Synthesis of methyl 9-phenyl-7H-benzocycloheptene-6-carboxylates from Baylis-Hillman adducts: Use of intramolecular Friedel-Crafts alkenylation reaction

Article abstract of DOI:10.1016/j.tetlet.2004.06.057

We developed a facile synthetic method for 9-phenyl-7H-benzocycloheptene derivatives from the Baylis-Hillman adducts. Our method involved intramolecular Friedel-Crafts alkenylation reaction of triple bond-tethered methyl cinnamates.

Full text of DOI:10.1016/j.tetlet.2004.06.057

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 6141–6146
Synthesis of methyl 9-phenyl-7H-benzocycloheptene-6-
carboxylates from Baylis–Hillman adducts: use of intramolecular
Friedel–Crafts alkenylation reaction
Saravanan GowriSankar, Ka Young Lee, Chang Gon Lee and Jae Nyoung Kim*
Department of Chemistry and Institute of Basic Science, Chonnam National University, Kwangju 500-757, South Korea
Received 28 April2004; revised 24 May 2004; accepted 11 June 2004
Available online 2 July 2004
Abstract—We developed a facile synthetic method for 9-phenyl-7H-benzocycloheptene derivatives from the Baylis–Hillman
adducts. Our method involved intramolecular Friedel–Crafts alkenylation reaction of triple bond-tethered methyl cinnamates.
ꢀ 2004 Elsevier Ltd. All rights reserved.
Although Friedel–Crafts alkylation reactions have been
extensively studied,1 little has been known about the
corresponding Friedel–Crafts alkenylation reaction with
either an alkyne2 or an alkenyl halide.3;4 A substituent
that can stabilize the vinyl cation must be attached for
the successful alkenylation with alkenyl halide.3;4 The
reaction involving alkyne itself suffers from side reac-
tions including polymerization.2c Recently, successful
intermolecular Friedel–Crafts alkenylation using zeolite
HSZ-360,2a GaCl3,4c;d M(OTf)n (M ¼ Sc, Zr, In)2c have
been reported. More recently, Reetz and Sommer re-
ported the novel gold-catalyzed hydroarylation of al-
kynes.2b
coumarins and a-pyrones via electrophilic cyclization.6
We were stimulated by their works and envisioned that
we could synthesize suitably substituted a-pyrone
derivatives starting from the Baylis–Hillman adducts
(Scheme 1). The requisite starting material 2a was pre-
pared from the reaction of Baylis–Hillman acetate 1a
and phenylethynylmagnesium bromide in THF at
room temperature in the presence of CuI (10 mol%) in
moderate yield.7 We expected that benzyl-substituted a-
pyrones could be synthesized via the electrophile-pro-
moted (e.g., Iþ or Hþ) lactonization followed by proton
transfer as shown in Scheme 1.
We examined the electrophile-promoted lactonization of
2a under various reaction conditions including the use
of iodine, iodine/LiI/AcOH, LiClO4 and found that all
conditions failed to give the desired pyrone derivative.6
Low molecular weight a-pyrones have been shown to be
potent HIV-1 protease inhibitors.5 Recently, Larock
and Rossi have reported an elegant synthesis of iso-
O
O
O
CH3
O
O
O
Ph
Ph
E = H or I
E
Ph
E
E
2a
Scheme 1.
Keywords: Baylis–Hillman adducts; Benzocycloheptene; Friedel–Crafts alkenylation.
* Corresponding author. Tel.: +82-62-530-3381; fax: +82-62-530-3389; e-mail: kimjn@chonnam.ac.kr
0040-4039/$ - see front matter ꢀ 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.06.057

6142
S. GowriSankar et al. / Tetrahedron Letters 45 (2004) 6141–6146
R2
COOMe
R2 OAc
THF, PhCCMgBr
COOMe
R1
R1
1a-f
2a-f
1a: R1 = H, R2 = H
1b: R1 = CH3, R2 = H
1c: R1 = Cl, R2 = H
1d: R1 = H, R2 = Cl
1e: R1 = Cl, R2 = Cl
1f: R1 = Ph, R2 = H
o
→
H2SO4, 0 C rt
R2
R2
COOMe
COOMe
R1
R1
3a-f
Scheme 2.
