Stereochemical revision of communiols D and H through synthesis

Article abstract of DOI:10.1016/j.tet.2005.10.078

Based on the previously revised stereochemistries for communiols A-C, the ent-8-epi- and ent-6-epi-stereoisomers of the original structures proposed for communiols D and H, respectively, were synthesized as highly probable candidates for their genuine str

Full text of DOI:10.1016/j.tet.2005.10.078

Tetrahedron 62 (2006) 1102–1109
Stereochemical revision of communiols D and H through synthesis
*
Masaru Enomoto, Takashi Nakahata and Shigefumi Kuwahara
Laboratory of Applied Bioorganic Chemistry, Graduate School of Agricultural Science, Tohoku University, Tsutsumidori-Amamiyamachi,
Aoba-ku, Sendai 981-8555, Japan
Received 29 September 2005; revised 27 October 2005; accepted 31 October 2005
Available online 15 November 2005
Abstract—Based on the previously revised stereochemistries for communiols A–C, the ent-8-epi- and ent-6-epi-stereoisomers of the
original structures proposed for communiols D and H, respectively, were synthesized as highly probable candidates for their genuine
structures by using the Sharpless asymmetric dihydroxylation as the source of chirality. Complete accord in spectral properties between each
synthetic candidate and the corresponding natural material as well as the fact that communiols A–D and H were all isolated from the same
fungal source, led us to the conclusion that the stereochemistries of communiols D and H should also be revised to their (3S,5S,7R,8S,11R)-
and (5S,7R,8S)-forms, respectively.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
Podospora communis, and determined their structures by
spectroscopic methods including extensive 2D NMR
experiments.1 Quite recently, they also reported the
isolation and structural determination of communiol H
together with three other structurally-related cyclopenta-
noids (communiols E–G) from cultures of the same fungus.2
Communiols A–C (3–5) showed significant antimicrobial
activity against Bacillus subtilis and Staphylococcus aureus,
while communiols D (1) and H (2) exhibited no such
activity. The 2,4-disubstituted tetrahydrofuran substructure
incorporated in 3–5 is relatively rare as a structural unit of
natural products and displays a characteristic difference in
substitution pattern from 2,5-disubstituted tetrahydrofurans
frequently found in annonaceous acetogenins3 or iono-
phores.4 The 3,7-disubstituted 2,8-dioxabicyclo[3.3.0]-
octane structure contained in communiol D (1) is also
rare, although some related structural units analogous to but
different in substitution and/or oxidation patterns from the
bicyclic portion of 1 have been found in many natural
products such as clerodane diterpenoids and fungal
metabolites.5 The structural uniqueness of communiols
A–C (3–5), coupled with their interesting biological
activity, prompted us to undertake the synthesis of 3–5,
which recently culminated in their stereochemical revision
as described in our previous paper,6 wherein the genuine
stereochemistries of communiols A, B and C were
concluded to be represented by structures ent-8-epi-3, ent-
8-epi-4 and ent-6-epi-5, respectively (Fig. 2). The corrected
stereochemistries of 3–5, as well as our presumption that the
structurally-related metabolites (communiols D and H) of
the same microbial origin should have the same stereo-
chemical arrangement as communiols A–C, led us to
In the course of their search for antimicrobial substances
produced by coprophilous (dung-colonizing) fungi, Gloer
and co-workers isolated four novel polyketide motabolites
(communiols A–D, Fig. 1) from horse dung-colonizing
H
O
O
3
HO
O
O
11
H
H
5
5
OHC
7
8
H
OH
OH
communiol D (1)
communiol H (2)
O
O
H
H
HO C
HO C
2
2
OH
OH
communiol A (3)
communiol B (4)
O
H
HO C
2
OH
communiol C (5)
Figure 1. Originally proposed stereochemistries for communiols A–D
and H.
Keywords: Communiol; Enantioselective synthesis; Asymmetric
dihydroxylation; Podospora communis; Dioxabicyclo[3.3.0]octane.
Corresponding author. Tel./fax: C81 22 717 8783;
e-mail: skuwahar@biochem.tohoku.ac.jp
*
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.10.078

M. Enomoto et al. / Tetrahedron 62 (2006) 1102–1109
1103
suppose that the genuine stereochemistries of communiols
D and H might be exhibited by structures ent-8-epi-1 and
ent-8-epi-2, respectively (see Scheme 1). Herein, we
describe the enantioselective synthesis of the newly
proposed stereoisomers for communiols D and H, which
eventually enabled us to revise their stereochemistries as
shown later in this paper.
hydroxyl group in D (threo isomer) at the final stage of
the synthesis, which might be avoidable by using erythro-D
possessing the opposite absolute configuration at the OH-
bearing stereogenic center. The preparation of the epimeric
lactone (erythro-D) would demand the asymmetric di-
hydroxylation of the (Z)-isomer of olefin E. However,
utilization of the (Z)-isomer as the substrate for the
Sharpless asymmetric dihydroxylation was considered to
be inappropriate based on a general rule that (Z)-olefinic
substrates give only modest enantioselectivities on exposure
to the asymmetric dihydroxylation conditions, while the
(E)-olefins can be converted into the corresponding diols
with constantly high enantioselectivities.8 This consider-
ation made us choose D as our synthetic intermediate,
despite the additional stereoinversion process required at a
later stage of the synthesis. As for ent-8-epi-2, transform-
ation of the common intermediate C into the target aldehyde
seemed to be effected straightforwardly through the
inversion of the C8-stereochemistry of C and chain-
elongation at its C5-side chain.
O
O
H
H
HO C
HO C
2
2
8
OH
OH
communiol A
communiol B
(ent-8-epi-3)
(ent-8-epi-4)
O
H
HO C
2
6
OH
communiol C
(ent-6-epi-5)
Figure 2. Revised stereochemistries for communiols A–C.
