Facile synthesis of γ-alkenylbutenolides from Baylis-Hillman adducts: Consecutive in-mediated Barbier allylation, PCC oxidation, isomerization, and Zn-mediated Barbier allylation

Article abstract of DOI:10.1016/j.tetlet.2011.09.125

Alkenylbutenolides were synthesized regioselectively in good to moderate yields from Baylis-Hillman adducts via a consecutive indium-mediated Barbier type reaction between Baylis-Hillman bromide and aldehyde, PCC oxidation of the homoallylic alcohol, doub

Full text of DOI:10.1016/j.tetlet.2011.09.125

Tetrahedron Letters 52 (2011) 6545–6549
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Facile synthesis of
c-alkenylbutenolides from Baylis–Hillman adducts:
consecutive in-mediated Barbier allylation, PCC oxidation, isomerization,
and Zn-mediated Barbier allylation
⇑
Jin Woo Lim, Ko Hoon Kim, Bo Ram Park, 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:
Alkenylbutenolides were synthesized regioselectively in good to moderate yields from Baylis–Hillman
adducts via a consecutive indium-mediated Barbier type reaction between Baylis–Hillman bromide
and aldehyde, PCC oxidation of the homoallylic alcohol, double bond isomerization, and zinc-mediated
Barbier type alkenylation protocol.
Received 18 August 2011
Revised 20 September 2011
Accepted 22 September 2011
Available online 5 October 2011
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
c
-Alkenylbutenolides
Baylis–Hillman adducts
Indium
Zinc
Barbier reaction
Butenolides are valuable synthetic intermediates and key struc-
tural sub-units of a variety of natural products.1,2 Due to their wide
range of biological activity there is a continuing need for the devel-
isomerization of 4a with Et3N afforded 5a. With this compound
5a, we examined an allylation in the presence of indium powder
(1.2 equiv) and allyl bromide (2.5 equiv) in refluxing THF (20 h);
however, the desired product 7a was formed in low yield (<10%).
When we increased the amounts of indium (3.0 equiv), the yield
of 7a increased slightly (31%). Moreover, indium metal is highly
expensive, thus we examined a zinc-mediated allylation. To our
delight, zinc-mediated allylation of 5a in the presence of zinc dust
(5.0 equiv) and allyl bromide (2.5 equiv) in refluxing THF (5 h) pro-
duced 7a in a reasonable yield (70%).2f
Encouraged by the results, we prepared the starting materials
5a–e from Baylis–Hillman bromides 1a–c via a three-step process,
namely, an indium-mediated Barbier type reaction, PCC oxidation,
and double bond isomerization.4a,b,6,7 The results are summarized
in Table 1. An indium-mediated Barbier reaction of 1 and 2 affor-
ded homoallylic alcohols 3a–e in good yields (81–95%) as syn-form,
as reported previously.4a,b,6 Oxidation of the alcohols 3 with PCC
(1.5 equiv, CH2Cl2, rt, 15 h) gave 4a–e in good to moderate yields
(62–90%).7 Treatment of 4a–e with Et3N (1.0 equiv, DMF, 90 °C,
2 h) afforded starting materials 5a–e in moderate yields (67–
74%).7 Although the corresponding E-isomer was formed in low
yield (8–13%) during the isomerization process, we separated the
major Z-isomer and used in the next step.
opment of simple and versatile methods for their synthesis.