However, when we treated the starting material 2a with
H2SO4 in CH2Cl2 we obtained methyl9-pheny-l7 H-
benzocycloheptenecarboxylate (3a)8;9 as the major
product (41%) and hydration product as the minor
(10%).10 For the hydration reaction, complete regio-
selectivity was observed to produce methyl 2-(3-oxo-3-
phenylpropyl)cinnamate.
As shown in Scheme 2 and in Table 1, starting materials
2b–f and the desired finalproducts 3b–f were synthesized
Table 1. Synthesis of 9-substituted-7H-benzocycloheptene derivatives 3
Entry
Conditions
2
Conditions
3
COOMe
Ph
COOMe
1
1a, THF, PhCCMgBr
(1.5 equiv), CuI (10 mol%),
0 ꢁC fi rt, 8 h
CH2Cl2, H2SO4 (1.2 equiv),
0 ꢁC fi rt, 12 h
2a (51%)
Ph
3a (41%)a
COOMe
COOMe
2
3
4
1b, THF, PhCCMgBr
(1.3 equiv), CuI (10 mol%),
0 ꢁC fi rt, 12 h
CH2Cl2, H2SO4 (1.2 equiv),
0 ꢁC fi rt, 12 h
H3C
H3C
Ph
2b (50%)
Ph
3b (47%)
COOMe
COOMe
1c, THF, PhCCMgBr
(1.5 equiv), CuI (10 mol%),
0 ꢁC fi rt, 8 h
CH2Cl2, H2SO4 (1.2 equiv),
0 ꢁC fi rt, 12 h
Cl
2c (60%)
Cl
Ph
Ph
3c (44%)
Cl
Cl
COOMe
COOMe
Ph
1d, THF, PhCCMgBr
(1.5 equiv), 0 ꢁC fi rt, 8 h
CH2Cl2, H2SO4 (1.2 equiv),
0 ꢁC fi rt, 9 h
2d (55%)
Ph
3d (62%)
Cl
Cl
COOMe
COOMe
Ph
5
1e, THF, PhCCMgBr
(1.3 equiv), CuI (10 mol%),
0 ꢁC fi rt, 8 h
CH2Cl2, H2SO4 (1.2 equiv),
0 ꢁC fi rt, 8 h
Cl
Cl
2e (46%)
Ph
3e (49%)

S. GowriSankar et al. / Tetrahedron Letters 45 (2004) 6141–6146
6143
Table 1 (continued)
Entry
Conditions
2
Conditions
3
COOMe
COOMe
Ph
6
1f, THF, PhCCMgBr
(1.8 equiv), 0 ꢁC fi rt, 8 h
CH2Cl2, H2SO4 (1.2 equiv),
0 ꢁC fi rt, 8 h
Ph
2f (63%)
Ph
Ph
3f (56%)
COOMe
COOMe
7
8
1a, THF, CH3CCMgBr
(1.3 equiv), 0 ꢁC fi rt, 7 h
CH2Cl2, H2SO4 (1.2 equiv),
0 ꢁC fi rt, 16 h
CH3
2g (75%)
H3C
3g (10%)b
COOMe
COOMe
1c, THF, CH3CCMgBr
(1.4 equiv), 0 ꢁC fi rt, 7 h
CH2Cl2, H2SO4 (1.2 equiv),
0 ꢁC fi rt, 12 h
Cl
2h (60%)
Cl
CH3
H3C
3h (24%)b
a Hydration product was isolated in about 10% yield.
b See text and Scheme 3.
