Pd-mediated synthesis of 2-arylquinolines and tetrahydropyridines from modified Baylis-Hillman adducts

Article abstract of DOI:10.1016/j.tetlet.2007.12.133

We synthesized 2-arylquinolines and tetrahydropyridines via palladium-mediated Heck type reactions starting from the Baylis-Hillman adducts. 2-Arylquinolines were prepared via the Heck type cyclization followed by concomitant aerobic oxidation.

Full text of DOI:10.1016/j.tetlet.2007.12.133

Available online at www.sciencedirect.com
Tetrahedron Letters 49 (2008) 1670–1673
Pd-mediated synthesis of 2-arylquinolines and tetrahydropyridines
from modified Baylis–Hillman adducts
Saravanan Gowrisankar, Hyun Seung Lee, Jeong Mi Kim, Jae Nyoung Kim *
Department of Chemistry and Institute of Basic Science, Chonnam National University, Gwangju 500-757, Republic of Korea
Received 14 December 2007; revised 27 December 2007; accepted 28 December 2007
Available online 11 January 2008
Abstract
We synthesized 2-arylquinolines and tetrahydropyridines via palladium-mediated Heck type reactions starting from the Baylis–
Hillman adducts. 2-Arylquinolines were prepared via the Heck type cyclization followed by concomitant aerobic oxidation.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords: 2-Arylquinolines; Tetrahydropyridines; Baylis–Hillman adducts; Palladium
Although palladium-mediated cyclizations have been
investigated extensively using various substrates, examples
on the synthesis of heterocyclic compounds starting from
Baylis–Hillman adducts were somewhat limited.1 Trost
and co-workers used Pd-mediated synthesis of dihydro-
benzofuran from Baylis–Hillman adducts.1e,f Very recently
Lamaty and co-workers reported the synthesis of nitrogen-
containing seven-membered ring compounds and oxygen-
containing five-membered ring compounds (Scheme 1).1a–c
In addition, Vasudevan and co-workers reported the
Lamaty1a,b
SES
Ph
N
Br
N
SES
COOMe
Ph
COOMe
Vasudevan1d
O2S
O2S
H N
Br
N
H
Ph
COOMe
Ph
COOMe
this work
HN
Ph
N
HN
Ph
Br
Ph
COOMe
COOMe
COOMe
Scheme 1.
*
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 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.12.133

S. Gowrisankar et al. / Tetrahedron Letters 49 (2008) 1670–1673
1671
synthesis of seven-membered cyclic compounds containing
sulfonamide linkage (Scheme 1).1d
we elevated the reaction temperature the reaction showed
the formation of many side products to make the separa-
tion of desired product tedious and make the yield eventu-
ally low. Actually the best yield of compound 2a (56%) was
obtained at room temperature after 7 days. With this com-
pound 2a in our hand, we examined a few reaction condi-
tions and we found that the conditions of Lamaty
(Pd(OAc)2/K2CO3/PEG-3400/DMF/80–90 °C)1a–c showed
the best results.6 We obtained desired 2-phenylquinoline-
3-carboxylic acid derivative 4a directly in moderate yield
(58%),4d–f,7 presumably via the Pd-mediated aerobic oxida-
tion5 of the intermediate dihydroquinoline 3a (Scheme 2).
Encouraged by the results, we prepared 2b–g (40–71%)
from the reactions between the corresponding Baylis–
Hillman acetates and 2-bromoanilines. After that, we
examined the generality of the novel one-pot reaction of
sequential Heck type cyclization and the following aerobic
oxidation. The results are summarized in Table 1. Desired
quinolines 4b–g were obtained in 53–69% yields in short
time in a one-pot reaction.
