Regioselective construction of polysubstituted pyridine ring from Baylis-Hillman adducts via sequential introduction of tosylamide, Michael reaction, aldol condensation, and elimination of TsH

Article abstract of DOI:10.1016/j.tetlet.2005.10.034

Facile synthetic method of polysubstituted pyridine derivatives was developed starting from the Baylis-Hillman adducts. The reaction involved sequential introduction of tosylamide, Michael addition, aldol condensation, elimination of p-toluenesulfinic aci

Full text of DOI:10.1016/j.tetlet.2005.10.034

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 8799–8803
Regioselective construction of polysubstituted pyridine ring
from Baylis–Hillman adducts via sequential introduction
of tosylamide, Michael reaction, aldol condensation,
and elimination of TsH
Da Yeon Park,a Mi Jung Lee,a Taek Hyeon Kimb and Jae Nyoung Kima,*
aDepartment of Chemistry and Institute of Basic Science, Chonnam National University, Gwangju 500-757, South Korea
bDepartment of Applied Chemistry, Chonnam National University, Gwangju 500-757, South Korea
Received 14 September 2005; accepted 7 October 2005
Available online 26 October 2005
Abstract—Facile synthetic method of polysubstituted pyridine derivatives was developed starting from the Baylis–Hillman adducts.
The reaction involved sequential introduction of tosylamide, Michael addition, aldol condensation, elimination of p-toluenesulfinic
acid, and isomerization process.
Ó 2005 Elsevier Ltd. All rights reserved.
Recently, syntheses of a variety of heterocyclic com-
pounds1a,b from Baylis–Hillman adducts have been
reported including the synthesis of quinolines,1c pyraz-
oles,1d and furans.1e However, to the best of our
knowledge, synthesis of pyridine derivatives from
Baylis–Hillman adducts has not been reported. The
prevalence of pyridines in nature and their central role
as versatile building blocks in the synthesis of natural
products as well as biologically active compounds have
led to a continued interest in the practical synthesis of
pyridine derivatives.2 In these respects, we now wish to
report the first synthesis of highly substituted pyridine
scaffold starting from the Baylis–Hillman adducts.3
spots corresponded to the two diastereomers of 4a,
which might be formed via Michael reaction of 2a and
MVK and the following aldol cyclization reaction of
3a.6 Thus, we did not try to separate the diastereomers
4a in pure states.7 Instead, we tried the next dehydration
reaction with crude mixtures of 4a after simple aqueous
workup. Dehydration was conducted in benzene with
catalytic amounts of p-TsOH under refluxing condi-
tions. We could obtain the expected compound 5a in
pure state by column chromatography after the reac-
tion.8 With this compound 5a in our hands we examined
a variety of conditions to convert 5a into the final pyri-
dine derivative 6a.9 The use of Cs2CO3 in DMF at
around 120–130 °C gave the best yield of product. The
use of K2CO3 (DMF, 90–100 °C, 30 h, 39%), DBU
(dioxane, reflux, 24 h, low yield), t-BuOK (THF, rt,
30 h, 44%), n-Bu4NF (THF, reflux, 5 h, 47%) all gave
lower yields than Cs2CO3 (DMF, 120 °C, 1 h, 56%)
conditions.
The Baylis–Hillman adducts derived from methyl vinyl
ketone or ethyl vinyl ketone were converted into their
acetates 1 (Ac2O, DMAP) and transformed to 2 by the
SN20 reaction with p-toluenesulfonamide as reported.4,5
Initially, we tried the synthesis of pyridine 6a starting
from 2a (Scheme 1). The reaction of 2a and methyl vinyl
ketone (MVK) under the influence of DBU in THF pro-
duced two major components on TLC, which were very
difficult to separate. Later, it was found that the two
By using the optimized reaction conditions we synthe-
sized pyridine derivatives 6b–f as shown in Table 1 in
reasonable yields. We prepared 6b and 6c without any
problems (entries 2 and 3). However, we found an inter-
esting isomerization during the synthesis of 5d (entry 4).
We obtained 5d in 38% yield. Instead we could isolate
another compound 5d0 in 31% yield and the structure
was confirmed by using various spectroscopic data
including NOE experiments as shown in Scheme 2.