without any problems in moderate yields.9;10 The reac-
tion mechanism (Scheme 2) involved the selective for-
mation of vinyl cation at the benzylic site following
intramolecular Friedel–Crafts alkenylation. The arene
moieties of 2a–f are in electron-deficient state due to the
electron withdrawing conjugated ester moiety. The
highly electron-deficient arene moiety of 2e underwent
the cyclization in a similar yield, very interestingly. In
these reactions, we cannot detect nor isolate the corre-
sponding naphthalene derivatives (vide infra), which
might be produced via the regioisomeric vinylcationic
intermediate. In some cases, we isolated the hydration
product during the conversion of 2 into 3 (vide supra).10
But, as mentioned above, one form of regioisomeric
hydration product was isolated as the sole product due
to the selective formation of vinylic cation at the ben-
zylic site. This meant that the vinylic cation at the
benzylic site would be much more stable than the other
regioisomeric vinylcation. As a next tria,l we carried
out the reaction of 2a in benzene in order to examine
the relative reactivities between the intramolecular se-
ven-membered ring formation and the intermolecular
COOMe
THF, CH3CCMgBr
1a or 1c
R1
CH3
2g (R1 = H)
2h (R1 = Cl)
H2SO4, 0oC →rt
COOMe
COOMe
R1
R1
CH3
CH3
(I)
(II)
COOMe
COOMe
COOMe
O
COOMe
O
R1
R1
R1
R1
CH3
H3C
20% (R1 = H)
18% (R1 = Cl)
3g (R1 = H, 10%)
3h (R1 = Cl, 24%)
not formed (R1 = H)
4% (R1 = Cl)
4g (R1 = H, 10%)
4h (R1 = Cl, 4%)
Scheme 3.

6144
S. GowriSankar et al. / Tetrahedron Letters 45 (2004) 6141–6146
EWG
EWG
N
Basavaiah
R
N
O
R
OH
EWG
EWG
EWG
COOMe
O
EWG
This work
R
R
Scheme 4.
Friedel–Crafts alkenylation with benzene. In the reac-
tion, we could isolate the benzocycloheptene derivative
3a as the sole product although the yield is lower than
the reaction in CH2Cl2. When we used Sc(OTf)3 in
dichloroethane2c instead of H2SO4 we could obtain
similar results (benzocycloheptene derivative as the
major product and trace amounts of hydration prod-
uct).
data was obtained from the Korea Basic Science Insti-
tute, Kwangju branch.
References and notes
1. For reviews of Friedel–Crafts alkylation reactions, see: (a)
Olah, G. A. In Friedel–Crafts and Related Reactions;
Wiley-Interscience: New York, 1964; Vol. II, part 1; (b)
Olah, G. A.; Krishnamurti, R.; Prakash, G. K. S. In
Friedel–Crafts Alkylations in Comprehensive Organic Syn-
thesis; Trost, B. M., Fleming, I., Eds.; Pergamon: Oxford,
1991.
2. Friedel–Crafts alkenylation of arenes using alkynes, see:
(a) Sartori, G.; Bigi, F.; Pastorio, A.; Porta, C.; Arienti,
A.; Maggi, R.; Moretti, N.; Gnappi, G. Tetrahedron Lett.
1995, 36, 9177; (b) Reetz, M. T.; Sommer, K. Eur. J. Org.
Chem. 2003, 3485; (c) Tsuchimoto, T.; Maeda, T.;
Shirakawa, E.; Kawakami, Y. Chem. Commun. 2000,
1573; (d) Asao, N.; Shimada, T.; Shimada, T.; Yamamoto,
Y. J. Am. Chem. Soc. 2001, 123, 10899; (e) Inoue, H.;
Chatani, N.; Murai, S. J. Org. Chem. 2002, 67, 1414; (f)
Martin-Matute, B.; Nevado, C.; Cardenas, D. J.; Echa-
varren, A. M. J. Am. Chem. Soc. 2003, 125, 5757, and
references cited therein.
When we tried the same reaction with methylgroup-
substituted starting materials 2g and 2h (prepared by
1-propynylmagnesium bromide), competitions were
observed. Two types of vinylcations might be formed ( I
and II in Scheme 3), and the reactions produced mix-
tures of products, namely, benzocycloheptene deriva-
tives (3g and 3h) and naphthalene derivatives (4g and
4h) and two kinds of hydration products in a variable
ratio.11 These results can be expected generally when we
consider the comparable stabilities of two vinyl cations I
and II.
