Facile and efficient synthesis of lactols by a domino reaction of 2,3-epoxy alcohols with a hypervalent iodine(III) reagent and its application to the synthesis of lactones and the asymmetric synthesis of (+)-tanikolide

Article abstract of DOI:10.1002/chem.200601341

The domino reaction of 2,3-epoxy-1-alcohol derivatives, namely tetrasubstituted 2,3-epoxy-1 -alcohols and 2- or 3-alkyl trisubstituted 2,3-epoxy-1-alcohols, with PhI(OCOCF₃)₂ in the presence of H₂O is described in detail.

Full text of DOI:10.1002/chem.200601341

DOI: 10.1002/chem.200601341
Facile and Efficient Synthesis of Lactols by a Domino Reaction of 2,3-Epoxy
Alcohols with a Hypervalent IodineACHTREU(NG III) Reagent and Its Application to the
Synthesis of Lactones and the Asymmetric Synthesis of (+)-Tanikolide
Hiromichi Fujioka, Satoshi Matsuda, Mai Horai, Eri Fujii, Maiko Morishita,
Natsuko Nishiguchi, Kayoko Hata, and Yasuyuki Kita*[a]
Abstract: The domino reaction of 2,3-
epoxy-1-alcohol derivatives, namely
tained from the 2,3-epoxy-1-alcohol de-
rivatives in a single operation. The ob-
tained lactols were successively con-
verted into the corresponding lactones.
This reaction is applicable to the con-
struction of optically active lactone
compounds. The asymmetric total syn-
thesis of (+)-tanikolide, an antifungal
marine natural product, has been effec-
tively achieved by using this reaction.
tetrasubstituted
and 2- or 3-alkyl trisubstituted 2,3-
epoxy-1-alcohols, with PhI(OCOCF3)2
2,3-epoxy-1-alcohols
AHCTREUNG
in the presence of H2O is described in
detail. In this reaction, several types of
lactol derivatives can be directly ob-
Keywords:
alcohols
·
domino
reactions · iodine · lactols · lactones
Introduction
epoxy-1-alcohol derivatives. Furthermore, subsequent oxida-
tive ring cleavage occurs when the rearranged product con-
tains a structural subunit, such as an a-hydroxy ketone
(Scheme 1).[5] Although there have been a few reports about
the reaction of a simple epoxide with hypervalent iodine-
Domino reactions have attracted much attention from the
viewpoint of ꢀgreenꢀ chemistry because they can save reac-
tion steps, reagents, and solvents.[1] Therefore, the develop-
ment of an efficient and practical domino reaction is one of
the important issues in the field of modern synthetic organic
AHCTREUNG
(III) reagents,[6] there has been no report on the reaction of
2,3-epoxy-1-alcohol derivatives with hypervalent iodine
reagents except for ours.[5]
ACHTREUNG(III)
chemistry. On the other hand, hypervalent iodineACTHRE(UNG III) re-
agents have received much attention due to their low toxici-
ty, ready availability, easy handling, and reactivity which is
similar to those of heavy metal reagents.[2] We have devel-
oped many kinds of novel reactions by using hypervalent
iodineACHTREUNG
(III) reagents[3] and have applied them to the total
synthesis of biologically active natural products, such as the
discorhabdin alkaloids,[4] which show potent antitumor activ-
ity. Hypervalent iodineACHTRE(UGN III) reagents have an interesting
dual reactivity comprising oxidation activity and Lewis acid-
ity. We have examined the reaction of 2,3-epoxy-1-alcohol
Scheme 1. The reactions of epoxy alcohol derivatives with PIFA in HFIP.
Bn=benzyl; HFIP=(CF3)2CHOH; PIFA=PhI(OCOCF3)2.
derivatives and hypervalent iodine
A
ACHTREUNG
cently reported that hypervalent iodineAHCTREUNG
Lewis acids (LA) to give rearranged products from 2,3-
We next examined the reaction of the 2,3-epoxy-1-alcohol
derivatives, bicyclic epoxy alcohols, and trisubstituted 3-
[a] Dr. H. Fujioka, S. Matsuda, M. Horai, E. Fujii, M. Morishita,
N. Nishiguchi, K. Hata, Prof. Dr. Y. Kita
alkyl-2,3-epoxy-1-alcohols with hypervalent iodineACHTREUNG(III) re-
agents in the presence of an oxygen nucleophile. We report-
ed that the domino-type reaction proceeded to give the lac-
tols in the presence of water by attack at the C3 position fol-
Graduate School of Pharmaceutical Sciences, Osaka University
1-6, Yamada-oka, Suita, Osaka, 565-0871 (Japan)
Fax : (+81)6-6879-8229
ꢀ
E-mail: kita@phs.osaka-u.ac.jp
lowed by C C bond cleavage. This reaction was successfully
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FULL PAPER
applied to the total asymmetric synthesis of (+)-tanikolide,
diol. Subsequently, oxidative cleavage of the 1,2-diol with
PIFA proceeded smoothly to afford the a-alkoxy keto alde-
hyde. Cleavage of the 1,2-diol is
an antifungal marine natural product (Scheme 2).[7]
one of the popular reactions in
the field of hypervalent iodine
chemistry.[8] In this reaction,
PIFA first acted as a Lewis acid
to accelerate the nucleophilic
ring opening of the epoxide by
the alcohol, and it then acted as
an oxidant to cleave the 1,2-
diol. Therefore, this reaction
clearly shows the interesting
dual character of PIFA, that is,
it acts not only as an oxidizing
agent, but also as a Lewis acid.
Scheme 2. The reactions of tetrasubstituted or 3-alkyl trisubstituted epoxy alcohols with PIFA in the presence
of water and the successive lactone formation. The structure of (+)-tanikolide is also shown.
The reactions, especially those in the presence of water,
provided a very useful domino reaction for producing lac-
tols. We examined this domino reaction in detail and found
that trisubstituted 2-alkyl-2,3-epoxy-1-alcohols gave a differ-
ent type of lactols, which were converted into the corre-
sponding lactones (Scheme 3). We now report a full account
of our study.
Recently, several groups reported domino reactions with
2,3-epoxy-1-alcohols.[9] However, most of their studies fo-
cused on the rearrangement and subsequent reaction. We
then became interested in this type of reaction and exam-
ined several kinds of substrates and oxygen nucleophiles to
reveal its generality.
After several investigations, we used water as a nucleo-
phile instead of the alcohol and found a novel domino-type
lactol formation reaction (Table 1, entries 6–8). Namely, the
5,6-membered spiro lactol 3a was obtained from 1a in 66%
yield (Table 1, entry 6), and the 6,6-membered spiro lactol
3b was obtained from 1b in 49% yield (Table 1, entry 7). In
the case of 1c, the tricyclic spiro lactol 3c was obtained in
78% yield (Table 1, entry 8). The most plausible reaction
mechanism is considered to be the same as that with the al-
cohol nucleophiles for part of the reaction (Scheme 4).
Scheme 3. The reactions of 2-alkyl trisubstituted epoxy alcohols with
PIFA in the presence of water and the successive lactone formation.
Table 1. Nucleophilic addition of oxygen nucleophiles to 2,3-epoxy alcohols and subsequent PIFA-mediated
oxidative cleavage of the 1,2-diol.
Results and Discussion
Reaction of 2,2,3,3-tetrasubsti-
tuted 2,3-epoxy-1-alcohols and
phenyliodine
acetate): The reactions of 2,3-
epoxy-1-alcohol derivatives in Entry
ACHTREUNG(III) bis(trifluoro-
Substrate
ROH
Product
2a (n=1, R=Me)
Yield [%][c]
1[a]
2[a]
3[a]
1a (n=1)
1b (n=2)
1b (n=2)
MeOH
MeOH
EtOH
41
67
52
bicyclic and tricyclic systems
with phenyliodine(III) bis(tri-
2b (n=2, R=Me)
2c (n=2, R=Et)
ACHTREUNG
fluoroacetate) (PIFA) in the
presence of an alcohol were
first examined (Table 1, en-
tries 1–5). a-Alkoxy keto alde-
hydes 2a–e were directly ob-
4[a]
5[a]
MeOH
EtOH
2d (R=Me)
2e (R=Et)
46
51
1c
tained from each of the 2,3- 6[b]
1a (n=1)
1b (n=2)
H2O
H2O
3a (n=1)
3b (n=2)
66[d]
49[d]
7[b]
epoxy-1-alcohols 1a–c in mod-
erate yield. A plausible reaction
mechanism with 1b as the sub-
strate is depicted in Scheme 4.
8[b]
1c
H2O
3c
78[d]
In the first instance, the alcohol
attacks the epoxide at the C3
position, which is activated by
[a] Reactions were carried out in alcohol. [b] Reactions were carried out in CH3CN/H2O 4:1. [c] Yield of iso-
PIFA, to produce the cis-1,2- lated product. [d] Product was obtained as a diastereomeric mixture.
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5239

Y. Kita et al.
cleavage of the 1,2-diol by
PIFA, and lactol formation.
However, the carbon atoms at
both the C2 and C3 positions
were supposed to be susceptible
to the nucleophilic addition of
water. The formation of two
triol intermediates, i and ii, is
Scheme 4. Plausible reaction mechanism for the formation of a-alkoxy keto aldehydes 2b and 2c and spiro
lactol 3b from 1b.
Thus, nucleophilic ring opening of the epoxide by water and
subsequent oxidative cleavage of the 1,2-diol occurred to
give the a-hydroxy keto aldehyde, as in the cases with the
alcohols. In these cases, however, an intramolecular nucleo-
philic attack of the hydroxy group on the aldehyde occurred
immediately, to afford the spiro lactol derivatives as shown
Scheme 6. Reaction of both the cis and trans isomers of the monocyclic
2,2,3-trisubstituted-2,3-epoxy-1-alcohols in the presence of water to form
lactol 7.
in Table 1.
In the case of the monocyclic tetrasubstituted 2,3-epoxy-
1-alcohol 4, the 1,6-diketone 5 was obtained by oxidative
ꢀ
cleavage of the C2 C3 bond via intermediate A, rather than
via intermediate B (Scheme 5). The factor that accelerates
the reaction via intermediate A is not clear at this stage. In
this case, no lactol formation occurred between the hydroxy
function and the ketone function.
then possible (Scheme 7). Furthermore, vicinal diol cleavage
at the C1 and C2 (a’ or c’) or C2 and C3 (b’ or d’) positions
is possible. It is extremely difficult to assume the reaction
mechanism from product 7 because both cases, that is, the
route via intermediate iii and the route via intermediate iv,
are considered to afford the same product (Scheme 7).