Our retrosynthetic analysis of ent-8-epi-1 and ent-8-epi-2 is
depicted in Scheme 1. The 2,8-dioxabicyclo[3.3.0]octane
structural unit in ent-8-epi-1 was considered to be installable
by the intramolecular Michael addition of lactol B into A,
which, in turn, would readily be converted into the target
molecule through inversion of the stereochemistry of the
C8–OH and subsequent reduction of the ester group. The
intermediate B would be obtainable from lactone C via
elongation of the C5-side chain and reduction of the lactone
moiety. Retrosynthetic dissection of the allyl substituent of
C would lead to known hydroxy lactone D, which had
previously been prepared from D-glutamic acid in modest
yields through four steps.7 In order to prepare D, we adopted
the Sharpless asymmetric dihydroxylation of olefinic ester
E followed by lactonization of the resulting diol, due to its
simple experimental operation as compared to the previous
procedure. In the synthetic plan presented in Scheme 1, we
need to invert the original (R)-stereochemistry of the
2. Results and discussion
Our synthesis of the common synthetic intermediate C
(10, in Scheme 2) began with the Sharpless asymmetric
dihydroxylation8,9 of known olefinic ester 610,11 using
AD-mix-b as the chiral catalyst. Exposure of the resulting
crude product consisting of diol 7 and its lactonization
product 8 to acidic conditions brought about complete
1
conversion of 7 into 8, whose H NMR spectrum was in
good agreement with that reported for an authentic sample
of 8 previously prepared from D-glutamic acid.7 The
absolute stereochemistry of 8 was confirmed by comparison
of its specific rotation value ([a]2D2 K41.3 (c 2.25, CH2Cl2))
with the literature value ([a]2D2 K46.2 (c 2.25, CH2Cl2)),7
and the enantiomeric excess of 8 was estimated to be
96% by analyzing the 1H NMR spectra of the corresponding
(R)- and (S)-MTPA esters.12 The protection of the hydroxyl
group of 8 as its TBDPS ether proceeded uneventfully to
H
H
O
O
O
HO
1
O
O
R O C
O
2
H
H
H
OHC
8
H
H
OH
OH
OH
ent-8-epi-1
ent-8-epi-2
A
HO
O
O
O
H
H
5
1
R O C
2
8
2
2
OR
OR
B
O
D
C
O
H
3
R O C
2
E
OH
Scheme 1. Retrosynthetic analysis of ent-8-epi-1 and ent-8-epi-2.

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M. Enomoto et al. / Tetrahedron 62 (2006) 1102–1109
O
AD-mix-β
CH SO NH
TsOH.H O
2
OH
O
CH Cl
3
2
2
2
2
H
(+ 8)
EtO C
EtO C
2
2
t-BuOH/H O
rt, 1 h
(89% from 6)
2
OH
0 ˚C, 12 h
OH
6
7
8
1) TBDPSCl
imidazole
LDA
allyl bromide
DMF, rt, 21 h
(quant)
O
O
O
H
O
H
2) recrystal. from
hexane/EtOAc
(75%)
THF/HMPA
–78 ˚C, 15 min
(64%)
OTBDPS
OTBDPS
9
10
Scheme 2. Synthesis of common synthetic intermediate 10.
afford 9 quantitatively. Quite fortunately, and expectedly to
some extent, the TBDPS ether 9 was obtained as crystals,
which enabled us to enrich the enantiomeric excess of 9 to
100% by a single recrystallization of the crystalline product
from hexane/ethyl acetate. The optical integrity of 9 was
checked by inspection of the 1H NMR spectra of the
corresponding (R)- and (S)-MTPA esters, which, in turn,
were prepared by treatment of the optically enriched silyl
ether 9 with TBAF and subsequent (R)- and (S)-MTPA
esterifications of the resulting alcohol 8 ([a]2D2 K46.8
(c 0.24, CH2Cl2)). The protected lactone 9 was then
subjected to well-documented trans-selective alkylation
with allyl bromide,13,14 which afforded an 8.3:1 mixture
of desired product 10 and the corresponding cis-allylation
product in 90% combined yield.15 Careful chromatographic
purification of the mixture, then, furnished diastereo-
merically pure trans-lactone 10 in 64% isolated yield.
D. Ozonolysis of 10 gave aldehyde 11, which without
purification was subjected to Wittig olefination conditions
to afford t-butyl ester 12. Chemoselective reduction of the
lactone carbonyl of 12 was achieved by using DIBAL in
CH2Cl2 to give lactol 13 as an inseparable 2.8:1 mixture of
epimers.15 Upon exposure to NaH in THF, the lactol 13
cyclized intramolecularly into a 6.3:1 mixture of desired
bis-THF derivative 14 and its C3-epimer in 53% combined
yield from 12.15 The preferential formation of the exo-
stereoisomer 14 could readily be rationalized by considering
thermodynamic stability among possible cyclization
products (Fig. 3). Of the two possible alkoxide inter-
mediates, 13a and 13b, the b-alkoxide intermediate (13b)
could not cyclize into 14b due to its extremely strained
trans-fused bicyclo[3.3.0]octane system. The intra-
molecular Michael cyclization of the other alkoxide 13a,
which should also arise from 13b through an open-chain
intermediate, would produce two bis-THF intermediates,
exo-14a and endo-14a, and higher thermodynamic stability
of exo-14a possessing the C3-substituent on the convex face
of the bicyclic system should have driven the equilibrium
via retro-Michael reaction from less stable endo-14a with
Having secured a sufficient amount of the common synthetic
intermediate 10, we next turned our attention to its
elaboration into ent-8-epi-1 (Scheme 3), which
we considered as the genuine structure for communiol
O , MeOH
–78 ˚C, 8 min
3
O
O
Ph P=CHCO t-Bu
O
O
3
2
H
H
10
OHC
t-BuO C
2
then Me S
CH Cl , rt, 19 h
2 2
2
–78 ˚C to rt, 2 h
(71% from 10)
OTBDPS
OTBDPS
11
12
H
HO
O
t-BuO C
O
O
H
DIBAL, CH Cl
NaH, THF
2
2
2
3
H
t-BuO C
2
–78 ˚C, 20 min
10 to 35 ˚C, 1 h
(53% from 12)
H
14
OTBDPS
OTBDPS
13
DEAD, Ph P
K CO
2 3
MeOH
3
H
H
O
O
3
TBAF, THF
p-(NO )C H CO H
2
6
4
2
t-BuO C
O
t-BuO C
O
11
2
2
H
H
5
H
rt, 2 days
(77%)
THF, rt, 3 h
(86%)
H O
2
7
rt, 2 h
(85%)
H
H
OH
OPNB
15
16
LiAlH
THF
4
H
O
t-BuO C
O
2
ent-8-epi-1
H
rt, 2 h
(79%)
H
OH
17
Scheme 3. Synthesis of ent-8-epi-1, the newly proposed structure for communiol D.

M. Enomoto et al. / Tetrahedron 62 (2006) 1102–1109
1105
(c 0.3, CH2Cl2)).1 On the basis of these facts, we concluded
that the stereochemistry of communiol D, including
its absolute configuration, should be represented by
ent-8-epi-1.
