Synthesis of chiral oxacyclic dienes via ruthenium-catalyzed enyne metathesis: Useful building blocks for chiral tricyclic oxygen derivatives

Article abstract of DOI:10.1016/S0040-4020(02)00548-3

Various chiral oxacyclic dienes were synthesized via enyne metathesis using Grubbs catalyst (PCy₃)₂Cl₂Ru=CHPh. A series of substrates bearing a 1,2-diol skeleton was prepared from (2S)-(benzyloxy)-propanal. The enyne metathesis proceeds smoothly in CH₂Cl₂ at 23°C with a low loading of catalyst (2.0mol%) under ethylene gas (1-2.5atm), giving good yields of products without epimerization at any stereogenic carbon. Heating compound 5 comprising a disubstituted alkyne in benzene (80°C) under nitrogen resulted in formation of two diastereomers via epimerization of the primary product. The epimerization occurs at the oxacyclic carbon rather than the benzyl carbon. Diels-Alder reactions of chiral oxacyclic dienes 19 and 22 with maleic anhydride, maleimide and benzoquinone proceeded with high diastereoselectivities, yielding a single cycloadduct efficiently at ambient conditions. The structures of Diels-Alder adducts were determined by ¹H NOE NMR spectra. The cycloadducts were formed via the approach of dienophiles to the diene in endo mode and opposite the substituent of the stereogenic center. The cycloadducts 29 and 31 were transformed into enantiopure tricyclic furans 35 and 38 after transformation of the (2S)-(silyloxy)ethyl group into an acetate group.

Full text of DOI:10.1016/S0040-4020(02)00548-3

TETRAHEDRON
Pergamon
Tetrahedron 58 +2002) 5627±5637
Synthesis of chiral oxacyclic dienes via ruthenium-catalyzed
enyne metathesis: useful building blocks for chiral tricyclic
oxygen derivatives
Hongyun Guo,a,² Reniguntala J. Madhushaw,a Fwu-Ming Shenb and Rai-Shung Liua,p
aDepartment of Chemistry, National Tsing-Hua University, Hsinchu 30043 Taiwan, ROC
bDepartment of Medical Technology, Yuanpei Institute of Science and Technology, Hsinchu, Taiwan, ROC
Received 3 April 2002; accepted 24 May 2002
AbstractÐVarious chiral oxacyclic dienes were synthesized via enyne metathesis using Grubbs catalyst +PCy3)2Cl2RuvCHPh. A series of
substrates bearing a 1,2-diol skeleton was prepared from +2S)-+benzyloxy)-propanal. The enyne metathesis proceeds smoothly in CH2Cl2 at
238C with a low loading of catalyst +2.0 mol%) under ethylene gas +1±2.5 atm), giving good yields of products without epimerization at any
stereogenic carbon. Heating compound 5 comprising a disubstituted alkyne in benzene +808C) under nitrogen resulted in formation of two
diastereomers via epimerization of the primary product. The epimerization occurs at the oxacyclic carbon rather than the benzyl carbon.
Diels±Alder reactions of chiral oxacyclic dienes 19 and 22 with maleic anhydride, maleimide and benzoquinone proceeded with high
diastereoselectivities, yielding a single cycloadduct ef®ciently at ambient conditions. The structures of Diels±Alder adducts were determined
1
by H NOE NMR spectra. The cycloadducts were formed via the approach of dienophiles to the diene in endo mode and opposite the
substituent of the stereogenic center. The cycloadducts 29 and 31 were transformed into enantiopure tricyclic furans 35 and 38 after
transformation of the +2S)-+silyloxy)ethyl groupinto an acetate group. q 2002 Elsevier Science Ltd. All rights reserved.
1. Introduction
compounds. One major problem with the use of these dienes
is the diversity of synthetic methods that often requires a
long procedure.1±4 Few of them aim toward the enantio-
speci®c synthesis of oxygen heterocyclic compounds via
Diels±Alder reaction.3a,4 A short and general synthesis of
Oxacyclic dienes +A)±+D) are useful building blocks for
complex oxygen heterocycles. Cycloaddition of these
dienes with electron-de®cient ole®ns normally proceeds
with high diastereoselectivities.1±4 This methodology
provides a short entry to framework of naturally occurring
Scheme 1.
Keywords: chiral oxacyclic dienes; enyne metathesis; diastereoselectivity;
tricyclic furan.
Scheme 2. Condition: +i) allylSiMe3, SnCl4; +ii) NaH, 1-bromo-but-2-yne;
+iii) +Pcy3)2Cl2RuvCHPh +2.0 mol%), benzene, N2, 808C, 8 h;
+iv) 2.0 mol% catalyst, CH2Cl2, 238C, 6 h, CH2vCH2 +1.0 atm);
+v) DEAD, PPh3, p-nitrobenzoic acid; +iv) Na2CO3, EtOH.
p
Corresponding author. Tel.: 1886-3-7521424; fax: 1886-3-5711082;
e-mail: rsliu@mx.nthu.edu.tw
Visiting scholar from Zhejiang Normal University, Zhejiang, China.
²
0040±4020/02/$ - see front matter q 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020+02)00548-3

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H. Guo et al. / Tetrahedron 58 ,2002) 5627±5637
Table 1. Synthesis of chiral dienes from enyne metathesis
Entry
1
Enyne
Conditionsa
Diene +yields)b
238C, 6 h
2
3
238C, 6 h
238C, 5 h
4
5
238C, 6 h
238C, 10 ha,c
6
7
238C, 6 hc
408C, 8 hc
8
238C, 40 h
9
238C, 40 h
a
Condition: [enyne]ˆ0.10 M, 2.0 mol% catalyst, 1.0 atm ethylene, CH2Cl2, 238C.
Yields were given after puri®cation from SiO2 column.
Condition: Ethylene, 2.5 atm.
b
c
chiral oxacyclic dienes will be valuable in synthetic organic
chemistry. Metal-catalyzed enyne metathesis seems to be a
convenient and general approach to achieve the synthesis
+Eq. 1).5±8 In this study, we report synthesis of various chiral
oxacyclic dienes via enyne metathesis using Grubbs catalyst
+PCy3)2Cl2RuvCHPh. Scheme 1 shows our strategy for
enantiospeci®c synthesis of complex oxygen heterocycles.
These oxacyclic dienes are designed to bear a +2S)-+alkoxy)-
ethyl groupderived from natural +2 S)-ethyl lactate. The
role of this substituent are twofold in synthetic application:

H. Guo et al. / Tetrahedron 58 ,2002) 5627±5637
5629
Scheme 3. Conditions: +1) RCCLi +1.0 equiv.), THF, 2788C, 4 h; +2) Bu4NF +1.0 equiv.); +3) NAH +1.1 equiv.), allylbromide; +4) DEAD, PPh3, p-nitro-
benzoic acid, Na2CO3; +5) CH2vCHMgBr, THF, 2788C; +6) NaH, RCCCH2Br; +7) propargylzinc bromide, rt.
+1) control of diastereoselective Diels±Alder reaction; and
+2) easy degradation into a common functionality after
cycloadditon reaction.
of 5a and b were 19 and 65%, respectively. This result
indicates that enyne metathesis with Grubbs catalyst at
808C can lead to epimerization of a chiral molecule;
a phenomenon has not been previously observed. The
epimerization can be circumvented by the use of ethylene
gas6a,b,9 +1.0 atm) to effect the metathesis at 238C +0.1 M,
CH2Cl2, 8 h). This condition afforded only diene 5b in 92%
yield. To determine the relative con®guration of 5a, we
prepared compound 7 via Mitsonobu reaction12a of the
alcohol 4, followed by a similar propargylation of the result-
ing alcohol 6. Metathesis of compound 7 +0.1 M) at 238C
gave only compound 5a +88%) of which the NMR spectra
and the [aD value [259.2 +c 2.6, CHCl3)] matched well with
those of the one [258.7 +c 2.6, CHCl3)] given in Eq. +2).
This information suggests that the epimerization occurred at
the pyranyl carbon rather than the benzylic carbon. The
mechanism for this epimerization is unclear at this stage.
Synthesis of oxygenated molecules via enyne metathesis
using Grubbs catalyst might encounter dif®culties according
to literature reports.9 Functional groups such as alcohols,
ether and silyl ethers do not react or perform very poorly
in enyne cross metathesis. Chelation of oxygen atom to
ruthenium carbene catalyst will impede catalytic reactivity.
In contrast with diene metathesis,10 we found that enyne
metathesis with Grubbs catalyst might result in epimeri-
zation of stereogenic carbon of an oxacyclic molecule,
and this problem might be avoided under more mild
condition.
2. Results and discussion
We extended this ruthenium-catalyzed metathesis to the
synthesis of various chiral oxacyclic dienes; the examples
are provided in Table 1. Synthesis of the substrates 8 and 9
follows the same procedures as those of enynes 4 and 7.