Alkyl- and -alkenylbutenolides have received a special attention
among the numerous butenolides.2 Although numerous synthetic
c-
c
approaches of butenolides have been reported, synthesis of
c-
alkenylbutenolides is somewhat limited.2 Recently Baylis–Hillman
adducts have been used for the synthesis of numerous cyclic and
acyclic compounds including
a-methylene-c-butyrolactones and
butenolides.3–5
Recently, we reported the synthesis of butenolide A from homo-
allylic alcohol 3a, prepared from Baylis–Hillman bromide 1a by an
indium-mediated Barbier reaction, via an acid-catalyzed lactoniza-
tion and a following Pd/C-catalyzed isomerization of double bond,
as shown in Scheme 1.4b DBU-mediated allylation of the buteno-
lide A produced a mixture of
c- and
a
-allyl products, 7a (14%)
-position
and 8a (67%).4b The introduction of an allyl group at the
c
was difficult by simply modifying the reaction conditions such as
base, temperature, and solvent. Thus we turned our attention to
another route for the selective synthesis of
-adduct) 7a, as shown in Scheme 1. Oxidation of homoallylic
alcohol 3a with PCC (pyridinium chlorochromate) afforded the
c-allylbutenolide
(c
corresponding
c-ketoester 4a (vide infra, Table 1). Double bond
With these compounds 5a–e we synthesized c-alkenylbuteno-
lides 7a–g, under zinc-mediated Barbier type allylation conditions,
as summarized in Table 2.7 The reactions of 5a with allyl bromide
(6a), methallyl bromide (6b), and crotyl bromide (6c) afforded
⇑
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.2011.09.125

6546
J. W. Lim et al. / Tetrahedron Letters 52 (2011) 6545–6549
allyl bromide
Zn/THF
Ph
Ph
O
Ph
Ph
OH
COOMe
3a (syn)
O
Ph
1. PCC
2. Et3N
O
PhCHO
In
COOMe
Br
+ no 8a
Ph
COOMe
(this work)
Ph
5a (Z)
7a (γ-adduct, 70%)
B-H bromide 1a
1. p-TsOH
2. Pd/C (cat H2)
O
Ph
O
allyl bromide
DBU/CH3CN
H
O
Ph
O
7a (γ-adduct, 14%)
+
Ph
Ref. 4b
Ph
8a (α-adduct, 67%)
A
Scheme 1.
Table 1
Synthesis of starting materials 5a–e
R2
O
R2
R1
OH
COOMe
R2
R1
O
Et3N
In
PCC
COOMe
Br
R1
COOMe
COOMe
R2-CHO
R1
(2a-c)
1a-c
4a-e
3a-e (syn)
5a-e (Z)
1a: R1 = Ph
2a: R2 = Ph
2b: R2 = 4-ClPh
1c: R1 = -CH=CHPh 2c: R2 = Me
1b: R1 = 2-BrPh
Entry
Substrates
3a (%)
4b (%)
5c (%)
1
2
3
4
5
1a + 2a
1a + 2b
1a + 2c
1b + 2a
1c + 2a
3a (95)
3b (94)
3c (81)
3d (92)
3e (88)
4a (90)
4b (89)
4c (62)
4d (89)
4e (84)
5a (71)
5b (72)
5c (67)
5d (68)
5e (74)
a
b
c
Conditions: 1 (2.0 mmol), 2 (1.1 equiv), aq THF, in (1.1 equiv), rt, 1 h; isolated yield syn isomer.
Conditions: 3 (1.5 mmol), CH2Cl2, PCC (1.5 equiv), rt, 15 h; isolated yield.
Conditions: 4 (1.0 mmol), DMF, Et3N (1.0 equiv), 90 °C, 2 h; isolated yield of Z-isomer.
Table 2
Synthesis of c-alkenylbutenolides 7a–g
R2
R1
O
6a-c
Zn/THF
R2
O
O
COOMe
6a: allyl bromide
6b: methallyl bromide
6c: crotyl bromide
R1
5a-e
7a-g
Entry
1
Substrate 5
6a–c
Product 7a (%)
Ph
Ph
O
COOMe
O
O
O
Ph
O
6a
6b
6c
5a
Ph
7a (70)
Ph
2
5a
5a
O
7b (81)
Ph
3b
O
Ph
Ph
7c (66)c

J. W. Lim et al. / Tetrahedron Letters 52 (2011) 6545–6549
6547
Table 2 (continued)
Entry
Substrate 5
6a–c
Product 7a (%)
Cl
Cl
O
O
O
4
5
6a
6a
COOMe
Ph
7d (69)
Ph
5b
Me
Ph
O
COOMe
O
O
Me
O
5c
Ph
7e (73)
Ph
O
COOMe
Ph
O
6
6a
6a
Br
5d
Br
O
7f (69)
Ph
O
COOMe
Ph
Ph
O
7
5e
7g (51)
Ph
a
Conditions: 5 (0.7 mmol), Zn (5.0 equiv), 6 (2.5 equiv) THF, reflux, 5 h, isolated yield.