Scheme 5. Reaction of monocyclic tetrasubstituted 2,3-epoxy alcohol 4.
Reaction of trisubstituted 2,3-epoxy-1-alcohols and PIFA:
The results in the preceding section, especially the forma-
tion of lactol units, the precursors of lactones, by the reac-
tions of the epoxy alcohols and PIFA in the presence of
water, are quite interesting because many biologically active
natural products contain the lactone moiety. The following
examinations were then performed in the presence of water.
For trisubstituted epoxy alcohols, we chose the monocyclic
2-alkyl-2,3-epoxy-1-alcohols and monocyclic 3-alkyl-2,3-
epoxy-1-alcohols as the substrates of the reaction.
Scheme 7. Possible reaction pathways for the transformation from cis-6 to
lactol 7.
To clarify which carbon atom is susceptible to the nucleo-
philic addition of water, we carried out the reaction with
methanol as a nucleophile (Scheme 8). As a result, in the
case of cis-6, nucleophilic addition of methanol occurred at
the C3 position and afforded two types of products, the acy-
clic keto acetal 8 and the cyclic 1,2-diol 9. Compound 8 is
the product obtained by nucleophilic addition of methanol
at the C3 position followed by oxidative cleavage of the 1,2-
diol with PIFA, and compound 9 is the 1,2-diol on the way
to 8. Indeed, treatment of 9 with PIFA afforded 8 in a quan-
titative yield. On the other hand, in the case of trans-6, 1,3-
diol 10, which is thought to be obtained by nucleophilic ad-
dition of methanol at the C2 position, was the major prod-
uct. Compound 8, which is supposed to be produced by oxi-
2-Alkyl-2,3-epoxy-1-alcohols: We first investigated the reac-
tion of both the cis and trans isomers of the monocyclic
2,2,3-trisubstituted 2,3-epoxy-1-alcohols cis-6 and trans-6
with PIFA in the presence of water. Although both the cis
and trans isomers afforded the acyl lactol 7 (with an epimer-
ic mixture at the hemiacetal carbon atom), the cis isomer
produced a better yield than the trans isomer (Scheme 6).
As described in the case of the 2,2,3,3-tetrasubstituted
2,3-epoxy-1-alcohol shown in Scheme 4, 7 was assumed to
be obtained by the domino reaction that included the nucle-
ophilic ring opening of the epoxide by water, oxidative
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Synthesis of Lactols and Lactones
FULL PAPER
orable due to the strong electron-withdrawing effect of the
OIPhACHTRE(UNG OCOCF3) unit. Furthermore, the interaction between
the epoxide and PIFA, which reacts with the secondary alco-
hol, would make the addition of water at the C3 position
more favorable in the cis isomer and also accelerates the re-
action rate compared with that with the trans isomer, which
is without such an interaction.
As shown above, we clarified the position of the nucleo-
philic ring opening of the 2-methyl epoxy alcohols, cis-6 and
trans-6, and found that cis-6 gave much better results than
the trans isomer. We next studied the oxidative cleavage
step of the 1,2-diol in Scheme 7. Scheme 10 shows the reac-
tion of the epoxy alcohol 11, containing deuterium, and
PIFA in the presence of water. When the oxidative cleavage
occurs between the C1 and C2 positions, the cis-2,3-epoxy-1-
alcohols with deuterium at the C1 position would produce
compound 12, in which the deuterium appears on the acetal
carbon atom, through path a). On the other hand, product
12’, in which the deuterium appears on the carbon atom
next to the acetyl group, would be obtained through path b)
by cleavage between the C2 and C3 positions. As a result of
the reaction, compound 11 exclusively afforded 12, with the
deuterium on the acetal carbon atom. This finding supports
the conclusion that the reaction probably predominantly
proceeds through path a).
Scheme 8. Reactions of both the cis and trans isomers of the monocyclic
2,2,3-trisubstituted-2,3-epoxy-1-alcohols in the presence of methanol.
dative cleavage of the 1,2-diol with PIFA, was only obtained
as a minor product.
These results suggest that the ring opening of the epoxide
by water proceeds in a trans diaxial fashion according to the
Fürst–Plattner rule,[10] as shown in Scheme 9. That is, the
Based on the above results in Schemes 8 and 10, a plausi-
ble reaction mechanism for the 2-substituted cis-2,3-epoxy-
1-alcohols and PIFA in the presence of water is depicted in
Scheme 11. Thus, the nucleophilic addition of water causing
the oxirane ring opening first occurs at the C3 position. In
the reaction, PIFA reacted with the hydroxy function which
accelerates the reaction rate and the nucleophilic addition at
ꢀ
the C3 position. Cleavage at the C1 C2 bond by forming a
five-membered transition state then gives the hydroxy keto
aldehyde, in which automatic lactol formation occurs to pro-
duce the lactol.
The reaction has generality and various kinds of 2-substi-
tuted 2,3-epoxy-1-alcohols, 13, are available. As shown in
Table 2, all of the reactions proceeded smoothly to afford
the corresponding lactol derivatives 14.
Scheme 9. Stereochemistry of the nucleophilic ring opening of epoxides.
3-Alkyl-2,3-epoxy-1-alcohols: The results of the reactions of
the monocyclic 3-alkyl-2,3-epoxy-1-alcohols, 15, have been
conformations of both epoxy al-
cohols are the chair forms, in
which the hydroxy groups are
located in equatorial positions.
In the case of cis isomer, the
addition of water at the C3 po-
sition then preferentially causes
trans diaxial opening of the ox-
irane ring. On the other hand,
the nucleophilic addition of
water at the C2 position causes
trans diaxial opening of the ox-
irane ring in the trans isomer,
but the C2 carbocation is unfav- Scheme 10. The reaction of the 2,3-epoxy alcohol analogue substituted with deuterium at the C1 position (11).
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5241

Y. Kita et al.
mation by nucleophilic attack of the hydroxy group of the
lactol on the aldehyde (Scheme 12). Various epoxy alcohols
were adapted to this reaction and produced bicyclic lactols
in good yields. In these cases, the reaction mechanism is ob-
vious from the structures of the products, and a plausible re-
action mechanism is depicted in Scheme 12. Thus, nucleo-
philic ring opening of the epoxide with water at the C3 posi-
tion and subsequent oxidative cleavage of the cis-1,2-diol at
ꢀ
the C1 C2 bond proceeded to give a hydroxy keto alde-
hyde. Automatic lactol formation occurred to produce the
oxacyclic lactol in the same manner as that in the reactions
of the 2-alkyl-2,3-epoxy-1-alcohols (Scheme 11). However,
the circumstances of the carbonyl group are different. The
carbonyl groups from the 2-
Scheme 11. Plausible reaction mechanism for the reaction of 2-substitut-
ed cis-2,3-epoxy-1-alcohols and PIFA in the presence of water.
alkyl-2,3-epoxy-1-alcohols
belong to the acetyl functions
Table 2. Domino-type lactol formation of 2-substituted-2,3-epoxy-1-alcohols.[a]
and are ketones. On the other
hand, the carbonyl groups from
the 3-alkyl-2,3-epoxy-1-alcohols
belong to the formyl functions
and are aldehydes. One more
Entry
Substrate
cis-6 (R=Me)
Product
Yield [%][b]
1
2
7 (R=Me)
14a (R=nBu)
55
81
lactol formation then occurred
for the 3-alkyl-2,3-epoxy-1-alco-
hols, probably due to the easier
formation of the lactol from the
alcohol and aldehyde compared
to that from the alcohol and
ketone.
13a (R=nBu)
3
4
13b
14b
14c
64
94
Transformation of lactols to lac-
tones: Since there are many
biologically active natural prod-
ucts containing lactone moieties
with asymmetric carbon centers,
an efficient synthetic method
for the construction of such a
13c
[a] Reactions were carried out with substrate (1 equiv) and PIFA (1 equiv) in CH3CN/H2O 4:1. [b] Yield of
isolated product. Product was obtained as a diastereomeric mixture.
reported previously in reference [7]. This reaction proceed-
ed in a different manner (Table 3). That is, bicyclic lactols 16
were obtained by the same type of reaction as that shown in
Table 2 followed by a subsequent intramolecular lactol for-
structural subunit is required for natural product synthesis.
As we had developed a novel and an efficient transforma-
tion of 2,3-epoxy-1-alcohols into lactols, we next tried to
convert the lactols into lactones. Table 4 shows the transfor-
mation of the monooxacyclic lactols into lactones. Bicyclic
lactols 3a and 3b were oxidized by Jones reagent to give the
corresponding lactones 17a and 17b, respectively. For oxida-
tion of the monocyclic lactols 14a and 14c, Jones reagent
gave unsuccessful results. After several trials, Ag2CO3/
Celite[11] was proven to be an effective oxidant for this pur-
pose and gave the corresponding lactones 17c and 17d. On
the other hand, Table 5 shows the conversion of the bisoxa-
cyclic lactols 16 f and 16g into lactones 19a and 19b. In
these cases, the conversion of the bisoxacyclic lactols 16 into
the monooxacyclic lactols 18 was first conducted by reduc-
tive opening of the lactol rings. Oxidation of the hydroxy
functions of the remaining lactols then gave the lactones 19.
Table 3. Domino-type lactol formation of 3-substituted-2,3-epoxy-1-alco-
hols.[a]
Entry
Substrate
R
Rꢀ
Product
Yield [%][b]
1
2
3
4
5
6
7
15a
15b
15c
15d
15e
15 f
15g
Me
Et
nC11H23
CH2CHMe2
CH2Ph
Ph
H
H
H
H
H
H
Me
16a
16b
16c
16d
16e
16 f
16g
62
74
72
67
72
53
65
Asymmetric total synthesis of (+)-tanikolide: (+)-Taniko-
lide ((+)-25) is a g-lactone metabolite of the marine cyano-
bacterium Lyngbya majuscula, which was collected on Tani-
Me
[a] Reactions were carried out with substrate (1 equiv) and PIFA
(1 equiv) in CH3CN/H2O 4:1. [b] Yield of isolated product.