H
O
1
R O C
O
2
3
H
H
2
OR
exo-14α
more stable
We next set about the synthesis of ent-8-epi-2, which
we presumed to be the real structure of communiol H
(Scheme 4). Deprotection of 10 and subsequent inversion
of the stereochemistry of the resulting alcohol 18 yielded
19. Methanolytic removal of its PNB group afforded 20,
the double bond of which was then cleaved by
ozonolysis to give aldehyde 21. Two-carbon elongation
of 21 by the Wittig reaction furnished the target
molecule, ent-8-epi-2. The 1H and 13C NMR data of
ent-8-epi-2 were completely identical with those of
natural communiol H,17 which enabled us to revise the
relative stereochemistry of communiol C to the 7,8-
erythro-form of its original structure proposed by Gloer
et al. As in the cases of communiols A and B, however,
the specific rotation value of synthetic ent-8-epi-2 ([a]D22
K12.9 (c 0.135, CH2Cl2)) was inconsistent with the
reported value for natural communiol H ([a]D K70
(c 0.1, CH2Cl2)), although they shared the same minus
sign. Actually, our synthetic ent-8-epi-2 seems to contain
a minute amount of dienal (less than 5%, as judged by
1H NMR) generated by an additional two-carbon
elongation toward the initially formed enal ent-8-epi-2,
but this large difference in specific rotation value seems
to be inexplicable by the contamination of such a slight
amount of analogous compound. Despite this ambiguity,
the complete agreement in 1H and 13C NMR data
between synthetic ent-8-epi-2 and natural communiol H
as well as the consideration of biogenetic similarity
among the metabolites isolated from the same fungal
source led us to the conclusion that the genuine
stereochemistry of communiol H should be depicted as
ent-8-epi-2.
O
O
14
H
1
R O C
2
2
OR
13α
H
O
13
NaH
1
R O C
O
2
H
H
2
OR
O
endo-14α
less stable
O
H
1
R O C
2
2
OR
3-epi-14
13β
H
O
1
R O C
O
2
H
H
14β
2
OR
extremely unstable
Figure 3. Preferential formation of 14.
the C3-side chain on the concave face to more stable exo-
14a leading eventually to 14 after aqueous workup. Since
the separation of the epimers was difficult at this stage, 14
was subjected, as the mixture, to deprotection of the silyl
group followed by the Mitsunobu inversion16 of the C8-
stereochemistry of the resulting alcohol 15 to give
diastereomerically pure 16 after simple chromatographic
purification. The stereochemistry of 16 was confirmed by
observing diagnostic NOE correlations between C3-H and
C7-H, and C5-H and C11-H. Finally, methanolysis of the
PNB-ester to 17 and subsequent reduction of the t-butyl
ester group afforded ent-8-epi-1. Direct comparison of the
1H and 13C NMR spectra of ent-8-epi-1 with those of natural
communiol D assured that these two samples were, as
expected, identical, and the optical rotation value of ent-8-
epi-1 ([a]2D2 C3.0 (c 0.22, CH2Cl2)) also exhibited good
agreement with that of natural communiol D ([a]D C2.7
3. Conclusion
In summary, the enantioselective total synthesis of ent-8-
epi-1 and ent-8-epi-2, which we presumed as the genuine
structures of communiols D and H, respectively, was
accomplished starting from known olefinic ester 6 in 12
and 9 steps, respectively, by using the Sharpless asymmetric
1
dihydroxylation as the source of chirality. The H and 13C
NMR data of ent-8-epi-1 and ent-8-epi-2 were identical with
those of natural communiols D and H, respectively, and
HF-TBAF
O
K CO
2 3
MeOH
DEAD, Ph P
3
O
THF
p-(NO )C H CO H
O
O
2
6
4
2
H
H
10
rt, 4 days
(quant)
rt, 30 min
(92%)
THF, rt,14 h
(72%)
OH
OPNB
18
19
O , MeOH
–78 ˚C, 3 min
Ph P=CHCHO
3
3
O
O
O
CH Cl
O
H
2
2
H
ent-8-epi-2
OHC
then Me S
rt, 2 days
2
–78 ˚C to rt
(87% from 20)
OH
OH
20
21
2 h
Scheme 4. Synthesis of ent-8-epi-2, the newly proposed structure for communiol H.

1106
M. Enomoto et al. / Tetrahedron 62 (2006) 1102–1109
furthermore, the specific rotation value of ent-8-epi-1
exhibited good agreement with that of natural communiol
D, which allowed us to revise the stereochemistry of
communiol D to 3S, 5S, 7R, 8S and 11R. With regard to
communiol H, despite considerable discrepancy in specific
rotation value, the complete accord in spectral properties
between ent-8-epi-2 and natural communiol H as well as the
fact that communiol H was isolated together with
communils A–D from the same fungal source, strongly
supported that genuine structure of commuiols H should be
ent-8-epi-2.
4.1.3. (4R,5R)-5-(t-Butyldiphenylsilyloxy)-4-heptanolide
(9). To a stirred solution of 8 (4.67 g, 32.4 mmol) in DMF
(23 ml) was added imidazole (1.22 g, 18.0 mmol) and
TBDPSCl (10.95 ml, 42.1 mmol) at rt. After 21 h, satd
NH4Cl aq was added, and the resulting mixture was
extracted with ether. The extract was successively washed
with water and brine, dried (MgSO4) and concentrated in
vacuo. The residue was chromatographed over SiO2
(hexane/ethyl acetate, 4:1) to give 12.4 g (quant) of 9 as a
white crystalline solid, recystallization of which from
hexane/ethyl acetate afforded 9.29 g (75%) of enantiomeri-
cally pure 9 as colorless prisms: mp 62.5–63 8C; [a]D22
K23.2 (c 1.00, CHCl3); IR (KBr) n 3070 (w), 3050 (w),
1780 (s), 1585 (w); 1H NMR d 0.73 (3H, t, JZ7.5 Hz), 1.05
(9H, s), 1.35–1.50 (1H, m), 1.58–1.74 (1H, m), 2.07–2.22
(2H, m), 2.40–2.65 (2H, m), 3.65 (1H, ddd, JZ7.2, 4.8,
3.3 Hz), 4.54 (1H, dt, JZ3.3, 6.9 Hz), 7.35–7.48 (6H, m),
7.67–7.74 (4H, m); 13C NMR d 9.5, 19.5, 23.2, 25.6, 27.0,
28.5, 76.1, 80.5, 127.5 (2C), 127.7 (2C), 129.7 (1C), 129.8
(1C), 133.2 (1C), 133.9 (1C), 135.8 (4C), 177.4; HRMS
(FAB) m/z calcd for C23H31O3Si ([MCH]C) 383.2042,
found 383.2046. Anal. Calcd for C23H30O3Si: C, 72.21; H,
7.90. Found: C, 72.47; H, 7.63.
4. Experimental
4.1. General
IR spectra were measured as films by a Jasco IR Report-100
1
spectrometer. H NMR spectra (300 or 500 MHz) and 13C
NMR spectra (75 or 125 MHz) were recorded with TMS as
an internal standard in CDCl3 by a Varian Gemini 2000
spectrometer or a Varian UNITYplus-500 spectrometer.