However, Heck type cyclizations using Baylis–Hillman
adducts as starting materials for the synthesis of quinolines
has not been reported to the best of our knowledge
(Scheme 1).1–3 Syntheses of suitably substituted quinolines
have received much attention due to their biological activ-
ity and the usefulness of them in organic synthesis for fur-
ther transformations.2–4 In these contexts, we decided to
examine the feasibility for the synthesis of quinolines start-
ing from Baylis–Hillman adducts. Scheme 1 showed our
synthetic rationale, which involved Pd-mediated Heck
reaction (6-endo) and concomitant aerobic oxidation.5
Thus we synthesized starting material 2a from Baylis–
Hillman acetate 1a and 2-bromoaniline by using the well-
known DABCO salt concept (sequential SN20–SN20
displacement reaction as in Scheme 2) in the Baylis–Hill-
man chemistry.2c,d,h However, the introduction of 2-bro-
moaniline at the secondary position required very long
reaction time (7–14 days at room temperature).2c,d When
COOMe
OAc
Ph
1. aq THF, DABCO
COOMe
Ph
HN
Ph
Br
N
2. 2-bromoaniline
rt, 7 days
AcO
N
1a
(I)
COOMe
2a
Pd(OAc)2 (0.1 equiv)
K2CO3 (2.0 equiv)
PEG-3400, DMF
80-90 oC, 2 h
HN
Ph
N
aereobic
oxidation
Ph
COOMe
COOMe
4a
3a
Scheme 2.
Table 1
Pd-mediated cyclizations of modified Baylis–Hillman adducts
R1
R1
a: Ar = Ph, R1 = H, R2 = Me
b: Ar = Ph, R1 = H, R2 = Et
c: Ar = 4-ClC6H4-, R1 = H, R2 = Me
d: Ar = 2-naphthyl, R1 = H, R2 = Me
e: Ar = Ph, R1 = Me, R2 = Me
f: Ar = 3-MeC6H4-, R1 = Me, R2 = Me
g: Ar = 4-PhC6H4-, R1 = Me, R2 = Me
Conditions
N
HN
Br
Ar
Ar
COOR2
COOR2
2a-g
4a-g
Entry
Substratea (%)
Conditionsb
Product (%)
1
2
3
4
5
6
7
a
2a (56)
2b (71)
2c (68)
2d (59)
2e (40)
2f (43)
2g (61)
80–90 °C, 2 h
80–90 °C, 1.5 h
80–90 °C, 1.5 h
90–100 °C, 1.5 h
80–90 °C, 1 h
80–90 °C, 1 h
90–100 °C, 2 h
4a (58)
4b (66)
4c (69)
4d (53)
4e (60)
4f (64)
4g (63)
Conditions: (i) Baylis–Hillman acetates 1 (1.0 equiv), aq THF, DABCO (1.1 equiv), rt, 15 min; (ii) 2-bromoanilines (1.0 equiv), rt, 7–14 days (7 days for
2a–c and 14 days 2d–g).
b
Conditions: substrate (1.0 equiv), Pd(OAc)2 (0.1 equiv), K2CO3 (2.0 equiv), PEG-3400, DMF.

1672
S. Gowrisankar et al. / Tetrahedron Letters 49 (2008) 1670–1673
Pd(OAc)2 (0.1 equiv)
K2CO3 (2.0 equiv)
PEG-3400, DMF
80-90 oC, 2 h
1. aq THF, DABCO
2. TsNH2
3. 2,3-dibromopropene
Ts
Ts
N
Br
N
1a
Ph
Ph
COOMe
COOMe
6a
5a
Scheme 3.
As a next step, to synthesize 2,3,5-trisubstituted pyridine
derivative such as 7a (vide infra) by using the same proto-
col of quinolines (Scheme 2 and Table 1), we tried the syn-
thesis of 2-bromoprophenylamine (–NHCH@C(Br)CH3 or
–NHCH2C(Br)@CH2) moiety-substituted Baylis–Hillman
adducts at the secondary position. However, the synthesis
was very difficult, thus we changed our strategy as shown
in Scheme 3 involving the use of N-tosyl analog 5a as the
starting material instead of N–H analog. We imagined that
elimination of p-toluenesulfinic acid and concomitant dou-
ble bond isomerization process after the Heck cyclization
of 5a could provide desired 2,3,5-trisubstituted pyridine
7a (Scheme 4, vide infra). Thus we prepared starting mate-
rials 5a–d as in Scheme 3 and Table 2 by following the pro-
cess: (i) introduction of tosylamide via the DABCO salt of
the corresponding Baylis–Hillman acetates,2c,d,h (ii) alkyl-
ation with 2,3-dibromopropene (for 5a–c) or with allyl
bromide (for 5d). Heck type cyclization of 5a produced
exo-methylene tetrahydropyridine 6a in moderate yield
(62%) under the conditions of Pd(OAc)2/K2CO3/PEG-
3400/DMF/80–90 °C (entry 1 in Table 2). However, it
was very difficult to convert 6a into the corresponding
2,3,5-trisubstituted pyridine 7a. We obtained only low yield
(22%) of 7a under the influence of 3.0 equiv of Cs2CO3 in
DMF at elevated temperature (Scheme 4). We synthesized
6b–d under similar conditions in view of the importance of
tetrahydropyridines8 and the synthetic applicability of
these exo-methylene tetrahydropyridines.8 The yield of
compound 6d was relatively low (34%) under the same con-
ditions, however, the yield was improved slightly (up to
46%) by using the conditions of Vasudevan (Pd(OAc)2/
P(o-Tol)3/Et3N/100–110 °C, entry 4).1d The whole results
are summarized in Table 2 and further synthetic applica-
tions of these compounds are currently underway.
Cs2CO3 (3.0 equiv)
N
DMF, 110 oC, 3 h
intractable
mixtures
6a
+
Ph
COOMe
7a (22%)
Scheme 4.
Table 2
Pd-mediated cyclizations of modified Baylis–Hillman adducts
Entry
Substratea (%)
Conditions
Product (%)
Ts
N
Pd(OAc)2 (0.1 equiv)
K2CO3 (2.0 equiv)
PEG-3400, DMF
80–90 °C, 2 h
Ts
N
Br
1
5a (92)
5b (84)
6a (62)
6b (60)
Ph
Ph
COOMe
COOMe
Ts
Ts
N
N
Br
Pd(OAc)2 (0.1 equiv)
K2CO3 (2.0 equiv)
PEG-3400, DMF
90–100 °C, 2.5 h
2
3
COOMe
COOMe
H3C
H3C
Ts
Pd(OAc)2 (0.1 equiv)
K2CO3 (2.0 equiv)
PEG-3400, DMF
90–100 °C, 2 h
Ts
N
N
Br
COOEt
N
5c (88)
5d (97)
6c (58)
Ph
Ph
COOEt
Ts
Br
Ts
N
Pd(OAc)2 (0.2 equiv)
P(o-Tol)3 (2.0 equiv)
Et3N (solvent)
4
6d (46)b
MeOOC
100–110 °C, 4 h
COOMe
a
Conditions: (i) N-tosyl aza-Baylis–Hillman adducts (1.0 equiv),2h 2,3-dibromopropene (for 5a–c, 1.2 equiv)/allyl bromide (for 5d, 1.2 equiv), K2CO3
(1.2 equiv), DMF, rt, 6 h, and the yields refer to the last alkylation step.
b
Compound 6d was obtained in 34% yield under the conditions: Pd(OAc)2 (0.1 equiv), K2CO3 (2.0 equiv), PEG-3400, DMF, 110–120 °C, 4 h.

S. Gowrisankar et al. / Tetrahedron Letters 49 (2008) 1670–1673
1673
(5 mL, 1:1) was added DABCO (123 mg, 1.1 mmol) at room temper-
ature. After 15 min, 2-bromoaniline (172 mg, 1.0 mmol) was added to
the reaction mixture and stirred at room temperature for 7 days. After
the usual aqueous workup and column chromatographic purification
process (hexanes/ether, 95:5) we obtained 2a (194 mg, 56%) as colorless
oil. A stirred mixture of 2a (173 mg, 0.5 mmol), palladium acetate
(11 mg, 0.05 mmol, 10 mol %), K2CO3 (138 mg, 1.0 mmol) in PEG-
3400 (160 mg)/DMF (2 mL) was heated to 80–90 °C for 2 h under N2.
After the usual aqueous workup and column chromatographic purifi-
cation process (hexanes/EtOAc, 9:1) we obtained 4a (77 mg, 58%) as
colorless oil. Other compounds were synthesized analogously and some
selected spectroscopic data of compounds 2a, 4a, 4e, 5a, 6a, and 6d are
as follows: Compound 2a: colorless oil; 56%; IR (film) 3410, 1720, 1593,
1496 cmꢀ1; 1H NMR (CDCl3, 300 MHz) d 3.72 (s, 3H), 4.85 (br s, 1H),
5.50 (s, 1H), 5.89 (s, 1H), 6.39 (s, 1H), 6.52–6.61 (m, 2H), 7.09–7.15 (m,
1H), 7.29–7.44 (m, 6H); 13C NMR (CDCl3, 75 MHz) d 52.02, 58.60,
109.95, 112.52, 118.40, 126.26, 127.43, 127.94, 128.38, 128.85, 132.37,
139.90, 139.97, 143.44, 166.51; ESIMS m/z 346 (M++1).
In summary, we prepared some 2-arylquinoline deriva-
tives via the palladium-mediated sequential cyclization and
concomitant aerobic oxidation process in a one-pot reaction
from modified Baylis–Hillman adducts. In addition, we pre-
pared some exo-methylene tetrahydropyridine derivatives.
References and notes
1. For the Pd-mediated synthesis of hetero- and carbocyclic compounds
from modified Baylis–Hillman adducts, see: (a) Ribiere, P.; Declerck,
V.; Nedellec, Y.; Yadav-Bhatnagar, N.; Martinez, J.; Lamaty, F.
Tetrahedron 2006, 62, 10456–10466; (b) Declerck, V.; Ribiere, P.;
Nedellec, Y.; Allouchi, H.; Martinez, J.; Lamaty, F. Eur. J. Org. Chem.
2007, 201–208; (c) Szlosek-Pinaud, M.; Diaz, P.; Martinez, J.; Lamaty,
F. Tetrahedron 2007, 63, 3340–3349; (d) Vasudevan, A.; Tseng, P.-S.;
Djuric, S. W. Tetrahedron Lett. 2006, 47, 8591–8593; (e) Trost, B. M.;
Thiel, O. R.; Tsui, H.-C. J. Am. Chem. Soc. 2003, 125, 13155–13164; (f)
Trost, B. M.; Thiel, O. R.; Tsui, H.-C. J. Am. Chem. Soc. 2002, 124,
11616–11617; (g) Park, J. B.; Ko, S. H.; Hong, W. P.; Lee, K.-J. Bull.
Korean Chem. Soc. 2004, 25, 927–930.
2. For the synthesis of quinolines, pyridines, and related compounds from
Baylis–Hillman adducts in our group, see: (a) Park, D. Y.; Lee, M. J.;
Kim, T. H.; Kim, J. N. Tetrahedron Lett. 2005, 46, 8799–8803; (b) Lee,
M. J.; Kim, S. C.; Kim, J. N. Bull. Korean Chem. Soc. 2006, 27, 439–
442; (c) Lee, C. G.; Lee, K. Y.; Lee, S.; Kim, J. N. Tetrahedron 2005,
61, 1493–1499; (d) Kim, S. C.; Gowrisankar, S.; Kim, J. N. Bull.
Korean Chem. Soc. 2005, 26, 1001–1004; (e) Lee, C. G.; Lee, K. Y.;
Gowrisankar, S.; Kim, J. N. Tetrahedron Lett. 2004, 45, 7409–7413; (f)
Lee, K. Y.; Kim, J. M.; Kim, J. N. Tetrahedron 2003, 59, 385–390; (g)
Kim, J. N.; Kim, H. S.; Gong, J. H.; Chung, Y. M. Tetrahedron Lett.
2001, 42, 8341–8344; (h) Kim, J. N.; Lee, H. J.; Lee, K. Y.; Kim, H. S.
Tetrahedron Lett. 2001, 42, 3737–3740; (i) Kim, J. N.; Lee, K. Y.; Kim,
H. S.; Kim, T. Y. Org. Lett. 2000, 2, 343–345.
3. For the synthesis of quinolines and related compounds from Baylis–
Hillman adducts by other groups, see: (a) Pathak, R.; Madapa, S.;
Batra, S. Tetrahedron 2007, 63, 451–460; (b) Madapa, S.; Singh, V.;
Batra, S. Tetrahedron 2006, 62, 8740–8747; (c) Narender, P.; Srinivas,
U.; Ravinder, M.; Ananda Rao, B.; Ramesh, C.; Harakishore, K.;
Gangadasu, B.; Murthy, U. S. N.; Jayathirtha Rao, V. Bioorg. Med.
Chem. 2006, 14, 4600–4609; (d) Basavaiah, D.; Reddy, R. J.; Rao, J. S.
Tetrahedron Lett. 2006, 47, 73–77; (e) Basavaiah, D.; Reddy, R. M.;
Kumaragurubaran, N.; Sharada, D. S. Tetrahedron 2002, 58, 3693–
3697; (f) O’Dell, D. K.; Nicholas, K. M. J. Org. Chem. 2003, 68, 6427–
6430; (g) O’Dell, D. K.; Nicholas, K. M. Tetrahedron 2003, 59, 747–
754; (h) Familoni, O. B.; Klaas, P. J.; Lobb, K. A.; Pakade, V. E.;
Kaye, P. T. Org. Biomol. Chem. 2006, 4, 3960–3965; (i) Familoni, O.
B.; Kaye, P. T.; Klaas, P. J. Chem. Commun. 1998, 2563–2564; (j) Yi,
H.-W.; Park, H. W.; Song, Y. S.; Lee, K.-J. Synthesis 2006, 1953–1960;
(k) Hong, W. P.; Lee, K. J. Synthesis 2006, 963–968.
4. For the synthesis of authentic samples of synthesized quinolines and
pyridines, see: (a) Odle, R.; Blevins, B.; Ratcliff, M.; Hegedus, L. S. J.
Org. Chem. 1980, 45, 2709–2710; (b) Rosa, A. M.; Lobo, A. M.;
Branco, P. S.; Prabhakar, S.; Pereira, A. M. D. L. Tetrahedron 1997,
53, 269–284; (c) Shao, H. W.; Cai, J. C. Chinese Chem. Lett. 1997, 8,
493–496; (d) Leleu, S.; Papamicael, C.; Marsais, F.; Dupas, G.;
Levacher, V. Tetrahedron: Asymmetry 2004, 15, 3919–3928; (e)
Penhoat, M.; Levacher, V.; Dupas, G. J. Org. Chem. 2003, 68, 9517–
9520; (f) Kanomata, N.; Nakata, T. Heterocycles 1998, 48, 2551–2558.
5. For the palladium-catalyzed aerobic oxidation of amines, see: (a)
Wang, J.-R.; Fu, Y.; Zhang, B.-B.; Cui, X.; Liu, L.; Guo, Q.-X.
Tetrahedron Lett. 2006, 47, 8293–8297; (b) Wang, J.-R.; Yang, C.-T.;
Liu, L.; Guo, Q.-X. Tetrahedron Lett. 2007, 48, 5449–5453.
Compound 4a: colorless oil; 58%; IR (film) 2924, 1730, 1487, 1269,
1
1232 cmꢀ1; H NMR (CDCl3, 300 MHz) d 3.74 (s, 3H), 7.42–7.51 (m,
3H), 7.58–7.66 (m, 3H), 7.79–7.85 (m, 1H), 7.92 (d, J = 8.4 Hz, 1H),
8.20 (d, J = 8.4 Hz, 1H), 8.66 (s, 1H); 13C NMR (CDCl3, 75 MHz) d
52.41, 125.06, 125.80, 127.27, 128.21 (2C), 128.55, 128.66, 129.57,
131.62, 139.20, 140.55, 148.45, 158.03, 168.37; ESIMS m/z 264 (M++1).
Anal. Calcd for C17H13NO2: C, 77.55; H, 4.98; N, 5.32. Found: C,
77.41; H, 5.12; N, 5.24.
Compound 4e: colorless oil; 60%; IR (film) 2949, 1728, 1437,
;
1269 cmꢀ1 1H NMR (CDCl3, 300 MHz) d 2.56 (s, 3H), 3.73 (s, 3H),
7.42–7.50 (m, 3H), 7.61–7.65 (m, 4H), 8.07 (d, J = 8.4 Hz, 1H), 8.55 (s,
1H); 13C NMR (CDCl3, 75 MHz) d 21.57, 52.33, 124.95, 125.81, 126.91,
128.15, 128.49, 128.50, 129.18, 133.95, 137.28, 138.47, 140.64, 147.06,
157.11, 168.50; ESIMS m/z 278 (M++1). Anal. Calcd for C18H15NO2:
C, 77.96; H, 5.45; N, 5.05. Found: C, 78.04; H, 5.42; N, 4.97.
Compound 5a: sticky oil; 92%; IR (KBr) 2952, 1724, 1630, 1439 cmꢀ1
;
1H NMR (CDCl3, 300 MHz) d 2.41 (s, 3H), 3.62 (s, 3H), 4.08 (d,
J = 17.7 Hz, 1H), 4.21 (d, J = 17.7 Hz, 1H), 5.29–5.31 (m, 1H), 5.50–
5.52 (m, 1H), 5.59 (d, J = 1.5 Hz, 1H), 6.22 (s, 1H), 6.39 (d, J = 1.2 Hz,
1H), 7.06–7.09 (m, 2H), 7.20–7.23 (m, 5H), 7.62 (d, J = 8.1 Hz, 2H); 13
C
NMR (CDCl3, 75 MHz) d 21.52, 52.08, 53.43, 62.12, 118.79, 127.60,
127.93, 128.01, 128.52, 128.56, 128.68, 129.41, 136.46, 137.25, 138.65,
143.54, 166.19; ESIMS m/z 464 (M++1).
Compound 6a: colorless oil; 62%; IR (film) 2925, 1726, 1342, 1163 cmꢀ1
;
1H NMR (CDCl3, 300 MHz) d 2.38 (s, 3H), 3.67 (s, 3H), 3.62–3.68 (m,
1H), 4.37 (d, J = 16.8 Hz, 1H), 5.19 (s, 1H), 5.24 (s, 1H), 6.00 (s, 1H), 7.06
(s, 1H), 7.16 (d, J = 8.4 Hz, 2H), 7.27–7.33 (m, 5H), 7.61 (d, J = 8.4 Hz,
2H); 13C NMR (CDCl3, 75 MHz) d 21.51, 43.10, 52.11, 55.36, 120.27,
127.46, 128.15, 128.16, 128.53(2C),129.26, 135.70, 136.55,137.37, 137.42,
143.44, 165.43;ESIMS m/z 384(M++1). Anal. Calcdfor C21H21NO4S:C,
65.78; H, 5.52; N, 3.65. Found: C, 65.57; H, 5.76; N, 3.39.
Compound 6d: colorless oil; 46%; IR (film) 2924, 1724, 1599, 1439 cmꢀ1
;
1H NMR (CDCl3, 300 MHz) d 2.26 (s, 3H), 3.83 (s, 3H), 4.12 (d,
J = 17.1 Hz, 1H), 4.42 (d, J = 17.1 Hz, 1H), 4.94 (s, 1H), 5.08 (s, 1H), 5.42
(s, 1H), 6.13 (s, 1H), 6.33 (s, 1H), 6.94 (d, J = 8.4 Hz, 2H), 6.95–7.00 (m,
1H), 7.05–7.18 (m, 2H), 7.30–7.34 (m, 1H), 7.45 (d, J = 8.4 Hz, 2H); 13
C
NMR (CDCl3, 75 MHz) d 21.33, 45.34, 52.26, 57.07, 109.44, 123.59,
127.46, 127.69, 127.77, 128.13, 128.73, 129.71, 131.45, 132.00, 135.20,
136.13, 140.50, 142.90, 166.22; ESIMS m/z 384 (M++1). Anal. Calcd for
C21H21NO4S:C, 65.78;H, 5.52;N, 3.65. Found:C, 65.63;H, 5.85;N, 3.49.
8. For the palladium-mediated synthesis of tetrahydropyridines and
tetrahydroquinolines and their synthetic applications, see: (a) Beccalli,
E. M.; Broggini, G.; Martinelli, M.; Masciocchi, N.; Sottocornola, S.
Org. Lett. 2006, 8, 4521–4524; (b) Soderberg, B. C. G.; Hubbard, J. W.;
Rector, S. R.; O’Neil, S. N. Tetrahedron 2005, 61, 3637–3649; (c)
Grigg, R.; Kordes, M. Eur. J. Org. Chem. 2001, 707–712; (d) Gai, X.;
Grigg, R.; Koppen, I.; Marchbank, J.; Sridharan, V. Tetrahedron Lett.
2003, 44, 7445–7448; (e) Grigg, R.; Sridharan, V.; Thayaparan, A.
Tetrahedron Lett. 2003, 44, 9017–9019; (f) Oh, C. H.; Park, S. J.
Tetrahedron Lett. 2003, 44, 3785–3787.
6. We examined a few conditions involving the variation of base (K2CO3,
Cs2CO3, Et3N) and solvent (CH3CN, DMF).
7. Typical procedure for the synthesis of 2a and 4a: To a stirred solution of
the Baylis–Hillman acetate (1a, 234 mg, 1.0 mmol) in aqueous THF