Facile synthesis of lactones and dihydronaphthalenes from methyl 2-isobutenyl (or 2-isopentenyl)cinnamates as the common intermediates

Article abstract of DOI:10.1016/j.tetlet.2004.07.070

We prepared three different types of compounds, two α-alkylidene- γ-butyrolactones and 3,4-dihydronaphthalene-2-carboxylic acid from methyl 2-isobutenylcinnamates or methyl 2-isopentenylcinnamates as the common intermediates, which were derived from the acetates of Baylis-Hillman adducts.

Full text of DOI:10.1016/j.tetlet.2004.07.070

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 6949–6953
Facile synthesis of lactones and dihydronaphthalenes from methyl
2-isobutenyl (or 2-isopentenyl)cinnamates as the
common intermediates
Saravanan GowriSankar, Chang Gon Lee and Jae Nyoung Kim*
Department of Chemistry and Institute of Basic Science, Chonnam National University, Kwangju 500-757, South Korea
Received 14 May 2004;revised 9 July 2004;accepted 16 July 2004
Available online 6 August 2004
Abstract—We prepared three different types of compounds, two a-alkylidene-c-butyrolactones and 3,4-dihydronaphthalene-2-carb-
oxylic acid from methyl 2-isobutenylcinnamates or methyl 2-isopentenylcinnamates as the common intermediates, which were
derived from the acetates of Baylis–Hillman adducts.
Ó 2004 Elsevier Ltd. All rights reserved.
Various a-alkylidene-c-butyrolactones are important
compounds due to the abundance of the skeleton in a
variety of natural products, especially in sesquiterpene
lactones and lignans.1 Also, they served as valuable syn-
thetic intermediates for the synthesis of many kinds of
natural products and biologically important sub-
stances.1–3 Some of the lactones showed interesting
pharmacological, fungicidal, and plant-growth regula-
tory activities.1–3 In view of their biological importance,
numerous synthetic methods have been reported.2–4
tion strategy would furnish the desired a-alkylidene-c-
butyrolactones 4. The reaction of the Baylis–Hillman
acetate 1a and isopropenylmagnesium bromide (2a) in
THF at 0–10°C gave the corresponding SN20 type com-
pound, methyl 2-isobutenylcinnamate (3a) in 75%
yield.8 With the compound 3a in our hands, we exam-
ined various reaction conditions. The reaction of 3a in
benzene in the presence of H2SO4 (3equiv) at room tem-
perature gave the 5,5-dimethyllactone derivative 4a in
72% yield as expected.9,10 Without the need of hydroly-
sis step of the ester moiety to the carboxylic acid func-
tionality, the lactonization step proceeded well with
the ester moiety.11
The dihydronaphthalene moiety is also found in many
lignans, a class of natural products found in plants.5 Re-
cently, some anilide derivatives of dihydronaphthalene
showed anti-HIV-1 activity.5a In these respects, a variety
of synthetic methods of dihydronaphthalenes have been
developed.6
It is interesting to note that the reaction of 3a in benzene
in the presence of H2SO4 (3equiv) at elevated tempera-
ture (60–70°C) gave the dimethyl 3,4-dihydronaphthal-
ene 5a in 72% yield.12 Initially, we thought that 5a
might be formed via the acid-catalyzed Friedel–Crafts
type reaction of 3a and the following acid hydrolysis
of the ester moiety during the reaction or separation
stage. However, we could not observe any trace
amounts of the corresponding methyl ester of 5a. This
means that the mechanism for the formation of 5a must
involve different reaction pathway. Thus, we examined
the reaction of the 5,5-dimethyllactone 4a and H2SO4
at elevated temperature (60–70°C) in benzene and we
could obtain 5a in high yield (87%). From the results
we could conclude that 5a was formed via the lactone
derivative 4a. Similar transformation have been pub-
lished by Mark and co-workers in a similar system.13
During the course of our studies on the chemical trans-
formations of the Baylis–Hillman adducts,7 we intended
to prepare a-benzylidene-c-butyrolactone derivatives.
Our synthetic rationale is depicted in Scheme 1. Intro-
duction of appropriate vinyl moiety onto the Baylis–
Hillman acetates 1 followed by acid-catalyzed lactoniza-
Keywords: Methyl 2-isobutenylcinnamates;Lactones;Dihydronaph-
thalenes;Baylis–Hillman adducts.
