Synthesis of fused tetrahydropyrans by hydroalkoxylation of δ-hydroxy allenes

Article abstract of DOI:10.1016/j.tet.2013.08.026

Fused tetrahydropyrans were synthesized by silver(I)- and mercury(II)-mediated intramolecular hydroalkoxylations of δ-hydroxy allenes installed on a tetrahydropyran template. Cyclization of simple allenes was promoted by silver perchlorate to afford vinyl-substituted trans-fused bis-tetrahydropyrans, whereas cyclization of methyl-substituted allenes at the internal allenic carbon atom was achieved more effectively with a catalytic amount of mercuric triflate rather than with silver salts.

Full text of DOI:10.1016/j.tet.2013.08.026

Tetrahedron 69 (2013) 9086e9095
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Tetrahedron
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Synthesis of fused tetrahydropyrans by hydroalkoxylation of
d-hydroxy allenes
*
Yumie Suzuki, Ayano Kuwabara, Yasuhiro Koizumi, Yuji Mori
Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya 468-8503, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 2 July 2013
Received in revised form 9 August 2013
Accepted 13 August 2013
Available online 20 August 2013
Fused tetrahydropyrans were synthesized by silver(I)- and mercury(II)-mediated intramolecular hy-
droalkoxylations of -hydroxy allenes installed on a tetrahydropyran template. Cyclization of simple
allenes was promoted by silver perchlorate to afford vinyl-substituted trans-fused bis-tetrahydropyrans,
whereas cyclization of methyl-substituted allenes at the internal allenic carbon atom was achieved more
effectively with a catalytic amount of mercuric triflate rather than with silver salts.
Ó 2013 Elsevier Ltd. All rights reserved.
d
Keywords:
Tetrahydropyran
Hydroalkoxylation
d-Hydroxy allenes
Silver(I)
Mercury(II)
1. Introduction
such as I have usually been prepared using the
p
-orbital assisted 6-
endo hydroxy epoxide opening method10 and
a
palladium-
Highly substituted tetrahydropyran rings are common struc-
tural units encountered in a number of biologically active natural
products such as acetogenins,1 polyether antibiotics,2 and ladder-
like marine polycyclic ethers.3 Their complex architecture has
attracted the attention of synthetic chemists, and a great deal of
effort has been devoted to the development of new methodologies
for tetrahydropyran synthesis.4,5 Among the many different ap-
proaches, intramolecular hydroalkoxylation of allenes with alco-
catalyzed cyclization of hydroxy allylic alcohols.11 The cyclization
precursor II could be readily prepared by the nucleophilic addition
of allenyl anion IV to aldehyde III. This retrosynthetic analysis en-
ables a short route to the vinyl-substituted tetrahydropyran I.
Herein, we report the reactivities and stereoselectivities of silver(I)-
and mercury(II)-mediated hydroalkoxylations of
templated on a tetrahydropyran ring.
d-hydroxy allenes
hols represents an attractive alternative in which
a new
H
carboneoxygen bond is formed by activation of an allenic double
bond by a metal cation such as silver, palladium, or gold followed by
nucleophilic attack by a hydroxy group. The metal-mediated
H
H
H
H
H
H
H
O
OH
OH
allenylation
O H
H
IV
6-exo
O
OH
O
O
O
hydroalkoxylation of a-, b-, and g-hydroxy allenes has been well
cyclization
H
H
studied and allows access to five- and six-membered oxygen het-
I
II
III
erocycles in
a
straightforward manner.6,7 However, hydro-
d-hydroxy allenes has rarely been studied. The few
Scheme 1. Retrosynthetic analysis of I.
alkoxylation of
reported examples are restricted to simple acyclic
d-hydroxy
allenes,8 and their application to the synthesis of fused polycyclic
ether ring systems remains unexplored.
2. Results and discussion
The requisite
In the course of our synthetic study on polycyclic ethers,9 we
have become interested in the hydroalkoxylation reaction of d-
hydroxy allene II to tetrahydropyran I (Scheme 1). Structural units
d
-hydroxy allenes were prepared by allenylation of
the optically active aldehyde 112 (Scheme 2). Regioselective addi-
tion of commercially available 1-trimethylsilyl-3-bromopropyne
with 1 in the presence of CrCl2 and trimethylchlorosilane13 affor-
ded allenic alcohols 2 and 3 in 60% and 24% yields, respectively.
Selective desilylation of the C-TMS group in the presence of the O-
* Corresponding author. E-mail address: mori@meijo-u.ac.jp (Y. Mori).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.08.026

Y. Suzuki et al. / Tetrahedron 69 (2013) 9086e9095
9087
1. BnBr, KHMDS
THF, -10 °C
80%
TMS
H
H
H
H
H
H
1. NaOMe
THF, 0 °C
OTBS
OTBS
OH
6
O
O
H
O
H
O
O
H
2. PPTS
2. TBAF, THF, rt
92%
OH
OH
OBn
≡
1. TMSC CCH2Br
MeOH, rt
CrCl2, TMSCl
THF, rt
2 (60%)
4
H
73% (two steps)
OTBS
CHO
2. PPTS
MeOH, rt
O
1. BnBr, KHMDS
THF, -10 °C
82%
TMS
OTBS
H
1
H
H
H
H
H
H
1. NaOMe
THF, 0 °C
OTBS
OH
7
OH
O
OH
OBn
2. PPTS
2. TBAF, THF, rt
98%
H
H
H
MeOH, rt
3 (24%)
5
75% (two steps)
Scheme 2. Synthesis of
d-hydroxy allenes 6 and 7.
TBS group was carried out under the [1,3]-Brook rearrangement
level (0.3 equiv) resulted in the incomplete consumption of 6 after
prolonged time (data not shown). A higher temperature shortened
the reaction time but lowered the yield (entry 3). The reactions
with AgBF4 and AgOTf were also effective in affording the product
in moderate yields (entries 4 and 5). It has been reported that
reaction conditions.14 Thus, treatment of 2 and 3 with sodium
methoxide in THF at 0 ꢀC yielded
a-trimethylsilyloxy allenes, whose
O-TMS groups were selectively removed by treatment with PPTS in
methanol to give alcohols 4 and 5 in good yields. In order to verify
the stereochemistry of 5, we attempted a reaction in which the
reagent control can be simply extended to 1, Corey’s asymmetric
allenylation of aldehyde 1 with (4R,5R)-2-bromo-1,3-bis(p-tolue-
nesulfonyl)-4,5-diphenyl-1,3,2-diazaborolidine.15 The sample pre-
pared by asymmetric allenylation was identical to 5, confirming the
(S)-configuration of the hydroxy group. Benzylation of 4 and 5
Hg(OCOCF3)2 can promote hydroalkoxylation of g-hydroxy allenes
under stoichiometric conditions,16 and, more recently, Nishizawa
reported that Hg(OTf)2 has a higher affinity for alkenes and al-
kynes and promotes intramolecular heterocyclization under very
mild reaction conditions with high catalytic turnover.17 However,
the reaction for hydroxy allenes has not been explored yet. We
therefore attempted to examine the use of Hg(OTf)2 for the
hydroalkoxylation of 6. The reaction caused significant de-
composition of the reaction mixture, even with a catalytic amount
(10 mol %) of Hg(OTf)2 at a lower temperature (0 ꢀC), and led to
a poor yield (entry 6).
followed by cleavage of the TBS ether with TBAF afforded
zyloxy -hydroxy allenes 6 and 7 in 74% and 80% yields, re-
spectively, after the two steps.
First, intramolecular hydroalkoxylation of 6 with silver salts
a-ben-
d
was studied (Table 1). The cyclization reaction of d-hydroxy allene
6 with AgNO3 under Gore’s standard conditions8a did not proceed
at ambient temperature. However, the cyclization was driven at
elevated temperatures over a longer reaction time (80 ꢀC, 40 h)
Hydroalkoxylation of the diastereomeric
was examined next. The cyclization was promoted by silver salts,
but the yields were generally low, and mixture of di-
d-hydroxy allene 7
a
with
4
equiv of AgNO3 in dioxane/H2O to afford bis-
astereoisomers was formed (Table 2). Treatment of 7 with AgClO4
or AgBF4 led to inseparable 8:1 mixtures of isomers 9 and 10 in
42% or 32% combined yields, respectively (entries 2 and 3). The
tetrahydropyran 8 in 40% yield as a single isomer (entry 1).
Treatment with 1.2 equiv of AgClO4 in 1,2-dichloroethane (DCE) at
Table 1
Hydroalkoxylation of 6
10.4% NOE
H
H
H
H
H
H
H
H
OH
O
O
7.2% NOE
O
H
O
H
O
H
OBn
OBn
OBn
6
8
NOEs of 8
Entry
Reagent
equiv
Solvent
Temp (ꢀC)
Time (h)
Yielda (%)
1
2
3
4
5
6
AgNO3
AgClO4
AgClO4
AgBF4
AgOTf
Hg(OTf)2
4.0
1.2
1.5
1.5
1.5
0.1
Dioxane/H2O
DCE
DCE
DCE
DCE
80
50
80
50
50
0
40
20
10
20
15
5
40
88
59
62
53
20
CH2Cl2
a
Isolated yield.
50 ꢀC for 20 h afforded product 8 in 88% yield (entry 2). 1H NMR
analysis of the isolated product showed the exclusive formation of
8, whose stereochemistry was unambiguously determined
according to the nuclear Overhauser effect (NOE) enhancements,
as shown. Decreasing the amount of the silver salt to a catalytic
diastereomeric ratio (dr) increased to 49:1 when AgOTf was
employed (entry 4). In contrast to the silver(I)-mediated reactions,
the mercury(II)-catalyzed hydroalkoxylation showed the opposite
diastereoselectivity to afford a 1:2 mixture of products in 59%
yield (entry 5).

9088
Y. Suzuki et al. / Tetrahedron 69 (2013) 9086e9095
Table 2
Hydroalkoxylation of 7
9.2% NOE
H
H
H
O
H
H
H
H
H
H
H
H
OH
O
O
H
O
OBn
H
O
OBn
O
OBn
O
OBn
H
H
3.5% NOE
NOEs of 9
7
9
10
Entry
Reagent
equiv
Solvent
Temp (ꢀC)
Time (h)
Yielda (%)
drb (9/10)
1
2
3
4
5
AgNO3
AgClO4
AgBF4
AgOTf
Hg(OTf)2
4.0
1.5
1.5
1.5
0.1
Acetone/H2O
DCE
DCE
DCE
CH2Cl2
50
50
50
50
0
32
24
30
20
15
NR
42
32
34
59
d
89:11
88:12
98:2
31:69
a
Isolated yield of a mixture of 9 and 10.
b
Determined by 1H NMR analysis.