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Synthesis of Lactols and Lactones
FULL PAPER
active 3-undecyl-2,3-epoxy-1-al-
cohol (+)-15c as the substrate.
First of all, the preparation of
the optically active 2,3-epoxy
alcohol (+)-15c was studied
(Scheme 14).
The
known
Scheme 12. Plausible reaction mechanism for the reaction of monocyclic 3-alkyl-2,3-epoxy-1-alcohols and
PIFA in the presence of water.
enone[14] 21 was subjected to
Coreyꢀs asymmetric reduction
by utilizing the chiral oxazabor-
olidine.[15] However, the enan-
tiomeric excess of the chiral
allyl alcohol (+)-22 proved to
be 77% ee by chiral HPLC
analysis. Knochel and co-work-
ers reported that the enone
containing the iodine atom at
the C2 position could be con-
verted into the chiral allyl alco-
hol with high enantiomeric
excess.[16] By taking their report
into account, we then prepared
Table 4. Transformation of lactols to lactones.
Entry
Substrate
Method of oxidation
Product
Yield [%][a]
17a 39
1
2
3a (n=1)
3b (n=2)
Jones oxidation
Jones oxidation
17b 95
3
4
14a (R=H)
14c (R=CHMe2) Ag2CO3/Celite
Ag2CO3/Celite
17c 52
17d 79
[a] Yield of isolated product.
Table 5. Reductive cleavage of lactols followed by oxidation to lactones.
Entry Substrate R1 R2 Method of reduction Product Yield [%][b]
1
2
16 f
16g
Ph
H
DIBAH[a]
19a
19b
57
98
Me Me NaBH4
[a] DIBAH=diisobutylaluminum hydride. [b] Yield of isolated product
after the two steps from 16.
Scheme 14. Preparation of optically active 2,3-epoxy-1-alcohol (+)-15c.
TMS: trimethylsilyl; acac: acetylacetone.
keli island, Madagascar, and its structure was determined by
Gerwick and co-workers in 1999.[12] It shows brine-shrimp
toxicity and antifungal activity. Although several groups
have already reported its asymmetric total synthesis,[13] we
planned an original and concise asymmetric total synthesis
of (+)-tanikolide in order to show the usefulness of our
method. The retrosynthetic analysis of (+)-tanikolide is de-
picted in Scheme 13. (+)-Tanikolide should be obtained by
the oxidation of a six-membered ring lactol, 20, which can
be obtained by selective reduction of the bicyclic lactol (+)-
16c. The optically active (+)-16c would be constructed by
our domino-type lactol formation reaction with the optically
2-iodoenone 23 according to the method of Sha and
Huang.[17] Thus, treatment of enone 21 with trimethylsilyl
azide followed by addition of iodine and pyridine gave the
iodocyclohexenone 23 via the iodoazide intermediate. Com-
pound 23 was subjected to Coreyꢀs asymmetric reduction to
give the iodoolefin alcohol (+)-24. Table 6 shows the selec-
tive reduction of the iodoolefin alcohol (+)-24 to (+)-22.
The radical conditions,[18] including the method developed
by us by using V-70L,[18b] succeeded in the conversion of
(+)-24 into (+)-22 with high yields (Table 6, entries 1 and
2). Although the catalytic hydrogenation of (+)-24 with a
Pd/C catalyst without quinoline gave a complex mixture
(Table 6, entry 3), the iodine atom was reduced in the best
yield by catalytic hydrogenation with the Pd/C catalyst in
the presence of quinoline (Table 6, entry 4).[19] These condi-
tions were then used for the conversion of the iodoolefin al-
cohol (+)-24 into the allyl alcohol (+)-22. The obtained
(+)-22 was found to have an ee value of 98%. The cis-selec-
tive epoxidation of (+)-22 according to the method of
Scheme 13. Retrosynthetic analysis of (+)-tanikolide ((+)-25).
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5243

Y. Kita et al.
Table 6. Selective reduction of iodoolefin ((+)-24).
using PIFA in the presence of water. The characteristic fea-
ture of our unique methodology is that various lactol deriva-
tives can be directly prepared from 2,3-epoxy-1-alcohols
under mild and environmentally benign conditions in a
simple and single operation. The lactols can be easily con-
verted into lactones. Furthermore, this reaction can be ap-
plied to the asymmetric total synthesis of (+)-tanikolide by
using optically active 2,3-epoxy alcohols. We believe this is a
powerful and reliable synthetic methodology for various lac-
tols and lactones with asymmetric quaternary carbon cen-
ters. Further extension of this reaction is currently in prog-
ress in our laboratory.
Entry
Reagent
Solvent
T
Yield [%][a]
1
2
3
4
Et3B, nBu3SnH[18a]
V-70L,[b] nBu3SnH[18b]
H2, 10% Pd/C
toluene
toluene
EtOH
0oC–RT
reflux
RT
84
88
complex mixture
96
H2, 10% Pd/C,[19]
quinoline, AcONa
EtOH
RT
[a] Yield of isolated product. [b] V-70L=2,2’-azobis-(2,4-dimethyl-4-me-
thoxyvaleronitrile).
Experimental Section
Sharpless and Michaelson[20] afforded the chiral 2,3-epoxy
alcohol (+)-15c.
All melting points are uncorrected. 1H NMR spectra were recorded at
300 MHz and 13C NMR spectra were recorded at 75 MHz with CDCl3 as
the solvent and SiMe4 as an internal standard. IR absorption spectra
(cmꢀ1) were recorded from KBr pellets. PIFA is commercially available.
Ag2CO3/Celite was purchased from Aldrich.
The chiral 2,3-epoxy alcohol (+)-15c was converted into
the bicyclic lactol (+)-16c in 72% yield by using PIFA in
the presence of water. Reduction of (+)-16c with DIBAH
followed by chemoselective oxidation of the lactol hydroxy
function with Ag2CO3/Celite[11] afforded (+)-tanikolide
((+)-25) in 57% yield over two steps (Scheme 15). The en-
General procedure for the preparation of 2,3-epoxy alcohols: 2,3-Epoxy
alcohols 1a,[21] 4,[5] cis-6,[22] 11,[23] 13b,[24] 13c,[25] 15a,[26] 15b,[27] 15e,[27]
15 f,[27] and 15g[28] were prepared according to the literature methods. 2,3-
Epoxy alcohols 1b,[29] 1c,[30] 13a,[31] and 15d,[32] were prepared from the
corresponding known enone by synthesis according to the literature pro-
cedures in a two-step sequence: DIBAH (1.2 mmol) was added to a stir-
red solution of the enone (1.0 mmol) in CH2Cl2 (10 mmol) at 08C under
N2. After the reaction mixture had been stirred for 1 h at that tempera-
ture, MeOH and Rochelleꢀs salt were added and the mixture was extract-
ed with CH2Cl2. The organic layer was washed with brine, dried over
Na2SO4, and evaporated in vacuo. The crude allyl alcohol was obtained.
tBuOOH (3 mmol) was added to the solution of the allyl alcohol in ben-
(acac)2 (0.05 mmol) at 58C.[20]
zene (10 mmol) in the presence of VOACHTREUNG
After the mixture had been stirred for 1 h, saturated aqueous Na2S2O3
was added and the mixture was extracted with AcOEt. The organic layer
was washed with brine, dried over Na2SO4, and evaporated in vacuo. The
residue was purified by silica gel column chromatography with hexane/
AcOEt (2:1!7:1) as the eluent, to give the cis-epoxy alcohol.
cis-1,6-EpoxybicycloACHTREU[NG 4.4.0]decan-7-ol (1b): Compound 1b was prepared
Scheme 15. Asymmetric total synthesis of (+)-tanikolide ((+)-25).
from the corresponding known enone[29] by the method described in the
general procedure. Colorless crystals; m.p. 688C (hexane/AcOEt);
1H NMR (300 MHz, CDCl3): d=1.25–2.22 (m, 15H), 3.77 ppm (brs, 1H);
13C NMR (75 MHz, CDCl3): d=16.7, 20.2, 20.4, 28.2, 30.4, 30.5, 30.8,
64.7, 65.6, 70.6 ppm; IR (KBr): n˜ =3418 cmꢀ; elemental analysis calcd
(%) for C10H16O2: C 71.39, H 9.59; found: C 71.35, H 9.44.
antiomeric excess of (+)-tanikolide was determined from
the
R-(+)-a-methoxy-a-(trifluoromethyl)phenylacetyl
(MTPA) ester of (+)-tanikolide. The absolute configuration
of allyl alcohol (+)-24 was deduced by reference to a report
by Corey and co-workers[15] and was unambiguously con-
firmed by comparison with the optical rotation value of the
natural (+)-tanikolide as reported by Gerwick and co-work-
ers.[12] It should be noted that no racemization occurred
during the synthetic process from the optically active 2,3-
epoxy alcohol (+)-15c. This total synthesis clearly shows
that our domino-type lactol formation reaction is applicable
to the synthesis of lactone derivatives with asymmetric qua-
ternary carbon centers.
cis-3a,9b-Epoxy-2,3,3a,4,5,9b-hexahydro-1H-cyclopenta[a]naphthalene-
3-ol (1c): Compound 1c was prepared from the corresponding known
enone[30] by the method described in the general procedure. Colorless oil;
1H NMR (300 MHz, CDCl3): d=1.69–1.86 (m, 2H), 1.93–2.06 (m, 1H),
2.13–2.24 (m, 1H), 2.49–2.91 (m, 4H), 4.22 (dd, J=17.6, 7.9 Hz, 1H),
7.11–7.37 ppm (m, 4H); 13C NMR (75 MHz, CDCl3): d=21.08, 25.42,
26.40, 30.11, 64.43, 70.80, 75.54, 126.59, 126.57, 128.12, 128.33, 133.34,
136.54 ppm; IR (KBr): n˜ =3383 cmꢀ1; elemental analysis calcd (%) for
C13H14O2: C 77.20, H 6.98; found: C 76.84, H, 7.03.