Keywords: Pyridines; Baylis–Hillman adducts; Michael reaction;
Cyclization.
*
Corresponding author. Tel.: +82 62 530 3381; fax: +82 62 530
3389; e-mail: kimjn@chonnam.ac.kr
0040-4039/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.10.034

8800
D. Y. Park et al. / Tetrahedron Letters 46 (2005) 8799–8803
TsNH2
K2CO3
aq THF
O
N
O
OAc O
MVK
DBU, THF
Ph
O
Ph
Ph
NH
Ts
Ts
3a
1a
2a
O
O
O
HO
p-TsOH
benzene
Cs2CO3
DMF
Ph
Ph
Ph
N
N
N
Ts
5a
Ts
4a
6a
Scheme 1.
Table 1. Synthesis of 3,4,5-trisubstituted pyridines
Entry
Substrate 2a (%)
Intermediate 5b (%)
Pyridine 6c (%)
O
O
O
Ph
Ph
1
Ph
NH
Ts
N
2a(66)
5a(87)
N
6a(56)
Ts
O
O
O
2
NH
Ts
N
Cl
Cl
N
Cl
6b (60)
2b (64)
Ts
5b (72)
O
O
O
3
4
NH
Ts
N
N
6c(64)
Ts
2c(64)
5c(80)
O
O
O
O
O
Ph
Ph
Ph
Ph
Ph
Ph
NH
Ts
N
5d (38)d
5e (85)
2d (51)
N
6d (53)
6e (53)
Ts
O
O
O
5
6
7
2a
2a
Ph
N
N
Ts
OMe
OMe
Ph
N
5f (61)
N
6f (52)
Ts
O
Ph
6a (53)
NH
Ms
N
2e (53)
5g (67)
Ms
a Substrate 1, TsNH2, or CH3SO2NH2 (1 equiv), aq THF, K2CO3 (1.2 equiv), reflux, 5–16 h.
b (1) Michael acceptor (1.5 equiv), DBU (0.5 equiv), THF, rt, 3–24 h, (2) aq workup, (3) benzene, p-TsOH (0.1 equiv), reflux, 1–5 h.
c DMF, Cs2CO3 (3 equiv), 120–130 °C, 0.5–3 h.
d The corresponding exo-ethylidene compound 5d0 was isolated in 31% yield.

D. Y. Park et al. / Tetrahedron Letters 46 (2005) 8799–8803
8801
3.3%
H
1.9%
O
H
O
1. MVK, DBU, THF
2. p-TsOH, benzene
Ph
Ph
+
2d
N
N
Ts
Ts
5d (38%)
5d' (31%)
Cs2CO3, DMF
Cs2CO3, DMF
6d (49%)
6d (53%)
Scheme 2.
Fortunately, however, the two compounds 5d and 5d0
could be changed to 6d in similar yields. The use of ethyl
vinyl ketone or methyl acrylate as the Michael acceptors
did not show any differences during the whole steps to
give 6e and 6f (entries 5 and 6) in moderate yields. As
the last entry, the use of methanesulfonamide instead
of p-toluenesulfonamide showed similar results (entry
7).
4. Synthesis of starting materials 2a–e was carried out by the
reaction of tosylamide and the Baylis–Hillman acetates in
the presence of K2CO3 in aq THF under refluxing
conditions according to the previous paper. (a) Kim, J.
N.; Chung, Y. M.; Im, Y. J. Tetrahedron Lett. 2002, 43,
6209; (b) Kim, J. N.; Lee, H. J.; Lee, K. Y.; Kim, H. S.
Tetrahedron Lett. 2001, 42, 3737.
5. Typical procedure for the synthesis of starting materials 2a:
To a stirred mixture of the Baylis–Hillman acetate (436 mg,
2.0 mmol) of benzaldehyde and methyl vinyl ketone and
p-toluenesulfonamide (342 mg, 2.0 mmol) in aq THF
(5 mL) was added K2CO3 (332 mg, 2.4 mmol) and heated
to reflux for 16 h. After the usual workupand column
chromatographic purification process (hexanes/ether, 5:2)
we obtained 2a as a white solid, 433 mg (66%). The other
compounds were synthesized analogously and the spectro-
scopic data are as follows.