A possible explanation for this diastereoselectivity may be
a cooperative chelating effect of the silver ions. Silver ions have
been reported to act as either -Lewis acids, -Lewis acids, or
both.18 We speculate that sliver ions can coordinate both the allenic
double bond and the benzyloxy oxygen to form a - and -co-
ordinated intermediate A, which allows 7 to adopt mainly a chair
conformation with an equatorial allenyl group during the
cyclization, resulting in predominant formation of the isomer 9
cyclization would directly provide a tetrahydropyran containing
a quaternary carbon atom that bears methyl and vinyl groups.
Such a structural unit has been constructed through 6-endo cy-
clization of a hydroxy epoxide with a double bond adjacent to the
epoxide moiety.19 Preparation of the hydroxy methylallenes began
from aldehyde 1 with the chromium(II)-mediated reaction with 1-
s
p
s
p
bromo-2-butyne, affording an inseparable 57:43 mixture of
a-
hydroxy allenes 11 and 12, which were then benzylated to give 13
and 14 in 40% and 30% yields from 1, respectively, after chro-
matographic separation (Scheme 4). Removal of the TBS group
(Scheme 3). In the case of the soft mercuric ion, a strong
p-co-
ordination with the allene seems to be favorable. The mercury(II)-
coordinated allenyl group in B rotates to an axial orientation (C)
to avoid the steric interaction with the benzyloxyl group, leading to
10 as a major isomer. The formation of the minor isomer in the
silver-mediated cyclization could be explained within the same
with TBAF afforded
yields.
d-hydroxy methylallenes 15 and 16 in high
scenario by considering the
p-coordinated silver intermediate in
Me
H
H
H
BnBr, TBAI
KHMDS
OTBS
OTBS
the configuration corresponding to C. In contrast, hydroxy allene 6
has no such steric interaction shown in B because the benzyloxy
group adopts an axial configuration, which would be a reason for
the selective formation of 8.
MeC CCH Br
≡
2
CHO
CrCl2, THF
O
O
Y
THF, -10°C
H
X
1
11 X = OH, Y = H
12 X = H, Y = OH
Me
H
Me
OTBS
H
H
OH
H
H
TBAF, THF
Y
Ag+
Ag+
Bn
O
Y
OH
7
9
O
O
H
X
O
X
H
H
13 X = OBn, Y = H (40% from 1)
14 X = H, Y = OBn (30% from 1)
15 X = OBn, Y = H (97%)
16 X = H, Y = OBn (94%)
A
Scheme 4. Synthesis of d-hydroxy methylallenes 15 and 16.
H
H
H
Hg+
OH
9
O
OBn
H
H
H
B
Hg+
Hydroalkoxylation of methylallene 15 with AgClO4 under the
conditions listed in entry of Table afforded bis-
7
2
1
tetrahydropyran 17 in only 26% yield along with a 15% yield of
an unexpected unsaturated ketone 18 (Table 3, entry 1). This
undesired side product was more significant in the AgBF4 and
AgOTf reactions, where the ketone was isolated in 44% and 34%
yields, respectively (entries 2 and 3). It would appear that the
steric bulk of the methyl group of the allene erodes the yield of
the cyclization. To our surprise, hydroalkoxylation of 15 with
Hg(OTf)2 proceeded smoothly at 0 ꢀC in 30 min in the presence of
10 mol % of the catalyst to afford the desired product 17 in 78%
yield, and the undesired side reaction was completely avoided
(entry 4). This result is in sharp contrast to that observed for
hydroxy allene 6 and indicates that the mercuric ion has a higher
Hg+
H
OBn
OH
10
O
H
C
Scheme 3.
We next examined the hydroalkoxylation of
that have a methyl group at the internal allenic carbon atom. Their
d
-hydroxy allenes

Y. Suzuki et al. / Tetrahedron 69 (2013) 9086e9095
9089
Table 3
Hydroalkoxylation of 15
10.1% NOE
Me
O
Me
Me
OH
H
H
Me
H
H
H
H
H
H
O
O
OH
Me
O
H
O
H
O
H
O
OBn
OBn
OBn
15
17
18
NOE of 17
Entry
Reagent
equiv
Solvent
Temp (ꢀC)
Time (h)
Yielda (%)
17
18
1
2
3
4
AgClO4
AgBF4
AgOTf
1.2
1.2
1.2
0.1
DCE
DCE
DCE
CH2Cl2
50
50
50
0
48
22
4
26
24
d
15
44
34
d
Hg(OTf)2
0.5
78
a
Isolated yield.
affinity for a methylallene than for a simple allene. The stereo-
chemistry of 17 was confirmed by the observation of a 10.1% NOE
enhancement between the hydrogen and the methyl group ad-
jacent to the newly formed ring oxygen.
Hydroxy methylallene 16 showed a lower reactivity than
allenes 7 and 15. Reaction with AgClO4 afforded a diastereomeric
mixture of products 19 and 20 in low yields (Table 4, entry 1). In
the reaction with AgBF4, 19 and 20 were obtained in a 29% com-
bined yield in a ratio of 2:1, as well as the unsaturated ketone 18 in
45% yield (entry 2). In contrast, the mercury(II)-catalyzed cycli-
zation with Hg(OTf)2 proceeded with the opposite stereo-
selectivity to afford a 1:3.5 mixture of cyclization products 19 and
20 in 71% yield (entry 4). The general trends of reactivity and
selectivity observed for methylallene 16 were similar to those
observed for allene 7.
It is possible that the formation of 17 and 18 could also be
explained by the
s- and p-coordination ability of silver (Scheme
5).18 The electron-rich methyl-substituted inner double bond of
the allene would assist in the elimination of the axially oriented
silver-coordinated benzyloxy group (E) to form an allenyl cation,
which would be followed by an attack by water on the central
allenic carbon atom during workup to afford the unsaturated ke-
tone 18.20
In order to evaluate the silver(I)-mediated hydroalkoxylation of
more complex molecules, two additional d-hydroxy allenes 28 and
29 were synthesized from the known aldehyde 2121 (Scheme 6).
Wittig olefination of the aldehyde gave olefin 22, which was
hydroborated with disiamylborane and then subjected to
DesseMartin oxidation to afford aldehyde 23 in good yield. Alle-
nylation with 1-trimethylsilyl-3-bromopropyne in the presence of
H
H
Me
Ag+
OH
OBn
Me
π−binding
O
O
H
17
CrCl2 afforded
respectively. Deprotection of the C-TMS group under basic condi-
tions gave the -hydroxy allenes 26 and 27. Because of the potential
usage of a hydroalkoxylation product in polyether synthesis, the
hydroxy group was acetylated instead of benzylated to give
acetoxy -hydroxy allenes 28 and 29 after removal of the trie-
thylsilyl group. Hydroalkoxylation of the -hydroxy allenes 28 and
a-hydroxy allenes 24 and 25 in 75% and 19% yields,
H
H
Ag+
D
a
15
OH2
a
-
OH
18
H
d
σ−binding
Ag+
BnO
d
29 was carried out under the best conditions obtained for 6 and 7.
Treatment of 28 with AgClO4 in DCE at 50 ꢀC afforded the cycliza-
tion product 30 in 71% yield. On the other hand, when the AgClO4-
E
Scheme 5.
Table 4
Hydroalkoxylation of 16
4.0% NOE
H
H
H
Me
H
H
Me
H
H
H
H
O
Me
O
O
Me
OH
18
O
OBn
O
OBn
O
OBn
O
OBn
H
H
H
H
7.2% NOE
16
19
20
NOEs of 20
Entry
Reagent
equiv
Solvent
Temp (ꢀC)
Time (h)
19 and 20
18 (%)
Yielda (%)
drb
1
2
3
4
AgClO4
AgBF4
AgOTf
1.7
1.5
1.5
0.1
DCE
DCE
DCE
CH2Cl2
50
50
50
0
38
27
16
0.5
19
29
Decomp.
71
57:43
68:32
d
45
d
d
Hg(OTf)2
22:78
a
Isolated yield of a mixture of 19 and 20.
b
Determined by 1H NMR analysis.

9090
Y. Suzuki et al. / Tetrahedron 69 (2013) 9086e9095
or Hg(OTf)2-mediated reaction was attempted with 29, the desired
product was not observed and only a complex mixture of products
was obtained.
spectrometers. The term ‘dried’ refers to the drying of an organic
solution over MgSO4 followed by filtration.
4.2. (R)-1-((2R,3S)-3-((tert-Butyldimethylsilyl)oxy)tetrahy-
dro-2H-pyran-2-yl)-3-(trimethylsilyl)penta-3,4-dien-2-ol (2)
and (S)-1-((2R,3S)-3-((tert-butyldimethylsilyl)oxy)tetrahydro-
2H-pyran-2-yl)-3-(trimethylsilyl)penta-3,4-dien-2-ol (3)
H
H
H
H
H
H
H
H
t-Bu
Si
t-Bu
Si
t-Bu
1. 2-methyl-2-butene
BH3; H2O2, NaOH
O
OTES
X
O
OTBS
CHO
t-Bu
O
O
O
O
2. Dess-Martin oxi.
77% (2 steps)
Ph3P=CH2
93%
To a suspension of CrCl2 (1.55 g, 12.6 mmol) in THF (25 mL) were
added successively aldehyde 1 (804 mg, 3.119 mmol) dissolved in
THF (25 mL), (3-bromoprop-1-ynyl)trimethylsilane (0.883 mL,
3.119 mmol), and chlorotrimethylsilane (0.790 mL, 6.238 mmol).
The reaction mixture was stirred at 0 ꢀC for 14 h. The reaction was
quenched with saturated aqueous NaHCO3 solution, and the re-
action mixture was extracted with EtOAc. The extract was washed
with water and brine, dried, and concentrated under reduced
pressure. A mixture of the crude product and PPTS (39 mg,
0.156 mmol) in methanol (20 mL) was stirred at room temperature
for 40 min. The reaction was quenched with Et3N (0.2 mL), and the
reaction mixture was concentrated under reduced pressure. Puri-
fication by flash chromatography (10% EtOAc in hexane) afforded
hydroxy allenes 2 (687 mg, 60%) and 3 (286 mg, 24%) as colorless
21 X = O
22 X = CH2
23
TMS
OTES
H
H
H
H
t-Bu
t-Bu
O
1. NaOMe, MeOH
2. K2CO3, MeOH
TMSC≡CCH2Br
CrCl2, THF
Si
O
Y
O
X
24 X = OH, Y = H (75%)
25 X = H, Y = OH (19%)
H
H
H
H
H
H
H
1. Ac2O
pyr.
t-Bu
Si
t-Bu
Si
t-Bu
O
OTES
O
OH
t-Bu
O
O
oils. Compound 2: [
a
]
24 þ28.2 (c 1.0, CHCl3); IR (CHCl3) 3466, 1928,
D
Y
Y
O
O
2. PPTS
MeOH
H
X
X
1472, 1463, 1251, 1128, 1096, 840 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d
4.52e4.42 (3H, m), 3.87 (1H, m), 3.41 (1H, ddd, J¼9.3, 9.3, 2.9 Hz),
26 X = OH Y = H (63% from 24)
27 X = H, Y = OH (66% from 25)
28 X = OAc, Y = H (86% from 26)
29 X = H, Y = OAc (87% from 27)
3.36 (1H, ddd, J¼8.8, 8.8, 4.4 Hz), 3.31 (1H, ddd, J¼11.2, 11.2, 3.4 Hz),
3.27 (1H, d, J¼7.3 Hz, OH), 2.09 (1H, ddd, J¼14.6, 4.9, 2.4 Hz), 2.00
(1H, m), 1.77 (1H, ddd, J¼14.6, 8.8, 2.4 Hz), 1.71e1.61 (2H, m), 1.43
(1H, m), 0.87 (9H, s), 0.15 (9H, s), 0.06 (3H, s), 0.05 (3H, s); 13C NMR
(100 MHz, CDCl3)
d 207.4, 100.3, 80.7, 71.0, 70.8, 68.4, 67.6, 38.2,
H
H
H
H
H
H
H
t-Bu
Si
t-Bu
Si
O
OH
O
O
AgClO4
33.5, 25.8, 25.5, 17.9, ꢁ0.8, ꢁ4.1, ꢁ4.7; HREIMS m/z calcd for
t-Bu
t-Bu
C
19H38O3Si2 (Mþ) 370.2360, found 370.2397.