trans-2,3-Epoxy-2-methylcyclohexanol (trans-6): p-Nitrobenzoic acid
(150 mg, 1.17 mmol) and triphenylphosphine (614 mg, 2.34 mmol) were
added to
a stirred solution of cis-6 (150 mg, 1.17 mmol) in THF
(11.7 mL) at 08C under N2. After diethylazodicarboxylate (DEAD; 40%
in toluene, 1.02 g, 2.34 mmol) in THF (3.7 mL) was added dropwise, the
reaction mixture was gradually warmed to room temperature and stirred
for 12 h. Saturated aqueous NaHCO3 solution was added and the reac-
tion mixture was extracted with AcOEt. The combined organic layer was
washed with brine, dried over Na2SO4, and evaporated in vacuo. After
the residue had been filtered through a pad of silica gel with hexane/
Conclusion
We have developed a novel and efficient transformation of
2,3-epoxy-1-alcohols into lactols in a single operation by
5244
www.chemeurj.org
ꢁ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2007, 13, 5238 – 5248

Synthesis of Lactols and Lactones
FULL PAPER
AcOEt 5:1 as the eluent, the filtrate was evaporated in vacuo. The ob-
tained crude product was dissolved in MeOH (6.0 mL), 5% NaOH
(3.5 mL) was added and the mixture was stirred for 1 h at room tempera-
ture. H2O was added and the resulting reaction mixture was extracted
with CH2Cl2. The combined organic layer was washed with brine, dried
over Na2SO4, and evaporated in vacuo. The residue was purified by silica
gel column chromatography with hexane/AcOEt 1:1 as the eluent to give
trans-6 (114.2 mg, 76%). Colorless oil; 1H NMR (300 MHz, CDCl3): d=
1.26–1.57 (m, 4H), 1.38 (s, 3H), 1.77–1.90 (m, 3H), 3.03 (m, 1H),
3.97 ppm (m, 1H); 13C NMR (75 MHz, CDCl3): d=14.4, 19.7, 23.8, 29.0,
3H), 2.0–2.2 (m, 2H), 2.35–2.7 (m, 3H), 2.8–2.9 (m, 1H), 3.0–3.35 (m,
4H), 7.19–7.5 (m, 4H), 9.69 ppm (s, 1H); 13C NMR (75 MHz, CDCl3):
d=15.4, 27.9, 32.6, 37.86, 37.87, 60.3, 82.7, 126.5, 127.0, 127.7, 128.0,
136.5, 137.5, 201.2, 209.8 ppm; IR (KBr): n˜ =1717, 1728 cmꢀ1; MS (FAB):
m/z: 255 [M+Na]+; HRMS (FAB): m/z: calcd for C14H16O3Na [M+Na]+:
255.0997; found: 255.1005.
General procedure for the reaction of 2,3-epoxy alcohols with PIFA in
the presence of water (Tables 1 (entries 6–8), 2 and 3; Schemes 5, 6,
and 10): PIFA (1 mmol) was added to a stirred solution of 2,3-epoxy alco-
hol (1 mmol) in CH3CN/H2O (v/v 4:1, 10 mL) at 08C and the mixture
was gradually warmed to room temperature. After completion of the re-
action (as checked by TLC), saturated aqueous Na2S2O3 solution was
added at 08C and the reaction mixture was extracted with AcOEt. The
combined organic layer was dried over Na2SO4 and evaporated in vacuo.
The residue was purified by silica gel column chromatography with
hexane/AcOEt 5:1 as the eluent to give the products in the yields shown
in the tables.
59.4, 60.4, 68.8 ppm; IR (KBr): n˜ =3393, 2941, 743 cmꢀ1
.
cis-2-Butyl-2,3-epoxycyclohexan-1-ol (13a): Compound 13a was prepared
from the corresponding known enone[31] by the method described in the
1
general procedure. Colorless oil; H NMR (300 MHz, CDCl3): d=0.87 (t,
J=6.9 Hz, 3H), 1.19–1.55 (m, 9H), 1.68–1.73 (m, 1H), 1.88–2.05 (m,
3H), 3.15 (m, 1H), 3.90 ppm (m, 1H); 13C NMR (75 MHz, CDCl3): d=
14.0, 15.8, 22.8, 24.3, 26.9, 30.3, 34.2, 61.3, 62.8, 67.3 ppm; IR (KBr): n˜ =
3445, 2936 cmꢀ1; MS (FAB): m/z: 171 [M+H]+; HRMS (FAB): m/z:
calcd for C10H19O2: 171.1385 [M+H]+; found: 171.1372.
[4.5]decan-6-one (3a): Colorless oil; 1H NMR
2-Hydroxy-1-oxaspiroACHTREUNG
(300 MHz, CDCl3): d=1.19–2.74 (m, 12H), 3.99 (brs, 2/5H), 4.30–4.37
(m, 3/5H), 5.55 (dd, J=4.9, 1.9 Hz, 3/5H), 5.60 ppm (d, J=3.8 Hz, 2/
5H); IR (KBr): n˜ =3418, 1713 cmꢀ1; MS (EI): m/z: 170 [M]+; HRMS
(EI): m/z: calcd for C9H14O3: 170.0943; found: 170.0943.
cis-2,3-Epoxy-3-isobutylcyclohexan-1-ol (15d): Compound 15d was pre-
pared from the corresponding known enone[32] by the method described
in the general procedure. Colorless oil; 1H NMR (300 MHz, CDCl3): d=
0.90 (d, J=6.6 Hz, 3H), 0.96 (d, J=6.6 Hz, 3H), 1.17–1.35 (m, 2H), 1.40–
1.90 (m, 8H), 3.10 (d, J=3.1 Hz, 1H), 3.99 ppm (m, 1H); 13C NMR
(75 MHz, CDCl3): d=18.0, 22.6, 23.2, 25.3, 26.4, 29.3, 46.5, 61.6, 63.6,
2-Hydroxy-1-oxaspiro
C
(3b): Colorless crystals;
66.8 ppm; IR (KBr): n˜ =3317 cmꢀ1 MS (FAB): m/z: 171 [M+H]+;
;
HRMS (FAB): m/z: calcd for C10H19O2 [M+H]+: 171.1385; found:
171.1394.
Spiro(tetrahydrofuran-2-ol-5-1’)-3’,4’-dihydro-1’H-naphthalene-2’-one
(3c): Colorless oil; 1H NMR (300 MHz, CDCl3): d=1.86–3.25 (m, 8H),
4.20 (brs, 1H), 5.81–5.89 (m, 4/5H), 5.95 (d, J=4.4 Hz, 1/5H), 7.15–
7.75 ppm (m, 4H); IR (KBr): n˜ =3410 cmꢀ1; MS (EI): m/z: 218 [M]+;
HRMS (EI): m/z: calcd for C13H14O3: 218.0943; found: 218.0958.
6-Hydroxyundecane-2,7-dione (5): Colorless oil; 1H NMR (300 MHz,
CDCl3): d=0.92 (t, J=7.2 Hz, 3H), 1.23–1.41 (m, 2H), 1.47–1.90 (m,
6H), 2.15 (s, 3H), 2.35–2.60 (m, 4H), 3.57 (brs, 1H), 2.35–2.60 ppm (m,
1H); 13C NMR (75 MHz, CDCl3): d=13.9, 19.1, 22.4, 25.7, 30.0, 32.8,
37.6, 42.9, 76.1, 208.3, 211.9 ppm; IR (KBr): n˜ =3479, 1713 cmꢀ1; MS
(EI): m/z: 200 [M]+; HRMS (EI): m/z: calcd for C11H20O3: 200.1412;
found: 200.1405.
1-(6-Hydroxytetrahydropyran-2-yl)ethanone (7): Colorless oil; 1H NMR
(300 MHz, CDCl3): d=1.18–1.41 (m, 2H), 1.52–1.65 (m, 3H), 1.75–1.93
(m, 3H), 2.11 (s, 3/2H), 2.17 (s, 3/2H), 3.88 (dd, J=11.4, 2.4 Hz, 1/2H),
4.40 (dd, J=12.0, 2.7 Hz, 1/2H), 4.73 (dd, J=9.3, 2.4 Hz, 1/2H), 5.34 ppm
(brs, 1/2H); IR (KBr): n˜ =3362, 1715 cmꢀ1; MS (EI): m/z: 144 [M]+;
HRMS (EI): m/z: calcd for C7H12O3: 144.0786; found: 144.0791.
3,7,7-Trimethoxyheptan-2-one (8): Colorless oil; 1H NMR (300 MHz,
CDCl3): d=1.37–1.47 (m, 2H), 1.55–1.66 (m, 4H), 2.14 (s, 3H), 3.29 (s,
6H), 3.33 (s, 3H), 3.53 (t, J=6.3 Hz, 1H), 4.33 ppm (t, J=5.7 Hz, 1H);
13C NMR (75 MHz, CDCl3): d=20.3, 25.1, 31.5, 32.1, 52.6, 52.7, 58.1,
87.2, 104.2, 211.4 ppm; IR (KBr): n˜ =2931, 1715, 1126 cmꢀ1; MS (FAB):
m/z: 227 [M+Na]+; HRMS (FAB): m/z: calcd for C10H20O4Na: 227.1259
[M+Na]+; found: 227.1261.
General procedure for the reaction of 2,3-epoxy alcohols with PIFA in
alcohol (Table 1, entries 1–5; Scheme 8): PIFA (1 mmol) was added to a
stirred solution of 2,3-epoxy alcohol (1 mmol) in alcohol (10 mL) at 08C
and the mixture was gradually warmed to room temperature. After com-
pletion of the reaction (as checked by TLC), the reaction mixture was
evaporated in vacuo. The residue was purified by silica gel column chro-
matography with hexane/AcOEt 5:1 as the eluent to give the products in
the yields shown in the table.
3-(1-Methoxy-2-oxocyclohexyl)propionaldehyde (2a): Colorless oil;
1H NMR (300 MHz, CDCl3): d=1.42–2.38 (m, 9H), 2.40–2.52 (m, 2H),
2.61–2.75 (m, 1H), 3.15 (s, 3H), 9.80 ppm (s, 1H); 13C NMR (75 MHz,
CDCl3): d=20.8, 23.4, 27.8, 36.8, 37.6, 39.4, 50.6, 81.8, 201.5, 211.6 ppm;
IR (KBr): n˜ =1720 cmꢀ1; MS (EI): m/z: 184 [M]+; HRMS (EI): m/z:
calcd for C10H16O3: 184.1099; found: 184.1113.
