An efficient synthesis of α-methylene-β-butyrolactones from Baylis-Hillman adducts via an In-mediated Barbier reaction and stereoselective lactonization under MeSO2Cl/Et3N conditions

Article abstract of DOI:10.1016/j.tetlet.2010.10.077

An efficient synthesis of trans-α-methylene-β-butyrolactones is disclosed from syn-homoallylic alcohols via the intramolecular mesylate displacement reaction promoted by nearby ester group under the influence of MsCl/Et₃N. syn-Homoallylic alcoh

Full text of DOI:10.1016/j.tetlet.2010.10.077

Tetrahedron Letters 51 (2010) 6568–6571
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
An efficient synthesis of a-methylene-c-butyrolactones from
Baylis–Hillman adducts via an In-mediated Barbier reaction and stereoselective
lactonization under MeSO2Cl/Et3N conditions
⇑
Bo Ram Park, Ko Hoon Kim, 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:
An efficient synthesis of trans-a-methylene-c-butyrolactones is disclosed from syn-homoallylic alcohols
Received 13 September 2010
Revised 4 October 2010
Accepted 7 October 2010
Available online 19 October 2010
via the intramolecular mesylate displacement reaction promoted by nearby ester group under the influ-
ence of MsCl/Et3N. syn-Homoallylic alcohols were prepared via the In-mediated Barbier reaction of the
bromides of Baylis–Hillman adducts.
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
a-Methylene-c-butyrolactones
Baylis–Hillman adducts
Indium
Barbier reaction
Lactonization
a
-Methylene-
c
-butyrolactone derivatives have attracted much
and cinnamyl bromides.2b,4 During our continuous studies on the
synthetic applicability of syn-homoallylic alcohols, we reasoned
out that trans-a-methylene-c-butyrolactone 4a could be synthe-
attention,1,2 because this moiety is found in a wide range of natural
substances and is a pivotal unit for their biological activities.1 Fur-
thermore,
ing materials for many important compounds.1,2 The easiest
method for the synthesis of -methylene- -butyrolactones
involved the reaction of allylic metal reagents and carbonyl com-
pounds to make homoallyl alcohols followed by acid-catalyzed
lactonization.2b,c,e,f,3b–e
a
-methylene-
c
-butyrolactones served as versatile start-
sized from syn-homoallylic alcohol 2a via the mesylate 3a, as
shown in Scheme 1 (path c). The mesylate 3a could be cyclized
to form 4a in an intramolecular SN2 manner by the nearby ester
moiety.5 The use of a strong acid3b–e and tedious separation of a
side product such as triphenylphosphine oxide3a could be avoided
under the conditions.
a
c
syn-Homoallylic alcohol 2a was formed as the major product in
the metal-mediated reactions of benzaldehyde and cinnamyl bro-
mide 1a or the acetate of Baylis–Hillman adduct, as shown in
Scheme 1.2f,3,4 An acid-catalyzed lactonization of the syn-homoal-
lylic alcohols mostly produced the corresponding cis-3,4-disubsti-
In order to examine the feasibility of our rationale, various syn-
homoallylic alcohols 2a–h were prepared as reported.2b,4,6 Various
conditions were examined with 2a as a model substrate, and we
found that the use of MsCl (1.5 equiv) and Et3N (1.8 equiv) in
CH2Cl2 (0 °C to rt) provides suitable conditions.7 trans-Lactone 4a
was isolated in high yield (89%) along with a trace amount (<2%)
of the corresponding cis-lactone 5a, which might be formed either
via a direct esterification reaction of 2a or in situ conversion of
mesylate 3a to the chloride and a following lactonization process.5c
The plausible reaction mechanism for the trans-lactone 4a is sug-
gested in Scheme 2. The mesylate 3a forms the corresponding oxo-
nium ion intermediate (I) via the intramolecular SN2-type attack of
the ester.5 The oxonium ion was converted to the trans-lactone 4a.
The use of TsCl instead of MsCl was found to be less effective and
the addition of DMAP (cat.) did not improve the yield of 4a.