Conditions: Reaction time 20 h.
b
c
Conditions: Mixture of syn/anti (ca. 20:1 based on 1H NMR).
Pd/C (cat)
2 balloon
O
H2SO4 (5.0 equiv)
PhH, reflux, 1 h
H
O
O
Ph
O
7a
7b
EtOH, rt, 3 h
Ph
9 (55%)
Ph
12 (100%)
Scheme 2.
Scheme 4.
7a–c in moderate to good yields (66–81%), respectively (entries
1–3). Similarly, -allylbutenolides 7d–g were synthesized in mod-
erate yields (51–73%) from 5b–e and allyl bromide.
Synthesis of various spirobutenolides has received much atten-
tion due to their interesting biological activities.8 Thus we exam-
ined the synthesis of spirobutenolide 9 via an acid-catalyzed
Friedel–Crafts reaction of 7b, as shown in Scheme 2. The phenyl
group at the b-position is conjugated to an electron-withdrawing
lactone moiety and cannot participate in the Friedel–Crafts
of compound 7f was examined. Two types of fused-butenolides 10
and 11 were obtained in a reasonable combined yield, as shown in
Scheme 3.7 The basic skeleton of 10 or 11 is closely related to that
of heritonin, a naturally occurring sesquiterpene lactone.9b,c
As a last synthetic application, a catalytic hydrogenation of 7a
c
(EtOH, Pd/C, under H2 balloon atmosphere) gave
c
-propyl deriva-
-alkylbute-
tive 12 in a quantitative yield.7 The result stated that
c
nolide2d,e,h could also be synthesized by introduction of an alkenyl
moiety and a following catalytic hydrogenation process Scheme 4.
reaction, while the phenyl group at the
c
-position can react with
In summary, we disclosed an efficient synthesis of c-alkenyl-
a
tertiary carbocation intermediate, generated under acidic
butenolides from the bromide of Baylis–Hillman adduct via a con-
secutive indium-mediated Barbier type reaction with aldehyde,
PCC oxidation, double bond isomerization, and zinc-mediated Bar-
bier type alkenylation protocol. In addition, we demonstrated the
conditions, to produce the desired spirobutenolide 9 in moderate
yield (55%).7
Various fused-butenolides have also received much attention
due to their interesting biological activities.9 As another synthetic
application of
synthetic applicability of three c-alkenylbutenolides. Further syn-
c
-allylbutenolide, a palladium-catalyzed cyclization
thetic applications are currently underway.10
H
Ph
O
Ph
O
O
O
Pd(OAc)2 (10 mol%)
PPh3 (20 mol%)
O
O
7f
+
Cs2CO3 (2.0 equiv)
DMF, 120 oC, 4 h
MeO
10 (53%)
11 (12%)
Heritonin
Scheme 3.

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J. W. Lim et al. / Tetrahedron Letters 52 (2011) 6545–6549
12:1), compound 5a was obtained as a white solid, 199 mg (71%). To a stirred
Acknowledgments
mixture of 5a (196 mg, 0.7 mmol) and allyl bromide (6a, 212 mg, 1.75 mmol) in
THF (2.0 mL) was added zinc dust (230 mg, 3.5 mmol), and the reaction
mixture was heated to reflux for 5 h. After dilution with THF, the reaction
mixture was filtered through a Celite pad. After removing the solvent and
column chromatographic purification process (hexanes/ether, 7:1), compound
7a was obtained as a white solid, 142 mg (70%). Other compounds were
synthesized similarly, and the known compounds 3a,4a,b,5m,11 3b,4b 3c,4a 3d,6c
4a,11 5a,4b and 7a4b were identified by comparison their spectroscopic data
with the reported. Selected spectroscopic data of unknown compounds 3e, 4c,
4e, 5e, 7b, 7e, 7f, 7g, 9, 10, 11, and 12 are as follows.
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.