Recently, Basavaiah and co-workers have reported the
synthesis of 2-benzazepines and 2-benzoxepines from
the Baylis–Hillman adducts.12 Our synthesis of 7H-
benzocycloheptene derivatives is a carbon surrogate of
Basavaiah’s syntheses (Scheme 4) as well as a new
achievement of our chemicaltransformations of the
Baylis–Hillman adducts.13
3. For alkenylation of arenas via vinyl cation trapping, see:
(a) Takeda, T.; Kanamori, F.; Matsusita, H.; Fujiwara, T.
Tetrahedron Lett. 1991, 32, 6563; (b) Gronheid, R.;
Lodder, G.; Okuyama, T. J. Org. Chem. 2002, 67, 693;
(c) Kitamura, T.; Kobayashi, S.; Taniguchi, H.; Rappo-
port, Z. J. Org. Chem. 1982, 47, 5003.
4. For other alkenylation of arenes, see: (a) Ishikawa, T.;
Okano, M.; Aikawa, T.; Saito, S. J. Org. Chem. 2001, 66,
4635; (b) Sangu, K.; Fuchibe, K.; Akiyama, T. Org. Lett.
2004, 6, 353; (c) Yamaguchi, M.; Kido, Y.; Hayashi, A.;
Hirama, M. Angew. Chem., Int. Ed. 1997, 36, 1313; (d)
Kido, Y.; Yoshimura, S.; Yamaguchi, M.; Uchimaru, T.
Bull. Chem. Soc. Jpn. 1999, 72, 1445; (e) Barluenga, J.;
Rodriguez, M. A.; Gonzalez, J. M.; Campos, P. J.
Tetrahedron Lett. 1990, 31, 4207.
In summary, we developed a facile synthetic method of
7H-benzocycloheptene derivatives. Our synthetic
scheme involved the novel intramolecular Friedel–
Crafts alkenylation reaction with electron-deficient
arene moiety. We are currently studying the feasibility
for the synthesis of further-reduced benzocycloheptene
derivatives by the reaction of Baylis–Hillman acetate
and styrene under the similar reaction conditions.
5. Vara Prasad, J. V. N.; Para, K. S.; Lunney, E. A.;
Ortwine, D. F.; Dunbar, J. B.; Fergunson, D.; Tummino,
P. J.; Hupe, D.; Tait, B. D.; Domagala, J. M.; Humblet,
C.; Bhat, T. N.; Liu, B.; Guerin, D. A. M.; Baldwin, E. T.;
Erickson, J. W.; Sawyer, T. K. J. Am. Chem. Soc. 1994,
116, 6989.
Acknowledgements
This work was supported by the grant (R05-2003-000-
10042-0) from the Basic Research Program of the Korea
Science and Engineering Foundation. Spectroscopic
6. Synthesis of isocoumarins and a-pyrones from acetylenic
compounds, see: (a) Rossi, R.; Carpita, A.; Bellina, F.;

S. GowriSankar et al. / Tetrahedron Letters 45 (2004) 6141–6146
6145
Stabile, P.; Mannina, L. Tetrahedron 2003, 59, 2067; (b)
Yao, T.; Larock, R. C. J. Org. Chem. 2003, 68, 5936; (c)
Yao, T.; Larock, R. C. Tetrahedron Lett. 2002, 43, 7401;
(d) Larock, R. C.; Doty, M. J.; Han, X. J. Org. Chem.
1999, 64, 8770; (e) Biagetti, M.; Bellina, F.; Carpita, A.;
Stabile, P.; Rossi, R. Tetrahedron 2002, 58, 5023; (f)
Oliver, M. A.; Gandour, R. D. J. Org. Chem. 1984, 49,
558.