O
O
DCE, 50 °C, 29 h
71%
H
H
O
24 þ39.3 (c 0.42, CHCl3); IR (CHCl3) 3469, 1929,
O
Compound 3: [a]
H
D
OAc
H
OAc
1472, 1463, 1250, 1095, 841 cmꢁ1
;
1H NMR (400 MHz, CDCl3)
28
30
d
4.50e4.41 (3H, m), 3.88 (1H, dddd, J¼10.7, 3.9, 1.9, 1.9 Hz), 3.83
Scheme 6.
(1H, s, OH), 3.35 (1H, ddd, J¼11.2, 11.2, 3.4 Hz), 3.31e3.25 (2H, m),
2.26 (1H, d, J¼14.6 Hz), 1.99 (1H, m), 1.72e1.60 (2H, m), 1.54 (1H,
ddd, J¼14.6, 10.3, 10.3 Hz), 1.42 (1H, m), 0.87 (9H, s), 0.15 (9H, s),
0.06 (6H, s); 13C NMR (100 MHz, CDCl3)
d 208.0, 100.2, 84.1, 71.6,
71.3, 70.6, 67.6, 39.4, 33.3, 25.8, 25.3, 17.9, ꢁ0.7, ꢁ4.1, ꢁ4.7; HREIMS
3. Conclusion
m/z calcd for C19H38O3Si2 (Mþ) 370.2360, found 370.2368.
In summary, we have demonstrated a new synthetic method
affording vinyl-substituted fused tetrahydropyrans through the
silver(I)- and mercury(II)-mediated intramolecular hydro-
4.3. (((2R,3S)-2-((R)-2-(Benzyloxy)penta-3,4-dien-1-yl)tetra-
hydro-2H-pyran-3-yl)oxy)(tert-butyl)dimethylsilane (4)
alkoxylation of
d-hydroxy allenes templated on a tetrahy-
To a solution of 2 (332 mg, 0.897 mmol) in THF (6 mL) at 0 ꢀC was
added NaOMe (387 mg, 7.167 mmol), and the reaction mixture was
stirred at 0 ꢀC for 7 h. The reaction was quenched with saturated
aqueous NH4Cl solution. The reaction mixture was extracted with
EtOAc, and the extract was washed with water and brine, dried, and
concentrated under reduced pressure. A mixture of the crude
product and PPTS (12 mg) in methanol (9 mL) was stirred at room
temperature for 30 min. The reaction was quenched with Et3N
(0.2 mL), and the reaction mixture was concentrated under reduced
dropyran ring. The reactivity and diastereoselectivity of the
hydroalkoxylation were strongly influenced by the configuration
of a substituent at the a-position of the allenyl group, especially
for reactions of methyl-substituted allenes. Further studies on
this reaction including other metals and its application to the
synthesis of natural products are in progress.
4. Experimental section
4.1. General methods
pressure. Purification by flash chromatography (12/20% EtOAc in
21
hexane) afforded alcohol 4 (196 mg, 73%) as a colorless oil. [
a]
D
All air- and moisture-sensitive reactions were carried out under
an argon atmosphere in dry, freshly distilled solvents under an-
hydrous conditions. Flash chromatography was carried out with
silica gel (spherical, neutral, particle size 40e50 mm). Melting
points are uncorrected. Chemical shifts are reported in parts per
þ34.2 (c 0.29, CHCl3); IR (CHCl3) 3470, 1956, 1463, 1254, 1096,
839 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d
5.28 (1H, q, J¼5.9 Hz), 4.84
(1H, dd, J¼6.6, 2.9 Hz), 4.82 (1H, d, J¼6.6 Hz), 4.47 (1H, m), 3.89 (1H,
dddd, J¼10.6, 3.7, 1.8, 1.8 Hz), 3.45e3.30 (3H, m), 3.24 (1H, d,
J¼5.9 Hz, OH), 2.05e1.98 (2H, m), 1.79 (1H, ddd, J¼14.7, 7.7, 2.9 Hz),
1.68e1.63 (2H, m), 1.50e1.39 (1H, m), 0.87 (9H, s), 0.06 (3H, s), 0.06
million (ppm) relative to internal TMS (
spectra and to the solvent signals ( 77.0 ppm for CDCl3 and
128.39 ppm for C6D6) for 13C NMR spectra. The high-resolution
mass spectra were recorded on magnetic sector EI and FAB mass
d
0.00 ppm) for 1H NMR
d
(3H, s); 13C NMR (100 MHz, CDCl3)
d 207.0, 94.7, 80.6, 77.1, 70.5, 67.7,
d
67.0, 38.0, 33.4, 25.7, 25.5, 17.9, ꢁ4.0, ꢁ4.8; HREIMS m/z calcd for
C
12H21O3Si ([Mꢁt-Bu]þ) 241.1260, found 241.1251.

Y. Suzuki et al. / Tetrahedron 69 (2013) 9086e9095
9091
4.4. (((2R,3S)-2-((S)-2-(Benzyloxy)penta-3,4-dien-1-yl)tetra-
hydro-2H-pyran-3-yl)oxy)(tert-butyl)dimethylsilane (5)
1088, 1045, 849 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d
7.36e7.26 (5H,
m), 5.14 (1H, ddd, J¼8.3, 6.8, 6.8 Hz), 4.86 (1H, ddd, J¼11.2, 6.8,
1.0 Hz), 4.81 (1H, ddd, J¼11.2, 6.3, 1.0 Hz), 4.68 and 4.43 (each 1H, d,
J¼11.7 Hz), 4.23 (1H, m), 3.86 (1H, m), 3.34 (1H, ddd, J¼9.3, 9.3,
4.4 Hz), 3.29 (1H, ddd, J¼11.2, 8.8, 6.4 Hz), 3.16 (1H, ddd, J¼9.8, 5.9,
4.4 Hz), 2.93 (1H, br s, OH), 2.09e1.97 (3H, m), 1.68e1.60 (2H, m),
Alcohol 5 (142 mg, 75%) was prepared from 3 (235 mg,
0.635 mmol) following the procedure described for 4. Colorless oil;
20
[
a]
þ40.9 (c 1.0, CHCl3); IR (CHCl3) 3466, 1958, 1472, 1253, 1096,
D
1077, 945, 837 cmꢁ1
;
1H NMR (400 MHz, CDCl3)
d
5.26 (1H, q,
1.37 (1H, m); 13C NMR (100 MHz, CDCl3)
d 208.7, 137.7, 128.4, 128.1,
J¼6.3 Hz), 4.83 (1H, d, J¼2.4 Hz), 4.81 (1H, d, J¼2.9 Hz), 4.44 (1H, m),
3.90 (1H, dddd, J¼10.7, 3.9, 1.9, 1.9 Hz), 3.75 (1H, s, OH), 3.36 (1H,
ddd, J¼11.2, 11.2, 3.9 Hz), 3.32e3.25 (2H, m), 2.18 (1H, ddd, J¼14.2,
2.4, 2.4 Hz), 1.99 (1H, m), 1.71e1.61 (2H, m), 1.53 (1H, ddd, J¼14.6,
9.8, 9.8 Hz), 1.43 (1H, m), 0.87 (9H, s), 0.07 (6H, s); 13C NMR
127.8, 90.9, 79.8, 76.0, 74.7, 70.5, 69.6, 67.8, 39.0, 32.0, 25.7; HREIMS
m/z calcd for C17H22O3 (Mþ) 274.1569, found 274.1528.
4.8. Typical procedure for the silver-mediated hydro-
alkoxylation of 6 (Table 1, entry 2)
(100 MHz, CDCl3) d 207.2, 94.5, 83.6, 76.9, 71.3, 69.7, 67.6, 38.9, 33.2,
25.7, 25.3, 17.9, ꢁ4.1, ꢁ4.8; HREIMS m/z calcd for C12H21O3Si ([Mꢁt-
To a solution of hydroxy allene 6 (390 mg, 1.423 mmol) in DCE
(14 mL) was added AgClO4 (340 mg, 1.637 mmol), and the reaction
mixture was stirred at 50 ꢀC for 20 h in the dark. The reaction was
quenched with saturated aqueous NH4Cl solution, and the mixture
was extracted with EtOAc. The extract was washed with water and
brine, dried, and concentrated under reduced pressure. Purification
by flash chromatography (20% EtOAc in hexane) afforded
Bu]þ) 241.1260, found 241.1243.
4.5. Asymmetric allenylation of aldehyde 1
According to the procedure of Corey et al.,15 aldehyde 1 (100 mg,
0.3876 mmol) was allenylated with the reagent prepared from
(4R,5R)-2-bromo-1,3-bis(p-toluenesulfonyl)-4,5-diphenyl-1,3,2-
diazaborolidine (224 mg, 0.4307 mmol), BBr3 (0.083 mL,
0.8614 mmol), and allenyltributylstannane (0.152 mL,
0.4094 mmol) to afford alcohol 5 (43 mg, 37%) and the recovered
(2R,3R,4aR,8aS)-3-(benzyloxy)-2-vinyloctahydropyrano[3,2-b]py-
29
ran (8) (yield 343 mg, 88%) as a colorless solid. Mp 40e43 ꢀC; [
a]
D
ꢁ38.6 (c 0.44, CHCl3); IR (CHCl3) 1496, 1455, 1340, 1280, 1090, 1021,
962 cmꢁ1; 1H NMR (400 MHz, CDCl3)
7.36e7.25 (5H, m), 5.97 (1H,
d
aldehyde 1 (61 mg, 61%) after flash chromatography (15% EtOAc in
ddd, J¼17.6, 10.7, 6.3 Hz), 5.31 (1H, ddd, J¼17.6, 1.5, 1.5 Hz), 5.20 (1H,
ddd, J¼10.7, 1.5, 1.5 Hz), 4.68 and 4.49 (each 1H, d, J¼12.2 Hz), 3.94
(1H, ddd, J¼6.4, 1.5, 1.5 Hz), 3.91 (1H, dddd, J¼11.2, 3.9, 1.9, 1.9 Hz),
3.63 (1H, ddd, J¼2.9, 2.9, 2.0 Hz), 3.45 (1H, dd, J¼11.2, 4.4 Hz), 3.42
(1H, dd, J¼11.2, 4.4 Hz), 3.13 (1H, ddd, J¼10.7, 8.8, 4.4 Hz), 2.35 (1H,
ddd, J¼13.2, 3.9, 3.4 Hz), 2.06 (1H, m), 1.82e1.70 (2H, m), 1.63 (1H,
m), 1.50 (1H, ddd, J¼13.2, 11.7, 2.4 Hz); 13C NMR (100 MHz, CDCl3)
20
hexane). [
a]
þ39.4 (c 1.0, CHCl3). The 1H and 13C NMR spectra
D
were identical to those of 5 prepared from 3.