Scheme 3 shows the synthetic protocol for the substrates
8±16 that were prepared from propargylation or allylation
of their parent alcohols, E±I. The synthesis of these
alcohol derivatives E,13 G, 14 H,15 I15 are well documented
in literature. The alcohol F used for synthesis of enyne 11
As shown in Scheme 2, +4S,5S)-5-+phenylmethoxy)hex-1-
en-4-ol +3) was prepared according to the procedure in
literature.11 Treatment of compound 3 with NaH and
1-bromo-but-2-yne gave enyne 4 in 82% yield. Metathesis
of compound 4 with Grubbs catalyst was performed in
benzene +0.15 M) at elevated temperatures +808C, 8 h)
under nitrogen to afford two diastereomers 5a and b
which were separable on silica column. The isolated yields

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H. Guo et al. / Tetrahedron 58 ,2002) 5627±5637
under a pressurised ethylene +2.5 atm) at 238C for 10 h.
Similarly, a pressurised ethylene +2.5 atm) is required to
facilitate metathesis of enynes 13 and 14 +entries 6 and 7)
to the corresponding dienes 22 and 23 in good yields. The
highly oxygenated functionalities enynes 15 and 16 did not
inhibit catalytic activity. The reaction is complete over a
prolong period +40 h) to give the pyranyl dienes 24 and 25
in good yields +.88%).
Scheme 4.
was obtained by Mitsonobu reaction12 of its epimer E
+RˆH, Eq. +2)). These substrates comprise a vinyl group
because the Grubbs catalyst do not work for 1,2- or
1,1-disubstituted ole®ns in enyne metathesis.6a,b Similar to
the preceding cases, the enynes 10±16 were treated with
ruthenium catalyst +2.0 mol%) in CH2Cl2 +0.10±0.12 M)
at 238C under ethylene gas +1.0±2.5 atm). The Grubbs
catalyst effected enyne metathesis of the substrate 8 and 9
+entries 1 and 2) tethered with a terminal alkyne, affording
the pyranyl dienes 17 and 18 in 86 and 87% isolated yields,
respectively.
Grubbs catalyst is not applicable to the two enynes 26 and
27 +Scheme 4). For compound 26 bearing a propiolate
group, no product was formed over a long period +40 h)
even under pressurised ethylene gas +2.5 atm). The starting
material 26 was recovered in 86% yield in this case. Enyne
metathesis with Grubbs catalyst with terminal electron-
de®cient alkynes proceeds with dif®culty. Hoye reported7e
that very slow addition +37 h) of Grubbs catalyst +10 mol%)
to the enyne J +0.1 M, CH2Cl2, 238C) afforded the corre-
sponding diene in 30±40% yield.7e The turnover number
was 2 if the catalyst was added in one-pot operation.
Metathesis on alkynyl ether 27 led to the formation of a
mixture of products even at 238C +3 h). The two major
components of products were not separable on silica column
for further characterization.
This approach is also applicable to a synthesis of furyl
dienes 19 and 20 for which the yields were 92 and 86%,
respectively. A similar furyl diene 21 +entry 5) was formed
in 67% yield from the enyne 12 bearing a long alkynyl
chain. The yield of compound 21 was increased to 81%
We examined diastereoselective Diels±Alder reactions of
dienes 19 and 22 with electron-de®cient ole®ns; the results
are shown in Table 2. The yields of cycloadducts are given
after puri®cation either from a preparative silica plate
+entries 1±4) or from crystallization from diethyl ether/
hexane +entry 5). Heating diene 19 with equimolar amount
of maleic anhydride and phenyl maleimide in toluene +908C,
2 h) afforded the cycloadducts 28 and 29 +entries 1 and 2) as
a single diastereomer; the yields were 86 and 93%, respec-
tively. Cycloaddition of compound 22 with maleic
anhydride and phenyl maleimide proceeded with high dia-
stereoselectivities in hot toluene +1108C, 6 h), yielding the
products 30 and 31 in 90 and 96% yields, respectively. With
the use of excess SnCl4 +5.0 equiv.), reaction of the diene 22
with benzoquinone +1.2 equiv.) in CH2Cl2 +238C, 12 h) led
to formation of a single stereoisomer 32 +82%) from which
the silyloxy groupwas removed. The stereochemistry of
Table 2. Asymmetric Diels±Alder reaction with dienophiles
Entry
Oxacyclic dienes
Dienophiles
Cycloadduct +yields)
1
2
3
1
compounds 29, 30 and 32 was determined according to H
NMR NOE spectra +see Section 3).
This information suggests that the dienophiles approached
the diene in endo mode and opposite the chiral +2S)-+silyl-
oxy)ethyl substituent. Scheme 5 shows several examples of
naturally occurring compounds which represent families of
drimane sesquiterpenes.16,17 The cycloadducts from pre-
ceding reactions appear to be useful building blocks if the
2S-+silyloxy)ethyl substituent is to be degraded. Treatment
of cycloadduct 29 with Pd/H2 +1.0 atm) resulted in selective
hydrogenation of the internal double bond, followed by the
removal of the silyloxy group, yielding the alcohol 33 in
83% yield. Oxidation of alcohol 33 with PCC afforded the
ketone 34 of which the structure was con®rmed by X-ray
diffraction study.18 Compound 34 was transformed into the
lactol 35 by m-CPBA oxidation, and the alkoxyalky group
of compound 34 is more prone to migration than an alkyl
4
5
19
groupin Baeyer±Villager oxidation. This transformation
was shown to proceed exclusively via retention of stereo-
chemistry. A similar transformation was performed on the
Conditions: +a) toluene, 908C, 2 h; +b) toluene 1108C, 6 h; +c) SnCl4
+5.0 equiv.) CH2Cl2, 238C.

H. Guo et al. / Tetrahedron 58 ,2002) 5627±5637
5631
Scheme 5.
tricyclic adduct 31 to give compounds 36 and 37 respec-
tively. Oxidation of ketone 37 with m-CPBA gave the
lactol 38 which has an acetate groupon the furanyl
C2-carbon.
ether, tetrahydrofuran and hexane were dried with sodium
benzophenone and distilled before use. Dichloromethane
was dried over CaH2 and distilled before use. +PCy3)2Cl2-
RuvCHPh, +S)-ethyl lactate, allyltrimethylsilane, pro-
pargyl bromide, 1-bromo-but-2-yne, allylbromide, SnCl4,
maleic anhydride, phenyl maleimide, benzoquinone,
ethylene gas and sodium hydride were obtained commer-
cially and used without puri®cation. The chiral alcohol 3,11
E,13 G,14 H15 and I15 was prepared according to the pro-
cedure in literature. Spectral data of compounds 33±35
were reported previously in our preceding paper.4
In summary, Grubbs catalyst in enyne metathesis is
effective in the synthesis of chiral oxacyclic dienes. We
observed that Grubbs catalyst might result in epimerization
of a stereogenic carbon of an oxacyclic molecule at high
reaction temperatures. We demonstrate that the 2-+silyl-
oxy)ethyl groupof oxacyclic dienes 19 and 22 effects
diastereoselective Diels±Alder reactions with electron-
de®cient ole®ns. The cycloadducts 29 and 31 were trans-
formed into enantiopure tricyclic furans 35 and 38 after
transformation of this silyloxy groupinto an acetate
group. This proves that oxacyclic dienes in this study
are useful building block for the framework of naturally
occurring compounds.
3.1.1. Synthesis of 1-{[11S,2S)-1-methyl-2-12-butynyl-
oxy)-4-pentenyl]oxy-methyl}benzene 14). To a THF solu-
tion +20 mL) of chiral alcohol 3 +0.41 g, 2.00 mmol) was
added NaH +48 mg, 2.1 mmol), and the mixtures were
stirred for 4 h at 238C before treatment of 1-bromo-but-2-
yne +0.33 g, 2.0 mmol). The solution was stirred for 8 h, and
quenched with a saturated NH4Cl solution. The solution was
concentrated, extracted with diethyl ether and eluted
through silica column +diethyl ether/hexaneˆ1/1) to give
the enyne 4 as a colorless oil +0.42 g, 1.64 mmol, 82%).
3. Experimental
3.1. General
[aD ˆ24.0 +c 0.55, CHCl3); IR +neat, cm21): 2241 +w),
25
1
1645 +w), 1600 +w); H NMR +400 MHz, CDCl3): d +m,
5H), 5.80±5.86 +m, 1H), 5.05 +d, 1H, Jˆ16.0 Hz), 5.02 +d,
1H, Jˆ11.0 Hz), 4.56 +ABq, Jˆ4.8 Hz, 2H), 4.20 +s, 2H),
3.60±3.66 +m, 1H), 3.48±3.53 +m, 1H), 2.35±2.42 +m, 1H),
Unless otherwise noted, all reactions were carried out under
a nitrogen atmosphere in oven-dried glassware using stan-
dard syringe, cannula and septa apparatus. Benzene, diethyl

5632
H. Guo et al. / Tetrahedron 58 ,2002) 5627±5637
2.21±2.26 +m, 1H), 1.83 +s, 3H), 1.18 +d, Jˆ4.4 Hz, 3H); 13
C
+0.92 g, 4.47 mmol, 46%). [a]D ˆ189.1 +c 5.0, CHCl3);
25
NMR +100 MHz, CDCl3): d 3.5, 15.2, 34.5, 58.5, 71.3, 75.7,
76.7, 80.6, 81.9, 116.6, 127.4, 127.7, 128.3, 135.4, 138.8;
HRMS calcd for C17H22O2: 258.1620, found 258.1617.
