Palladium-catalyzed epimerization of γ-alkenyl-γ-butyrolactone derivatives

Article abstract of DOI:10.1016/j.tet.2010.08.035

γ-Alkenyl-α,β,γ-trisubstituted-γ- butyrolactones (12-16) and γ-alkenyl-furofurandione derivatives (21-Z-24-Z; 21-E-24-E; 25-Z-28-Z; and 25-E-28-E) were successfully epimerized in high yield by a palladium catalyst.

Full text of DOI:10.1016/j.tet.2010.08.035

Tetrahedron 66 (2010) 8468e8475
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Palladium-catalyzed epimerization of g-alkenyl-g-butyrolactone derivatives
*
Yung-Son Hon , Hsien-Fan Chen, Chen-Yi Kao, Ching-Zong Luo
Department of Chemistry and Biochemistry, National Chung Cheng University, Chia-Yi 62102, Taiwan, ROC
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 25 May 2010
Received in revised form 10 August 2010
Accepted 13 August 2010
Available online 19 August 2010
g
(
-Alkenyl-
21-Z-24-Z; 21-E-24-E; 25-Z-28-Z; and 25-E-28-E) were successfully epimerized in high yield by a pal-
ladium catalyst.
a,b,g-trisubstituted-g-butyrolactones (12e16) and g-alkenyl-furofurandione derivatives
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
Furofurandione
TsujieTrost reaction
Palladium-catalyzed allylation
Allylic isomerization
Epimerization
OAc
OAc
1. Introduction
R
R
THF, 1.5 h
PdCl (MeCN)2
The TsujieTrost reaction is the palladium-catalyzed allylation of
Br
Br
ð3Þ
2
nucleophiles, such as active methylenes, enolates, amines, and
phenols with allylic compounds, such as allyl acetates, allyl car-
bonates, and allyl bromides. The reaction occurs via intermediate
allylpalladium complexes, typically with overall retention of ste-
reochemistry (Eq.1).1 Inthe absence of anucleophile, Pd-catalyzed
allylic isomerization is possible. For example, substituted bicyclo
O
O
5
O
6
O
e5
Complete transfer of chirality in the [3,3]-sigmatropic rear-
rangement of allylic acetates 5 can be catalyzed by Pd (Eq. 3). The
reaction has been applied to stereocontrolled synthesis of prosta-
glandins that possess either the C-l5(S) or C-15(R) configuration.
2
þ
[
2.2.2]oct-5-en-2-one (3) can be converted to cis-fused hydro-
6
benzofuran derivative (4) when catalyzed by Pd(0) (Eq. 2).
7,8
We have completed the total syntheses of furofurandione
Tsuji-Trost
natural products by using 4-endo-hydroxy-2-oxabicyclo[3.3.0]oct-
R
PdL2
R
Reaction
R
9
7-en-3-one (7) as a building block. In this process, the key step
NuH
1
1A PdX
π-allyl complex
NuH: EWGCH EWG, R'SH,
2
ð1Þ
ð2Þ
is palladium-catalyzed epimerization of the g-alkenyl substituted
X
Nu
10
X: OAc, Br,
OCO Me
of bislactones. To the best of our knowledge, studies of the
2
3
2
recombination of the h p-allyl complex to give epimerized allylic
2
R'NH , ArOH
esters are rare in the literature. Herein, we describe palladium-
catalyzed epimerization of g-alkenyl-g-butyrolactone derivatives.
cat. Pd(PPh ) ,
2. Results and discussions
3
4
Ac
O
PPh , THF, rt
O
3
2.1. Synthesis of g-alkenyl-a,b,g-trisubstituted-g-
O
3
Ac
O
4
butyrolactones and their Pd-catalyzed epimerization
The endo-hydroxylactone 7 was treated with sodium hydride
and benzyl bromide to give the corresponding benzyl ether 8 and
exo-benzyloxylactone 9. Due to the
it was epimerized in situ to give 9 as the major product. Ozonolysis
a-acidity of the benzyl ether 8,
*
Corresponding author. Tel.: þ886 5 2720411x66412; fax: þ886 5 2721040;
e-mail address: cheysh@ccu.edu.tw (Y.-S. Hon).
0
040-4020/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.08.035

Y.-S. Hon et al. / Tetrahedron 66 (2010) 8468e8475
8469
ꢁ
of lactone 7 in CH
2
Cl
2
at ꢀ78 C followed by reduction with Me
2
S
A plausible mechanism for the palladium-catalyzed epimeriza-
tion is illustrated using the example of conversion of compound 12
gave tricyclic hemiacetal 10 as a 10:1 mixture of two diastereomers
in 68% yield. The axial anomer was the major isomer, as confirmed
by its 2D-NOESY spectrum (Scheme 1).
to 12a in Figure 1. The coordination of the Pd(0)-catalyst to the
2
double bond forms an
h
p
-allyl complex. An oxidative addition,
3
during which the leaving group is expelled, gives the
complex A. The isomerization from A to B occurs to relieve A
strain. The interconversion of intermediate B to C is ascribed to
electrostatic attraction of the ion pair. Recombination of the CeO
h p-allyl
1,3
-
O
O
11
BnO
O
a
BnO
8%
O
O
+
bond of C causes
group isomerization. The torsional strain from
is relieved. The double bond geometry of the
retained (Fig. 1).
g
-stereogenic center epimerization and
and substituents
-substituent is
g-octenyl
2
56%
8
9
b
g
HO
O
b
HO
O
O
7
b
6
8%
O
O
O
O
10
single bond
rotation
Pd(0)
HO
O
HO
O
H
ꢁ
Scheme 1. Reagents and conditions: (a) NaH, BnBr, THF, 0 C to rt; 8 h. (b) (1) O
3
,
allylic
R
R
H
relieve
CH
2
Cl
2
, ꢀ78 ꢁC; (2) Me
2
S, CH
2
Cl
2
, 0 C, 6 h.
ꢁ
12
displacement
S 2
1,3
A
strain
LnPd
R = n-Hexyl
O
N
R
A
The tricyclic hemiacetal 10 reacted with 2 equiv of Ph
CHC 13-n (11) or 2 equiv of Ph P]CHCO Me (13) to give the
corresponding Z,Z-Wittig product 12 in 36% yield and E,E-Wittig
product 14 in 77% yield, respectively. Compound 8 was cleaved by
3
P]
R
O
H
6
H
3
2
11
HO
O
HO
O
H
C-O Bond
formation
H
R
H
R
electrostatic
attraction of
the ion pair
ozone followed by reduction with Me
reacted with 2 equiv of Ph P]CHCO
2
S. The resulting product was
Me (13) to give the corre-
LnPd
LnPd
R
R
3
2
B
sponding E,E-Wittig product 15 in 77% yield. Similarly, compound 9
was converted to the corresponding E,E-Wittig product 16 in 76%
yield (Scheme 2).
O
C
H
O
α
HO
β
epimerization
γ
unchanged
12a
R
O
O
R
Changed to E-form
HO
O
a
HO
O
c, 5 h
n-hexyl
82%
γ
Figure 1. Plausible mechanism of the Pd-catalyzed epimerization of compound 12.
36%
1
2a
2.2. Synthesis of g-alkenyl-furofurandione derivatives and
their Pd-catalyzed epimerization
10
1
2
n-hexyl
n-hexyl
n-hexyl
O
O
b
c, 14 h
82%
MeO C
HO
O
Tricyclic hemiacetal 10 reacted with semistable phosphonium
ylide 17 to give separable lactols 21Z (52%) and 21E (14%). Com-
pound 10 reacted with semistable phosphonium ylide 18 to give
lactol 22Z in 78% yield stereoselectively. The hemiacetal 10 reacted
with semistable phosphonium ylides 19e20 to give Wittig products
γ
HO
77%
O
MeO C
2
2
14
1
4a
CO Me
2
O
CO Me
2
O
23Ze24Z and 23Ee24E, respectively. The cis-isomer is the major
BnO
O
one in each case. In this study, there were two pathways for epi-
merization starting from lactols 22Ze24Z and 22Ee24E. The oxi-
dation of lactol to lactone followed by epimerization is pathway A
in Scheme 3, and the epimerization of lactol followed by oxidation
is pathway B in Scheme 3.
By way of pathway A, lactols 21Ze24Z were oxidized by
Jones reagent to give the corresponding bislactones 25Ze28Z,
respectively, in high yields. The trans-analogues 21Ee24E were
oxidized by Jones reagent to give the corresponding bislactones
25Ee28E, respectively, in high yields. Both bislactones 25Z and
BnO
O
d, b
7
γ
c, 17 h
81%
8
7% MeO C
2
MeO C
2
1
5a
15
CO Me
2
CO Me
2
O
O
d, b
6%
MeO C
9
c, 96 h
81%
BnO
O
BnO
O
7
γ
MeO C
2
2
16
16a
CO Me
CO Me
2
2
25E were treated with Pd catalyst to give the same epimerized
Scheme 2. Reagents and conditions: (a) 2 equiv Ph
3
P]CHC
6
H
13 (11), THF; (b) 2 equiv
P, THF, rt; (d) (1) O
product 25a, in which the -stereogenic center was epimerized
and the Z-olefinic side chain of 25Z was converted to a more stable
E-form. Similarly, both 26Ze28Z and 26Ee28E were converted to
g
Ph
CH
3
P]CHCO
2
Me (13), THF; (c) 0.1 equiv Pd(OAc)
2
, 1 equiv Ph
3
3
,
, ꢀ78 ꢁC; (2) Me
ꢁ
2
Cl
2
2
S, CH
2
Cl
2
, 0 C, 6 h.
26ae28a, respectively (Scheme 3).
All of the substituents of
g-alkenyl-
g-butyrolactones 12, 14, and
By way of pathway B, the lactol 21Z was epimerized with Pd
1
5 were syn to each other. When they were treated with palladium
catalyst, their -chiral centers were epimerized to give the corre-
sponding 12ae15a. In the case of compound 12, -chiral center
epimerization was concomitant with -(Z)-octenyl group isomeri-
zation. Interestingly, the geometry of its -(Z)-octenyl group was
unchanged. The relative stereochemistries of compound 16 at the
, and positions were anti-syn to each other. Its -chiral center
catalyst first. The crude product was then oxidized by Jones reagent
to give furofurandione 25a, in which the -stereogenic center was
g
g
g
epimerized and the Z-olefinic side chain was isomerized to a more
stable E-form. Similarly, both 26Ze28Z and 26Ee28E were con-
verted to 26ae28a, respectively (Scheme 3).
g
b
13
a
,
Interestingly, under Sonogashira coupling reaction conditions,
b
g
g
vinyl bromide 26Z reacted with 1-hexyne to give the crossed
coupling product 29 in 71% yield. The crossed coupling epimeri-
zation at the C-4 chiral center and the isomerization of the Z-double
was also epimerized by the palladium catalyst to give the corre-
sponding antieanti diastereomer 16a (Scheme 2).