4-(1-Methoxy-2-oxocyclohexyl)butyraldehyde
(2b):
Colorless
oil;
1H NMR (300 MHz, CDCl3): d=1.40–2.06 (m, 9H), 2.12–2.35 (m, 2H),
2.46–2.54 (m, 2H), 2.62–2.75 (m, 1H), 3.16 (s, 3H), 9.78 ppm (t, J=
1.5 Hz, 1H); 13C NMR (75 MHz, CDCl3): d=15.2, 20.8, 27.9, 30.2, 36.9,
39.4, 43.9, 50.7, 82.2, 202.0, 212.4 ppm; IR (KBr): n˜ =1717 cmꢀ1; MS (EI):
m/z: 198 [M]+; HRMS (EI): m/z: calcd for C11H18O3: 198.1256; found:
198.1248.
4-(1-Ethoxy-2-oxocyclohexyl)butyraldehyde (2c): Colorless oil; 1H NMR
(300 MHz, CDCl3): d=1.21 (t, J=7.0 Hz, 3H), 1.37–2.07 (m, 7H), 2.16–
2.32 (m, 4H), 2.50 (td, J=7.0, 1.3 Hz, 2H), 2.71 (td, J=12.5, 5.7 Hz, 1H),
3.01–3.13 (m, 1H), 3.36–3.52 (m, 1H), 9.79 ppm (t, J=1.2 Hz, 1H);
13C NMR (75 MHz, CDCl3): d=15.1, 15.6, 20.6, 28.0, 30.6, 37.3, 39.3,
43.9, 58.3, 82.0, 202.2, 213.2 ppm; IR (KBr): n˜ =1720 cmꢀ1; MS (EI): m/z:
212 [M]+; HRMS (EI): m/z: calcd for C12H20O3: 212.1412; found:
212.1416.
6-Methoxy-1-methylcyclohexane-1,2-diol (9): Colorless oil; 1H NMR
(300 MHz, CDCl3): d=1.09–1.26 (m, 1H), 1.13 (s, 3H), 1.46–1.71 (m,
4H), 1.89 (m, 1H), 2.29 (brs, 2H), 3.33 (m, 1H), 3.34 (s, 3H), 3.67 ppm
(m, 1H); 13C NMR (75 MHz, CDCl3): d=20.38, 25.25, 31.58, 32.23, 52.75,
58.13, 87.22, 104.16 ppm: IR (KBr): n˜ =3416, 2937, 1101 cmꢀ1
; MS
(FAB): m/z: 161 [M+H]+; HRMS (FAB): m/z: calcd for C8H17O3:
3-(1-Methoxy-2-oxo-1,2,3,4-tetrahydronaphthalen-1-yl)propionaldehyde
(2d): Colorless oil; 1H NMR (300 MHz, CDCl3): d=2.04–2.2 (m, 2H),
2.45–2.6 (m, 3H), 2.86–2.95 (m, 1H), 3.0–3.25 (m, 2H), 3.07 (s, 3H),
7.23–7.45 (m, 4H), 9.68 ppm (t, J=1.1 Hz, 1H); 13C NMR (75 MHz,
CDCl3): d=28.0, 32.5, 37.92, 37.95, 52.9, 83.3, 126.7, 127.2, 127.9, 128.2,
136.8, 136.9, 201.1, 209.7 ppm; IR (KBr): n˜ =1710, 1722 cmꢀ1; MS (EI):
m/z: 198 [M]+; HRMS (EI): m/z: calcd for C11H18O3: 198.1256; found:
198.1248
161.1178 [M+H]+; found: 161.1154.
2-Methoxy-2-methylcyclohexane-1,3-diol (10): Colorless oil; 1H NMR
(300 MHz, CDCl3): d=1.12 (s, 3H), 1.27–1.49 (m, 2H), 1.59–1.82 (m,
4H), 3.23 (s, 3H), 3.81 (dd, J=11.1, 4.5 Hz, 1H), 3.88 ppm (m, 1H);
13C NMR (75 MHz, CDCl3): d=13.4, 18.2, 28.4, 29.8, 49.0, 69.9, 71.9,
80.0 ppm; IR (KBr): n˜ =3362, 2941, 1074 cmꢀ1; MS (EI): m/z: 160 [M]+;
HRMS (EI): m/z: calcd for C8H16O3: 160.1122; found: 160.1099.
3-(1-Ethoxy-2-oxo-1,2,3,4-tetrahydronaphthalen-1-yl)propionaldehyde
1-(6-Hydroxy-6-deuterio-4-isopropenyltetrahydropyran-2-yl)ethanone
(2e): Colorless oil; 1H NMR (300 MHz, CDCl3): d=1.17 (t, J=7.9 Hz,
(12): Colorless oil; 1H NMR (300 MHz, CDCl3): d=1.21–1.37 (m, 2H),
Chem. Eur. J. 2007, 13, 5238 – 5248
ꢁ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
5245

Y. Kita et al.
1.73 (s, 3H), 1.84–2.06 (m, 3H), 2.20 (s, 2/3H), 2.26 (s, 1/3H), 2.67 (m,
1H), 3.97 (dd, J=12.0, 2.7 Hz, 1H), 4.51 (dd, J=12.0, 2.4 Hz, 1H), 4.73
(m, 1H), 4.77 ppm (m, 1H); IR (KBr): n˜ =3369, 1715 cmꢀ1; MS (EI):
m/z: 185 [M]+; HRMS (EI): m/z: calcd for C10H15DO3: 185.1161; found:
185.1183.
(s, 3H), 1.41–1.66 (m, 4H), 2.84 (brs, 1H), 5.16 (s, 1H), 5.69 ppm (t, J=
2.1 Hz, 1H); 13C NMR (75 MHz, CDCl3): d=20.5, 27.9, 31.1, 35.6, 41.3,
46.1, 81.4, 97.0, 101.9 ppm; IR (KBr): n˜ =3418 cmꢀ1; elemental analysis
calcd (%) for C9H16O3: C 62.77, H 9.36; found: C 62.59, H 9.16.
General procedure for the transformation of lactols into lactones
(Tables 4 and 5)
1-(6-Hydroxytetrahydropyran-2-yl)pentan-1-one (14a): Colorless oil;
1H NMR (300 MHz, CDCl3): d=0.83 (t, J=7.5 Hz, 3H), 1.18–1.39 (m,
4H), 1.43–1.63 (m, 4H), 1.80–1.94 (m, 3H), 2.44 (t, J=7.2 Hz, 1H), 2.53
(t, J=7.2 Hz, 1H), 3.88 (dd, J=11.4, 2.7 Hz, 1/2H), 4.40 (dd, J=11.7,
2.7 Hz, 1/2H), 4.72 (dd, J=9.3, 2.1 Hz, 1/2H), 5.34 ppm (brs, 1/2H); IR
(KBr): n˜ =3360, 1713 cmꢀ1; MS (FAB): m/z: 209 [M+Na]+; HRMS
(FAB): m/z: calcd for C10H18O3Na: 209.1154 [M+Na]+; found: 209.1152.
Oxidation with Ag2CO3/Celite (Method A): Ag2CO3/Celite (10 mmol) was
added to a solution of lactol (1 mmol) in benzene (10 mL) and the reac-
tion mixture was refluxed for 1 h under an N2 atmosphere. The reaction
mixture was cooled to room temperature, diluted with AcOEt, and fil-
tered through a pad of Celite. The filtrate was evaporated in vacuo. The
residue was purified by silica gel column chromatography with hexane/
AcOEt 1:1 as the eluent to give the products in the yields shown in
Tables 4 and 5.
ACHTREUNG(2S*,4S*)-1-(6-Hydroxy-4-isopropenyltetrahydropyran-2-yl)ethanone
(14b):[33] Colorless oil; 1H NMR (300 MHz, CDCl3): d=1.19–1.32 (m,
4H), 1.53 (m, 1H), 1.72 (s, 3H), 1.88 (m, 1H), 2.01 (m, 1H), 2.18 (s, 2/
3H), 2.24 (s, 1/3H), 2.65 (m, 1H), 3.95 (dd, J=11.6, 2.4 Hz, 1/3H), 4.49
(dd, J=11.9, 2.43 Hz, 2/3H), 4.73 (m, 2H), 4.85 (d, J=9.2 Hz, 1/3H),
Jones oxidation (Method B; Table 4): After H2SO4 (11 mmol) was added
to a stirred solution of CrO3 (7 mmol) in H2O (1 mL), H2O (2 mL) was
to the solution (preparation of Jones reagent). The Jones reagent was
added slowly to a stirred solution of lactol (10 mmol) in acetone (6 mL)
with the reaction temperature kept at 208C. After the reaction mixture
had been stirred for 3 h, NaHSO3 was added slowly until the orange
color of the CrO3 had disappeared. The reaction mixture was extracted
with diethyl ether. The combined organic layer was washed with brine,
saturated NaHCO3 solution, and brine, and then dried over MgSO4 and
evaporated in vacuo. The residue was purified by silica gel column chro-
matography with hexane/AcOEt 1:1 as the eluent to give the products in
the yields shown in Table 4.
5.51 ppm (d, J=2.7 Hz, 2/3H); IR (KBr): n˜ =3342, 1715 cmꢀ1
.
ACHTREUNG(2S*,4S*)-1-(6-Hydroxy-4-isopropyltetrahydropyran-2-yl)-ethanone (14c):
Colorless oil; 1H NMR (300 MHz, CDCl3): d=0.86 (d, J=6.6 Hz, 3/2H),
0.88 (d, J=6.6 Hz, 3/2H), 0.99–1.08 (m, 1H), 1.28–1.56 (m, 3H), 1.70–
1.84 (m, 2H), 1.92–1.96 (m, 1H), 2.17 (s, 3/2H), 2.23 (s, 3/2H), 3.87 (dd,
J=11.7, 2.4 Hz, 1/2H), 4.41 (dd, J=11.7, 2.7 Hz, 1/2H), 4.76 (dd, J=9.6,
2.4 Hz, 1/2H), 5.47 ppm (d, J=3.3 Hz 1/2H); IR (KBr): n˜ =3418,
1715 cmꢀ1; MS (FAB): m/z: 209 [M+Na]+; HRMS (FAB): m/z: calcd for
C10H18O3Na: 209.1154 [M+Na]+; found: 209.1168.