Optical rotation values were measured with a Horiba Septa-
300 polarimeter, and mass spectra were obtained with a Jeol
JMS-700 spectrometer. Merck silica gel 60 (70–230 mesh)
was used for silica gel column chromatography.
4.1.4. Determination of the enentiomeric excess of 9. A
solution of the optically enriched silyl ether 9 (1.00 g,
2.61 mmol) in THF (5 ml) was added to a stirred solution of
TBAF–HF in THF (prepared by adding several drops of
40% aq HF to 4 ml of 1 M TBAF in THF, pH ca. 7, checked
by a pH-test paper). The mixture was stirred for 2 days at rt,
diluted with satd NaHCO3 aq and then extracted with ethyl
acetate. The extract was successively washed with water
and brine, dried (MgSO4) and concentrated in vacuo. The
residue was chromatographed over SiO2 (hexane/ethyl
acetate, 5:1) to give 269 mg (71%) of 8 as a colorless oil
([a]2D2 K46.8 (c 0.24, CH2Cl2)). The enantiomeric excess of
8 just obtained from enriched 9 was determined to be 100%
by the same protocol as described above.
4.1.1. (4R,5R)-5-Hydroxy-4-heptanolide (8). To a stirred
mixture of AD-mix-b (53.3 g) and MeSO2NH2 (3.62 g,
38.0 mmol) in water–t-BuOH (1/1, 430 ml) was added a
solution 6 (5.94 g, 38.0 mmol) in water–t-BuOH (1/1,
30 ml) at 0 8C. After 12 h, Na2S2O3 was added, and the
resulting mixture was stirred for 3 h at rt. The mixture was
extracted with ethyl acetate, and the extract was succes-
sively washed with water and brine, dried (MgSO4) and
concentrated in vacuo. The residue containing 7 and 8 (1:1,
1
as judged by H NMR) was dissolved in CH2Cl2 (130 ml),
and TsOH$H2O (1.60 g) was added to the solution. The
mixture was stirred for 1.5 h at rt, and then successively
washed with satd NaHCO3 aq and brine, dried (MgSO4) and
concentrated in vacuo. The residue was chromatographed
over SiO2 (hexane/ethyl acetate, 3:1) to give 4.88 g (89%
from 6) of 8 as a colorless oil: [a]2D2 K41.3 (c 2.25, CH2Cl2);
IR n 3430 (m), 1765 (s), 1190 (s), 750 (s); 1H NMR d 1.03
(3H, t, JZ7.5 Hz), 1.50–1.70 (2H, m), 1.96 (1H, d, JZ
4.5 Hz, OH), 2.06–2.20 (1H, m), 2.20–2.33 (1H, m), 2.48–
2.70 (2H, m), 3.45–3.56 (1H, m), 4.45 (1H, dt, JZ4.5,
7.5 Hz); 13C NMR d 9.9, 24.1, 26.0, 28.7, 75.0, 82.6, 177.2;
HRMS (FAB) m/z calcd for C7H13O3 ([MCH]C) 145.0865,
found 145.0869.
4.1.5. (2S,4R,5R)-2-Allyl-5-(t-butyldiphenylsilyloxy)-4-
heptanolide (10). To a stirred solution of LDA, prepared
by treating a solution of diisopropylamine (0.263 ml,
1.88 mmol) and HMPA (0.311 ml, 1.79 mmol) in THF
(7 ml) with butyllithium (1.6 M in hexane, 1.12 ml,
1.79 mmol) at K10 8C, was added dropwise a solution of
9 (684 mg, 1.79 mmol) in THF (7 ml) at K78 8C. After
20 min, a solution of allyl bromide (0.155 ml, 1.79 mmol) in
THF (3 ml) was added, and the resulting mixture was stirred
for 20 min at K78 8C. After the addition of satd NH4Cl aq,
the mixture was extracted with ether. The extract was
successively washed with water and brine, dried (MgSO4)
and concentrated in vacuo. The residue was chromato-
graphed over SiO2 (hexane/ethyl acetate, 20:1) to give
680 mg (90%) of a mixture of 10 and its cis-allylation
epimer in a ratio of 8.3:1.15 Repeated SiO2-column
chromatography of the mixture yielded 481 mg (64%) of
pure 10 as a colorless oil: [a]2D2 K10.9 (c 1.00, CHCl3); IR n
3080 (w), 3050 (w), 1770 (s), 1110 (s), 705 (s); 1H NMR d
0.70 (3H, t, JZ7.5 Hz), 1.04 (9H, s), 1.39 (1H, ddq, JZ
13.8, 5.4, 7.5 Hz), 1.59–1.74 (1H, m), 1.94 (1H, dt, JZ13.2,
8.1 Hz), 2.16–2.33 (2H, m), 2.51–2.61 (1H, m), 2.78–2.89
(1H, m), 3.63 (1H, ddd, JZ7.8, 5.1, 3.3 Hz), 4.48 (1H, ddd,
JZ8.1, 3.9, 3.3 Hz), 5.10 (1H, br d, JZ11.1 Hz), 5.11 (1H,
4.1.2. Determination of the enantiomeric excess of 8.
According to the literature,12 8 (2.0 mg) was treated with
2 equiv of (R)- and (S)-MTPA chloride in pyridine to give
(S)- and (R)-MTPA esters, respectively, which were
analyzed, without purification, by 1H NMR (500 MHz).
The methoxy signal of the (R)-MTPA ester derived from 8
was observed at d 3.51 as a singlet, while that from ent-8
contained as an impurity appeared at d 3.58 as a singlet, and
each chemical shift was confirmed by the 1H NMR spectrum
of the (S)-MTPA ester. Calculation of the ratio of the two
peak areas revealed the enantiomeric excess of 8 to be 96%.

