Synthesis of (+)-Cladospolide C

Article abstract of DOI:10.1021/jo061767y

(+)-Cladospolide C was synthesized in eight steps with 5% total yield, using methyl acrylate, (3R,4R)-1,5-hexadiene-3,4-diol, and (6R)-6-hepten-2-ol as the starting materials. Two cross-metathesis reactions and Yamaguchi esterification were applied to assemble the three units into (+)-Cladospolide C. Unsuccessful routes using ring-closing metathesis are also discussed.

Full text of DOI:10.1021/jo061767y

the synthesis of Cladospolide C are limited. Banwell’s group
modified their synthesis of Cladospolide B to prepare (-)-
Cladospolide C.9 Although one of their chiral building blocks,
cis-(1S,2S)-1,2-dihydro-3-chlorocatechol, was economically pre-
pared from the enzymatic oxidation of chlorobenzene, the
required (1R,2R)-counterpart for synthesizing the naturally
occurring (+)-1 is difficult to prepare in this way. Very recently,
Sharma’s group also reported their synthesis of Cladospolide
C from 4-pentyn-1-ol utilizing asymmetric aldol and epoxidation
reactions to form the stereocenters.10 However, their assignment
on the absolute configuration of natural Cladospolide C is
opposite to previous work.1,9,10
Synthesis of (+)-Cladospolide C
Chun-Yi Chou and Duen-Ren Hou*
Department of Chemistry, National Central UniVersity, Jung-Li
City, Taoyuan, Taiwan 320
drhou@cc.ncu.edu.tw
ReceiVed August 28, 2006
(+)-Cladospolide C was synthesized in eight steps with 5%
total yield, using methyl acrylate, (3R,4R)-1,5-hexadiene-
3,4-diol, and (6R)-6-hepten-2-ol as the starting materials.
Two cross-metathesis reactions and Yamaguchi esterification
were applied to assemble the three units into (+)-Clado-
spolide C. Unsuccessful routes using ring-closing metathesis
are also discussed.
Herein, we report the total synthesis of (+)-Cladospolide C
(1) using methyl acrylate, (3R,4R)-1,5-hexadiene-3,4-diol (5),
and (6R)-6-hepten-2-ol (6) as the starting materials. Olefin
metathesis and the Yamaguchi esterification process were
applied to assemble the three parts into 1 (Scheme 1).
Cladospolide C (1) is a 12-membered macrolide isolated from
the metabolites of the soil fungus Cladosporium tenuissimum.1
Its diastereomers, Cladospolide A (2) and Cladospolide B (3),
are prevalent in the metabolites of various Cladosporium species
of fungi, and these macrolides 1-3 are plant growth regulators.2-5
They all showed inhibitory effects to shoot elongation of rice
seedlings.1 Interestingly, Cladospolide A promotes root growth
of lettuce seedlings, but Cladospolide B has opposite effects.5b,c
Cladospolide D (4), a 4-oxo lactone, also shows antimicrobial
activity against Mucor racemosus and Pyricularia oryzae, but
its stereochemistry has not been determined.6 Cladospolides A
and B have attracted synthetic chemists’ attention, and their total
syntheses have been reported.7,8 On the other hand, reports of
We first attempted to form the macrolactone by ring-closing
metathesis (RCM, Scheme 2). The C2-symmetric (3R,4R)-1,5-
hexadiene-3,4-diol (5) was prepared from D-mannitol according
to Burke’s procedure and protected as the ketal 7.11 Cross-
metathesis of 7 with commercially available 5-hexenol catalyzed
by second-generation Grubbs catalyst 8 gave the alcohol 9. On
the basis of 1H NMR analysis, E-olefin 9 was dominant (>90%).
Acrylation of 9 with acryloyl chloride provided triene 10.
Unfortunately, ring-closing metathesis of triene 10 failed.
Various substrate concentrations (0.001-0.005 M) in refluxing
CH2Cl2 or ClCH2CH2Cl were examined; however, only uni-
dentified mixtures were produced. Although it is reasonable to
propose that RCM between the two terminal olefins is practical,
the electron-deficient acrylate unit and the required rigid
alignment for RCM may account for this disappointing result.