In summary, we developed an efficient synthetic route
for 3,4,5-trisubstituted pyridine derivatives starting from
the Baylis–Hillman adducts of methyl vinyl ketone and
ethyl vinyl ketone. The synthesis was achieved by
following the successive steps: (i) introduction of tosyl-
amide, (ii) Michael addition, (iii) aldol condensation,
(iv) elimination of p-toluenesulfinic acid, and finally
isomerization of double bond.
Compound 2a: 66%; white solid, mp120–121 °C; IR (KBr)
3271, 1658, 1161 cmꢀ1; 1H NMR (CDCl3, 300 MHz): d 2.33
(s, 3H), 2.41 (s, 3H), 3.89 (d, J = 6.6 Hz, 2H), 5.29
(t, J = 6.6 Hz, 1H), 7.24–7.67 (m, 10H); 13C NMR (CDCl3,
75 MHz): d 21.44, 25.41, 39.95, 127.20, 128.79, 129.55,
129.57, 129.71, 133.77, 135.73, 136.46, 143.33, 144.11,
200.45.
References and notes
1. (a) Basavaiah, D.; Rao, A. J.; Satyanarayana, T. Chem.
Rev. 2003, 103, 811; (b) Kim, J. N.; Lee, K. Y. Curr. Org.
Chem. 2002, 6, 627; (c) Lee, K. Y.; Kim, J. M.; Kim, J. N.
Tetrahedron 2003, 59, 385; (d) Lee, K. Y.; Kim, J. M.; Kim,
J. N. Tetrahedron Lett. 2003, 44, 6737; (e) Kim, J. M.; Lee,
K. Y.; Lee, S.; Kim, J. N. Tetrahedron Lett. 2004, 45, 2805.
2. For recent synthesis of pyridine derivatives, see: (a) Suzuki,
D.; Nobe, Y.; Watai, Y.; Tanaka, R.; Takayama, Y.; Sato,
F.; Urabe, H. J. Am. Chem. Soc. 2005, 127, 7474; (b) Xi, Z.;
Sato, K.; Gao, Y.; Lu, J.; Takahashi, T. J. Am. Chem. Soc.
2003, 125, 9568; (c) Charette, A. B.; Grenon, M.; Lemire,
A.; Pourashraf, M.; Martel, J. J. Am. Chem. Soc. 2001, 123,
11829; (d) Palacios, F.; Herran, E.; Rubiales, G.; Ezpeleta,
J. M. J. Org. Chem. 2002, 67, 2131; (e) Beccalli, E. M.;
Contini, A.; Trimarco, P. Tetrahedron Lett. 2004, 45, 3447;
(f) Heller, B.; Sundermann, B.; Buschmann, H.; Drexler,
H.-J.; You, J.; Holzgrabe, U.; Heller, E.; Oehme, G. J. Org.
Chem. 2002, 67, 4414; (g) Pal, M.; Batchu, V. R.; Dager, I.;
Swamy, N. K.; Padakanti, S. J. Org. Chem. 2005, 70, 2376,
and further references cited therein.
Compound 2b: 64%; white solid, mp88–89 °C; IR (KBr)
3271, 1662, 1327, 1161 cmꢀ1; 1H NMR (CDCl3, 300 MHz):
d 2.34 (s, 3H), 2.43 (s, 3H), 3.82 (d, J = 6.6 Hz, 2H), 5.29 (t,
J = 6.6 Hz, 1H), 7.28 (d, J = 8.4 Hz, 2H), 7.40 (s, 4H), 7.53
(s, 1H), 7.67 (d, J = 8.4 Hz, 2H); 13C NMR (CDCl3,
75 MHz): d 21.49, 25.41, 39.92, 127.23, 129.13, 129.67,
130.91, 132.22, 135.91, 136.25, 136.31, 142.70, 143.53,
200.21.