7.68 (s, 4H), 7.85 (s, 1H); 13C NMR (CDCl3) d 18.86,
52.36, 81.05, 87.06, 123.58, 127.06, 127.27, 127.57, 127.74,
127.81, 128.16, 128.88, 130.35, 131.72, 133.88, 140.23,
140.33, 141.82, 167.74; Mass (70 eV) m=z (rel. intensity)
115 (100), 165 (50), 293 (66), 337 (37), 352 (Mþ, 30). 2g: 1H
NMR (CDCl3) d 1.82 (t, J ¼ 2:4 Hz, 3H), 3.32 (q,
J ¼ 2:4 Hz, 2H), 3.86 (s, 3H), 7.32–7.56 (m, 5H), 7.73 (s,
1H); 13C NMR (CDCl3) d 3.70, 18.06, 52.25, 76.22, 76.25,
128.43, 128.54, 128.90, 129.67, 135.02, 140.04, 167.86. 2h:
IR (neat) 1716, 1281, 1219 cmꢀ1; 1H NMR (CDCl3) d 1.81
(t, J ¼ 2:7 Hz, 3H), 3.28 (q, J ¼ 2:7 Hz, 2H), 3.86 (s, 3H),
7.37–7.50 (m, 4H), 7.66 (s, 1H); 13C NMR (CDCl3) d 3.67,
18.00, 52.33, 75.85, 76.58, 128.80, 128.93, 130.98, 133.39,
134.91, 138.69, 167.59; Mass (70 eV) m=z (rel. intensity) 43
(100), 153 (79), 189 (35), 213 (23), 248 (Mþ, 22). Synthesis
of 3a as a typicalprocedure: To a stirred soul tion of the
acetylenic compound 2a (276 mg, 1 mmol) in CH2Cl2
(5 mL) was added H2SO4 (12 mg, 1.2 mmol) at 0 ꢁC and
stirred at room temperature for 8 h. After usualaqueous
workup process and column chromatographic purification
process (hexanes/ether, 99:1) we obtained the desired
products 3a as an oil, 113 mg (41%). The other compounds
were synthesized similarly and the spectroscopic data are
7. In some cases, the purified compounds 2 have some
inseparable impurities and made the next step problem-
atic. In those cases (entries 1–3 and entry 5) we used CuI
(10 mol%) during the preparation of 2 and we could
obtain pure compounds.
8. For the chemistry of benzocycloheptene and related
systems, see: (a) Perron-Sierra, F.; Dizier, D. S.; Bertrand,
M.; Genton, A.; Tucker, G. C.; Casara, P. Bioorg. Med.
Chem. Lett. 2002, 12, 3291; (b) Kirmse, W.; Sluma, H.-D.
J. Org. Chem. 1988, 53, 763; (c) Bonvallet, P. A.; Todd, E.
M.; Kim, Y. S.; McMahon, R. J. J. Org. Chem. 2002, 67,
9031; (d) Ewing, G. D.; Paquette, L. A. J. Org. Chem.
1975, 40, 2965; (e) Battye, P. J.; Jones, D. W. J. Chem.
Soc., Chem. Commun. 1984, 1458; (f) Saito, K.; Ishihara,
H. Bull. Chem. Soc. Jpn. 1985, 58, 2664; (g) Pomerantz,
M.; Gruber, G. W. J. Am. Chem. Soc. 1967, 89, 6798; (h)
Saito, K.; Ishihara, H. Bull. Chem. Soc. Jpn. 1987, 60,
4447; (i) Kryczka, B.; Descotes, G. Bull. Pol. Acad. Sci.
