Stereoselective synthesis of the C1-C29 part of amphidinol 3

Article abstract of DOI:10.1021/jo502322m

Stereoselective synthesis of the C1-C29 part of amphidinol 3 (AM3) was achieved. The C1-C20 part was assembled from three building blocks via regioselective cross metathesis to form the C4-C5 double bond and addition of an alkenyllithium and a lithium acetylide to two Weinreb amides followed by asymmetric reduction to form the C9-C10 and C14-C15 bonds, respectively. The C21-C29 part was synthesized via successive cross metathesis and oxa-Michael addition sequence to construct the 1,3-diol system at C25 and C27 and Brown asymmetric crotylation to introduce the stereogenic centers at C23 and C24. Coupling of the C1-C20 and C21-C29 parts was achieved by Julia-Kocienski olefination and regio- and stereoselective dihydroxylation of the C20-C21 double bond in the presence of the C4-C5 and C8-C9 double bonds to afford the C1-C29 part of AM3.

Full text of DOI:10.1021/jo502322m

Article
pubs.acs.org/joc
Stereoselective Synthesis of the C1−C29 Part of Amphidinol 3
Takeshi Tsuruda, Makoto Ebine, Aya Umeda, and Tohru Oishi*
Department of Chemistry, Faculty and Graduate School of Sciences, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka
812-8581, Japan
S
* Supporting Information
ABSTRACT: Stereoselective synthesis of the C1−C29 part of amphidinol 3 (AM3) was achieved. The C1−C20 part was
assembled from three building blocks via regioselective cross metathesis to form the C4−C5 double bond and addition of an
alkenyllithium and a lithium acetylide to two Weinreb amides followed by asymmetric reduction to form the C9−C10 and C14−
C15 bonds, respectively. The C21−C29 part was synthesized via successive cross metathesis and oxa-Michael addition sequence
to construct the 1,3-diol system at C25 and C27 and Brown asymmetric crotylation to introduce the stereogenic centers at C23
and C24. Coupling of the C1−C20 and C21−C29 parts was achieved by Julia−Kocienski olefination and regio- and
stereoselective dihydroxylation of the C20−C21 double bond in the presence of the C4−C5 and C8−C9 double bonds to afford
the C1−C29 part of AM3.
Rychnovsky,14 Marko,15 Crimmins,16 and our groups.8,9,17
́
INTRODUCTION
■
Although synthesis of the polyol moiety of AM3 has been
reported, we envisaged an alternative synthetic route based on
the revised structure of AM3 as shown in Scheme 1. The C1−
C29 part (2) was to be synthesized through Julia−Kocienski
olefination18,19 from aldehyde 3 and sulfone 4, followed by
regio- and stereoselective dihydroxylation20 of the C20−C21
double bond. The C1−C20 part (3) would be derived from
terminal olefins 5 and 6 via cross metathesis,8,21 and 6 would be
derived from Weinreb amide 822 through the formation of the
C9−C10 and C14−C15 bonds via the addition of an
alkenyllithium derived from iodoalkene 7 and a lithium
acetylide derived from 9, respectively, followed by asymmetric
reduction. Sulfone 4, corresponding to the C21−C29 part, was
to be synthesized from α,β-unsaturated aldehyde 10 derived
from the terminal olefin 11 via cross metathesis with acrolein
12,11a followed by acid-catalyzed oxa-Michael addition reported
by Evans23 to construct the 1,3-diol system at C25 and C27 and
Brown asymmetric crotylation24 to induce the stereogenic
centers at C23 and C24. In this strategy, it was a challenging
task to construct the C20−C21 diol moiety by dihydroxylation
of the C20−C21 double bond in the presence of the C4−C5
and the C8−C9 double bonds. There was also the question of
whether the cross metathesis of 5 and 6, also a key step, would
proceed efficiently, although we have reported a similar
coupling strategy.8
Amphidinol 3 (AM3, 1, Figure 1), a marine natural product
produced by the dinoflagellate Amphidinium klebsii, shows
antifungal and hemolytic activity.1 The biological activity of
AM3 can be accounted for by the formation of ion-permeable
pores in a sterol-dependent manner.2 A number of congeners of
amphidinol3 have been isolated to date, including luteophano-
l,4a,b,e lingshuiol,4c,d karatungiol,4f karlotoxin,4g,i carteraol,4h and
amdigenol.4j Although it has been difficult to determine the
molecular structure of AM3 due to the limited availability of the
natural product and the presence of a number of stereogenic
centers on the long acyclic carbon chain, the stereochemistry of
AM3 was determined in 1999 by the J-based configuration
analysis (JBCA) method,5 the modified Mosher method,6 and
degradation of the natural product. During the course of our
studies confirming the structure of AM3 based on chemical
synthesis, the absolute configuration at C45 was confirmed to
be R,7 while those at C2 and C51 were revised as R and S,
respectively.8,9 Therefore, total synthesis of AM3 is necessary to
confirm the complete stereochemistry. Herein, we report the
stereoselective synthesis of the C1−C29 part (2) correspond-
ing to the polyol moiety of AM3 (Figure 1).
RESULTS AND DISCUSSION
■
The striking structural features of AM3, represented by the
presence of a long hydrophilic polyol chain, highly substituted
tetrahydropyran ring systems, and a hydrophobic polyene unit,
have attracted considerable attention in the synthetic
community,10 and a number of synthetic studies of AM3
have been reported by Cossy,11 Paquette,12 Roush,13
Received: October 10, 2014
© XXXX American Chemical Society
A
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Figure 1. Structures of amphidinol 3 (AM3, 1) and the C1−C29 part of AM3 (2).
Scheme 1. Retrosynthetic Analysis of the C1−C29 Part (2) of AM3
The synthetic route for the C1−C20 part (3) of AM3 is
shown in Scheme 2. Racemic alcohol 14 was prepared from
acrolein 12 and an organozinc reagent derived from propargyl
bromide 13 in 68% yield after distillation.25 Hydrostannyla-
tion26 of the terminal alkyne 14 with Bu3SnH and Pd2(dba)3·
CHCl3 (dba = dibenzylideneacetone) resulted in the formation
of stannane 15 (58%), which was subjected to tin−halogen
exchange reaction to furnish iodoalkene 16 (95%). Sharpless
kinetic resolution27 of racemic alcohol 16 using L-(+)-dicyclo-
hexyltartrate (DCHT) furnished allylic alcohol 17 in 39% yield
and with >99% ee. The enantiomeric excess was determined by
HPLC analysis using a chiral column, and the absolute
configuration was determined by the modified Mosher method
(see the Supporting Information). Protection of the secondary
alcohol as a TBS ether gave 7 (97%). Next, the known Weinreb
amide 822 was treated with 1.2 equiv of the lithium acetylide
derived from alkyne 928 by treatment with n-BuLi to afford
ketone 18 in 81% yield. Noyori asymmetric hydrogen transfer
to 18 with catalyst 1929 proceeded smoothly to give propargylic
alcohol 20 in 90% yield and with 94% ee. The enantiomeric
excess was determined by conversion to MTPA esters, and the
absolute configuration was determined by the modified Mosher
method (see the Supporting Information). Hydrogenation of
alkyne 20 with Pd/C(en)30 (89%) was followed by protection
of the secondary alcohol 21 as a TBS ether to furnish 22 (99%),
corresponding to the C6−C20 part. Treatment of the Weinreb
amide 22 with alkenyllithium derived from iodoolefin 7 by
treatment with n-BuLi resulted in the formation of enone 23
(99%), which was subjected to CBS reduction using 2431 to
afford allylic alcohol 25 in 99% yield and with 95:5 selectivity.
The diastereomeric ratio was determined by conversion to
MTPA esters, and the absolute configuration was determined
by the modified Mosher method (see the Supporting
Information). After protection of the secondary alcohol 25 as
TBS ether 6 (99%), one of the crucial steps of the present
synthesis, a cross metathesis reaction with the known olefin 532
was carried out (Table 1). There are two problems in
conducting cross metathesis: (i) competitive formation of
homodimers and (ii) isolation of the products from a complex
mixture of starting materials and possible homodimers. To
overcome the latter problem, we carried out the cross
metathesis using a combination of a polar substrate (alcohol
B
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a
Scheme 2. Synthesis of the C1−C20 (3) Part of AM3
a
Key: (a) 13, Zn, 1,2-dibromoethane, TMSCl, THF, rt, 20 min; then 12, THF, −78 to 0 °C, 12 h, 68%; (b) Pd2(dba)3·CHCl3, Cy3PHBF4, i-Pr2EtN,
n-Bu3SnH, CH2Cl2, 0 °C to rt, 1 h, 58%; (c) I2, CH2Cl2, 0 °C, 10 min, 95%; (d) L-(+)-DCHT, Ti(Oi-Pr)4, TBHP, MS4A (molecular sieves 4A), −20
°C, 9 days, 39% (> 99%ee); (e) TBSCl, imidazole, DMF, 0 °C, 2 h, 97%; (f) n-BuLi, HCCC4H8OPMB (9), −78 to −20 °C, THF, 1 h, 81%; (g)
19, i-PrOH, rt, 2 h, 90%, 94%ee; (h) H2, Pd/C(en), rt, 24 h, 89%; (i) TBSCl, imidazole, DMF, 0 °C, 4 h, 99%; (j) 7, n-BuLi, THF, −78 °C, 10 min;
then 22, THF, −50 °C, 8 min, 99%; (k) 24, BH3·SMe2, toluene, −78 to −30 °C, 2 h, 99% (dr = 95:5); (l) TBSCl, imidazole, DMF, 0 °C, 4 h, 99%;
(m) 5, Grubbs second-generation catalyst (26), CH2Cl2, 45 °C, 3 h, 70%, E/Z = 13:1, 70%; (n) TBSOTf, 2,6-lutidine, 0 °C, 10 min, 100%; (o)
DDQ, pH 7 buffer, CH2Cl2, rt, 1 h; (p) SO3·Py, DMSO, Et3N, 0 °C to rt, 3 h, 67% (two steps).
5) and a less polar substrate (TBS ether 6) because the polarity
of the product 27 is between those of 5 and 6, while the
homodimer derived from 6 would be less polar than 6 and that
derived from 5 would be more polar than 5. Thus, a solution of
olefin 5 and 6 in a 3:1 ratio in CH2Cl2 was treated with the
second-generation Grubbs catalyst 2633 under reflux to afford
the coupling product 27 in 38% yield in an E/Z ratio of 13:1
with 56% recovery of 6 (entry 1). As a byproduct, the dimeric
compound 30 was formed in 31% yield, which corresponds to a
62% yield based on the monomer unit. When 26 was replaced
with Zhan 1B catalyst (29),34 the yield of 27 dropped to 26%,
with recovery of 6 at 72% and the formation of dimer 30 in
34% yield (68% based on the monomer unit) (entry 2). As the
reason for the low yield of 27 was the competitive formation of
homodimer 30 derived from 5, because the free hydroxy group
accelerated coordination to the Ru catalyst, the ratio of 6 was
increased (5:6 = 1:1.3), and the yield of 27 increased slightly to
40% (entry 3). When the ratio was increased to 5:6 = 1:3, the
yield of the desired product improved dramatically to afford 27
in 70% yield with 70% recovery of 6 (entry 4). The homodimer
30 was formed in 20% yield as a byproduct, but a possible
dimer derived from 6 was not detectable, and the desired
product 27 was easily separated from the starting material 6 and
the homodimer 30 by silica gel column chromatography.
Having obtained the coupling product 27, we moved on to
the synthesis of the C1−C20 part. Protection of the secondary
alcohol as a TBS ether 28 (100%) followed by removal of the
PMB group with DDQ and Parikh−Doering oxidation35 of the
resulting primary alcohol gave aldehyde 3 (67%, two steps),
corresponding to the C1−C20 part of AM3.
Next, synthesis of the C21−C29 part (4) commenced with
protection of the known alcohol 3136 as TES ether 11 (99%),
as shown in Scheme 3. Cross metathesis of the terminal olefin
11 and acrolein 12 using Hoveyda−Grubbs second-generation
catalyst 3237 afforded 10 in 72% yield, while the reaction using
Grubbs second-generation catalyst 26 resulted in a low yield of
C
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Table 1. Cross-Metathesis Reaction of 5 and 6
substrate/ratio
a
b
c
entry
catalyst
5
6
yield of 27 (%)
recovery of 6 (%)
yield of 30 (%)
1
2
3
4
Grubbs second (26)
Zhan 1B (29)
3
3
1
1
1
1
38
26
40
70
56
72
61
70
31 (62)
34 (68)
d
Grubbs second (26)
Grubbs second (26)
1.3
3
ND
a
b
c
All reactions were carried out under reflux in CH2Cl2. 10 mol % catalyst was used in each reaction. The number in parentheses is the yield based
d
on the monomer unit. Not determined.
10 (19%). The α,β-unsaturated aldehyde 10 was subjected to
oxa-Michael reaction as reported by Evans,23 using acetalde-
hyde and Bi(NO3)3·5H2O to furnish acetal 33, and the
resulting aldehyde was reduced with NaBH4 to yield primary
alcohol 34 in 87% yield for two steps. Protection of the primary
alcohol 34 as the NAP (2-naphthylmethyl) ether 35 with
NAPBr and NaH (82%) and removal of the TBS group with
TBAF gave alcohol 36 (96%). Oxidation of the primary alcohol
with Dess−Martin periodinane (DMP)38 gave aldehyde 37
followed by Brown asymmetric crotylation using 3824 to afford
39 as a single isomer in 61% yield over two steps. The absolute
configuration of alcohol 39 was determined by the modified
Mosher method (see the Supporting Information). Hydrolysis
of acetal 39 with p-TsOH·H2O in THF/MeOH/H2O at 60 °C
for 20 h gave triol 40 in 42% yield, with recovery of 39 at 53%
(89% yield based on recovered starting material); this was
followed by protection of the resulting triol 40 as a TBS ether
to yield 41 (98%). Hydroboration of the terminal olefin 41
with dicyclohexylborane followed by oxidative workup gave
primary alcohol 42 in 91% yield. Treatment of 42 with 1-
phenyl-1H-tetrazole-5-thiol 43 in the presence of Ph3P and
diisopropyl azodicarboxylate (DIAD) furnished sulfide 44 in
91% yield. Although oxidation of lipophilic sulfide 44 with
Mo7(NH4)6O24·4H2O and H2O2 was sluggish under the two-
phase reaction conditions to obtain sulfone 4 in 78% yield after
6 days, that with m-chloroperbenzoic acid (MCPBA)
proceeded more rapidly to afford 4 in 86% yield.
Having synthesized the C1−C20 part 3 and the C21−C29
part 4, we moved on to the synthesis of the C1−C29 part 2
(Scheme 4). Julia−Kocienski olefination19 of aldehyde 3 with
sulfone 4 using KHMDS as a base at −78 °C to room
temperature for 22 h proceeded smoothly to afford the
coupling product 45 in 86% yield in an E/Z = 20:1 ratio. The
next task was the crucial step of the present synthesis:
dihydroxylation of the C20−C21 double bond in the presence
of the C4−C5 and the C8−C9 double bonds. Fortunately,
regio- and stereoselective dihydroxylation of olefin 45 at the
less-hindered site was achieved by Sharpless asymmetric
dihydroxylation20 using (DHQ)2PHAL as a ligand to afford
β-diol 46 along with the corresponding α-diol in a 4.8:1 ratio in
62% yield. The diastereoselectivity was improved by using
monomeric ligand DHQ-MEQ (dihydroquinine 4-methyl-2-
quinolyl ether)39 to furnish 46 along with the corresponding α-
diol in 13:1 ratio in 65% yield. The diol 46 was separated from
the corresponding α-diol by silica gel column chromatography
and protected as a TBS ether to give 47 (93%), and the NAP
group of 47 was removed with DDQ to afford alcohol 48
(83%). Finally, the primary alcohol was converted to terminal
olefin 2 by the Nishizawa−Grieco method40 using 2-nitro-
phenyl selenocyanate and Me3P followed by treatment with
H2O2 to afford the C1−C29 part 2 in 97% yield. The longest
linear sequence was 21 steps from acrolein 12, and the total
yield was 1.7%, with an 82% average yield.