Encouraged by the results we carried out the synthesis of trans-
lactones 4b–h, and the results are summarized in Table 1.6,7 The
reactions of 2b, 2d, 2g, and 2h afforded desired trans-lactones 4b,
4d, 4g, and 4h (entries 2, 4, 7 and 8) in moderate to good yields
tuted
a-methylene-c
-butyrolactones.2f,4b In order to prepare the
trans-lactone 4a from syn-homoallyl alcohol, Kabalka et al. used
CBr4/PPh3 to convert the alcohol moiety into a good leaving group,
a phosphonium salt, and carried out the lactonization (path a).3a
Hall3b,c and Ramachandran3d,e used strong acids, TfOH and In
(OTf)3, respectively, to form the benzylic carbocation intermediate
for the preparation of trans-lactone (path b).
Very recently we reported the synthesis of indeno[2,1-a]inda-
ne4a and
c
-hydroxybutenolides4b from syn-homoallylic alcohols,
prepared by the In-mediated Barbier-type reaction of aldehydes
⇑
Corresponding author.
E-mail address: kimjn@chonnam.ac.kr (J.N. Kim).
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.10.077

B. R. Park et al. / Tetrahedron Letters 51 (2010) 6568–6571
6569
OAc
COOMe
(i) Pd
(ii) PhCHO
Ph
Ph
OH
COOMe
PPh3
O
Ph
Ph
Ph
O
- PPh3O
CBr4/PPh3
Ph
Ph
O
(a)
O
B
O
O
B
O
Kabalka
COOMe
2a
4a
COOMe
Ar
Ar
Ar
O
O
R
O
Hall: TfOH
O
O
(b)
(c)
O
B
Me
Me
R
R
Ramachandran: In(OTf)3
R
O
O
Ar-CHO
Ph
OH
COOMe
Ph
Ph
OMs
COOMe
Ph
Ph
O
COOMe
Br
MsCl/Et3N
In/PhCHO
Ph
O
This Work
Ph
4a
1a
2a
3a
Scheme 1.
Ph
Ph
O
OMs
Ph
Ph
- MeSO3Me
MsCl/Et3N
- Et3NHCl
O
Me
O
2a
4a
O
Me
(I)
MsO
3a
Scheme 2.
Table 1
Synthesis of trans-lactone from syn homolytic alcohol
R2
OH
COOMe
R2
R1
5 (cis)
R2
R1
O
O
Conditionsa
O
O
R1
+
2 (syn)
4 (trans)
Entry
R1
R2
2b (%)
Time (h)
Productsc (%)
Reportedd (%)
1
2
3
4
5
6
7
8
Ph
Ph
4-MePh
Ph
Ph
Ph
Me
Me
Me
2a (93)
2b (91)
2c (81)
2d (86)
2e (80)
2f (81)
2g (84)
2h (84)
2
4
6
2
4a (89)
4b (77)
4c (50)
4d (86)
4e (85)f
4f (48)
4g (87)
4h (72)
56 (4a),3a 91 (4a)3d
80 (4b/5b = 69/31)3d
0 (4c)3a
4-ClPh
4-MeOPh
4-MePh
Me
Cinnamyl
Ph
98 (4d)3d
30 mine
No data
No data
6
2
4
49 (4g),3a 85 (4g)3d
85 (4h/5h = 45/55)3d
3-ClPh
a
b
c
d
e
f
Conditions: MsCl (1.5 equiv), Et3N (1.8 equiv), CH2Cl2, 0 °C to rt.
Isolated yield of syn isomer prepared as reported.2a,3a,4b
Trace amounts of cis-lactone were observed on TLC (<3%).
We showed the reported data of Kabalka and Ramachandran.
Corresponding mesylate 3e was isolated in 89% instead of 4e.
trans-Lactone 4e was synthesized by heating 3e in toluene (9h) in the presence of DAMP (10%).
(72–87%). However, the reactions of p-methoxyphenyl derivative
2c (entry 3) and cinnamyl derivative 2f (entry 6) showed low
yields of products, unexpectedly. Increased amounts of side prod-
ucts were observed on TLC. The reaction of 2e did not produce
4e at all under the same conditions (entry 5). As compared with
other benzylic (2a–d, 2g and 2h) or allylic mesylate (2f), the corre-
sponding mesylate 3e is a secondary alkyl one and the ester-med-
iated lactonization of 3e was ineffective at room temperature.
Fortunately when the mesylate 3e was heated to reflux in toluene
in the presence of DMAP (10%) the lactonization occurred smoothly
to afford 4e in 85%. It is interesting to note that the reactions with
the corresponding ethyl or n-hexyl esters of 2a showed somewhat
diminished yield of 4a (75% and 55%, respectively). Increased
amounts of side products were observed for the ethyl and hexyl es-
ters. The results might be due to the increased steric interference
during formation of the corresponding oxonium ion intermediate.
In order to overcome the low yields of trans-lactones in some
cases (entries 3 and 6 in Table 1) we examined the lactonization
of 2 under acid-catalyzed reaction conditions, as shown in Scheme
3. The reaction of 2a under acid-catalyzed conditions (p-TsOH,
CH2Cl2, rt) produced a cis-lactone 5a exclusively, presumably via
the Fischer esterification mechanism as reported.3a,4b We could

6570
B. R. Park et al. / Tetrahedron Letters 51 (2010) 6568–6571
R2
R1
OH
O
- MeOH
OMe
H
R2
R1
OH
COOMe
R2
R1
R2
R1
O
O
p-TsOH (10%)
CH2Cl2, rt, time
O
O
+
2
4
5
R2
R1
R2
R1
OH2
- H2O
COOMe
COOMe
Entry
Substrate
Time (h)
Product (%)a
1
2
2a
2c
1
4
4a (0),b 5a (95)
4c (62), 5c (20)
3
4
5
6
2c
2c
2f
24
72
1
4c (78), 5c (10)
4c (81), 5c (8)
4f (21), 5f (70)
4f (52), 5f (37)
2f
72
aIsolated yield. bCompound 4a was not observed after 24 h.
Scheme 3.
not observe the formation of any trace amount of a trans-lactone
4a even after 24 h under the conditions.3c However, the reaction
of 2c produced the desired trans-lactone 4c in 62% yield (entry
2), and the yield of 4c increased to 81% when the reaction mixture
was stirred for a long time (entry 4).8 The formation of 4c must in-
volve the carbocation intermediate, and the ratio of 4c/5c might be
the result of relative thermodynamic stabilities of the lactones. The
p-methoxy substituent of 2c could stabilize the benzylic carbocat-
ion intermediate.3c,3d The slow conversion of 5c to 4c could be ex-
plained by ring-opening of 5c to the carbocation intermediate and
re-cyclization to the more stable 4c, as observed by Hall in a sim-
ilar case.3c The reaction of cinnamyl derivative 2f produced a cis-
lactone 5f as the major product (70%) when we stop the reaction
in short time (entry 5); however, the yield of a trans-lactone 4f in-
creased to 52% after 72 h (entry 6). The results stated that the ratio
of cis/trans-lactones is highly dependent on the carbocation stabil-
ity and the relative thermodynamic stabilities under the acid-cat-
alyzed lactonization conditions.
References and notes
1. For the leading reviews on the synthesis and biological activity of
a-methylene-
c
-butyrolactones, see: (a) Kitson, R. R. A.; Millemaggi, A.; Taylor, R. J. K. Angew.
Chem., Int. Ed. 2009, 48, 9426–9451. and further references cited therein; (b)
Hoffmann, H. M. R.; Rabe, J. Angew. Chem., Int. Ed. Engl. 1985, 24, 94–110; (c)
Lepoittevin, J.-P.; Berl, V.; Gimenez-Arnau, E. Chem. Rec. 2009, 9, 258–270; (d)
Elford, T. G.; Hall, D. G. Synthesis 2010, 893–907.
2. For the synthesis of a-methylene-c-butyrolactones, see: (a) Lee, A. S.-Y.; Chang,
Y.-T.; Wang, S.-H.; Chu, S.-F. Tetrahedron Lett. 2002, 43, 8489–8492; (b) Paquette,
L. A.; Mendez-Andino, J. Tetrahedron Lett. 1999, 40, 4301–4304; (c)
Ramachandran, P. V.; Garner, G.; Pratihar, D. Org. Lett. 2007, 9, 4753–4756; (d)
Le Lamer, A.-C.; Gouault, N.; David, M.; Boustie, J.; Uriac, P. J. Comb. Chem. 2006,
8, 643–645; (e) Lee, K. Y.; Park, D. Y.; Kim, J. N. Bull. Korean Chem. Soc. 2006, 27,
1489–1492; (f) Kabalka, G. W.; Venkataiah, B. Tetrahedron Lett. 2005, 46, 7325–
7328.
3. For the stereoselective synthesis of trans-lactones from syn-homoallylic
alcohols, see: (a) Kabalka, G. W.; Venkataiah, B.; Chen, C. Tetrahedron Lett.
2006, 47, 4187–4189. and further references cited therein.; (b) Yu, S. H.;
Ferguson, M. J.; McDonald, R.; Hall, D. G. J. Am. Chem. Soc. 2005, 127, 12808–
12809; (c) Elford, T. G.; Arimura, Y.; Yu, S. H.; Hall, D. G. J. Org. Chem. 2007, 72,
1276–1284; (d) Ramachandran, P. V.; Pratihar, D.; Biswas, D. Org. Lett. 2006, 8,
3877–3879; (e) Ramachandran, P. V.; Pratihar, D. Org. Lett. 2007, 9, 2087–
2090.
4. For our recent synthetic applications of homoallyl alcohols, see: (a) Kim, K. H.;
Lee, H. S.; Kim, S. H.; Kim, S. H.; Kim, J. N. Chem. Eur. J. 2010, 16, 2375–2380; (b)
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.
5. For the synthesis of lactone and related compounds via the intramolecular
mesylate displacement promoted by ester or carboxylate anion, see: (a) Barco,
A.; Baricordi, N.; Benetti, S.; Risi, C. D.; Pollini, G. P.; Zanirato, V. Tetrahedron
2007, 63, 4278–4283; (b) Vedejs, E.; Larsen, S. D. J. Am. Chem. Soc. 1984, 106,
3030–3032; (c) White, J. D.; Amedio, J. C., Jr.; Gut, S.; Ohira, S.; Jayasinghe, L. R. J.
Org. Chem. 1992, 57, 2270–2284; (d) El Moncef, A.; El Hadrami, E. M.; Gonzalez,
M. A.; Zaballos, E.; Zaragoza, R. J. Tetrahedron 2010, 66, 5173–5184.
6. Preparation of starting materials 2a–h: The starting materials 2a–h were
prepared according to the reported procedure by the In-mediated Barbier-type
reaction of corresponding aldehydes and the cinnamyl bromides of Baylis–
Hillman adducts.2b,4b The compounds 2a,3a,4b 2b4b and 2g3a are known, and the
spectroscopic data of unknown compounds 2c–f and 2h are as follows.
In summary, we disclosed an efficient synthetic method of
trans-a-methylene-c-butyrolactone derivatives from the easily
available syn-homoallylic alcohols under MsCl/Et3N conditions. In
addition, the yields of trans-lactones could be increased using the
equilibrium process under acid-catalyzed conditions when the
yield was low under MsCl/Et3N conditions.
Acknowledgments
This work was supported by the National Research Foundation
of Korea Grant funded by the Korean Government (2010-0015675).
Spectroscopic data were obtained from the Korea Basic Science
Institute, Gwangju branch.

B. R. Park et al. / Tetrahedron Letters 51 (2010) 6568–6571
6571
Compound 2c: 81%; colorless oil; IR (film) 3504, 2949, 1720, 1612, 1513,
1250 cmÀ1 1H NMR (CDCl3, 300 MHz) d 2.02 (br s, 1H), 2.31 (s, 3H), 3.55 (s, 3H),
spectroscopic data were identical with the reported.3d Other compounds 4c–h
were synthesized analogously and the selected spectroscopic data of unknown
compounds 4c, 4e, 4f and 4h are as follows.
;
3.76 (s, 3H), 4.24 (d, J = 8.4 Hz, 1H), 5.16 (d, J = 8.4 Hz, 1H), 5.74 (s, 1H), 6.19 (s,
1H), 6.82 (d, J = 8.7 Hz, 2H), 7.12 (d, J = 7.8 Hz, 2H), 7.22 (d, J = 8.7 Hz, 2H), 7.23
(d, J = 7.8 Hz, 2H); 13C NMR (CDCl3, 75 MHz) d 20.97, 51.75, 53.86, 55.12, 75.32,
113.52, 126.41, 128.17, 128.91, 129.23, 134.16, 135.78, 136.70, 141.22, 159.02,
166.94; ESIMS m/z 327 (M++H). Anal. Calcd for C20H22O4: C, 73.60; H, 6.79.
Found: C, 73.87; H, 6.67.
Compound 4c: 50%; colorless oil; IR (film) 1768, 1613, 1514, 1250, 1177 cmÀ1
;
1H NMR (CDCl3, 300 MHz) d 2.35 (s, 3H), 3.80 (s, 3H), 4.01 (ddd, J = 7.8, 3.3 and
3.0 Hz, 1H), 5.29 (d, J = 7.8 Hz, 1H), 5.43 (d, J = 3.0 Hz, 1H), 6.41 (d, J = 3.3 Hz, 1H),
6.86 (d, J = 9.0 Hz, 2H), 7.04 (d, J = 7.8 Hz, 2H), 7.15 (d, J = 9.0 Hz, 2H), 7.17 (d,
J = 7.8 Hz, 2H); 13C NMR (CDCl3, 75 MHz) d 21.07, 55.11, 55.26, 85.99, 114.05,
123.56, 127.11, 128.34, 129.80, 130.09, 134.96, 137.66, 140.20, 159.86, 169.62;
ESIMS m/z 295 (M++H). Anal. Calcd for C19H18O3: C, 77.53; H, 6.16. Found: C,
77.72; H, 6.33.
Compound 2d: 86%; colorless oil; IR (film) 3503, 3026, 1720, 1624, 1438, 1250,
1143 cmÀ1 1H NMR (CDCl3, 300 MHz) d 1.94 (d, J = 3.0 Hz, 1H), 2.32 (s, 3H), 3.57
;
(s, 3H), 4.31 (d, J = 8.1 Hz, 1H), 5.22 (dd, J = 8.1 and 3.0 Hz, 1H), 5.79 (s, 1H), 6.23
(s, 1H), 7.10 (d, J = 7.8 Hz, 2H), 7.19 (d, J = 7.8 Hz, 2H), 7.25–7.36 (m, 5H); 13C
NMR (CDCl3, 75 MHz) d 21.11, 51.83, 54.16, 75.62, 126.70, 126.91, 127.17,
128.51, 128.93, 129.16, 137.44, 138.80, 138.98, 141.08, 166.94; ESIMS m/z 297
(M++H). Anal. Calcd for C19H20O3: C, 77.00; H, 6.80. Found: C, 77.26; H, 6.68.
Compound 2e: 80%; colorless oil; IR (film) 3537, 2971, 1720, 1624, 1439, 1255,
Compound 4e: 85%; white solid; mp 37–39 °C; IR (KBr) 1767, 1387, 1224,
1162 cmÀ1 1H NMR (CDCl3, 300 MHz) d 1.47 (d, J = 6.0 Hz, 3H), 3.72 (ddd, J = 7.8,
;
3.3 and 2.7 Hz, 1H), 4.48 (dq, J = 7.8 and 6.0 Hz, 1H), 5.39 (d, J = 2.7 Hz, 1H), 6.35
(d, J = 3.3 Hz, 1H), 7.19–7.23 (m, 2H), 7.29–7.41 (m, 3H); 13C NMR (CDCl3,
75 MHz) d 19.79, 54.41, 81.71, 123.31, 127.86, 128.31, 129.10, 138.32, 140.34,
169.64; ESIMS m/z 189 (M++H). Anal. Calcd for C12H12O2: C, 76.57; H, 6.43.
Found: C, 76.64; H, 6.65.
1149 cmÀ1 1H NMR (CDCl3, 300 MHz) d 1.24 (d, J = 6.3 Hz, 3H), 1.70 (br s, 1H),
;
3.68 (s, 3H), 3.84 (d, J = 7.2 Hz, 1H), 4.32–4.40 (m, 1H), 5.85 (s, 1H), 6.35 (s, 1H),
7.19–7.39 (m, 5H); 13C NMR (CDCl3, 75 MHz) d 21.45, 51.96, 54.25, 69.02,
125.95, 127.12, 128.58, 129.10, 138.94, 141.66, 167.21; ESIMS m/z 221 (M++H).
Anal. Calcd for C13H16O3: C, 70.89; H, 7.32. Found: C, 71.05; H, 7.25.
Compound 4f: 48%; colorless oil; IR (film) 1768, 1494, 1454, 1307, 1284 cmÀ1 1H
;
NMR (CDCl3, 300 MHz) d 3.98 (ddd, J = 7.8, 3.3 and 3.0 Hz, 1H), 4.96 (dd, J = 7.8
and 6.9 Hz, 1H), 5.46 (d, J = 3.0 Hz, 1H), 6.24 (dd, J = 15.9 and 6.9 Hz, 1H), 6.42 (d,
J = 3.3 Hz, 1H), 6.59 (d, J = 15.9 Hz, 1H), 7.21–7.42 (m, 10H); 13C NMR (CDCl3,
75 MHz) d 53.23, 85.35, 123.95, 124.82, 126.75, 127.97, 128.39, 128.43, 128.65,
129.18, 133.87, 135.51, 137.94, 139.44, 169.40; ESIMS m/z 277 (M++H). Anal.
Calcd for C19H16O2: C, 82.58; H, 5.84. Found: C, 82.39; H, 5.91.
Compound 2f: 81%; colorless oil; IR (film) 3480, 3026, 1717, 1438, 1253,
1143 cmÀ1 1H NMR (CDCl3, 300 MHz) d 1.90 (br s, 1H), 3.62 (s, 3H), 4.13 (d,
;
J = 7.5 Hz, 1H), 4.83 (dd, J = 7.5 and 7.2 Hz, 1H), 5.85 (s, 1H), 6.20 (dd, J = 15.9 and
7.2 Hz, 1H), 6.35 (s, 1H), 6.60 (d, J = 15.9 Hz, 1H), 7.19–7.39 (m, 10H); 13C NMR
(CDCl3, 75 MHz) d 51.96, 53.06, 74.17, 126.49, 126.78, 127.19, 127.69, 128.48,
128.59, 129.13, 130.04, 131.90, 136.53, 138.52, 141.02, 167.23; ESIMS m/z 309
(M++H). Anal. Calcd for C20H20O3: C, 77.90; H, 6.54. Found: C, 77.69; H, 6.86.
Compound 2h: 84%; colorless oil; IR (film) 3504, 2950, 1713, 1438, 1270,
Compound 4h: 72%; white solid; mp 78–80 °C; IR (KBr) 1768, 1308, 1252, 1209,
1134 cmÀ1 1H NMR (CDCl3, 300 MHz) d 1.34 (d, J = 6.9 Hz, 3H), 2.88–2.97 (m,
;
1H), 4.88 (d, J = 7.8 Hz, 1H), 5.61 (d, J = 3.0 Hz, 1H), 6.33 (d, J = 3.3 Hz, 1H), 7.21–
7.25 (m, 1H), 7.30–7.35 (m, 3H); 13C NMR (CDCl3, 75 MHz) d 15.95, 43.31, 84.88,
121.44, 123.91, 125.92, 128.91, 130.12, 134.78, 139.86, 140.49, 169.63; ESIMS
m/z 223 (M++H), 225 (M++2+H). Anal. Calcd for C12H11ClO2: C, 64.73; H, 4.98.
Found: C, 64.97; H, 5.11.
1154 cmÀ1 1H NMR (CDCl3, 300 MHz)
; d 1.01 (d, J = 7.2 Hz, 3H), 2.63 (d,
J = 2.7 Hz, 1H), 3.05–3.14 (m, 1H), 3.78 (s, 3H), 4.86 (dd, J = 3.6 and 2.7 Hz, 1H),
5.59 (s, 1H), 6.29 (s, 1H), 7.19–7.28 (m, 3H), 7.36 (s, 1H); 13C NMR (CDCl3,
75 MHz) d 12.29, 42.64, 52.12, 74.76, 124.33, 126.33, 126.52, 127.25, 129.26,
133.98, 142.15, 144.73, 168.06; ESIMS m/z 255 (M++H), 257 (M++2+H). Anal.
Calcd for C13H15ClO3: C, 61.30; H, 5.94. Found: C, 61.54; H, 6.11.
8. Typical procedure for the synthesis of 4c (entry 4 in Scheme 3): To a stirred
solution of 2c (163 mg, 0.5 mmol) in dry CH2Cl2 (1.5 mL) was added
p-TsOH (10 mg) and stirred at room temperature for 72 h. After the usual
aqueous workup and column chromatographic purification process (hexanes/
EtOAc, 20:1) compound 4c was obtained as colorless oil (119 mg, 81%)
7. Typical procedure for the synthesis of 4a: To a stirred solution of 2a (141 mg,
0.5 mmol) and Et3N (91 mg, 0.9 mmol) in dry CH2Cl2 (1.0 mL) was added a
solution of MsCl (86 mg, 0.75 mmol) in CH2Cl2 (0.3 mL) at 0 °C for 5 min by gas-
tight syringe under N2 atmosphere. The reaction mixture was stirred at room
temperature for 2 h. After the usual aqueous workup and column
chromatographic purification process (hexanes/EtOAc, 15:1) compound 4a
along with 5c (12 mg, 8%). Other entries in Scheme
2 were carried out
similarly, and the spectroscopic data of unknown compounds 5c and 5f are as
follows.
Compound 5c: 8%; colorless oil; IR (film) 1768, 1613, 1514, 1251, 1177 cmÀ1 1H
;
was obtained as
a
white solid (mp 73–75 °C) 111 mg (89%), and the
NMR (CDCl3, 300 MHz) d 2.22 (s, 3H), 3.72 (s, 3H), 4.59 (ddd, J = 8.1, 3.3 and
2.7 Hz, 1H), 5.53 (d, J = 2.7 Hz, 1H), 5.76 (d, J = 8.1 Hz, 1H), 6.48 (d, J = 3.3 Hz, 1H),
6.63 (d, J = 7.8 Hz, 2H), 6.65 (d, J = 9.0 Hz, 2H), 6.76 (d, J = 9.0 Hz, 2H), 6.90 (d,
J = 7.8 Hz, 2H); 13C NMR (CDCl3, 75 MHz) d 20.95, 51.78, 55.15, 82.57, 113.29,
124.38, 127.17, 128.31, 128.87, 129.17, 133.13, 136.98, 138.28, 159.20, 170.86;
ESIMS m/z 295 (M++H). Anal. Calcd for C19H18O3: C, 77.53; H, 6.16. Found: C,
77.85; H, 6.27.
spectroscopic data were identical with the reported.2c,3d
When we used the procedure of 4a for the synthesis of 4b–h the yields of
products decreased to some extent (5–10%) due to the increased formation of
side products. Thus we used the following procedure for the synthesis of 4b–h.
Typical procedure for the synthesis of 4b: To a stirred solution of 2b (159 mg,
0.5 mmol) and Et3N (91 mg, 0.9 mmol) in dry CH2Cl2 (1.0 mL) was added a
solution of MsCl (86 mg, 0.75 mmol) in CH2Cl2 (0.3 mL) at 0 °C for 5 min by gas-
tight syringe under N2 atmosphere. The reaction mixture was stirred at 0 °C for
15 min. The reaction mixture was poured into cold aqueous NH4Cl and extracted
with ether. The organic layer was separated, dried with MgSO4, and the solvent
was evaporated under reduced pressure. The crude reaction mixture was
dissolved in CH2Cl2 (2.0 mL) and stirred for 4 h. After removal of CH2Cl2 and
column chromatographic purification process (hexanes/EtOAc, 12:1) compound
Compound 5f: 37% (entry 6 in Scheme 3); colorless oil; IR (film) 1764, 1496,
1453, 1313, 1262, 1142 cmÀ1 1H NMR (CDCl3, 300 MHz) d 4.52 (ddd, J = 8.1, 3.0
;
and 2.7 Hz, 1H), 5.39 (dd, J = 8.1 and 6.6 Hz, 1H), 5.61 (dd, J = 15.9 and 6.6 Hz,
1H), 5.62 (d, J = 2.7 Hz, 1H), 6.51 (d, J = 3.0 Hz, 1H), 6.55 (d, J = 15.9 Hz, 1H), 7.09–
7.37 (m, 10H); 13C NMR (CDCl3, 75 MHz) d 50.54, 81.24, 124.78 (2C), 126.61,
127.88, 128.11, 128.52, 128.73, 129.29, 133.00, 135.81, 136.74, 138.09, 170.20;
ESIMS m/z 277 (M++H). Anal. Calcd for C19H16O2: C, 82.58; H, 5.84. Found: C,
82.72; H, 6.03.
4b was obtained as
a white solid (mp 78–79 °C) 109 mg (77%), and the