References and notes
Compound 3e: 88%; colorless oil; IR (film) 3482, 3027, 2950, 1716, 1439,
1149 cmÀ1 1H NMR (CDCl3, 300 MHz) d 2.67 (br s, 1H), 3.71 (s, 3H), 3.64–3.77
;
1. For selected leading references on butenolide-containing substances, see: (a)
Carter, N. B.; Nadany, A. E.; Sweeney, J. B. J. Chem. Soc., Perkin Trans. 1 2002,
2324–2342; (b) Takahashi, S.; Maeda, K.; Hirota, S.; Nakata, T. Org. Lett. 1999, 1,
2025–2028; (c) Sorg, A.; Blank, F.; Bruckner, R. Synlett 2005, 1286–1290; (d)
Chia, Y.-C.; Chang, F.-R.; Wu, Y.-C. Tetrahedron Lett. 1999, 40, 7513–7514; (e)
Koseki, K.; Ebata, T.; Kadokura, T.; Kawakami, H.; Ono, M.; Matsushita, H.
Tetrahedron 1993, 49, 5961–5968; (f) Liu, Y.; Song, F.; Guo, S. J. Am. Chem. Soc.
2006, 128, 11332–11333; (g) Boukouvalas, J.; McCann, L. C. Tetrahedron Lett.
2010, 51, 4636–4639; (h) Boukouvalas, J.; Loach, R. P. J.Org. Chem. 2008, 73,
8109–8112.
(m, 1H), 5.00 (d, J = 6.3 Hz, 1H), 5.61 (s, 1H), 6.19 (s, 1H), 6.39–6.51 (m, 2H),
7.19–7.37 (m, 10H); 13C NMR (CDCl3, 75 MHz) d 52.01, 54.00, 75.72, 126.33,
126.63, 126.97, 127.44, 127.53, 127.55, 128.08, 128.48, 133.71, 136.86, 140.32,
141.87, 167.28; ESIMS m/z 309 [M+H]+. Anal. Calcd for C20H20O3: C, 77.90; H,
6.54. Found: C, 77.74; H, 6.62.
Compound 4c: 62%; colorless oil; IR (film) 1719, 1138 cmÀ1 1H NMR (CDCl3,
;
300 MHz) d 2.22 (s, 3H), 3.78 (s, 3H), 4.99 (s, 1H), 5.24 (s, 1H), 6.38 (s, 1H), 7.17–
7.21 (m, 2H), 7.29–7.41 (m, 3H); 13C NMR (CDCl3, 75 MHz) d 29.61, 52.16, 60.44,
127.89, 128.13, 129.07, 129.61, 134.80, 139.55, 167.16, 205.77; ESIMS m/z 219
[M+H]+. Anal. Calcd for C13H14O3: C, 71.54; H, 6.47. Found: C, 71.77; H, 6.29.
Compound 4e: 84%; pale yellow solid, mp 128–130 °C; IR (KBr) 1717, 1684,
2. For some examples of
c-alkyl- and c-alkenylbutenolides, see: (a) Cui, H.-L.;
Huang, J.-R.; Lei, J.; Wang, Z.-F.; Chen, S.; Wu, L.; Chen, Y.-C. Org. Lett. 2010, 12,
720–723; (b) Jiang, Y.-Q.; Shi, Y.-L.; Shi, M. J. Am. Chem. Soc. 2008, 130, 7202–
7203; (c) Cho, C.-W.; Krische, M. J. Angew. Chem., Int. Ed. 2004, 43, 6689–6691;
(d) van Oeveren, A.; Feringa, B. L. J. Org. Chem. 1996, 61, 2920–2921. and further
references cited therein; (e) Ma, S.; Lu, L.; Lu, P. J. Org. Chem. 2005, 70, 1063–
1065; (f) Arlt, A.; Koert, U. Synthesis 2010, 917–922; (g) Wu, Y.; Yao, W.; Pan, L.;
Zhang, Y.; Ma, C. Org. Lett. 2010, 12, 640–643; (h) Rosso, G. B.; Pilli, R. A.
Tetrahedron Lett. 2006, 47, 185–188; (i) Virolleaud, M.-A.; Piva, O. Synlett 2004,
2087–2090; (j) Zhang, J.; Blazecka, P. G.; Berven, H.; Belmont, D. Tetrahedron
Lett. 2003, 44, 5579–5582; For the synthesis of b-alkenylbutenolides, see: (k)
Ma, S.; Yu, Z. J. Org. Chem. 2003, 68, 6149–6152; (l) Jefford, C. W.; Sledeski, A.