We rearranged our synthesis to circumvent the RCM involv-
ing the acrylate unit (Scheme 3). Thus, cross-metathesis (CM)
between diene 7 and excess methyl acrylate (10 equiv) was
* Corresponding author. Phone: 88-63-422-7151 ext. 65981. Fax: 88-63-
422-7664.
(1) Fujii, Y.; Fukuda, A.; Hamasaki, T.; Ichimoto, I.; Nakajima, H.
Phytochemistry 1995, 40, 1443.
(2) Dai, H.-Q.; Kang, Q.-J.; Li, G.-H.; Shen, Y.-M. HelV. Chim. Acta
2006, 89, 527.
(3) Jadulco, R.; Proksch, P.; Wray, V.; Sudarsono, Berg, A.; Graefe, U.
J. Nat. Prod. 2001, 64, 527.
(4) Smith, C. J.; Abbanat, D.; Bernan, V. S.; Maiese, W. M.; Greenstein,
M.; Jompa, J.; Tahir, A.; Ireland, C. M. J. Nat. Prod. 2000, 63, 142.
(5) (a) Hirota, H.; Hirota, A.; Sakai, H.; Isogai, A.; Takahashi, T. Bull.
Chem. Soc. Jpn. 1985, 58, 2147. (b) Hirota, A.; Sakai, H.; Isogai, A. Agric.
Biol. Chem. 1985, 49, 731. (c) Hirota, A.; Isogai, A.; Sakai, H. Agric. Biol.
Chem. 1981, 45, 799.
(6) Zhang, H.; Tomoda, H.; Tabata, N.; Miura, H.; Namikoshi, M.;
Yamaguchi, Y.; Masuma, R.; Omura, S. J. Antibiot. 2001, 54, 635.
(7) Synthesis of Cladospolide A: (a) Banwell, M. G.; Loong, D. T. J.
Org. Biomol. Chem. 2004, 2, 2050. (b) Banwell, M. G.; Jolliffe, K. A.;
Loong, D. T. J.; McRae, K. J.; Vounatsos, F. J. Chem. Soc., Perkin Trans.
1 2002, 22. (c) Solladie, G.; Almario, A. Tetrahedron: Asymmetry 1995,
6, 559. (d) Solladie, G.; Antonio, A. Pure Appl. Chem. 1994, 66, 2159. (e)
Ichimoto, I.; Sato, M.; Kirihata, M.; Ueda, H. Chem. Express 1987, 2, 495.
(f) Maemoto, S.; Mori, K. Chem. Lett. 1987, 109. (g) Mori, K.; Maemoto,
S. Liebigs Ann. Chem. 1987, 863.
(8) Synthesis of Cladospolide B: (a) Pandey, S. K.; Kumar, P.
Tetrahedron Lett. 2005, 46, 6625. (b) Austin, K. A. B.; Banwell, M. G.;
Loong, D. T. J.; Rae, A. D.; Willis, A. C. Org. Biomol. Chem. 2005, 3,
1081.
(9) Banwell, M. G.; Loong, D. T. J.; Willis, A. C. Aust. J. Chem. 2005,
58, 511.
(10) Sharma, G. V. M.; Reddy, K. L.; Reddy, J. J. Tetrahedron Lett.
2006, 47, 6537.
(11) (a) Burke, S. D.; Voight, E. A. Org. Lett. 2001, 3, 237. (b) Burke,
S. D.; Sametz, G. M. Org. Lett. 1999, 1, 71. (c) Kang, S. H.; Ryu, D. H.
Chem. Commun. 1996, 355.
(12) Chatterjee, A. K.; Choi, T. L.; Sanders, D. P.; Grubbs, R. H. J. Am.
Chem. Soc. 2003, 125, 11360.