M. Enomoto et al. / Tetrahedron 62 (2006) 1102–1109
1107
dm, JZ15.9 Hz), 5.67–5.81 (1H, m), 7.35–7.48 (6H, m),
7.65–7.72 (4H, m); 13C NMR d 9.6, 19.5, 25.7, 27.0, 28.9,
35.5, 39.1, 76.6, 78.4, 117.7, 127.5 (2C), 127.7 (2C), 129.7
(1C), 129.9 (1C), 133.1 (1C), 133.9 (1C), 134.5, 135.81
(2C), 135.83 (2C), 179.1; HRMS (FAB) m/z calcd for
C26H35O3Si ([MCH]C) 423.2355, found 423.2358.
27.1, 28.1, 33.5, 38.9, 41.5, 42.8, 75.3, 76.4, 80.7, 81.1,
109.0, 127.38 (2C), 127.44 (2C), 129.4 (1C), 129.5 (1C),
134.0 (1C), 134.6 (1C), 135.9 (2C), 136.0 (2C), 170.2;
HRMS (FAB) m/z calcd for C31H44O5SiNa ([MCNa]C)
547.2856, found 547.2857.
4.1.8. t-Butyl [(2S,3aS,5R,6aR)-5-((R)-1-hydroxypropyl)-
hexahydrofuro[2,3-b]furan-2yl]acetate (15). To a stirred
solution of 14 (112 mg, 0.214 mmol) in THF (0.5 ml) was
added a solution of TBAF (1 M in THF, 0.641 ml,
0.641 mmol) at rt. After 2 days, the reaction mixture was
diluted with water and extracted with ethyl acetate. The
extract was washed with brine, dried (MgSO4) and
concentrated in vacuo. The residue was chromatographed
over SiO4 (hexane/ethyl acetate, 4:1) to give 47.0 mg (77%)
of a 6.3:1 mixture of 15 and its C3-epimer as a colorless oil:
[a]2D2 K0.92 (c 0.50, CHCl3); IR n 3050 (br w), 1730 (s),
4.1.6. (2S,4R,5R)-2-[3-(t-Butoxycarbonyl)-2-propenyl]-5-
(t-butyldiphenylsilyloxy)4-heptanolide (12). Ozone was
bubbled into a stirred solution of 10 (1.00 g, 2.34 mmol) in
methanol (10 ml) for 8 min at K78 8C. After the addition of
Me2S (1.7 ml), the mixture was allowed to gradually warm
to rt and concentrated in vacuo to give 1.22 g of
crude aldehyde 11 as a pale yellow oil, which was then
dissolved in CH2Cl2 (2.5 ml). To this solution was added
Ph3P]CHCO2t-Bu (980 mg, 2.82 mmol), and the mixture
was stirred for 19 h at rt, diluted with water and extracted
with ethyl acetate. The extract was successively washed
with water and brine, dried (MgSO4) and concentrated in
vacuo. The residue was chromatographed over SiO2
(hexane/ethyl acetate, 15:1) to give 877 mg (71% from
10) of 12 as a colorless oil: [a]2D2 K3.54 (c 1.00, CHCl3); IR
n 3060 (w), 3045 (w), 1770 (s), 1710 (s), 1655 (m); 1H NMR
d 0.71 (3H, t, JZ7.4 Hz), 1.04 (9H, s), 1.35–1.46 (1H, m),
1.50 (9H, s), 1.62–1.74 (1H, m), 1.90 (1H, dt, JZ12.9,
9.0 Hz), 2.21–2.34 (2H, m), 2.67–2.77 (1H, m), 2.83–2.95
(1H, m), 3.62 (1H, ddd, JZ8.4, 4.8, 2.7 Hz), 4.50 (1H, ddd,
JZ9.0, 3.6, 2.7 Hz), 5.80 (1H, d, JZ15.6 Hz), 6.74 (1H, dt,
JZ15.6, 7.5 Hz), 7.36–7.46 (6H, m), 7.64–7.71 (4H, m);
13C NMR d 9.6, 19.5, 25.8, 27.0, 28.1, 29.3, 33.7, 38.6,
76.6, 78.3, 80.5, 125.7, 127.6 (2C), 127.8 (2C), 129.8 (1C),
130.0 (1C), 133.0 (1C), 133.8 (1C), 135.78 (2C), 135.82
(2C), 143.1, 165.4, 178.4; HRMS (FAB) m/z calcd for
C31H42O5SiNa ([MCNa]C) 545.2699, found 545.2703.
1
1150 (s), 1020 (s); H NMR d 1.00 (3H, t, JZ7.4 Hz),
1.40–1.55 (2H, m), 1.45 (9H, s), 1.70–1.85 (2H, m),
1.89–2.02 (2H, m), 2.14 (1H, d, JZ4.0 Hz, OH), 2.32
(1H, dd, JZ15.6, 7.5 Hz), 2.64 (1H, dd, JZ15.6, 6.0 Hz),
2.95–3.04 (1H, m), 3.24–3.33 (1H, m), 4.06 (1H, dt, JZ9.6,
5.7 Hz), 4.39–4.49 (1H, m), 5.75 (1H, d, JZ4.8 Hz); 13C
NMR d 10.1, 26.7, 28.1, 34.8, 38.7, 41.5, 43.2, 75.2, 75.9,
80.8, 82.8, 108.8, 170.1; HRMS (FAB) m/z calcd for
C15H27O5 ([MCH]C) 287.1859, found 287.1861.
4.1.9. t-Butyl [(2S,3aS,5R,6aR)-5-((S)1-(p-nitrobenzoyl-
oxy)propyl)hexahydrofuro[2,3-b]furan-2-yl]acetate (16).
To a stirred solution of 15 (47.2 mg, 0.165 mmol), Ph3P
(130 mg, 0.494 mmol) and p-nitrobenzoic acid (83 mg,
0.494 mmol) in THF (2 ml) was added diethylazodicarbox-
ylate (90 ml, 0.494 mmol) at 0 8C, and the mixture was
stirred for 3 h at rt. The reaction mixture was quenched with
satd NaHCO3 aq and extracted with ethyl acetate. The
extract was washed with brine, dried (MgSO4) and
concentrated in vacuo. The residue was chromatographed
over SiO2 (hexane/ethyl acetate, 5:1) to give 62.0 mg (86%)
of 16 as a pale yellow oil: [a]2D2 K16.8 (c 1.02, CHCl3); IR n
3110 (w), 1720 (s), 1525 (m), 1270 (s); 1H NMR d 0.98 (3H,
t, JZ7.5 Hz), 1.45 (9H, s), 1.72–1.91 (4H, m), 1.98 (1H,
ddd, JZ12.0, 5.4, 1.8 Hz), 2.08 (1H, dt, JZ12.9, 9.2 Hz),
2.32 (1H, dd, JZ15.6, 7.5 Hz), 2.65 (1H, dd, JZ15.6,
6.0 Hz), 2.93–3.04 (1H, m), 4.34 (1H, dt, JZ9.3, 5.7 Hz),
4.39–4.49 (1H, m), 5.16 (1H, dt, JZ8.4, 4.8 Hz), 5.72 (1H,
d, JZ4.9 Hz), 8.21 (2H, d, JZ9.0 Hz), 8.30 (2H, d, JZ
8.7 Hz); 13C NMR d 9.6, 23.9, 28.0, 34.2, 38.6, 41.4, 42.5,
75.8, 77.7, 80.1, 80.9, 109.0, 123.6, 130.8, 135.8, 150.7,
164.3, 170.3; HRMS (FAB) m/z calcd for C22H29O8NNa
([MCNa]C) 458.1791, found 458.1794.