IR +neat, cm21): 3403 +br s), 1645 +w), 1598 +w); 1H NMR
+400 MHz, CDCl3): d 726±7.35 +m, 5H), 5.83 +m, 1H), 5.14
+d, Jˆ18.8 Hz, 1H), 5.06 +d, Jˆ11.2 Hz, 1H), 4.57 +ABq,
Jˆ2.0 Hz, 2H), 3.75 +m, 1H), 3.56 +m, 1H), 2.24 +m, 2H),
2.05 +br s, 1H), 1.19 +d, Jˆ6.4 Hz, 3H); 13C NMR
+100 MHz, CDCl3): d 13.8, 36.9, 70.7, 72.6, 77.3, 117.5,
127.6, 127.7, 128.4, 134.9, 138.3; HRMS calcd for
C13H18O2: 206.1307, found 206.1303.
3.2. Enyne metathesis of compound 4
Method A. To a benzene solution +20 mL) was added
compound 4 +0.24 g, 0.93 mmol) and +PCy3)2Cl2RuvCHPh
+16.0 mg, 1.9£1022 mmol) under nitrogen, and the mixtures
were heated at 808C for 8 h. The solution was ®ltered over a
short silica bed and chromatographed over a preparative
silica plate +diethyl ether/hexaneˆ1/1) to afford the diene
5a +46 mg, 0.17 mmol, 19%) and 5b +159 mg, 0.61 mmol,
65%) as colorless oil.
3.2.4. Synthesis of 1-{[11S,2R)-2-12-butynyloxy)-1-methyl
-4-pentenyl]oxy-methyl}benzene 17). This compound was
prepared similarly from the chiral alcohol 6, NaH and
1-bromo-but-2-yne; the yield of the enyne 7 was +90%).
25
[a]D ˆ261.2 +c 3.6, CHCl3); IR +neat, cm21): 2235 +w),
1
1643 +w); H NMR +400 MHz, CDCl3): d 7.26±7.35 +m,
5H), 5.83 +m, 1H), 5.07 +d, Jˆ16.0 Hz, 1H), 5.02 +d, Jˆ
11.0 Hz, 1H), 4.58 +ABq, Jˆ10.8 Hz, 2H), 4.19 +d, Jˆ
1.6 Hz, 2H), 3.64 +m, 1H), 3.52 +m, 1H), 2.39 +m, 1H),
2.24 +m, 1H), 1.83 +s, 3H), 1.20 +d, Jˆ6.4 Hz, 3H); 13C
NMR +100 MHz, CDCl3): d 3.8, 15.5, 34.7, 58.7, 71.2,
71.5, 77.6, 80.8, 82.1, 116.9, 127.7, 127.9, 128.5, 135.6,
139.1; HRMS calcd for C17H22O2: 258.16.20, found 258.1613.
Method B. To a CH2Cl2 solution +20 mL) was added com-
pound 4 +0.24 g, 0.93 mmol), +PCy3)2Cl2RuvCHPh +16.0
mg, 1.9£1022 mmol) under ethylene gas +1.0 atm), and the
mixtures were stirred at 238C for 8 h. Workupof this mixture
in a similar fashion afforded the diene 5b in 92% yield.
3.2.1. Spectral data for 12R)-2-[11S)-1-1benzyloxy)ethyl]-
23
5-isopropenyl-3,6-dihydro-2H-pyran 15a). [a]D ˆ258.7
1
+c 3.6, CHCl3); IR +neat, cm21): 1645 +w), 1600 +w); H
3.2.5. Enyne metathesis of compound 7. To a CH2Cl2
solution +20 mL) of compound 7 +0.24 g, 0.93 mmol) was
added +PCy3)2Cl2RuvCHPh +16.0 mg, 1.9£1022 mmol)
under ethylene gas +1.0 atm), and the mixtures were stirred
at 238C for 8 h. Work upof this mixture afforded the diene
5a +0.22 g, 0.82 mmol) in 88% yield. The [a]D value [259.2
+c 2.6, CHCl3)] and 1H NMR spectral data of this compound
matched with that of 5a [a]D value [258.7 +c 2.6, CHCl3)]
in the preceding reaction.
NMR +400 MHz, CDCl3): d 7.25±7.37 +m, 5H), 5.91 +d,
Jˆ6.0 Hz, 1H), 4.82 +s, 1H), 4.72 +s, 1H), 4.64 +d, Jˆ
3.6 Hz, 2H), 4.42 +ABq, Jˆ2.5 Hz, 2H), 3.57 +m, 1H),
3.51 +m, 1H), 2.26 +m, 1H), 2.03 +m, 1H), 1.87 +s, 3H),
1.20 +d, Jˆ6.4 Hz, 3H); 13C NMR +100 MHz, CDCl3): d
16.0, 20.8, 27.1, 66.8, 72.0, 76.9, 77.3, 110.5, 121.7,
127.0, 127.9, 128.0, 136.2, 139.5, 140.7; HRMS calcd for
C17H22O2: 258.1620, found 258.1614.
3.2.6. Synthesis and spectral data of 1-{[11S,2S)-1-methyl-
2-12-propynyloxy)-4-pentenyl]oxy-methyl}benzene 18).
The reaction of the alcohol 3 with NaH and benzyl bromide
3.2.2. Spectral data for 12S)-2-[11S)-1-1benzyloxy)ethyl]-
23
5-isopropenyl-3,6-dihydro-2H-pyran 15b). [a]D ˆ152.9
1
+c 1.8, CHCl3); IR +neat, cm21): 1641 +w), 1604 +w); H
23
gave the enyne 8 in 87% yield. [a]D ˆ130.3 +c 2.5,
NMR +400 MHz, CDCl3): d 7.15±7.25 +m, 5H), 5.85 +s,
1H), 4.73 +s, 1H), 4.62 +s, 1H), 4.50 +ABq, Jˆ12.4 Hz,
2H), 4.31 +ABq, Jˆ2.0 Hz, 2H), 3.45 +m, 1H), 3.33 +m,
1H), 2.01±2.15 +m, 2H), 1.77 +s, 3H), 1.15 +d, Jˆ6.4 Hz,
3H); 13C NMR +100 MHz, CDCl3): d 15.4, 20.3, 26.7, 66.6,
71.6, 76.4, 76.6, 109.6, 121.4, 127.3, 127.7, 128.3, 135.8,
139.0, 140.0; HRMS calcd for C17H22O2: 258.1620, found
258.1614.
CHCl3); IR +neat, cm21): 2223 +w), 1642 +w), 1603 +w);
1H NMR +400 MHz, CDCl3): d 7.25±7.35 +m, 5H), 5.85
+m, 1H), 5.09 +1H, d, Jˆ17.2 Hz), 5.02 +1H, d, Jˆ
10.6 Hz), 4.57 +2H, ABq, Jˆ8.0 Hz), 4.24 +s, 2H), 3.63
+1H, m), 3.53 +1H, m), 2.38 +1H, m), 2.37 +1H, s), 2.23
+1H, m), 1.20 +d, Jˆ2.4 Hz, 3H); 13C NMR +100 MHz,
CDCl3): d 15.3, 34.5, 57.9, 71.3, 73.9, 75.9, 80.4, 80.9,
116.9, 127.5, 127.7, 128.3, 135.0, 138.7; HRMS calcd for
C16H20O2: 244.1463, found 244.1461.