10.1021/jo061767y CCC: $33.50 © 2006 American Chemical Society
Published on Web 11/29/2006
J. Org. Chem. 2006, 71, 9887-9890
9887

TABLE 1. Cross-Metathesis between 7 and Methyl Acrylate
SCHEME 1. Retrosynthetic Analysis of Cladospolide C
entry
solvent
T (°C)
time
yielda (%)
1
2
3
CH2Cl2
neat
toluene
toluene
toluene
toluene
40
80
120
120
120
120
16
16
3
3
3
0
16
29
40
44
45
4b
5c
6c
SCHEME 2
16
a Isolated yields. b Phenol (50 mol %) was added. c p-Cresol (50 mol
%) was added.
of using catalysts with bidentate, oxygenated carbenes, such as
the Hoveyda-Grubbs catalyst,14 adding these beneficial addi-
tives could be an inexpensive alternative for cross-metathesis.15
Furthermore, extending the reaction time to 16 h did not increase
the yield of product significantly. Only the E-diastereomer of
1
12 was observed in the H NMR spectrum. The ester 12 was
hydrolyzed to acid 13 and coupled with chiral alcohol 616 to
form triene 14 in good yield. Ring-closing metathesis of 14
provided the cyclized lactone 15 but in dismal yield (11%), even
after numerous trials.17
The failure or low yield of RCM in the previous two routes
hampered further synthetic exploration. On the other hand, the
success of both CM reactions for preparing compounds 12 and
9 prompted us to adopt a new approach with two consecutive
cross-metatheses and then cyclization (Scheme 4). Diene 16 was
efficiently prepared from compounds 12 and 6 in 60% yield.
Because Cladospolide C is an R,â-unsaturated ester, selective
hydrogenation of diene 16 to preserve the conjugated olefin
moiety was desired. After several attempts, we were unable to
effect the desired selective hydrogenation. This is consistent
with the observations by Trost et al. in their efforts to
hydrogenate a related substrate.18 Consequently, diene 16 was
completely reduced to the saturated ester 17, the hydrolysis of
which afforded the acid 18. Cyclization of 18 to lactone 19 was
achieved by Yamaguchi esterification.19
SCHEME 3
The R,â-unsaturated ester 20 was regenerated by selenylation/
deselenylation.20 Here, we found that fresh phenylselenenyl
bromide, prepared in situ from diphenyl diselenide and bromine,
gave a better yield (57%, two steps) than using commercial
phenylselenenyl bromide.21
(+)-Cladospolide C was produced after the acetonide moiety
of 20 was removed under an acidic condition.8a The H and
1
performed first.12 However, this reaction proved to be elusive,
and further adjustments in the reaction conditions were required.
Some selective experimental results are summarized in Table
1. The desired product 12 was not formed when the reaction
was performed in dichloromethane. Using excess methyl acrylate
as the solvent and raising the reaction temperature to 80 °C
gave only a trace of 12 (16%, entry 2). Performing the CM in
refluxing toluene further improved the yield to 29%. Clearly,
higher reaction temperatures were helpful in driving this
metathesis reaction. We were glad to find that the yield can be
further optimized to almost 50% by adding phenol or p-cresol
(50 mol %) as reported by Forman et al. (entries 4-6).13 Instead
13C NMR spectra from our synthetic 1 are consistent with those
(14) Hoveyda, A. H.; Gillingham, D. G.; Van Veldhuizen, J. J.; Kataoka,
O.; Garber, S. B.; Kingsbury, J. S.; Harrity, J. P. A. Org. Biomol. Chem.
2004, 2, 8, and references cited therein.
(15) Michaelis, S.; Blechert, S. Org. Lett. 2005, 7, 5513.
(16) Dixon, D. J.; Ley, S. V.; Tate, E. W. J. Chem. Soc., Perkin Trans.
1 2000, 2385. (R)-Propylene oxide is commercially available and used to
prepare compound 6.
(17) Difficulty in formation of 12-membered rings using RCM has been
observed: (a) Ghosh, A. K.; Gong, G. J. Org. Chem. 2006, 71, 1085. (b)
Helmboldt, H.; Koehler, D.; Hiersemann, M. Org. Lett. 2006, 8, 1573.