4.6. (2R,3S)-2-((R)-2-Hydroxypenta-3,4-dien-1-yl)tetrahydro-
2H-pyran-3-ol (6)
To a solution of alcohol 4 (138 mg, 0.463 mmol), benzyl bromide
(0.165 mL, 1.390 mmol), and Bu4NI (51 mg, 0.139 mmol) in THF
(9.2 mL) at ꢁ10 ꢀC was added KHMDS (1.07 mL of a 0.5 M solution
in toluene, 0.535 mmol), and the reaction mixture was stirred at
ꢁ10 ꢀC for 1 h. The reaction was quenched with saturated aqueous
NH4Cl solution. The reaction mixture was extracted with EtOAc,
and the extract was washed with water and brine, dried, and
concentrated under reduced pressure. Purification by flash chro-
matography (4% EtOAc in hexane) afforded benzyloxy allene
(142 mg, 80%).
d 138.1, 135.8, 128.3, 127.9, 127.6, 116.7, 81.1, 78.4, 75.9, 74.1, 71.4,
68.1, 33.1, 29.2, 25.7; HREIMS m/z calcd for C17H22O3 (Mþ) 274.1569,
found 274.1559.
4.9. Mercury-catalyzed hydroalkoxylation of 6 (Table 1, entry
6)
To a solution of 6 (61 mg, 0.223 mmol) in CH2Cl2 (4 mL) at 0 ꢀC
was added Hg(OTf)2 (11 mg, 0.022 mmol), and the reaction mixture
was stirred at 0 ꢀC for 5 h. The reaction was quenched with satu-
rated aqueous NaHCO3 solution, and the reaction mixture was
extracted with EtOAc. The extract was washed with water and
brine, dried, and concentrated under reduced pressure. Purification
by flash chromatography (20% EtOAc in hexane) afforded 8 (9.0 mg,
20%).
To a solution of benzyloxy allene (142 mg, 0.477 mmol) in THF
(4.8 mL) was added TBAF (0.955 mL of a 1.0 M solution in THF,
0.955 mmol), and the reaction mixture was stirred at room tem-
perature for 1.5 h. The reaction mixture was extracted with EtOAc,
and the extract was washed with water and brine, dried, and
concentrated under reduced pressure. Purification by flash chro-
matography (50% EtOAc in hexane) afforded hydroxy allene 6
4.10. Silver-mediated hydroalkoxylation of 7 (Table 2, entry 2)
(92 mg, 92%) as a colorless oil. [
a]
29 þ68.8 (c 0.61, CHCl3); IR (CHCl3)
D
3594, 3402, 1954, 1497, 1454, 1093, 939, 849 cmꢁ1
;
1H NMR
The procedure described for 6 was followed with 7 (139 mg,
0.507 mmol) and AgClO4 (160 mg, 0.760 mmol) in DCE (10 mL).
Purification by flash chromatography (15% EtOAc in hexane) affor-
ded a mixture of 9 and 10 (58 mg, 42%, 9/10¼89:11 by 1H NMR
analysis). Analytical samples were obtained by repeated flash
chromatography (3% EtOAc in CH2Cl2). The isomer 10 was eluted
slightly faster than the isomer 9. (2R,3S,4aR,8aS)-3-(Benzyloxy)-2-
(400 MHz, CDCl3)
d
7.34e7.26 (5H, m), 5.13 (1H, ddd, J¼8.3, 6.8,
6.8 Hz), 4.87e4.76 (2H, m), 4.69 and 4.47 (each 1H, d, J¼11.7 Hz),
4.15 (1H, m), 3.82 (1H, m), 3.27e3.20 (2H, m), 3.17 (1H, ddd, J¼8.8,
6.8, 4.4 Hz), 2.80 (1H, d, J¼4.4 Hz, OH), 2.15 (1H, ddd, J¼14.6, 10.7,
3.9 Hz), 2.10 (1H, m), 1.72 (1H, ddd, J¼14.6, 6.8, 2.4 Hz), 1.68e1.60
(2H, m), 1.35 (1H, m); 13C NMR (100 MHz, CDCl3)
d 208.5, 137.9,
128.4, 128.3, 128.1, 127.8, 127.7, 91.5, 79.6, 76.1, 74.4, 70.8, 70.3, 67.5,
40.4, 32.7, 25.5; HREIMS m/z calcd for C17H22O3 (Mþ) 274.1569,
found 274.1525.
vinyloctahydropyrano[3,2-b]pyran (9): colorless prisms, mp
27
37e39 ꢀC; [
a
]
þ51.4 (c 0.27, CHCl3); IR (CHCl3) 1496, 1454, 1355,
D
1280, 1093, 989, 935 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d 7.36e7.25
(5H, m), 5.96 (1H, ddd, J¼17.2, 10.6, 6.2 Hz), 5.42 (1H, ddd, J¼17.2,
1.8, 1.8 Hz), 5.28 (1H, ddd, J¼10.6, 1.8, 1.1 Hz), 4.61 and 4.47 (each
1H, d, J¼11.4 Hz), 3.91 (1H, dddd, J¼10.6, 4.0, 1.8, 1.8 Hz), 3.75 (1H,
dd, J¼9.2, 6.2 Hz), 3.37 (1H, m), 3.28 (1H, ddd, J¼11.4, 9.5, 4.8 Hz),
3.08 (1H, ddd, J¼11.4, 9.2, 4.4 Hz), 2.96 (1H, ddd, J¼11.4, 8.8, 4.0 Hz),
2.47 (1H, ddd, J¼11.4, 4.4, 4.4 Hz), 2.08 (1H, m), 1.80e1.65 (2H, m),
1.52 (1H, q, J¼11.4 Hz), 1.43 (1H, m); 13C NMR (100 MHz, CDCl3)
4.7. (2R,3S)-2-((S)-2-(Benzyloxy)penta-3,4-dien-1-yl)tetrahy-
dro-2H-pyran-3-ol (7)
Hydroxy allene 7 (99 mg, 80%) was prepared from 5 (134 mg,
0.449 mmol) following the procedure described for 6. Colorless oil;
[
a]
27 ꢁ2.34 (c 1.13, CHCl3); IR (CHCl3) 3421, 1954, 1497, 1454, 1349,
D

9092
Y. Suzuki et al. / Tetrahedron 69 (2013) 9086e9095
d
138.1, 135.9, 128.4, 127.8, 127.7, 117.8, 81.3, 77.6, 77.4, 76.6, 71.4,
4.12. (2R,3S)-2-((R)-2-(Benzyloxy)-3-methylpenta-3,4-dien-1-
yl)tetrahydro-2H-pyran-3-ol (15)
67.8, 35.9, 29.2, 25.4; HREIMS m/z calcd for C17H22O3 (Mþ) 274.1569,
found 274.1539.
(2S,3S,4aR,8aS)-3-(Benzyloxy)-2-vinyloctahydropyrano[3,2-b]py-
The procedure described for 6 was followed with 13 (140 mg,
0.349 mmol) and TBAF (1.05 mL of a 1.0 M solution in THF,
1.05 mmol) in THF (3.5 mL). Purification by flash chromatography
24
ran (10): colorless oil; [
a
]
D
ꢁ61.5 (c 0.38, CHCl3); IR (CHCl3) 1498,
1455, 1353, 1282, 1075, 1040, 960 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d
7.36e26 (5H, m), 6.22 (1H, ddd, J¼17.6, 10.7, 5.4 Hz), 5.49 (1H, ddd,
(50% EtOAc in hexane) afforded hydroxy methylallene 15 (98 mg,
25
J¼17.6, 1.9, 1.9 Hz), 5.45 (1H, ddd, J¼10.7, 1.9, 1.9 Hz), 4.58 and 4.54
(each 1H, d, J¼12.2 Hz), 4.52 (1H, m), 3.89 (1H, m), 3.77 (1H, ddd,
J¼12.2, 5.8, 4.4 Hz), 3.39e3.30 (2H, m), 2.96 (1H, ddd, J¼11.7, 9.3,
4.4 Hz), 2.23 (1H, ddd, J¼11.7, 4.4, 4.4 Hz), 1.97 (1H, m), 1.78e1.67
(2H, m), 1.63 (1H, q, J¼11.7 Hz), 1.36 (1H, m); 13C NMR (100 MHz,
97%) as a colorless oil. [
a
]
D
þ58.0 (c 1.0, CHCl3); IR (CHCl3) 3392,
1958, 1497, 1454, 1373, 1093, 852 cmꢁ1; 1H NMR (400 MHz, CDCl3)
7.37e7.26 (5H, m), 4.73 (1H, m), 4.68 (1H, m), 4.60 and 4.34 (each
d
1H, d, J¼11.7 Hz), 4.14 (1H, dd, J¼10.7, 2.4 Hz), 3.82 (1H, m),
3.28e3.20 (2H, m), 3.15 (1H, ddd, J¼8.8, 6.3, 4.9 Hz), 2.93 (1H, br,
OH), 2.21 (1H, ddd, J¼15.1, 10.7, 4.4 Hz), 2.11 (1H, m), 1.69 (3H, t,
J¼3.4 Hz), 1.68e1.61 (3H, m), 1.35 (1H, m); 13C NMR (100 MHz,
CDCl3)
d 138.0, 132.2, 128.4, 127.7, 127.6, 119.9, 77.6, 74.8, 74.1, 70.7,
70.2, 67.9, 32.3, 29.3, 25.6; HREIMS m/z calcd for C17H22O3 (Mþ)
274.1569, found 274.1566.
CDCl3) d 206.8, 137.8, 128.3, 128.2, 127.7, 97.9, 80.1, 74.7, 71.0, 70.1,
67.6, 38.7, 32.7, 25.5, 12.7; HREIMS m/z calcd for C18H24O3 (Mþ)
288.1725, found 288.1721.