W.; Boukouvalas, J. J. Chem. Soc. Chem., Commun. 1988, 364–365.
1447 cmÀ1 1H NMR (CDCl3, 300 MHz) d 3.74 (s, 3H), 5.45 (d, J = 8.7 Hz, 1H), 5.84
;
(s, 1H), 6.34 (dd, J = 15.9 and 8.7 Hz, 1H), 6.47 (s, 1H), 6.56 (d, J = 15.9 Hz, 1H),
7.20–7.58 (m, 8H), 8.02–8.07 (m, 2H); 13C NMR (CDCl3, 75 MHz) d 51.88, 52.23,
124.98, 126.43, 127.94 (2C), 128.55, 128.62, 128.72, 133.13, 134.80, 136.19,
136.40, 138.83, 166.68, 197.99; ESIMS m/z 307 [M+H]+. Anal. Calcd for C20H18O3:
C, 78.41; H, 5.92. Found: C, 78.19; H, 5.87.
Compound 5e: 74%; white solid, mp 126–128 °C; IR (KBr) 1720, 1675, 1262 cmÀ1
;
1H NMR (CDCl3, 300 MHz) d 2.25 (s, 3H), 3.55 (s, 3H), 6.56 (d, J = 16.5 Hz, 1H),
7.21–7.57 (m, 9H), 7.92–7.96 (m, 2H); 13C NMR (CDCl3, 75 MHz) d 13.82, 51.96,
122.77, 125.69, 127.14, 128.53, 128.63, 128.68, 129.12, 133.04, 136.03, 136.63,
138.39, 148.01, 167.27, 197.45; ESIMS m/z 307 [M+H]+. Anal. Calcd for C20H18O3:
C, 78.41; H, 5.92. Found: C, 78.68; H, 6.04.
3. For the general reviews 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) Radha
Krishna, P.; Sachwani, R.; Reddy, P. S. Synlett 2008, 2897–2912; (g) Kim, J. N.;
Lee, K. Y. Curr. Org. Chem. 2002, 6, 627–645; (h) Lee, K. Y.; Gowrisankar, S.; Kim,
J. N. Bull. Korean Chem. Soc. 2005, 26, 1481–1490; (i) Gowrisankar, S.; Lee, H. S.;
Kim, S. H.; Lee, K. Y.; Kim, J. N. Tetrahedron 2009, 65, 8769–8780.
Compound 7b: 81%; colorless oil; IR (film) 1756, 1445, 1334 cmÀ1 1H NMR
;
(CDCl3, 300 MHz) d 1.72 (s, 3H), 1.90 (s, 3H), 2.82 (d, J = 14.4 Hz, 1H), 3.12 (d,
J = 14.4 Hz, 1H), 4.60 (s, 1H), 4.84 (s, 1H), 6.82–6.85 (m, 2H), 7.21–7.36 (m, 8H);
13C NMR (CDCl3, 75 MHz) d 9.68, 24.19, 43.29, 89.99, 116.56, 124.66, 125.96,
128.25 (2C), 128.32, 129.05, 131.62, 137.54, 139.21, 163.79, 173.86. (one carbon
is overlapped); ESIMS m/z 305 [M+H]+. Anal. Calcd for C21H20O2: C, 82.86; H, 6.62.
Found: C, 82.53; H, 6.76.
Compound 7e:73%;colorless oil; IR (film)1757 cmÀ1 1HNMR (CDCl3, 300 MHz) d
;
1.54 (s, 3H), 1.82 (s, 3H), 2.43 (ddt, J = 14.4, 6.9 and 1.2 Hz 1H), 2.59 (ddt, J = 14.4,
7.2 and 1.2 Hz, 1H), 5.04–5.15 (m, 2H), 5.61–5.76 (m, 1H), 7.21–7.26 (m, 2H),
7.40–7.50 (m, 3H); 13C NMR (CDCl3, 75 MHz) d 9.47, 23.85, 41.85, 87.82, 119.75,
125.66, 127.65, 128.83, 129.10, 131.10, 132.15, 163.98, 173.25; ESIMS m/z 229
[M+H]+. Anal. Calcd for C15H16O2: C, 78.92; H, 7.06. Found: C, 78.59; H, 7.31.