(18) Trost, B. M.; Aponick, A. J. Am. Chem. Soc. 2006, 128, 3931.
(19) (a) Inanaga, J.; Hirata, K.; Saeki, H.; Katsuki, T.; Yamaguchi, M.
Bull. Chem. Soc. Jpn. 1979, 52, 1989. (b) Hikota, M.; Tone, H,; Horita,
K.; Yonemitsu, O. J. Org. Chem. 1990, 55, 7.
(13) Forman, G. S.; McConnell, A. E.; Tooze, R. P.; van Rensburg,
W. J.; Meyer, W. H.; Kirk, M. M.; Dwyer, C. L.; Serfontein, D.
Organometallics 2005, 24, 4528.
(20) Reich, H. J.; Renga, J. M.; Reich, I. L. J. Am. Chem. Soc. 1975,
97, 5434.
(21) Zimmerman, H. E.; Fleming, S. A. J. Org. Chem. 1985, 50, 2539.
9888 J. Org. Chem., Vol. 71, No. 26, 2006

SCHEME 4. Approach with Two Consecutive
Cross-Metatheses
2942, 2864, 1726, 1659, 1450, 1345, 1255, 1204, 1157, 1001, 950
cm-1; HRMS (FAB) calcd for [M + H]+ (C11H17O4) 213.1127,
found 213.1122.
(E)-Methyl 3-((4R,5R)-5-((R,E)-6-Hydroxyhept-1-enyl)-2,2-
dimethyl-1,3-dioxolan-4-yl) Acrylate (16). Compound 12 (150 mg,
0.71 mmol), alcohol 6 (121 mg, 1.06 mmol), p-cresol (38 mg, 0.35
mmol), and Grubbs’ catalyst 8 (30 mg, 0.035 mmol) in dichlo-
romethane (2 mL) were refluxed for 16 h under nitrogen. The
solvent was removed under reduced pressure, and the crude product
was purified by column chromatography (SiO2/ethyl acetate/
hexanes, 1:1; Rf 0.50) to give compound 16 (110 mg, 0.37 mmol,
1
60%) as a brown oil. H NMR (CDCl3, 500 MHz) δ 1.15 (d, 3H,
J ) 6.2 Hz), 1.3-1.49 (m, 4H), 1.37 (s, 3H), 1.38 (s, 3H), 1.59
(brs, 1H), 1.89-2.18 (m, 2H), 3.71 (s, 3H), 3.71-3.81 (m, 1H),
4.05 (dd, J ) 8.2 and 8.2 Hz 1H), 4.18 (ddd, J ) 8.2, 5.2, and 1.5
Hz, 1H), 5.42 (dd, J ) 15.4 and 7.9 Hz, 1H), 5.73-5.83 (m, 1H),
6.07 (d, J ) 15.6 Hz, 1H), 6.82 (dd, J ) 15.6 and 5.2 Hz, 1H); 13
C
NMR (CDCl3, 50 MHz) δ 23.5, 24.9, 26.7, 27.1, 32.1, 38.7, 51.7,
67.8, 79.9, 82.0, 109.7, 122.1, 125.4, 137.4, 143.5, 166.4; [R]20
D
+12.9 (c 0.11, CHCl3); IR (neat) 3400, 2976, 2915, 2851, 1724,
1659, 1425, 1360, 1301, 1240, 1150, 981, 895 cm-1; HRMS (FAB)
calcd for [M + H]+ (C16H27O5) 299.1858, found 299.1852.
Methyl 3-((4R,5R)-5-((R)-6-Hydroxyheptyl)-2,2-dimethyl-1,3-
dioxolan-4-yl) Propanoate (17). A suspension of compound 16
(220 mg, 0.073 mmol), Pd/C (5%, 30 mg), and methanol (5 mL)
was placed in a bomb and filled with hydrogen (20 bar) at room
temperature. The pressure was released after 2 h, and the reaction
mixture was filtered with a plug of silica gel and concentrated to
1
give 17 (215 mg, 0.71 mmol, 97%) as a colorless oil. H NMR
reported for natural Cladospolide C and Banwell’s work.1,9 The
specific rotation of our product 1 is +58.2 (c 0.5, MeOH), also
close to the reported value (+59.7, c 0.4, MeOH) for natural
Cladospolide C,1 and has the opposite rotation as compared to
that of Banwell’s enantiomer.9 Therefore, our results support
the original stereochemical assignment for Cladospolide C.