4.11. (((2R,3S)-2-((R)-2-(Benzyloxy)-3-methylpenta-3,4-dien-
1-yl)tetrahydro-2H-pyran-3-yl)oxy)(tert-butyl)dimethylsilane
(13) and (((2R,3S)-2-((S)-2-(benzyloxy)-3-methylpenta-3,4-
dien-1-yl)tetrahydro-2H-pyran-3-yl)oxy)(tert-butyl)dime-
thylsilane (14)
4.13. (2R,3S)-2-((S)-2-(Benzyloxy)-3-methylpenta-3,4-dien-1-
yl)tetrahydro-2H-pyran-3-ol (16)
The procedure described for 6 was followed with 14 (106 mg,
0.265 mmol). Purification by flash chromatography (50% EtOAc in
To a suspension of CrCl2 (1.62 g, 13.181 mmol) in THF (26 mL)
were added a solution of aldehyde 1 (836 mg, 3.283 mmol) in THF
(6 mL) and 1-bromobut-2-yne (0.567 mL, 6.477 mmol), and the
reaction mixture was stirred at room temperature for 1 h. The re-
action was quenched with water, and the mixture was extracted
with EtOAc. The extract was washed with water and brine, dried,
and concentrated under reduced pressure. Purification by flash
chromatography (15/20/30% EtOAc in hexane) afforded an in-
separable mixture of methylallenes 11 and 12 (836 mg, 83%) as
a colorless oil. The diastereomeric ratio was determined to be 57:43
by 1H NMR analysis.
27
hexane) afforded 16 (72 mg, 94%) as a colorless oil. [
a
]
ꢁ2.13 (c
D
0.88, CHCl3); IR (CHCl3) 3474, 1957, 1497, 1454, 1373, 1271, 1088,
1047, 851 cmꢁ1 1H NMR (400 MHz, CDCl3)
;
d
7.36e7.26 (5H, m),
4.78e4.67 (2H, m), 4.57 and 4.36 (each 1H, d, J¼11.2 Hz), 4.21 (1H,
dd, J¼7.8, 4.9 Hz), 3.87 (1H, m), 3.30e3.25 (2H, m), 3.10 (1H, ddd,
J¼8.3, 6.3, 3.4 Hz), 2.59 (1H, d, J¼4.4 Hz, OH), 2.10e2.02 (2H, m),
1.95 (1H, ddd, J¼15.1, 4.9, 2.9 Hz), 1.68 (3H, t, J¼2.9 Hz), 1.68e1.60
(2H, m), 1.38 (1H, m); 13C NMR (100 MHz, CDCl3)
d 206.9, 137.9,
128.4, 128.2, 127.7, 97.4, 80.3, 74.6, 70.0, 69.2, 67.9, 36.2, 32.0, 25.8,
12.6; HREIMS m/z calcd for
C
18H24O3 (Mþ) 288.1725, found
288.1708.
To a solution of the above mixture of 11 and 12 (198 mg,
0.636 mmol) in THF at ꢁ10 ꢀC were successively added benzyl
bromide (1.4 mL, 0.699 mmol), Bu4NI (70 mg, 0.191 mmol), and
KHMDS (1.4 mL of a 0.5 M solution in toluene, 0.700 mmol). The
reaction mixture was stirred at ꢁ10 ꢀC for 1 h. The reaction was
quenched with saturated aqueous NH4Cl solution, and the mixture
was extracted with EtOAc. The extract was washed with water and
brine, dried, and concentrated under reduced pressure. Purification
by flash chromatography (4/8% EtOAc in hexane) gave methyl-
4.14. Hydroalkoxylation of 15 with silver salt (Table 3, entry 1)
The procedure described for 6 was followed with 15 (145 mg,
0.502 mmol) and AgClO4 (125 mg, 0.604 mmol) in DCE (5 mL).
Purification by flash chromatography (15/60% EtOAc in hexane)
afforded 17 (37 mg, 26%) and the unsaturated ketone 18 (15 mg,
15%) as colorless oils, which were eluted in this order.
(2R,3R,4aR,8aS)-3-(Benzyloxy)-2-methyl-2-vinyloctahydropyrano
allenes 13 (121 mg, 48%) and 14 (92 mg, 36%) as colorless oils,
29
which were eluted in this order. Compound 13: [
a]
þ72.8 (c 1.0,
[3,2-b]pyran (17): [
a
]
25 ꢁ48.8 (c 0.26, CHCl3); IR (CHCl3) 1496, 1455,
D
D
CHCl3); IR (CHCl3) 1957, 1496, 1463, 1361, 1258, 1094, 1027, 944,
1373, 1238, 1095, 929 cmꢁ1; 1H NMR (400 MHz, C6D6)
d
7.32e7.07
838 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d
7.37e7.23 (5H, m), 4.68 (1H,
(5H, m), 6.11 (1H, dd, J¼17.6, 10.7 Hz), 5.40 (1H, dd, J¼17.6, 1.9 Hz),
5.08 (1H, dd, J¼10.7, 1.9 Hz), 4.37 and 4.20 (each 1H, d, J¼11.7 Hz),
3.71 (1H, dd, J¼11.2, 3.9 Hz), 3.59 (1H, ddd, J¼11.7, 9.3, 4.4 Hz), 3.43
(1H, ddd, J¼9.7, 9.7, 4.4 Hz), 3.13 (1H, m), 3.09 (1H, dd, J¼3.4,
2.4 Hz), 2.24 (1H, ddd, J¼13.2, 3.9, 3.9 Hz), 1.91 (1H, m), 1.74 (1H,
ddd, J¼13.7, 12.2, 2.9 Hz), 1.57e1.45 (2H, m), 1.19 (1H, m), 1.14 (3H,
m), 4.62 (1H, m), 4.55 and 4.35 (each 1H, d, J¼12.2 Hz), 4.17 (1H, dd,
J¼11.2, 2.9 Hz), 3.78 (1H, m), 3.28 (1H, ddd, J¼8.8, 8.8, 1.9 Hz),
3.28e3.20 (2H, m), 2.31 (1H, ddd, J¼14.1, 10.7, 1.9 Hz), 1.98 (1H, m),
1.67 (3H, t, J¼2.9 Hz), 1.66e1.59 (2H, m), 1.44 (1H, m), 1.34 (1H, ddd,
J¼14.1, 10.2, 2.9 Hz), 0.88 (9H, s), 0.06 (3H, s), 0.05 (3H, s); 13C NMR
(100 MHz, CDCl3)
d
206.8, 139.0, 128.1, 127.7, 127.2, 98.2, 78.7, 75.7,
s); 13C NMR (100 MHz, CDCl3)
d 142.4, 138.2, 128.2, 128.1, 127.6,
74.2, 71.8, 69.4, 67.6, 36.7, 33.7, 25.8, 18.0, 13.0, ꢁ4.0, ꢁ4.7; HREIMS
112.5, 78.8, 77.1, 74.6, 71.5, 71.2, 68.2, 29.6, 29.58, 25.9, 20.9;
m/z calcd for C24H38O3Si (Mþ) 402.2590, found 402.2578.
HREIMS m/z calcd for C18H24O3 (Mþ) 288.1725, found 288.1742.
Compound 14: [
a
]
D
29 þ10.1 (c 0.99, CHCl3); IR (CHCl3) 1957, 1463,
(E)-5-((2R,3S)-3-Hydroxytetrahydro-2H-pyran-2-yl)-3-
29
1371, 1252, 1096, 839 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d
7.36e7.23
methylpent-3-en-2-one (18): [
a
]
D
þ24.1 (c 0.23, CHCl3); IR (CHCl3)
(5H, m), 4.69 (1H, dq, J¼9.8, 2.9 Hz), 4.62 (1H, dq, J¼9.8, 3.4 Hz),
4.55 and 4.36 (each 1H, d, J¼11.7 Hz), 4.19 (1H, dd, J¼10.2, 4.4 Hz),
3.84 (1H, m), 3.31 (1H, ddd, J¼10.7, 8.8, 4.9 Hz), 3.22 (1H, ddd,
J¼11.2, 11.2, 3.4 Hz), 2.96 (1H, ddd, J¼10.2, 8.8, 1.9 Hz), 2.15 (1H, ddd,
J¼13.7, 10.2, 1.9 Hz), 1.99 (1H, m), 1.71e1.60 (3H, m), 1.65 (3H, t,
3605, 3451, 1662, 1438, 1368, 1278, 1094, 1035, 944, 872 cmꢁ1
;
1H
6.78 (1H, ddd, J¼6.8, 6.8, 1.0 Hz), 3.92 (1H,
NMR (400 MHz, CDCl3)
d
dddd, J¼10.7, 4.4, 1.9, 1.9 Hz), 3.42e3.32 (2H, m), 3.18 (1H, ddd,
J¼8.3, 8.3, 2.9 Hz), 2.79 (1H, dddd, J¼16.1, 6.3, 2.9, 1.0 Hz), 2.45 (1H,
ddd, J¼16.1, 8.3, 8.3 Hz), 2.33 (3H, s), 2.14 (1H, m), 1.80 (3H, d,
J¼1.0 Hz), 1.77e1.65 (2H, m), 1.48 (1H, d, J¼5.8 Hz, OH), 1.42 (1H,
J¼3.4 Hz), 1.40 (1H, m), 0.87 (9H, s), 0.05 (3H, s), 0.048 (3H, s); 13
C
NMR (100 MHz, CDCl3)
d
207.7, 138.8, 128.2, 127.9, 127.3, 96.6, 80.0,
m); 13C NMR (100 MHz, CDCl3)
d 199.9, 140.0, 139.0, 81.5, 70.3, 67.8,
78.4, 73.5, 71.0, 70.1, 67.6, 35.4, 33.7, 25.8, 25.7, 17.9, 11.9, ꢁ4.0, ꢁ4.7;
33.2, 32.0, 25.5, 11.4; HREIMS m/z calcd for C11H18O3 (Mþ) 198.1256,
HREIMS m/z calcd for C24H38O3Si (Mþ) 402.2590, found 402.2575.
found 198.1241.

Y. Suzuki et al. / Tetrahedron 69 (2013) 9086e9095
9093
4.15. Mercury-catalyzed hydroalkoxylation of 15 (Table 3,
entry 4)
4.9 Hz), 3.81 (1H, t, J¼10.0 Hz), 3.77 (1H, ddd, J¼11.7, 9.3, 4.9 Hz),
3.60 (1H, m), 3.43 (1H, ddd, J¼11.2, 9.3, 4.9 Hz), 3.34 (1H, ddd,
J¼10.3, 9.3, 4.4 Hz), 2.39 (1H, ddd, J¼12.2, 4.9, 4.9 Hz), 1.58 (1H, q,
J¼11.2 Hz), 1.05 (9H, s), 0.99 (9H, s), 0.95 (9H, t, J¼7.8 Hz), 0.60 (6H,
To a solution of 15 (10.3 mg, 0.036 mmol) in CH2Cl2 (0.4 mL) was
added Hg(OTf)2 (1.8 mg, 0.0036 mmol), and the reaction mixture was
stirred at 0 ꢀC for 30 min. The reaction was quenched with saturated
aqueous NaHCO3 solution, and the reaction mixture was extracted
with EtOAc. The extract was washed with water and brine, dried, and
concentrated under reduced pressure. Purification by flash chro-
matography (25% EtOAc in hexane) afforded 17 (8.0 mg, 78%).
q, J¼7.8 Hz); 13C NMR (100 MHz, CDCl3)
d 135.6, 117.5, 82.8, 76.8,
72.2, 70.1, 66.9, 42.7, 27.4, 27.1, 22.6, 19.9, 6.8, 5.0; HRFABMS m/z
calcd for C22H45O4Si2 (MHþ) 429.2856, found 429.2851.