4. For our recent contributions on the synthesis of a-methylene-c-butyrolactones
and butenolides from Baylis–Hillman adducts, see: (a) Park, B. R.; Kim, K. H.;
Kim, J. N. Tetrahedron Lett. 2010, 51, 6568–6571; (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;
(c) Park, B. R.; Kim, S. H.; Kim, Y. M.; Kim, J. N. Tetrahedron Lett. 2011, 52, 1700–
1704; (d) Kim, S. H.; Kim, S. H.; Lee, K. Y.; Kim, J. N. Tetrahedron Lett. 2009, 50,
5744–5747; (e) Lee, C. G.; Lee, K. Y.; Kim, S. J.; Kim, J. N. Bull. Korean Chem. Soc.
2007, 28, 719–720; (f) Lee, K. Y.; Lee, H. S.; Kim, J. N. Tetrahedron Lett. 2007, 48,
2007–2011; (g) Gowrisankar, S.; Kim, S. J.; Kim, J. N. Tetrahedron Lett. 2007, 48,
289–292; (h) Lee, K. Y.; Park, D. Y.; Kim, J. N. Bull. Korean Chem. Soc. 2006, 27,
1489–1492; (i) Gowrisankar, S.; Lee, C. G.; Kim, J. N. Tetrahedron Lett. 2004, 45,
6949–6953.
Compound 7f:69%; colorless oil; IR (film) 1762, 1433, 1334 cmÀ1 1H NMR (CDCl3,
;
300 MHz) d 1.72 (s, 1.5H), 1.76 (s, 1.5H), 2.88–3.14 (m, 2H), 5.04–5.30 (m, 2H),
5.69–5.84 (m, 1H), 6.98–7.50 (m, 8H), 7.53 (d, J = 7.8 Hz, 0.5H), 7.68 (d, J = 7.8 Hz,
0.5H); 13C NMR (CDCl3, 75 MHz) d 9.73, 9.89, 40.76, 41.57, 90.28, 90.87, 119.48,
120.21, 122.50, 124.23, 124.72, 126.52, 126.61, 127.13, 127.23, 127.79, 128.33,
128.41, 130.36, 130.41, 130.90, 131.68, 131.90, 132.43, 133.06, 133.29, 135.67,
137.64, 161.63, 163.27, 173.04, 173.47. (four carbons are overlapped); ESIMS m/z
369 [M+H]+, 371 [M+H+2]+. Anal. Calcd for C20H17BrO2: C, 65.05; H, 4.64. Found:
C, 65.34; H, 4.76. It is interesting to note that compound 7f exists as an
atropisomeric mixture (ca. 1:1) around the C–C single bond between 2-
bromophenyl and butenolide moieties. The methyl peaks (d = 1.72 and
1.76 ppm) of 7f in 1H NMR spectrum coalesced a little when we took the
spectrum in DMSO-d6 at 50–60 °C; however, the rotation was not free even at the
temperature.
5. For the contributions of other groups on the synthesis of
a-methylene-c-
butyrolactones and butenolides from Baylis–Hillman adducts, see: (a) Patil, S.
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2327–2339; (i) Choudhury, P. K.; Foubelo, F.; Yus, M. Tetrahedron Lett. 1998, 39,
3581–3584; (j) Franck, X.; Figadere, B. Tetrahedron Lett. 2002, 43, 1449–1451;
(k) Lee, A. S.-Y.; Chang, Y.-T.; Wang, S.-H.; Chu, S.-F. Tetrahedron Lett. 2002, 43,
8489–8492; (l) Kabalka, G. W.; Venkataiah, B. Tetrahedron Lett. 2005, 46, 7325–
7328; (m) Kabalka, G. W.; Venkataiah, B.; Chen, C. Tetrahedron Lett. 2006, 47,
4187–4189.
Compound 7g: 51%; pale yellow oil; IR (film) 1737, 1684, 1457 cmÀ1 1H NMR
;
(CDCl3, 300 MHz) d2.12 (s, 3H), 3.03(dd, J = 14.4and 7.2 Hz, 1H), 3.31(dd, J = 14.4
and 6.9 Hz, 1H), 5.08–5.19 (m, 2H), 5.52–5.67 (m, 1H), 6.68 (d, J = 16.5 Hz, 1H),
6.82 (d, J = 16.5 Hz, 1H), 7.28–7.43 (m, 10H); 13C NMR (CDCl3, 75 MHz) d 9.52,
39.89, 88.48, 117.55, 120.14, 124.98, 126.03, 127.03, 128.72 (2C), 128.80, 129.39,
130.24, 135.64, 138.19, 138.40, 157.47, 173.63; ESIMS m/z 317 [M+H]+. Anal.