In summary, (+)-Cladospolide C was synthesized in eight
steps with 5% overall yield, starting with mannitol-derived diene
5. An approach involving two CM reactions and ring closure
by Yamaguchi esterification proved to be effective in this case,
in preference to routes using RCM. With Grubbs’ catalyst 8,
unfavorable factors, such as the rigid/strained structure and
product liability, for effecting RCM with compounds 10 and
14 were difficult to overcome; however, the CM successfully
provided an alternative solution for the synthesis of (+)-
Cladospolide C (1).
(CDCl3, 200 MHz) δ 1.13 (d, 3H, J ) 6.2 Hz), 1.25-1.51 (m,
16H), 1.59-1.95 (m, 3H), 2.29-2.59 (m, 2H), 3.47-3.58 (m, 2H),
3.63 (s, 3H), 3.67-3.85 (m, 1H); 13C NMR (CDCl3, 50 MHz) δ
23.4, 25.5, 25.9, 27.2, 27.3, 27.9, 29.6, 30.4, 32.7, 39.2, 51.6, 67.9,
79.8, 80.6, 108.1, 173.7; [R]20 +16.0 (c 0.16, CHCl3); IR (neat)
D
3415, 2933, 2859, 1713, 1377, 1216, 1064, 934 cm-1; HRMS
(FAB) calcd for [M + H]+ (C16H31O5) 303.2171, found 303.2178.
3-((4R,5R)-5-((R)-6-Hydroxyheptyl)-2,2-dimethyl-1,3-dioxolan-
4-yl) Propanoic Acid (18). Aqueous lithium hydroxide (43 mg,
1.04 mmol, in 2.5 mL of water) was added to the solution of ester
17 (210 mg, 0.69 mmol) in THF (2.5 mL). After stirring at room
temperature for 16 h, the reaction mixture was acidified to pH 4
with diluted HCl(aq) (1 N) and extracted with ethyl acetate (20 mL
× 3). The combined organic layer was dried over Na2SO4, filtered,
and concentrated to give the acid 18 (200 mg, 0.69 mmol, 99%) as
a colorless oil. 1H NMR (CDCl3, 200 MHz) δ 1.15 (d, 3H, J ) 6.2
Hz), 1.22-1.55 (m, 16H), 1.63-1.97 (m, 2H), 2.32-2.62 (m, 2H),
3.48-3.67 (m, 2H), 3.67-3.91 (m, 1H), 4.71-4.94 (br, 2H); 13C
NMR (CDCl3, 50 MHz) δ 23.3, 25.4, 25.7, 27.1, 27.3, 27.6, 29.4,
Experimental Procedures
30.4, 32.5, 38.9, 68.2, 79.8, 80.5, 108.2, 177.9; [R]20 +14.9 (c
D
1.0, CHCl3); IR (neat) 3415, 2933, 2859, 1713, 1377, 1241, 1216,
1064, 934 cm-1; HRMS (FAB) calcd for [M + H]+ (C15H29O5)
289.2015, found 289.2017.