6-Hydroxymethyl-6-phenyltetrahydropyran-2-one (19a): Colorless oil;
1H NMR (300 MHz, CDCl3): d=1.55 (m, 1H), 1.76 (m, 1H), 2.17 (dt, J=
13.8, 4.2 Hz, 1H), 2.29 (dd, J=12.6, 4.2 Hz, 1H), 2.35–2.49 (m, 2H),
2.55–2.61 (m, 1H), 3.60 (A in ABq, J=12.3 Hz, 1H), 3.71 (B in ABq, J=
12.3 Hz, 1H), 7.22–7.34 ppm (m, 5H); 13C NMR (75 MHz, CDCl3): d=
15.8, 27.7, 29.2, 69.9, 88.4, 125.2 (2C), 127.9, 128.8 (2C), 140.3,
171.9 ppm; IR (KBr): n˜ =3333, 1715 cmꢀ1; elemental analysis calcd (%)
for C12H14O3: C 69.88, H 6.84; found: C 69.57, H 6.83.
ACHTREUNG(1S*,5S*)-1-Methyl-6,8-dioxabicycloCAHTRE[UGN 3.2.1]octan-7-ol (16a): Colorless oil;
1H NMR (300 MHz, CDCl3): d=1.29 (s, 3H), 1.47–1.81 (m, 6H), 3.10
(brs, 1H), 5.15 (s, 1H), 5.68 ppm (s, 1H); 13C NMR (75 MHz, CDCl3):
d=16.0, 20.1, 28.7, 32.3, 81.6, 97.3, 102.3 ppm; IR (KBr): n˜ =3406 cmꢀ1
;
MS (FAB): m/z: 167 [M+Na]+; HRMS (FAB): m/z: calcd for
C7H12O3Na: 167.0684: [M+Na]+; found: 167.0677.
ACHTREUNG(1S*,5S*)-1-Ethyl-6,8-dioxabicycloCAHTRE[UGN 3.2.1]octan-7-ol (16b): Colorless oil;
1H NMR (300 MHz, CDCl3): d=0.94–1.01 (m, 3H), 1.44–1.80 (m, 8H),
3.07 (brs, 1H), 5.19 (s, 1H), 5.68 ppm (s, 1H); 13C NMR (75 MHz,
CDCl3): d=8.2, 15.8, 26.9, 28.6, 29.1, 84.2, 97.1, 102.5 ppm; IR (KBr): n˜ =
3406 cmꢀ1; elemental analysis calcd (%) for C8H14O3: C 60.74, H 8.92;
found: C 60.35, H 8.70.
6-Hydroxymethyl-4,4,6-trimethyltetrahydropyran-2-one (19b): Colorless
oil; 1H NMR (300 MHz, CDCl3): d=1.05 (s, 3H), 1.13 (s, 3H), 1.40 (s,
3H), 1.54 (d, J=13.7 Hz, 1H), 1.96 (d, J=13.7 Hz, 1H), 2.30 (s, 2H),
2.78 (s, 1H), 3.41 (d, J=11.9 Hz, 1H), 3.56 ppm (d, J=11.9 Hz, 1H);
13C NMR (75 MHz, CDCl3): d=25.8, 28.3, 30.5 (2C), 41.4, 43.2, 70.2,
83.6, 72.3 ppm; IR (KBr): n˜ =3402, 1715, 1066 cmꢀ1; elemental analysis
calcd (%) for C9H16O3: C 62.77, H 9.36; found: C 62.74, H 9.23.
ACHTREUNG(1S*,5S*)-1-Undecyl-6,8-dioxabicycloACHTRE[UNG 3.2.1]octan-7-ol (16c): Colorless
1
crystals; m.p. 458C (hexane); H NMR (300 MHz, CDCl3): d=0.88 (t, J=
6.6 Hz, 3H), 1.26 (m, 20H), 1.51–1.72 (m, 6H), 3.27 (brs, 1H), 5.17 (s,
1H), 5.67 ppm (s, 1H); 13C NMR (75 MHz, CDCl3): d=14.0, 15.8, 22.6,
23.8, 29.1, 29.2, 29.3, 29.5 (2C), 29.6 (2C), 30.2, 31.8, 34.0, 83.9, 97.1,
102.2 ppm; IR (KBr): n˜ =3360 cmꢀ1; elemental analysis calcd (%) for
C17H32O3: C 71.79, H 11.34; found: C 71.58, H 11.09.
1-Oxaspiro
pound were identical to those reported in the literature.[34]
1-Oxaspiro
[5.5]undecane-2,7-dione (17b): Colorless oil; 1H NMR
ACHTRE[UNG 4.5]decane-2,6-dione (17a): The spectral data for this com-
AHCTREUNG
(300 MHz, CDCl3): d=1.75–1.91 (m, 4H), 2.03–2.11 (m, 2H), 2.38 (dd,
J=6.0, 5.1 Hz, 2H), 2.49 (m, 2H), 2.59 (m, 2H), 2.71 ppm (dd, J=6.3,
6.3 Hz, 2H); 13C NMR (75 MHz, CDCl3): d=21.0, 22.5, 24.0, 35.9, 36.1,
42.4 (2C), 201.8, 203.5 ppm; IR (KBr): n˜ =2932, 1713 cmꢀ1; MS (FAB):
m/z: 205 [M+Na]+; HRMS (FAB): m/z: calcd for C10H14O3Na: 205.0841
[M+Na]+; found: 205.0865.
ACHTREUNG(1S*,5S*)-1-Isobutyl-6,8-dioxabicycloACHTRE[UNG 3.2.1]octan-7-ol (16d): Colorless
1
oil; H NMR (300 MHz, CDCl3): d=0.94 (d, J=6.6 Hz, 3H), 0.99 (d, J=
6.6 Hz, 3H), 1.47–1.95 (m, 9H), 2.92 (brs, 1H), 5.16 (s, 1H), 5.66 (s, 1H),
5.68 ppm (s, 1H); 13C NMR (75 MHz, CDCl3): d=15.9, 23.5, 23.8, 24.0,
29.0, 29.1, 42.1, 83.8, 97.6, 102.2 ppm; IR (KBr): n˜ =3412 cmꢀ1; elemental
analysis calcd (%) for C10H18O3: C 64.49, H 9.74; found: C 64.56, H 9.57.
6-Acetyl-tetrahydropyran-2-one (17c): The spectral data for this com-
pound were identical to those reported in the literature.[35]
ACHTREUNG(1S*,5S*)-1-Benzyl-6,8-dioxabicycloACHTRE[UNG 3.2.1]octan-7-ol (16e): Colorless
crystals; m.p. 1038C ( EtO); 1H NMR (300 MHz, CDCl3): d=1.34–1.77
cis-6-Acetyl-4-isopropyltetrahydropyran-2-one (17d): Colorless oil;
1H NMR (300 MHz, CDCl3): d=0.85 (d, J=6.6 Hz, 6H), 1.27 (m, 1H),
1.50 (m, 1H), 1.73 (m, 1H), 2.08–2.22 (m, 2H), 2.25 (s, 3H), 2.66 (ddd,
J=17.8, 5.9, 1.9 Hz, 1H), 4.53 ppm (dd, J=11.9, 3.2 Hz, 1H); 13C NMR
(75 MHz, CDCl3): d=19.2 (2C), 25.9, 28.7, 32.3, 34.0, 37.7, 83.7, 169.8,
205.8 ppm; IR (KBr): n˜ =1717 cmꢀ1; MS (EI): m/z: 184 [M]+; HRMS
(EI): m/z: calcd for C10H16O3: 184.1099; found: 184.1112.
2
(m, 6H), 2.95 (A in ABq, J=13.9 Hz, 1H), 3.01 (B in ABq, J=13.9 Hz,
1H), 3.09 (brs, 1H), 5.23 (s, 1H), 5.75 (s, 1H), 7.19–7.34 ppm (m, 5H);
13C NMR (75 MHz, CDCl3): d=15.7, 28.9, 29.2, 40.0, 83.9, 97.2, 102.8,
126.5, 128.2 (2C), 130.4 (2C), 136.5 ppm; IR (KBr): n˜ =3406 cmꢀ1; MS
(EI): m/z: 220 [M]+; HRMS (EI): m/z: calcd for C13H16O3: 220.1099;
found: 220.1116.
ACHTREUNG(1S*,5S*)-1-Phenyl-6,8-dioxabicycloCAHTRE[UGN 3.2.1]octan-7-ol (16 f): Colorless oil;
Asymmetric total synthesis of (+)-tanikolide (Schemes 14 and 15): The
enantiomeric excess values of optically active compounds were deter-
mined by chiral HPLC analysis by using Daicel Chiralcel OD columns
with hexanes/iPrOH as the eluent.
1H NMR (300 MHz, CDCl3): d=1.40–2.62 (m, 5H), 3.04 (t, J=7.2 Hz, 4/
5H), 3.13 (s, 1/5H), 5.27 (d, J=4.8 Hz, 1/5H), 5.50 (t, J=9.9 Hz, 4/5H),
5.65 (s, 1/5H), 5.86 (s, 4/5H), 7.24–7.50 ppm (m, 5H); IR (KBr): n˜ =
3400 cmꢀ1; elemental analysis calcd (%) for C12H14O3: C 69.88, H 6.84;
found: C 69.73, H 6.85.
2-Iodo-3-undecylcyclohex-2-enone (23): Azidotrimethylsilane (1.3 mL,
5.0 mmol) was added to a stirred solution of the known enone[14] 21
(91.6 mg, 0.36 mmol) in CH2Cl2 (0.5 mL) at 08C under N2. After the reac-
tion mixture had been stirred for 2 h, I2 (1.28 g, 5.0 mmol) in CH2Cl2
A
ACHTRE[UGN 3.2.1]octan-7-ol (16g): Color-
5246
www.chemeurj.org
ꢁ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2007, 13, 5238 – 5248

Synthesis of Lactols and Lactones
FULL PAPER
(0.54 mL) and pyridine (3.0 mL) were added dropwise. The reaction mix-
ture was gradually warmed to room temperature and stirred for 24 h.[17]
Saturated aqueous Na2S2O3 solution was added to the reaction mixture
and the resulting mixture was extracted with Et2O. The organic layer was
washed with 10% HCl, saturated aqueous NaHCO3 solution, and brine.