Compound 2c: 64%; white solid, mp114–115 °C; IR (KBr)
3271, 2924, 1658, 1327, 1161 cmꢀ1 1H NMR (CDCl3,
;
300 MHz): d 2.33 (s, 3H), 2.40 (s, 3H), 2.42 (s, 3H), 3.90
(d, J = 6.6 Hz, 2H), 5.23 (t, J = 6.6 Hz, 1H), 7.25 (d, J =
8.1 Hz, 2H), 7.27 (d, J = 8.1 Hz, 2H), 7.37 (d, J = 8.1 Hz,
2H), 7.54 (s, 1H), 7.67 (d, J = 8.1 Hz, 2H); 13C NMR
(CDCl3, 75 MHz): d 21.42, 21.48, 25.39, 40.11, 127.26,
129.61 (2C), 129.73, 130.97, 135.00, 136.55, 140.27, 143.34,
144.39, 200.47.
Compound 2d: 51%; white solid, mp135–137 °C; IR (KBr)
3275, 2924, 1662, 1331, 1161 cmꢀ1 1H NMR (CDCl3,
;
300 MHz): d 1.10 (t, J = 7.2 Hz, 3H), 2.42 (s, 3H), 2.70
(q, J = 7.2 Hz, 2H), 3.89 (d, J = 6.6 Hz, 2H), 5.24
(t, J = 6.6 Hz, 1H), 7.27 (d, J = 8.1 Hz, 2H), 7.37–7.47
(m, 5H), 7.60 (s, 1H), 7.67 (d, J = 8.1 Hz, 2H); 13C NMR
(CDCl3, 75 MHz): d 8.29, 21.48, 30.31, 40.29, 127.24,
128.84, 129.56, 129.63 (2C), 133.92, 135.30, 136.54, 142.79,
143.36, 203.10.
3. For our recent publications on the chemical transforma-
tions of Baylis–Hillman adducts, see: (a) Gowrisankar, S.;
Lee, K. Y.; Kim, J. N. Tetrahedron Lett. 2005, 46, 4859; (b)
Lee, K. Y.; Gowrisankar, S.; Kim, J. N. Tetrahedron Lett.
2005, 46, 5387; (c) Lee, C. G.; Lee, K. Y.; Lee, S.; Kim,
J. N. Tetrahedron 2005, 61, 1493, and further references
cited therein.

8802
D. Y. Park et al. / Tetrahedron Letters 46 (2005) 8799–8803
Compound 2e: 53%; white solid, mp63–65 °C; IR (KBr)
Compound 5d (24/2 h): 38%; clear oil; IR (film) 1682, 1597,
1350, 1246,1161 cmꢀ1; 1H NMR (CDCl3, 300 MHz): d 0.94
(t, J = 7.2 Hz, 3H), 2.30 (s, 3H), 2.38 (q, J = 7.2 Hz, 2H),
2.41 (s, 3H), 4.09 (s, 2H), 4.18 (s, 2H), 6.77 (s, 1H), 7.18–
7.55 (m, 9H); 13C NMR (CDCl3, 75 MHz): d 14.47, 21.47,
22.01, 30.20, 44.91, 46.12, 127.64, 127.91, 128.61, 129.07,
129.52, 129.58, 130.23, 131.55, 134.28, 135.96, 141.76,
143.77, 200.96.
3282, 1662, 1319, 1149 cmꢀ1; 1H NMR (CDCl3, 300 MHz):
d 2.49 (s, 3H), 2.95 (s, 3H), 4.10 (d, J = 6.3 Hz, 2H), 5.08
(t, J = 6.3 Hz, 1H), 7.41–7.53 (m, 5H), 7.73 (s, 1H); 13C
NMR (CDCl3, 75 MHz): d 25.58, 39.52, 39.58, 128.89,
129.45, 129.85, 133.72, 135.96, 144.51, 200.31.
6. For the applications of aldol type condensation reaction in
the transformations of Baylis–Hillman adducts, see: (a)
Kim, J. N.; Kim, J. M.; Lee, K. Y. Synlett 2003, 821; (b)
Im, Y. J.; Lee, C. G.; Kim, H. R.; Kim, J. N. Tetrahedron
Lett. 2003, 44, 2987; (c) Kim, J. N.; Im, Y. J.; Kim, J. M.