4.18. 2-((4aR,6S,7R,8aS)-2,2-Di-tert-butyl-7-((triethylsilyl)oxy)
hexahydropyrano[3,2-d][1,3,2]dioxasilin-6-yl)acetaldehyde
(23)
4.16. Silver-mediated hydroalkoxylation of 16 (Table 4, entry
2)
To a solution of BH3$THF (5.15 mL of a 1.03 M solution in THF,
5.30 mmol) was added 2-methyl-2-butene (1.12 mL, 10.6 mmol) at
The procedure described for 6 was followed with 16 (18.2 mg,
0.063 mmol) and AgBF4 (18.4 mg, 0.095 mmol) in DCE (1 mL). Pu-
rification of the product by flash chromatography (20/60% EtOAc in
hexane) afforded a mixture of 19 and 20 (5.2 mg, 29%, 19/20¼68:32
by 1H NMR analysis) and the unsaturated ketone 18 (5.6 mg, 45%) as
colorless oils. Analytical samples of 19 and 20 were obtained by re-
peated purification by flash chromatography (3% EtOAc in CH2Cl2).
The isomer 20 was eluted slightly faster than the isomer 19.
0
ꢀC, and the solution was stirred at 0 ꢀC for 1 h. This dis-
iamylborane solution was added to a solution of olefin 22 (402 mg,
0.94 mmol) in THF (9.4 mL) at 0 ꢀC. The reaction mixture was stirred
at 0 ꢀC for 1 h, and then 3 M NaOH (5.3 mL) and 30% H2O2 (5.31 mL)
were added. After stirred for 75 min at room temperature, the re-
action mixture was extracted with EtOAc. The extract was washed
with water, aqueous Na2S2O3 solution, and brine, dried, and con-
centrated under reduced pressure. Purification by flash chroma-
tography (20% EtOAc in hexane) gave alcohol (374 mg, 89%) as
(2R,3S,4aR,8aS)-3-(Benzyloxy)-2-methyl-2-vinyloctahydropyrano[3,2-
25
b]pyran (19): mp 66e69 ꢀC; [
a]
D
þ10.8 (c 0.44, CHCl3); IR (CHCl3)
a colorless oil. [
a]
27 ꢁ45.8 (c 1.0, CHCl3); IR (CHCl3) 3528, 1473, 1091,
D
1456, 1353, 1209, 1088, 930 cmꢁ1
;
1H NMR (400 MHz, C6D6)
1059, 1010, 826 cmꢁ1
;
1H NMR (400 MHz, CDCl3)
d
4.10 (1H, dd,
d
7.23e7.06 (5H, m), 6.23 (1H, dd, J¼17.6,1.9 Hz), 5.56 (1H, dd, J¼17.6,
J¼9.8, 4.9 Hz), 3.77 (1H, t, J¼9.8 Hz), 3.80e3.71 (3H, m), 3.45 (1H,
ddd, J¼10.7, 8.8, 4.4 Hz), 3.38e3.28 (2H, m), 2.38 (1H, ddd, J¼12.2,
4.4, 4.4 Hz), 2.33 (1H, br, OH), 2.08 (1H, m), 1.61 (1H, m), 1.53 (1H, q,
J¼11.7 Hz), 1.04 (9H, s), 0.99 (9H, s), 0.97 (9H, t, J¼7.8 Hz), 0.63 (6H,
1.9 Hz), 5.10 (1H, dd, J¼10.7, 1.9 Hz), 4.33 and 4.20 (each 1H, d,
J¼11.7 Hz), 3.31 (1H, m), 3.33 (1H, dd, J¼11.7, 4.4 Hz), 3.71 (1H, ddd,
J¼10.3, 8.8, 3.9 Hz), 3.07 (1H, ddd, J¼11.6, 11.6, 2.4 Hz), 2.78 (1H, ddd,
J¼11.7, 9.3, 4.4 Hz), 2.32 (1H, ddd, J¼11.7, 4.4, 4.4 Hz), 1.89 (1H, m),
1.74 (1H, q, J¼11.7 Hz),1.47 (1H, m),1.40 (3H, s),1.33 (1H, m),1.22 (1H,
q, J¼7.8 Hz); 13C NMR (100 MHz, CDCl3)
d 82.8, 77.1, 72.1, 69.9, 66.7,
61.3, 42.4, 34.0, 27.4, 27.0, 22.6,19.9, 6.8, 5.0; HRFABMS m/z calcd for
m); 13C NMR (100 MHz, C6D6)
d
143.9, 128.5, 128.1, 127.9, 127.6, 112.5,
C
22H47O5Si2 (MHþ) 447.2962, found 447.2954.
79.7, 78.0, 71.4, 70.9, 67.8, 31.9, 30.2, 26.0, 16.3; HREIMS m/z calcd for
C
To a solution of the alcohol obtained above (374 mg, 0.838 mmol)
18H24O3 (Mþ) 288.1725, found 288.1706.
in CH2Cl2 (8.38 mL) and pyridine (0.34 mL) was added DesseMartin
periodinane (427 mg, 1.006 mmol) at 0 ꢀC, and the reaction mixture
was stirred at room temperature for 30 min. The reaction was
quenched with aqueous Na2S2O3 solution and the mixture was
extracted with EtOAc. The extract was washed with water, saturated
aqueous NaHCO3 solution, and brine, dried, and concentrated under
(2S,3S,4aR,8aS)-3-(Benzyloxy)-2-methyl-2-vinyloctahydropyrano
25
[3,2-b]pyran (20): mp 34e36 ꢀC; [
a
]
ꢁ16.8 (c 0.26, CHCl3); IR
D
(CHCl3) 1454, 1354, 1091, 1075, 1028, 934 cmꢁ1; 1H NMR (400 MHz,
C6D6)
d
7.22e7.07 (5H, m), 6.30 (1H, dd, J¼17.1, 11.2 Hz), 5.53 (1H,
dd, J¼17.1, 1.9 Hz), 5.26 (1H, dd, J¼11.2, 1.9 Hz), 4.40 and 4.17 (each
1H, d, J¼11.7 Hz), 3.71 (1H, dddd, J¼12.2, 4.9, 1.5, 1.5 Hz), 3.48 (1H,
ddd, J¼10.7, 9.3, 3.9 Hz), 3.25 (1H, dd, J¼11.7, 4.4 Hz), 3.08 (1H, ddd,
J¼12.2, 12.2, 2.4 Hz), 2.86 (1H, ddd, J¼11.7, 9.3, 3.9 Hz), 2.34 (1H,
ddd, J¼11.2, 3.9, 3.9 Hz), 1.90 (1H, m), 1.68 (1H, q, J¼11.7 Hz), 1.49
(3H, s), 1.43 (1H, m), 1.34 (1H, m), 1.20 (1H, m); 13C NMR (100 MHz,
reduced pressure. Purification by flash chromatography (10% EtOAc
27
in hexane) gave aldehyde 23 (320 mg, 86%) as a colorless oil. [
a
]
D
ꢁ42.6 (c 1.0, CHCl3); IR (CHCl3) 1727, 1473, 1238, 1095, 1010, 973,
827 cmꢁ1 1H NMR (400 MHz, CDCl3)
;
d
9.74 (1H, t, J¼2.4 Hz), 4.09
(1H, dd, J¼10.3, 4.9 Hz), 3.75 (1H, m), 3.74 (1H, t, J¼10.3 Hz), 3.70 (1H,
m), 3.45 (1H, ddd, J¼10.7, 8.8, 4.4 Hz), 3.33 (1H, ddd, J¼9.7, 9.7,
4.4 Hz), 2.76 (1H, ddd, J¼16.6, 3.9, 2.0 Hz), 2.47e2.38 (2H, m), 1.56
(1H, q, J¼11.7 Hz), 1.04 (9H, s), 0.99 (9H, s), 0.96 (9H, t, J¼7.8 Hz), 0.62
C6D6)
d 138.7, 128.5, 128.1, 127.9, 127.7, 115.9, 81.0, 78.5, 71.7, 71.2,
67.7, 32.9, 29.9, 28.8, 26.0; HREIMS m/z calcd for C18H24O3 (Mþ)
288.1725, found 288.1735.
(6H, q, J¼7.8 Hz); 13C NMR (100 MHz, CDCl3)
d 200.8, 77.7, 77.2, 72.1,
4.17. (4aR,6S,7R,8aS)-2,2-Di-tert-butyl-7-((triethylsilyl)oxy)-6-
vinylhexahydropyrano[3,2-d][1,3,2]dioxasiline (22)
69.9, 66.7, 46.2, 42.4, 27.4, 27.0, 22.6, 19.9, 6.8, 5.0; HRFABMS m/z
calcd for C22H45O5Si2 (MHþ) 445.2806, found 445.2821.
To a suspension of Ph3PCH3$Br (1.44 g, 4.036 mmol) in THF
(5.0 mL) was added KHMDS (7.06 mL of a 0.5 M solution in toluene,
3.530 mmol) at 0 ꢀC, and the reaction mixture was stirred for 1 h.
The resulting yellow solution was cooled to ꢁ80 ꢀC, and a solution
of aldehyde 21 (434 mg, 1.009 mmol) in THF (4.8 mL) was added.