Calcd for C22H20O2: C, 83.51; H, 6.37. Found: C, 83.26; H, 6.35.
Compound 9: 55%;pale yellowoil; IR (film)1752 cmÀ1;1HNMR (CDCl3, 300 MHz)
d 1.19 (s, 3H), 1.41 (s, 3H), 2.12 (s, 3H), 2.20 (d, J = 14.1 Hz, 1H), 2.29 (d, J = 14.1 Hz,
1H), 6.98–7.01 (m, 2H), 7.14–7.16 (m, 1H), 7.26–7.36 (m, 5H), 7.41–7.46 (m, 1H);
13C NMR (CDCl3, 75 MHz) d 10.50, 28.69, 31.41, 43.22, 50.24, 95.78, 123.11,
123.72, 125.19, 127.74, 128.41, 128.62, 129.33, 130.45, 131.77, 138.28, 154.02,
159.87, 173.62; ESIMS m/z 305 [M+H]+. Anal. Calcd for C21H20O2: C, 82.86; H,
6.62. Found: C, 82.73; H, 6.39.
6. For the synthesis of syn-homoallylic alcohols and their synthetic applications,
see: (a) Kim, K. H.; Kim, S. H.; Park, S.; Kim, J. N. Tetrahedron 2011, 67, 3328–
3336; (b) Kim, K. H.; Lee, H. S.; Kim, S. H.; Kim, S. H.; Kim, J. N. Chem. Eur. J.
2010, 16, 2375–2380; (c) Kim, K. H.; Kim, S. H.; Park, B. R.; Kim, J. N. Tetrahedron
Lett. 2010, 51, 3368–3371.
7. Typical procedure for the synthesis of 4a, 5a, and 7a: To a stirred solution of
homoallylic alcohol 3a (423 mg, 1.5 mmol) in CH2Cl2 (4.0 mL) was added PCC
(485 mg, 2.25 mmol) at room temperature and stirred for 15 h. After dilution
with CH2Cl2, the reaction mixture was filtered through a Celite pad. After the
aqueous extractive workup and column chromatographic purification process
(hexanes/EtOAc, 9:1), compound 4a was obtained as a white solid, 378 mg
(90%). A stirred mixture of 4a (280 mg, 1.0 mmol) and Et3N (101 mg, 1.0 mmol)
in DMF (2.0 mL) was heated to 90 °C for 2 h. After the aqueous extractive
workup and column chromatographic purification process (hexanes/ether,
Compound 10: 53%; pale yellow solid, mp 158–160 °C; IR (KBr) 1751, 1656 cmÀ1
;
1H NMR (CDCl3, 300 MHz) d 2.23 (s, 3H), 3.01 (dt, J = 13.8 and 2.4 Hz, 1H), 3.65 (d,
J = 13.8 Hz, 1H), 5.15 (d, J = 2.4 Hz, 1H), 5.66 (d, J = 2.4 Hz, 1H), 7.18–7.29 (m, 5H),
7.37–7.47 (m, 2H), 7.69–7.74 (m, 2H); 13C NMR (CDCl3, 75 MHz) d 10.35, 45.50,
85.54, 114.61, 121.86, 125.03, 126.01, 127.85, 128.63, 128.80, 129.07, 129.13,
130.68, 135.26, 137.91, 137.99, 158.21, 173.96; ESIMS m/z 289 [M+H]+. Anal.
Calcd for C20H16O2: C, 83.31; H, 5.59. Found: C, 83.19; H, 5.82.