3.2.3. Synthesis of 14R,5S)-5-1phenylmethoxy)hex-1-en-
4-ol 16). To a toluene solution +25 mL) of DEAD +1.81 g,
10.4 mmol) and PPh3 +2.73 g, 10.4 mmol) added the alcohol
3 +2.00 g, 9.70 mmol), and the solution was stirred for 1 h
before p-nitrobenzoic acid +1.74 g, 10.4 mmol) was added at
238C. The mixture was stirred for 8 h, and ®ltered to remove
white precipitates. To the toluene ®ltrate was added water
+10 mL), and the organic layer was separated, concentrated
and eluted through a short silica column to afford the
ester product +2.60 g, 7.31 mmol). To a methanol solution
+10.0 mL) of this ester +2.60 g, 7.31 mmol) was added
K2CO3 +1.72 g) solution, and the mixture was stirred for
6 h before quenched with a NH4Cl solution. The solution
was concentrated dried over MgSO4, and the organic layer
was extracted with diethyl ether +20 mL). The etherate
solution was concentrated and eluted through a silica
column to afford the chiral alcohol as a colorless oil
3.2.7. Spectral data of 1-{[11S,2R)-1-methyl-2-12-propy-
nyloxy)-4-pentenyl]oxy-methyl}benzene 19). Enyne 9 was
prepared from the alcohol 6, NaH and benzyl bromide; the
23
yield was 87%. [a]D ˆ147.0 +c 1.5, CHCl3); IR +neat,
cm21): 2223 +w), 1651 +w), 1599 +w); 1H NMR +400
MHz, CDCl3): d 7.25±7.35 +m, 5H), 5.82 +m, 1H), 5.09
+d, Jˆ17.0 Hz, 1H), 5.04 +d, Jˆ10.5 Hz, 1H), 4.57 +ABq,
Jˆ8.0 Hz, 2H), 4.24 +s, 2H), 3.64 +m, 1H), 2.38 +m, 1H),
1.20 +d, Jˆ2.4 Hz, 3H); 13C NMR +100 MHz, CDCl3): d
15.3, 34.5, 57.9, 71.3, 73.9, 75.9, 80.4, 80.9, 116.9, 127.5,
127.7, 128.3, 135.0, 138.7; HRMS calcd for C16H20O2:
244.1463, found 244.1461.
3.2.8. Spectral data for 13R,4S)-3-1allyloxy)-4-
[dimethyl1tert-butyl)siloxy]-1-pentyne 110). Enyne 10

H. Guo et al. / Tetrahedron 58 ,2002) 5627±5637
5633
was prepared similarly from the alcohol E +RˆH), NaH and
CHCl3); IR +neat, cm21): 2218 +w), 1640 +w); H NMR
75.7, 81.9, 84.3, 119.1, 135.8; HRMS calcd for
C15H28SiO2: 268.4705, found 268.4708.
23
allyl bromide, and the yield was 87%. [a]D ˆ227.0 +c 2.0,
1
+400 MHz, CDCl3): d 5.86 +m, 1H), 5.31 +d, Jˆ16.8 Hz,
1H), 5.16 +d, 1H, Jˆ10.2 Hz), 4.25 +m, 1H), 3.96 +m, 1H),
3.88 +d, Jˆ4.4 Hz, 2H), 2.37 +s, 1H), 1.20 +d, Jˆ6.4 Hz,
3H), 0.84 +s, 9H), 0.09 +s, 3H), 0.05 +s, 3H); 13C NMR
+100 MHz, CDCl3): d 25.0, 24.6, 18.1, 19.7, 25.8, 70.1,
70.6, 73.9, 74.3, 81.5, 117.3, 134.3; HRMS calcd for
C14H26SiO2: 254.1702, found 254.1700.
3.2.13. Spectral data for 14R)-4-[11S)-1-1allyloxy)-3-
butynyl]-2,2-dimethyl-1,3-dioxolane 115). Alcohol H,
NaH and allyl bromide gave enyne 15 as a colorless oil
+86% yield). [a]D ˆ114.8 +c 1.1, CHCl3); IR +cm21):
23
1
2234 +w), 1656 +w); H NMR +400 MHz, CDCl3): d 5.89
+m, 1H), 5.28 +d, Jˆ17.2 Hz, 1H), 5.18 +d, Jˆ10.4 Hz, 1H),
4.26±4.21 +m, 1H), 4.19±4.13 +m, 1H), 4.07 +dd, Jˆ8.4,
7.6 Hz, 1H), 3.94 +dd, Jˆ8.4 Hz, 1H), 3.50±3.46 +m, 1H),
2.60 +dd, Jˆ17.2, 5.2 Hz, 1H), 2.60 +dd, Jˆ17.2, 4.6 Hz,
1H), 2.01 +t, Jˆ2.4 Hz, 1H), 1.40 +s, 3H), 1.34 +s, 3H);
13C NMR +100 MHz, CDCl3): d 21.2, 25.4, 26.9, 66.7,
70.4, 71.6, 76.6, 76.9, 80.6, 109.5, 117.6, 134.7; HRMS
calcd for C12H18O3: 210.2724, found 210.2715.
3.2.9. Spectral data for 13S,4S)-3-1allyloxy)-4-[dimethyl-
1tert-butyl)siloxy]-1-pentyne 111). This compound was
prepared similarly from the alcohol F, NaH and allyl
23
bromide; the yield was 96%. [a]D ˆ133.8 +c 0.65,
1
CHCl3); IR +neat, cm21): 2230 +w), 1644 +w); H NMR
+400 MHz, CDCl3): d 5.87 +m, 1H), 5.27 +d, Jˆ
16.8 Hz, 1H), 5.16 +d, Jˆ10.2 Hz, 1H), 4.24 +dd, Jˆ10.2,
4.5 Hz, 1H), 3.94 +dd, Jˆ10.2, 7.0 Hz, 1H), 3.88 +m,
2H), 2.39 +s, 1H), 1.22 +d, Jˆ6.4 Hz, 3H), 0.87 +s, 9H),
0.09 +s, 3H), 0.05 +s, 3H); 13C NMR +100 MHz, CDCl3): d
24.4, 24.6, 18.3, 19.8, 26.0, 70.3, 70.4, 74.4, 81.1, 117.5,
134.6; HRMS calcd for C14H26SiO2: 254.1702, found
254.1698.
3.2.14. Spectral data for 14R,5R)-4-[11R)-1-1allyloxy)-3-
butynyl]-5-[1benzyloxy)methyl]-2,2-dimethyl-1,3-dioxo-
lane 116). Alcohol I, NaH and allyl bromide gave enyne 16
23
as a colorless oil +86% yield). [a]D ˆ111.2 +c 1.0, CHCl3);
IR +cm21): 2234 +w), 1656 +w); 1H NMR +400 MHz,
CDCl3): d 7.27 +m, 5H), 5.80 +m, 1H), 5.24 +d, Jˆ
17.2 Hz, 1H), 5.13 +d, Jˆ10.8 Hz, 1H), 4.64±4.55 +ABq,
Jˆ12.0 Hz, 2H), 4.23±4.17 +m, 1H), 4.02 +m, 1H), 3.86
+t, Jˆ6.8 Hz, 1H), 3.71 +dd, Jˆ10.4, 10.0 Hz, 1H), 3.57
+m, 2H), 2.58 +dd, Jˆ17.2, 3.6 Hz, 1H), 2.44 +dd, Jˆ17.2,
4.0 Hz, 1H), 1.99 +t, Jˆ2.4 Hz, 1H), 1.41 +s, 3H), 1.39 +s,
3H); 13C NMR +100 MHz, CDCl3): d 21.2, 27.0, 27.1, 70.2,
71.3, 71.4, 73.3, 77.8, 78.0, 78.8, 80.5, 109.6, 117.4, 127.6,
127.7, 128.2, 134.5, 138.0; HRMS calcd for C20H26O4:
330.4231, found 330.4233.
3.2.10. Spectral data for 12S,3R)-3-1allyloxy)-2-[tert-
dimethyl1tert-butyl)-siloxy]-4-unde-cyne 112). Enyne 12
was prepared from chiral alcohol E +RˆC6H13), NaH and
23
allyl bromide, and the yield was 88%. [a]D ˆ243.6 +c 4.8,
CHCl3); IR +neat, cm21): 2230 +w), 1643 +w), 1600 +w); 1H
NMR +400 MHz, CDCl3): d 5.88 +m, 1H), 5.28 +d,
Jˆ18.2 Hz, 1H), 5.15 +d, Jˆ10.4 Hz, 1H), 4.23 +m, 1H),
4.00 +m, 1H), 3.83 +m, 2H), 2.19 +t, Jˆ4.0 Hz, 2H), 1.53
+m, 2H), 1.38 +m, 2H), 1.29 +m, 4H), 1.21 +d, Jˆ6.4 Hz,
3H), 0.87 +t, Jˆ6.2 Hz, 3H), 0.86 +s, 9H), 0.10 +s, 3H), 0.05
+s, 3H); 13C NMR +100 MHz, CDCl3): d 25.0, 24.5, 14.3,
18.5, 19.1, 20.0, 22.8, 26.1, 28.8, 28.9, 31.6, 70.1, 71.4,
74.6, 77.9, 87.2, 117.2, 135.1; HRMS calcd for
C20H38SiO2: 338.2641, found 338.2644.