1986, 33, 475; (j) Buu-Hoi, N. P.; Jacquignon, P.; Roussel,
O. Bull. Soc. Chim. Fr. 1962, 1652; (k) Huisgen, R.; Juppe,
G. Chem. Ber. 1961, 94, 2332.
1
as follows. 3a: IR (neat) 1712, 1277, 1203 cmꢀ1; H NMR
(CDCl3) d 2.78 (d, J ¼ 7:5 Hz, 2H), 3.83 (s, 3H), 6.12 (t,
J ¼ 7:5 Hz, 1H), 7.13–7.59 (m, 9H), 7.77 (s, 1H); 13C
NMR (CDCl3) d 24.93, 52.13, 126.58, 127.16, 127.21,
127.58, 128.09, 129.01, 130.24, 131.15, 132.38, 136.11,
137.65, 139.57, 141.78, 142.91, 166.65; Mass (70 eV) m=z
(rel. intensity) 43 (100), 202 (1), 215 (2), 275 (Mþ)1, 1). 3b:
IR (neat) 1709, 1277, 1200 cmꢀ1; 1H NMR (CDCl3) d 2.29
(s, 3H), 2.77 (d, J ¼ 7:5 Hz, 2H), 3.82 (s, 3H), 6.09 (t,
J ¼ 7:5 Hz, 1H), 7.07–7.41 (m, 8H), 7.75 (s, 1H); 13C
NMR (CDCl3) d 21.38, 24.96, 52.05, 127.07, 127.38,
127.76, 128.07, 128.98, 130.25, 131.32, 131.36, 133.58,
137.23, 137.79, 139.46, 141.68, 143.03, 166.72; Mass
(70 eV) m=z (rel. intensity) 43 (100), 107 (53), 215 (45),
9. Synthesis of 2a as a typicalprocedure: To a stirred
solution of the Baylis–Hillman acetate 1a (234 mg,
1 mmol) in dry THF (2 mL) was added CuI (20 mg,
10 mol%). To the reaction mixture was added dropwise
the solution of phenylethynylmagnesium bromide (1 M
solution in THF, 1.5 mL, 1.5 mmol) at 0 ꢁC and stirred
further at room temperature for 8 h. After usualaqueous
workup process and column chromatographic purification
process (hexanes/ether, 99:1) we obtained the desired
products 2a as an oil, 141 mg (51%). The other compounds
were synthesized similarly and the spectroscopic data are
1
231 (24), 290 (Mþ, 25). 3c: H NMR (CDCl3) d 2.78 (d,
J ¼ 7:5 Hz, 2H), 3.83 (s, 3H), 6.14 (t, J ¼ 7:5 Hz, 1H),
7.12–7.45 (m, 8H), 7.71 (s, 1H); 13C NMR (CDCl3) d
24.91, 52.20, 126.93, 127.48, 128.30, 128.54, 128.94,
130.68, 131.60, 132.65, 133.07, 134.53, 136.58, 140.93,
141.10, 142.14, 166.38; Mass (70 eV) m=z (rel. intensity) 94
(59), 107 (92), 251 (23), 310 (Mþ, 21), 312 (Mþ+2, 8). 3d:
IR (neat) 1712, 1269, 1203 cmꢀ1; 1H NMR (CDCl3) d 2.75
(d, J ¼ 7:5 Hz, 2H), 3.84 (s, 3H), 6.22 (t, J ¼ 7:5 Hz, 1H),
7.11–7.44 (m, 8H), 7.97 (s, 1H); 13C NMR (CDCl3) d
25.12, 52.25, 127.32, 127.64, 127.73, 128.17, 128.88,
129.56, 129.64, 133.20, 133.54, 133.90, 134.40, 141.20,
141.36, 142.46, 166.25; Mass (70 eV) m=z (rel. intensity) 94
(55), 107 (100), 215 (99), 251 (26), 310 (Mþ, 18), 312
1
as follows. 2a: IR (neat) 2950, 1712, 1273, 1219 cmꢀ1; H
NMR (CDCl3) d 3.61 (s, 2H), 3.88 (s, 3H), 7.24–7.61 (m,
10H), 7.81 (s, 1H); 13C NMR (CDCl3) d 18.76, 52.35,
80.94, 87.09, 123.59, 127.69, 127.79, 128.14, 128.63,
129.04, 129.72, 131.71, 134.94, 140.72, 167.73; Mass
(70 eV) m=z (rel. intensity) 115 (56), 202 (47), 215 (100),
1
261 (30), 276 (Mþ, 19). 2b: H NMR (CDCl3) d 2.38 (s,
3H), 3.61 (s, 2H), 3.86 (s, 3H), 7.23–7.51 (m, 9H), 7.78 (s,
1H); 13C NMR (CDCl3) d 18.79, 21.41, 52.29, 80.87, 87.25,
123.68, 126.78, 127.77, 128.15, 129.39, 129.86, 131.73,
132.12, 139.34, 140.81, 167.89; Mass (70 eV) m=z (rel.