Tetrahedron Lett. 2002, 43, 6597.
Compound 5d0: 31%; clear oil; IR (film) 1712, 1597, 1346,
1165 cmꢀ1 1H NMR (CDCl3, 300 MHz): d 1.69 (d, J =
;
6.9 Hz, 3H), 2.19 (s, 3H), 2.42 (s, 3H), 2.92 (dd, J = 12.0
and 5.1 Hz, 1H), 3.49 (dd, J = 13.5 and 2.1 Hz, 1H), 3.60
(t, J = 4.2 Hz, 1H), 4.03 (dd, J = 12.0 and 3.3 Hz, 1H), 4.46
(d, J = 13.5 Hz, 1H), 5.95 (q, J = 6.9 Hz, 1H), 6.65 (s, 1H),
7.13–7.63 (m, 9H); 13C NMR (CDCl3, 75 MHz): d 13.96,
21.50, 28.38, 46.17, 47.32, 50.11, 125.84, 127.05, 127.39,
127.72, 128.47, 129.00, 129.67, 133.31, 134.62, 134.94,
136.06, 143.71, 206.23.
7. One of the major components of 4a was separated
by column chromatography in pure state as a white solid
in 60% yield: mp128–130 °C; IR (KBr) 3491, 2924, 1701,
1346, 1161 cmꢀ1 1H NMR (CDCl3, 300 MHz): d 1.24
;
(s, 3H), 2.31 (s, 3H), 2.43 (s, 3H), 2.45 (s, 1H, OH), 2.81–
3.03 (m, 3H), 3.80–3.87 (m, 1H), 4.68 (dd, J = 13.2 and
2.1 Hz, 1H), 6.88 (s, 1H), 7.20–7.59 (m, 9H); 13C NMR
(CDCl3, 75 MHz): d 21.55, 22.52, 32.50, 44.83, 45.34,
58.42, 73.33, 124.66, 127.33, 127.68, 128.54, 128.84,
129.83, 132.96, 135.93, 138.59, 143.93, 208.78. However,
we did not determine the stereochemistry of this major
component.
Compound 5e (6/1 h): 85%; clear oil; IR (film) 2927, 1693,
1342, 1165 cmꢀ1 1H NMR (CDCl3, 300 MHz): d 1.12
;
(t, J = 7.5 Hz, 3H), 1.86 (s, 3H), 2.42 (s, 3H), 2.57 (q, J =
7.5 Hz, 2H), 4.03 (s, 2H), 4.16 (s, 2H), 6.70 (s, 1H), 7.16–
7.57 (m, 9H); 13C NMR (CDCl3, 75 MHz): d 8.15, 15.84,
21.79, 36.17, 45.25, 46.39, 128.05, 128.08, 128.87, 129.31,
129.74, 129.81, 131.77, 133.12, 134.26, 134.27, 136.23,
143.99, 205.69.
8. Typical procedure for the synthesis of intermediate 5a: To a
stirred mixture of tosylamide derivative 2a (329 mg,
1.0 mmol) and methyl vinyl ketone (105 mg, 1.5 mmol) in
THF (4 mL) was added DBU (76 mg, 0.5 mmol) and stirred
at room temperature for 6 h. After the reaction we could
observe two major components on TLC, which must be
the corresponding two diastereoisomers resulting from the
consecutive Michael addition and aldol reaction. The
separation was not carried out. Instead, desired portion
was separated by simple aq workup and removal of solvent
as a crude state. The crude mixtures was dissolved in
benzene and subjected to dehydration conditions, p-TsOH
(19 mg, 0.1 mmol), reflux, 1 h. The desired dehydration
product 5a was separated after aq workup and column
chromatographic purification process (hexanes/EtOAc,
5:1), 332 mg (87%) as a white solid. The other compounds
were synthesized analogously (reaction time is mentioned in
the parenthesis: the first refer to the cyclization and the
second dehydration) and the spectroscopic data are as
follows.