3.2.15. Spectral data for 12S)-2-[11S)-1-1benzyloxy)-
ethyl]-5-vinyl-3,6-dihydro-2H-pyran 117). Enyne meta-
thesis of compound 8 afforded diene 17 as a colorless oil
+86%). [a]D ˆ256.6 +c 5.0, CHCl3); IR +neat, cm21): 1641
23
1
+w), 1600 +w); H NMR +400 MHz, CDCl3): d 7.25±7.34
+m, 5H), 6.24 +dd, Jˆ18.0, 11.2 Hz, 1H), 5.81 +d, 1H, Jˆ
4.5 Hz), 4.93 +d, Jˆ18.0 Hz, 1H), 4.61 +ABq, Jˆ11.2 Hz,
2H), 4.49 +d, Jˆ10.4 Hz, 1H), 4.29 +d, Jˆ10.4 Hz, 1H),
3.50±3.60 +m, 2H), 2.26 +br t, Jˆ8.3 Hz, 1H), 1.99
+m, 1H), 1.09 +d, Jˆ2.8 Hz, 3H); 13C NMR +100 MHz,
CDCl3): d 15.4, 26.8, 65.7, 71.6, 76.4, 76.7, 110.8, 125.5,
127.4, 127.7, 128.3, 135.0, 135.8, 138.9; HRMS calcd for
C16H20O2: 244.1463, found 244.1457.
3.2.11. Spectral data for 13S,4R)-3-12-propynyloxy)-4-
1tert-butyldimethylsiloxy)-1-pentene 113). Alcohol
G
+RˆH), NaH and propargyl bromide yielded enyne 13 as
23
a colorless oil +87%). [a]D ˆ274.8 +c 1.5, CHCl3); IR
1
+cm21): 2241 +w), 1631 +w); H NMR +400 MHz, CDCl3):
d 5.66 +m, 1H), 5.29 +d, Jˆ10.0 Hz, 1H), 5.28 +d, Jˆ
17.0 Hz, 1H), 4.19 +dd, Jˆ2.4, 2.0 Hz, 1H), 4.03 +dd,
Jˆ2.4, 2.0 Hz, 1H), 3.78 +m, 1H), 3.70 +m, 1H), 2.34
+t, Jˆ2.8 Hz, 1H), 1.13 +d, Jˆ5.6 Hz, 2H), 0.85 +s, 9H),
0.03 +s, 3H), 0.02 +s, 3H); 13C NMR +100 MHz, CDCl3): d
20.1, 26.0, 55.7, 70.8, 73.9, 80.4, 84.5, 119.6, 135.3; HRMS
calcd for C14H26SiO2: 254.4437, found 254.4432.
3.2.16. Spectral data for 12R)-2-[11S)-1-1benzyloxy)-
ethyl]-5-vinyl-3,6-dihydro-2H-pyran 118). Enyne meta-
thesis of compound 9 afforded diene 18 as a colorless oil
23
+87%). [a]D ˆ128.4 +c 1.3, CHCl3); IR +neat, cm21): 1641
1
+w), 1601 +w); H NMR +400 MHz, CDCl3): d 7.25±7.32
+m, 5H), 6.24 +dd, Jˆ18.0, 10.8 Hz, 1H), 5.83 +br s, 1H),
4.92 +d, Jˆ18.0 Hz, 1H), 4.89 +d, Jˆ10.8 Hz, 1H), 4.58
+ABq, Jˆ12.0 Hz, 2H), 3.55 +m, 1H), 3.44 +m, 1H), 2.39
+m, 1H), 2.13 +m, 1H), 1.23 +d, Jˆ6.4 Hz, 3H); 13C NMR
+100 MHz, CDCl3): d 16.3, 26.5, 65.7, 71.4, 76.7, 76.9,
111.2, 125.4, 127.5, 127.9, 128.5, 135.4, 136.2, 138.5;
HRMS calcd for C16H20O2: 244.1463, found 244.1460.
3.2.12. Spectral data for 13S,4R)-3-12-butynyloxy)-4-
1tert-butyldimethylsiloxy)-1-pentene 114). Alcohol
G
+RˆH), NaH and 1-brom-2-butyne yielded enyne 14 as a
23
colorless oil +95%). [a]D ˆ245.1 +c 1.5, CHCl3); IR
1
+cm21): 1909 +s), 1654 +m); H NMR +400 MHz, CDCl3):
d 5.68 +m, 1H), 5.25 +d, Jˆ10.0 Hz, 1H), 5.22 +d, Jˆ
16.6 Hz, 1H), 4.06 +ABq, Jˆ13.8 Hz, 1H), 3.76 +m, 1H),
3.63 +m, 1H), 1.83 +s, 3H), 1.15 +d, Jˆ6.0 Hz, 3H), 0.87 +s,
9H), 0.03 +s, 3H), 0.02 +s, 3H); 13C NMR +100 MHz,
CDCl3): d 24.3, 24.4, 3.7, 18.3, 20.2, 26.0, 56.4, 70.9,
3.2.17. Spectral data for [dimethyl1tert-butyl)siloxy]11S)-
1-[12R)-3-vinyl-2,5-dihy-dro-2-furanyl]ethyl ether 119).
Enyne metathesis of compound 10 afforded diene 19 as a

5634
H. Guo et al. / Tetrahedron 58 ,2002) 5627±5637
23
colorless oil +92%). [a]D ˆ116.6 +c 0.8, CHCl3); IR +neat,
metathesis of compound 15 afforded diene 24 as a colorless
23
1
cm21): 1641 +w); H NMR +400 MHz, CDCl3): d 6.39
oil +88%). [a]D ˆ255.3 +c 1.5, CHCl3); 1H NMR
+dd, Jˆ18.0, 11.6 Hz, 1H), 5.87 +br s, 1H), 5.16 +d, Jˆ
18.0 Hz, 1H), 5.07 +d, 1H, Jˆ10.8 Hz, 1H), 4.87 +br s),
4.67 +m, 2H), 4.10 +m, 1H), 1.17 +d, Jˆ6.4 Hz, 3H), 0.85
+s, 9H), 0.07 +s, 3H), 0.05 +s, 3H); 13C NMR +100 MHz,
CDCl3): d 24.4, 24.4, 16.6, 18.3, 25.9, 70.3, 75.5, 89.5,
116.0, 126.6, 129.8, 139.1; HRMS calcd for C14H26SiO2:
254.1702, found 254.1699.
+400 MHz, CDCl3): d 6.33 +dd, Jˆ17.6 Hz, 1H), 5.67
+d, Jˆ2.4 Hz, 1H), 5.16 +d, Jˆ17.2 Hz, 1H), 4.98 +d, Jˆ
10.4 Hz, 1H), 4.23 +s, 1H), 4.07 +dd, Jˆ8.4, 7.6 Hz, 1H),
4.04±3.99 +m, 1H), 3.91 +dd, Jˆ8.4, 8.0 Hz, 1H), 3.45±3.39
+m, 1H), 2.36±2.32 +m, 1H), 2.14±2.07 +m, 1H), 1.38 +s,
3H), 1.33 +s, 3H); 13C NMR +100 MHz, CDCl3): d 25.1,
26.5, 26.6, 65.7, 67.1, 74.6, 77.9, 109.2, 111.6, 126.0,
133.0, 137.8; HRMS calcd for C12H18O3: 210.2724, found
210.2722.
3.2.18. Spectral data for [dimethyl1tert-butyl)siloxy]11S)-
1-[12S)-3-vinyl-2,5-dihydro-2-furanyl]ethyl ether 120).
Enyne metathesis of compound 11 afforded diene 20 as a
3.2.23. Spectral data for 12R)-2-[14R,5R)-5-[1benzyloxy)-
methyl]-2,2-dimethyl-1,3-dioxolan-4-yl]-4-vinyl-3,6-di-
hydro-2H-pyran 125). Enyne metathesis of compound 16
23
colorless oil +86%). [a]D ˆ18.8 +c 1.1, CHCl3); IR +neat,
cm21): 1641 +w); 1H NMR +400 MHz, CDCl3): d 6.41 +dd,
Jˆ18.0, 10.6 Hz, 1H), 5.89 +br, s, 1H), 5.22 +d, Jˆ17.6 Hz,
1H), 5.12 +d, Jˆ7.2 Hz, 1H), 4.77 +s, 1H), 4.65 +m, 1H),
4.56 +m, 1H), 4.03 +m, 1H), 1.17 +d, Jˆ6.4 Hz, 3H), 0.84 +s,
9H), 20.01 +s, 3H), 20.05 +s, 3H); 13C NMR +100 MHz,
CDCl3): d 24.4, 24.9, 17.9, 19.8, 25.9, 69.3, 75.2, 88.7,
115.9, 126.7, 130.0, 138.8; HRMS calcd for C14H26SiO2:
254.1702, found 254.1698.
23
afforded diene 25 as a colorless oil +92%). [a]D ˆ2187.5
1
+c 1.5, CHCl3); IR +cm21): 1666 +w), H NMR +400 MHz,
CDCl3): d 7.35±7.25 +m, 5H), 6.36 +dd, Jˆ17.2, 10.8 Hz,
1H), 5.70 +d, Jˆ1.6 Hz, 1H), 5.18 +d, Jˆ17.6 Hz, 1H), 5.01
+d, Jˆ10.8 Hz, 1H), 4.60 +ABq, Jˆ14.4 Hz, 2H), 4.25±4.21
+m, 1H), 4.20±4.17 +m, 1H), 3.82 +t, Jˆ7.2 Hz, 1H), 3.74
+dd, Jˆ10.4 Hz, 1H), 3.61 +dd, Jˆ10.8 Hz, 1H), 3.57±3.53
+m, 1H), 2.37±2.19 +m, 2H), 1.42 +s, 3H), 1.40 +s, 3H); 13C
NMR +100 MHz, CDCl3): d 26.5, 27.1, 27.1, 65.9, 71.3,
73.4, 75.0, 79.3, 79.6, 109.8, 111.7, 125.9, 127.5, 127.6,
128.3, 133.1, 137.9, 138.1; HRMS calcd for C20H26O4:
330.4231, found 330.4226.