CONCLUSION
■
In conclusion, stereoselective synthesis of the C1−C29 part of
AM3 was achieved. The C1−20 part was constructed via
regioselective cross metathesis to form the C4−C5 double
bond, addition of lithium acetylide to a Weinreb amide
followed by asymmetric reduction (C14−C15 bond forma-
tion), and addition of an alkenyllithium to a Weinreb amide
followed by asymmetric reduction (C9−C10 bond formation).
The C21−C29 part was synthesized via successive cross
metathesis, oxa-Michael addition, and Brown asymmetric
crotylation followed by coupling of the C1−C20 aldehyde
and the C21−C29 sulfone by Julia−Kocienski olefination and
then regio- and stereoselective dihydroxylation of the C20−
C21 double bond in the presence of the C4−C5 and C8−C9
double bonds. Further studies toward the total synthesis of
AM3 are currently in progress in our laboratory.
EXPERIMENTAL SECTION
■
General Methods for Organic Synthesis. All reactions sensitive
to air or moisture were performed under argon atmosphere with dry
glassware unless otherwise noted in particular. The dehydrated
solvents CH2Cl2, tetrahydrofuran (THF), toluene, and N,N-
D
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a
Scheme 3. Synthesis of the C21−C29 (4) Part of AM3
a
(a) TESCl, imidazole, DMF, 0 °C to rt, 30 min, 99%; (b) Hoveyda−Grubbs second-generation cat. (32), CH2Cl2, 35 °C, 5 h, 72%; (c) CH3CHO,
Bi(NO3)3·5H2O, CH2Cl2, 30 °C, 67 h; (d) NaBH4, MeOH, 0 °C, 10 min, 87% (2 steps); (e) NAPBr, NaH, DMF, 0 °C, 80 min, 82%; (f) TBAF,
THF, rt, 40 min, 96%; (g) DMP, CH2Cl2, rt, 2.5 h, 89%; (h) 38 (Ipc = isopinocampheyl), THF, −78 °C to rt, 8.5 h, 69%; (i) p-TsOH·H2O, THF,
MeOH, H2O, 60 °C, 20 h, 42%, recovery of 39 53% (89% brsm); (j) TBSOTf, 2,6-lutidine, CH2Cl2, 0 °C, 30 min, 98%; (k) BH3·SMe2, cyclohexene,
THF, 0 °C to rt, 30 min; then aq NaOH, H2O2, rt, 2 h, 91%; (l) 43, PPh3, DIAD, THF, 0 °C, 10 min, 91%; (m) MCPBA, CH2Cl2, 0 °C, 39 h, 86%.
dimethylformamide (DMF) were used without further dehydration.
Propargyl bromide, Bu3SnH, and Et3N were distilled before use.
Molecular sieves 4A (MS4A) were preactivated by heating in vacuo.
All other chemicals were obtained from local venders and used as
supplied unless otherwise stated. Thin-layer chromatography (TLC)
to −10 °C. To this mixture was added a solution of propargyl bromide
13 (54.4 mL, 718 mmol) in THF (78 mL) slowly via cannula. The
mixture was stirred for 1 h below −10 °C and then cooled to −78 °C.
To the mixture was added a solution of freshly distilled acrolein 12
(24.0 mL, 359 mmol) in THF (600 mL) over 1 h via dropping funnel.
The resulting mixture was gradually warmed to 0 °C over 12 h and
quenched with saturated aqueous NH4Cl (200 mL). The mixture was
extracted with Et2O, and the combined organic layer was washed with
H2O and saturated aqueous solution of NaCl, dried over anhydrous
Na2SO4, filtered, and concentrated under reduced pressure to remove
THF and Et2O. The residue was purified by distillation (56 °C/20
mmHg) to give known alcohol 1425 (23.6 g, 246 mmol, 68%) as a
colorless oil.
(E)-6-(Tributylstannyl)hexa-1,5-dien-3-ol (15). A mixture of
Pd2(dba)3·CHCl3 (538 mg, 0.520 mmol), tricyclohexylphosphonium
tetrafluoroborate (766 mg, 2.08 mmol), and i-Pr2NEt (0.75 mL, 4.2
mmol) in CH2Cl2 (1 L) was stirred at room temperature for 10 min.
To this mixture was added a solution of alcohol 14 (10.0 g, 104 mmol)
in CH2Cl2 (75 mL + 2 × 5 mL rinse) at room temperature. The
reaction mixture was cooled to −10 °C, and a solution of Bu3SnH
(35.0 mL, 130 mmol) in CH2Cl2 (115 mL) was added via dropping
funnel over 10 min. The resultant solution was stirred at 0 °C for 30
min and then warmed to room temperature. After 30 min, the reaction
mixture was concentrated and purified by silica gel column
chromatography (hexane/ethyl acetate = 70/1 → 50/1 with addition
was performed using precoated TLC glass plates (silica gel 60 F254
,
0.25 mm thickness) for the reaction analyses. Silica gel was used for
column chromatography (spherical, neutral, 100−210 μm) or for flash
chromatography (40−50 μm). Optical rotations were recorded on a
polarimeter. IR spectra were recorded on FT/IR equipment. 1H NMR
spectra were recorded at 600 or 400 MHz, and 13C NMR spectra were
recorded at 150 or 100 MHz. Chemical shifts were reported in ppm
from tetramethylsilane (TMS) with reference to internal residual
solvent [1H NMR: CHCl3 (7.26), C6D5H (7.16); 13C NMR: CDCl3
(77.16), C6D6 (128.0)]. The following abbreviations are used to
designate the multiplicities: s = singlet, d = doublet, t = triplet, q =
quartet, m = multiplet, brs = broad singlet. High-resolution mass
spectra (HRMS) were recorded on ESI-TOF or APCI-TOF
equipment.
Hex-1-en-5-yn-3-ol (14). To a suspension of zinc powder (47.0 g,
718 mmol) in THF (650 mL) was added 1,2-dibromoethane (6.2 mL,
72 mmol) and the mixture heated to 65 °C for 10 min. After the
mixture was allowed to cool to 25 °C and stirred for 20 min,
chlorotrimethylsilane (9.1 mL, 72 mmol) was added dropwise via
syringe. The mixture was stirred vigorously for 20 min and then cooled
E
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a
Scheme 4. Synthesis of the C1−C29 (2) Part of AM3
a
(a) KHMDS, THF, −78 °C, 4 h then rt, 18 h, 86%; (b) K2OsO4·2H2O, DHQ-MEQ, K2CO3, K3Fe(CN)6, MeSO2NH2, t-BuOH, t-BuOMe, H2O, 0
°C, 69 h, 65%, dr =13:1; (c) TBSOTf, 2,6-lutidine, CH2Cl2, 0 °C, 10 min, 93%; (d) DDQ, pH 7 buffer, CH2Cl2, 0 °C, 1 h, then NaBH4, MeOH,
THF, 0 °C, 10 min, 83%; (e) o-O2NC6H4SeCN, Me3P, MS4A, THF, rt, 30 min; then aq H2O2, rt, 2.5 h, 97%.
of 1 v/v% Et3N) to afford vinylstannane 15 (23.4 g, 60.5 mmol, 58%)
as a colorless oil: Rf = 0.48 (hexane/ethyl acetate = 6/1); IR (neat)
of TBHP (3.2 M in CH2Cl2, 5.9 mL, 19 mmol) via syringe over 10
min. After the mixture was stirred for 165.5 h, TBHP (3.2 M in
CH2Cl2, 4.2 mL, 13 mmol) was added. After 47 h, the reaction was
quenched with ice-cold FeSO4/citric acid solution (39 g of FeSO4
heptahydrate and 12.2 g of citric acid monohydrate in 118 mL water)
at −20 °C. The mixture was warmed to room temperature and stirred
for 30 min before filtering through a pad of Celite. The filtrate was
extracted with ethyl acetate. The organic layer was washed with water
and saturated aqueous NaCl, dried over anhydrous Na2SO4, filtered,
and concentrated under reduced pressure. The residue was purified by
silica gel column chromatography (hexane/ethyl acetate = 10/1 → 4/1
→ 1/1) to give allylic alcohol 17 (2.36 g, 10.5 mmol, 39%, er =
99.97:0.03) as a yellow oil. The enantiomeric ratio of alcohol 17 was
determined by HPLC using chiral column (CHIRALPAK AD, ϕ 4.6 ×
250 mm, eluted with 5% i-PrOH in hexane, 0.5 mL/min, detected at
260 nm), tR = 16.3 min ((R)-17), tR = 26.1 min ((S)-17): Rf = 0.47
1
3727, 3353, 2955, 2925, 1599, 1463, 921 cm−1; H NMR (600 MHz,
CDCl3) δ 6.07 (d, J = 18.6 Hz, 1H), 5.93 (dt, J = 18.6, 6.6 Hz, 1H),
5.90 (ddd, J = 17.4, 10.2, 6.6 Hz, 1H), 5.25 (ddd, J = 17.4, 1.2, 1.2 Hz,
1H), 5.12 (ddd, J = 10.2, 1.2, 1.2 Hz, 1H), 4.20−4.17 (m, 1H), 2.47−
2.43 (m, 1H), 2.38−2.33 (m, 1H), 1.71−1.70 (m, 1H), 1.54−1.42 (m,
6H), 1.33−1.26 (m, 6H), 0.93−0.82 (m, 15H); 13C NMR (150 MHz,
CDCl3) δ 144.3, 140.5, 133.4, 114.7, 71.7, 46.0, 29.3 (3C), 27.4 (3C),
13.8 (3C), 9.6 (3C); HRMS (ESI-TOF) m/z [M + Na]+ calcd for
C18H36OSnNa 411.1680, found 411.1663.
(E)-6-Iodohexa-1,5-dien-3-ol (16). To a solution of vinyl-
stannane 15 (23.4 g, 60.5 mmol) in CH2Cl2 (302 mL) was added a
solution of I2 (23.0 g, 90.7 mmol) in CH2Cl2 (450 mL) via cannula at
0 °C. After 10 min, the reaction was quenched with saturated aqueous
Na2S2O3. The separated organic layer was washed with saturated
aqueous NaCl, dried over anhydrous Na2SO4, filtered, and
concentrated under reduced pressure. The residue was purified by
silica gel column chromatography (hexane/ethyl acetate = 50/1→10/
1) to give iodoolefin 16 (12.9 g, 57.5 mmol, 95%) as a colorless oil: Rf
= 0.53 (hexane/ethyl acetate = 2/1); IR (neat) 3360, 2904, 1605,
1423, 1218, 990, 926 cm−1; 1H NMR (600 MHz, CDCl3) δ 6.55 (dt, J
= 14.4, 7.8 Hz, 1H), 6.16 (d, J = 14.4 Hz, 1H), 5.87 (ddd, J = 17.4,
10.8, 6.0 Hz, 1H), 5.27 (d, J = 17.4 Hz, 1H), 5.17 (d, J = 10.8 Hz, 1H),
4.21−4.18 (m, 1H), 2.35−2.26 (m, 2H), 1.60 (d, J = 4.2 Hz, 1H); 13C
NMR (150 MHz, CDCl3) δ 141.9, 139.8, 115.6, 77.9, 71.5, 43.5;
HRMS (ESI-TOF) m/z [M + Na]+ calcd for C6H9IONa 246.9590,
found 246.9591.
(hexane/ethyl acetate = 3/1); [α]24 +4.3 (c 1.0, CHCl3); IR (neat)
D
1
3734, 3357, 2902, 1636, 1606, 1473, 990 cm−1; H NMR (400 MHz,
CDCl3) δ 6.55 (dt, J = 15.0, 7.2 Hz, 1H), 6.16 (dt, J = 15.0, 1.2 Hz,
1H), 5.87 (ddd, J = 16.8, 10.4, 6.0 Hz, 1H), 5.27 (dt, J = 16.8, 1.2 Hz,
1H), 5.17 (dt, J = 10.4, 1.2 Hz, 1H), 4.22−4.17 (m, 1H), 2.37−2.25
(m, 2H), 1.60 (d, J = 4.8 Hz, 1H); 13C NMR (150 MHz, CDCl3) δ
141.9, 139.8, 115.7, 77.8, 71.6, 43.6; HRMS (APCI-TOF) m/z [M +
H]+ calcd for C6H10IO 224.9771, found 224.9773.
(R,E)-tert-Butyl((6-iodohexa-1,5-dien-3-yl)oxy)dimethyl-
silane (7). To a solution of alcohol 17 (1.93 g, 8.63 mmol) in DMF
(12.3 mL) were added imidazole (1.76 g, 25.9 mmol) and TBSCl
(1.95 g, 13.0 mmol) at 0 °C. After the mixture was stirred for 2 h, the
reaction mixture was quenched with saturated aqueous NH4Cl and
extracted with Et2O. The organic layer was washed with saturated
aqueous NaCl, dried over anhydrous Na2SO4, filtered, and
concentrated under reduced pressure. Purification by silica gel column
chromatography (hexane/ethyl acetate = 100/1) afforded TBS ether 7
(2.84 g, 8.39 mmol, 97%) as a colorless oil: Rf = 0.83 (hexane/ethyl
(R,E)-6-Iodohexa-1,5-dien-3-ol (17). A solution of L-(+)-DCHT
(6.31 g, 20.1 mmol) and iodoolefin 16 (6.00 g, 26.8 mmol) in CH2Cl2
(125 mL + 3 × 2 mL rinse) was added to a suspension of activated
powdered MS4A (3.0 g) in CH2Cl2 (3 mL). The mixture was cooled
to −20 °C and stirred for 30 min. To this mixture was added Ti(O-i-
Pr)4 (4.0 mL, 13 mmol) with stirring for 30 min followed by addition
F
DOI: 10.1021/jo502322m
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The Journal of Organic Chemistry
Article
acetate =7/1); [α]23 −4.5 (c 1.0, CHCl3); IR (neat) 3709, 3628,
imidazole (1.14 g, 16.8 mmol) and TBSCl (1.27 g, 8.40 mmol) at 0
°C. After the mixture was stirred for 4 h, the reaction was quenched
with saturated aqueous NH4Cl and extracted with Et2O. The organic
layer was washed with saturated aqueous NaCl, dried over anhydrous
Na2SO4, filtered, and concentrated under reduced pressure.
Purification by silica gel column chromatography (hexane/ethyl
acetate = 10/1→2/1) afforded TBS ether 22 (3.45 g, 6.97 mmol,
D
1652, 1558, 983, 771 cm−1; 1H NMR (600 MHz, CDCl3) δ 6.50 (ddd,
J = 14.4, 7.8, 7.8 Hz, 1H), 6.04 (d, J = 14.4 Hz, 1H), 5.78 (ddd, J =
17.4, 10.8, 5.4 Hz, 1H), 5.18 (d, J = 17.4 Hz, 1H), 5.07 (d, J = 10.8 Hz,
1H), 4.15−4.12 (m, 1H), 2.24−2.20 (m, 2H), 0.90 (s, 9H), 0.06 (s,
3H), 0.03 (s, 3H); 13C NMR (150 MHz, CDCl3) δ 143.0, 140.7,
114.5, 77.4, 72.7, 44.7, 26.0 (3C), 18.4, −4.4, −4.7; HRMS (APCI-
TOF) m/z [M + H]+ calcd for C12H24IOSi 339.0636, found 339.0616.