Preparation of Compound 12 with Cross Metathesis. A 10
mL round-bottomed flask equipped with a condenser and a stir bar
was flame-dried under vacuum and filled with nitrogen after
cooling. Compound 711 (500 mg, 3.24 mmol), methyl acrylate (2.79
g, 32.4 mmol), p-cresol (170 mg, 1.62 mmol), and toluene (1 mL)
were added to the flask by syringe. Grubbs’ catalyst 8 (13.7 mg,
0.016 mmol) in toluene (1 mL) was also added to the mixture. The
reaction was refluxed for 3 h. After being cooled to room
temperature, the solvent was removed under reduced pressure. The
crude product was purified by column chromatography (SiO2/ethyl
acetate/hexanes, 1:5; Rf 0.50) to give pure compound 12 (309 mg,
1.45 mmol, 45%) as a light-yellow oil. 1H NMR (CDCl3, 200 MHz)
δ 1.43 (s, 3H), 1.45 (s, 3H), 3.73 (s, 3H), 4.11 (dd, J ) 8.3 and 7.1
Hz, 1H), 4.22 (ddd, J ) 8.3, 5.3, and 1.4 Hz, 1H), 5.29 (dd, J )
10.4 and 1 Hz, 1H), 5.38 (dd, J ) 17.3 and 1 Hz, 1H), 5.81 (ddd,
J ) 17.3, 10.4, and 7.1 Hz, 1H), 6.1 (dd, J ) 15.7 and 1.4 Hz,
1H), 6.85 (dd, J ) 15.7 and 5.3 Hz, 1H); 13C NMR (CDCl3, 50
MHz) δ 26.7, 26.9, 51.7, 79.8, 82.1, 110.0, 119.9, 122.3, 133.5,
(+)-Dihydro Cladospolide C Ethylene Acetal 19. 2,4,6-
Trichlorobenzoyl chloride (90 mg, 0.37 mmol) was added to a
solution of compound 18, triethylamine (41 mg, 0.40 mmol), and
THF (3 mL) in an ice/water bath. The reaction was stirred for 1 h
at 0 °C, diluted with toluene (27 mL), and transferred into a solution
of DMAP (205 mg, 0.168 mmol) and toluene (27 mL). The resulting
mixture was refluxed for 1 h and quenched with sat. NaHCO3(aq)
(10 mL) after being cooled to room temperature. The aqueous layer
was separated and extracted with ethyl acetate (10 mL × 3). The
combined organic layer was washed with sat. CuSO4(aq) (10 mL),
water (10 mL), and sat. NaCl(aq) (10 mL); dried over Na2SO4;
filtered; and concentrated. The crude product was further purified
by column chromatography (SiO2/ethyl acetate/hexanes, 1:5; Rf
0.50) to give lactone 19 (45 mg, 0.17 mmol, 55%) as a light-yellow
oil. 1H NMR (CDCl3, 200 MHz) δ 1.19 (d, 3H, J ) 6.4 Hz), 1.27-
1.52 (m, 14H), 1.53-1.74 (m, 2H), 2.47 (t, 2H, J ) 5.9 Hz), 3.61-
143.1, 166.4; [R]20 -11.0 (c 1.7, CHCl3); IR (neat) 3025, 2984,
D
J. Org. Chem, Vol. 71, No. 26, 2006 9889

85 (m, 2H), 4.91-5.16 (m, 1H); 13C NMR (CDCl3, 50 MHz) δ
1462, 1370, 1252, 1051, 857 cm-1; HRMS (FAB) calcd for [M +
H]+ (C15H25O4) 269.1753, found 269.1758.
19.4, 19.9, 20.6, 26.8, 27.1, 27.1 27.6, 28.1, 31.5, 32.3, 70.9, 77.1,
79.2, 107.4, 172.4; [R]20 +4.2 (c 0.9, CHCl3,); IR (neat) 3444,
(+)-Cladospolide C (1)1. Trifluoroacetic acid (0.45 mL) was
added to a solution of lactone 20 (15.8 mg, 0.060 mmol) and
acetonitrile/water (2:1, v/v, 0.9 mL) at 0 °C. The ice/water bath
was removed, and the reaction was stirred at room temperature for
another 1 h, diluted with dichloromethane (40 mL), washed with
sat. NaHCO3(aq) (20 mL), dried over Na2SO4, filtered, and concen-
trated to give compound 1 (11 mg, 0.047 mmol, 82%) as a colorless
solid. Mp 90-91 °C; [R]20D +58.2 (c 0.5, MeOH); IR (neat) 3402,
2933, 2860, 1715, 1646, 1461, 1260, 1036 cm-1; 1H NMR (CDCl3,
500 MHz) δ 1.05-1.79 (m, 10H), 1.28 (d, 3H, J ) 6.3 Hz), 2.35-
2.69 (brs, 2H), 3.49-3.61 (m, 1H), 3.96 (dd, J ) 7.9 and 9.1 Hz,
1H), 4.85-5.06 (m, 1H), 6.03 (d, 1H, J ) 15.8 Hz), 6.79 (dd, J )
9.1 and 15.8 Hz, 1H); 13C NMR (CDCl3, 125 MHz) δ 20.8, 24.0,
24.5, 27.3, 32.1, 33.9, 74.3, 76.5, 77.5, 124.5, 145.3, 166.7.