3.2.19. Spectral data for 12R)-2-[12R)-3-11-hexylvinyl)-
2,5-dihydro-2-furanyl]ethyl ether 121). Enyne metathesis
of compound 12 afforded diene 21 as a colorless oil +81%).
[a]D ˆ18.4 +c 1.1, CHCl3); IR +neat, cm21): 1654 +w); 1H
23
NMR +400 MHz, CDCl3): d 5.82 +d, Jˆ1.6 Hz, 1H), 5.08 +s,
1H), 4.97 +s, 1H), 4.86 +br s, 1H), 4.65 +d, Jˆ1.6 Hz, 1H),
4.13 +m, 1H), 2.24 +t, Jˆ3.6 Hz, 2H), 1.20±1.45 +m, 11H),
1.05 +d, Jˆ6.4 Hz, 3H), 0.85 +s, 9H), 0.12 +s, 3H), 0.05 +s,
3H); 13C NMR +100 MHz, CDCl3): d 24.4, 24.6, 14.0,
16.2, 18.2, 22.6, 23.2, 25.8, 28.3, 29.1, 36.9, 70.3, 76.2,
90.1, 113.1, 123.5, 140.3, 140.5; HRMS calcd for
C20H38SiO2: 338.2641, found 338.2640.
23
3.2.24. Spectral data for compound 26. [a]D ˆ118.6 +c
1
2.0, CHCl3); IR +cm21): 2245 +w), 1665 +w); H NMR
+400 MHz, CDCl3): d 5.85 +m, 1H), 5.32 +d, Jˆ16.0 Hz,
1H), 5.28 +d, Jˆ11.6 Hz, 1H), 5.13 +dd, Jˆ7.1, 4.5 Hz,
1H), 3.95 +m 1H), 2.85 +s, 1H), 1.09 +d, Jˆ6.0 Hz, 3H),
0.87 +s, 9H), 0.05 +s, 3H), 0.04 +s, 3H); 13C NMR
+100 MHz, CDCl3): d 24.8, 24.7, 18.0, 19.5, 25.7, 69.1,
74.5, 74.8, 81.0, 120.0, 131.6, 185.7; HRMS calcd for
C14H24SiO3: 268.4273, found 268.4267.
3.2.20. Spectral data for 12R)-2-[11S)-1-1tert-butyl-
dimethylsiloxy)ethyl]-4-vinyl-2,5-dihydro-furan 122).
Enyne metathesis of compound 13 afforded diene 22 as a
23
3.2.25. Spectral data for the enyne 27. [a]D ˆ14.4 +c
2.0, CHCl3); IR +cm21): 2251 +w), 1666 +w); H NMR
23
colorless oil +94%). [a]D ˆ1111.5 +c 1.5, CHCl3); IR
1
1
+neat, cm21): 1654 +w); H NMR +400 MHz, CDCl3): d
+400 MHz, CDCl3): d 7.26±7.41 +m, 5H), 5.80 +m, 1H),
5.16 +d, Jˆ10.2 Hz, 1H), 5.10 +d, 1H, Jˆ17.6 Hz), 4.56
+ABq, Jˆ12.0 Hz, 2H), 4.04 +m, 1H), 3.79 +m, 1H), 2.53±
2.40 +m, 2H), 2.09 +s, 1H), 1.22 +d, Jˆ6.4 Hz, 3H); 13C
NMR +100 MHz, CDCl3): d 15.1, 27.1, 33.5, 71.5, 74.0,
90.2, 90.6, 118.3, 127.6, 127.8, 128.3, 132.8, 138.2;
HRMS calcd for C15H18O2: 230.1306, found 230.1300.
6.49 +dd, Jˆ17.6, 10.8 Hz, 1H), 5.80 +d, Jˆ1.60 Hz, 1H),
5.13 +d, Jˆ11.2 Hz, 1H), 4.95 +d, Jˆ17.6 Hz, 1H), 4.76±
4.67 +m, 1H), 4.60±4.59 +m, 1H), 3.72±3.68 +m, 1H), 1.14
+d, Jˆ6.0 Hz, 3H), 0.85 +s, 9H), 0.03 +s, 3H), 0.02 +s, 3H);
13C NMR +100 MHz, CDCl3): d 24.63, 24.25, 18.2, 20.3,
26.0, 71.5, 74.5, 91.5, 116.3, 126.4, 129.8, 139.6; HRMS
calcd for C14H26SiO2 254.4705, found 254.4701.
3.2.26. Synthesis of 13aS,6R,8aR,8bR)-8-[11S)-1-1tert-
butyldimethylsiloxy)ethyl]-1,3,3a,4,6,8,8a,8b-octahydro-
furo[3,4-e]isobenzofuran-1,3-dione 128). To a toluene
solution +2.0 mL) of the diene 19 +66 mg, 0.26 mmol) was
added maleic anhydride +24 mg, 0.25 mmol), and the
mixture was heated in toluene +908C, 2 h). The solution
was concentrated, dried over MgSO4, and eluted through a
preparative silica plate to afford the cycloadduct 28 +76 mg,
2.2 mmol, 86%) as a colorless oil. [a]Dˆ220.4 +c 0.95,
3.2.21. Spectral data for 12R)-2-[11S)-1-1tert-butyl-
dimethylsiloxy)ethyl]-4-isopropenyl-2,5-dihydrofuran
123). Enyne metathesis of compound 14 afforded diene 23 as
23
a colorless oil +89%). [a]D ˆ223.6 +c 0.45, CHCl3); IR
1
+cm21): 1656 +w), H NMR +400 MHz, CDCl3): d 5.81 +d,
Jˆ2.0 Hz, 1H), 4.95 +s, 1H), 4.73 +m, 1H), 4.62±4.61 +m,
1H), 3.68 +m, 1H), 1.92 +s, 3H), 1.16 +d, Jˆ6.0 Hz, 3H),
0.86 +s, 9H), 0.043 +s, 3H), 0.031 +s, 3H); 13C NMR +100
MHz, CDCl3): d 24.9, 24.5, 18.0, 20.2, 20.4, 25.7, 71.4,
75.1, 91.8, 113.7, 123.7, 136.4, 141.1; HRMS calcd for
C15H28SiO2 268.4705, found 268.4708.
1
CHCl3); IR +neat, cm21): 1846 +s), 1771 +s); H NMR
+500 MHz, CDCl3): d 5.83 +br s, 1H), 4.27 +m, 2H), 4.15
+s, 1H), 3.82 +m, 1H), 3.53 +m, 1H), 3.43 +m, 1H), 2.84 +dd,
1H, Jˆ16.5, 10.0 Hz, 1H), 2.22 +m, 1H), 1.11 +d, Jˆ6.5 Hz,
3H), 0.83 +s, 9H), 0.02 +s, 3H), 20.01 +s, 3H); 13C NMR
+125 MHz, CDCl3): d 24.6, 24.5, 18.0, 19.5, 24.5, 25.8,
3.2.22. Spectral data for 12S)-2-[14R)-2,2-dimethyl-1,3-
dioxolan-4-yl]-4-vinyl-3,6-dihydro-2H-pyran 124). Enyne

H. Guo et al. / Tetrahedron 58 ,2002) 5627±5637
5635
38.4, 40.3, 41.4, 68.7, 70.4, 84.1, 117.1, 136.5, 144.1, 171.0,
173.8; HRMS calcd for C18H28SiO5: 352.1706, found
352.1699.
3.2.29. Synthesis of 11R,5aR,8aS,8bR)-7-phenyl-1-[11S)-
1-1tert-butyldimethylsiloxy)ethyl]-3,5,5a,6,7,8,8a,8b-
octahydro-1H-furo[3,4-e]isoindole-6,8-dione 131). Heat-
ing a toluene solution +1108C, 6 h) of the diene 22 +50.9
mg, 0.196 mmol) with phenyl maleimide +34.0 mg, 0.196
mmol) afforded the cycloadduct 31 +81 mg, 0.189 mmol) in
96% yield after puri®cation from preparative silica plate.