1
1
intensity) 43 (100), 115 (8), 215 (10), 290 (Mþ, 1). 2c: H
(Mþ+2, 8). 3e: IR (neat) 2962, 1716, 1265, 1092 cmꢀ1; H
NMR (CDCl3) d 3.58 (s, 2H), 3.88 (s, 3H), 7.25–7.55 (m,
9H), 7.75 (s, 1H); 13C NMR (CDCl3) d 18.71, 52.43, 81.25,
86.63, 123.41, 127.91, 128.18, 128.26, 128.91, 131.02,
131.69, 133.35, 135.10, 139.37, 167.47. 2d: IR (neat)
NMR (CDCl3) d 2.75 (d, J ¼ 7:5 Hz, 2H), 3.84 (s, 3H),
6.24 (t, J ¼ 7:5 Hz, 1H), 7.10–7.45 (m, 7H), 7.89 (s, 1H);
13C NMR (CDCl3) d 25.15, 52.36, 127.65, 127.72, 128.40,
128.85, 129.34, 130.53, 132.42, 132.47, 132.93, 133.81,
135.18, 140.46, 141.75, 142.31, 166.04; Mass (70 eV) m=z
(rel. intensity) 106 (81), 215 (100), 249 (53), 285 (36), 344
(Mþ, 41), 346 (Mþ+2, 29). 3f: IR (neat) 1709, 1277,
2951, 1720, 1288, 1211 cmꢀ1 1H NMR (CDCl3) d 3.50
;
(s, 2H), 3.88 (s, 3H), 7.23–7.70 (m, 9H), 7.90 (s, 1H); 13C
NMR (CDCl3) d 18.82, 52.29, 81.18, 86.75, 123.39, 126.72,
127.75, 128.06, 129.52 (2C), 130.01, 130.36, 131.56, 133.42,
134.17, 137.42, 166.98; Mass (70 eV) m=z (rel. intensity)
107 (52), 115 (73), 215 (100), 275 (29), 310 (Mþ, 10), 312
1
1207 cmꢀ1; H NMR (CDCl3) d 2.83 (d, J ¼ 7:5 Hz, 2H),
3.84 (s, 3H), 6.16 (t, J ¼ 7:5 Hz, 1H), 7.18–7.58 (m, 13H),
7.81 (s, 1H); 13C NMR (CDCl3) d 25.04, 52.13, 125.41,
127.13, 127.23, 127.58, 127.66, 128.17, 128.75, 128.95,
129.63, 130.84, 132.20, 135.15, 137.42, 139.84, 139.96,
140.24, 141.78, 142.77, 166.62; Mass (70 eV) m=z (rel.
intensity) 91 (56), 144 (67), 215 (49), 293 (82), 352 (Mþ,
100). 3g: 1H NMR (CDCl3) d 2.13 (s, 3H), 2.61 (d,
J ¼ 7:2 Hz, 2H), 3.83 (s, 3H), 5.86 (t, J ¼ 7:2 Hz, 1H),
1
(Mþ +2, 3). 2e: H NMR (CDCl3) d 3.48 (s, 2H), 3.89 (s,
3H), 7.19–7.41 (m, 6H), 7.46 (d, J ¼ 2:1 Hz, 1H), 7.64 (d,
J ¼ 8:1 Hz, 1H), 7.82 (s, 1H); 13C NMR (CDCl3) d 18.95,
52.54, 81.58, 86.45, 123.35, 127.27, 127.98, 128.22, 129.58,
130.19, 131.27, 131.68, 132.10, 135.07, 135.43, 136.41,
166.93. 2f: IR (neat) 1712, 1277, 1208 cmꢀ1
;
1H NMR
1
(CDCl3) d 3.66 (s, 2H), 3.89 (s, 3H), 7.24–7.64 (m, 10H),
7.31–7.63 (m, 4H), 7.66 (s, 1H). 3h: H NMR (CDCl3) d

6146
S. GowriSankar et al. / Tetrahedron Letters 45 (2004) 6141–6146
2.11 (s, 3H), 2.61 (d, J ¼ 7:2 Hz, 2H), 3.83 (s, 3H), 5.87 (t,
Methyl p-chloro-2-(3-oxobutyl)cinnamate: 1H NMR
(CDCl3) d 2.15 (s, 3H), 2.63–2.70 (m, 2H), 2.75–2.81 (m,
2H), 3.82 (s, 3H), 7.25–7.42 (m, 5H), 7.65 (s, 1H). Methyl
p-chloro-2-(2-oxobutyl)cinnamate: 1H NMR (CDCl3) d
1.10 (t, J ¼ 7:5 Hz, 3H), 2.57 (q, J ¼ 7:5 Hz, 2H), 3.56 (s,
2H), 3.80 (s, 3H), 7.21–7.37 (m, 4H), 7.86 (s, 1H).