The reaction mixture was stirred at ꢁ80 ꢀC for 1.5 h and then at
room temperature for 1 h. The reaction was quenched with satu-
rated aqueous NH4Cl solution, and the mixture was extracted with
Et2O. The extract was washed with water and brine, dried, and
concentrated under reduced pressure. Purification by flash chro-
matography (3% EtOAc in hexane) gave olefin 22 (402 mg, 93%) as
4.19. (S)- and (R)-1-((4aR,6S,7R,8aS)-2,2-Di-tert-butyl-7-
((triethylsilyl)oxy)hexahydropyrano[3,2-d][1,3,2]dioxasilin-6-
yl)-3-(trimethylsilyl)penta-3,4-dien-2-ol (24 and 25)
The procedure of allenylation described for 1 was followed with
23 (166 mg, 0.373 mmol). Purification by flash chromatography
(5/10% EtOAc in hexane) afforded 24 (146 mg, 75%) and 25 (40 mg,
19%) as colorless oils. The isomer 25 was eluted slightly faster than
isomer 24. Compound 24: [
a
]
D
28 ꢁ42.7 (c 1.0, CHCl3); IR (CHCl3) 3510,
1928, 1473, 1250, 1144, 1092, 1010, 826 cmꢁ1
;
1H NMR (400 MHz,
CDCl3)
d
4.57 (1H, dd, J¼11.2, 2.9 Hz), 4.46 (1H, dd, J¼11.2, 2.9 Hz),
a colorless oil. [
a
]
D
28 ꢁ44.6 (c 1.0, CHCl3); IR (CHCl3) 1473, 1414, 1387,
4.43 (1H, m), 4.11 (1H, dd, J¼10.2, 4.4 Hz), 3.76 (1H, t, J¼10.2 Hz),
3.74 (1H, m), 3.51e3.43 (2H, m), 3.28 (1H, ddd, J¼10.2, 10.2, 5.4 Hz),
2.69 (1H, br, OH), 2.37 (1H, ddd, J¼11.2, 4.4, 4.4 Hz), 2.06 (1H, ddd,
J¼14.6, 8.3, 2.4 Hz), 1.70 (1H, ddd, J¼14.6, 8.8, 2.4 Hz), 1.53 (1H, q,
1365, 1238, 1088, 1011, 937, 826 cmꢁ1
;
1H NMR (400 MHz, CDCl3)
d
5.85 (1H, ddd, J¼16.6, 10.7, 5.9 Hz), 5.33 (1H, ddd, J¼16.6, 1.9,
1.9 Hz), 5.21 (1H, ddd, J¼16.6, 1.9, 1.9 Hz), 4.17 (1H, dd, J¼9.8,

9094
Y. Suzuki et al. / Tetrahedron 69 (2013) 9086e9095
J¼11.2 Hz), 1.04 (9H, s), 0.99 (9H, s), 0.96 (9H, t, J¼7.8 Hz), 0.62 (6H,
reaction mixture was stirred at room temperature for 1 h. The re-
action mixture was coevaporated with pentane three times to
dryness. Purification by flash chromatography (10% EtOAc in hex-
ane) afforded acetate (17.2 mg, 88%) as a colorless oil. A mixture of
the acetate obtained above and PPTS (1.8 mg) in methanol (1.0 mL)
was stirred at room temperature for 2 h. The reaction was quenched
with Et3N (0.2 mL) and the reaction mixture was concentrated
under reduced pressure. Purification by flash chromatography (10%
q, J¼7.8 Hz), 0.14 (9H, s); 13C NMR (100 MHz, CDCl3)
d 207.2, 100.3,
80.2, 77.1, 72.2, 71.3, 69.8, 67.8, 66.8, 42.6, 38.5, 27.4, 27.0, 22.6, 19.9,
6.8, 5.0, ꢁ0.9; HRFABMS m/z calcd for C28H57O5Si3 (MHþ) 557.3514,
found 557.3529.
Compound 25: [
a]
26 ꢁ39.6 (c 1.0, CHCl3); IR (CHCl3) 3509, 1929,
D
1473, 1249, 1092, 1010, 843, 826 cmꢁ1
;
1H NMR (400 MHz, CDCl3)
d
4.46 (2H, s), 4.10 (1H, dd, J¼10.2, 4.9 Hz), 3.76 (1H, t, J¼10.2 Hz),
3.74 (1H, m), 3.45e3.29 (3H, m), 3.23 (1H, br, OH), 2.36 (1H, ddd,
J¼12.2, 4.4, 4.4 Hz), 2.26 (1H, ddd, J¼14.1, 2.4, 2.4 Hz), 1.60e1.48
(2H, m), 1.04 (9H, s), 0.98 (9H, s), 0.97 (9H, t, J¼7.8 Hz), 0.62 (6H, q,
EtOAc in hexane) afforded 28 (13 mg, 86% for the two steps) as
25
a colorless oil. [
a
]
ꢁ74.9 (c 0.47, CHCl3); IR (CHCl3) 3602, 3460,
D
1957, 1733, 1473, 1373, 1247, 1090, 1026, 827 cmꢁ1
;
1H NMR
5.45 (1H, m), 5.29 (1H, q, J¼6.8 Hz), 4.91e4.82
J¼7.8 Hz), 0.15 (9H, s); 13C NMR (100 MHz, CDCl3)
d
208.0, 99.8, 83.4,
(400 MHz, CDCl3)
d
77.1, 71.9, 71,2, 70.8, 70.2, 66.7, 42.4, 39.1, 27.4, 27.0, 22.6, 19.9, 6.8,
5.0, ꢁ0.8; HRFABMS m/z calcd for C28H57O5Si3 (MHþ) 557.3514,
found 557.3531.
(2H, m), 4.12 (1H, dd, J¼10.2, 4.9 Hz), 3.76 (1H, m), 3.75 (1H, t,
J¼10.2 Hz), 3.41 (1H, m), 3.21 (1H, ddd, J¼10.2, 10.2, 4.9 Hz), 3.16
(1H, ddd, J¼9.3, 9.3, 2.4 Hz), 2.48 (1H, ddd, J¼11.7, 4.4, 4.4 Hz), 2.24
(1H, ddd, J¼12.2, 9.8, 2.4 Hz), 2.07 (3H, s), 1.68 (1H, ddd, J¼12.2, 9.3,
3.4 Hz), 1.49 (1H, q, J¼11.7 Hz), 1.03 (9H, s), 0.99 (9H, s); 13C NMR
4.20. (S)-1-((4aR,6S,7R,8aS)-2,2-Di-tert-butyl-7-((triethylsilyl)
oxy)hexahydropyrano[3,2-d][1,3,2]dioxasilin-6-yl)penta-3,4-
dien-2-ol (26)
(100 MHz, CDCl3) d 208.1, 170.5, 91.2, 78.2, 77.8, 77.1, 72.2, 69.7, 68.0,
66.7, 42.1, 36.6, 27.4, 27.0, 22.6, 21.2, 19.9; HRFABMS m/z calcd for
C
21H37O6Si (MHþ) 413.6004, found 413.5985.
The procedure described for 4 was followed with 24 (99 mg,
0.1784 mmol) and NaOMe (48 mg, 0.8921 mmol) in THF (1.8 mL). A
mixture of the crude product (96.8 mg) and K2CO3 (7.2 mg) in
methanol (1.7 mL) was stirred at room temperature for 1 h. The
reaction was quenched with saturated aqueous NH4Cl solution, and
the mixture was extracted with EtOAc. The extract was washed
with water and brine, dried, and concentrated under reduced
4.23. (R)-1-((4aR,6S,7R,8aS)-2,2-Di-tert-butyl-7-
hydroxyhexahydropyrano[3,2-d][1,3,2]dioxasilin-6-yl)penta-
3,4-dien-2-yl acetate (29)
The procedure described for 28 was followed with 27 (36 mg,
0.0744 mmol). Purification by flash chromatography (10% EtOAc in
hexane) afforded 27 (26 mg, 87% for the two steps) as a colorless oil.
pressure. Purification by flash chromatography (6/10% EtOAc in
24
[a]
24 þ0.99 (c 0.59, CHCl3); IR (CHCl3) 3601, 3420, 1956, 1731, 1472,
hexane) afforded 26 (55 mg, 63%) as a colorless oil. [
a
]
ꢁ44.9 (c
D
D
1368, 1249, 1090, 1030, 827 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d
5.49
1.0, CHCl3); IR (CHCl3) 3510, 1956, 1473, 1239, 1090, 1056, 1010,
826 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d
5.28 (1H, q, J¼6.8 Hz), 4.86
(1H, m), 5.25 (1H, q, J¼6.8 Hz), 4.90 (1H, ddd, J¼11.2, 6.8, 2.0 Hz),
4.85 (1H, ddd, J¼11.2, 6.3, 2.0 Hz), 4.09 (1H, dd, J¼10.2, 5.4 Hz), 3.78
(1H, t, J¼10.2 Hz), 3.76 (1H, ddd, J¼10.7, 8.8, 4.4 Hz), 3.42 (1H, m),
3.26e3.17 (2H, m), 2.47 (1H, ddd, J¼11.7, 4.4, 4.4 Hz), 2.19 (1H, ddd,
J¼14.6, 7.3, 2.9 Hz), 2.04 (3H, s), 1.82 (1H, ddd, J¼14.6, 8.8, 6.3 Hz),
(1H, d, J¼2.9 Hz), 4.84 (2H, dd, J¼6.8, 2.9 Hz), 4.43 (1H, m), 4.11 (1H,
dd, J¼9.8, 4.9 Hz), 3.76 (1H, t, J¼10.2 Hz), 3.74 (1H, ddd, J¼11.2, 9.2,
4.4 Hz), 3.52e3.43 (2H, m), 3.30 (1H, ddd, J¼10.2, 10.2, 4.9 Hz), 2.58
(1H, d, J¼6.3 Hz, OH), 2.38 (1H, ddd, J¼11.7, 4.4, 4.4 Hz), 2.02 (1H,
ddd, J¼14.6, 8.8, 2.4 Hz), 1.70 (1H, ddd, J¼14.6, 8.3, 2.9 Hz), 1.54 (1H,
q, J¼11.7 Hz), 1.04 (9H, s), 0.99 (9H, s), 0.97 (9H, t, J¼7.8 Hz), 0.62
1.70 (1H, br, OH),1.47 (1H, q, J¼11.7 Hz),1.03 (9H, s), 0.99 (9H, s); 13
C
NMR (100 MHz, CDCl3)
d 208.5, 170.3, 90.5, 79.5, 77.5, 77.1, 72.1,
(6H, q, J¼7.8 Hz); 13C NMR (100 MHz, CDCl3)
d 206.8, 94.7, 79.9, 77.5,
77.1, 72.2, 69.7, 66.8, 66.4, 42.5, 38.3, 27.4, 27.0, 22.63, 19.9, 6.8, 5.0;
69.5, 66.8, 42.0, 36.3, 27.4, 27.0, 22.6, 21.3, 19.9; HRFABMS m/z calcd
for C21H37O6Si (MHþ) 413.6004, found 413.6019.
HRFABMS m/z calcd for
C
25H49O5Si2 (MHþ) 485.3119, found
485.3142.
4.24. (4aR,5aS,7S,8S,9aR,10aS)-2,2-Di-tert-butyl-8-
vinyloctahydro-4H-pyrano[20,30:5,6]pyrano[3,2-d][1,3,2]dioxa-
silin-7-yl acetate (30)
4.21. (R)-1-((4aR,6S,7R,8aS)-2,2-Di-tert-butyl-7-((triethylsilyl)
oxy)hexahydropyrano[3,2-d][1,3,2]dioxasilin-6-yl)penta-3,4-
dien-2-ol (27)
The procedure described for 6 was followed with 28 (7.7 mg,
0.0194 mmol) and AgClO4 (8.1 mg 0.0388 mmol) in DCE (0.5 mL).