8470
Y.-S. Hon et al. / Tetrahedron 66 (2010) 8468e8475
1
0
to give the corresponding aldehyde, which was treated with
vinylmagnesium bromide to give the -butyrolactones (33-syn
a, b, c, or d
g
and 33-anti; 35-syn and 35-anti; 37-syn and 37-anti). Two di-
O
astereomers were separated by silica gel column chromatography
O
(Scheme 5).
O
O
pathway A
pathway A
HO
e
O
O
+
HO
R
O
O
O
R
O
R = Ph 21Z
R = Br 22Z
52% + 21E14%
78% + 22E --
56% + 23E 14%
e
Bn
+
a, b, c
a, b, c
O
OEt
O
Ph
Ph
33-syn
R = CH=CH 23Z
2
R = (E)-CH=CHBu-n 24Z 62% + 24E 14%
O
33-anti
3
2
O
O
O
O
O
O
O
pathway B
O
+
O
O
OEt
H
R
H
R
O
R
f, e
R
f, e
R
R = Ph 25E 88%
R = Br 26E -----
R = Ph 35-syn
R = Ph 35-anti
R = Ph 25Z 87%
R = Br 26Z 88%
R = Ph 34
R = OTBS 37-syn R = OTBS 37-anti
R = OTBS 36
R = CH=CH 27E 85%
R = CH=CH 27Z 85%
2
, ꢀ78 ꢁC; (2) Et
2
Scheme 5. Reagents and conditions:(a) (1) O
CHMgBr; (c) Separation.
3
, CH
2
Cl
2
3 2
N; (b) CH ]
R = (E)-CH=CHBu-n 28E 86%
R = (E)-CH=CHBu-n 28Z 85%
O
O
O
f
f
O
When the
treated with Pd catalyst in tetrahydrofuran for 48 h, a mixture of
3-syn and 33-anti in a ratio of 65:35 with 74% mass recovery
a-benzyl-g-vinyl-g-butyrolactone 33-syn was
R
3
R = Ph 25a
R = Br 26a
84% from 25Z; 84% from 25E (Path A)
2% from 21Z; 73% from 21E (Path B)
81% from 26Z (Path A)
2% from 22Z (Path B)
82% from 27Z; 83% from 27E (Path A)
1% from 23Z; 71% from 23E (Path B)
was obtained (Table 1, entry 1). The product ratio was de-
termined by integration of the benzylic methylene resonance
peaks of the crude products. Similarly, when compound 33-anti
was treated with Pd catalyst, it gave a 63:37 mixture of the
epimerized 33-syn and starting material 33-anti (entry 2). Pre-
sumably, the relative energy difference between 33-syn and 33-
anti is not big enough to allow the reactant and product existing
7
7
R = CH=CH 27a
2
7
R = (E)-CH=CHBu-n 28a 83% from 28Z; 82% from 28E (Path A)
0% from 24Z; 71% from 24E (Path B)
7
P]CHPh (17), THF, ꢀ78 ꢁC to
in an equilibrium state. The epimerization of b-phenyl-g-vinyl-g-
Scheme 3. Reagents and conditions: (a) (1) 1.1 equiv Ph
3
ꢁ
butyrolactone 35-syn for 40 h gave a mixture of 35-syn and 35-
anti in a ratio of 91:9 with 81% mass recovery (entry 3). The
product ratio was determined by integration of the peaks of the
benzylic proton. When 35-anti was used as the reactant, a similar
equilibrium ratio of 35-syn and 35-anti was obtained (entry 4).
rt, 13 h; (2) separation; (b) (1) 1.1 equiv Ph
separation; (c) (1) 1.1 equiv (E)-Ph
separation; (d) (1) 1.1 equiv Ph P]CHCH]CH
3
P]CHBr (18), THF, ꢀ78 C to rt, 13 h; (2)
ꢁ
3
P]CHCH]CH
2
(19), THF, ꢀ78 C to rt, 13 h; (2)
ꢁ
3
Ph
2 3
P]CHBu-n (20), THF, ꢀ78 C to rt,
ꢁ
1
3 h; (2) separation; (e) Jones reagent, acetone, 0 C, 2 h; (f) 0.1 equiv Pd(OAc)
2
, 1 equiv
3
Ph P, THF, rt.
The epimerization of b-silyoxy-g-vinyl-g-butyrolactone 37-syn for
bond occurred in the same flask. The catalytic hydrogenation of
compound 29 yielded the corresponding saturated product 30
in 91% yield (Scheme 4). Compound 30 is known to introduce an
32 h gave a mixture of 37-syn and 37-anti in a ratio of 54:46 with
81% mass recovery (entry 5). The product ratio was determined
by integration of the vinylic proton. When 37-anti was used as
the reactant, a similar equilibrium ratio of 37-syn and 37-anti was
obtained (entry 6).
14
a
-methylene moiety to give avenaciolide (31).
O
O
Table 1
Pd-catalyzed epimerization of di-substituted-
g
-vinyl-
g
-butyrolactones 33e37
a
O
b
O
O
O
7
1%
Entry Reactant Time (h) Product ratio
Mass recovery yield (%)
Br
O
O
a
a
1
2
3
4
5
6
33-syn
33-anti
35-syn
35-anti
37-syn
37-anti
48
48
40
40
32
36
33-syn/33-anti¼65:35
33-syn/33-anti¼63:37
81
79
81
78
81
78
26Z
29
b
Bu
35-syn/35-anti¼91:9
O
b
c
c
35-syn/35-anti¼90:10
37-syn/37-anti¼54:46
37-syn/37-anti¼57:43
O
O ref. 11
Avenaciolide (31)
91%
O
a
Determined by integration of the peaks of the benzylic proton (
d
3.31 for 33-syn;
3.41e3.43 for
d 5.82 for 37-syn;
Oct-n
0
d
3
d
3.21 for 33-anti).
3
b
Determined by integration of the peaks of the benzylic proton (
5-syn; 3.86e3.91 for 35-anti).
d
ꢁ
Scheme 4. Reagents and conditions: (a) cat. PdCl (PPh ) , cat. CuI, Et N, THF, 60 C,
2 3 2 3
d
5
h; (b) (1) H
2
, Pd/C, EtOAc, rt.
c
Determined by integration the peaks of the vinylic proton (
5.97 for 37-anti).
2
.3. Synthesis of di-substituted-
g
-vinyl-
g
-butyrolactones and
3. Conclusions
their Pd-catalyzed epimerization
The
and -alkenyl-furofurandione derivatives (21-Ze24-Z; 21-Ee24-
E) were successfully epimerized in high yield by a palladium
catalyst. Their -(Z)-alkenyl substituent was also isomerized to
g-alkenyl-a,b,g-trisubstituted-g-butyrolactones (12e16)
The
according to JohnsoneClaisen rearrangement.
was cleaved by ozone, followed by treatment with triethylamine
g
,
d
-unsaturated esters 32, 34, and 36 were prepared
g
15,16
The double bond
17
g

Y.-S. Hon et al. / Tetrahedron 66 (2010) 8468e8475
8471
a more stable E-form. For the di-substituted-
g
-vinyl-
g
-butyro-
4.3. General procedure of the double bond cleavage by ozone
3-hydroxy-2,5,10-trioxa-tricyclo[5.2.1.0 ]decan-6-one (10)
4
,8
lactones (33, 35, 36), Pd-catalyzed epimerization could only at-
tain an equilibrium mixture. The Sonogashira coupling of vinyl
bromide 26Z with 1-hexyne gave crossed coupling product 29.
This reaction is highly efficient because three different reactions
are involved in the same flask. Compound 29 is an important
precursor of the avenaciolide (31).
A 100 mL of two-necked flask fitted with a glass tube to admit
ozone, a CaCl drying tube, and a magnetic stirring bar were
2
charged with compound 7 (280 mg, 2.0 mmol) in CH
2
Cl
2
(20 mL).
ꢁ
The flask was cooled to ꢀ78 C and ozone was bubbled through the
solution. When the solution turned blue, ozone addition was
stopped. Nitrogen was passed through the solution until the blue
4
4
. Experimental
color was discharged. To the reaction mixture was added Me
2
S
(525 mg, 0.28 mL). After the addition, the cooling bath was re-
.1. General
moved and the reaction mixture was stirred at rt. The reaction was
complete in 6 h and the reaction mixture was concentrated, chro-
matographed on the silica gel column to give a mixture of two
diastereomers (axialeequatorial¼10:1) 10 (234 mg, 1.36 mmol) in
All reactions were carried out under nitrogen. Unless otherwise
noted, materials were obtained from commercial suppliers and
used without further purification. Melting points were determined
by using a ThomaseHoover melting point apparatus and were
uncorrected. The 1H and C NMR spectra were recorded on
a Bruker Avance DPX400 spectrometer, and chemical shifts were
given in parts per million downfield from tetramethylsilane (TMS).
IR spectra were taken with a PerkineElmer 682 spectrophotom-
eter and only noteworthy absorptions were listed. Mass spectra
were measured on a JEOL JMS-700/Shimazu QP2010 (National
Cheng Kung University) by electronic impact at 70 eV (unless
otherwise indicated). High Resolution Mass Spectroscopy (HRMS)
was measured on a Finnigan/Thermo Quest MAT mass spectrom-
eter (National Chung Hsing University). ESI was measured on a ESI
trap tadem mass spectrometer (Thermo Finnigan LCQ-DUO, CA,
USA) (National Sun Yat-sen University). Compound 7 was prepared
68% yield as a colorless oil. TLC R
f
¼0.28 (hexane/EtOAc¼1:4). Axial
1
anomer: H NMR (acetone-d
6
, 400 MHz) 6.21 (s, 1H), 5.46 (d,
d
13
J¼3.6 Hz, 1H), 5.02 (s, 1H), 4.69 (d, J¼8.3 Hz, 1H), 4.37 (d, J¼4.8 Hz,
1H), 3.53 (ddd, J¼3.6, 4.8, and 8.3 Hz, 1H), 2.97 (d, J¼12.4 Hz, 1H),
13
1.79 (ddd, J¼3.6, 3.6, and 12.4 Hz, 1H); C NMR (acetone-d
6
,
100 MHz)
H NMR (acetone-d , 400 MHz)
d
173.9, 98.9, 91.8, 81.1, 76.6, 37.4, 30.6. Equatorial anomer:
1
6
d
6.21 (s, 1H), 5.51 (d, J¼10.4 Hz,
1H), 5.06 (d, J¼8.7 Hz, 1H), 4.86 (dd, J¼2.2 and 8.7 Hz, 1H), 4.28 (d,
J¼5.2 Hz, 1H), 3.53 (ddd, J¼2.2, 3.8, and 5.2 Hz, 1H), 2.54 (d,
13
J¼12.9 Hz, 1H), 1.84 (ddd, J¼3.8, 10.4, and 12.9 Hz, 1H); C NMR
6
(acetone-d , 100 MHz) d 174.2, 99.6, 90.1, 81.2, 76.3, 38.3, 30.4; IR
ꢀ
1
(CH
2
Cl
2
): 3472, 3059, 2957, 1740, 1440, 1230, 1131, 1038 cm ; EI
þ
Mass (m/z): 172 (M , 24), 143 (27), 128 (63), 97 (100), 82 (53), 69
7 8 5
(94), 55 (32); HRMS (m/z) calcd for C H O 172.0372, found:
172.0368.
9
by the reported procedure.
4
.2. (3S
cyclopenta[b]furan-2-one (8) and (3R
benzyloxy)-3,3a,4,6a-tetrahydro-2H-cyclopenta[b]furan-2-
one (9)
*
,3aR
*
,6aR
*
)-3-(Benzyloxy)-3,3a,4,6a-tetrahydro-2H-
4.4. (3aR
*
,4R
*
,6aS
*
)-2-Hydroxy-4-[(Z)-1-octenyl]perhydro-
0
*
,3aR ,6aR )-3-
*
*
furo[3,4-b]furan-6-one (12 ) and (3S
[(Z)-2-nonenyl]-5-[(Z)-1-octenyl]tetrahydro-2-furanone (12)
*
,4R
*
,5R )-3-hydroxy-4-
*
(
þ ꢀ
3 2 6
To a flask containing Ph P eCH eC H13en Br (1042 mg,
To a flask containing NaH (4.02 g, 100.2 mmol, 60% dispersion in
2.36 mmol) in THF (12 mL) was added n-BuLi (1.48 mL, 2.36 mmol,
ꢁ
mineral oil) in THF (110 mL) was added a solution of compound 7
1.6 M in hexane) at ꢀ78 C and stirred for 15 min. To the resulted
ꢁ
(
1
(
8
11.7 g, 83.5 mmol) in THF (50 mL) dropwise at 0 C and stirred it for
ylide solution was added a solution of compound 10 (200 mg,
1.18 mmol) in THF (2 mL). After the addition, the cooling bath was
removed and the reaction mixture was warmed slowly to rt. After
0 min. To the resulted solution was added benzyl bromide
ꢁ
11.9 mL, 100.2 mmol) at 0 C and then warmed slowly to rt. After
ꢁ
ꢁ
h, the reaction mixture was cooled at 0 C and quenched with
12 h, the reaction mixture was cooled at 0 C and quenched with
saturated NaHCO
with ethyl acetate and the organic layer was dried over MgSO
concentrated, and chromatographed on the silica gel column to
give compound 8 (5.38 g, 23.4 mmol, 28% yield) and compound 9
3
solution. The aqueous solution was extracted
a saturated NH
with ethyl acetate and the organic layer was dried over MgSO
concentrated, and chromatographed on the silica gel column to
4
Cl solution. The aqueous solution was extracted
4
,
4
,
0
13
give compound 12 (48 mg, 0.19 mmol, 16% yield) and compound
12 (143 mg, 0.42 mmol, 36% yield).
(
10.76 g, 46.76 mmol, 56% yield). Compound 8: TLC R
f
¼0.34 (hex-
7.32e7.40 (m, 5H),
.19 (dd, J¼5.6 and 2.8 Hz, 1H), 5.88e5.91 (m, 1H), 5.25 (dd, J¼6.6
1
0
12
¼0.45 (hexane/EtOAc¼3:1); 1H NMR
ane/EtOAc¼3:1); H NMR (CDCl
3
, 400 MHz)
d
Compound 12 : TLC R
(CDCl , 400 MHz) d 5.70e5.78 (m, 2H), 5.36e5.67 (m, 6H), 4.90 (d,
f
6
3
and 2.2 Hz, 1H), 4.94 (d, J¼12.0 Hz, 1H), 4.77 (d, J¼12.0 Hz, 1H), 4.39
J¼8.0 Hz, 1H), 4.83 (d, J¼8.8 Hz, 1H), 3.48e3.53 (m, 1H), 3.23e3.30
(
(
1
2
d, J¼9.2 Hz, 1H), 3.06e3.13 (m, 1H), 2.76e2.84 (m, 1H), 2.34e2.42
m,1H); 13C NMR (CDCl
,100 MHz) 174.5,140.3,137.0,128.4,128.0,
27.9, 127.8, 85.7, 74.3, 72.7, 39.6, 31.3; IR (CH
(m, 1H), 2.90 (s, 1H), 2.80 (s, 1H), 1.95e2.27 (m, 8H), 1.15e1.33 (m,
13
3
d
8H), 0.87e0.90 (m, 6H); C NMR (CDCl
3
, 100 MHz)
d
164.7, 163.9,
2
Cl
2
): 3063, 2931,
137.1, 135.1, 125.8, 123.5, 100.4, 99.4, 78.5, 78.0, 75.8, 73.9, 42.6, 40.7,
34.4, 33.4, 31.6, 30.8, 29.23, 29.25, 28.8, 28.2, 28.0, 22.56, 22.55,
ꢀ
1
þ
860, 1774, 1144, 1103, 995 cm ; EI Mass (m/z): 230 (M , 0.43), 124
(
23), 91 (100), 79 (32), 67 (27); HRMS (m/z) calcd for C14
H
14
O
3
14.0; IR (CH
2
Cl
2
): 3458, 3198, 3025, 2967, 1776, 1432, 1253,
ꢀ
1
þ
2
30.0943, found: 230.0938. Compound 9: TLC R
f
¼0.41 (hexane/
7.31e7.39 (m, 5H),
.01e6.03 (m, 1H), 5.86e5.89 (m, 1H), 5.49e5.50 (m, 1H), 4.98 (d,
J¼11.8 Hz, 1H), 4.73 (d, J¼11.8 Hz, 1H), 3.90 (d, J¼5.8 Hz, 1H),
1125 cm ; EI Mass (m/z): 254 (M , 13), 131 (59), 104 (100), 77 (47);
1
EtOAc¼3:1); H NMR (CDCl
3
, 400 MHz)
d
HRMS (m/z) calcd for C14
Compound 12: TLC R
(CDCl , 400 MHz) d 5.71e5.78 (m, 1H), 5.52e5.57 (m, 1H),
22 4
H O 254.1518, found: 254.1515.
6
f
¼0.52 (hexane/EtOAc¼4:1); 1H NMR
3
13
3
(
7
1
.01e3.07 (m, 1H), 2.67e2.75 (m, 1H), 2.28e2.34 (m, 1H); C NMR
CDCl , 100 MHz) 175.0, 137.1, 136.8, 129.5, 128.5, 128.2, 127.1, 87.0,
9.5, 72.3, 43.2, 36.6; IR (CH
5.32e5.46 (m, 2H), 5.23e5.28 (m, 1H), 4.49e4.54 (m, 1H),
2.65e2.71 (m, 1H), 2.55 (s, 1H), 1.95e2.34 (m, 6H), 1.27e1.39 (m,
16H), 0.86e0.88 (m, 6H); C NMR (CDCl
3
d
13
2
Cl
2
): 3065, 2926, 2858, 1776, 1123,
3
, 100 MHz) d 177.2, 136.5,
ꢀ
1
þ
020, 919 cm ; EI Mass (m/z): 230 (M , 0.10), 124 (45), 91 (100), 79
132.2, 126.0, 123.9, 76.6, 70.6, 44.9, 31.7, 31.6, 29.3, 29.2, 28.9, 28.8,
(
2
37), 67 (24); HRMS (m/z) calcd for C14
30.0945.
H
14
O
3
230.0943, found:
27.8, 27.3, 22.6, 22.5, 21.0, 14.05, 14.02; IR (CH
3048, 2913, 1783, 1452, 1235, 1199 cm ; EI Mass (m/z): 336 (M , 4),
2
Cl
2
): 3458, 3125,
ꢀ
1
þ

8472
Y.-S. Hon et al. / Tetrahedron 66 (2010) 8468e8475
2
3
61 (68), 55 (100), 53 (15); HRMS (m/z) calcd for C21
36.2664, found: 336.2659.
H
36
O
3
reduction with Ph
reaction mixture was concentrated. To a flask containing crude
product in THF (12 mL) was added Ph P]CHCO Me (735.6 mg,
3
P (262.3 mg, 1.0 mmol). After stirring for 3 h, the
3
2
4
.5. General procedure of the Pd-catalyzed epimerization
2.2 mmol) at rt and stirred for 3 h. The reaction mixture was con-
centrated and chromatographed on the silica gel column to give
4
.5.1. (3S ,4R ,5S )-3-Hydroxy-4-[(Z)-2-nonenyl]-5-[(E)-1-octenyl]-
*
*
*
compound 15 (291.7 mg, 0.78 mmol, 77% yield) as a pale yellow oil.
1
tetrahydro-2-furanone (12a). Under nitrogen atmosphere, to a so-
lution of compound 12 (100 mg, 0.30 mmol) in THF (6 mL) were
added Pd(OAc)
.30 mmol) at rt. After stirring for 5 h, the reaction mixture was
filtered through Celite. The filtrate was concentrated and chroma-
tographed on the silica gel column to give compound 12a (83 mg,
TLC R
f
¼0.43 (hexane/EtOAc¼3:1); H NMR (CDCl
3
, 400 MHz)
d
7.32e7.37 (m, 5H), 6.82 (dt, J¼7.2 and 15.6 Hz, 1H), 6.27 (dd, J¼8.0
2
(7.3 mg, 0.03 mmol) and Ph
3
P
(86.6 mg,
and 11.6 Hz, 1H), 6.10 (ddd, J¼1.2, 6.8, and 8.0 Hz, 1H), 6.01 (dd,
J¼1.2 and 11.6 Hz, 1H), 5.81 (dd, J¼1.2 and 15.6 Hz, 1H), 4.92 (d,
J¼12.0 Hz,1H), 4.68 (d, J¼12.0 Hz, 1H), 4.10 (d, J¼6.4 Hz, 1H), 3.74 (s,
3H), 3.71 (s, 3H), 2.96e3.03 (m, 1H), 2.39e2.47 (m, 1H), 2.26e2.33
0
1
3
0
.25 mmol, 82% yield) as a pale yellow oil. TLC R
f
¼0.48 (hexane/
(m, 1H); C NMR (CDCl
3
, 100 MHz) d 173.5, 166.4, 165.8, 145.3,
1
EtOAc¼4:1); H NMR (CDCl
3
, 400 MHz) d
5.80 (dt, J¼6.8 and
144.2, 136.4, 128.6, 128.3, 128.2, 123.1, 122.8, 76.6, 73.4, 72.3, 51.7,
1
1
5.6 Hz, 1H), 5.50e5.56 (m, 1H), 5.44 (ddt, J¼1.2, 6.8, and 15.6 Hz,
51.4, 43.0, 26.1; IR (CH
1456,1326,1248,1158 cm ; EI Mass (m/z): 374 (M , 0.25),169 (19),
2
Cl
2
): 3143, 3126, 2976, 1789, 1784, 1775,
ꢀ
1
þ
H), 5.30e5.38 (m, 1H), 4.71 (dd, J¼4.4 and 6.8 Hz, 1H), 4.48 (d,
J¼6.8 Hz, 1H), 2.57 (s, 1H), 2.28e2.43 (m, 1H), 1.98e2.13 (m, 6H),
22 7
98, 91 (100), 65 (5); HRMS (m/z) calcd for C20H O 374.1366,
found: 374.1360.
13
1
1
3
.27e1.39 (m, 16H), 0.88 (t, J¼7.2 Hz, 6H); C NMR (CDCl
00 MHz) 176.9, 136.2, 133.3, 126.0, 125.2, 83.1, 68.9, 45.9, 32.1,
1.7, 31.6, 29.5, 28.9, 28.76, 28.71, 27.3, 23.1, 22.6, 22.5, 14.0; IR
3
,
d
4.5.5. Methyl (E)-4-(2S
*
,3R
*
,4R )-4-(benzyloxy)-2-[(E)-3-methoxy-
*
ꢀ1
(
CH
2
Cl
2
): 3466, 3148, 3092, 2956, 1766, 1477, 1245, 1123 cm ; EI
Mass (m/z): 336 (M , 1.74), 261 (33), 55 (100), 53 (14); HRMS (m/z)
calcd for C21H O 336.2664, found: 336.2668.
36 3
3-oxo-1-propenyl]-5-oxotetrahydro-3-furanyl-2-butenoate
(15a). Compound 15a was prepared by the general procedure of
the Pd-catalyzed epimerization described in Section 4.5. Starting
from compound 15 (100 mg, 0.35 mmol) gave compound 15a
þ
4
.5.2. Methyl (E)-4-(2R
oxo-1-propenyl]-5-oxotetrahydro-3-furanyl-2-butenoate
a flask containing compound 10 (150 mg, 0.87 mmol) in CH
12 mL) was added Ph P]CHCO Me (610.9 mg, 1.83 mmol) at rt
*
,3R
*
,4R
*
)-4-(hydroxy)-2-[(E)-3-methoxy-3-
(14). To
Cl
(106.0 mg, 0.28 mmol) in 81% yield. Compound 15a: TLC R
f
¼0.38
1
(hexane/EtOAc¼3:1); H NMR (CDCl
3
, 400 MHz) d 7.32e7.40 (m,
2
2
5H), 6.76e6.87 (m, 2H), 6.12 (dd, J¼1.2 and 15.6 Hz, 1H), 5.88 (d,
J¼13.2 Hz, 1H), 4.90 (d, J¼11.6 Hz, 1H), 4.86 (dd, J¼6.0 and 6.0 Hz,
1H), 4.62 (d, J¼11.6 Hz, 1H), 4.06 (d, J¼5.6 Hz, 1H), 3.76 (s, 3H), 3.73
(
3
2
and stirred for 3 h. The reaction mixture was concentrated and
chromatographed on the silica gel column to give compound 14
13
3
(s, 3H), 2.65e2.69 (m, 1H), 2.26e2.35 (m, 2H); C NMR (CDCl ,
(
193.3 mg, 0.67 mmol) as a colorless oil in 77% yield. The polarity of
product 14 is very close to that of Ph PO. The purification of com-
pound 14 from Ph PO is tedious. The contamination of Ph PO did
not affect the following Pd-catalyzed epimerization reaction. TLC
100 MHz)
d
172.2, 166.1, 165.6, 144.0, 141.7, 136.1, 128.5, 128.3, 128.2,
Cl ): 3156,
3
123.7, 123.2, 80.3, 72.8, 72.2, 51.9, 51.5, 45.1, 27.2; IR (CH
3094, 2956, 1784, 1781, 1771, 1423, 1354, 1218, 1115 cm ; EI Mass
(m/z): 374 (M , 0.33), 169 (21), 98 (45), 91 (100), 65 (7); HRMS (m/z)
calcd for C20
2
2
ꢀ
1
3
3
þ
1
R
d
f
¼0.25 (hexane/EtOAc¼1:1);
H
NMR (CDCl
3
,
400 MHz)
22
H O
7
374.1366, found: 374.1363.
6.92e6.85 (m, 2H), 6.15 (dd, J¼1.6 and 15.6 Hz, 1H), 5.85 (dd, J¼1.6
and 15.6 Hz, 1H), 5.11 (ddd J¼2.0, 5.6 and 6.0 Hz, 1H, OCHCH]CH),
4.5.6. Methyl (E)-4-(2R
*
,3R ,4R )-4-(benzyloxy)-2-[(E)-3-methoxy-
*
*
4
1
1
5
.61 (d, J¼7.2 Hz, 1H, CHOH), 3.75 (s, 3H), 3.71 (s, 3H), 2.97e2.90 (m,
3-oxo-1-propenyl]-5-oxotetrahydro-3-furanyl-2-butenoate
(16). Compound 9 was cleaved by ozone according to the general
procedure described in Section 4.3. Compound 9 (193.3 mg,
1
3
H), 2.52e2.47 (m, 1H), 2.26e2.19 (m, 1H); C NMR (CDCl
175.6, 166.6, 165.6, 145.4, 140.7, 123.6, 123.6, 78.4, 69.7,
2.0, 51.6, 43.8, 26.1; IR (CH Cl ): 3358, 2950, 2917, 2851,1783, 1712,
3
,
00 MHz)
d
2
2
0.52 mmol) in CH
duction with Ph P (136.4 mg, 0.52 mmol). After stirring for 3 h, the
reaction mixture was concentrated. To a flask containing crude
product in THF (12 mL) was added Ph P]CHCO Me (367.8 mg,
.1 mmol) at rt and stirred for 3 h. The reaction mixture was con-
2 2
Cl (6 mL) reacted with ozone followed by re-
ꢀ
1
1
655, 1441, 1313, 1280, 1194, 1171, 1137, 1038, 981 cm ; EI Mass (m/
3
þ
z): 284 (M , 1.2), 169 (38), 98 (100), 65 (52); HRMS (m/z) calcd for
284.0896, found: 284.0899.
C
H
13 16
O
7
3
2
1
4
.5.3. Methyl
oxo-1-propenyl]-5-oxotetrahydro-3-furanyl-2-butenoate
14a). Compound 14a was prepared by the general procedure of
(E)-4-(2S
*
,3R
*
,4S
*
)-4-hydroxy-2-[(E)-3-methoxy-3-
centrated and chromatographed on the silica gel column to give
compound 16 (150.0 mg, 0.40 mmol, 76% yield) as a pale yellow oil.
1
(
TLC R
d
f
¼0.49 (hexane/EtOAc¼3:1); H NMR (CDCl
3
, 400 MHz)
the Pd-catalyzed epimerization described in Section 4.5. Starting
from compound 14 (100 mg, 0.35 mmol) gave compound 14a
81.5 mg, 0.29 mmol) in 82% yield. TLC
7.29e7.39 (m, 5H), 6.79e6.88 (m, 2H), 6.12 (dd, J¼1.6 and 16.0 Hz,
1H), 5.87 (d, J¼15.6 Hz, 1H), 5.22 (dd, J¼1.6 and 6.4 Hz, 1H), 5.03 (d,
J¼11.2 Hz, 1H), 4.68 (d, J¼11.2 Hz, 1H), 3.89 (d, J¼8.4 Hz, 1H), 3.75 (s,
(
R
f
¼0.48 (hexane/
1
13
EtOAc¼1:1); H NMR (CDCl
3
, 400 MHz)
d
6.86e6.96 (m, 2H), 6.11
3H), 3.72 (s, 3H), 2.81e2.89 (m, 1H), 2.30e2.36 (m, 1H); C NMR
(
4
2
dd, J¼1.6 and 15.6 Hz, 1H), 5.96 (d, J¼15.6 Hz, 1H), 4.90 (ddd, J¼1.6,
(CDCl
128.2, 128.1, 123.7, 123.5, 76.6, 75.7, 72.3, 51.8, 51.5, 44.2, 30.2; IR
(CH Cl ): 3156, 3095, 2908, 1792, 1786, 1781, 1425, 1377, 1214,
1196 cm ; EI Mass (m/z): 374 (M , 0.81), 169 (25), 98 (44), 91
3
, 100 MHz) d 173.2, 165.9, 165.3, 143.7, 140.2, 136.4, 128.4,
.8 and 4.8 Hz, 1H), 4.50 (d, J¼6.8 Hz, 1H), 3.77 (s, 3H), 3.75 (s, 3H),
13
.70e2.77 (m, 1H), 2.52e2.58 (m, 1H), 2.22e2.29 (m, 1H); C NMR
,100 MHz) 175.4,166.3,165.7,144.2,142.1,124.2,122.7, 79.6,
7.7, 52.0, 51.7, 44.2, 28.1; IR (CH
2
2
ꢀ1
þ
(
CDCl
3
d
6
1
2
Cl
2
): 3457, 3149, 3023, 2944, 1789,
22 7
(100), 65 (11); HRMS (m/z) calcd for C20H O 374.1366, found:
374.1364.
ꢀ
1
þ
782, 1778, 1325, 1237, 1082 cm ; EI Mass (m/z): 284 (M , 1.23),
16 7
169 (41), 98 (100), 65 (54); HRMS (m/z) calcd for C13H O
2
84.0896, found: 284.0898.
4.5.7. Methyl (E)-4-(2S
*
,3R
*
,4R )-4-(benzyloxy)-2-[(E)-3-methoxy-
*
3
-oxo-1-propenyl]-5-oxotetrahydro-3-furanyl-2-butenoate
4
3
(
.5.4. Methyl (E)-4-(2R
*
,3R
*
,4R
*
)-4-(benzyloxy)-2-[(E)-3-methoxy-
(16a). Compound 16a was prepared by the general procedure of
the Pd-catalyzed epimerization described in Section 4.5. Starting
from compound 16 (100 mg, 0.35 mmol) gave compound 16a
-oxo-1-propenyl]-5-oxotetrahydro-3-furanyl-2-butenoate
15). Compound 8 was cleaved by ozone according to the general
procedure described in Section 4.3. Compound 8 (230.1 mg,
.0 mmol) in CH Cl (10 mL) reacted with ozone followed by
(106.0 mg, 0.28 mmol) in 81% yield. Compound 16a: TLC R
f
¼0.42
1
1
2
2
(hexane/EtOAc¼3:1); H NMR (CDCl
3
, 400 MHz) d 7.31e7.41 (m,

Y.-S. Hon et al. / Tetrahedron 66 (2010) 8468e8475
8473
5
H), 6.75e6.87 (m, 2H), 6.13 (dd, J¼1.2 and 15.6 Hz, 1H), 5.80 (d,
(dd, J¼7.2 and 16.0 Hz, 1H), 5.07 (d, J¼7.6 Hz, 1H), 4.94 (dd, J¼7.2
and 7.2 Hz, 1H), 3.25 (dddd, J¼4.0, 7.2, 7.6, and 9.2 Hz, 1H), 2.98 (d,
J¼15.6 Hz, 1H), 5.06 (d, J¼11.6 Hz, 1H), 4.75 (d, J¼11.6 Hz, 1H), 4.57
13
(
3
dd, J¼6.0 and 6.0 Hz,1H), 3.98 (d, J¼9.6 Hz,1H), 3.77 (s, 3H), 3.73 (s,
J¼9.2 and 18.0 Hz, 1H), 2.67 (dd, J¼4.0 and 18.0 Hz, 1H); C NMR
1
3
H), 2.38e2.48 (m, 3H); C NMR (CDCl
3
, 100 MHz)
d
173.2, 165.9,
3
(CDCl , 100 MHz) d 171.4, 169.7, 138.3, 135.6, 128.5, 128.2, 127.7,
1
65.6, 142.7, 141.1, 136.3, 128.6, 128.5, 128.4, 124.4, 123.7, 77.9, 76.0,
123.4, 78.4, 75.6, 38.8, 30.5; IR (CH
1760, 1438, 1356, 1155 cm ; EI Mass (m/z): 244 (M , 3), 131 (6), 104
(100), 77 (51); HRMS (m/z) calcd for C14H O 244.0736, found:
12 4
2
Cl
2
): 3198, 3124, 2926, 1766,
ꢀ
1
þ
72.4, 52.0, 51.6, 46.8, 31.3; IR (CH
2
Cl
2
): 3102, 3088, 2905, 1787, 1783,
ꢀ1
þ
1769, 1456, 1377, 1245, 1123 cm ; EI Mass (m/z): 374 (M , 0.83),
169 (25), 98 (51), 91 (100), 65 (13); HRMS (m/z) calcd for C20
22
H O
7
244.0738.
374.1366, found: 374.1361.
4
.5.10. (3aR
*
,4R
*
,6aS )-4-[(Z)-2-Bromo-1-ethenyl]perhydro-furo-
*
4
.5.8. (3aR
*
,4R
*
,6aS
*
)-4-[(Z)-2-Phenyl-1-ethenyl]perhydro-furo[3,4-
,4R ,6aS )-4-[(E)-2-phenyl-1-
[3,4-b]furan-2,6-dione (26Z). Compound 26Z was prepared by the
general procedure described in 4.11. Compound 10 (367 mg,
2.13 mmol) reacted with ylide 18 to give compound 22Z (413.8 mg,
1.66 mmol, 78% yield). The lactol 22Z (123 mg, 0.49 mmol) was
oxidized by Jones reagent to give compound 26Z as a white solid
b]furan-2,6-dione (25Z) and (3aR
ethenyl]perhydro-furo[3,4-b]furan-2,6-dione (25E). To a flask con-
*
*
*
þ
ꢀ
taining Ph
3
P eCH
2
ePh Br (1018 mg, 2.35 mmol) in THF (8 mL) was
ꢁ
added n-BuLi (1.47 mL, 2.35 mmol, 1.6 M in hexane) at ꢀ78 C and
stirred for 15 min. To the resulted ylide 17 solution was added
a solution of compound 10 (367 mg, 2.13 mmol) in THF (2 mL). The
(107.4 mg, 0.43 mmol) in 88% yield. TLC R
f
¼0.55 (hexane/
ꢁ
1
EtOAc¼2:1); mp: 84.9e85.7 C; H NMR (CDCl
3
, 400 MHz) 6.61
(dd, J¼2.0, and 7.6 Hz,1H), 6.35 (dd, J¼6.8 and 7.6 Hz,1H), 5.52 (ddd,
d
ꢁ
reaction was stirred at ꢀ78 C for 1 h and the reaction mixture was
warmed slowly to rt. After 12 h, the reaction mixture was cooled at
J¼2.0, 6.8, and 7.0 Hz, 1H), 5.15 (d, J¼6.8 Hz, 1H), 3.78e3.86 (m, 1H),
ꢁ
13
0
C and quenched with a saturated NH
4
Cl (10 mL) solution. The
2.73 (dd, J¼9.8 and 18.6 Hz,1H), 2.59 (dd, J¼7.4 and 18.6 Hz,1H);
C
aqueous solution was extracted with ethyl acetate and the organic
layer was dried over MgSO , concentrated, and chromatographed
on the silica gel column to give compound 21Z (270.2 mg,
.11 mmol, 52% yield) and compound 21E (72.3 mg, 0.29 mmol, 14%
NMR (CDCl
28.3; IR (CH
3
, 100 MHz)
d 173.0, 169.7, 129.6, 113.2, 77.5, 75.9, 38.5,
ꢀ1
4
2
Cl ): 3054, 2987, 1801, 1265, 1190, 1160, 1078 cm ; ESI
2
þ
79
Mass (m/z): 269 (M þ23); HRMS (m/z) calcd for C
8 7 4
H BrO Na
1
268.9425, found: 268.9427.
yield). To a solution of lactol 21Z (123 mg, 0.50 mmol) in 5 mL of
ꢁ
acetone was added Jones reagent at 0 C dropwise until the per-
4.5.11. (3aR
*
,4S
*
,6aS )-4-[(E)-2-Bromo-1-ethenyl]perhydro-furo[3,4-
*
ꢁ
sistence of the orange solution. After stirring at 0 C for 30 min, the
excess Jones reagent was quenched by 2-propanol. The reaction
was diluted by water (2 mL) and extracted with CH
b]furan-2,6-dione (26a). Compound 26a was prepared by the
general procedure of the Pd-catalyzed epimerization described in
Section 4.5. Starting from compound 26Z (216.7 mg, 0.89 mmol)
gave compound 26a (177.3 mg, 0.72 mmol) in 81% yield. Compound
26a can also be prepared from compound 22Z sequentially by Pd-
2 2
Cl . The organic
layer was dried over anhydrous MgSO . The filtrate was concen-
4
trated and chromatographed on the silica gel column to give
compound 25Z as a white solid (106 mg, 0.43 mmol) in 87% yield.
Similarly, the lactol 21E (50.0 mg, 0.20 mmol) was also oxidized by
Jones reagent to give 25E as a white solid (42.9 mg, 0.18 mmol) in
catalyzed epimerization and Jones oxidation (pathway B, 72%
1
yield). TLC R
f
¼0.24 (hexane/EtOAc¼2:1); H NMR (CDCl
3
, 400 MHz)
d
6.63 (dd, J¼0.8 and 13.6 Hz, 1H), 6.26 (dd, J¼6.8 and 13.6 Hz, 1H),
8
8% yield.
5.03 (d, J¼7.6 Hz, 1H), 4.75 (dd, J¼5.6 and 6.8 Hz, 1H), 3.19 (dddd,
Compound 25Z: TLC
9.6e80.4 C; H NMR (CDCl
R
f
¼0.33 (hexane/EtOAc¼1:1); mp
J¼4.4, 5.6, 7.6, and 9.2 Hz, 1H), 2.97 (dd, J¼9.2 and 18.6 Hz, 1H), 2.60
ꢁ
1
13
7
3
, 400 MHz) 7.20e7.43 (m, 5H), 6.96
d
(dd, J¼4.4 and 18.6 Hz, 1H); C NMR (CDCl
3
, 100 MHz) d 173.2,
(
d, J¼11.6 Hz, 1H), 5.69 (dd, J¼8.8, and 11.6 Hz, 1H), 5.53 (dd, J¼8.8
169.5, 133.3, 119.6, 83.8, 76.3, 40.7, 32.1; IR (CH
2
Cl
2
): 3055, 2989,
ꢀ1
þ
and 8.8 Hz, 1H), 5.13 (d, J¼8.0 Hz, 1H), 3.57 (dddd, J¼8.0, 8.0, 8.8,
1798, 1421, 1266, 1199, 1148, 1075 cm ; EI Mass (m/z): 246 (M ,
0.6), 183 (4) 139 (14), 123 (45), 95 (52), 81 (100), 55 (27); HRMS
(m/z) calcd for C H BrO 245.9528, found: 245.9522.
8 7 4
and 9.6 Hz, 1H), 2.77 (dd, J¼8.0 and 18.4 Hz, 1H), 2.70 (dd, J¼9.6 and
8.4 Hz, 1H); 13C NMR (CDCl
, 100 MHz)
d
173.3, 170.0, 137.3, 134.9,
79
1
3
1
3
2 2
28.7, 128.5, 128.3, 123.9, 77.2, 75.5, 39.8, 28.3; IR (CH Cl ): 3187,
ꢀ
1
052, 2963, 1789, 1787, 1415, 1398, 1184 cm ; EI Mass (m/z): 244
*,4R**,6aS*
4.5.12. (3aR )-4-[(1Z)-1,3-Butadienyl]perhydro-furo[3,4-b]-
þ
(
M , 13), 131 (39), 104 (100), 77 (17); HRMS (m/z) calcd for C14
H
12
O
4
furan-2,6-dione (27Z) and (3aR
*
,4R ,6aS )-4-[(1E)-1,3-butadienyl]
*
*
2
44.0736, found: 244.0729.
perhydro-furo[3,4-b]furan-2,6-dione (27E). Compounds 27Z and 27E
were prepared by the general procedure described in Section 4.5.7.
Compound 10 (300 mg, 1.74 mmol) reacted with ylide 19 to give
compound 23Z (191.2 mg, 0.97 mmol, 56% yield) and compound
23E (47.8 mg, 0.24 mmol, 14% yield). The lactol 23Z (100 mg,
0.51 mmol) was oxidized by Jones reagent to give compound 27Z as
a white solid (84.1 mg, 0.43 mmol) in 85% yield. The lactol 23E
(32 mg, 0.16 mmol) was oxidized by Jones reagent to give compound
27E as a white solid (26.4 mg, 0.14 mmol) in 85% yield.
Compound 25E: TLC
R
f
¼0.25 (hexane/EtOAc¼1:1) mp
ꢁ
1
8
1.8e82.6 C; H NMR (CDCl
3
, 400 MHz) 7.29e7.41 (m, 5H), 6.82
d
(
d, J¼16.0 Hz, 1H), 6.07 (dd, J¼6.4 and 16.0 Hz, 1H), 5.35 (dd, J¼6.4
and 6.4 Hz, 1H), 5.20 (d, J¼8.4 Hz, 1H), 3.64 (ddt, J¼6.4, 8.4, and
13
8
d
.8 Hz, 1H), 2.70 (d, J¼8.8 Hz, 2H); C NMR (CDCl
3
, 100 MHz)
171.2, 169.3, 138.1, 135.8, 128.3, 128.1, 127.9, 122.8, 77.8, 76.0, 38.7,
3
0.7; IR (CH
2
Cl
2
): 3165, 3024, 2954, 1778, 1772, 1424, 1305,
ꢀ
1
þ
1174 cm ; EI Mass (m/z): 244 (M , 25), 131 (42), 104 (100), 77 (19);
HRMS (m/z) calcd for C14
H
12
O
4
244.0736, found: 244.0726.
Compound 27Z: TLC
7.2e88.1 C; H NMR (CDCl
R
f
¼0.48 (hexane/EtOAc¼1:1); mp
ꢁ
1
8
3
, 400 MHz)
d
6.51 (ddd, J¼10.8, 11.2,
4
.5.9. (3aR ,4S ,6aS )-4-[(E)-2-Phenyl-1-ethenyl]perhydro-furo[3,4-
*
*
*
and 18.8 Hz, 1H), 6.35 (dd, J¼11.2 and 11.2 Hz, 1H), 5.59 (dd, J¼7.2
and 7.2 Hz, 1H), 5.39e5.47 (m, 3H), 5.15 (d, J¼8.0 Hz, 1H), 3.60 (ddt,
b]furan-2,6-dione (25a). Compound 25a was prepared by the
general procedure of the Pd-catalyzed epimerization described in
Section 4.5. Starting from compound 25Z (216.7 mg, 0.89 mmol)
gave compound 25a (182.4 mg, 0.75 mmol) in 84% yield. Starting
from compound 25E (216.7 mg, 0.89 mmol) gave compound 25a
13
J¼7.2, 8, and 8.8 Hz, 1H), 2.66 (d, J¼8.8 Hz, 2H); C NMR (CDCl
3
,
100 MHz)
d 173.3, 170.1, 135.4, 130.1, 123.3, 123.0, 76.5, 75.3, 39.8,
28.1; IR (CH
2
Cl
2
): 3156, 3048, 2933, 1781, 1777, 1325, 1298,
ꢀ1
þ
1184 cm ; EI Mass (m/z): 194 (M , 2.34), 169 (21), 98 (100), 65
(
182.4 mg, 0.75 mmol) in 84% yield. Compound 25a can also be
(31); HRMS (m/z) calcd for C10
H
10
O
4
194.0579, found: 194.0577.
¼0.42 (hexane/EtOAc¼1:1) mp
, 400 MHz) 6.34e6.48 (m, 2H), 5.58
prepared from either 21E or 21Z sequentially by Pd-catalyzed
epimerization and Jones oxidation (pathway B).
Compound 27E: TLC R
f
ꢁ
1
89.6e90.3 C; H NMR (CDCl
3
d
Compound 25a: TLC R
CDCl , 400 MHz)
f
¼0.21 (hexane/EtOAc¼1:1); 1H NMR
(dd, J¼6.4 and 14.8 Hz,1H), 5.38 (d, J¼16.0 Hz,1H), 5.30 (d, J¼9.2 Hz,
(
3
d
7.33e7.42(m, 5H), 6.75 (d, J¼16.0 Hz, 1H), 6.16
1H), 5.21 (dd, J¼6.4 and 6.4 Hz, 1H), 5.15 (d, J¼8.4 Hz, 1H), 3.57

8474
Y.-S. Hon et al. / Tetrahedron 66 (2010) 8468e8475
(
2
1
1
dddd, J¼4.4, 6.4, 8.4, and 8.4 Hz, 1H), 2.65 (dd, J¼4.4 and 8.4 Hz,
gave compound 28a (173.4 mg, 0.76 mmol) in 83% yield. Starting
from compound 28E (200 mg, 0.68 mmol) gave compound 28a
(164 mg, 0.65 mmol) in 82% yield. Compound 28a can also be
prepared from either 24Z or 24E sequentially by Pd-catalyzed
13
3
H); C NMR (CDCl , 100 MHz) d 173.3, 169.9, 136.0, 134.6, 124.4,
21.3, 78.4, 76.6, 39.7, 28.1; IR (CH
2
Cl
2
): 3184, 3092, 2988, 1784,
ꢀ1
þ
776, 1324, 1287, 1176 cm ; EI Mass (m/z): 194 (M , 3), 169 (41), 98
(
1
100), 65 (33); HRMS (m/z) calcd for C10
94.0574.
H
10
O
4
194.0579, found:
epimerization and Jones oxidation (pathway B). TLC R
f
¼0.5 (hex-
ꢁ
1
ane/EtOAc¼2:1); mp: 60.8e61.5 C; H NMR (CDCl
3
, 400 MHz)
d
6.33 (dd, J¼10.4 and 15.2 Hz, 1H), 6.04 (dd, J¼7.2 and 15.2 Hz, 1H),
4
.5.13. (3aR
*
,4S
*
,6aS
*
)-4-[(1E)-1,3-Butadienyl]perhydro-furo[3,4-b]-
5.87 (dt, J¼7.2 and 15.2 Hz, 1H), 5.51 (dd, J¼7.2 and 15.2 Hz, 1H),
5.01 (d, J¼7.2 Hz, 1H), 4.77 (dd, J¼6.8 and 10.4 Hz,1H), 3.11e3.17 (m,
1H), 2.93 (dd, J¼9.2 and 18.4 Hz, 1H), 2.59 (dd, J¼4.0 and 18.4 Hz,
1H), 2.12 (td, J¼7.2 and 13.6 Hz, 2H), 1.25e1.42 (m, 4H), 0.90 (t,
furan-2,6-dione (27a). Compound 27a was prepared by the general
procedure of the Pd-catalyzed epimerization described in Section
4
pound 27a (82.7 mg, 0.43 mmol) in 82% yield. Starting from com-
pound 27E (60 mg, 0.31 mmol) gave compound 27a (49.9 mg,
0
.5. Starting from compound 27Z (100 mg, 0.52 mmol) gave com-
1
3
J¼6.8 Hz, 3H); C NMR (CDCl
3
,100 MHz)
d
172.8,170.5,140.0,135.9,
Cl ):
127.8, 124.0, 84.4, 77.1, 41.3, 32.3, 32.2, 31.0, 22.1, 13.8; IR (CH
2925, 2854, 1790, 1212, 1145, 1074 cm ; EI Mass (m/z): 250 (M ,
58), 138 (23) 113 (29), 81 (100), 68 (44), 55 (69); HRMS (m/z) calcd
2
2
ꢀ1
þ
.26 mmol) in 83% yield. Compound 27a can also be prepared from
either 22Z or 22E sequentially by Pd(0)-epimerization and Jones
1
oxidation (pathway B). TLC R
CDCl , 400 MHz)
6.29e6.41 (m, 2H), 5.67 (dd, J¼6.0 and 14.0 Hz,
H), 5.37 (d, J¼13.2 Hz, 1H), 5.30 (d, J¼10.4 Hz, 1H), 5.02 (d,
J¼7.6 Hz, 1H), 4.81 (dd, J¼6.0 and 6.0 Hz, 1H), 3.15 (dddd, J¼4.0, 6.0,
.6, and 9.2 Hz, 1H), 2.94 (dd, J¼9.2 and 18.0 Hz, 1H), 2.61 (dd, J¼4.0
f
¼0.38 (hexane/EtOAc¼1:1); H NMR
18 4
for C14H O 250.1205, found: 250.1211.
(
1
3
d
4.5.16. (3aR
furan-2,6-dione (29). To a mixture of vinyl bromide 26Z (100 mg,
0.40 mmol), PdCl (PPh (5.6 mg, 0.008 mmol), and CuI (3.1 mg,
0.0016 mmol) in THF (10 mL) was added Et N (0.05 mL, 0.4 mmol)
*
,4S
*
,6aS
*
)-4-[(E)-1-Octen-3-ynyl]perhydro-furo[3,4-b]-
7
2
3 2
)
13
and 18.0 Hz, 1H); C NMR (CDCl
3
, 100 MHz)
d
172.3, 169.6, 137.1,
3
1
34.0, 123.9, 121.1, 79.1, 76.1, 39.8, 27.9; IR (CH
2
Cl
2
): 3175, 3065,
and 1-hexyne (0.13 mL, 1.2 mmol) in THF (1 mL). The reaction was
heated to 60 C for 5 h. The reaction mixture was filtered through
ꢀ
1
þ
ꢁ
2
915, 1765, 1763, 1316, 1298, 1125 cm ; EI Mass (m/z): 194 (M , 6),
169 (45), 98 (100), 65 (31); HRMS (m/z) calcd for C10
H
10
O
4
194.0579,
Celite. The filtrate was concentrated and chromatographed on silica
found: 194.0578.
gel column to give product 29 (71.3 mg, 0.29 mmol, 71% yield) as
1
a pale yellow oil. TLC R
400 MHz)
f
¼0.63 (hexane/EtOAc¼2:1); H NMR (CDCl
3
,
4.5.14. (3aR
*
,4R
*
,6aS
*
)-4-[(1Z,3E)-1,3-Octadienyl]perhydro-furo[3,4-
,4R ,6aS )-4-[(1E,3E)-1,3-octa-
d
5.96 (dd, J¼6.0 and 15.6 Hz, 1H), 5.85 (d, J¼15.6 Hz, 1H),
b]furan-2,6-dione (28Z) and (3aR
*
*
*
5.02 (d, J¼7.6 Hz, 1H), 4.78 (dd, J¼6.0 and 6.0 Hz, 1H), 3.12e3.19 (m,
1H), 2.95 (dd, J¼9.2 and 18.4 Hz, 1H), 2.60 (dd, J¼4.0 and 18.4 Hz,
1H), 2.32 (td, J¼2.0 and 7.2 Hz, 1H), 1.25e1.57 (m, 4H), 0.92 (t,
dienyl]perhydro-furo[3,4-b]furan-2,6-dione (28E). Compounds 28Z
and 28E were prepared by the general procedure described in
Section 4.5.7. Compound 10 (300 mg, 1.74 mmol) reacted with ylide
13
J¼7.2 Hz, 3H); C NMR (CDCl
3
, 100 MHz)
d
173.0, 169.2, 134.7, 116.0,
Cl ): 2960,
2
0 to give compound 24Z (272.2 mg, 1.08 mmol, 62% yield) and
compound 18E (60.5 mg, 0.24 mmol, 14% yield). The lactol 24Z
100 mg, 0.40 mmol) was oxidized by pyridinium chlorochromate
83.3, 77.2, 76.3, 40.9, 32.1, 30.4, 21.9, 19.0, 13.5; IR (CH
2
2
ꢀ
1
2934, 2217, 1797, 1266, 1205, 1145, 1076 cm ; EI Mass (m/z): 248
þ
(
(M , 20), 178 (18), 108 (55), 93 (100), 79 (88), 65 (56); HRMS (m/z)
to give compound 28Z as a white solid (85.0 mg, 0.34 mmol) in 85%
yield. The lactol 24E (30.1 mg, 0.14 mmol) was oxidized by pyr-
idinium chlorochromate to give compound 228Z as a white solid
calcd for C14
H
16
O
4
248.1049, found: 248.1048.
4.5.17. (3aR
*
,4S
*
,6aS )-4-Octylperhydro-furo[3,4-b]furan-2,6-dione
*
(
27.8 mg, 0.12 mmol) in 86% yield.
(30). A mixture of enyne 29 (50 mg, 0.20 mmol) and 10%Pd/C
(2.0 mg, 0.02 mmol) in ethyl acetate (2 mL) was stirred under hy-
drogen balloon for 9 h. The reaction mixture was filtered through
Celite. The filtrate was concentrated and chromatographed on silica
Compound 28Z: TLC
R
f
¼0.47 (hexane/EtOAc¼2:1); mp:
1.5e62.3 C; 1H NMR (CDCl
ꢁ
, 400 MHz)
d
6.31 (dd, J¼11.0 and
6
1
3
2.9 Hz, 1H), 6.16 (dd, J¼7.5 and 12.9 Hz, 1H), 5.93 (dt, J¼7.2
and 14.8 Hz, 1H), 5.58 (dd, J¼7.5 and 14.8 Hz, 1H), 5.23 (dd, J¼8.0
and 11.0 Hz, 1H), 5.13 (d, J¼8.4 Hz, 1H), 3.58 (ddt, J¼8.0, 8.4, and
gel column to give product 30 (46.6 mg, 0.18 mmol, 91% yield) as
1
a colorless oil. TLC R
400 MHz)
f
¼0.72 (hexane/EtOAc¼1.5:1); H NMR (CDCl
3
,
8
1
d
.8 Hz, 1H), 2.66 (d, J¼8.8 Hz, 2H), 2.15 (td, J¼7.2 and 7.2 Hz, 1H),
d
5.01 (d, J¼7.6 Hz, 1H), 4.34 (td, J¼5.2 and 7.6 Hz, 1H),
13
.30e1.43 (m, 4H), 0.91 (t, J¼7.2 Hz, 3H); C NMR (CDCl
3
, 100 MHz)
3.01e3.07 (m, 1H), 2.94 (dd, J¼9.2 and 18.0 Hz, 1H), 2.55 (dd, J¼4.0
173.4, 170.1, 141.8, 135.5, 123.6, 119.7, 76.6, 75.4, 39.9, 32.6, 30.9,
and 18.0 Hz, 1H), 1.83e1.87 (m, 2H), 1.27e1.48 (m, 12H), 0.88 (t,
13
2
1
8
8.2, 22.2, 13.8 (CH
147, 1077 cm ; EI Mass (m/z): 250 (M , 72), 129, 110 (38), 91 (90),
3
); IR (CH
2
Cl
2
): 3055, 2964, 1799, 1266, 1197,
J¼6.8 Hz, 3H); C NMR (CDCl
3
, 100 MHz)
d
173.4, 169.7, 84.7, 77.2,
Cl ):
ꢀ
1
þ
40.2, 35.4, 32.8, 31.7, 29.2, 29.1, 29.1, 24.9, 22.6, 14.0; IR (CH
2
2
ꢀ
1
þ
1 (100), 67 (63), 54 (53); HRMS (m/z) calcd for C14
H
18
O
4
250.1205,
3054, 2928, 1797, 1265, 1145, 1076 cm ; EI Mass (m/z): 254 (M ,
3.9), 179 (14), 150 (22), 113 (46), 97 (100), 55 (86); HRMS (m/z) calcd
found: 250.1206.
Compound 28E: TLC
R
f
¼0.35 (hexane/EtOAc¼2:1); mp:
, 400 MHz)
6.39 (dd, J¼10.4 and
22 4
for C14H O 254.1518, found: 254.1510.
ꢁ
6
1
1
3.6e64.2 C; 1H NMR (CDCl
3
d
5.2 Hz, 1H), 6.05 (dd, J¼10.4 and 15.2 Hz, 1H), 5.86 (dt, J¼6.8 and
5.2 Hz, 1H), 5.42 (dd, J¼10.4 and 15.2 Hz), 5.18 (dd, J¼6.8
and 10.4 Hz, 1H), 5.14 (d, J¼8.0 Hz, 1H), 3.54 (ddd, J¼8.0, 8.8, and
0.4 Hz, 1H), 2.65 (d, J¼8.8 Hz, 2H), 2.12 (td, J¼6.8 and 9.9 Hz, 1H),
4.5.18. (3S
and (3R
Under nitrogen atmosphere, to a solution of compound 33-syn
(100 mg, 0.49 mmol) in THF (4 mL) were added Pd(OAc) (11.0 mg,
0.049 mmol) and Ph P (141.4 mg, 0.30 mmol) at rt. After stirring for
*
,5S
*
)-3-Benzyl-5-vinyltetrahydro-2-furanone
(33-syn)
*
,5S
*
)-3-benzyl-5-vinyltetrahydro-2-furanone (33-anti).
1
1
d
2
13
.29e1.41 (m, 4H), 0.90 (t, J¼7.2 Hz, 3H); C NMR (CDCl
3
, 100 MHz)
3
173.4, 170.1, 139.7, 136.4, 127.8, 121.0, 79.0, 76.6, 39.7, 32.2, 30.9,
40 h, the reaction mixture was filtered through Celite. The filtrate
was concentrated and chromatographed on the silica gel column to
give a mixture of compound 33-syn and 33-anti in 81% mass re-
covery yield. Their ratio was determined by the integration of the
2
1
C
8.1, 22.1, 13.8; IR (CH
2
Cl
2
): 3056, 2928, 1793, 1286, 1150, 1073,
ꢀ1
þ
005 cm ; ESI Mass (m/z): 273 (M þ23); HRMS (m/z) calcd for
14
H
18
O
4
Na 273.1103, found: 273.1105.
benzylic proton (d 3.31 for 33-syn; d 3.21 for 33-anti). If the reactant
4
.5.15. (3aR ,4S ,6aS )-4-[(1E,3E)-1,3-Octadienyl]perhydro-furo[3,4-
*
*
*
of the Pd-catalyzed epimerization was 33-anti, a mixture of com-
pound 33-syn and 33-anti in 79% mass recovery yield.
b]furan-2,6-dione (28a). Compound 28a was prepared by the
general procedure of the Pd-catalyzed epimerization described in
Section 4.5. Starting from compound 28Z (210.0 mg, 0.84 mmol)
Compound 33-syn: TLC R
(CDCl , 400 MHz)
f
¼0.56 (hexane/EtOAc¼4:1); 1H NMR
3
d
7.18e7.32 (m, 5H), 5.80 (ddd, J¼6.0, 10.4, and

Y.-S. Hon et al. / Tetrahedron 66 (2010) 8468e8475
8475
1
7.2 Hz, 1H), 5.34 (d, J¼17.2 Hz, 1H), 5.23 (d, J¼10.4 Hz, 1H), 4.75 (dt,
J¼6.0 and 10.4 Hz, 1H), 3.31 (dd, J¼4.0 and 13.6 Hz, 1H), 2.90e2.94
m, 1H), 2.71 (dd, J¼2.0 and 13.6 Hz, 1H), 2.33e2.40 (m, 1H),
.67e1.75 (m, 1H); 13C NMR (CDCl
, 100 MHz) 177.8, 138.9, 136.5,
28.7, 128.4, 127.9, 120.8, 116.6, 79.7, 38.2, 37.1, 34.3; IR (CH Cl ):
32 h, the reaction mixture was filtered through Celite. The filtrate
was concentrated and chromatographed on the silica gel column to
give a mixture of compound 37-syn and 37-anti in 81% mass re-
covery yield. Their ratio was determined by the integration of the
vinylic proton (d 5.86 for 37-syn; d 6.00 for 37-anti). If the reactant
of the Pd-catalyzed epimerization was 37-anti, a mixture of com-
pound 37-syn and 37-anti in 78% mass recovery yield.
(
1
1
3
d
2
2
ꢀ
1
3133, 2944, 1787, 1423, 1346, 1105, 1015 cm ; ESI Mass (m/z): 225
þ
(
2
M þ23); HRMS (m/z) calcd for C13
14 2
H O Na 225.0891, found:
25.0890.
Compound 37-syn: TLC R
(CDCl , 400 MHz)
f
¼0.50 (hexane/EtOAc¼6:1); 1H NMR
Compound 33-anti: TLC R
f
¼0.53 (hexane/EtOAc¼4:1); 1H NMR
3
d
5.82 (ddd, J¼5.6, 10.8, and 17.2 Hz, 1H), 5.41 (d,
(
CDCl
3
, 400 MHz)
d
7.19e7.33 (m, 5H), 5.81 (ddd, J¼5.2, 10.8, and
J¼17.2 Hz, 1H), 5.30 (d, J¼10.8 Hz, 1H), 4.70e4.72 (m, 1H), 4.24 (dt,
1
4
1
7.2 Hz, 1H), 5.30 (d, J¼17.2 Hz, 1H), 5.20 (d, J¼10.8 Hz, 1H),
J¼4.0 and 6.4 Hz, 1H), 2.74 (dd, J¼6.4 and 17.6 Hz, 1H), 2.44 (dd,
13
.78e4.82 (m, 1H), 3.21 (dd, J¼4.4 and 14.0 Hz, 1H), 2.87e2.93 (m,
H), 2.77 (dd, J¼9.6 and 14.0 Hz, 1H), 2.13e2.21 (m, 1H), 2.02e2.09
J¼4.0 and 17.6 Hz, 1H), 0.88 (s, 9H), 0.03 (s, 6H); C NMR (CDCl
3
,
100 MHz)
d
174.5, 132.8, 118.1, 87.4, 72.5, 37.3, 25.4, 17.8, ꢀ4.90,
m, 1H); 13C NMR (CDCl
, 100 MHz)
d
178.3, 138.2, 135.5, 128.8,
ꢀ4.93; IR (CH
Cl
2
): 3123, 2978, 1745, 1423, 1315, 1105, 1025 cm
ꢀ1
;
(
3
2
þ
128.7, 126.9, 116.8, 77.9, 40.2, 36.1, 33.0; IR (CH
2
Cl
2
): 3145, 2925,
ESI Mass (m/z): 265 (M þ23); HRMS (m/z) calcd for C12
22 3
H O SiNa
ꢀ
1
þ
1
785, 1415, 1222, 1145, 1035 cm ; ESI Mass (m/z): 225 (M þ23);
265.1236, found: 265.1235.
HRMS (m/z) calcd for C13
H
14
O
2
Na 225.0891, found: 225.0892.
Compound 37-anti: TLC R
CDCl , 400 MHz)
f
¼0.56 (hexane/EtOAc¼6:1); 1H NMR
(
3
d
5.97 (ddd, J¼6.0, 10.4 and 16.8 Hz, 1H), 5.43 (d,
4
.5.19. (4S
and (4R
Under nitrogen atmosphere, to a solution of compound 35-syn
100 mg, 0.53 mmol) in THF (5 mL) were added Pd(OAc) (11.9 mg,
P (139.0 mg, 0.53 mmol) at rt. After stirring for
0 h, the reaction mixture was filtered through Celite. The filtrate
*
,5R
*
)-4-Phenyl-5-vinyltetrahydro-2-furanone
(35-syn)
J¼16.8 Hz, 1H), 5.35 (d, J¼10.4 Hz, 1H), 4.75e4.81 (m, 1H),
4.46e4.52 (m, 1H), 2.73 (dd, J¼6.8 and 17.6 Hz, 1H), 2.48 (dd, J¼4.4
*
,5R
*
)-4-phenyl-5-vinyltetrahydro-2-furanone (35-anti).
13
3
and 17.6 Hz, 1H), 0.86 (s, 9H), 0.01 (s, 6H); C NMR (CDCl ,
(
2
100 MHz)
d
173.6, 132.8, 120.8, 79.7, 73.4, 36.5, 27.5, 19.4, ꢀ4.3,
1
ꢀ
;
0
.053 mmol) and Ph
3
ꢀ4.5; IR (CH
2
Cl
2
): 3138, 2945, 1758, 1333, 1325, 1145, 1075 cm
þ
4
ESI Mass (m/z): 265 (M þ23); HRMS (m/z) calcd for C12
22 3
H O SiNa
was concentrated and chromatographed on the silica gel column to
give a mixture of compound 35-syn and 35-anti in 81% mass re-
covery yield. Their ratio was determined by the integration of the
265.1236, found: 265.1235.
Acknowledgements
benzylic proton (d 3.41e3.43 for 35-syn; d 3.86e3.91 for 35-anti). If
the reactant of the Pd-catalyzed epimerization was 35-anti, a mix-
We are grateful to the National Science Council, National Chung
Cheng University, and Academia Sinica for financial support.
ture of compound 35-syn and 35-anti in 78% mass recovery yield.
1
Compound 35-anti: TLC R
CDCl , 400 MHz)
2.8 Hz, 1H), 5.29 (dt, J¼1.2 and 12.8 Hz, 1H), 5.25 (dt, J¼1.2 and
f
¼0.78 (hexane/EtOAc¼4:1); H NMR
(
1
6
3
d
7.24e7.39 (m, 5H), 5.90 (ddd, J¼6.0, 7.2, and
References and notes
.0 Hz, 1H), 4.86 (dd, J¼7.2 and 7.2 Hz, 1H), 3.41 (ddd, J¼7.2, 8.8,
1
. Tsuji, J. Acc. Chem. Res. 1969, 2, 144e152.
2. Trost, B. M. Angew. Chem., Int. Ed. Engl. 1989, 28, 1173e1192.
3. Tsuji, J. J. Synth. Org. Chem. Jpn. 1999, 57, 1036e1050.
. Trost, B. M.; Crawley, M. L. Chem. Rev. 2003, 103, 2921e2944.
. Helmchen, G.; Pfaltz, A. Acc. Chem. Res. 2000, 33, 336e345.
6. Tanaka, T.; Patra, D.; Murakami, K.; Kanda, A.; Hamano, K.; Yamamoto, S.; Satoh,
C.; Iwata, C. Tetrahedron Lett. 1996, 37, 7809e7810.
7. Greico, P. A.; Takigawa, T.; Bongers, S. L.; Tanaka, H. J. Am. Chem. Soc. 1980, 102,
and 10.4 Hz, 1H), 2.97 (dd, J¼8.8 and 17.2 Hz, 1H), 2.79 (dd, J¼10.4
and 17.2 Hz, 1H); 1 C NMR (CDCl
3
3
, 100 MHz) d 175.2, 138.0, 133.8,
4
5
1
29.0, 127.8, 127.2, 118.6, 86.6, 47.8, 36.5; IR (CH
2
Cl
2
): 3157, 2988,
ꢀ1
þ
1
776, 1466, 1306, 1128, 1073 cm ; ESI Mass (m/z): 211 (M þ23);
HRMS (m/z) calcd for C12
Compound 35-anti: TLC R
CDCl , 400 MHz)
12 2
H O Na 211.0735, found: 211.0733.
¼0.75 (hexane/EtOAc¼4:1); 1H NMR
f
7
587e7588.
8. Tamaru, Y.; Yamada, Y.; Ochiai, H.; Nakajo, E.; Yoshida, Z. Tetrahedron 1984, 40,
791e1793.
(
(
1
3
d
7.12e7.36 (m, 5H), 5.33e5.36 (m, 2H), 5.19e5.23
1
m, 1H), 5.13e5.16 (m, 1H), 3.86e3.91 (m, 1H), 2.90 (dd, J¼8.0 and
13
9. (a) Lubineau, A.; Auge, J.; Lubin, N. Tetrahedron Lett. 1991, 32, 7529e7530; (b)
MacKeith, R. A.; McCague, R.; Olivo, H. F.; Roberts, S. M.; Taylor, S. J. C.; Xiong, H.
Bioorg. Med. Chem. 1994, 2, 387e394.
10. Hon, Y.-S.; Chen, H. F. Tetrahedron Lett. 2007, 48, 8611e8614.
11. Hoffman, R. Chem. Rev. 1989, 89, 1841e1860.
7.2 Hz, 1H), 2.83 (dd, J¼7.6 and 17.2 Hz, 1H); C NMR (CDCl
00 MHz) 176.2, 132.0, 128.7, 127.8, 127.6, 118.5, 83.3, 45.1, 33.9; IR
CH Cl
3
,
1
d
ꢀ1
(
(
2
2
): 3122, 2954, 1756, 1452, 1322, 1156, 1071 cm ; ESI Mass
þ
m/z): 211 (M þ23); HRMS (m/z) calcd for C12
12 2
H O Na 211.0735,
1
2. (3aR
(
*
,4R
*
,6aS
12 ) was isolated in 16% yield. The detail is shown in the Experimental part.
3. (a) Bellina, F.; Biagetti, A.; Carpita, A.; Rossi, R. Tetrahedron 2001, 57,
857e2870; (b) Chinchilla, R.; Nájera, C. Chem. Rev. 2007, 107, 874e922.
4. (a) Parker, W. L.; Johnson, F. J. Org. Chem. 1973, 38, 2489e2496; (b) Parker, W. L.;
*
)-2-Hydroxy-4-[(Z)-1-octenyl]perhydrofuro-[3,4-b]furan-6-one
found: 211.0732.
0
1
2
4
.5.20. (4R
tetrahydro-2-furanone (37-syn) and (4S
,1-dimethylsilyl]oxy-5-vinyltetrahydro-2-furanone (37-anti). Under
nitrogen atmosphere, to a solution of compound 37-syn (100 mg,
*
,5R
*
)-4-1-(tert-Butyl)-1,1-dimethylsilyl]oxy-5-vinyl-
1
*
,5R )-4-1-(tert-butyl)-
*
Johnson, F. J. Am. Chem. Soc. 1969, 91, 7208e7209; (c) van Tamelen, E. E.; Bach,
S. R. J. Am. Chem. Soc. 1955, 77, 4683e4684.
5. Johnson, W. S.; Werthemann, L.; Bartlett, W. R.; Brocksom, T. J.; Li, T.; Faulkner,
D. J.; Petersen, M. R. J. Am. Chem. Soc. 1970, 92, 741e743.
6. Song, J.; Hollingsworth, R. I. Tetrahedron: Asymmetry 2001, 12, 387e391.
1
1
0
.41 mmol) in THF (7 mL) were added Pd(OAc)
2
(9.3 mg,
1
0
.041 mmol) and Ph P (107.5 mg, 0.41 mmol) at rt. After stirring for
3
17. Hon, Y.-S.; Lin, S. W.; Lu, L.; Chen, Y. J. Tetrahedron 1995, 51, 5019e5034.