J ¼ 7:2 Hz, 1H), 7.28–7.56 (m, 3H), 7.59 (s, 1H).
10. During the synthesis of 3a, the corresponding acid-
catalyzed hydration product, methyl 2-(3-oxo-3-phenyl-
propyl)cinnamate, was isolated in about 10% yield; 1H
NMR (CDCl3) d 2.95–3.01 (m, 2H), 3.20–3.26 (m, 2H),
3.84 (s, 3H), 7.30–7.59 (m, 8H), 7.77 (s, 1H), 7.98 (d,
J ¼ 8:4 Hz, 2H).
12. For the construction of fused seven-membered rings from
the Baylis–Hillman adducts, see: (a) Basavaiah, D.;
Satyanarayana, T. Chem. Commun. 2004, 32; (b) Basava-
iah, D.; Sharada, D. S.; Veerendhar, A. Tetrahedron Lett.
2004, 45, 3081.
13. For our recent publications on the Baylis–Hillman reaction,
see: (a) Kim, J. M.; Lee, K. Y.; Lee, S.-K.; Kim, J. N.
Tetrahedron Lett. 2004, 45, 2805; (b) Lee, K. Y.; Kim, J. M.;
Kim, J. N. Tetrahedron Lett. 2003, 44, 6737; (c) Kim, J. N.;
Kim, J. M.; Lee, K. Y. Synlett 2003, 821; (d) Im, Y. J.; Lee,
C. G.; Kim, H. R.; Kim, J. N. Tetrahedron Lett. 2003, 44,
2987; (e) Lee, K. Y.; Kim, J. M.; Kim, J. N. Synlett 2003,
357; (f) Kim, J. N.; Lee, H. J.; Lee, K. Y.; Gong, J. H.
Synlett 2002, 173; (g) Lee, K. Y.; Kim, J. M.; Kim, J. N.
Tetrahedron 2003, 59, 385, and references cited therein.
11. Spectroscopic data of naphthalenes 4g–h and hydration
products are as follows. The Rf values of benzocyclohept-
enes and naphthalenes were similar, thus we separated
them together. The two types of hydration products also
have similar Rf values and we separated them together. 4g:
1H NMR (CDCl3) d 1.41 (t, J ¼ 7:5 Hz, 3H), 3.14 (q,
J ¼ 7:5 Hz, 2H), 3.98 (s, 3H), 7.50–7.65 (m, 2H), 7.93 (s,
1H), 7.96 (d, J ¼ 8:7 Hz, 1H), 8.80 (d, J ¼ 8:1 Hz, 1H),
1
8.47 (s, 1H). 4h: H NMR (CDCl3) d 1.40 (t, J ¼ 7:2 Hz,
3H), 3.10 (q, J ¼ 7:2 Hz, 2H), 3.98 (s, 3H), 7.50–8.05 (m,
4H), 8.43 (s, 1H). Methyl2-(3-oxobuty)lcinnamate:
1H
NMR (CDCl3) d 2.15 (s, 3H), 2.65–2.71 (m, 2H), 2.77–
2.84 (m, 2H), 3.82 (s, 3H), 7.30–7.42 (m, 5H), 7.72 (s, 1H).