N-Methoxy-11-((4-methoxybenzyl)oxy)-N-methyl-5-oxoun-
dec-6-ynamide (18). To a solution of alkyne 9 (2.85 g, 13.1 mmol)
in THF (120 mL) at −78 °C was added n-BuLi (1.6 M in hexane, 6.8
mL, 10.8 mmol) dropwise. After the mixture was stirred at 0 °C for 30
min, the mixture was added dropwise to a solution of amide 8 (4.75 g,
21.8 mmol) in THF (78 mL) at −20 °C and stirred for 30 min. The
reaction was quenched with saturated aqueous NH4Cl and extracted
with ethyl acetate. The organic layer was washed with saturated
aqueous NaCl, dried over anhydrous Na2SO4, filtered, and
concentrated under reduced pressure. Purification by silica gel column
chromatography (hexane/ethyl acetate = 3/1 → 2/1 → 1/1) afforded
ynone 18 (3.30 g, 8.79 mmol, 81%) as a yellow oil: Rf = 0.23 (hexane/
ethyl acetate =1/1); IR (neat) 2935, 2857, 2209, 1666, 1612, 1511,
99%) as a colorless oil: Rf = 0.55 (hexane/ethyl acetate =1/1); [α]23
D
−0.38 (c 1.0, CHCl3); IR (neat) 3727, 3626, 2931, 2855, 1669, 1512,
1
1248, 1096, 1037, 1003, 835 cm−1; H NMR (600 MHz, CDCl3) δ
7.26 (d, J = 9.0 Hz, 2H), 6.87 (d, J = 9.0 Hz, 2H), 4.43 (s, 2H), 3.80
(s, 3H), 3.67 (s, 3H), 3.65 (q, J = 6.0 Hz, 1H), 3.43 (t, J = 6.0 Hz,
2H), 3.17 (s, 3H), 2.45−2.40 (m, 2H), 1.72−1.57 (m, 4H), 1.50−1.39
(m, 4H), 1.37−1.25 (m, 6H), 0.88 (s, 9H), 0.04 (s, 3H), 0.03 (s, 3H);
13C NMR (150 MHz, CDCl3) δ 174.8, 159.2, 131.0, 129.3 (2C), 113.9
(2C), 72.6, 72.3, 70.3, 61.3, 55.4, 37.1, 36.9, 32.3 (2C), 29.89, 29.86,
26.4, 26.1, 25.4 (3C), 20.7, 18.3, −4.3 (2C); HRMS (ESI-TOF) m/z
[M + Na]+ calcd for C27H49NO5SiNa 518.3272, found 518.3267.
(5R,13R,E)-13-(6-((4-Methoxybenzyl)oxy)hexyl)-
2,2,3,3,15,15,16,16-octamethyl-5-vinyl-4,14-dioxa-3,15-disila-
heptadec-7-en-9-one (23). To a solution of iodoolefin 7 (2.70 g,
8.00 mmol) in THF (80 mL) at −78 °C was added n-BuLi (1.6 M in
hexane, 4.6 mL, 7.4 mmol) via syringe and the mixture stirred at −78
°C for 10 min. To this mixture was added a solution of compound 22
(3.04 g, 6.14 mmol) in THF (8.8 mL + 2 × 1.0 mL rinse) through a
cannula and the mixture stirred at −50 °C for 8 min. The reaction
mixture was quenched with saturated aqueous NH4Cl and extracted
with Et2O. The organic layer was dried over anhydrous Na2SO4,
filtered, and concentrated under reduced pressure. The residue was
purified by silica gel column chromatography (hexane/ethyl acetate
=30/1→10/1) to give enone 23 (3.93 g, 6.08 mmol, 99%) as a
1
1457, 1244, 1100, 1032, 820 cm−1; H NMR (600 MHz, CDCl3) δ
7.25 (d, J = 8.4 Hz, 2H), 6.88 (d, J = 8.4 Hz, 2H), 4.43 (s, 2H), 3.81
(s, 3H), 3.67 (s, 3H), 3.46 (t, J = 6.0 Hz, 2H), 3.17 (s, 3H), 2.63 (t, J =
7.2 Hz, 2H), 2.46 (t, J = 7.2 Hz, 2H), 2.38 (t, J = 6.6 Hz, 2H), 1.99 (q,
J = 7.2 Hz, 2H), 1.73−1.65 (m, 4H); 13C NMR (150 MHz, CDCl3) δ
187.7, 173.8, 159.3, 130.6, 129.3 (2C), 113.9 (2C), 94.2, 81.0, 72.7,
69.3, 61.3, 55.4, 44.7, 32.2, 30.7, 29.0, 24.7, 18.92, 18.85; HRMS
(APCI-TOF) m/z [M + H]+ calcd for C21H30NO5 376.2119, found
376.2119.
(S)-5-Hydroxy-N-methoxy-11-((4-methoxybenzyl)oxy)-N-
methylundec-6-ynamide (20). To a solution of ynone 18 (3.30 g,
8.79 mmol) in i-PrOH (80 mL) at room temperature was added
Ru[(S,S)-Tsdpen](p-cymene) 19 (52.7 mg, 87.9 μmol). After 1 h,
catalyst 19 (52.7 mg, 87.9 μmol) was again added, and the reaction
mixture was stirred for another 1 h. The organic solvent was removed
under reduced pressure, and the residue was purified by flash silica gel
column chromatography (hexane/ethyl acetate = 2/1→1/3) to give
alcohol 20 (2.98 g, 7.89 mmol, 90%) as a brown oil: Rf = 0.28
(hexane/ethyl acetate = 1/2); [α]24D −2.3 (c 0.53, CHCl3); IR (neat)
colorless oil: Rf = 0.42 (hexane/ethyl acetate = 7/1); [α]22 −4.3 (c
D
1.0, CHCl3); IR (neat) 3727, 2929, 2855, 1698, 1676, 1586, 1248,
1173, 1092, 1006, 938, 835, 774 cm−1; 1H NMR (600 MHz, CDCl3) δ
7.26 (d, J = 8.4 Hz, 2H), 6.87 (d, J = 8.4 Hz, 2H), 6.79 (ddd, J = 15.6,
7.2, 7.2 Hz, 1H), 6.10 (d, J = 15.6 Hz, 1H), 5.80 (ddd, J = 16.8, 10.8,
7.2 Hz, 1H), 5.19 (d, J = 16.8 Hz, 1H), 5.08 (d, J = 10.8 Hz, 1H), 4.43
(s, 2H), 4.24 (ddd, J = 7.2, 7.2, 7.2 Hz, 1H), 3.80 (s, 3H), 3.63 (dddd,
J = 6.0, 6.0, 6.0, 6.0 Hz, 1H), 3.43 (t, J = 7.2 Hz, 2H), 2.54−2.52 (m,
2H), 2.40 (dd, J = 7.2, 7.2 Hz, 2H), 1.69−1.57 (m, 4H), 1.46−1.38
(m, 4H), 1.38−1.25 (m, 6H), 0.89 (s, 9H), 0.88 (s, 9H), 0.05 (s, 3H),
0.04 (s, 3H), 0.03 (s, 6H); 13C NMR (150 MHz, CDCl3) δ 200.5,
159.2, 143.3, 140.7, 132.6, 131.0, 129.3 (2C), 114.7, 113.9 (2C), 72.8,
72.6, 72.2, 70.3, 55.4, 41.4, 40.2, 37.1, 36.7, 29.89, 29.87, 26.4, 26.1
(3C), 25.9 (3C), 25.4, 20.2, 18.33, 18.27, −4.3 (2C), −4.7 (2C);
HRMS (ESI-TOF) m/z [M + Na]+ calcd for C37H66O5Si2Na
669.4341, found 669.4333.
1
3408, 2935, 2857, 1644, 1586, 1513, 1456, 1100, 1033, 822 cm−1; H
NMR (600 MHz, CDCl3) δ 7.26 (d, J = 9.0 Hz, 2H), 6.88 (d, J = 9.0
Hz, 2H), 4.43 (s, 2H), 4.36 (t, J = 6.0 Hz, 1H), 3.81 (s, 3H), 3.68 (s,
3H), 3.45 (t, J = 6.0 Hz, 2H), 3.18 (s, 3H), 2.49−2.48 (m, 2H), 2.22
(dt, J = 7.2, 1.8 Hz, 2H), 1.84−1.66 (m, 6H), 1.60−1.55 (m, 2H); 13C
NMR (150 MHz, CDCl3) δ 174.6, 159.3, 130.8, 129.4 (2C), 113.9
(2C), 85.3, 81.5, 72.7, 69.6, 62.4, 61.3, 55.4, 37.9, 32.3, 31.5, 29.0, 25.5,
20.2, 18.7; HRMS (ESI-TOF) m/z [M + Na]+ calcd for
C21H31NO5Na 400.2094, found 400.2083.
(5R,9R,13R,E)-13-(6-((4-Methoxybenzyl)oxy)hexyl)-
2,2,3,3,15,15,16,16-octamethyl-5-vinyl-4,14-dioxa-3,15-disila-
heptadec-7-en-9-ol (25). To a solution of enone 23 (3.50 g, 5.41
mmol) and (S)-Me-CBS reagent 24 (3.00 g, 10.8 mmol) in toluene
(54 mL) at −78 °C was added BH3·SMe2 (1.00 mL, 10.8 mmol) via
syringe over a period of 3 min. After the mixture was stirred at −30 °C
for 2 h, the reaction was quenched by sequential addition of MeOH
followed by saturated aqueous NH4Cl and extracted with ethyl acetate.
The organic layer was washed with saturated aqueous NaCl, dried over
anhydrous Na2SO4, filtered, and concentrated under reduced pressure.
Purification by silica gel column chromatography (hexane/ethyl
acetate = 6/1) afforded allylic alcohol 25 (3.49 g, 5.38 mmol, 99%
dr = 95:5) as a yellow oil: Rf = 0.23 (hexane/ethyl acetate = 5/1);
(R)-5-Hydroxy-N-methoxy-11-((4-methoxybenzyl)oxy)-N-
methylundecanamide (21). To a solution of alcohol 20 (2.98 g,
7.89 mmol) in THF (72 mL) was added 4.3% Pd/C(en) (303 mg)
and the mixture stirred under a hydrogen atmosphere (balloon) at
room temperature for 24 h. The reaction mixture was filtered through
Celite and concentrated under reduced pressure. The residue was
purified by column chromatography (hexane/ethyl acetate =1/1→1/
2) to give alcohol 21 (2.67 g, 7.00 mmol, 89%) as a colorless oil: Rf =
0.17 (hexane/ethyl acetate = 1/2); [α]22 −1.1 (c 0.42, CHCl3); IR
D
(neat) 3431, 2930, 2855, 1655, 1511, 1460, 1385, 1301, 1246, 1173,
1096, 992, 821, 774 cm−1; 1H NMR (600 MHz, CDCl3) δ 7.26 (d, J =
9.0 Hz, 2H), 6.88 (d, J = 9.0 Hz, 2H), 4.42 (s, 2H), 3.80 (s, 3H), 3.68
(s, 3H), 3.58−3.56 (m, 1H), 3.42 (t, J = 6.0 Hz, 2H), 3.18 (s, 3H),
2.46 (brs, 2H), 1.80−1.71 (m, 2H), 1.69−1.57 (m, 2H), 1.54−1.26
(m, 10H); 13C NMR (150 MHz, CDCl3) δ 174.8, 159.2, 130.9, 129.4
(2C), 113.9 (2C), 72.6, 71.4, 70.3, 61.3, 55.4, 37.5, 37.2, 32.3, 31.7,
29.8, 29.7, 26.3, 25.8, 20.4; HRMS (ESI-TOF) m/z [M + Na]+ calcd
for C21H35NO5Na 404.2407, found 404.2403.
[α]24 −5.7 (c 1.0, CHCl3); IR (neat) 3441, 2929, 2856, 1613, 1512,
D
1463, 1249, 1082, 1038, 834, 774 cm−1; 1H NMR (600 MHz, CDCl3)
δ 7.26 (d, J = 9.0 Hz, 2H), 6.88 (d, J = 9.0 Hz, 2H), 5.80 (ddd, J =
16.8, 10.8, 6.0 Hz, 1H), 5.62 (ddd, J = 14.4, 6.6, 6.6 Hz, 1H), 5.48 (dd,
J = 14.4, 7.2 Hz, 1H), 5.15 (d, J = 16.8 Hz, 1H), 5.04 (d, J = 10.8 Hz,
1H), 4.43 (s, 2H), 4.13 (ddd, J = 6.0, 6.0, 6.0 Hz, 1H), 4.04 (ddd, J =
7.2, 7.2, 7.2 Hz, 1H), 3.80 (s, 3H), 3.63−3.59 (m, 1H), 3.43 (t, J = 6.0
Hz, 2H), 2.28−2.18 (m, 2H), 1.61−1.57 (m, 2H), 1.44−1.25 (m,
14H), 0.89 (s, 9H), 0.88 (s, 9H), 0.05 (s, 3H), 0.03 (s, 3H), 0.02 (s,
6H); 13C NMR (150 MHz, CDCl3) δ 159.2, 141.2, 135.7, 131.0, 129.4
(R)-5-((tert-Butyldimethylsilyl)oxy)-N-methoxy-11-((4-
methoxybenzyl)oxy)-N-methylundecanamide (22). To a solu-
tion of alcohol 21 (2.67 g, 7.00 mmol) in DMF (8.8 mL) were added
G
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(2C), 128.0, 114.0, 113.9 (2C), 73.7, 73.3, 72.7, 72.3, 70.4, 55.4, 41.3,
37.6, 37.2, 37.1, 29.9 (2C), 26.4, 26.1 (3C), 26.0 (3C), 25.5, 21.4, 18.4,
18.3, −4.2 (2C), −4.3, −4.6; HRMS (ESI-TOF) m/z [M + Na]+ calcd
for C37H68O5Si2Na 671.4503, found 671.4481.
organic layer was washed with saturated aqueous NaHCO3 and
saturated aqueous NaCl, dried over anhydrous Na2SO4, filtered, and
concentrated under reduced pressure. Purification by silica gel column
chromatography (hexane/ethyl acetate = 100/1 → 40/1) afforded
TBS ether 28 (627 mg, 0.527 mmol, 100%) as a colorless oil: Rf = 0.58
(5R,9R,13R,E)-9-((tert-Butyldimethylsilyl)oxy)-13-(6-((4-
methoxybenzyl)oxy)hexyl)-2,2,3,3,15,15,16,16-octamethyl-5-
vinyl-4,14-dioxa-3,15-disilaheptadec-7-ene (6). To a solution of
allylic alcohol 25 (3.49 g, 5.38 mmol) in DMF (7.2 mL) were added
imidazole (1.12 g, 16.2 mmol) and TBSCl (1.20 g, 8.08 mmol) at 0
°C. After the mixture was stirred at 0 °C for 4 h, the reaction was
quenched with saturated aqueous NH4Cl and extracted with Et2O.
The organic layer was washed with saturated aqueous NaCl, dried over
anhydrous Na2SO4, filtered, and concentrated under reduced pressure.