Compound 5f (24/5 h): 61%; white solid, mp108–110 °C;
1
IR (KBr) 1716, 1350, 1250, 1165 cmꢀ1; H NMR (CDCl3,
300 MHz): d 2.13 (s, 3H), 2.41 (s, 3H), 3.77 (s, 3H), 4.11
(s, 2H), 4.15 (s, 2H), 6.82 (s, 1H), 7.18–7.56 (m, 9H); 13C
NMR (CDCl3, 75 MHz): d 15.26, 21.46, 44.91, 46.20, 51.72,
123.02, 127.70, 127.95, 128.57, 129.09, 129.41, 130.97,
131.91, 134.14, 135.83, 142.11, 143.57, 166.73.
Compound 5g (6/1 h): 67%; yellow solid, mp125–127 °C;
IR (KBr) 1682, 1335, 1153 cmꢀ1 1H NMR (CDCl3,
;
300 MHz): d 2.18 (s, 3H), 2.38 (s, 3H), 2.74 (s, 3H), 4.21
(s, 2H), 4.33 (s, 2H), 7.00 (s, 1H), 7.23–7.43 (m, 5H); 13C
NMR (CDCl3, 75 MHz): d 15.89, 30.53, 37.36, 44.62, 45.93,
128.10, 128.70, 129.09, 130.76, 131.60, 133.01, 135.59,
136.07, 201.49.
9. Typical procedure for the synthesis of pyridine 6a: To a
stirred solution of 5a (191 mg, 0.5 mmol) in dry DMF
(2 mL) was added Cs2CO3 (490 mg, 1.5 mmol) and heated
to 120–130 °C for 1 h. After the usual workupand column
chromatographic purification process (hexanes/EtOAc, 5:1)
we obtained 6a as clear oil, 63 mg (56%). The other
compounds were synthesized analogously (reaction time is
mentioned in the parenthesis) and the spectroscopic data
are as follows.
Compound 5a (6/1 h): 87%; white solid, mp79–80 °C; IR
(KBr) 1682, 1350, 1161 cmꢀ1
;
1H NMR (CDCl3,
300 MHz): d 1.93 (s, 3H), 2.31 (s, 3H), 2.42 (s, 3H), 4.06
(s, 2H), 4.16 (s, 2H), 6.75 (s, 1H), 7.17–7.56 (m, 9H); 13C
NMR (CDCl3, 75 MHz): d 15.60, 21.46, 30.55, 44.98, 46.12,
127.70, 127.87, 128.57, 129.03, 129.44, 130.19, 131.64,
132.48, 133.95, 135.86, 135.91, 143.69, 201.45.
Compound 6a (1 h): 56%; clear oil; IR (film) 1689, 1454,
1281 cmꢀ1 1H NMR (CDCl3, 300 MHz): d 2.36 (s, 3H),
;
Compound 5b (3/1 h): 72%; white solid, mp70–71 °C; IR
2.62 (s, 3H), 4.05 (s, 2H), 7.07–7.32 (m, 5H), 8.47 (s, 1H),
8.76 (s, 1H); 13C NMR (CDCl3, 75 MHz): d 16.20, 30.28,
36.75, 126.49, 128.40, 128.66, 134.81, 135.81, 138.53,
145.76, 148.04, 152.88, 200.99.
(KBr) 2927, 1682, 1350, 1161 cmꢀ1 1H NMR (CDCl3,
;
300 MHz): d 1.93 (s, 3H), 2.31 (s, 3H), 2.42 (s, 3H), 4.04
(s, 2H), 4.10 (s, 2H), 6.69 (s, 1H), 7.12 (d, J = 8.4 Hz, 2H),
7.26 (d, J = 8.4 Hz, 2H), 7.37 (d, J = 8.1 Hz, 2H), 7.55
(d, J = 8.1 Hz, 2H); 13C NMR (CDCl3, 75 MHz): d 15.55,
21.44, 30.51, 44.80, 46.06, 127.65, 128.67, 128.78, 129.48,
130.27, 132.35, 132.93, 133.72, 133.78, 134.32, 135.42,
143.81, 201.38.