3.2.27. Synthesis of 13R,5aS,8aR,8bS)-3-[11S)-1-1tert-
butyldimethylsiloxy)ethyl]-3,5,5a,6,7,8,8a,8b-octahydro-
1H-furo[3,4-e]isoindole-6,8-dione 129). Heating a toluene
solution of the diene 19 +908C, 2 h) with phenyl maleimide
afforded the cycloadduct 29 in 93% yield after puri®cation
from preparative silica plate. [a]Dˆ212.2 +c 1.1, CHCl3);
25
[a]D ˆ248.0 +c 0.6, CHCl3); IR +cm21): 1770 +m), 1716
1
+m); H NMR +400 MHz, CDCl3): d 7.35±7.15 +m, 5H),
5.69 +br, 1H), 4.67 +dd, Jˆ6.4 Hz, 1H), 4.40 +dd, Jˆ
13.2 Hz, 1H), 4.23 +dd, Jˆ13.2 Hz, 1H), 4.02±3.98 +m,
1H), 3.39 +dd, Jˆ8.8 Hz, 1H), 3.30 +dt, Jˆ8.8, 1.2 Hz,
1H), 2.92±2.86 +m, 2H), 2.25±2.19 +m, 1H), 1.25 +d, Jˆ
6.4 Hz, 3H), 0.09 +s, 9H), 0.07 +s, 9H), 0.04 +s, 3H); 13C
NMR +100 MHz, CDCl3): d 24.7, 24.4, 18.0, 20.9, 25.7,
26.0, 40.2, 40.9, 41.8, 69.2, 70.0, 83.5, 113.6, 126.3, 129.0,
129.1, 131.8, 134.5, 145.2, 176.5, 178.5; HRMS calcd for
C24H33NO4Si: 427.2179, found 427.2176.
1
IR +neat, cm21): 1778 +s), 1711 +s); H NMR +500 MHz,
CDCl3): d 7.41 +t, Jˆ8.0 Hz, 2H), 7.35 +t, Jˆ8.0 Hz,
1H), 6.98 +d, Jˆ8.0 Hz, 2H), 5.82 +br s, 1H), 4.38 +dd,
Jˆ8.2, 7.6 Hz, 1H), 4.28 +dd, Jˆ8.2, 7.1 Hz, 1H), 4.13 +s,
1H), 3.82 +m, 1H), 3.39 +t, Jˆ7.5 Hz, 1H), 3.26 +t,
Jˆ7.5 Hz, 1H), 2.95 +dd, Jˆ15.0, 7.5 Hz 1H), 2.83 +m,
1H), 2.19 +m, 1H), 1.12 +d, Jˆ6.5 Hz, 3H), 0.85 +s, 9H),
0.06 +s, 3H), 0.03 +s, 3H); 13C NMR +500 MHz, CDCl3): d
24.6, 24.5, 17.9, 19.5, 24.4, 25.8, 38.9, 39.8, 40.6, 68.9,
70.3, 84.1, 117.0, 126.3, 128.5, 129.0, 131.8, 143.6, 176.2,
178.4; HRMS calcd for C24H33SiO4N: 427.2179, found
427.2177.
3.2.30. Synthesis of 11R,5aR,9aS,9bR)-1-[11S)-1-hydro-
xyethyl]-1,3,5,5a,6,9,9a,9b-octahydro benzo[e]isobenzo-
furan-6,9-dione 132). To a CH2Cl2 solution +3.0 mL) of
the diene 22 +110 mg, 0.39 mmol) and benzoquinone
+425 mg, 3.94 mmol) was added SnCl4 +1.96 mL, 1.96
mmol), and the mixture was stirred at 238C for 12 h. To
this mixture was added NaHCO3 solution, and the organic
layer was extracted with diethyl ether, dried over MgSO4
and evaporated to dryness. Recrystallization of the resi-
dues in a saturated diethyl ether/hexane solution afforded
compound 32 as colorless solid +80.0 mg, 0.32 mmol, 82%).
25
[a]D ˆ259.0 +c 0.6, CHCl3); IR +cm21): 3059 +m), 2900
1
+m), 1687 +s); H NMR +400 MHz, CDCl3): d 6.60 +d,
Jˆ7.6 Hz, 1H), 6.56 +d, Jˆ7.6 Hz, 1H), 5.4±5.3 +m, 1H),
4.66 +dd, Jˆ9.6, 9.2 Hz, 1H), 4.48 +dd, Jˆ13.2, 3.2 Hz, 1H),
4.37 +dd, Jˆ12.8, 4.4 Hz, 1H), 4.01±3.96 +m, 1H), 3.66 +t,
Jˆ4.8 Hz, 1H), 3.17 +m, 1H), 2.74 +m, 1H), 2.40 +m, 1H),
2.25 +m, 1H), 2.07 +s, 1H), 1.25 +d, Jˆ6.4 Hz, 3H); 13C
NMR +100 MHz, CDCl3): d 18.9, 26.7, 41.3, 47.5, 48.9,
68.9, 69.6, 82.3, 112.4, 137.2, 140.6, 140.7, 198.0, 200.7;
HRMS calcd for C14H16O4: 248.1049, found 248.1041.
3.2.28. Synthesis of 13aR,8R,8aR,8bS)-8-[11S)-1-1tert-
butyldimethylsiloxy)ethyl]-1,3,3a,4,6,8,8a,8b-octahydro-
furo[3,4-e]isobenzofuran-1,3-dione 130). Heating
a
toluene solution +1108C, 6 h) of the diene 22 +70 mg,
0.275 mmol) with maleic anhydride +27.0 mg, 0.275
mmol) afforded the cycloadduct 30 +87 mg, 0.25 mmol) in
90% yield after puri®cation from preparative silica plate.
25
[a]D ˆ215.7 +c, 1.5 CHCl3); IR +cm21): 1844 +m), 1788
+m); 1H NMR +400 MHz, CDCl3): d 5.70 +m, 1H), 4.45 +dd,
Jˆ6.8, 6.4 Hz, 1H), 4.39 +dd, Jˆ12.6, 2.1 Hz, 1H), 4.25 +dd,
Jˆ12.6, 3.1 Hz, 1H), 4.0±3.9 +m, 1H), 3.51 +dd, Jˆ9.6 Hz,
1H), 3.43 +dt, Jˆ8.0, 1.6 Hz, 1H), 2.83±2.77 +m, 2H), 2.26±
2.18 +m, 1H), 1.22 +d, Jˆ6.4 Hz, 3H), 0.85 +s, 9H), 0.06 +s,
3H), 0.02 +s, 3H); 13C NMR +100 MHz, CDCl3): d 24.6,
24.41, 18.0, 20.9, 25.3, 25.7, 39.8, 41.3, 42.8, 69.3, 70.1,
83.6, 114.0, 145.7, 171.5, 174.1; HRMS calcd for
C18H28SiO5: 321.1706, found 321.1700.
3.2.31. Synthesis of 11R,3aS,5aR,8aS,8bS)-1-[hydroxy-
ethyl]-7-phenylperhydrofuro[3,4-e]isoindole-6,8-dione
136). To compound 31 +100 mg, 0.247 mmol) in 5 mL
MeOH was added Pd/C +52.14 mg, 0.049 mmol) under
1 atm H2 and the mixtures were stirred for 12 h. The catalyst
was ®ltered off through a small bed of celite. To the ®ltrate
was added excess Bu4NF and the mixtures were stirred for
4 h. The solution was concentrated and eluted through
a silica column +ether/hexaneˆ2/1) to give alcohol 36
25
+65 mg, 0.203 mmol, 88%, Rfˆ0.23). [a]D ˆ247.5 +c
1
1.0, CHCl3); IR +cm21): 3392 +br), 1607 +s); H NMR
+400 MHz, CDCl3): d 7.23±7.48 +m, 5H), 4.70 +t, Jˆ
4.0 Hz, 1H), 4.07 +t, Jˆ8.0 Hz, 1H), 3.92±3.87 +m, 1H),
3.38 +t, Jˆ9.2 Hz, 1H), 3.20 +dt, Jˆ2.0, 8.0 Hz, 1H), 3.11

5636
H. Guo et al. / Tetrahedron 58 ,2002) 5627±5637
2. +a) Breitmaier, E.; Ruffer, U. Synthesis 1989, 623.
+b) Cornwall, P.; Dell, C. P.; Knight, D. W. J. Chem. Soc.,
Perkin Trans. 1 1993, 2395. +c) Chemler, S. R.; Iserloh, U.;
Danishefsky, S. I. Org. Lett. 2001, 3, 2949.
+dd, Jˆ6.4, 9.2 Hz, 1H), 2.68±2.62 +m, 1H), 2.53±2.42 +m,
1H), 2.20±2.13 +m, 2H), 2.03±1.83 +m, 2H), 1.21 +d,
Jˆ6.0 Hz, 3H), 1.15±1.04 +m, 1H); 13C NMR +75 MHz,
CDCl3): d 178.7, 178.6, 131.8, 129.1, 128.6, 126.3, 83.7,
74.35, 68.80, 40.02, 39.7, 36.7, 23.7, 21.4, 18.3; HRMS
calcd for C18H21NO4: 315.1470, found 315.1481.