D
2982, 2933, 2858, 1730, 1456, 1369, 1253, 1065 cm-1; HRMS
(FAB) calcd for [M + H]+ (C15H27O4) 271.1909, found 271.1897.
(+)-Cladospolide C Ethylene Acetal 20. Lithium diisopropyl
amide (LDA), freshly prepared from n-BuLi (1.6 M, 0.35 mL, 0.57
mmol) and disopropyl amine in THF (0.4 mL), was added to a
solution of compound 19 (64 mg, 0.24 mmol) and THF (0.4 mL)
at -78 °C. After stirring at -78 °C for 1 h, the solution of enolate
was added to a solution of phenylselenenyl bromide (40 mg, 0.17
mmol) and THF (0.4 mL) and stirred for another 1 h at -78 °C.
The reaction was quenched with sat. NH4Cl(aq) (4 mL), diluted with
water (2 mL), and extracted with ether (5 mL × 3). The combined
organic layer was washed with water (1 mL), dried over Na2SO4,
filtered, and concentrated to give a yellow crude oil (128 mg).
Dichloromethane (3 mL), pyridine (48 mg, 0.60 mmol), and
hydrogen peroxide (35% in water, 102 mg, 3.0 mmol) were added
to the crude selenenylated compound at 0 °C, stirred, and warmed
up to room temperature in 15 h. The reaction mixture was washed
with water (2 mL), dried over Na2SO4, filtered, and concentrated.
The crude product was further purified by column chromatography
(SiO2/ethyl acetate/hexanes, 1:5; Rf 0.41) to give lactone 20 (36.5
mg, 0.14 mmol, 57%) as a light-yellow oil. 1H NMR (CDCl3, 500
MHz) δ 1.15-1.26 (m, 3H), 1.29 (d, 3H, J ) 6.4 Hz), 1.35-1.49
(m, 8H), 1.52-1.62 (m, 3H), 1.64-1.72 (m, 1H), 1.9-2.01(m, 1H),
3.81-3.93 (m, 1H), 4.02 (dd, J ) 9 Hz, J ) 9 Hz, 1H), 4.95-4.98
(m, 1H), 6.20 (d, 1H, J ) 15.8 Hz), 6.77 (dd, J ) 9.5 and 15.8 Hz,
1H); 13C NMR (CDCl3, 125 MHz) δ 20.6, 24.9, 25.1, 26.8, 27.2,
Acknowledgment. This research was supported by the
National Science Council (NSC 94-2113-M-008-007), Taiwan.
The authors are grateful to Professor John C. Gilbert for helpful
comments. The authors thank Ms. Ping-Yu Lin at the Institute
of Chemistry, Academia Sinica, and the Valuable Instrument
Center in National Central University for obtaining mass
analyses.
Supporting Information Available: Experimental details for
the preparation of compounds 7, 9, 10, and 13-15 and detailed
spectroscopic data of all new compounds 7, 9, 10, 12-20, and 1.
This material is available free of charge via the Internet at
http://pubs.acs.org.
27.8, 29.5, 35.4, 75.4, 80.1, 80.4, 109.3, 125.9, 143.9, 166.6; [R]20
D
+12.0 (c 0.22, CHCl3); IR (neat) 2982, 2934, 2864, 1719, 1648,
JO061767Y
9890 J. Org. Chem., Vol. 71, No. 26, 2006