4.1.7. t-Butyl [(2S,3aS,5R,6aR)5-((R)-1-(t-butyldiphenyl-
silyloxy)propyl)hexahydrofuro[2,3-b]furan-2-yl]acetate
(14). To a stirred solution of 12 (169 mg, 0.322 mmol) in
CH2Cl2 (3 ml) was added dropwise a solution of DIBAL
(0.94 M in hexane, 0.377 ml, 0.355 mmol) at K78 8C. After
20 min, the reaction mixture was quenched with a saturated
potassium sodium tartrate aqueous solution, stirred for an
additional 1.5 h at ambient temperature, and extracted with
ethyl acetate. The extract was washed with brine, dried
(Na2SO4) and concentrated in vacuo to give 185 mg of a
2.8:1 epimeric mixture of lactols 13 as a pale yellow oil,15
which was then dissolved in THF (3 ml). To the solution
was added NaH (0.355 mmol) at K10 8C, and the mixture
was stirred for 1 h at 35 8C. The reaction mixture was
poured into satd NH4Cl aq at 0 8C and extracted with ethyl
acetate. The extract was washed with brine, dried (MgSO4)
and concentrated in vacuo. The residue was chromato-
graphed over SiO2 (hexane/ethyl acetate, 7:1) to give
89.0 mg (53% from 12) of a 6.3:1 mixture15 of 14 and its
C3-epimer as a colorless oil: [a]2D2 C15.8 (c 1.00, CHCl3);
IR n 3060 (w), 3045 (w), 1730 (s), 1150 (m), 1110 (s),
1015 (m); 1H NMR d 0.74 (3H, t, JZ7.4 Hz), 1.05 (9H, s),
1.28–1.40 (1H, m), 1.51–1.75 (3H, m), 1.82–1.90 (1H, m),
1.96–2.08 (1H, m), 2.29 (1H, dd, JZ15.3, 7.8 Hz), 2.62
(1H, dd, JZ15.3, 6.0 Hz), 2.84–2.94 (1H, m), 3.58 (1H, dt,
JZ3.9, 6.0 Hz), 4.20 (1H, ddd, JZ8.1, 6.6, 4.2 Hz),
4.27–4.37 (1H, m), 5.70 (1H, d, JZ4.9 Hz), 7.32–7.45
(6H, m), 7.66–7.74 (4H, m); 13C NMR d 10.0, 19.5, 25.7,
4.1.10. t-Butyl [(2S,3aS,5R,6aR)-5-((S)-1-hydroxy-
propyl)hexahydrofuro[2,3-b]furan-2-yl]acetate (17). To
a stirred solution of 16 (20 mg, 0.047 mmol) in methanol
(1 ml) was added 1 M K2CO3 aq (1 ml, 1 mmol) at 0 8C, and
the mixture was stirred at rt for 2 h. After the addition of
satd NH4Cl aq, the reaction mixture was extracted with
ethyl acetate. The extract was washed with brine, dried
(MgSO4) and concentrated in vacuo. The residue was
chromatographed over SiO2 (hexane/ethyl acetate, 1:1) to
give 11 mg (85%) of 17 as a colorless oil: [a]2D2 K5.73
(c 0.565, CHCl3); IR n 3470 (br m), 1725 (s), 1150 (s), 1010
1
(s), 755 (s); H NMR d 0.99 (3H, t, JZ7.4 Hz), 1.34–1.46

1108
M. Enomoto et al. / Tetrahedron 62 (2006) 1102–1109
(2H, m), 1.45 (9H, s), 1.62 (1H, ddd, JZ12.9, 6.3, 2.1 Hz),
1.80 (1H, dt, JZ12.6, 9.3 Hz), 1.98 (1H, ddd, JZ12.9, 5.4,
2.1 Hz), 2.01 (1H, br s, OH), 2.11 (1H, dt, JZ12.6, 9.9 Hz),
2.32 (1H, dd, JZ15.3, 6.9 Hz), 2.63 (1H, dd, JZ15.3,
6.0 Hz), 2.92–3.02 (1H, m), 3.73–3.80 (1H, m), 4.13 (1H,
ddd, JZ9.9, 5.7, 3.3 Hz), 4.39–4.49 (1H, m), 5.75 (1H, d,
JZ4.9 Hz); 13C NMR d 10.2, 25.4, 28.0, 30.9, 38.8, 41.6,
42.8, 72.3, 76.1, 80.8, 82.4, 108.7, 170.3; HRMS (FAB) m/z
calcd for C15H27O5 ([MCH]C) 287.1858, found 287.1860.
(MgSO4) and concentrated in vacuo. The residue was
chromatographed over SiO2 (hexane/ethyl acetate, 7:1) to
give 114 mg (72%) of 19 as a pale yellow oil: [a]2D2 C4.54
(c 1.15, CHCl3); IR n 3080 (w), 1770 (s), 1725 (s), 1525 (s),
1265 (s); 1H NMR d 1.02 (3H, t, JZ7.4 Hz), 1.83 (2H, qui,
JZ7.5 Hz), 2.13 (1H, ddd, JZ13.5, 8.4, 7.8 Hz), 2.26–2.40
(2H, m), 2.52–2.62 (1H, m), 2.74–2.86 (1H, m), 4.66 (1H,
dt, JZ8.4, 5.1 Hz), 5.15 (1H, dm, JZ9.6 Hz), 5.16 (1H, dm,
JZ17.1 Hz), 5.29 (1H, dt, JZ5.1, 6.5 Hz), 5.77 (1H, ddt,
JZ17.1, 9.6, 6.9 Hz), 8.17–8.22 (2H, m), 8.29–8.34
(2H, m); 13C NMR d 9.6, 23.3, 28.1, 35.1, 38.5, 76.6,
77.7, 118.4, 123.7, 130.8, 133.9, 135.0, 150.8. 164.1, 177.9;
HRMS (FAB) m/z calcd for C17H20O6N ([MCH]C)
334.1290, found 334.1291.
