colorless oil; IR (film) 2949, 1710, 1362, 1184 cmÀ1 1H
;
NMR (CDCl3, 300 MHz) d 2.41 (d, J = 7.5 Hz, 3H), 3.84 (s, 3H), 7.26–7.39 (m, 2H),
7.44–7.47 (m, 1H), 7.61–7.68 (m, 2H), 7.82 (d, J = 7.5 Hz, 1H); 13C NMR (CDCl3,
75 MHz) d 16.21, 51.35, 123.29, 124.40, 127.31, 127.75, 129.59, 136.79, 137.23,
137.55, 138.66, 140.16, 165.19; ESIMS m/z 223 (M++Na). Anal. Calcd for
C13H12O2: C, 77.98; H, 6.04. Found: C, 78.23; H, 6.25.
Compound 6g-E: 36%; pale yellow oil; IR (film) 3054, 2919, 2215, 1447 cmÀ1
;
1H NMR (CDCl3, 300 MHz) d 7.18 (ddd, J = 7.5, 7.5 and 1.2 Hz, 1H), 7.31 (ddd,
J = 7.5, 7.5 and 0.9 Hz, 1H), 7.42–7.53 (m, 5H), 7.58–7.67 (m, 4H); 13C NMR
(CDCl3, 75 MHz) d 113.22, 115.57, 123.24, 123.56, 128.29, 128.68, 128.95,
129.42, 129.47, 133.83, 135.01, 136.73, 137.68, 141.00, 141.74; ESIMS m/z 252
(M++Na). Anal. Calcd for C17H11N: C, 89.06; H, 4.84; N, 6.11. Found: C, 88.94; H,
4.97; N, 6.02.
Compound 6g-Z: 27%; pale yellow oil; IR (film) 3058, 2217, 1443 cmÀ1 1H NMR
;
(CDCl3, 300 MHz) d 7.35–7.51 (m, 6H), 7.58–7.62 (m, 2H), 7.74–7.77 (m, 2H),
7.91 (s, 1H); 13C NMR (CDCl3, 75 MHz) d 108.01, 116.71, 119.72, 122.93, 128.24,
128.45, 128.59, 129.82, 130.88, 133.70, 133.89, 135.74, 137.49, 138.22, 147.94;
ESIMS m/z 252 (M++Na).
10. Typical synthetic procedure of 3a: To a stirred solution of cinnamyl bromide 1a
(668 mg, 2.0 mmol)7,8 and benzaldehyde (2a, 233 mg, 2.2 mmol) in aqueous
THF (1:1, 4 mL) was added indium powder (250 mg, 2.2 mmol) and stirred at
room temperature for 1 h. After the usual aqueous extractive workup and
column chromatographic purification process (hexanes/EtOAc/CH2Cl2, 15:1:1)
compound 3a (syn) was obtained as colorless oil, 664 mg (92%). Other
compounds 3b–h were prepared similarly, and the selected spectroscopic
data of 3a and 3g are as follows.
11. For the similar Pd-catalyzed 1,4-elimination, see: (a) Tsuji, J.; Yamakawa, T.;
Kaito, M.; Mandai, T. Tetrahedron Lett. 1978, 19, 2075–2078; (b) Takacs, J. M.;
Lawson, E. C.; Clement, F. J. Am. Chem. Soc. 1997, 119, 5956–5957. and further
references cited therein; (c) Shimizu, I.; Matsumoto, Y.; Shoji, K.; Ono, T.;
Satake, A.; Yamamoto, A. Tetrahedron Lett. 1996, 37, 7115–7118; (d) Mikami,
K.; Ohmura, H. Org. Lett. 2002, 4, 3355–3357.
12. For the photoisomerization of similar compounds, see: (a) Barr, J. W.; Bell, T.
W.; Catalano, V. J.; Cline, J. I.; Phillips, D. J.; Procupez, R. J. Phys. Chem. A 2005,
109, 11650–11654; (b) Abdur Rahman, S. M.; Sonoda, M.; Ono, M.; Miki, K.;
Tobe, Y. Org. Lett. 2006, 8, 1197–1200.
Compound 3a (syn): 92%; colorless oil; IR (film) 3479, 2949, 1716, 1437,
1144 cmÀ1 1H NMR (CDCl3, 300 MHz) d 2.03 (d, J = 3.6 Hz, 1H), 3.57 (s, 3H),
;
4.86 (d, J = 7.8 Hz, 1H), 5.33 (dd, J = 7.8 and 3.6 Hz, 1H), 5.71 (t, J = 0.9 Hz, 1H),