The layer was then dried over Na2SO4 and evaporated in vacuo. The resi-
due was purified by silica gel column chromatography with hexane/
AcOEt 8:1 to give 23 (108.8 mg, 80%) as a brownish oil: 1H NMR
(300 MHz, CDCl3): d=0.85 (t, J=6.5 Hz, 3H), 1.24–1.31 (m, 16H), 1.47–
1.52 (m, 2H), 1.89–1.98 (m, 2H), 2.46–2.60 ppm (m, 6H); 13C NMR
(75 MHz, CDCl3): d=14.0, 22.3, 22.6, 26.9, 29.2, 29.3, 29.4, 29.5 (3C),
31.8, 32.5, 36.5, 44.8, 106.6, 170.2, 192.2 ppm; IR (KBr): n˜ =1682,
analysis calcd (%) for C17H32O2: C 76.06, H 12.02; found: C 75.93, H
11.81.
A
ACHTREUNG
a
(175.6 mg, 0.65 mmol) in CH3CN/H2O (v/v 4:1, 6.5 mL) at 08C. After the
reaction mixture had been stirred for 12 h at room temperature, saturat-
ed aqueous Na2S2O3 solution was added. The solution was extracted with
AcOEt. The organic layer was dried over Na2SO4 and evaporated in
vacuo. The residue was purified by silica gel column chromatography
with hexane/AcOEt 5:1 as the eluent to give (+)-16c (134.0 mg, 72%) as
colorless crystals. M.p. 458C (hexane); [a]2D6:4 =+54.17 (c=0.54 in
CHCl3).
1583 cmꢀ1
;
MS (EI): m/z: 376 [M]+; HRMS (EI): m/z: calcd for
(+)-Tanikolide ((+)-25): DIBAH (0.94m in hexane, 1.04 mL, 0.98 mmol)
was added to a stirred solution of (+)-16c (79.9 mg, 0.28 mmol) in
CH2Cl2 (2.8 mL) at ꢀ158C under N2 and gradually warmed to 08C. After
the reaction mixture had been stirred for 30 min at the same tempera-
ture, MeOH and Rochelleꢀs salt were added and the mixture was extract-
ed with CH2Cl2. The organic layer was dried over Na2SO4 and evaporated
in vacuo. Ag2CO3 on Celite[10] (772 mg, 2.8 mmol) was added to the solu-
tion of the obtained crude lactol in benzene (2.8 mL) and the mixture
was refluxed for 45 min. The cooled reaction mixture was diluted with
AcOEt and filtered through a pad of Celite. The filtrate was evaporated
in vacuo. The residue was purified by silica gel column chromatography
with hexane/AcOEt 1:1 as the eluent to give (+)-tanikolide ((+)-25;
45.9 mg, 57%) as colorless crystals. M.p. 448C (hexane); [a]2D5:9 =+2.60
(c=1.08 in CHCl3) (lit.:[11] [a]D25 =+2.3 (c=0.65 in CHCl3)); 1H NMR
(300 MHz, CDCl3): d=0.81 (t, J=6.6 Hz, 3H), 1.19 (m, 18H), 1.54–1.90
(m, 7H), 2.40 (t, J=6.5 Hz, 2H), 2.57 (brs, 1H), 3.48 (d, J=12.0 Hz,
1H), 3.60 ppm (d, J=12.0 Hz, 1H); 13C NMR (75 MHz, CDCl3): d=14.1,
16.6, 22.6, 23.4, 26.6, 29.3, 29.4, 29.5 (2C), 29.6, 29.7, 29.9, 31.8, 36.7, 67.4,
86.6, 171.9 ppm; IR (KBr): n˜ =3396, 1715 cmꢀ1; MS (FAB): m/z: 285
[M+Na]+; HRMS (FAB): m/z: calcd for C17H33O3: 285.2429 [M+H]+;
found: 285.2452.
C17H29IO: 376.1263; found: 376.1253.
(R)-2-Iodo-3-undecylcyclohex-2-enol ((+)-24): (S)-5,5-diphenyl-2-methyl-
3,4-propano-1,3,2-oxazaborolidine (1m in toluene, 0.080 mL, 0.080 mmol)
in THF (0.5 mL) was added dropwise to a solution of BH3·Me2S ( 2m in
THF, 40 mL, 0.080 mmol) at 08C under N2. After the reaction mixture
had been stirred for 30 min, 23 (30.0 mg, 0.080 mmol) in THF (0.25 mL)
was added slowly.[15] After the resulting mixture had been stirred for a
further 30 min, MeOH was added and the solvent was removed in vacuo.
The residue was purified by silica gel column chromatography with ben-
zene/AcOEt 70:1 as the eluent to give (+)-24 (28.0 mg, 93%) as colorless
crystals. M.p. 488C (hexane); [a]2D1:1 =+47.83 (c=1.12 in CHCl3);
1H NMR (300 MHz, CDCl3): d=0.85 (t, J=6.7 Hz, 3H), 1.24–1.37 (m,
18H), 1.61–1.88 (m, H), 2.11–2.22 (m, 5H), 4.26 ppm (t, J=4.4 Hz, 1H);
13C NMR (75 MHz, CDCl3): d=14.1, 18.6, 22.7, 27.1, 29.3, 29.4 (2C),
29.5, 29.6, 29.6, 31.5, 31.9 (2C), 42.8, 74.0, 104.2, 146.5 ppm; IR (KBr):
n˜ =3441, 1682 cmꢀ1; MS (EI): m/z: 378 [M]+; HRMS (EI): m/z: calcd for
C17H31IO: 378.1420; found: 378.1430.
(R)-3-Undecylcyclohex-2-enol ((+)-22)
By catalytic hydrogenation in the presence of quinoline:[19] 10% Pd/C
(120 mg) was added to a solution of (+)-24 (454 mg, 1.2 mmol), sodium
acetate, and quinoline (catalytic amount) in MeOH (120 mL). After
being stirred under a H2 atmosphere (1 atm) for 1 h, the reaction mixture
was filtered through a pad of Celite. H2O was added to the filtrate and
the mixture was extracted with CH2Cl2. The combined organic layer was
evaporated in vacuo. The residue was purified by silica gel column chro-
matography with benzene/AcOEt 70:1 as the eluent to give (+)-22
(28.0 mg, 93%).
By radical reduction:[18a] Et3B ( 1m in hexane, 69.9 mL, 0.070 mmol) and
Bu3SnH (23.5 mL, 0.090 mmol) were added to a stirred solution of (+)-24
(18.9 mg, 0.050 mmol) in toluene (0.5 mL) at 08C under N2.[18a] After the
reaction mixture had been stirred for 3 h at room temperature, MeOH
was added and evaporated in vacuo. The residue was purified by silica
gel column chromatography with hexane/AcOEt 7:1 as the eluent to give
(+)-22 (10.6 mg, 84%) as a colorless oil. [a]2D5:6 =+27.36 (c=1.15 in
CHCl3); 1H NMR (300 MHz, CDCl3): d=0.88 (t, J=6.5 Hz, 3H), 1.26–
1.98 (m, 27H), 4.19 (brs, 1H), 5.48 ppm (brs, 1H); 13C NMR (75 MHz,
CDCl3): d=14.1, 19.1, 22.6, 27.5, 28.4, 29.3 (2C), 29.5, 29.6 (3C), 31.9
(2C), 37.6, 65.8, 123.5, 142.6 ppm; IR (KBr): n˜ =3344 cmꢀ1; MS (EI):
m/z: 252 [M]+; HRMS (EI): m/z: calcd for C17H32O; 252.2453; found:
252.2461.
Acknowledgement
This work was supported by a Grant-in-Aid for Scientific Research (S)
and a Grant-in-Aid for Scientific Research for Exploratory Research
from the Japan Society for the Promotion of Science and by a Grant-in-
Aid for Scientific Research on Priority Areas (17035047) from the Minis-
try of Education, Culture, Sports, Science, and Technology, Japan.
[1] a) L. F. Tietze, U. Beifuss, Angew. Chem. 1993, 105, 137–170;
Angew. Chem. Int. Ed. Engl. 1993, 32, 131–163; b) R. A. Bunce, Tet-
rahedron 1995, 51, 13103–13159; c) L. F. Tietze, Chem. Rev. 1996,
96, 115–136; d) P. J. Parsons, C. S. Penkett, A. J. Shell, Chem. Rev.
1996, 96, 195–206.
[2] a) Y. Kita, H. Tohma, T. Yakura, Trends Org. Chem. 1992, 113–128;
b) Y. Kita, T. Takada, H. Tohma, Pure Appl. Chem. 1996, 68, 627–
630; c) P. J. Stang, V. V. Zhdankin, Chem. Rev. 1996, 96, 1123–1178;
d) V. V. Zhdankin, P. J. Stang, Chem. Rev. 2002, 102, 2523–2584;
e) H. Tohma, Y. Kita, J. Synth. Org. Chem. Jpn. 2004, 62, 116–127;
f) T. Wirth, Angew. Chem. 2005, 117, 3722–3731; Angew. Chem. Int.
Ed. 2005, 44, 3656–3665.
[3] a) Y. Tamura, T. Yakura, J. Haruta, Y. Kita, J. Org. Chem. 1987, 52,
3927–3930; b) Y. Kita, H. Tohma, K. Kikuchi, M. Inagaki, T.
Yakura, J. Org. Chem. 1991, 56, 435–438; c) H. Tohma, S. Takizawa,
T. Maegawa, Y. Kita, Angew. Chem. 2000, 112, 1362–1364; Angew.
Chem. Int. Ed. 2000, 39, 1306–1308; d) H. Tohma, A. Maruyama, A.
Maeda, T. Maegawa, T. Dohi, M. Shiro, T. Morita, Y. Kita, Angew.
Chem. 2004, 116, 3679–3682; Angew. Chem. Int. Ed. 2004, 43, 3595–
3598; e) T. Dohi, A. Maruyama, M. Yoshimura, K. Morimoto, H.
Tohma, Y. Kita, Angew. Chem. 2005, 117, 6349–6352; Angew.
Chem. Int. Ed. 2005, 44, 6193–6196; f) T. Dohi, K. Morimoto, Y.