4.1.11. (S)-1-[(2R,3aS,5S,6aR)-5-(2-Hydroxyethyl)hexa-
hydrofuro[2,3-b]furan2-yl]-1-propanol (ent-8-epi-1). To
a stirred suspension of LiAlH4 (3.5 mg, 0.092 mmol) in
THF (0.5 ml) was added dropwise a solution of 17 (11 mg,
0.039 mmol) in THF (0.5 ml) at 0 8C, and the mixture was
stirred for 1 h at rt. To the mixture was successively added
ethyl acetate and a large amount of SiO2. The resulting
slurry was stirred for 30 min and filtered through a pad of
Celite. The filter cake was washed with 2-propanol, and the
combined filtrate and washings were concentrated in vacuo.
The residue was chromatographed over SiO2 (hexane/ethyl
acetate, 1:5) to give 6.7 mg (79%) of ent-8-epi-1 as a
colorless oil: [a]2D2 C3.0 (c 0.22, CH2Cl2); IR n 3395 (br s),
4.1.14. (2S,4R,5S)-2-Allyl-5-hydroxy-4-heptanolide (20).
To a stirred solution of 19 (54.0 mg, 0.163 mmol) in
methanol (0.5 ml) was added a catalytic amount of K2CO3
at 0 8C, and the mixture was stirred at rt for 30 min. The
reaction mixture was filtered through a pad of Celite, and the
filter cake was washed with ethyl acetate. The combined
filtrate and washings were concentrated in vacuo, and the
residue was chromatographed over SiO2 (hexane/ethyl
acetate, 4:1) to give 27.5 mg (92%) of 20 as a colorless
oil: [a]2D2 K0.84 (c 0.56, CHCl3); IR n 3445 (br m), 3080
(w), 1750 (s), 1180 (m); 1H NMR d 1.02 (3H, t, JZ7.5 Hz),
1.42–1.54 (2H, m), 1.93 (1H, ddd, JZ13.2, 8.1, 6.9 Hz),
2.03 (1H, d, JZ4.5 Hz, OH), 2.22–2.34 (1H, m), 2.40 (1H,
ddd, JZ13.2, 9.9, 5.1 Hz), 2.51–2.61 (1H, m), 2.78–2.89
(1H, m), 3.78–3.86 (1H, m), 4.41 (1H, ddd, JZ8.1, 5.1,
3.3 Hz), 5.12 (1H, dm, JZ10.2 Hz), 5.14 (1H, dm, JZ
16.8 Hz), 5.78 (1H, ddt, JZ16.8, 10.2, 6.9 Hz); 13C NMR d
9.9, 25.1, 26.5, 35.3, 39.2, 73.4, 80.6, 118.0, 134.5, 179.4;
HRMS (FAB) m/z calcd for C10H17O3 ([MCH]C)
185.1178, found 185.1178.
1
1090 (m), 1005 (s); H NMR d 0.99 (3H, t, JZ7.5 Hz),
1.36–1.46 (2H, m), 1.62 (1H, ddd, JZ12.9, 6.5, 2.1 Hz),
1.72 (1H, ddt, JZ14.3, 8.4, 6.0 Hz), 1.76–1.88 (2H, m),
1.89 (1H, ddd, JZ13.0, 5.9, 2.5 Hz), 1.99 (1H, br s, OH),
2.13 (1H, dt, JZ12.6, 9.9 Hz), 2.29 (1H, br s, OH),
2.91–3.02 (1H, m), 3.72–3.83 (3H, m), 4.13 (1H, ddd, JZ
9.9, 6.0, 3.3 Hz), 4.24–4.34 (1H, m), 5.78 (1H, d, JZ
4.9 Hz); 13C NMR d 10.4, 25.4, 31.1, 37.7, 39.4, 42.6, 60.9,
72.4, 79.1, 82.6, 108.9; HRMS (FAB) m/z calcd for
C11H21O4 ([MCH]C) 217.1440, found 217.1444.
4.1.12. (2S,4R,5R)-2-Allyl-5-hydroxy-4-heptanolide (18).
To a stirred solution of TBAF–HF in THF (prepared by
adding a few drops of 40% aq HF to 0.71 ml of 1 M TBAF
in THF, pH ca. 7, checked by a pH-test paper) was added a
solution of 10 (200 mg, 0.473 mmol) in THF (1.0 ml) at rt.
After 4 days, the reaction mixture was quenched with satd
NaHCO3 aq and extracted with ethyl acetate. The extract
was washed with brine, dried (MgSO4) and concentrated in
vacuo. The residue was chromatographed over SiO2
(hexane/ethyl acetate, 1:1) to give 88 mg (quant) of 18 as
a colorless oil: [a]2D2 K15.4 (c 1.00, CHCl3); IR n 3440 (br
4.1.15. (2S,4R,5S)-2-(3-Formyl-2-propenyl)-5-hydroxy-
4-heptanolide (ent-8-epi-2). Ozone was bubbled into a
stirred solution of 20 (27.5 mg, 0.149 mmol) in methanol
(1 ml) for 3 min at K78 8C. After the addition of Me2S
(0.3 ml), the mixture was allowed to gradually warm to
rt and concentrated in vacuo. The residue was roughly
chromatographed over SiO2 (hexane/ethyl acetate, 3:1) to
give 26.9 mg 21 as
a colorless oil, which was
immediately dissolved in CH2Cl2 (0.5 ml). To this
solution was added Ph3P]CHCHO (87.9 mg,
0.289 mmol), and the mixture was stirred for 2 days at
rt. After concentration of the reaction mixture, the
residue was chromatographed over SiO2 (hexane/ethyl
acetate, 1:5) to give 27.5 mg (87% from 20) of ent-8-epi-
2 as a colorless oil (ent-8-epi-2/two carbon-homologated
dienalZ95:5): [a]D22 K12.9 (c 0.135, CH2Cl2); IR n 3445
(m), 2750 (w), 1760 (s), 1685 (s), 1170 (m), 975 (m),
805 (m), 745 (m); 1H NMR d 1.02 (3H, t, JZ7.4 Hz),
1.43–1.55 (2H, m), 1.90 (1H, dt, JZ13.2, 8.4 Hz), 2.01
(1H, d, JZ3.9 Hz, OH), 2.50 (1H, ddd, JZ13.2, 9.6,
3.6 Hz), 2.48–2.59 (1H, m), 2.85 (1H, dddd, JZ15.0,
6.5, 5.5, 1.5 Hz), 2.95–3.06 (1H, m), 3.80–3.89 (1H, m),
4.45 (1H, dt, JZ8.4, 3.5 Hz), 6.20 (1H, ddt, JZ15.6,
8.0, 1.5 Hz), 6.84 (1H, dt, JZ15.6, 7.1 Hz), 9.55 (1H, d,
JZ8.0 Hz); 13C NMR d 10.3, 25.7, 27.4, 34.4, 38.7,
73.8, 80.7, 135.1, 153.5, 178.4, 193.7; HRMS (EI) m/z
calcd for C11H16O4 (MC) 212.1048, found 212.1041.