*
Corresponding author. Tel.: +82-62-530-3381;fax: +82-62-530-
3389;e-mail: kimjn@chonnam.ac.kr
0040-4039/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.07.070

6950
S. GowriSankar et al. / Tetrahedron Letters 45 (2004) 6949–6953
OAc
MgBr
COOMe
R2
COOMe
2a-b
THF, 0-10 oC
rt, 6-10 h, 70-86%
R1
R2
R1
3a-e
1a-c
PhH, rt, 5-12 h
H2SO4 (3 equiv)
70-76%
CHCl3, 30 oC, 6-9 h
m-CPBA (1.5 equiv)
56-84%
PhH, 60 oC, 7-40 h
H2SO4 (3 equiv)
55-72%
O
O
COOH
O
O
R1
R1
R1
R2
OH
R2
4a-e
R2
5a-e
6a-e
PhH, H2SO4, 60-70 oC
5a (26 h, 87%)
5b (38 h, 86%)
Scheme 1.
The mechanism for the formation 3,4-dihydronaphthal-
enes 5a from 4a could be explained as follows as shown
in Scheme 2: sequential protonation, ring-opening to
carbocation intermediate (I), and Friedel–Crafts reac-
tion. The arene moiety of (I) has low nucleophilicity
due to the conjugation with the electron withdrawing
carboxylic acid moiety. Thus, the successful Friedel–
Crafts reaction is interesting.
ing epoxide and eventually 5-methyl-5-hydroxymethyl-
lactone derivative 6a.4 Actually, the reaction afforded
the corresponding 5-methyl-5-hydroxymethyl lactone
6a in 84% yield during the epoxidation stage directly.14
In the reaction, generated m-chlorobenzoic acid might
act as the acid catalyst for the lactonization step. In
order to facilitate the lactonization rate we added cata-
lytic amounts of trifluoroacetic acid in some cases (for
6d and 6e) depending upon the substrates (Scheme 3).
Diastereo- isomeric mixtures of the corresponding syn
and anti forms were formed for the cases of 6d and 6e
As a next trial, we examined the reaction of 3a and m-
CPBA in CHCl3 in order to synthesize the correspond-
O
Friedel-Crafts
OH
3a
5a
—H
(I)
H2SO4
rt
H2SO4
60-70 oC
HSO4
CH3
O
CH3
O
O
O
O
O
4a
Scheme 2.
30 oC (for 6a-c)
CF3COOH (cat.) (for 6d-e)
m-CPBA
COOMe
rt
6
3
R1
R2
O
Scheme 3.

S. GowriSankar et al. / Tetrahedron Letters 45 (2004) 6949–6953
6951
Table 1. Synthesis of 3, 4, 5, and 6
Heterocycles 1985, 23, 661;(f) Lee, E.;Hur, C. U.;Geong,
Y. C.;Rhee, Y. H.;Chang, M. H. J. Chem. Soc., Chem.
Commun. 1991, 9, 1314;(g) Larson, G. L.;Betancourtde
Perez, M. B. J. Org. Chem. 1985, 50, 5257;(h) Tanaka, M.;
Mukaiyama, C.;Mitsuhashi, H.;Wakamatsu, T. Tetra-
hedron Lett. 1992, 33, 4165;(i) Tanaka, M.;Mitsuhashi,
H.;Wakamatsu, T. Tetrahedron Lett. 1992, 33, 4161;(j)
Berkowitz, D. B.;Choi, S.;Maeng, J.-H. J. Org. Chem.
2000, 65, 847;(k) Chen, M.-J.;Lo, C.-Y.;Chin, C.-C.;Liu,
R.-S. J. Org. Chem. 2000, 65, 6362, and further references
cited therein.
Entry
R1
R2
3
4
5
6
a
b
c
d
e
H
Cl
H
75
70
73
81
86
72
76
70
70
75
72
70
60
57
55
84
81
69
62
56
H
CH3
H
H
CH3
CH3
Cl
2. For the synthesis of a-alkylidene-c-butyrolactones and
their synthetic utilities, see: (a) Grigg, R.;Savic, V. Chem.
Commun. 2000, 2381;(b) Johnston, D.;Francon, N.;
Edmonds, D. J.;Procter, D. J. Org. Lett. 2001, 3, 2001;(c)
Gagnier, S. V.;Larock, R. C. J. Org. Chem. 2000, 65,
1525;(d) Rossi, R.;Bellina, F.;Bechini, C.;Mannina, L.;
Vergamini, P. Tetrahedron 1998, 54, 135;(e) Ballini, R.;
Marcantoni, E.;Perella, S. J. Org. Chem. 1999, 64, 2954;
(f) Liang, K.-W.;Li, W.-T.;Peng, S.-M.;Wang, S.-L.;Liu,
R.-S. J. Am. Chem. Soc. 1997, 119, 4404;(g) Lee, K.;
Jackson, J. A.;Wiemer, D. F. J. Org. Chem. 1993, 58,
5967;(h) Martin, L. D.;Stille, J. K. J. Org. Chem. 1982,
47, 3630;(i) Minami, T.;Niki, I.;Agawa, T. J. Org. Chem.
1974, 39, 3236;(j) Zimmer, H.;Rothe, J. J. Org. Chem.
1959, 24, 28;(k) Liu, B.;Chen, M.-J.;Lo, C.-Y.;Liu, R.-S.
Tetrahedron Lett. 2001, 42, 2533;(l) Chen, M.-J.;Lo, C.-Y.;
Liu, R.-S. Synlett 2000, 1205;(m) Masuyama, Y.;Nimura,
Y.;Kurusu, Y. Tetrahedron Lett. 1991, 32, 225.
3. For the synthesis of lactones by using Baylis–Hillman
chemistry, see: (a) Brzezinski, L. J.;Rafel, S.;Leahy, J. W.
J. Am. Chem. Soc. 1997, 119, 4317;(b) Paquette, L. A.;
Mendez-Andino, J. Tetrahedron Lett. 1999, 40, 4301;(c)
Choudhury, P. K.;Foubelo, F.;Yus, M. Tetrahedron Lett.
1998, 39, 3581;(d) Gonzalez, A. G.;Silva, M. H.;Padron,
J. I.;Leon, F.;Reyes, E.;Alvarez-Mon, M.;Pivel, J. P.;
Quintana, J.;Estevez, F.;Bermejo, J. J. Med. Chem. 2002,
45, 2358;(e) Ramachandran, P. V.;Rudd, M. T.;
Burghardt, T. E.;Reddy, M. V. R. J. Org. Chem. 2003,
68, 9310.
4. Mali, R. S.;Babu, K. N. Helv. Chim. Acta 2002, 85, 3525.
5. For the biological activities of dihydronaphthalene deriv-
atives, see: (a) Shiraishi, M.;Aramaki, Y.;Seto, M.;
Imoto, H.;Nishikawa, Y.;Kanzaki, N.;Okamoto, M.;
Sawada, H.;Nishimura, O.;Baba, M.;Fujino, M. J. Med.
Chem. 2000, 43, 2049;(b) Datta, P. K.;Yau, C.;Hooper,
T. S.;Yvon, B. L.;Charlton, J. L. J. Org. Chem. 2001, 66,
8606;(c) Reynolds, A. J.;Scott, A. J.;Turner, C. I.;
Sherburn, M. S. J. Am. Chem. Soc. 2003, 125, 12108;(d)
Cordi, A. A.;Berque-Bestel, I.;Persigand, T.;Lacoste,
J.-M.;Newman-Tancredi, A.;Audinot, V.;Millan, M. J.
J. Med. Chem. 2001, 44, 787.
1.5%
H
H
O
O
H
H
H3C
H
2.2%
4c
Figure 1.
in variable ratios (Scheme 3).14 During the synthesis of
6a–e we did not observe nor isolate the corresponding
six-membered lactones.
By using 3a as a model compound we prepared three dif-
ferent compounds, 4a, 5a, 6a in good to moderate yields
by slightly modifying the reaction conditions. We tried
the reaction conditions with other substrates 3b–e and
the results are summarized in Table 1.
The configuration of the double bond of lactones 4a–e is
thought to be as E by comparison with the chemical
shift data of the previously reported.3,4,7 The NOE
experiment with 4c also confirmed the configuration as
E. Irradiation of the aromatic proton showed 2.2%
NOE increment of the vinyl peak (Fig. 1).
In conclusion, we prepared some interesting three differ-
ent types of compounds from same starting material by
using simple operations. The studies for the application
of this methodology toward some natural products and
biologically active candidates are underway in our labo-
ratory.
6. For the synthesis of dihydronaphthalene derivatives, see:
(a) Asao, N.;Kasahara, T.;Yamamoto, Y. Angew. Chem.,
Int. Ed. 2003, 42, 3504;(b) Hamura, T.;Miyamoto, M.;
Imura, K.;Matsumoto, T.;Suzuki, K. Org. Lett. 2002, 4,
1675;(c) Rayabarapu, D. K.;Chiou, C.-F.;Cheng, C.-H.
Org. Lett. 2002, 4, 1679;(d) Lautens, M.;Hiebert, S.;
Renaud, J.-L. Org. Lett. 2000, 2, 1971;(e) Hamura, T.;
Acknowledgement
This work was supported by Korea Research Founda-
tion Grant (KRF-2002-015-CP0215).
Miyamoto, M.;Matsumoto, T.;Suzuki, K.
Org. Lett.
2002, 4, 229;(f) Nishizawa, M.;Takao, H.;Yadav, V. K.;
Imagawa, H.;Sugihara, T. Org. Lett. 2003, 5, 4563;(g)
Chatani, N.;Inoue, H.;Ikeda, T.;Murai, S. J. Org. Chem.
2000, 65, 4913;(h) Lautens, M.;Hiebert, S. J. Am. Chem.
Soc. 2004, 126, 1437;(i) Lautens, M.;Fagnou, K.;Rovis,
T. J. Am. Chem. Soc. 2000, 122, 5650.
References and notes
1. For the biological activities of a-alkylidene-c-butyrolac-
tone derivatives, see: (a) Rao, Y. S. Chem. Rev. 1976, 76,
625;(b) Hoffmann, H. M. R.;Rabe, J. Angew. Chem., Int.
Ed. Engl. 1985, 24, 94;(c) Grieco, P. A. Synthesis 1975, 67;
(d) Ohfune, Y.;Grieco, P. A.;Wang, C. L. J.;Maetich, G.
J. Am. Chem. Soc. 1978, 100, 5946;(e) Banerji, J.;Das, B.
7. For our recent papers on Baylis–Hillman chemistry, 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.

6952
S. GowriSankar et al. / Tetrahedron Letters 45 (2004) 6949–6953
M.;Kim, J. N. Tetrahedron Lett. 2003, 44, 6737;(c) Kim,
Compound 4c: 70%;mp 96–97 °C; 1H NMR (CDCl3) d
1.48 (s, 6H), 2.39 (s, 3H), 3.02 (d, J = 2.7Hz, 2H), 7.24 (d,
J = 8.1Hz, 2H), 7.37 (d, J = 8.1Hz, 2H), 7.54 (t,
J = 3.0Hz, 1H); 13C NMR (CDCl3) d 21.37, 28.77,
41.30, 81.58, 124.87, 129.54, 129.86, 131.92, 136.61,
140.11, 171.61.
J. N.;Kim, J. M.;Lee, K. Y. Synlett 2003, 9, 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) Chung, Y. M.;Gong, J.
H.;Kim, T. H.;Kim, J. N. Tetrahedron Lett. 2001, 42,
9023;(h) Lee, K. Y.;Kim, J. M.;Kim, J. N. Tetrahedron
2003, 59, 385, and further references cited therein.
Compound 4d: 70%;oil; 1H NMR (CDCl3) d 0.98 (t,
J = 7.5Hz, 3H), 1.44 (s, 3H), 1.76 (q, J = 7.5Hz, 2H), 2.94
(dd, J = 17.4 and 3.0Hz, 1H), 3.07 (dd, J = 17.4 and
3.0Hz, 1H), 7.39–7.51 (m, 5H), 7.56 (t, J = 3.0Hz, 1H);
13C NMR (CDCl3) d 7.97, 26.52, 34.26, 39.17, 84.13,
126.09, 128.83, 129.66, 129.88, 134.75, 136.39, 171.62.
Compound 4e: 75%;oil; 1H NMR (CDCl3) d 0.98 (t,
J = 7.5Hz, 3H), 1.45 (s, 3H), 1.76 (q, J = 7.5Hz, 2H), 2.91
(dd, J = 17.4 and 3.0Hz, 1H), 3.03 (dd, J = 17.4 and
3.0Hz, 1H), 7.41 (s, 4H), 7.50 (t, J = 3.0Hz, 1H); 13C
NMR (CDCl3) d 7.96, 26.53, 34.26, 39.09, 84.22, 126.71,
129.11, 131.01, 133.20, 134.97, 135.64, 171.32.
8. Typical synthesis of methyl 2-isobutenylcinnamate 3a: To
a stirred solution of the Baylis–Hillman acetate 1a
(468mg, 2mmol) in dry THF (5mL) was added dropwise
a solution of isopropenylmagnesium bromide (2a, 0.5M
solution in THF, 5.2mL) at ꢀ10°C and stirred at room
temperature for 6h. After the normal aqueous workup
and column chromatographic purification process (hex-
ane/ether, 20:1), desired 3a was isolated in 75% (324mg).
Other starting materials were prepared similarly and their
spectroscopic data are as follows. Compound 3a: 75%; 1H
NMR (CDCl3) d 1.84 (s, 3H), 3.19 (s, 2H), 3.80 (s, 3H),
4.66–4.70 (m, 1H), 4.85 (quintet, J = 1.5Hz, 1H), 7.31–
7.40 (m, 5H), 7.84 (s, 1H); 13C NMR (CDCl3) d 23.76,
35.53, 52.27, 110.46, 128.65, 128.86, 129.40, 130.52,
135.63, 140.86, 143.63, 168.98.
11. The reaction of 3a in acetonitrile in the presence of H2SO4
afforded the lactone 4a in lower yield than in benzene. The
use of LiClO4 instead of H2SO4 did not produce any
lactone product.
12. Typical synthesis of 4,4-dimethyl-3,4-dihydronaphthalene-
2-carboxylic acid (5a): To a stirred solution of 3a (216mg,
1mmol) in benzene (3mL) was added H2SO4 (295mg,
3mmol) and stirred at 60–70°C for 24h. After the normal
aqueous workup and column chromatographic purifica-
tion process (hexane/ether, 5:1), desired 5a was isolated in
72% (146mg). Other dihydronaphthalene derivatives were
prepared similarly and their spectroscopic data are as
follows.
Compound 3b: 70%; 1H NMR (CDCl3) d 1.84 (d,
J = 0.3Hz, 3H), 3.15 (s, 2H), 3.81 (s, 3H), 4.65–4.66 (m,
1H), 4.85 (quintet, J = 1.5Hz, 1H), 7.29–7.36 (m, 4H),
7.77 (s, 1H); 13C NMR (CDCl3) d 23.72, 35.50, 52.35,
110.61, 128.90, 130.36, 130.67, 131.09, 134.03, 139.52,
143.37, 168.69.
Compound 3c: 73%; 1H NMR (CDCl3) d 1.84 (d,
J = 0.6Hz, 3H), 2.36 (s, 3H), 3.19 (s, 2H), 3.80 (s, 3H),
4.67–4.68 (m, 1H), 4.84 (quintet, J = 1.5Hz, 1H), 7.18 (d,
1
Compound 5a: 72%;mp 104–105 °C; H NMR (CDCl3) d
1.30 (s, 6H), 2.54 (d, J = 1.2Hz, 2H), 7.19–7.39 (m, 4H),
7.67 (s, 1H); 13C NMR (CDCl3) d 28.37, 34.04, 36.90,
124.01, 126.45, 127.05, 129.48, 130.65, 131.09, 138.52,
146.13, 173.23.
J = 8.1Hz, 2H), 7.29 (d, J = 8.1 Hz, 2H), 7.81 (s, 1H); 13
C
NMR (CDCl3) d 21.48, 23.71, 35.56, 52.18, 110.35, 129.37,
129.49, 129.55, 132.74, 139.02, 140.92, 143.53, 169.08.
Compound 3d: 81%; 1H NMR (CDCl3) d 1.59 (s, 3H),
1.60 (d, J = 7.0Hz, 3H), 3.35 (s, 2H), 3.80 (s, 3H), 5.32 (q,
J = 7.0Hz, 1H), 7.27–7.56 (m, 5H), 7.76 (s, 1H); 13C NMR
(CDCl3) d 13.49, 22.75, 29.41, 52.17, 120.75, 128.51,
128.58, 129.53, 131.61, 133.49, 135.94, 140.43, 169.30. In
1
Compound 5b: 70%;mp 207–208 °C; H NMR (CDCl3) d
1.28 (s, 6H), 2.52 (d, J = 1.2Hz, 2H), 7.19–7.20 (m, 2H),
7.33 (s, 1H), 7.61 (s, 1H); 13C NMR (CDCl3) d 28.20,
29.69, 34.35, 36.64, 124.70, 126.63, 127.26, 129.61, 130.52,
136.29, 137.22, 147.95, 172.18.
1
1
the H NMR spectrum of 3d, the other minor diastereo-
Compound 5c: 60%;mp 196–198 °C; H NMR (CDCl3) d
isomer appeared in about 15% intensity.
1.28 (s, 6H), 2.38 (s, 3H), 2.52 (s, 2H), 7.03 (d, J = 7.5Hz,
2H), 7.17 (s, 1H), 7.66 (s, 1H); 13C NMR (CDCl3) d 21.88,
28.38, 34.03, 36.97, 124.89, 125.89, 127.08, 128.52, 129.52,
138.54, 140.95, 146.14, 173.30.
Compound 3e: 86%; 1H NMR (CDCl3) d 1.60 (d,
J = 6.6Hz, 3H), 1.70 (s, 3H), 3.14 (s, 2H), 3.80 (s, 3H),
5.13 (q, J = 6.6Hz, 1H), 7.27–7.36 (m, 4H), 7.73 (s, 1H);
13C NMR (CDCl3) d 13.48, 17.09, 36.35, 52.14, 118.45,
128.67, 130.56, 131.19, 132.99, 133.97, 134.54, 139.08,
Compound 5d: 57%;oil; 1H NMR (CDCl3) d 0.79 (t,
J = 7.5Hz, 3H), 1.28 (s, 3H), 1.60 (q, J = 7.5Hz, 2H), 2.42
(dd, J = 17.1 and 1.8Hz, 1H), 2.69 (d, J = 17.1Hz, 1H),
7.18–7.37 (m, 4H), 7.64 (s, 1H); 13C NMR (CDCl3) d 8.92,
25.67, 32.40, 34.00, 37.22, 125.10, 126.37, 126.87, 129.54,
130.26, 131.57, 138.54, 144.95, 173.00.
1
168.73. In the H NMR spectrum of 3e, the other minor
diastereoisomer appeared in about 15% intensity.
9. Matsuo, K.;Hasuike, Y. Chem. Pharm. Bull. 1989, 37,
2803.
1
10. Typical synthesis of 3-benzylidene-5,5-dimethyldihydro-
furan-2-one (4a): To a stirred solution of 3a (216mg,
1mmol) in benzene (3mL) was added H2SO4 (295mg,
3mmol) cautiously at 0–10°C and stirred further for 6h at
room temperature. After the normal aqueous workup and
column chromatographic purification process (hexane/
ether, 10:1), desired 4a was isolated in 72% (145mg). Other
lactone derivatives were prepared similarly and their
spectroscopic data are as follows.
Compound 5e: 55%;mp 199–200 °C; H NMR (CDCl3) d
0.80 (t, J = 7.5Hz, 3H), 1.28 (s, 3H), 1.58 (q, J = 7.5Hz,
2H), 2.39 (dd, J = 17.4 and 2.1Hz, 1H), 2.69 (d, J =
17.4Hz, 1H), 7.15–7.26 (m, 3H), 7.59 (s, 1H); 13C NMR
(CDCl3) d 8.86, 25.54, 32.30, 33.66, 37.53, 125.62, 126.55,
127.18, 130.07, 130.56, 136.02, 137.31, 146.87, 172.62.
13. Filler, R.;Mark, L. H.;Piasek, E. J. J. Org. Chem. 1959,
24, 1780.
14. Typical synthesis of 3-benzylidene-5-methyl-5-hydroxy-
methyldihydrofuran-2-one (6a): To a stirred solution of
3a (216mg, 1mmol) in chloroform (5mL) was added m-
CPBA (ca. 75%, 345mg, 1.5mmol) at room temperature
and stirred further for 6h at around 30°C. After the normal
aqueous workup and column chromatographic purifica-
tion process (hexane/ether, 10:1), desired 6a was isolated in
84% (183mg). Other lactone derivatives were prepared
similarly and their spectroscopic data are as follows.
Compound 4a: 72%;oil; 1H NMR (CDCl3) d 1.49 (s, 6H),
3.04 (d, J = 2.7Hz, 2H), 7.37–7.50 (m, 5H), 7.58 (t,
J = 2.7Hz, 1H); 13C NMR (CDCl3) d 28.85, 41.38, 81.73,
126.14, 128.87, 129.71, 129.90, 134.78, 136.69, 171.48.
1
Compound 4b: 76%;mp 104–106 °C; H NMR (CDCl3) d
1.49 (s, 6H), 3.01 (d, J = 3.0Hz, 2H), 7.40 (s, 4H), 7.51 (t,
J = 3.0Hz, 1H); 13C NMR (CDCl3) d 28.76, 41.18, 81.76,
126.69, 129.06, 130.95, 133.12, 135.16, 135.60, 171.10.

S. GowriSankar et al. / Tetrahedron Letters 45 (2004) 6949–6953
6953
Compound 6a: 84%; 1H NMR (CDCl3) d 1.45 (s, 3H), 2.02
(br s, 1H), 2.90 (dd, J = 17.7 and 3.0Hz, 1H), 3.33 (dd,
J = 17.7 and 3.0Hz, 1H), 3.58 (d, J = 12.0Hz, 1H), 3.76 (d,
J = 12.0Hz, 1H), 7.37–7.52 (m, 5H), 7.57 (t, J = 3.0Hz,
1H); 13C NMR (CDCl3) d 23.78, 36.08, 68.32, 83.60,
125.47, 128.89, 129.86, 130.04, 134.63, 136.89, 171.65.
Compound 6b: 81%; 1H NMR (CDCl3) d 1.44 (s, 3H), 2.55
(br s, 1H), 2.84 (dd, J = 17.7 and 3.0Hz, 1H), 3.32 (dd,
J = 17.7 and 3.0Hz, 1H), 3.56 (d, J = 12.3Hz, 1H), 3.78 (d,
J = 12.3Hz, 1H), 7.37–7.44 (m, 4H), 7.48 (t, J = 3.0Hz,
1H); 13C NMR (CDCl3) d 23.76, 35.98, 68.17, 83.80,
126.25, 129.16, 131.14, 133.09, 135.28, 135.83, 171.52.
Compound 6c: 69%; 1H NMR (CDCl3) d 1.42 (s, 3H), 2.38
(s, 3H), 2.85 (dd, J = 17.1 and 3.0Hz, 1H), 3.33 (dd,
J = 17.1 and 3.0Hz, 1H), 3.56 (d, J = 12.3Hz, 1H), 3.60 (br
s, 1H), 3.75 (d, J = 12.3Hz, 1H), 7.21 (d, J = 8.1Hz, 2H),
7.38 (d, J = 8.1Hz, 2H), 7.50 (t, J = 3.0Hz, 1H); 13C NMR
(CDCl3) d 21.39, 23.70, 36.01, 68.06, 83.82, 124.38, 127.47,
129.54, 130.04, 131.82, 133.11, 136.73, 140.23, 172.18.
Compound 6d: 62%; 1H NMR (CDCl3) d 1.26 (d,
J = 6.6Hz, 3H), 1.42 (s, 3H), 2.85 (dd, J = 17.7 and
3.0Hz, 1H), 3.27 (dd, J = 17.7 and 3.0Hz, 1H), 3.40
(br s, 1H), 3.79 (q, J = 6.6Hz, 1H), 7.30–7.51 (m, 5H),
7.53 (t, J = 3.0Hz, 1H); 13C NMR (CDCl3) 16.91,
22.56, 36.70, 72.35, 85.79, 125.41, 128.78, 129.74, 129.95,
134.50, 136.65, 171.68. In the 1H NMR spectrum of 6d, the
other minor diastereoisomer appeared in about 10%
intensity.
Compound 6e: 56%; 1H NMR (CDCl3) d 1.28 (d,
J = 6.6Hz, 3H), 1.44 (s, 3H), 2,83 (dd,J = 17.7 and
3.0Hz, 1H), 3.25 (dd, J = 17.7 and 3.0Hz, 1H), 3.75–3.84
(m, 1H), 7.41 (s, 4H), 7.50 (t, J = 3.0Hz, 1H); 13C NMR
(CDCl3) d 17.11, 22.54, 36.84, 72.59, 85.73, 125.99, 129.21,
131.15, 133.07, 135.41, 135.90, 171.20. In the 1H NMR
spectrum of 6e, the other minor diastereoisomer appeared
in about 20% intensity. We separated the major isomer in
pure state by column chromatography and obtained the
above 13C NMR spectrum.