Compound 11: 12%; pale yellow oil; IR (film) 1753 cmÀ1 1H NMR (CDCl3,
;
300 MHz) d 2.08 (s, 3H), 2.17 (s, 3H), 6.35 (s, 1H), 7.20–7.46 (m, 9H); 13C NMR

J. W. Lim et al. / Tetrahedron Letters 52 (2011) 6545–6549
6549
(CDCl3, 75 MHz) d 9.34, 19.48, 88.07, 121.34, 124.99, 125.17, 126.86, 128.13,
128.28, 128.33, 128.43, 128.53, 130.60, 134.45, 134.93, 138.67, 160.58, 174.21;
ESIMS m/z 289 [M+H]+. Anal. Calcd for C20H16O2: C, 83.31; H, 5.59. Found: C,
83.05; H, 5.64.
9. For the synthesis and biological activity of fused-butenolides, see: (a) Miles, D.
H.; Lho, D. S.; de la Cruz, A. A.; Gomez, E. D.; Weeks, J. A.; Atwood, J. L. J. Org.
Chem. 1987, 52, 2930–2932; (b) Silveira, C. C.; Machado, A.; Braga, A. L.;
Lenardao, E. J. Tetrahedron Lett. 2004, 45, 4077–4080; (c) Chavan, S. P.; Govande,
C. A. Green Chem. 2002, 4, 194–195; (d) Chavan, S. P.; Subba Rao, Y. T.; Govande,
C. A.; Zubaidha, P. K.; Dhondge, V. D. Tetrahedron Lett. 1997, 38, 7633–7634; (e)
Chavan, S. P.; Thakkar, M.; Kalkote, U. R. Tetrahedron Lett. 2007, 48, 643–646; (f)
Demir, A. S.; Gercek, Z.; Duygu, N.; Igdir, A. C.; Reis, O. Can. J. Chem. 1999, 77,
1336–1339; (g) Bagal, S. K.; Adlington, R. M.; Brown, R. A. B.; Baldwin, J. E.
Tetrahedron Lett. 2005, 46, 4633–4637; (h) Keltjens, R.; Vadivel, S. K.; Gelder, R.
D.; Klunder, A. J. H.; Zwaneburg, B. Eur. J. Org. Chem. 2003, 1749–1758.
10. Ring-closing metathesis (RCM) reaction of 7g was examined with second-
generation Grubbs catalyst. However, a dimerization product was formed as a
1:1 mixture of cis and trans. Unfortunately we did not obtain any trace amount
of RCM product even though the reaction was carried out under highly diluted
conditions. The reason is not clear at this stage.
Compound 12: 100%; white solid, mp 112–114 °C; IR (KBr) 1757, 1262 cmÀ1 1H
;
NMR (CDCl3, 300 MHz) d 0.92 (t, J = 7.5 Hz, 3H), 1.32–1.44 (m, 2H), 1.88 (s, 3H),
1.99–2.10 (m, 1H), 2.24–2.35 (m, 1H), 6.79–6.84 (m, 2H), 7.17–7.23 (m, 2H),
7.28–7.39 (m, 6H); 13C NMR (CDCl3, 75 MHz) d 9.57, 13.97, 16.50, 37.80, 90.74,
124.40, 125.79, 127.89, 128.17, 128.38, 128.46, 129.05, 131.75, 137.88, 164.10,
174.20; ESIMS m/z 293 [M+H]+. Anal. Calcd for C20H20O2: C, 82.16; H, 6.89. Found:
C, 82.01; H, 7.08.
8. For the synthesis and biological activity of spirobutenolides, see: (a) Patel, R.
M.; Argade, N. P. Synthesis 2010, 1188–1194; (b) Murakami, T.; Morikawa, Y.;
Hashimoto, M.; Okuno, T.; Harada, Y. Org. Lett. 2004, 6, 157–160; (c) Robertson,
J.; Dallimore, J. W. P. Org. Lett. 2005, 7, 5007–5010; (d) Robertson, J.; Meo, P.;
Dallimore, J. W. P.; Doyle, B. M.; Hoarau, C. Org. Lett. 2004, 6, 3861–3863; (e)
Shanmugam, P.; Viswambharan, B. Synlett 2008, 2763–2768; (f) Shanmugam,
P.; Vaithiyanathan, V. Tetrahedron 2008, 64, 3322–3330.
11. Kim, J. M.; Lee, S.; Kim, S. H.; Lee, H. S.; Kim, J. N. Bull. Korean Chem. Soc. 2008,
29, 2215–2220.