Compound 6b (20 min): 60%; clear oil; IR (film) 1689, 1493,
1281 cmꢀ1 1H NMR (CDCl3, 300 MHz): d 2.34 (s, 3H),
;
2.62 (s, 3H), 4.02 (s, 2H), 7.02 (d, J = 8.7 Hz, 2H), 7.25
(d, J = 8.7 Hz, 2H), 8.45 (s, 1H), 8.77 (s, 1H); 13C NMR
(CDCl3, 75 MHz): d 16.19, 30.25, 36.12, 128.79, 129.69,
132.37, 134.84, 135.30, 137.04, 145.70, 148.26, 152.80,
200.84.
Compound 5c (5/2 h): 80%; white solid, mp119–121 °C; IR
(KBr) 1678, 1350, 1242, 1161 cmꢀ1 1H NMR (CDCl3,
;
300 MHz): d 1.93 (s, 3H), 2.31 (s, 3H), 2.39 (s, 3H), 2.42
(s, 3H), 4.06 (s, 2H), 4.18 (s, 2H), 6.73 (s, 1H), 7.08
(d, J = 8.1 Hz, 2H), 7.21 (d, J = 8.1 Hz, 2H), 7.25 (d, J =
8.1 Hz, 2H), 7.55 (d, J = 8.1 Hz, 2H); 13C NMR (CDCl3,
75 MHz): d 15.65, 21.26, 21.49, 30.57, 45.09, 46.17, 127.75,
129.05, 129.32, 129.43, 130.37, 131.03, 132.07, 133.01,
134.07, 136.32, 137.94, 143.66, 201.40.
Compound 6c (30 min): 64%; clear oil; IR (film) 1689,
1281 cmꢀ1 1H NMR (CDCl3, 300 MHz): d 2.31 (s, 3H),
;
2.35 (s, 3H), 2.61 (s, 3H), 4.00 (s, 2H), 6.97 (d, J = 8.1 Hz,
2H), 7.09 (d, J = 8.1 Hz, 2H), 8.46 (s, 1H), 8.74 (s, 1H); 13
C
NMR (CDCl3, 75 MHz): d 16.16, 20.91, 30.27, 36.32,
128.28, 129.31, 134.78, 135.45, 136.04 (2C), 145.68, 147.95,
152.84, 201.00.

D. Y. Park et al. / Tetrahedron Letters 46 (2005) 8799–8803
8803
Compound 6d (30 min): 53%; clear oil; IR (film) 1689,
1277 cmꢀ1 1H NMR (CDCl3, 300 MHz):
1.07 (t,
4.05 (s, 2H), 7.08–7.32 (m, 5H), 8.45 (s, 1H), 8.67 (s, 1H);
13C NMR (CDCl3,75 MHz): d 8.11, 16.13, 35.99, 36.80,
126.51, 128.45, 128.68, 135.44, 135.76, 138.57, 145.22,
146.97, 152.48, 204.51.
;
d
J = 7.5 Hz, 3H), 2.62 (s, 3H), 2.82 (q, J = 7.5 Hz, 2H),
4.08 (s, 2H), 7.08–7.32 (m, 5H), 8.45 (s, 1H), 8.75 (s, 1H);
13C NMR (CDCl3, 75 MHz): d 14.55, 22.41, 30.49, 35.88,
126.54, 128.50, 128.68, 134.29, 135.14, 139.22, 148.33,
151.41, 153.62, 200.94.
Compound 6f (3 h): 52%; clear oil; IR (film) 1724,
1288 cmꢀ1 1H NMR (CDCl3, 300 MHz): d 2.45 (s, 3H),
;
3.91 (s, 2H), 4.06 (s, 3H), 7.06–7.31 (m, 5H), 8.48 (s, 1H),
8.91 (s, 1H); 13C NMR (CDCl3, 75 MHz): d 16.29, 36.78,
52.18, 126.47, 126.86, 128.37, 128.65, 135.31, 138.62,
147.62, 149.71, 153.26, 167.12.
Compound 6e (1 h): 53%; clear oil; IR (film) 1693,
1454 cmꢀ1
;
1H NMR (CDCl3, 300 MHz):
d
1.21 (t,
J = 7.2 Hz, 3H), 2.30 (s, 3H), 2.92 (q, J = 7.2 Hz, 2H),