Purification by silica gel column chromatography (hexane/ethyl
acetate = 60/1→20/1) afforded TBS ether 6 (4.05 g, 5.30 mmol,
(hexane/ethyl acetate =10/1); [α]23 −0.08 (c 1.00, CHCl3); IR
D
(neat) 3734, 2928, 2856, 1653, 1616, 1508, 1472, 1250, 1113, 835,
1
774, 701 cm−1; H NMR (600 MHz, C6D6) δ 7.84−7.82 (m, 4H),
7.30−7.25 (m, 8H), 6.83 (d, J = 8.4 Hz, 2H), 5.82 (ddd, J = 15.6, 7.2,
7.2 Hz, 1H), 5.81 (ddd, J = 15.6, 7.2, 7.2 Hz, 1H), 5.68 (dd, J = 15.6,
6.6 Hz, 1H), 5.64 (dd, J = 15.6, 6.6 Hz, 1H), 4.38 (s, 2H), 4.22 (ddd, J
= 6.6, 6.6, 6.6 Hz, 1H), 4.21 (ddd, J = 6.6, 6.6, 6.6 Hz, 1H), 3.94−3.91
(m, 1H), 3.80−3.75 (m, 2H), 3.74−3.70 (m, 1H), 3.38 (t, J = 7.2 Hz,
2H), 3.32 (s, 3H), 2.57−2.44 (m, 2H), 2.42−2.33 (m, 2H), 1.75−1.62
(m, 4H), 1.61−1.49 (m, 4H), 1.47−1.42 (m, 4H), 1.41−1.30 (m, 4H),
1.21 (s, 9H), 1.07 (s, 9H), 1.05 (s, 9H), 1.04 (s, 9H), 0.99 (s, 9H),
0.19 (s, 3H), 0.18 (s, 3H), 0.16 (s, 3H), 0.15 (s, 3H), 0.13 (s, 3H),
0.12 (s, 3H), 0.10 (s, 3H), 0.05 (s, 3H); 13C NMR (150 MHz, C6D6)
δ 159.7, 136.7, 136.3, 136.1 (4C), 134.1 134.0, 131.6, 130.1 (4C),
129.3 (2C), 128.3 (2C), 126.6, 126.5, 114.1 (2C), 74.3, 74.0, 73.3,
72.8, 72.7, 70.3, 67.6, 54.8, 42.1, 39.5, 37.8, 37.7, 37.6, 30.4, 30.3, 27.2
(3C), 26.9, 26.3 (6C), 26.24 (3C), 26.18 (3C), 25.8, 21.8, 19.5, 18.54,
18.52, 18.44, 18.37, −3.6, −3.9, −4.0, −4.1, −4.2, −4.37, −4.39, −4.5;
HRMS (ESI-TOF) m/z [M + Na]+ calcd for C68H120O7Si5Na
1211.7773, found 1211.7775.
99%) as a colorless oil: Rf = 0.53 (hexane/ethyl acetate = 6/1); [α]24
D
−6.1 (c 1.0, CHCl3); IR (neat) 3728, 2928, 2855, 1613, 1512, 1463,
1249, 1081, 1039, 834, 773 cm−1; 1H NMR (600 MHz, CDCl3) δ 7.26
(d, J = 9.0 Hz, 2H), 6.88 (d, J = 9.0 Hz, 2H), 5.79 (ddd, J = 17.4, 10.2,
6.0 Hz, 1H), 5.49 (ddd, J = 15.6, 7.2, 7.2 Hz, 1H), 5.42 (dd, J = 15.6,
7.2 Hz, 1H), 5.14 (d, J = 17.4 Hz, 1H), 5.03 (d, J = 10.2 Hz, 1H), 4.43
(s, 2H), 4.11 (dd, J = 6.0, 6.0 Hz, 1H), 4.01−3.99 (m, 1H), 3.80 (s,
3H), 3.61−3,58 (m, 1H), 3.43 (t, J = 7.2 Hz, 2H), 2.28−2.17 (m, 2H),
1.62−1.57 (m, 2H), 1.49−1.25 (m, 14H), 0.89 (s, 9H), 0.88 (s, 18H),
0.05 (s, 3H), 0.032 (s, 3H), 0.030 (s, 3H), 0.02 (s, 6H), 0.01 (s, 3H);
13C NMR (150 MHz, CDCl3) δ 159.2, 141.2, 136.4, 131.0, 129.3
(7R,11R,12E,15R,16E,19R)-7,11,15,19-Tetrakis((tert-butyldi-
methylsilyl)oxy)-20-((tert-butyldiphenylsilyl)oxy)icosa-12,16-
dienal (3). To a solution of PMB ether 28 (115 mg, 96.6 μmol) in
CH2Cl2/pH 7 buffer (v/v = 3:1, 1.6 mL) at 0 °C was added DDQ
(28.5 mg, 0.126 mmol). The resultant mixture was stirred at room
temperature for 2 h before being quenched with saturated aqueous
NaHCO3 and saturated aqueous Na2S2O3 at 0 °C. The mixture was
extracted with ethyl acetate, and the organic layer was washed with
saturated aqueous NaCl, dried over anhydrous Na2SO4, filtered, and
concentrated under reduced pressure. Purification by flash silica gel
column chromatography (hexane/ethyl acetate = 15/1→10/1)
afforded mixture of alcohol and anisaldehyde (110 mg). The mixture
was used in next reaction without further purification.
(2C), 125.9, 114.0, 113.9 (2C), 73.83, 73.77, 72.7, 72.4, 70.4, 55.4,
41.3, 38.9, 37.33, 37.26, 29.9 (2C), 26.4, 26.1 (6C), 26.0 (3C), 25.5,
21.3, 18.4 (2C), 18.3, −4.0, −4.2 (2C), −4.4, −4.5, −4.6; HRMS (ESI-
TOF) m/z [M + Na]+ calcd for C43H82O5Si3Na 785.5362, found
785.5364.
(6R,8E,10R,12E,14R,18R)-10,14-Bis((tert-butyldimethylsilyl)-
oxy)-18-(6-((4-methoxybenzyl)oxy)hexyl)-2,2,20,20,21,21-hex-
amethyl-3,3-diphenyl-4,19-dioxa-3,20-disiladocosa-8,12-dien-
6-ol (27). To a solution of terminal olefin 6 (1.01 g, 1.32 mmol) and
homoallylic alcohol 5 (149 mg, 0.483 mmol) in CH2Cl2 (2.2 mL)
under reflux was added a solution of Grubbs second-generation
catalyst 26 (37 mg, 44 μmol) in CH2Cl2 (1.4 mL + 2 × 0.2 mL rinse).
After the mixture was stirred under reflux for 3 h, the reaction was
quenched with Et3N at 0 °C and stirred for 1 h at room temperature.
The solution was concentrated under reduced pressure and the residue
was purified by silica gel column chromatography (hexane/ethyl
acetate = 50/1, 30/1, 20/1, 1/1) to give alcohol 27 (329 mg, 0.306
mmol, 70%) as a brown oil, with recovery of olefin 6 (758 mg, 0.993
mmol, 75%): Rf = 0.50 (hexane/ethyl acetate = 5/1); [α]22D −0.29 (c
0.99, CHCl3); IR (neat) 3734, 2929, 2856, 1653, 1588, 1513, 1463,
To a solution of crude alcohol in CH2Cl2 (0.96 mL) at 0 °C were
added DMSO (0.10 mL, 1.4 mmol), Et3N (0.10 mL, 0.72 mmol), and
SO3·py (69.2 mg, 0.435 mmol). After the mixture was stirred at room
temperature for 3 h, the reaction was quenched with saturated aqueous
NH4Cl at 0 °C and extracted with ethyl acetate. The organic layer was
washed with saturated aqueous NaCl, dried over anhydrous Na2SO4,
filtered, and concentrated under reduced pressure. Purification by flash
silica gel column chromatography (hexane/ethyl acetate = 50/1→20/
1) gave aldehyde 3 (69.2 mg, 64.8 μmol, 67% for the two steps) as a
1
1249, 1112, 1077, 834, 774, 702 cm−1; H NMR (600 MHz, C6D6) δ
7.76−7.75 (m, 4H), 7.27 (d, J = 8.4 Hz, 2H), 7.25−7.24 (m, 6H), 6.83
(d, J = 8.4 Hz, 2H), 5.77 (ddd, J = 15.0, 7.2, 7.2 Hz, 1H), 5.70 (ddd, J
= 15.0, 7.8, 7.8 Hz, 1H), 5.61 (dd, J = 15.0, 7.2 Hz, 1H), 5.55 (dd, J =
15.0, 6.0 Hz, 1H), 4.38 (s, 2H), 4.20−4.18 (m, 1H), 4.15 (dd, J = 6.0,
6.0 Hz, 1H), 3.80−3.75 (m, 1H), 3.74−3.71 (m, 1H), 3.66 (dd, J =
10.2, 3.6 Hz, 1H), 3.59 (dd, J = 7.8, 7.2 Hz, 1H), 3.38 (t, J = 7.2 Hz,
2H), 3.32 (s, 3H), 2.36−2.27 (m, 2H), 2.25−2.16 (m, 3H), 1.71−1.62
(m, 4H), 1.60−1.50 (m, 4H), 1.46−1.41 (m, 4H), 1.41−1.31 (m, 4H),
1.13 (s, 9H), 1.06 (s, 9H), 1.04 (s, 9H), 1.03 (s, 9H), 0.17 (s, 6H),
0.15 (s, 3H), 0.13 (s, 6H), 0.10 (s, 3H); 13C NMR (150 MHz, C6D6)
δ 159.7, 136.7, 136.3, 136.0 (4C), 133.8 (2C), 131.6, 130.2 (4C),
129.3 (2C), 128.3 (2C), 126.7, 126.5, 114.1 (2C), 74.2, 73.9, 72.8,
72.7, 71.9, 70.3, 68.2, 54.8, 42.0, 39.4, 37.8, 37.7, 36.5, 30.4, 30.3, 27.1
(3C), 26.8, 26.3 (6C), 26.2 (3C), 25.8, 21.7, 19.5, 18.53, 18.51, 18.4,
−3.7, −3.9, −4.05, −4.08, −4.4, −4.5; HRMS (ESI-TOF) m/z [M +
Na]+ calcd for C62H106O7Si4Na 1097.6908, found 1097.6878.
(6R,8E,10R,12E,14R,18R)-6,10,14-Tris((tert-butyldimethyl-
silyl)oxy)-18-(6-((4-methoxybenzyl)oxy)hexyl)-2,2,20,20,21,21-
hexamethyl-3,3-diphenyl-4,19-dioxa-3,20-disiladocosa-8,12-
diene (28). To a solution of alcohol 27 (568 mg, 0.528 mmol) in
CH2Cl2 (4.2 mL) at 0 °C were added 2,6-lutidine (0.15 mL, 1.3
mmol) and TBSOTf (0.15 mL, 0.63 mmol). After the mixture was
stirred at 0 °C for 10 min, the reaction mixture was quenched with
saturated aqueous NaHCO3 and extracted with ethyl acetate. The
colorless viscous oil: Rf = 0.52 (hexane/ethyl acetate = 10/1); [α]26
D
+0.97 (c 0.49, CHCl3); IR (neat) 3839, 3073, 2928, 2856, 2710, 1731,
1
1653, 1472, 1462, 1234, 1112, 1074, 971, 834, 774, 702 cm−1; H
NMR (600 MHz, C6D6) δ 9.34 (s, 1H), 7.83−7.82 (m, 4H), 7.30−
7.25 (m, 6H), 5.81 (ddd, J = 15.6, 6.6, 6.6 Hz, 2H), 5.68 (dd, J = 15.6,
6.0 Hz, 1H), 5.64 (dd, J = 15.6, 6.6 Hz, 1H), 4.24−4.19 (m, 2H),
3.94−3.89 (m, 1H), 3.79−3.75 (m, 2H), 3.72−3.67 (m, 1H), 2.56−
2.43 (m, 2H), 2.42−2.33 (m, 2H), 1.84 (t, J = 7.2 Hz, 2H), 1.73−1.42
(m, 8H), 1.39−1.21 (m, 4H), 1.21 (s, 9H), 1.14−1.08 (m, 2H), 1.07
(s, 9H), 1.05 (s, 9H), 1.03 (s, 9H), 0.99 (s, 9H), 0.19 (s, 3H), 0.18 (s,
3H), 0.151 (s, 3H), 0.145 (s, 3H), 0.12 (s, 6H), 0.10 (s, 3H), 0.05 (s,
3H); 13C NMR (150 MHz, C6D6) δ 136.7, 136.3, 136.1 (4C), 134.1
134.0, 131.6, 130.1 (4C), 128.3 (2C), 126.7, 126.5, 74.3, 74.0, 73.3,
72.6, 67.6, 43.8, 42.1, 39.5, 37.8, 37.7, 37.6, 37.4, 29.7 (2C), 27.2 (3C),
26.28 (3C), 26.25 (6C), 26.2, 25.4, 22.3, 21.7, 19.5, 18.53, 18.52,
18.42, 18.37, −3.6, −3.9, −4.0, −4.1, −4.2, −4.37, −4.40, −4.5; HRMS
(ESI-TOF) m/z [M + Na]+ calcd for C60H110O6Si5Na 1089.7041,
found 1089.7047.
(S)-6-Allyl-8,8-diethyl-2,2-dimethyl-3,3-diphenyl-4,7-dioxa-
3,8-disiladecane (11). To a solution of alcohol 31 (7.90 g, 17.0
mmol) and imidazole (2.20 g, 33.0 mmol) in DMF (72 mL) was
added TESCl (4.30 mL, 26.0 mmol) at 0 °C. After the mixture was
stirred at room temperature for 30 min, the reaction was quenched
H
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Article
with saturated aqueous NaHCO3 at 0 °C and extracted with Et2O. The
organic layer was washed saturated aqueous NaCl, dried over
anhydrous Na2SO4, filtered, and concentrated under reduced pressure.
Purification by silica gel column chromatography (hexane/ethyl
acetate = 50/1→35/1→20/1) afforded TES ether 11 (7.60 g, 17.0
mmol, 99%) as a colorless oil: Rf = 0.49 (hexane/ethyl acetate = 20/
66.9, 60.7, 38.1, 33.5, 27.0 (3C), 21.2, 19.4; HRMS (ESI-TOF) m/z
[M + Na]+ calcd for C24H34O4SiNa 437.2119, found 437.2115.
tert-Butyl(((2S,4S,6S)-2-methyl-6-(2-(naphthalen-2-ylmeth-
oxy)ethyl)-1,3-dioxan-4-yl)methoxy)diphenylsilane (35). To a
solution of alcohol 34 (3.50 g, 8.44 mmol) and 2-naphthylmethyl
bromide (2.13 g, 10.1 mmol) in DMF (84 mL) at 0 °C was added
NaH (ca. 60% dispersion in mineral oil, 372 mg, 9.28 mmol). After the
mixture was stirred for 2.5 h at 0 °C, 2-naphthylmethyl bromide (1.07
g, 5.01 mmol) and NaH (ca. 60% dispersion in mineral oil, 169 mg,
4.22 mmol) were added, and the mixture was stirred for 1 h. The
resultant mixture was quenched with saturated aqueous NH4Cl and
extracted with Et2O. The organic layer was washed with saturated
aqueous NaCl, dried over anhydrous Na2SO4, filtered, and
concentrated under reduced pressure. The residue was purified by
silica gel column chromatography (hexane/ethyl acetate = 15/1 → 10/
1 → 5/1→1/1) to give NAP ether 35 (3.82 g, 6.89 mmol, 82%) as a
colorless oil with recovery of starting material 34 (0.52 g, 1.25 mmol,
1); [α]26 −5.2 (c 1.2, CHCl3); IR (neat) 3072, 2954, 2932, 2875,
D
2359, 2341, 1462, 1428, 1390, 1362, 1239, 1110, 1005, 961, 913, 856,
1
822, 738, 701 cm−1; H NMR (600 MHz, CDCl3) δ 7.68−7.66 (m,
4H), 7.44−7.36 (m, 6H), 5.84 (ddt, J = 17.2, 10.3, 6.9 Hz, 1H), 5.07
(dd, J = 17.2, 2.0 Hz, 1H), 5.03 (dd, J = 10.3, 2.0 Hz, 1H), 3.78−3.73
(m, 1H), 3.56 (dd, J = 9.6, 4.8 Hz, 1H), 3.50 (dd, J = 9.6, 6.8 Hz, 1H),
2.49−2.44 (m, 1H), 2.27−2.22 (m, 1H), 1.05 (s, 9H), 0.89 (t, J = 8.3
Hz, 9H), 0.52 (q, J = 8.3 Hz, 6H); 13C NMR (150 MHz, CDCl3) δ
135.8 (2C), 135.7 (2C), 135.3, 133.9, 133.8, 129.7 (2C), 127.8 (4C),
117.0, 72.8, 67.4, 39.2, 27.0 (3C), 19.3, 7.0 (3C), 5.0 (3C); HRMS
(ESI-TOF) m/z [M + Na]+ calcd for C27H42O2Si2Na 477.2616, found
477.2608.
15%): Rf = 0.41 (hexane/ethyl acetate = 10/1); [α]26 −9.3 (c 1.4,
D
CHCl3); IR (neat) 3050, 2929, 2857, 2359, 1589, 1508, 1472, 1428,
1378, 1340, 1145, 1106, 1057, 998, 948, 905, 854, 821, 773, 741, 702
cm−1; 1H NMR (600 MHz, CDCl3) δ 7.85−7.67 (m, 8H), 7.49−7.35
(m, 9H), 4.70−4.65 (m, 3H), 3.85−3.80 (m, 1H), 3.79−3.74 (m, 2H),
3.69−3.65 (m, 1H), 3.61−3.56 (m, 2H), 1.89−1.78 (m, 2H), 1.61
(ddd, J = 13.0, 2.1, 2.1 Hz, 1H), 1.31−1.24 (m, 1H), 1.26 (d, J = 4.8
Hz, 3H), 1.05 (s, 9H); 13C NMR (150 MHz, CDCl3) δ 136.2, 135.81
(2C), 135.79 (2C), 133.8, 133.5, 133.1, 129.8, 129.7, 128.3, 128.0,
127.8, 127.7 (5C), 126.5, 126.2, 126.0, 125.9, 98.5, 76.7, 73.2 (2C),
67.0, 66.3, 36.4, 33.8, 27.0 (3C), 21.1, 19.4; HRMS (ESI-TOF) m/z
[M + Na]+ calcd for C35H42O4SiNa 577.2745, found 577.2721.
((2S,4S,6S)-2-Methyl-6-(2-(naphthalen-2-ylmethoxy)ethyl)-
1,3-dioxan-4-yl)methanol (36). To a solution of TBDPS ether 35
(783 mg, 1.41 mmol) in THF (14 mL) at 0 °C was added TBAF (1 M
in THF, 1.7 mL, 1.7 mmol). After the mixture was stirred at room
temperature for 40 min, the reaction was quenched with saturated
aqueous NH4Cl at 0 °C and extracted with ethyl acetate. The organic
layer was washed with saturated aqueous NaCl, dried over anhydrous
Na2SO4, filtered, and concentrated under reduced pressure.
Purification by silica gel column chromatography (hexane/ethyl
acetate = 5/1 → 3/1 → 1/1) afforded alcohol 36 (429 mg, 1.35
mmol, 96%) as a colorless oil: Rf = 0.35 (hexane/ethyl acetate = 1/1);
(S,E)-6-((tert-Butyldiphenylsilyl)oxy)-5-((triethylsilyl)oxy)hex-
2-enal (10). To a solution of olefin 11 (522 mg, 1.15 mmol) and
acrolein 12 (0.25 mL, 3.4 mmol) in CH2Cl2 (7.7 mL) was added
Hoveyda−Grubbs second-generation catalyst 32 (36 mg, 57 μmol).
After the mixture was stirred at 35 °C for 3.4 h, acrolein (0.17 mL, 2.3
mmol) and Hoveyda−Grubbs second-generation catalyst (7.0 mg, 12
μmol) were added. After the mixture was stirred at 35 °C for 1.6 h, the
solution was filtered through a pad of silica gel and concentrated under
reduced pressure. The residue was purified by silica gel column
chromatography (hexane/ethyl acetate = 40/1→30/1→25/1) to give
aldehyde 10 (400 mg, 0.828 mmol, 72%) as a colorless oil: Rf = 0.18
(hexane/ethyl acetate = 20/1); [α]26D −4.1 (c 1.8, CHCl3); IR (neat)
3071, 2954, 2932, 2875, 2359, 1694, 1589, 1462, 1427, 1390, 1362,
1
1239, 1189, 1112, 1006, 978, 822, 739, 701 cm−1; H NMR (400
MHz, CDCl3) δ 9.47 (d, J = 8.2 Hz, 1H), 7.66−7.63 (m, 4H), 7.45−
7.37 (m, 6H), 6.88 (dt, J = 15.8, 7.6 Hz, 1H), 6.17 (dd, J = 15.8, 8.2
Hz, 1H), 3.88−3.84 (m, 1H), 3.59 (dd, J = 10.1, 4.6 Hz, 1H), 3.46
(dd, J = 10.1, 8.3 Hz, 1H), 2.74−2.69 (m, 1H), 2.61−2.53 (m, 1H),
1.05 (s, 9H), 0.86 (t, J = 7.8 Hz, 9H), 0.49 (q, J = 7.8 Hz, 6H); 13C
NMR (150 MHz, CDCl3) δ 194.0, 155.4, 135.7 (2C), 135.7 (2C),
135.1, 133.5, 133.4, 130.0 (2C), 127.9 (4C), 71.6, 67.2, 38.0, 27.0
(3C), 19.4, 6.9 (3C), 4.9 (3C); HRMS (ESI-TOF) m/z [M + Na]+
calcd for C28H42O3Si2Na 505.2565, found 505.2556.
(2S,4S,6S)-6-(((tert-Butyldiphenylsilyl)oxy)methyl)-2-methyl-
1,3-dioxan-4-yl)ethan-1-ol (34). To a solution of aldehyde 10 (396
mg, 0.820 mmol) and acetaldehyde (1.0 mL, 16 mmol) in CH2Cl2 (8.2
mL) at 0 °C was added Bi(NO3)3·5H2O (40 mg, 82 μmol). After the
mixture was stirred at 30 °C for 67 h, the reaction was quenched with
saturated aqueous NaHCO3 at 0 °C and extracted with CH2Cl2. The
organic layer was washed with saturated aqueous NaCl, dried over
anhydrous Na2SO4, filtered, and concentrated under reduced pressure
to give crude aldehyde 33 as a colorless oil. This material was used in
the next reaction without further purification.
[α]26 −12.2 (c 0.75, CHCl3); IR (neat) 3444, 3053, 2990, 2918,
D
2865, 2360, 2341, 1602, 1509, 1412, 1378, 1340, 1236, 1166, 1140,
1
1097, 1039, 967, 943, 903, 854, 820, 770, 752 cm−1; H NMR (600
MHz, CDCl3) δ 7.85−7.76 (m, 4H), 7.50−7.45 (m, 3H), 4.72 (q, J =
4.8 Hz, 1H), 4.68 (d, J = 12.4 Hz, 1H), 4.65 (d, J = 12.4 Hz, 1H),
3.87−3.82 (m, 1H), 3.79−3.75 (m, 1H), 3.69−3.65 (m, 1H), 3.63−
3.59 (m, 2H), 3.58−3.53 (m, 1H), 1.97 (brs, 1H), 1.91−1.85 (m, 1H),
1.83−1.77 (m, 1H), 1.44−1.34 (m, 2H), 1.30 (d, J = 4.8 Hz, 3H); 13C
NMR (150 MHz, CDCl3) δ 136.1, 133.4, 133.1, 128.3, 128.0, 127.8,
126.5, 126.2, 126.0, 125.9, 98.7, 76.7, 73.2, 73.1, 66.1, 65.8, 36.3, 32.4,
21.1; HRMS (ESI-TOF) m/z [M + Na]+ calcd for C19H24O4Na
339.1567, found 339.1582.
To a solution of crude aldehyde 33 in MeOH (8.2 mL) at 0 °C was
added NaBH4 (31 mg, 0.82 mmol). After the mixture was stirred at 0
°C for 10 min, the reaction was quenched with saturated aqueous
NH4Cl and extracted with ethyl acetate. The organic layer was washed
with saturated aqueous NaCl, dried over anhydrous Na2SO4, filtered,
and concentrated under reduced pressure. Purification by silica gel
column chromatography (hexane/ethyl acetate = 10/1 → 5/1→2/1)
afforded alcohol 34 (296 mg, 0.714 mmol, 87% for two steps) as a
(2S,4S,6S)-2-Methyl-6-(2-(naphthalen-2-ylmethoxy)ethyl)-
1,3-dioxane-4-carbaldehyde (37). To a solution of alcohol 36 (280
mg, 0.885 mmol) in CH2Cl2 (8.5 mL) at 0 °C was added Dess−
Martin periodinane (940 mg, 2.22 mmol). After the mixture was
stirred at room temperature for 2.5 h, the reaction was quenched with
saturated aqueous NaHCO3 at 0 °C and was extracted with ethyl
acetate. The organic layer was washed with saturated aqueous NaCl,
dried over anhydrous Na2SO4, filtered, and concentrated under
reduced pressure to give crude aldehyde 37 as a colorless oil.
Purification of the residue by silica gel column chromatography
(hexane/ethyl acetate = 3/1→1/1) afforded aldehyde 37 (247 mg,
0.786 mmol, 89%) as a colorless oil: Rf = 0.33 (hexane/ethyl acetate =
1/1); [α]25D −23.1 (c 1.6, CHCl3); IR (neat) 3054, 2989, 2920, 2866,
1737, 16031509, 1435, 1411, 1376, 1338, 1219, 1093, 963, 901, 853,
25
colorless syrup: Rf = 0.15 (hexane/ethyl acetate = 3/1); [α]D −11.8
(c 1.5, CHCl3); IR (neat) 3380, 3070, 3050, 2930, 2857, 2360, 2341,
1632, 1589, 1488, 1472, 1445, 1428, 1415, 1389, 1362, 1341, 1305,
1240, 1188, 1144, 1110, 1050, 998, 949, 893, 854, 823, 801, 741, 701
cm−1; 1H NMR (600 MHz, CDCl3) δ 7.68−7.66 (m, 4H), 7.44−7.35
(m, 6H), 4.71 (q, J = 4.8 Hz, 1H), 3.91−3.86 (m, 1H), 3.83−3.75 (m,
4H), 3.59 (dd, J = 10.3, 5.5 Hz, 1H), 2.28−2.26 (m, 1H), 1.84−1.73
(m, 2H), 1.58 (dt, J = 13.1, 2.1 Hz, 1H), 1.41−1.35 (m, 1H), 1.30 (d, J
= 4.8 Hz, 3H), 1.05 (s, 9H); 13C NMR (150 MHz, CDCl3) δ 135.80
(2C), 135.77 (2C), 133.7, 129.8 (2C), 127.8 (5C), 98.5, 76.7, 75.8,
1
818, 772 cm−1; H NMR (400 MHz, CDCl3) δ 9.62 (s, 1H), 7.86−
7.80 (m, 3H), 7.77 (s, 1H), 7.52−7.43 (m, 3H), 4.76 (q, J = 5.0 Hz,
1H), 4.69 (d, J = 11.9 Hz, 1H), 4.65 (d, J = 11.9 Hz, 1H), 4.15−4.09
(m, 1H), 3.93−3.84 (m, 1H), 3.67 (ddd, J = 9.2, 7.8, 5.0 Hz, 1H), 3.59
I
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(ddd, J = 9.2, 5.5, 5.5 Hz, 1H), 1.94−1.75 (m, 3H), 1.47−1.36 (m,
1H), 1.35 (d, J = 5.5 Hz, 3H); 13C NMR (150 MHz, CDCl3) δ 200.5,
135.9, 133.4, 133.1, 128.3, 128.0, 127.8, 126.6, 126.3, 126.0, 125.9,
98.8, 80.1, 73.3, 73.1, 65.8, 36.1, 31.2, 21.0; HRMS (ESI-TOF) m/z
[M + Na]+ calcd for C19H22O4Na 337.1410, found 337.1411.
hexane. The organic layer was washed with saturated aqueous KHSO4,
NaHCO3, and NaCl, dried over anhydrous Na2SO4, filtered, and
concentrated under reduced pressure. Purification by silica gel column
chromatography (hexane/ethyl acetate = 50/1→40/1) afforded TBS
ether 41 (304 mg, 0.413 mmol, 98%) as a colorless oil: Rf = 0.24
(1R,2S)-2-Methyl-1-((2S,4S,6S)-2-methyl-6-(2-(naphthalen-2-
ylmethoxy)ethyl)-1,3-dioxan-4-yl)but-3-en-1-ol (39). To a sus-
pension of t-BuOK (dried at 80 °C under vacuum for 18 h, 530 mg,
4.72 mmol) in freshly distilled THF (4.0 mL) at −78 °C was added
liquid cis-2-butene (0.42 mL, 4.7 mmol) followed by n-BuLi (1.6 M in
n-hexane, 2.6 mL, 4.2 mmol). The mixture was stirred at −45 °C for
15 min and then cooled to −78 °C. To this mixture was added a
solution of (+)-Ipc2BOMe (1.49 g, 4.71 mmol) in THF (2.5 mL) via
cannula, and after 30 min, BF3·Et2O (0.52 mL, 4.2 mmol) and a
solution of aldehyde 37 (294 mg, 0.935 mmol) in THF (2.5 mL, dried
over MS4A) were sequentially added. After the mixture was stirred at
−78 °C for 6.5 h, the reaction was quenched with 3 M aqueous NaOH
(4.0 mL) followed by 30% H2O2 (1.9 mL) and then stirred at room
temperature for 2 h. The organic layer was separated, and the aqueous
layer was extracted with ethyl acetate. The combined organic layers
were washed with saturated aqueous NaCl, dried over anhydrous
Na2SO4, filtered, and concentrated under reduced pressure.
Purification by silica gel column chromatography (hexane/ethyl
acetate = 7/1→5/1→3/1→1/1) afforded homoallylic alcohol 39
(240 mg, 0.648 mmol, 69%) as a colorless oil: Rf = 0.40 (hexane/ethyl
(hexane/ethyl acetate = 50/1); [α]23 −32.9 (c 0.54, CHCl3); IR
D
(neat) 2955, 2928, 2886, 2856, 2359, 2342, 1472, 1462, 1407, 1387,
1361, 1342, 1254, 1124, 1095, 1047, 1024, 1005, 947, 868, 835, 810,
1
774, 749 cm−1; H NMR (600 MHz, CDCl3) δ 7.83−7.76 (m, 4H),
7.48−7.43 (m, 3H), 5.68 (ddd, J = 17.8, 8.9, 8.9 Hz, 1H), 5.01−4.98
(m, 2H), 4.66 (d, J = 12.4 Hz, 1H), 4.62 (d, J = 12.4 Hz, 1H), 3.98−
3.93 (m, 1H), 3.75−3.73 (m, 1H), 3.65−3.58 (m, 2H), 3.44−3.42 (m,
1H), 2.16 (q, J = 6.9 Hz, 1H), 1.93−1.87 (m, 1H), 1.85−1.80 (m,
1H), 1.57−1.51 (m, 2H), 0.99 (d, J = 6.9 Hz, 3H), 0.90 (s, 9H), 0.86
(s, 9H), 0.85 (s, 9H), 0.13 (s, 3H), 0.05 (s, 6H), 0.04 (s, 3H), 0.02 (s,
3H), 0.01 (s, 3H); 13C NMR (150 MHz, CDCl3) δ 141.9, 136.4,
133.5, 133.1, 128.1, 128.0, 127.8, 126.5, 126.1, 126.0, 125.8, 114.9,
81.6, 73.3, 72.4, 67.5, 67.2, 43.1, 40.5, 36.4, 26.3 (6C), 26.0 (3C), 18.6,
18.23, 18.19, 17.8, −3.01, −3.04, −4.1, −4.3, −4.6, −4.8; HRMS (ESI-
TOF) m/z [M + Na]+ calcd for C39H70O4Si3Na 709.4474, found
709.4484.
(3S,4R,5S,7S)-4,5,7-Tris((tert-butyldimethylsilyl)oxy)-3-meth-
yl-9-(naphthalen-2-ylmethoxy)nonan-1-ol (42). To a solution of
BH3·SMe2 (0.13 mL, 1.3 mmol) in THF (0.2 mL) was added
cyclohexene (0.27 mL, 2.6 mmol) at 0 °C. After the mixture was
stirred at 0 °C for 15 min, the reaction mixture was allowed to warm to
room temperature. After 1 h, the solution was cooled to 0 °C, and a
solution of olefin 41 (302 mg, 0.439 mmol) in THF (1.2 mL + 2 × 0.6
mL rinse) was added via cannula. After the mixture was stirred at room
temperature for 25 min, the reaction was cooled to 0 °C and treated
with 3 M aqueous NaOH (3.2 mL) and 30% H2O2 (1.1 mL). After the
mixture was stirred at room temperature for 2 h, the reaction was
quenched with saturated aqueous Na2S2O3 at 0 °C and was extracted
with ethyl acetate. The organic layer was washed with saturated
aqueous NaCl, dried over anhydrous Na2SO4, filtered, and
concentrated under reduced pressure. Purification by silica gel column
chromatography (hexane/ethyl acetate = 7/1→5/1) afforded alcohol
42 (283 mg, 0.399 mmol, 91%) as a colorless syrup: Rf = 0.31
(hexane/ethyl acetate = 5/1); [α]23D −26.2 (c 0.43, CHCl3); IR (neat)
3420, 2953, 2928, 2885, 2856, 1472, 1361, 1254, 1095, 1005, 939, 835,
acetate = 3/1); [α]23 −37.7 (c 0.64, CHCl3); IR (neat) 3478, 3055,
D
2958, 2924, 2867, 2360, 2341, 1640, 1603, 1509, 1442, 1412, 1378,
1337, 1272, 1236, 1125, 1092, 1031, 997, 954, 914, 854, 817, 770, 751
1
cm−1; H NMR (600 MHz, CDCl3) δ 7.86−7.80 (m, 3H), 7.78 (s,
1H), 7.50−7.44 (m, 3H), 5.70 (ddd, J = 17.2, 10.3, 7.6 Hz, 1H), 5.04
(d, J = 17.2 Hz, 1H), 5.03 (d, J = 10.3 Hz, 1H), 4.71 (q, J = 5.5 Hz,
1H), 4.68 (d, J = 12.4 Hz, 1H), 4.66 (d, J = 12.4 Hz, 1H), 3.83−3.77
(m, 1H), 3.70−3.65 (m, 2H), 3.63−3.58 (m, 1H), 3.53 (dd, J = 7.6,
4.1 Hz, 1H), 2.37−2.29 (m, 1H), 2.11 (brs, 1H, OH), 1.91−1.79 (m,
2H), 1.56−1.51 (m, 2H), 1.28 (d, J = 4.8 Hz, 3H), 1.10 (d, J = 6.9 Hz,
3H); 13C NMR (150 MHz, CDCl3) δ 140.4, 136.1, 133.4, 133.1,
128.3, 128.0, 127.8, 126.5, 126.2, 126.0, 125.9, 115.4, 98.6, 76.8, 75.9,
73.2, 73.1, 66.2, 39.4, 36.4, 29.8, 21.2, 16.1; HRMS (ESI-TOF) m/z
[M + Na]+ calcd for C23H30O4Na 393.2036, found 393.2038.
(3S,5S,6R,7S)-7-Methyl-1-(naphthalen-2-ylmethoxy)non-8-
ene-3,5,6-triol (40). To a solution of alcohol 39 (83.0 mg, 0.224
mmol) in MeOH (0.7 mL), H2O (0.7 mL) and THF (0.7 mL) at 0 °C
was added p-TsOH·H2O (130 mg, 0.686 mmol). After the mixture was
stirred at 60 °C for 20 h, the reaction was quenched with saturated
aqueous NaHCO3 at 0 °C and was extracted with ethyl acetate. The
organic layer was washed with saturated aqueous NaCl, dried over
anhydrous Na2SO4, filtered, and concentrated under reduced pressure.
Purification by silica gel column chromatography (hexane/ethyl
acetate = 5/1 → 3/1 → 1/2) afforded triol 40 (32 mg, 0.094
mmol, 42%, 89% brsm) as a colorless syrup, and alcohol 39 (44.0 mg,
0.119 mmol, 53%) was recovered: Rf = 0.16 (hexane/ethyl acetate = 1/
1
774, 749, 678, 666 cm−1; H NMR (600 MHz, CDCl3) δ 7.83−7.78
(m, 4H), 7.47−7.43 (m, 3H), 4.66 (d, J = 12.4 Hz, 1H), 4.62 (d, J =
12.4 Hz, 1H), 4.01−3.96 (m, 1H), 3.69−3.58 (m, 4H), 3.55−3.51 (m,
1H), 3.50−3.49 (m, 1H), 1.95−1.90 (m, 1H), 1.82−1.77 (m, 1H),
1.71−1.60 (m, 4H), 1.30−1.24 (m, 1H), 0.90 (s, 9H), 0.87 (s, 9H),
0.85 (s, 9H), 0.84 (d, J = 6.9 Hz, 3H), 0.12 (s, 3H), 0.05 (s, 3H × 3),
0.03 (s, 3H), 0.01 (s, 3H), one −OH proton is missing; 13C NMR
(150 MHz, CDCl3) δ 136.2, 133.5, 133.1, 128.2, 128.0, 127.8, 126.6,
126.1 (2C), 125.9, 81.6, 73.4, 72.8, 67.4, 67.3, 61.4, 41.6, 37.3, 36.2,
34.6, 26.2 (6C), 26.0 (3C), 18.6, 18.19, 18.16, 15.8, −3.19, −3.23,
−4.1, −4.3, −4.6, −4.7; HRMS (ESI-TOF) m/z [M + Na]+ calcd for
C39H72O5Si3Na 727.4580, found 727.4585.
1); [α]24 −6.6 (c 0.63, CHCl3); IR (neat) 3392, 3057, 2921, 2866,
D
2366, 2357, 1639, 1603, 1509, 1420, 1369, 1341, 1272, 1172, 1123,
1-Phenyl-5-(((3S,4R,5S,7S)-4,5,7-tris((tert-butyldimethylsilyl)-
oxy)-3-methyl-9-(naphthalen-2-ylmethoxy)nonyl)thio)-1H-tet-
razole (44). To a solution of alcohol 42 (627 mg, 0.889 mmol), PPh3
(317 mg, 1.78 mmol), and 5-mercapto-1-phenyl-1H-tetrazole 43 (466
mg, 1.78 mmol) in THF (8.9 mL) at 0 °C was added DIAD (1.9 M in
toluene, 0.94 mL, 1.8 mmol) via syringe. The reaction was stirred at 0
°C for 10 min before being quenched with saturated aqueous NH4Cl.
The mixture was extracted with ethyl acetate. The organic layer was
washed with saturated aqueous NaCl, dried over anhydrous Na2SO4,
filtered, and concentrated under reduced pressure. Purification by flash
silica gel column chromatography (hexane/ethyl acetate = 15/1→5/1)
gave sulfide 44 (698 mg, 0.806 mmol, 91%) as a colorless syrup: Rf =
1
1089, 999, 916, 855, 817, 751 cm−1; H NMR (600 MHz, CDCl3) δ
7.86−7.76 (m, 4H), 7.51−7.42 (m, 3H), 5.72 (ddd, J = 17.2, 10.3, 7.6
Hz, 1H), 5.05−5.01 (m, 2H), 4.69 (s, 2H), 4.15−4.11 (m, 1H), 3.89−
3.86 (m, 1H), 3.81−3.78 (m, 1H), 3.74−3.70 (m, 1H), 3.42 (dd, J =
7.6, 4.9 Hz, 1H), 2.37 (q, J = 6.9 Hz, 1H), 1.91−1.84 (m, 1H), 1.78−
1.73 (m, 1H), 1.70−1.68 (m, 2H), 1.11 (d, J = 6.9 Hz, 3H); 13C NMR
(150 MHz, CDCl3) δ 140.9, 135.1, 133.4, 133.2, 128.6, 128.0, 127.9,
126.8, 126.4, 126.2, 125.7, 115.1, 77.1, 73.8, 72.9, 72.5, 69.5, 40.2, 37.1,
36.8, 16.0; HRMS (ESI-TOF) m/z [M + Na]+ calcd for C21H28O4Na
367.1880, found 367.1885.
(5R,6S,8S)-5-((S)-But-3-en-2-yl)-6-((tert-butyldimethylsilyl)-
oxy)-2,2,3,3,10,10,11,11-octamethyl-8-(2-(naphthalen-2-yl-
methoxy)ethyl)-4,9-dioxa-3,10-disiladodecane (41). To a sol-
ution of triol 40 (145 mg, 0.421 mmol) and 2,6-lutidine (0.44 mL, 3.8
mmol) in CH2Cl2 (4.2 mL) at 0 °C was added TBSOTf (0.58 mL, 2.5
mmol). After the mixture was stirred at 0 °C for 30 min, the reaction
was quenched with saturated aqueous NaHCO3 and extracted with
0.57 (hexane/ethyl acetate = 7/1); [α]26 −29.0 (c 0.95, CHCl3); IR
D
(neat) 3734, 3628, 3056, 2954, 2928, 2856, 1599, 1500, 1472, 1387,
1252, 1092, 1044, 939, 835, 740 cm−1; 1H NMR (600 MHz, CDCl3) δ
7.82−7.79 (m, 4H), 7.57−7.50 (m, 5H), 7.47−7.41 (m, 3H), 4.63
(ddd, J = 6.0, 6.0, 6.0 Hz, 2H), 3.96−3.95 (m, 1H), 3.64−3.56 (m,
3H), 3.52−3.47 (m, 2H), 3.28−3.24 (m, 1H), 1.97−1.89 (m, 2H),
J
DOI: 10.1021/jo502322m
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
1.82−1.78 (m, 1H), 1.73−1.67 (m, 1H), 1.60−1.51 (m, 3H), 0.92 (d, J
= 6.6 Hz, 3H), 0.88 (s, 9H), 0.848 (s, 9H), 0.846 (s, 9H), 0.11 (s, 3H),
0.034 (s, 3H), 0.030 (s, 3H), 0.027 (s, 3H), 0.01 (s, 6H); 13C NMR
(150 MHz, CDCl3) δ 154.4, 136.3, 133.9, 133.4, 133.1, 130.2, 129.9
(2C), 128.2, 128.0, 127.8, 126.5, 126.1, 126.0, 125.8, 123.9 (2C), 81.1,
73.3, 72.9, 67.4, 67.1, 42.0, 37.1, 36.5, 33.2, 31.8, 26.2 (6C), 26.0 (3C),
18.5, 18.2 (2C), 14.5, −3.2, −3.3, −4.1, −4.3, −4.6 (2C); HRMS (ESI-
TOF) m/z [M + Na]+ calcd for C46H76N4O4SSi3Na 887.4787, found
887.4824.
42.15, 42.12, 39.5, 38.5, 38.1, 37.8, 37.7, 37.6, 37.2, 33.2, 30.2, 30.0,
27.2 (3C), 26.5 (6C), 26.31 (3C), 26.29 (3C), 26.25 (3C), 26.21
(3C), 26.19 (3C), 25.7, 21.8, 19.5, 18.8, 18.6, 18.53, 18.45, 18.38 (2C),
18.36, 15.9, −2.8, −3.0, −3.6, −3.7, −3.9, −4.0, −4.06, −4.13, −4.2,
−4.37, −4.40 (3C), −4.46; HRMS (ESI-TOF) m/z [M + Na]+ calcd
for C99H180O9Si8Na 1760.1674, found 1760.1686.
(6R,8E,10R,12E,14R,18R,24S,25S,27S,28R,29S,31S)-
6,10,14,18,28,29-Hexakis((tert-butyldimethylsilyl)oxy)-
2,2,27,33,33,34,34-heptamethyl-31-(2-(naphthalen-2-ylmeth-
oxy)ethyl)-3,3-diphenyl-4,32-dioxa-3,33-disilapentatriaconta-
8,12-diene-24,25-diol (46). A mixture of K2OsO4·2H2O (4.9 mg, 13
μmol), DHQ-MEQ (49.9 mg, 107 μmol), K3Fe(CN)6 (263 mg, 800
μmol), K2CO3 (111 mg, 800 μmol), and MeSO2NH2 (76.1 mg, 800
μmol) in t-BuOH/H2O (v/v = 1:1, 4.4 mL) was stirred at room
temperature for 30 min. To this suspension at 0 °C was added a
solution of olefin 45 (464 mg, 0.267 mmol) in t-BuOMe (3.2 mL + 3
× 0.4 mL rinse) via cannula. After the mixture was stirred at 0 °C for
69 h, the reaction was quenched with saturated aqueous Na2S2O3 and
stirred at 0 °C for 30 min. The mixture was extracted with ethyl
acetate. The organic layer was washed with saturated aqueous NaCl,
dried over anhydrous Na2SO4, filtered, and concentrated under
reduced pressure. The residue was purified by flash silica gel column
chromatography (hexane/ethyl acetate = 30/1 → 12/1 → 10/1) to
afford diol 46 as a mixture of diastereoisomers (308 mg, 0.174 mmol,
65%, dr =13:1) as a colorless viscous syrup: Rf = 0.16 (hexane/ethyl
acetate = 10/1); [α]25D −14.3 (c 1.10, CHCl3); IR (neat) 3734, 3649,
3178, 2952, 2928, 2856, 1716, 1653, 1636, 1472, 1461, 1362, 1252,
1070, 1005, 833, 772, 701 cm−1; 1H NMR (600 MHz, C6D6) δ 7.83−
7.65 (m, 8H), 7.46−7.44 (m, 1H), 7.32−7.26 (m, 8H), 5.813 (ddd, J =
15.0, 6.6, 6.6 Hz, 1H), 5.807 (ddd, J = 15.0, 6.6, 6.6 Hz, 1H), 5.68 (dd,
J = 15.0, 6.6 Hz, 1H), 5.64 (dd, J = 15.0, 7.2 Hz, 1H), 4.51 (d, J = 11.4
Hz, 1H), 4.47 (d, J = 11.4 Hz, 1H), 4.31−4.28 (m, 1H), 4.24−4.20
(m, 2H), 3.96−3.90 (m, 2H), 3.80−3.72 (m, 5H), 3.62 (d, J = 6.6 Hz,
1H), 3.25−3.20 (m, 1H), 3.19−3.15 (m, 1H), 2.57−2.43 (m, 2H),
2.43−2.33 (m, 2H), 2.12−2.07 (m, 2H), 2.03−1.99 (m, 1H), 1.90−
1.83 (m, 2H), 1.76−1.28 (m, 17H), 1.23−1.18 (m, 1H), 1.21 (s, 9H),
1.10 (s, 9H), 1.07 (s, 9H), 1.06 (s, 9H), 1.041 (s, 9H), 1.035 (s, 9H),
1.02 (s, 9H), 0.99 (s, 9H), 0.95 (d, J = 7.2 Hz, 3H), 0.34 (s, 3H), 0.28
(s, 3H), 0.21 (s, 3H), 0.20 (s, 3H), 0.190 (s, 3H), 0.187 (s, 9H), 0.17
(s, 3H), 0.16 (s, 3H), 0.15 (s, 3H), 0.13 (s, 3H), 0.10 (s, 3H), 0.05 (s,
3H); 13C NMR (150 MHz, C6D6) δ 136.7, 136.4, 136.3, 136.1 (4C),
134.1, 133.99, 133.96, 133.6, 130.1 (4C), 128.5 (2C), 128.0 (2C),
127.3, 126.7, 126.6, 126.5, 126.3 (2C), 126.1, 82.9, 75.3, 74.3, 74.0,
73.7, 73.3 (2C), 72.7, 72.6, 67.61, 67.56, 67.2, 42.1, 41.7, 39.5 (2C),
37.79, 37.77, 37.6, 36.4, 34.22, 34.15, 30.6 (2C), 27.2 (3C), 26.52
(3C), 26.46 (3C), 26.30 (6C), 26.25 (3C), 26.21 (3C), 26.18 (3C),
25.9, 21.8, 19.5, 18.9, 18.6, 18.52, 18.46, 18.40, 18.37 (2C), 16.3, −2.9,
−3.0, −3.6, −3.8, −3.9, −4.01, −4.03, −4.1, −4.2, −4.36, −4.39 (3C),
−4.5; HRMS (ESI-TOF) m/z [M + Na]+ calcd for C99H182O11Si8Na
1794.1729, found 1794.1726.
1-Phenyl-5-(((3S,4R,5S,7S)-4,5,7-tris((tert-butyldimethylsilyl)-
oxy)-3-methyl-9-(naphthalen-2-ylmethoxy)nonyl)sulfonyl)-1H-
tetrazole (4). To a solution of sulfide 44 (622 mg, 0.719 mmol) in
CH2Cl2 (9.6 mL) at 0 °C was added m-CPBA (989 mg, 3.96 mmol).
After the mixture was stirred at 0 °C for 39 h, the reaction was
quenched with saturated aqueous Na2S2O3 and saturated aqueous
NaHCO3. The mixture was extracted with ethyl acetate, washed with
saturated aqueous NaCl, dried over anhydrous Na2SO4, filteredm and
concentrated under reduced pressure. Purification by flash silica gel
column chromatography (hexane/ethyl acetate = 10/1→3/1) gave
sulfone 4 (555 mg, 0.619 mmol, 86%) as a colorless viscous syrup: Rf =
0.5 (hexane/ethyl acetate = 7/1 × 2); [α]25 −25.6 (c 0.93, CHCl3);
D
IR (neat) 3734, 3628, 2954, 2928, 2856, 1596, 1558, 1497, 1472, 1340,
1
1254, 1093, 939, 835, 774 cm−1; H NMR (600 MHz, CDCl3) δ
7.83−7.77 (m, 4H), 7.69−7.67 (m, 2H), 7.63−7.54 (m, 3H), 7.47−
7.44 (m, 3H), 4.66−4.60 (m, 2H), 4.00−3.97 (m, 1H), 3.76−3.71 (m,
1H), 3.65−3.57 (m, 4H), 3.53−3.52 (m, 1H), 2.09−2.05 (m, 1H),
1.93−1.89 (m, 1H), 1.81−1.77 (m, 1H), 1.73−1.68 (m, 2H), 1.62−
1.54 (m, 2H), 0.91 (d, J = 4.8 Hz, 3H), 0.89 (s, 9H), 0.86 (s, 9H), 0.85
(s, 9H), 0.13 (s, 3H), 0.051 (s, 6H), 0.046 (s, 3H), 0.019 (s, 3H),
0.015 (s, 3H); 13C NMR (150 MHz, CDCl3) δ 153.6, 136.3, 133.5,
133.2, 133.1, 131.6, 129.9 (2C), 128.1, 128.0, 127.8, 126.5, 126.12,
126.08, 125.9, 125.2 (2C), 80.9, 73.3, 73.1, 67.2, 67.0, 54.9, 42.1, 36.9,
36.4, 26.3, 26.2 (6C), 26.0 (3C), 18.5, 18.2 (2C), 14.8, −3.20, −3.27,
−4.1, −4.3, −4.6, −4.7; HRMS (ESI-TOF) m/z [M + Na]+ calcd for
C46H76N4O6SSi3Na 919.4686, found 919.4662.
(6R, 8E, 10R, 12E, 14R, 18R, 24E, 27S, 28R, 29S, 31S)-
6,10,14,18,28,29-Hexakis((tert-butyldimethylsilyl)oxy)-
2,2,27,33,33,34,34-heptamethyl-31-(2-(naphthalen-2-ylmeth-
oxy)ethyl)-3,3-diphenyl-4,32-dioxa-3,33-disilapentatriaconta-
8,12,24-triene (45). To a solution of aldehyde 3 (411 mg, 0.385
mmol) and sulfone 4 (554 mg, 0.617 mmol) in THF (12 mL) at −78
°C was added KHMDS (0.5 M in THF, 1.2 mL, 0.6 mmol). After the
mixture was stirred at −78 °C for 4 h, the reaction was allowed to
warm to room temperature and stirred for 18 h. The reaction was
quenched with saturated aqueous NH4Cl at 0 °C and extracted with
ethyl acetate. The organic layer was washed with saturated aqueous
NaCl, dried over anhydrous Na2SO4, filtered, and concentrated under
reduced pressure. Purification by flash silica gel column chromatog-
raphy (hexane/ethyl acetate = 80/1 → 30/1 → 15/1) gave triene 45
(576 mg, 0.331 mmol, 86%) as a colorless viscous syrup: Rf = 0.78
(6R,8E,10R,12E,14R,18R,24S,25S,27S,28R,29S,31S)-
6,10,14,18,24,25,28,29-Octakis((tert-butyldimethylsilyl)oxy)-
2,2,27,33,33,34,34-heptamethyl-31-(2-(naphthalen-2-ylmeth-
oxy)ethyl)-3,3-diphenyl-4,32-dioxa-3,33-disilapentatriaconta-
8,12-diene (47). To a solution of diol 46 (308 mg, 0.174 mmol) in
CH2Cl2 (3.4 mL) were added 2,6-lutidine (0.16 mL, 1.4 mmol) and
TBSOTf (0.16, 0.70 mmol) at 0 °C. After being stirred at 0 °C for 10
min, the reaction mixture was quenched with saturated aqueous
NaHCO3 and extracted with ethyl acetate. The organic layer was
washed with saturated aqueous NaHCO3 and saturated aqueous NaCl,
dried over anhydrous Na2SO4, filtered, and concentrated under
reduced pressure. Purification by flash silica gel column chromatog-
raphy (hexane/ethyl acetate = 150/1→15/1) afforded TBS ether 47
(323 mg, 0.162 mmol, 93%) as a colorless viscous syrup: Rf = 0.73
(hexane/ethyl acetate = 10/1); [α]25 −12.0 (c 1.29, CHCl3); IR
D
(neat) 3734, 2953, 2928, 2856, 1716, 1653, 1636, 1507, 1462, 1362,
1
1254, 1091, 1005, 835, 774, 740 cm−1; H NMR (600 MHz, C6D6) δ
7.83−7.65 (m, 8H), 7.49−7.47 (m, 1H), 7.32−7.25 (m, 8H), 5.81
(ddd, J = 16.2, 6.6, 6.6 Hz, 1H), 5.80 (ddd, J = 15.0, 6.6, 6.6 Hz, 1H),
5.69 (dd, J = 15.0, 6.0 Hz, 1H), 5.63 (dd, J = 16.2, 6.6 Hz, 1H), 5.53
(ddd, J = 16.2, 6.0, 6.0 Hz, 1H), 5.46 (ddd, J = 16.2, 6.0, 6.0 Hz, 1H),
4.58 (d, J = 12.0 Hz, 1H), 4.51 (d, J = 12.0 Hz, 1H), 4.30−4.27 (m,
1H), 4.24−4.21 (m, 2H), 3.93−3.89 (m, 1H), 3.86−3.85 (m, 1H),
3.79−3.75 (m, 3H), 3.75−3.72 (m, 1H), 3.70−3.69 (m, 1H), 3.67−
3.64 (m, 1H), 2.56−2.42 (m, 2H), 2.42−2.29 (m, 3H), 2.14−2.11 (m,
2H), 2.10−2.06 (m, 2H), 1.94−1.89 (m, 1H), 1.87−1.83 (m, 1H),
1.74−1.30 (m, 16H), 1.20 (s, 9H), 1.08 (s, 9H), 1.07 (s, 9H), 1.05 (s,
9H), 1.04 (s, 9H), 1.03 (s, 9H), 1.03 (d, J = 8.4 Hz, 3H), 1.01 (s, 9H),
0.99 (s, 9H), 0.33 (s, 3H), 0.28 (s, 3H), 0.21 (s, 3H), 0.192 (s, 3H),
0.187 (s, 3H), 0.18 (s, 3H), 0.17 (s, 6H), 0.16 (s, 3H), 0.14 (s, 6H),
0.12 (s, 3H), 0.10 (s, 3H), 0.05 (s, 3H); 13C NMR (150 MHz, C6D6)
δ 136.8, 136.7, 136.3, 136.1 (4C), 134.1, 134.0 (2C), 133.6, 132.6,
130.1 (4C), 129.1, 128.3 (2C), 128.0 (3C), 126.8, 126.6, 126.5, 126.3
(2C), 126.0, 81.6, 74.3, 74.0, 73.7, 73.5, 73.2, 72.7, 67.5, 67.34, 67.26,
(hexane/ethyl acetate = 10/1); [α]25 −24.5 (c 1.01, CHCl3); IR
D
(neat) 3750, 3734, 3676, 2953, 2928, 2856, 1716, 1653, 1636, 1522,
1
1472, 1459, 1362, 1254, 1086, 1005, 835, 773, 701 cm−1; H NMR
(600 MHz, C6D6) δ 7.83−7.66 (m, 8H), 7.49−7.48 (m, 1H), 7.32−
7.26 (m, 8H), 5.81 (ddd, J = 15.0, 7.2, 7.2 Hz, 1H), 5.80 (ddd, J =
15.0, 7.2, 7.2 Hz, 1H), 5.68 (dd, J = 15.0, 6.6 Hz, 1H), 5.63 (dd, J =
15.0, 6.6 Hz, 1H), 4.59 (d, J = 11.4 Hz, 1H), 4.52 (d, J = 11.4 Hz, 1H),
K
DOI: 10.1021/jo502322m
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
4.35−4.31 (m, 1H), 4.24−4.19 (m, 2H), 3.97−3.86 (m, 3H), 3.84−
3.64 (m, 7H), 2.57−2.43 (m, 2H), 2.43−2.32 (m, 2H), 2.26−2.14 (m,
2H), 2.05−1.89 (m, 3H), 1.83−1.34 (m, 18H), 1.21 (s, 9H), 1.12 (s,
9H), 1.13−1.11 (m, 3H), 1.07 (s, 9H), 1.05 (s, 18H), 1.04 (s, 18H),
1.03 (s, 9H), 1.01 (s, 9H), 0.99 (s, 9H), 0.36 (s, 3H), 0.30 (s, 3H),
0.25 (s, 3H), 0.24 (s, 3H), 0.23 (s, 3H), 0.22 (s, 3H), 0.19 (s, 3H),
0.182 (s, 6H), 0.175 (s, 3H), 0.17 (s, 3H), 0.16 (s, 3H), 0.15 (s, 9H),
0.13 (s, 3H), 0.10 (s, 3H), 0.05 (s, 3H); 13C NMR (150 MHz, C6D6)
δ 136.8, 136.7, 136.3, 136.1 (4C), 134.1, 134.0 (2C), 133.6, 130.1
(4C), 128.3 (2C), 128.2, 128.0 (2C), 126.8, 126.6, 126.5, 126.34,
126.27, 126.0, 83.7, 75.8, 74.7, 74.3, 74.0, 73.5, 73.3, 72.8, 72.7, 67.6,
67.3 (2C), 42.8, 42.1, 39.5, 37.8 (2C), 37.6, 37.4, 36.0, 34.3, 30.71,
30.69, 27.7, 27.2 (3C), 26.6 (3C), 26.4 (3C), 26.31 (6C), 26.25 (6C),
26.23 (3C), 26.18 (6C), 26.0, 21.8, 19.5, 18.8, 18.6, 18.5, 18.45, 18.38
(2C), 18.34, 18.31, 18.29, 14.0, −2.9, −3.0, −3.62, −3.64 (2C), −3.8,
−3.9, −4.0 (2C), −4.1, −4.2, −4.26, −4.28, −4.31, −4.35, −4.39 (2C),
−4.5; HRMS (ESI-TOF) m/z [M + Na]+ calcd for C111H210O11Si10Na
2022.3458, found 2022.3477.
aqueous NaHCO3 and Na2S2O3 at 0 °C. After being diluted with Et2O,
the mixture was filtered through cotton and extracted with Et2O. The
organic layer was washed with saturated aqueous NaCl, dried over
anhydrous Na2SO4, filtered, and concentrated under reduced pressure.
The residue was purified by flash silica gel column chromatography
(hexane/ethyl acetate = 100/1 → 20/1) to afford triene 2 (235 mg,
0.127 mmol, 97%) as a yellow viscous syrup: Rf = 0.43 (hexane/ethyl
acetate = 20/1); [α]25D −19.7 (c 1.03, CHCl3); IR (neat) 3727, 3621,
2954, 2929, 2890, 2857, 1732, 1593, 1506, 1472, 1428, 1362, 1254,
1
1085, 972, 835, 773, 701 cm−1; H NMR (600 MHz, C6D6) δ 7.83−
7.80 (m, 4H), 7.30−7.25 (m, 6H), 6.02 (ddd, J = 16.8, 10.8, 6.6 Hz,
1H), 5.81 (ddd, J = 15.0, 7.8, 7.8 Hz, 1H), 5.80 (ddd, J = 15.0, 7.2, 7.2
Hz, 1H), 5.69 (dd, J = 15.0, 6.0 Hz, 1H), 5.64 (dd, J = 15.0, 6.6 Hz,
1H), 5.37 (d, J = 16.8 Hz, 1H), 5.14 (d, J = 10.8 Hz, 1H), 4.51−4.48
(m, 1H), 4.24−4.19 (m, 2H), 3.94−3.86 (m, 3H), 3.80−3.73 (m, 5H),
2.57−2.43 (m, 2H), 2.43−2.32 (m, 2H), 2.18−2.13 (m, 1H), 2.06−
1.91 (m, 3H), 1.82−1.36 (m, 17H), 1.20 (s, 9H), 1.12−1.11 (m, 3H),
1.11 (s, 9H), 1.07 (s, 9H), 1.058 (s, 9H), 1.056 (s, 18H), 1.039 (s,
9H), 1.036 (s, 18H), 0.99 (s, 9H), 0.33 (s, 3H), 0.243 (s, 3H), 0.239
(s, 3H), 0.23 (s, 3H), 0.20 (s, 6H), 0.19 (s, 3H), 0.18 (s, 6H), 0.171 (s,
3H), 0.165 (s, 3H), 0.158 (s, 3H), 0.156 (s, 3H), 0.154 (s, 3H), 0.148
(s, 3H), 0.12 (s, 3H), 0.10 (s, 3H), 0.05 (s, 3H); 13C NMR (150 MHz,
C6D6) δ 141.8, 136.7, 136.3, 136.1 (4C), 134.1, 134.0, 130.1 (4C),
128.3 (2C), 126.6, 126.5, 115.1, 83.3, 75.8, 74.5, 74.3, 74.0, 73.3, 72.9,
72.7, 72.3, 67.5, 43.1, 42.1, 39.5, 37.8 (2C), 37.6, 36.2, 33.6, 30.74,
30.70, 27.7, 27.2 (3C), 26.6 (3C), 26.4 (3C), 26.31 (6C), 26.26 (6C),
26.21 (3C), 26.18 (6C), 25.9, 21.8, 19.5, 18.8, 18.6 (2C), 18.53, 18.45
(2C), 18.38, 18.32, 18.30, 14.1, −2.8, −3.0, −3.6, −3.7, −3.8, −3.9,
−4.03 (2C), −4.05, −4.19, −4.23 (3C), −4.27, −4.34, −4.36, −4.39,
−4.5; HRMS (ESI-TOF) m/z [M + Na]+ calcd for C100H200O10Si10Na
1864.2726, found 1864.2778.
(3S,5S,6R,7S,9S,10S,16R,20R,21E,24R,25E,28R)-
3,5,6,9,10,16,20,24,28-Nonakis((tert-butyldimethylsilyl)oxy)-
29-((tert-butyldiphenylsilyl)oxy)-7-methylnonacosa-21,25-
dien-1-ol (48). To a solution of NAP ether 47 (321 mg, 0.160 mmol)
in CH2Cl2/pH 7 buffer (v/v = 3:1, 2.1 mL) at 0 °C was added DDQ
(72.8 mg, 0.322 mmol). After the mixture was stirred for 1 h at 0 °C,
the reaction was quenched with saturated aqueous NaHCO3 and
saturated aqueous Na2S2O3. The mixture was extracted with ethyl
acetate, and the organic layer was washed with saturated aqueous
NaCl, dried over anhydrous Na2SO4, filtered, and concentrated under
reduced pressure. The residue was dissolved in MeOH/THF (v/v =
1:1, 1.6 mL) and cooled to 0 °C. NaBH4 (60.6 mg, 1.60 mmol) was
added to the mixture and stirred for 10 min. The reaction mixture was
quenched with saturated aqueous NH4Cl and extracted with ethyl
acetate. The organic layer was washed with saturated aqueous NaCl,
dried over anhydrous Na2SO4, filtered, and concentrated under
reduced pressure. Purification by flash silica gel column chromatog-
raphy (hexane/ethyl acetate = 80/1 → 50/1 → 9/1) afforded alcohol
48 (247 mg, 0.133 mmol, 83%) as a colorless viscous syrup: Rf = 0.48
ASSOCIATED CONTENT
■
S
* Supporting Information
1H and 13C NMR spectra of new compounds. This material is
available free of charge via the Internet at http://pubs.acs.org.
(hexane/ethyl acetate = 12/1); [α]25 −22.6 (c 0.90, CHCl3); IR
D
AUTHOR INFORMATION
Corresponding Author
*E-mail: oishi@chem.kyushu-univ.jp.
(neat) 3727, 3624, 3492, 2954, 2929, 2894, 2857, 1723, 1665, 1584,
■
1
1472, 1425, 1361, 1254, 1083, 1005, 835, 773, 702 cm−1; H NMR
(600 MHz, C6D6) δ 7.83−7.80 (m, 4H), 7.31−7.26 (m, 6H), 5.81
(ddd, J = 15.6, 7.2, 7.2 Hz, 1H), 5.80 (ddd, J = 15.6, 7.2, 7.2 Hz, 1H),
5.68 (dd, J = 15.6, 6.6 Hz, 1H), 5.63 (dd, J = 15.6, 7.2 Hz, 1H), 4.31−
4.27 (m, 1H), 4.24−4.19 (m, 2H), 3.94−3.86 (m, 4H), 3.82−3.73 (m,
6H), 2.57−2.43 (m, 2H), 2.43−2.33 (m, 2H), 2.17−2.12 (m, 1H),
2.03−1.92 (m, 4H), 1.82−1.35 (m, 18H), 1.21 (s, 9H), 1.12−1.10 (m,
3H), 1.12 (s, 9H), 1.07 (s, 9H), 1.06 (s, 9H), 1.05 (s, 9H), 1.042 (s,
9H), 1.038 (s, 9H), 1.03 (s, 18H), 0.99 (s, 9H), 0.35 (s, 3H), 0.28 (s,
3H), 0.25 (s, 3H), 0.218 (s, 3H), 0.215 (s, 3H), 0.194 (s, 3H), 0.191
(s, 3H), 0.186 (s, 6H), 0.18 (s, 3H), 0.17 (s, 3H), 0.162 (s, 3H), 0.156
(s, 3H), 0.154 (s, 3H), 0.151 (s, 3H), 0.13 (s, 3H), 0.10 (s, 3H), 0.05
(s, 3H); 13C NMR (150 MHz, C6D6) δ 136.7, 136.3, 136.1 (4C),
134.1, 134.0, 130.1 (4C), 128.3 (2C), 126.6, 126.5, 83.6, 75.8, 74.7,
74.3, 74.0, 73.3, 72.8, 72.7, 69.0, 67.6, 60.0, 42.1, 41.9, 39.5, 38.6, 37.8
(2C), 37.6, 35.9, 34.2, 30.72, 30.69, 27.7, 27.2 (3C), 26.6 (3C), 26.4
(3C), 26.31 (9C), 26.25 (6C), 26.2 (6C), 25.9, 21.8, 19.5, 18.8, 18.6,
18.5, 18.45, 18.42, 18.38, 18.32, 18.30, 18.27, 14.2, −2.9, −3.0, −3.6,
−3.7, −3.77, −3.80, −3.9, −4.0 (2C), −4.1, −4.2, −4.26, −4.34 (3C),
−4.4, −4.46, −4.47; HRMS (ESI-TOF) m/z [M + Na]+ calcd for
C100H202O11Si10Na 1882.2832, found 1882.2858.
(5R,7S,8R,9S,11S,12S,18R,22R,23E,26R,27E,30R)-
7,8,11,12,18,22,26,30-Octakis((tert-butyldimethylsilyl)oxy)-
2,2,3,3,9,34,34-heptamethyl-33,33-diphenyl-5-vinyl-4,32-
dioxa-3,33-disilapentatriaconta-23,27-diene (2). To a mixture of
alcohol 48 (244 mg, 0.131 mmol), o-O2NPhSeCN (149 mg, 0.655
mmol), and activated powdered MS4A (110 mg) in THF (0.5 mL) at
55 °C was added Me3P (1.0 M in THF, 2.6 mL, 2.6 mmol) via syringe
at once. After the mixture was stirred at room temperature for 30 min,
30% H2O2 (595 μL, 5.24 mmol) was added. The resultant mixture was
stirred for 3 h before the reaction was quenched with saturated
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported in part by a fund from Kyushu
University, Funds for the Development of Human Resources in
Science and Technology originating from the Ministry of
Education, Culture, Sports, Science and Technology (MEXT),
and by a Grant-in-Aid for Young Scientists (B) from the Japan
Society for the Promotion of Science (JSPS), and JST ERATO
Lipid Active Structure.
REFERENCES
■
(1) (a) Satake, M.; Murata, M.; Yasumoto, T.; Fujita, T.; Naoki, H. J.
Am. Chem. Soc. 1991, 113, 9859−9861. (b) Murata, M.; Matsuoka, S.;
Matsumori, N.; Paul, G. K.; Tachibana, K. J. Am. Chem. Soc. 1999, 121,
870−871. (c) Swasono, R. T.; Kanemoto, M.; Matsumori, N.; Oishi,
T.; Murata, M. Heterocycles 2011, 82, 1359−1369.
(2) (a) Paul, G. K.; Matsumori, N.; Konoki, K.; Murata, M.;
Tachibana, K. J. Mar. Biotechnol. 1997, 5, 124−128. (b) Houdai, T.;
Matsuoka, S.; Matsumori, N.; Murata, M. Biochim. Biophys. Acta 2004,
1667, 91−100. (c) Houdai, T.; Matsuoka, S.; Morsy, N.; Matsumori,
N.; Satake, M.; Murata, M. Tetrahedron 2005, 61, 2795−2802.
(d) Morsy, N.; Houdai, T.; Konoki, K.; Matsumori, N.; Oishi, T.;
Murata, M. Bioorg. Med. Chem. 2008, 16, 3084−3090. (e) Swasono, R.;
Mouri, R.; Morsy, N.; Matsumori, N.; Oishi, T.; Murata, M. Bioorg.
L
DOI: 10.1021/jo502322m
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
Med. Chem. Lett. 2010, 20, 2215−2218. (f) Espiritu, R. A.; Matsumori,
N.; Tsuda, M.; Murata, M. Biochemistry 2014, 53, 3287−3293.
(3) (a) Morsy, N.; Matsuoka, S.; Houdai, T.; Matsumori, N.; Adachi,
S.; Murata, M.; Iwashita, T.; Fujita, T. Tetrahedron 2005, 61, 8606−
8610. (b) Echigoya, R.; Rhodes, L.; Oshima, Y.; Satake, M. Harmful
Argae 2005, 4, 383−389. (c) Morsy, N.; Houdai, T.; Matsuoka, S.;
Matsumori, N.; Adachi, S.; Oishi, T.; Murata, M.; Iwashita, T.; Fujita,
T. Bioorg. Med. Chem. 2006, 14, 6548−6554. (d) Meng, Y.; Van
Wagoner, R. M.; Misner, I.; Tomas, C.; Wright, J. L. C. J. Nat. Prod.
2010, 73, 409−415. (e) Nuzzo, G.; Cutignano, A.; Sardo, A.; Fontana,
A. J. Nat. Prod. 2014, 77, 1524−1527.
(16) Crimmins, M. T.; Martin, T. J.; Martinot, T. A. Org. Lett. 2010,
12, 3890−3893.
(17) Kanemoto, M.; Murata, M.; Oishi, T. J. Org. Chem. 2009, 74,
8810−8813.
(18) Blakemore, P. R.; Cole, W. J.; Kocienski, P. J.; Morley, A. Synlett
1998, 26−28.
(19) For recent reviews, see: (a) Blakemore, P. R. J. Chem. Soc.,
Perkin Trans. 1 2002, 2563−2585. (b) Aïssa, C. Eur. J. Org. Chem.
2009, 1831−1844. (c) Chatterjee, B.; Bera, S.; Mondal, D.
Tetrahedron: Asymmetry 2014, 25, 1−55.
(20) (a) Kolb, H. C.; VanNieuwenhze, M. S.; Sharpless, K. B. Chem.
Rev. 1994, 94, 2483−2547. (b) Sharpless, K. B.; Amberg, W.; Bennani,
Y. L.; Crispino, G. A.; Hartung, J.; Jeong, K. S.; Kwong, H. L.;
Morikawa, K.; Wang, Z. M.; Xu, D.; Zhang, X.-L. J. Org. Chem. 1992,
57, 2768−2771.
(21) (a) Grubbs, R. H.; Chang, S. Tetrahedron 1998, 54, 4413−4450.
(b) Chatterjee, A. K.; Morgan, J. R.; Scholl, M.; Grubbs, R. H. J. Am.
Chem. Soc. 2000, 122, 3783−3784. (c) Morgan, J. R.; Grubbs, R. H.
Org. Lett. 2000, 2, 3153−3155.
(4) (a) Doi, Y.; Ishibashi, M.; Nakamichi, H.; Kosaka, T.; Ishikawa,
T.; Kobayashi, J. J. Org. Chem. 1997, 62, 3820−3823. (b) Kubota, T.;
Tsuda, M.; Doi, Y.; Takahashi, A.; Nakamichi, H.; Ishibashi, M.;
Fukushi, E.; Kawabata, J.; Kobayashi, J. Tetrahedron 1998, 54, 14455−
14464. (c) Huang, X.-C.; Zhao, D.; Guo, Y.-W.; Wu, H.-M.; Lin, L.-P.;
Wang, Z.-H.; Ding, J.; Lin, Y.-S. Bioorg. Med. Chem. Lett. 2004, 14,
3117−3120. (d) Huang, X.-C.; Zhao, D.; Guo, Y.-W.; Wu, H.-M.;
Trivellone, E.; Cimino, G. Tetrahedron Lett. 2004, 45, 5501−5504.
(e) Kubota, T.; Takahashi, A.; Tsuda, M.; Kobayashi, J. Marine Drugs
2005, 3, 113−118. (f) Washida, K.; Koyama, T.; Yamada, K.; Kita, M.;
Uemura, D. Tetrahedron Lett. 2006, 47, 2521−2525. (g) Van Wagoner,
R. M.; Deeds, J. R.; Satake, M.; Ribeiro, A. A.; Place, A. R.; Wright, J. L.
C. Tetrahedron Lett. 2008, 49, 6457−6461. (h) Huang, S.-J.; Kuo, C.-
M.; Lin, Y.-C.; Chen, Y.-M.; Lu, C.-K. Tetrahedron Lett. 2009, 50,
2512−2515. (i) Peng, J.; Place, A. R.; Yoshida, W.; Anklin, C.;
Hamann, M. T. J. Am. Chem. Soc. 2010, 132, 3277−3279. (j) Inuzuka,
T.; Yamamoto, Y.; Yamada, K.; Uemura, D. Tetrahedron Lett. 2012, 53,
239−242.
(22) (a) Einhorn, J.; Einhorn, C.; Luche, J. L. Synth. Commun. 1990,
20, 1105−1112. (b) Niu, T.; Zhang, W.; Huang, D.; Xu, C.; Wang, H.;
Hu, Y. Org. Lett. 2009, 11, 4474−4477.
(23) Evans, P. A.; Grisin, A.; Lawler, M. J. Am. Chem. Soc. 2012, 134,
2856−2859.
(24) Brown, H. C.; Bhat, K. S. J. Am. Chem. Soc. 1986, 108, 5919−
5923.
(25) (a) Bohlmann, F.; Herbst, P. Chem. Ber. 1959, 92, 1319−1328.
(b) Yu, L.; Woo, K. S.; Krische, J. M. J. Am. Chem. Soc. 2011, 133,
13876−13879.
(26) Darwish, A.; Lang, A.; Kim, T.; Chong, J. M. Org. Lett. 2008, 10,
861−864.
(27) (a) Katsuki, T.; Sharpless, K. B. J. Am. Chem. Soc. 1980, 102,
5974−5976. (b) Martin, V. S.; Woodard, S. S.; Katsuki, T.; Yamada,
Y.; Ikeda, M.; Sharpless, K. B. J. Am. Chem. Soc. 1981, 103, 6237−
6240. (c) Gao, Y.; Hanson, R. M.; Klunder, J. M.; Ko, S. Y.;
Masamune, H.; Sharpless, K. B. J. Am. Chem. Soc. 1987, 109, 5765−
5780.
(5) Matsumori, N.; Kaneno, D.; Murata, M.; Nakamura, H.;
Tachibana, K. J. Org. