Direct one-pot introduction of 2-methylpyridines to Baylis-Hillman adducts via base-mediated 3-aza-Cope rearrangement

Article abstract of DOI:10.1016/j.tetlet.2011.07.101

An efficient and regioselective introduction method of 2-methylpyridines to the secondary position of Baylis-Hillman adducts has been developed. A base treatment of 2-methylpyridinium salt of Baylis-Hillman bromide generated N-allylenamine intermediate wh

Full text of DOI:10.1016/j.tetlet.2011.07.101

Tetrahedron Letters 52 (2011) 5039–5042
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Direct one-pot introduction of 2-methylpyridines to Baylis–Hillman adducts
via base-mediated 3-aza-Cope rearrangement
Hyun Seung Lee a, Sangku Lee b, Se Hee Kim a, Jae Nyoung Kim a,
⇑
a Department of Chemistry and Institute of Basic Science, Chonnam National University, Gwangju 500-757, Republic of Korea
b Immune Modulator Research Center, KRIBB, Daejeon 305-806, Republic of Korea
a r t i c l e i n f o
a b s t r a c t
Article history:
An efficient and regioselective introduction method of 2-methylpyridines to the secondary position of
Baylis–Hillman adducts has been developed. A base treatment of 2-methylpyridinium salt of Baylis–Hill-
man bromide generated N-allylenamine intermediate which underwent a facile 3-aza-Cope rearrange-
ment under mild conditions to produce the product.
Received 15 July 2011
Accepted 19 July 2011
Available online 31 July 2011
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Baylis–Hillman adducts
Aza-Cope rearrangement
2-Methylpyridines
Chemical transformations of Baylis–Hillman adducts have re-
ceived much attention during the last two decades. Various cyclic
and acyclic compounds have been prepared from Baylis–Hillman
adducts by a variety of chemical transformations.1 One of the use-
ful transformations of Baylis–Hillman adducts starts from the for-
mation of amine salts of Baylis–Hillman bromides.2 As shown in
Scheme 1, a DABCO salt of Baylis–Hillman bromide has been fre-
quently used for the introduction of a nucleophile at the secondary
position of a Baylis–Hillman adduct.2 Some nitrogen atom-contain-
ing heterocycles, such as pyridine can form the corresponding salts
with Baylis–Hillman bromide, and the salts were used as interme-
diates for the synthesis of more complex substances.3 As an exam-
ple, Basavaiah et al. reported a reaction between the Baylis–
Hillman bromide and pyridine in the presence of K2CO3 to afford
indolizine derivative via the consecutive salt formation and 1,5-
cyclization of in situ generated nitrogen ylide.3a Subsequently a
similar approach was applied to the bromide of Baylis–Hillman ad-
ducts of isatin by Shanmugam et al.3b
During our continuous studies on chemical transformations of
Baylis–Hillman adducts, we were interested in the introduction
of a 2-pyridylmethyl moiety into the Baylis–Hillman adduct.4 The
synthesis was carried out previously via a sequential introduction
of allyl 2-pyridylacetate into Baylis–Hillman adduct, and a palla-
dium-catalyzed decarboxylative protonation protocol, as shown
in Scheme 2. However, both secondary and primary adducts, 3a
and 4a, were produced as a 1:1 mixture.4 In order to introduce a
2-pyridylmethyl moiety directly into the Baylis–Hillman adducts,
we examined the reaction of Baylis–Hillman bromide 1a and pico-
line (2a) instead of using allyl 2-pyridylacetate. At the outset of our
experiments, the reaction of 1a and 2a was performed in the pres-
ence of Pd(OAc)2/PPh3/Cs2CO3 in CH3CN (reflux, 2 h), based on the
recent palladium-catalyzed CAH functionalization of picoline
EWG
N
Nu
R
R
DABCO
Nu
EWG
R
(Ref. 2)
N
OH
EWG
Br
R
EWG
EWG
R
R
EWG
N
pyridine
(Ref. 3a)
N
B-H adduct
B-H bromide
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 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.07.101

5040
H. S. Lee et al. / Tetrahedron Letters 52 (2011) 5039–5042
1. TBAF/THF
O
N
O
3a:4a = 1:1
3a only
COOMe
2. Pd0/Et3N/HCOOH
two-step (Ref. 4)
Ph
N
COOMe
Br
Ph
COOMe
N
Ph
1a
2a
N
3a
4a
one-pot (this work)
Scheme 2.
3-aza-Cope
rearrangement
K2CO3
2a
H2C
Ph
N
H3C
Ph
N
H2C
Ph
N
3a (77%)
1a
Br
reflux, 3 h
CH3CN
reflux
1 h
COOMe
COOMe
I
COOMe
resonance-stabilized enamine II
K2CO3
1,5-cyclization
/aerobic oxidation
Ph
N
CH3
N
CH3
N
CH3
Ph
Ph
MeOOC
5
COOMe
COOMe
resonance-stabilized nitrogen ylide III
Scheme 3.
derivatives.5 A secondary adduct 3a was formed as a major product
(62%) along with a trace amount of 4a (<5%). Very interestingly, the
reaction of 1a and 2a (Cs2CO3, CH3CN, reflux, 3 h) showed the same
results (64% of 3a and 4% of 4a) without a palladium catalyst. Thus,
we examined regioselective introduction of 2-pyridylmethyl moi-
ety at the secondary position of a Baylis–Hillman adduct to obtain
3a (Scheme 2).
Table 1
One-pot synthesis of pyridylmethyl derivativesa
CH3CN
K2CO3
2a-h
3a-h
1a
+
reflux, 1 h
reflux, 3 h
N
N
A few trials revealed that formation of N-cinnamylpicolinium
salt I was crucial for the clean reaction and high yield of 3a before
the treatment with a base, as shown in Scheme 3. As noted above
4a was formed together, albeit in low yield, when we ran the reac-
tion of 1a and 2a in the presence of a base from the starting point
of the reaction. In addition, the use of K2CO3 was sufficient as a
base. Under the optimized conditions, formation of the primary ad-
duct 4a was not observed in any trace amount and the yield of 3a
increased to 77%.6 Based on the above results, the reaction mecha-
nism for the formation of 3a could be proposed, as also shown in
Scheme 3. Refluxing a mixture of 1a and 2a (1a:2a = 1:2) in CH3CN
for 1 h generated N-cinnamylpicolinium salt I. Treatment of I with
a base afforded a resonance-stabilized enamine intermediate II.
Subsequent 3-aza-Cope rearrangement7,8 of this enamine afforded
the product 3a. In the reaction, we did not observe the formation of
indolizine derivative 5 that could be produced via the nitrogen
ylide intermediate III.3a
Encouraged by the results, we carried out the reactions of 1a,
as a representative example, with various pyridine derivatives,
2,5-lutidine (2b), 2,3-lutidine (2c), 5-ethyl-2-picoline (2d), 2,3,5-
trimethylpyridine (2e), 2-ethylpyridine (2f), 2-benzylpyridine
(2g) and 1-methylisoquinoline (2h). The results are summarized
in Table 1. The corresponding pyridinium salts were formed quan-
titatively by refluxing the mixture of 1a and 2a–h in CH3CN for 1–
4 h. After the formation of salt, addition of K2CO3 and maintaining
the reaction mixture under refluxing conditions for 3 h furnished
the desired products 3b–h in good yields (69–89%).
Ph
Ph
Ph
Ph
Ph
COOMe
3a (77)
COOMe
3b (82)
N
N
COOMe
COOMe
3c (89)
3d (73)
Me
Ph
N
N
COOMe
COOMe
3f (80)b
3e (83)
Ph
Ph
N
N
COOMe
3g (85)b
Ph
COOMe
3h (69)c
a Conditions: (i) 1a (1.0 equiv), 2a–h (2.0 equiv), CH3CN, reflux,
1 h; (ii) K2CO3 (2.0 equiv), reflux, 3 h.
b Single isomer (syn/anti was not determined) was formed.
c Salt formation (step i) required 4 h.

H. S. Lee et al. / Tetrahedron Letters 52 (2011) 5039–5042
5041
Table 2
try. Isoquinoline derivative 3h was obtained in a moderate yield
(69%) although somewhat longer reaction time (4 h) was required
for the salt formation with 2h, presumably due to its lower
nucleophilicity than the other 2-methylpyridine derivatives 2a–g.
However, the reactions of 1a with 2-methylquinoline, 8-methyl-
quinoline and 2,6-lutidine failed due to their sluggish salt
formations. The reaction of a Baylis–Hillman bromide 1b, bearing
a nitrile moiety, showed the same reactivity with that of 1a. As
summarized in Table 2, we performed the reactions with four
pyridine derivatives 2a–d and obtained 3i–l in good yields
(68–78%).
The reaction of 1a and 4-picoline (2i) produced the same type
product 3m in 56% yield, as shown in Scheme 4. However, the reac-
tion mechanism for the formation of 3m is thought to be some-
what different from that of 3a–l. Deprotonation of N-
cinnamylpicolinium salt IV at the 4-methyl group produced dien-
amine intermediate V. Nucleophilic substitution reaction of IV
with dienamine V generated VI, and the following nucleophilic dis-
placement of VI with 2i afforded the product 3m along with IV.
Similarly, the reaction of 1a and 2,4-lutidine (2j) produced two
products, 3n and 6, as shown in Scheme 5. Compound 3n was
formed via salt formation, deprotonation at the 2-methyl group,
and subsequent aza-Cope rearrangement as in the cases of 3a–l.
The formation of compound 6 (as a 1:1 diastereomeric mixture)
could be explained via salt formation, deprotonation at the 4-
methyl group, nucleophilic substitution reaction as in Scheme 4
to form VII, deprotonation at the 2-methyl group, and the final
aza-Cope rearrangement.
One-pot synthesis of pyridylmethyl derivativesa
1. CH3CN, reflux, 1 h
2. K2CO3, reflux, 3 h
Ph
Br
+
2a-d
3i-l
CN
N
1b
N
Ph
Ph
Ph
CN
3i (68)
CN
3j (69)
N
N
Ph
CN
CN
3k (78)
3l (70)
a
Conditions: (i) 1b (1.0 equiv), 2a–d (2.0 equiv), CH3CN,
reflux, 1 h; (ii) K2CO3 (2.0 equiv), reflux, 3 h.
Ph
COOMe
2i
K2CO3
N
1a
N
Ph
3m (56%)
N
IV
COOMe
- IV
Ph
The reactions of picoline (2a) failed completely under the same
conditions when we use cinnamyl bromide or allyl bromide in-
stead of Baylis–Hillman bromide. The results implied that the
cyclization of II leading to 3a might be a stepwise Michael-type
addition and elimination of a pyridyl moiety (an intramolecular
SN20 type reaction) of the former canonical structure instead of
aza-Cope rearrangement of the latter canonical structure,8 as
shown in Scheme 6. However, further studies must be needed for
a detail reaction mechanism.
K2CO3
N
COOMe
Ph
IV
COOMe
- 2i
N
N
Ph
2i
Ph
V
COOMe
COOMe
VI
In summary, a base treatment of various 2-methylpyridinium
salts of Baylis–Hillman bromides generated N-allylenamine inter-
mediates. The intermediates underwent a facile 3-aza-Cope rear-
rangement under mild conditions to produce 2-pyridylmethyl-
substituted Baylis–Hillman adducts, regioselectively.
Scheme 4.
It is interesting to note that 3f and 3g were obtained as single
isomers although we did not confirm their syn/anti stereochemis-
Ph
COOMe
N
N
N
2j
N
aza-Cope
K2CO3
1a
+
Ph
N
Ph
Ph
COOMe
COOMe
COOMe
Ph
(deprotonation at 2-CH3)
3n (46%)
6 (25%)
COOMe
K2CO3
aza-Cope
Ph
Ph
COOMe
COOMe
K2CO3
- 2j
N
N
N
N
Ph
Ph
Ph
Ph
COOMe
COOMe
COOMe
(deprotonation at 2-CH3)
VII
COOMe
(deprotonation at 4-CH3)
Scheme 5.

5042
H. S. Lee et al. / Tetrahedron Letters 52 (2011) 5039–5042
aza-Cope
rearrangement
intramolecular SN2' type
addition-elimination
H2C
Ph
N
3a
H2C
Ph
N
3a
concerted mechanism
stepwise mechanism
COOMe
COOMe
resonance-stabilized enamine II
Scheme 6.
142.85, 149.20, 159.53, 167.13; ESI-MS m/z 268 (M++H). Anal. Calcd for
17H17NO2: C, 76.38; H, 6.41; N, 5.24. Found: C, 76.63; H, 6.77; N, 5.03.
Compound 3d: 73%; colorless oil; IR (film) 1720, 1487, 1445, 1271, 1253,
1139 cmꢀ1 1H NMR (CDCl3, 300 MHz)
1.19 (t, J = 7.5 Hz, 3H), 2.56 (q,
J = 7.5 Hz, 2H), 3.20 (dd, J = 13.8 and 8.4 Hz, 1H), 3.36 (dd, J = 13.8 and 7.8 Hz,
1H), 3.61 (s, 3H), 4.50 (dd, J = 8.4 and 7.8 Hz, 1H), 5.76 (s, 1H), 6.30 (s, 1H), 6.85
(d, J = 7.8 Hz, 1H), 7.10–7.25 (m, 5H), 7.29 (d, J = 7.8 Hz, 1H), 8.34 (s, 1H); 13C
NMR (CDCl3, 75 MHz) d 15.14, 25.52, 42.53, 46.29, 51.67, 122.88, 124.73, 126.30,
127.94, 128.11, 135.29, 136.41, 141.98, 142.76, 148.72, 156.62, 167.05; ESI-MS
m/z 296 (M++H). Anal. Calcd for C19H21NO2: C, 77.26; H, 7.27; N, 4.74. Found: C,
77.32; H, 7.44; N, 4.82.
Acknowledgments
C
This work was supported by the National Research Foundation
of Korea Grant funded by the Korean Government (2011-0002570).
Spectroscopic data were obtained from the Korea Basic Science
Institute, Gwangju branch.
;
d
References and notes
Compound 3g: 85%; white solid, mp 166–168 °C; IR (KBr) 1714, 1435, 1263,
1143 cmꢀ1 1H NMR (CDCl3, 300 MHz) d 3.61 (s, 3H), 4.72 (d, J = 12.3 Hz, 1H),
;
1. For the general review on Baylis–Hillman reaction, see: (a) Basavaiah, D.; Rao, A.
J.; Satyanarayana, T. Chem. Rev. 2003, 103, 811–891; (b) Basavaiah, D.; Reddy, B.
S.; Badsara, S. S. Chem. Rev. 2010, 110, 5447–5674; (c) Singh, V.; Batra, S.
Tetrahedron 2008, 64, 4511–4574; (d) Declerck, V.; Martinez, J.; Lamaty, F. Chem.
Rev. 2009, 109, 1–48; (e) Ciganek, E. In Organic Reactions; Paquette, L. A., Ed.;
John Wiley & Sons: New York, 1997; Vol. 51, pp 201–350; (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) Radha Krishna, P.; Sachwani, R.;
Reddy, P. S. Synlett 2008, 2897–2912; (i) Gowrisankar, S.; Lee, H. S.; Kim, S. H.;
Lee, K. Y.; Kim, J. N. Tetrahedron 2009, 65, 8769–8780.
2. For the synthetic applications of DABCO salt of Baylis–Hillman adduct, see: (a)
Chung, Y. M.; Gong, J. H.; Kim, T. H.; Kim, J. N. Tetrahedron Lett. 2001, 42, 9023–
9026; (b) Kim, J. N.; Lee, H. J.; Lee, K. Y.; Gong, J. H. Synlett 2002, 173–175; (c)
Gong, J. H.; Kim, H. R.; Ryu, E. K.; Kim, J. N. Bull. Korean Chem. Soc. 2002, 23, 789–
790; (d) Baidya, M.; Remennikov, G. Y.; Mayer, P.; Mayr, H. Chem. Eur. J. 2010, 16,
1365–1371; (e) Cui, H.-L.; Feng, X.; Peng, J.; Lei, J.; Jiang, K.; Chen, Y.-C. Angew.
Chem., Int. Ed. 2009, 48, 5737–5740; (f) Li, J.; Wang, X.; Zhang, Y. Tetrahedron
Lett. 2005, 46, 5233–5237.
3. For the reactions of Baylis–Hillman adducts and pyridine derivatives, see: (a)
Basavaiah, D.; Devendar, B.; Lenin, D. V.; Satyanarayana, T. Synlett 2009, 411–
416; (b) Viswambharan, B.; Selvakumar, K.; Madhavan, S.; Shanmugam, P. Org.
Lett. 2010, 12, 2108–2111; (c) Basavaiah, D.; Satyanarayana, T. Tetrahedron Lett.
2002, 43, 4301–4303; (d) Sreevani, R.; Manjula, A.; Rao, B. V. J. Heterocycl. Chem.
2011, 48, 586–591; (e) Bode, M. L.; Kaye, P. T. J. Chem. Soc., Perkin Trans. 1 1990,
2612–2613.
4. Kim, J. M.; Kim, S. H.; Lee, H. S.; Kim, J. N. Tetrahedron Lett. 2009, 50, 1734–1737.
5. For the palladium-catalyzed activation of picoline derivatives, see: (a) Qian, B.;
Guo, S.; Shao, J.; Zhu, Q.; Yang, L.; Xia, C.; Huang, H. J. Am. Chem. Soc. 2010, 132,
3650–3651; (b) Song, G.; Su, Y.; Gong, X.; Han, K.; Li, X. Org. Lett. 2011, 13, 1968–
1971; (c) Niwa, T.; Yorimitsu, H.; Oshima, K. Org. Lett. 2007, 9, 2373–2375; (d)
Burton, P. M.; Morris, J. A. Org. Lett. 2010, 12, 5359–5361; (e) Trost, B. M.;
Thaisrivongs, D. A. J. Am. Chem. Soc. 2008, 130, 14092–14093; (f) Trost, B. M.;
Thaisrivongs, D. A. J. Am. Chem. Soc. 2009, 131, 12056–12057.
5.07 (d, J = 12.3 Hz, 1H), 5.73 (s, 1H), 6.16 (s, 1H), 6.95–7.20 (m, 11H), 7.29 (d,
J = 7.8 Hz, 1H), 7.54 (t, J = 7.8 Hz, 1H), 8.53 (d, J = 4.8 Hz, 1H); 13C NMR (CDCl3,
75 MHz) d 50.35, 51.83, 57.65, 121.25, 123.00, 125.30, 126.18 (2C), 127.86,
128.01, 128.47, 128.78, 136.38, 140.60, 141.44, 142.12, 149.32, 162.08, 167.17;
ESI-MS m/z 344 (M++H). Anal. Calcd for C23H21NO2: C, 80.44; H, 6.16; N, 4.08.
Found: C, 80.28; H, 6.41; N, 3.97.
Compound 3i: 68%; colorless oil; IR (film) 2221, 1590, 1438, 1268 cmꢀ1 1H NMR
;
(CDCl3, 300 MHz) d 3.30 (dd, J = 13.8 and 7.2 Hz, 1H), 3.43 (dd, J = 13.8 and
8.7 Hz, 1H), 4.23 (dd, J = 8.7 and 7.2 Hz, 1H), 5.72 (s, 1H), 5.77 (s, 1H), 7.05-7.10
(m, 2H), 7.20–7.34 (m, 5H), 7.51 (t, J = 7.5 Hz, 1H), 8.53 (d, J = 4.8 Hz, 1H); 13C
NMR (CDCl3, 75 MHz) d 41.46, 49.72, 117.73, 121.46, 123.81, 126.03, 127.33,
127.39, 128.64, 130.61, 136.22, 139.53, 149.32, 157.81; ESI-MS m/z 235 (M++H).
Anal. Calcd for C16H14N2: C, 82.02; H, 6.02; N, 11.96. Found: C, 81.89; H, 6.25; N,
11.87.
Compound 3m: 56%; colorless oil; IR (film) 1718, 1600, 1250, 1139 cmꢀ1 1H
;
NMR (CDCl3, 300 MHz) d 3.04 (dd, J = 13.8 and 9.3 Hz, 1H), 3.21 (dd, J = 13.8 and
6.6 Hz, 1H), 3.67 (s, 3H), 4.21 (dd, J = 9.3 and 6.6 Hz, 1H), 5.69 (s, 1H), 6.33 (s,
1H), 6.96 (d, J = 5.1 Hz, 2H), 7.12–7.27 (m, 5H), 8.40 (d, J = 5.1 Hz, 2H); 13C NMR
(CDCl3, 75 MHz) d 39.98, 47.04, 51.91, 124.32, 124.91, 126.80, 128.04, 128.36,
140.76, 142.57, 148.72, 149.45, 166.92; ESI-MS m/z 268 (M++H). Anal. Calcd for
C
17H17NO2: C, 76.38; H, 6.41; N, 5.24. Found: C, 76.57; H, 6.34; N, 5.17.
Compound 3n: 46%; colorless oil; IR (film) 1721, 1605, 1443, 1271, 1142 cmꢀ1
;
1H NMR (CDCl3, 300 MHz) d 2.21 (s, 3H), 3.17 (dd, J = 13.8 and 8.4 Hz, 1H), 3.34
(dd, J = 13.8 and 7.8 Hz, 1H), 3.62 (s, 3H), 4.51 (dd, J = 8.4 and 7.8 Hz, 1H), 5.76 (s,
1H), 6.31 (s, 1H), 6.76 (s, 1H), 6.86 (d, J = 5.1 Hz, 1H), 7.11–7.27 (m, 5H), 8.34 (d,
J = 5.1 Hz, 1H); 13C NMR (CDCl3, 75 MHz) d 20.77, 42.83, 46.23, 51.66, 122.10,
124.25, 124.75, 126.30, 127.91, 128.10, 141.95, 142.70, 146.89, 148.78, 159.12,
167.05; ESI-MS m/z 282 (M++H). Anal. Calcd for C18H19NO2: C, 76.84; H, 6.81; N,
4.98. Found: C, 76.59; H, 6.97; N, 5.06.
7. For the leading references on thermal and palladium-catalyzed aza-Cope
rearrangement, see: (a) Majumdar, K. C.; Bhattacharyya, T.; Chattopadhyay, B.;
Sinha, B. Synthesis 2009, 2117–2142; (b) Welch, J. T.; DeCorte, B.; DeKimpe, N. J.
Org. Chem. 1990, 55, 4981–4983; (c) Weston, M. H.; Nakajima, K.; Back, T. G. J.
Org. Chem. 2008, 73, 4630–4637; (d) Walters, M. A. J. Org. Chem. 1996, 61, 978–
983; (e) Lee, C. G.; Lee, K. Y.; Lee, S.; Kim, J. N. Tetrahedron 2005, 61, 1493–1499;
(f) Nakamura, H.; Yamamoto, Y. Handbook of Organopalladium Chemistry for
Organic Synthesis; Wiley Interscience, 2002. pp 2919–2934; (g) Murahashi, S.-I.;
Makabe, Y.; Kunita, K. J. Org. Chem. 1988, 53, 4489–4495; Palladium-catalyzed
decarboxylative allylation through a tandem decarboxylation/N-allylation/aza-
Cope rearrangement of 2-azaarene derivatives has been reported: (h) Waetzig, S.
R.; Tunge, J. A. J. Am. Chem. Soc. 2007, 129, 4138–4139.
8. For a different discussion on the mechanism of aza-Cope rearrangement, see: (a)
Holtgrewe, C.; Diedrich, C.; Pape, T.; Grimme, S.; Hahn, F. E. Eur. J. Org. Chem.
2006, 3116–3124; (b) Winter, R. F.; Rauhut, G. Chem. Eur. J. 2002, 8, 641–649; (c)
Mariano, P. S.; Dunaway-Mariano, D.; Huesmann, P. L. J. Org. Chem. 1979, 44,
124–133.
6. Typical experimental procedure for the synthesis of compound 3a: A mixture of
Baylis–Hillman bromide 1a (255 mg, 1.0 mmol)1–4 and picoline (2a, 186 mg,
2.0 mmol) in CH3CN (2.0 mL) was heated to reflux for 60 min. To the reaction
mixture, K2CO3 (276 mg, 2.0 mmol) was added and maintain refluxing
temperature for 3 h. After the usual aqueous extractive workup and column
chromatographic process (hexanes/ether/CH2Cl2, 1:1:3) compound 3a was
obtained as colorless oil, 206 mg (77%). Other compounds were synthesized
similarly and the selected spectroscopic data of 3a, 3d, 3g, 3i, 3m, and 3n are as
follows.
Compound 3a: 77%; colorless oil; IR (film) 1720, 1438, 1249, 1143 cmꢀ1 1H NMR
;
(CDCl3, 300 MHz) d 3.23 (dd, J = 13.8 and 8.4 Hz, 1H), 3.39 (dd, J = 13.8 and
7.2 Hz, 1H), 3.63 (s, 3H), 4.51 (dd, J = 8.4 and 7.2 Hz, 1H), 5.76 (s, 1H), 6.31 (s,
1H), 6.92 (d, J = 7.5 Hz, 1H), 7.05 (dd, J = 7.5 and 4.8 Hz, 1H), 7.11–7.25 (m, 5H),
7.46 (t, J = 7.5 Hz, 1H), 8.50 (d, J = 4.8 Hz, 1H); 13C NMR (CDCl3, 75 MHz) d 43.07,
46.41, 51.79, 121.15, 123.46, 124.82, 126.44, 128.02, 128.23, 135.98, 141.89,