1
m), 3075 (w), 1755 (s), 1180 (m); H NMR d 1.02 (3H, t,
JZ7.4 Hz), 1.51–1.69 (2H, m), 1.84 (1H, d, JZ6.0 Hz,
OH), 2.06 (1H, ddd, JZ13.2, 8.4, 7.2 Hz), 2.22–2.35 (2H,
m), 2.52–2.62 (1H, m), 2.80–2.91 (1H, m), 3.45–3.54
(1H, m), 4.41 (1H, dt, JZ8.4, 4.4 Hz), 5.14 (1H, dt, JZ
17.1, 2.1 Hz), 5.16 (1H, d, JZ10.2 Hz), 5.78 (1H, ddt,
JZ17.1, 10.2, 6.9 Hz); 13C NMR d 10.0, 26.2, 29.5, 35.3,
39.1, 75.3, 80.5, 118.0, 134.3, 179.1; HRMS (FAB) m/z
calcd for C10H17O3 ([MCH]C) 185.1178, found 185.1178.
4.1.13. (2S,4R,5S)-2-Allyl-5-(p-nitrobenzoyloxy)-4-
heptanolide (19). To a stirred solution of 18 (90.0 mg,
0.473 mmol), Ph3P (186 mg, 0.710 mmol) and p-nitro-
benzoic acid (119 mg, 0.710 mmol) in THF (4 ml) was
added diethylazodicarboxylate (0.129 ml, 0.710 mmol) at
0 8C, and the mixture was stirred for 14 h at rt. The reaction
mixture was quenched with satd NaHCO3 aq and extracted
with ethyl acetate. The extract was washed with brine, dried

M. Enomoto et al. / Tetrahedron 62 (2006) 1102–1109
1109
9. Avedissian, H.; Sinha, S. C.; Yazbak, A.; Sinha, A.; Neogi, P.;
Sinha, S.; Keinan, E. J. Org. Chem. 2000, 65, 6035–6051.
10. Odinokov, V. N.; Vakhidov, R. R.; Shakhmaev, R. M.;
Zorin, V. V. Khim. Prir. Soedin. 1996, 936–939.
`
11. Bruyere, D.; Bouyssi, D.; Balme, G. Tetrahedron 2004, 60,
4007–4017.
Acknowledgements
We are grateful to Prof. Gloer (University of Iowa) for
valuable discussions and for providing the copies of the
NMR spectra of natural communiol D. We also thank Ms.
Yamada (Tohoku University) for measuring NMR and MS
spectra. This work was supported, in part, by a Grant-in-Aid
for Scientific Research (B) from the Ministry of Education,
Culture, Sports, Science and Technology of Japan (No.
16380075).
12. Kuwahara, S.; Ishikawa, J.; Leal, W. S.; Hamade, S.; Kodama, O.
Synthesis 2000, 1930–1935.
13. Sells, T. B.; Nair, V. Tetrahedron 1994, 50, 117–138.
´
14. Bouchard, H.; Soulie, J.; Lallemand, J. Y. Tetrahedron Lett.
1991, 32, 5957–5958.
15. The ratio of 10 and its cis-isomer (8.3:1) was calculated from
the peak areas of the proton signals (500 MHz 1H NMR)
assignable to 7-H (communiol numbering) of each epimer
(d 4.48 for 10, and d 4.37 for the cis-isomer). Comparison of
the peak areas of the hemiacetalic proton signals of the
epimeric mixture 13 (d 4.95 and 5.25) indicated their ratio to
be 2.8:1. The acetalic protons of 14 and its C3-epimer were
observed at d 5.70 and d 5.58, respectively, which showed the
ratio of them to be 6.3:1.
References and notes
1. Che, Y.; Gloer, J. B.; Scott, J. A.; Malloch, D. Tetrahedron
Lett. 2004, 45, 6891–6894.
2. Che, Y.; Araujo, A. R.; Gloer, J. B.; Scott, J. A.; Malloch, D.
J. Nat. Prod. 2005, 68, 435–438.
`
3. Bermejo, A.; Figadere, B.; Zafra-Polo, M.-C.; Barrachina, I.;
Estornell, E.; Cortes, D. Nat. Prod. Rep. 2005, 22, 269–303.
4. Wierenga, W. In ApSimon, J., Ed.; The Total Synthesis of
Natural Products; Wiley: New York, 1981; Vol. 4,
pp 263–351.
16. Mitsunobu, O. Synthesis 1981, 1–28.
17. The 1H and 13C NMR data for ent-8-epi-2 shown in the Section
4 were recorded with TMS as an internal standard in CDCl3,
while the published data for natural communiol H are reported
to have been obtained by using the solvent signals (dH 7.24, dC
77.0) as internal standards.2 This difference brought about
subtle disagreement in the NMR chemical shifts between
synthetic ent-8-epi-2 and natural communiol H (see Section 4
and Ref. 2). However, we were able to make sure that the two
samples were identical by regarding the chemical shifts due to
CHCl3 and CDCl3 in our measurements as 7.24 and 77.0 ppm,
respectively.
5. Lorenzo, E.; Alonso, F.; Yus, M. Tetrahedron 2000, 56,
1745–1757 and references cited therein.
6. Kuwahara, S.; Enomoto, M. Tetrahedron Lett. 2005, 46,
6297–6300.
ˆ
7. Larcheveque, M.; Lalande, J. Bull. Soc. Chim. Fr. 1987,
116–122.
8. Kolb, H. C.; VanNiewenhze, M. S.; Sharpless, K. B. Chem.
Rev. 1994, 94, 2483–2547.