Purification by flash chromatography (10% EtOAc in hexane) affor-
The procedure described for 26 was followed with 25 (67 mg,
0.1210 mmol). Purification by flash chromatography (10% EtOAc in
hexane) afforded 27 (39 mg, 66%) as a colorless oil. [
24
ded 30 (5.5 mg, 71%) as a colorless oil. [
a
]
24 ꢁ4.87 (c 0.40, CHCl3); IR
D
a]
ꢁ43.9 (c
D
(CHCl3) 1736, 1473, 1375, 1241, 1101, 1048, 941 cmꢁ1
;
1H NMR
0.61, CHCl3); IR (CHCl3) 3505, 1957, 1472, 1239, 1090, 1060, 1009,
826 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d
5.24 (1H, q, J¼5.8 Hz), 4.83
(400 MHz, CDCl3)
d
5.76 (1H, ddd, J¼17.6, 10.7, 5.4 Hz), 5.35 (1H,
ddd, J¼17.6, 1.5, 1.5 Hz), 5.22 (1H, ddd, J¼10.7, 1.5, 1.5 Hz), 5.16 (1H,
m), 4.13 (1H, dd, J¼9.8, 4.9 Hz), 4.04 (1H, ddd, J¼5.4, 2.9, 1.5 Hz),
3.85 (1H, ddd, J¼11.2, 9.3, 4.9 Hz), 3.80 (1H, t, J¼10.2 Hz), 3.43 (1H,
ddd, J¼11.7, 9.3, 4.4 Hz), 3.39 (1H, ddd, J¼10.2, 9.3, 4.9 Hz), 3.20 (1H,
ddd, J¼11.7, 9.3, 4.4 Hz), 2.47 (1H, ddd, J¼11.7, 4.4, 4.4 Hz), 2.22 (1H,
ddd, J¼13.7, 4.4, 3.4 Hz), 2.09 (3H, s), 1.74e1.64 (2H, m), 1.04 (9H, s),
(2H, m), 4.43 (1H, m), 4.10 (1H, dd, J¼10.2, 4.9 Hz), 3.77 (1H, t,
J¼10.2 Hz), 3.75 (1H, ddd, J¼11.2, 8.8, 4.9 Hz), 3.45e3.28 (3H, m),
3.19 (1H, d, J¼1.5 Hz, OH), 2.37 (1H, ddd, J¼11.7, 4.4, 4.4 Hz), 2.16
(1H, ddd, J¼14.1, 3.4, 2.0 Hz), 1.58e1.48 (2H, m), 1.04 (9H, s), 0.98
(9H, s), 0.97 (9H, t, J¼7.8 Hz), 0.63 (6H, q, J¼7.8 Hz); 13C NMR
(100 MHz, CDCl3)
d 207.2, 94.3, 82.8, 77.1, 77.08, 72.0, 70.3, 69.3,
0.99 (9H, s); 13C NMR (100 MHz, CDCl3)
d
170.5, 133.9, 117.4, 97.1,
66.6, 42.4, 38.8, 27.4, 27.0, 22.6, 19.9, 6.8, 5.0; HRFABMS m/z calcd
for C25H49O5Si2 (MHþ) 485.3119, found 485.3102.
77.8, 76.5, 73.8, 72.7, 70.4, 66.7, 38.3, 33.9, 27.4, 27.0, 22.6, 21.0, 19.9;
HRFABMS m/z calcd for
C
21H37O6Si (MHþ) 413.6004, found
413.6037.
4.22. (S)-1-((4aR,6S,7R,8aS)-2,2-Di-tert-butyl-7-
hydroxyhexahydropyrano[3,2-d][1,3,2]dioxasilin-6-yl)penta-
3,4-dien-2-yl acetate (28)
Acknowledgements
To a solution of 26 (18 mg, 0.03719 mmol) and DMAP (1.0 mg) in
pyridine (0.5 mL) was added acetic anhydride (0.5 mL), and the
This work was supported by JSPS KAKENHI Grant Number
24590033.

Y. Suzuki et al. / Tetrahedron 69 (2013) 9086e9095
9095
del Campo, T.; Soriano, E.; Marco-Contelles, J. L. Chem.dEur. J. 2009, 15,
9127e9138; (e) Sawama, Y.; Sawama, Y.; Krause, N. Org. Biomol. Chem. 2008, 6,
3573e3579; (f) Yu, X.; Seo, S. Y.; Marks, T. J. J. Am. Chem. Soc. 2007, 129,
7244e7245; (g) Deutsch, C.; Gockel, B.; Hoffmann-Roder, A.; Krause, N. Synlett
2007, 1790e1794.
Supplementary data
Supplementary data associated with this article can be found in
the online version, at http://dx.doi.org/10.1016/j.tet.2013.08.026.
€
8. (a) Audin, P.; Doutheau, A.; Gore, J. Tetrahedron Lett. 1982, 23, 4337e4340; (b)
Kang, S.-K.; Baik, T.-G.; Kulak, A. N. Synlett 1999, 324e326; (c) Yamamoto, T.;
Matsuda, H.; Utsumi, Y.; Hagiwara, T.; Kanisawa, T. Tetrahedron Lett. 2002, 43,
9077e9080; (d) Zhang, Z.; Liu, C.; Kinder, R. E.; Han, X.; Qian, H.; Widenhoefer,
R. A. J. Am. Chem. Soc. 2006, 128, 9066e9073; (e) Hamilton, G. L.; Kang, E. J.;
Mba, M.; Toste, F. D. Science 2007, 317, 496e499; (f) Zhang, Z.; Widenhoefer, R.
A. Angew. Chem., Int. Ed. 2007, 46, 283e285; (g) Jung, M. S.; Kim, W. S.; Shin, Y.
H.; Jin, H. J.; Kim, Y. S.; Kang, E. J. Org. Lett. 2012, 14, 6262e6265.
9. (a) Mori, Y.; Yaegashi, K.; Furukawa, H. Tetrahedron Lett. 1999, 40,
7239e7242; (b) Furuta, H.; Takase, T.; Hayashi, H.; Noyori, R.; Mori, Y. Tet-
rahedron 2003, 59, 9767e9777; (c) Sakai, T.; Sugimoto, A.; Mori, Y. Org. Lett.
2011, 13, 5850e5853.
References and notes
ꢀ
1. Bermejo, A.; Figadere, B.; Zafra-Polo, M.-C.; Barrachina, I.; Estornell, E.; Cortes,
D. Nat. Prod. Rep. 2005, 22, 269e303.
2. Polyether Antibiotics; Westley, J. W., Ed.; Marcel Dekker: New York, NY, 1983;
Vols. I and II.
3. (a) Kornprobst, J.-M. Encyclopedia of Marine Natural Products; Wiley-Blackwell:
Weinheim, Germany; (b) Yasumoto, T.; Murata, M. Chem. Rev. 1993, 93,
1897e1909; (c) Murata, M.; Yasumoto, T. Nat. Prod. Rep. 2000, 17, 293e314; (d)
Yasumoto, T. Chem. Rec. 2001, 1, 228e242.
10. Nicolaou, K. C.; Prasad, C. V. C.; Somers, P. K.; Hwang, C.-K. J. Am. Chem. Soc.
4. For reviews, see: (a) Clarke, P. A.; Santos, S. Eur. J. Org. Chem. 2006, 2045e2053;
(b) Larrosa, I.; Romea, P.; Urpí, F. Tetrahedron 2008, 64, 2683e2723; (c) Olier, C.;
Kaafarani, M.; Gastaldi, S.; Bertrand, M. P. Tetrahedron 2010, 66, 413e445.
5. For reviews on the synthesis of polytetrahydropyrans and marine polycyclic
ethers, see: (a) Inoue, M. Chem. Rev. 2005, 105, 4379e4405; (b) Nakata, T. Chem.
Rev. 2005, 105, 4314e4347; (c) Nicolaou, K. C.; Frederick, M. O.; Aversa, R. J.
Angew. Chem., Int. Ed. 2008, 47, 7182e7225.
1989, 111, 5330e5334.
11. Yokoyama, H.; Nakayama, S.; Murase, M.; Miyazawa, M.; Yamaguchi, S.; Hirai, Y.
Heterocycles 2009, 77, 211e215.
12. Nicolaou, K. C.; Hwang, C.-K.; Marron, B. E.; DeFrees, S. A.; Couladouros, E. A.;
Abe, Y.; Carroll, P. J.; Snyder, J. P. J. Am. Chem. Soc. 1990, 112, 3040e3054.
13. Inoue, M.; Nakada, M. Angew. Chem., Int. Ed. 2006, 45, 252e255.
14. Brook, A. G.; Chrusciel, J. J. Organometallics 1984, 3, 1317e1318.
15. Corey, E. J.; Yu, C.-M.; Lee, D.-H. J. Am. Chem. Soc. 1990, 112, 878e879.
16. Walkup, R. D.; Park, G. J. Am. Chem. Soc. 1990, 112, 1597e1603.
17. Nishizawa, M.; Imagawa, H.; Yamamoto, H. Org. Biomol. Chem. 2010, 8, 511e521.
18. Yamamoto, Y. J. Org. Chem. 2007, 72, 7817e7831.
19. Nicolaou, K. C.; Nugiel, D. A.; Couladouros, E.; Hwang, C.-K. Tetrahedron 1990,
46, 4517e4552.
20. (a) Leandri, G.; Monti, H.; Bertrand, M. Tetrahedron 1974, 30, 289e293; (b)
Nikam, S. S.; Chu, K.-H.; Wang, K. K. J. Org. Chem. 1986, 51, 745e747.
21. (a) Hiramatsu, N.; Takahashi, N.; Noyori, R.; Mori, Y. Tetrahedron 2005, 61,
8589e8597; (b) Mori, Y.; Hayashi, H. J. Org. Chem. 2001, 66, 8666e8668.
6. For reviews, see: (a) Bates, R. W.; Satcharoen, V. Chem. Soc. Rev. 2002, 31, 12e21;
ꢁ
~
(b) Alvarez-Corral, M.; Munoz-Dorado, M.; Rodoriguez-García, I. Chem. Rev. 2008,
108, 3174e3198; (c) Weibel, J.-M.; Blanc, A.; Pale, P. Chem. Rev. 2008, 108,
3149e3173; (d) Gorin, D.; Sherry, B. D.; Toste, D. Chem. Rev. 2008,108, 3351e3378;
(e) Muzart, J. Tetrahedron 2008, 64, 5815e5849; (f) Majumdar, K. C.; Debnath, P.;
Roy, B. Heterocycles 2009, 78, 2661e2728; (g) Sengupta, S.; Shi, X. ChemCatChem
2010, 2, 609e619; (h) Yu, S.; Ma, S. Angew. Chem., Int. Ed. 2012, 51, 3074e3112.
7. For recent examples, see: (a) Alcaide, B.; Almendros, P.; Carrascosa, R.; Martinez
del Campo, T. Chem.dEur. J. 2010, 16, 13243e13252; (b) Gockel, B.; Krause, N.
Eur. J. Org. Chem. 2010, 311e316; (c) Arbour, J. L.; Rzepa, H. S.; White, A. J. P.; Hii,
K. K. Chem. Commun. 2009, 7125e7127; (d) Alcaide, B.; Almendros, P.; Martinez