Kiyono, A. Maruyama, H. Tohma, Y. Kita, Chem. Commun. 2005,
A
ACHTRE[UGN 4.1.0]heptan-2-ol ((+)-15c): VO-
ACHTREUNG
(310 mg, 1.2 mmol) in benzene (10 mL) at 08C under N2. After the reac-
tion mixture had been stirred for 1 h at room temperature, tBuOOH
(0.4 mL, 3.7 mmol) in benzene was added at 08C and stirred for 1.5 h at
room temperature.[20] The reaction mixture was poured into saturated
aqueous Na2S2O3 solution and extracted with AcOEt. The organic layer
was washed with brine, dried over Na2SO4, and evaporated in vacuo. The
residue was purified by silica gel column chromatography with hexane/
AcOEt 3:1 as the eluent to give (+)-15c (315 mg, 96%) as colorless crys-
tals. M.p. 438C (hexane); [a]2D5:6 =+21.19 (c=1.56 in CHCl3); 1H NMR
(300 MHz, CDCl3): d=0.88 (t, J=6.7 Hz, 3H), 1.26–1.80 (m, 26H), 2.18
(brs, 1H), 3.13 (d, J=2.9 Hz, 1H), 3.98 ppm (brs, 1H); 13C NMR
(75 MHz, CDCl3): d=4.1, 18.2, 22.6, 24.7, 26.6, 29.1, 29.3, 29.5 (2C), 29.6
(3C), 31.9, 37.4, 61.4, 64.4, 66.9 ppm; IR (KBr): n˜ =3418 cmꢀ1; elemental
Chem. Eur. J. 2007, 13, 5238 – 5248
ꢁ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
5247

Y. Kita et al.
2930–2932; g) T. Dohi, K. Morimoto, A. Maruyama, Y. Kita, Org.
Lett. 2006, 8, 2007–2010.
M. Iwata, M. Makida, Y. Masaki, Chem. Pharm. Bull. 2004, 52, 848–
852; i) T. Ohgiya, K. Nakamura, S. Nishiyama, Bull. Chem. Soc. Jpn.
2005, 78, 1549–1554; j) F. Wu, R. Hong, J. Khan, X. Liu, L. Deng,
Angew. Chem. 2006, 118, 4407–4411; Angew. Chem. Int. Ed. 2006,
45, 4301–4305.
[4] a) Y. Kita, H. Tohma, M. Inagaki, K. Hatanaka, T. Yakura, J. Am.
Chem. Soc. 1992, 114, 2175–2180; b) H. Tohma, Y. Harayama, M.
Hashizume, M. Iwata, M. Egi, Y. Kita, Angew. Chem. 2002, 114,
358–360; Angew. Chem. Int. Ed. 2002, 41, 348–350; c) H. Tohma, Y.
Harayama, M. Hashizume, M. Iwata, Y. Kiyono, M. Egi, Y. Kita, J.
Am. Chem. Soc. 2003, 125, 11235–11240; d) Y. Harayama, M. Yosh-
ida, D. Kamimura, Y. Kita, Chem. Commun. 2005, 1764–1766; e) Y.
Harayama, M. Yoshida, D. Kamimura, Y. Wada, Y. Kita, Chem.
Eur. J. 2006, 12, 4893–4899.
[14] J.-P. Barnier, V. Morisson, I. Volle, L. Blanco, Tetrahedron: Asym-
metry 1999, 10, 1107–1117.
[15] E. J. Corey, R. K. Bakshi, S. Shibata, C.-P. Chen, V. K. Singh, J. Am.
Chem. Soc. 1987, 109, 7925–7926.
[16] S. Demay, K. Harms, P. Knochel, Tetrahedron Lett. 1999, 40, 4981–
4984.
[5] Y. Kita, S. Matsuda, E. Fujii, S. Kitagaki, R. Inoguchi, K. Hata, H.
Fujioka, Heterocycles 2005, 66, 309–317.
[6] S. Spyroudis, A. Varvoglis, J. Org. Chem. 1981, 46, 5231–5233.
[7] Y. Kita, S. Matsuda, E. Fujii, M. Horai, K. Hata, H. Fujioka, Angew.
Chem. 2005, 117, 6007–6010; Angew. Chem. Int. Ed. 2005, 44, 5857–
5860.
[17] C.-K. Sha, S.-J. Huang, Tetrahedron Lett. 1995, 36, 6927–6928.
[18] a) K. Nozaki, K. Oshima, K. Utimoto, Bull. Chem. Soc. Jpn. 1991,
64, 403–409; b) Y. Kita, A. Sano, T. Yamaguchi, M. Oka, K. Gotan-
da, M. Matsugi, Tetrahedron Lett. 1997, 38, 3549–3552.
[19] F. Chouteau, K. Addi, M. Bꢂnꢂchie, T. Prangꢂ, F. Khuong-Huu, Tet-
rahedron 2001, 57, 6229–6238.
[8] a) R. Criegee, H. Beucker, Justus Liebigs Ann. Chem. 1939, 541,
218–238; b) M. Ohno, I. Oguri, S. Eguchi, J. Org. Chem. 1999, 64,
8995–9000.
[20] K. B. Sharpless, R. C. Michaelson, J. Am. Chem. Soc. 1973, 95,
6136–6137.
[21] Y. Kita, S. Kitagaki, Y. Yoshida, S. Mihara, D.-F. Fang, M. Kondo, S.
Okamoto, R. Imai, S. Akai, H. Fujioka, J. Org. Chem. 1997, 62,
4991–4997.
[22] K. Kaneda, K. Jitsukawa, T. Itoh, S. Teranishi, J. Org. Chem. 1980,
45, 3004–3009.
[23] T. Hirata, T. Higata, K. Shimoda, D. I. Ito, S. Izumi, J. Labelled
Compd. Radiopharm. 1997, 39, 285–290.
[24] A. Yasuda, H. Yamamoto, H. Nozaki, Bull. Chem. Soc. Jpn. 1979,
52, 1757–1759.
[25] V. R. Tadwalker, M. Narayanaswamy, A. S. Rao, Indian J. Chem.
1971, 9, 1223–1226.
[26] K. Mori, B. G. Hazra, R. J. Pfeiffer, A. K. Gupta, B. S. Lindgren, Tet-
rahedron 1987, 43, 2249–2254.
[27] See reference [9g].
[9] a) X. Li, B. Wu, X. Z. Zhao, Y. X. Jia, Y. Q. Tu, D. R. Li, Synlett
2003, 623–626; b) D. R. Li, W. J. Xia, Y. Q. Tu, F. M. Zhang, L. Shi,
Chem. Commun. 2003, 798–799; c) X.-D. Hu, C.-A. Fan, F.-M.
Zhang, Y. Q. Tu, Angew. Chem. 2004, 116, 1734–1737; Angew.
Chem. Int. Ed. 2004, 43, 1702–1705; d) S. Matsubara, H. Yamamoto,
K. Oshima, Angew. Chem. 2002, 114, 2961–2964; Angew. Chem. Int.
Ed. 2002, 41, 2837–2839; e) Y. Q. Tu, L. D. Sun, P. Z. Wang, J. Org.
Chem. 1999, 64, 629–633; f) C.-A. Fan, B.-M. Wang, Y.-Q. Tu, Z.-L.
Song, Angew. Chem. 2001, 113, 3995–3998; Angew. Chem. Int. Ed.
2001, 40, 3877–3880; g) C.-A. Fan, X.-D. Hu, Y.-Q. Tu, B.-M. Wang,
Z.-L. Song, Chem. Eur. J. 2003, 9, 4301–4310; h) B. M. Trost, Z. T.
Ball, E.-J. Kang, Org. Lett. 2005, 7, 4911–4913; i) S. Jana, C. Guin,
S. C. Roy, J. Org. Chem. 2005, 70, 8252–8254.
[10] a) E. L. Eliel, N. L. Allinger, S. J. Angyal, G. A. Morrison, Confor-
mational Analysis, Wiley-Interscience, New York, 1965, p. 102; b) A.
Fürst, P. A. Plattner, Abstract of Papers, 12th International Congress
of Pure and Applied Chemistry, New York, 1951, p. 409.
[11] M. Fetizon, M. Golfier, P. Mourgues, Tetrahedron Lett. 1972, 13,
4445–4448.
[28] G. Magnusson, S. Thorꢂn, J. Org. Chem. 1973, 38, 1380–1384.
[29] P. von Zezschwitz, F. Petry, A. de Meijere, Chem. Eur. J. 2001, 7,
4035–4046.
[30] S. V. Gagner, R. L. Larock, J. Am. Chem. Soc. 2003, 125, 4804–
4807.
[31] E. Negishi, Z. Tan, S.-Y. Liou, B. Liao, Tetrahedron 2000, 56,
10197–10207.
[32] M. dꢀAugustin, L. Palais, A. Alexakis, Angew. Chem. 2005, 117,
1400–1402; Angew. Chem. Int. Ed. 2005, 44, 1376–1378.
[33] K. Sakai, Y. Ishiguro, K. Funakoshi, K. Ueno, H. Suemune, Tetrahe-
dron Lett. 1984, 25, 961–964.
[12] I. P. Singh, K. E. Milligan, W. H. Gerwick, J. Nat. Prod. 1999, 62,
1333–1335.
[13] a) R. M. Kanada, T. Taniguchi, K. Ogasawara, Synlett 2000, 1019–
1021; b) H. Tanaka, Y. Kozuki, K. Ogasawara, Tetrahedron Lett.
2002, 43, 4175–4178; c) H. Mizutani, M. Watanabe, T. Honda, Tetra-
hedron 2002, 58, 8929–8936; d) A. E. Koumbis, K. M. Dieti, M. G.
Vikentiou, J. K. Gallos, Tetrahedron Lett. 2003, 44, 2513–2516;
e) M. Carda, S. Rodriguez, E. Castillo, A. Bellido, S. Diaz-Oltra,
M. J. Alberto, Tetrahedron 2003, 59, 857–864; f) J. M. Shomaker, B.
Borhan, Org. Biomol. Chem. 2004, 2, 621–624; g) T. Ohgiya, S.
Nishiyama, Tetrahedron Lett. 2004, 45, 8273–8275; h) H. Arasaki,
[34] D. Desmaꢃle, J. dꢀAngelo, Tetrahedron Lett. 1989, 30, 345–348.
[35] J. K. Crandall, E. Rambo, Tetrahedron 2002, 58, 7027–7036.
Received: September 19, 2006
Revised: January 15, 2007
Published online: March 23, 2007
5248
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