3. +a) Arrayas, R. G.; Liebeskind, L. S. J. Am. Chem. Soc. 2001,
123, 6185. +b) Li, W.-T.; Pan, M.-H.; Wu, Y.-R.; Wang, S.-L.;
Liao, F.-L.; Liu, R.-S. J. Org. Chem. 2000, 65, 3761.
+c) Cheng, M.-H.; Yang, G.-M.; Chow, J.-F.; Lee, G.-H.; Peng,
S.-M.; Liu, R.-S. J. Chem. Soc., Chem. Commun. 1992, 934.
4. Pei, C.-C.; Liu, R.-S. Org. Lett. 2001, 3, 1295.
3.2.32. Synthesis of 11R,3aS,5aR,8aS,8bS)-1-acetyl-7-
phenylperhydrofuro[3,4-e]isoindole-6,8-dione 137). To a
dichloromethane solution +5 mL) of compound 36 +25 mg,
0.0793 mmol) was added PCC +34.2 mg, 0.159 mmol) and
5. For a review of enyne metathesis, see Mori, M. Topics in
Organometallic Chemistry; FuÈrstner, A., Ed.; Springer:
Berlin, 1998; Vol. 1, p133.
Ê
dry molecular sieves 4 A +35 mg) and the mixtures were
stirred for 3 h under room temperature. The solution was
®ltered through celite, concentrated and chromatographed
on a silica column +ether/hexaneˆ2/1) to give compound 37
+22.8 mg, 0.0726 mmol, 91%, Rfˆ0.24) as a colorless oil.
6. +a) Kitamura, T.; Mori, M. Org. Lett. 2001, 3, 1161. +b) Mori,
M.; Kitamura, T.; Sakakibara, N.; Sato, Y. Org. Lett. 2000, 2,
543. +c) Mori, M.; Sakakibara, N.; Kinoshita, A. J. Am. Chem.
Soc. 1997, 119, 12388. +d) Kinoshita, A.; Mori, M. J. Org.
Chem. 1996, 61, 8356. +e) Mori, M.; Tonogaki, K.;
Nishiguchi, N. J. Org. Chem. 2002, 67, 224. +f) Mori, M.;
Kitamura, T.; Sato, Y. Synthesis 2001, 654. +g) Kitamura,
T.; Sato, Y.; Mori, M. Chem. Commun. 2001, 1258.
7. +a) Duboc, R.; Henaut, C.; Savignac, M.; Genet, J.-P.;
Bhatnagar, N. Tetrahedron Lett. 2001, 2461. +b) Clark, J. S.;
Trevitt, G. P.; Boyall, D.; Stammen, B. J. Chem. Soc., Chem.
Commun. 1998, 2629. +c) Clark, J. S.; Hamelin, O. Angew.
Chem. 2000, 112, 380. +d) Stragies, R.; Voigtmann, U.;
Blechert, S. Tetrahedron Lett. 2000, 41, 5465. +e) Hoye,
T. R.; Donaldson, S. M.; Vos, T. Org. Lett. 1999, 1, 277.
8. +a) Barrett, A. G. M.; Baugh, S. P. D.; Braddock, C.; Flack, K.;
Gibson, V. C.; Giles, M. R.; Marshall, E. L.; Procopiou, P. A.;
White, A. J. P.; Williams, D. J. J. Org. Chem. 1998, 63, 7893.
+b) Barrett, A. G. M.; Baugh, S. P. D.; Braddock, C.; Flack, K.;
Gibson, V. C.; Procopiou, P. A. J. Chem. Soc., Chem.
Commun. 1997, 1375. +c) Renaud, J.; Graf, C.-D.; Oberer,
L. Angew. Chem., Int. Ed. Engl. 2000, 39, 3101. +d) Schuster,
M.; Lucas, N.; Blechert, S. Chem. Commun. 1997, 823.
+e) Stragies, R.; Schuster, M.; Blechert, S. Angew. Chem.,
Int. Ed. Engl. 1997, 36, 2518. +f) SchuÈrer, S. C.; Blechert, S.
Synlett 1998, 166. +g) Schuster, M.; Blechert, S. Tetrahedron
Lett. 1998, 39, 2295. +h) Stragies, R.; Schuster, M.; Blechert,
S. Chem. Commun. 1999, 237. +i) SchuÈrer, S. C.; Blechert, S.
Synlett 1999, 1879. +j) SchuÈrer, S. C.; Blechert, S. Chem.
Commun. 1999, 1203. +k) SchuÈrer, S. C.; Blechert, S.
Tetrahedron Lett. 1999, 40, 1877. +l) Kotha, S.; Halder, S.;
Brahmachary, E.; Ganesh, T. Synlett 2000, 853.
[a]D ˆ216.7 +c 1.0 CHCl3); IR +cm21): 1782 +m), 1708
25
+s), 1604 +m); 1H NMR +500 MHz, CDCl3): d 7.46±7.26 +m,
5H), 4.99 +d, Jˆ4.5 Hz, 1H), 4.16 +t, Jˆ8.5 Hz, 1H), 3.47 +t,
Jˆ8.0 Hz, 1H), 3.25±3.17 +m, 2H), 2.91±2.87 +m, 1H),
2.50±2.45 +m, 1H), 2.23 +s, 3H), 2.12±2.08 +m, 1H),
1.89±1.81 +m, 2H), 1.15±1.09 +m, 1H); 13C NMR
+125 MHz, CDCl3): d 209.8, 178.5, 177.8, 131.6, 129.1,
128.6, 126.2, 84.9, 75.1, 39.6, 38.0, 26.2, 22.8, 21.9;
HRMS calcd for C18H19NO4: 313.1314, found 313.1324.
3.2.33. Synthesis of 11S,3aS,5aR,8aS,8bS)-6,8-dioxo-7-
phenylperhydrofuro[3,4-e]isoindol-1-yl-acetate 138). To
a dichloromethane solution +5 mL) of 37 +50.0 mg, 0.16
mmol) were added sodium hydrogen carbonate +20.3 mg,
0.239 mmol) and m-chloroperbenzoic acid +88.1 mg, 0.477
mmol) at 08C. The solution was stirred for 8 h and added
with aqueous sodium sul®te solution, and washed with
aqueous sodium hydrogen carbonate. The solution was
extracted with dichloromethane, dried over MgSO4 and
eluted through a short silica bed +diethyl ether) to afford
25
lactol 38 +49.4 mg, 0.150 mmol, 94%, Rfˆ0.55), [a]D
ˆ
1
114.5 +c 1.0, CH2Cl2); IR +cm21): 1713 +s), 1597 +m); H
NMR +400 MHz, CDCl3): d 7.46±7.22 +m, 5H), 6.45 +d,
Jˆ2.0 Hz, 1H), 4.26 +t, Jˆ8.0 Hz, 1H), 3.66 +dd, Jˆ8.8,
4.4 Hz, 1H), 3.34 +t, Jˆ7.6 Hz, 1H), 3.15±3.13 +m, 1H),
2.88±2.83 +m, 1H), 2.68±2.65 +m, 1H), 2.04 +s, 3H),
1.95±1.93 +m, 2H), 1.81±1.79 +m, 1H), 1.25±1.22 +m,
1H); 13C NMR +100 MHz, CDCl3): d 178.2, 176.6, 170.3,
129.7, 129.1, 128.6, 100.1, 76.2, 43.5, 38.9, 37.7, 35.5, 23.9,
21.8, 21.1; HRMS calcd for C18H19NO5: 329.1263, found
329.1282.
9. +a) Smulik, J. A.; Diver, S. T. Org. Lett. 2000, 2, 2271.
+b) Smulik, J. A.; Diver, S. T. J. Org. Chem. 2000, 65,
1788. +c) Kinoshita, A.; Mori, M. Tetrahedron 1999, 55, 8155.
10. +a) Trnka, T. M.; Grubbs, R. H. Acc. Chem. Res. 2001, 34, 18.
+b) Furstner, A. Angew. Chem., Int. Ed. Engl. 2000, 39, 3013.
11. Stojanovic, A.; Renaud, P.; Schenk, K. Helv. Chim. Acta 1998,
81, 268.
Acknowledgements
The authors wish to thank National Science Council,
Taiwan for support of this work.
12. Mitsonobu, O. Synthesis 1980, 1.
13. Chen, M.-J.; Lo, C.-Y.; Chin, C.-C.; Liu, R.-S. J. Org. Chem.
2000, 65, 6362.
14. Ley, S. V.; Armstrong, A.; Diez-Martin, D.; Ford, M. J.; Grice,
P. J. Chem. Soc., Perkin Trans. 1 1991, 667.
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tungsten-mediated [312]-cycloaddition reactions. The latter
method is a non-metathesis reaction which used stoichio-
metric amount of propargyltungsten complexes. See Ref. 4.
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18. Crystal structure of compound 34 and spectral data of
compounds 33±35 have appeared in our previous study
which described the synthesis of chiral dienes based on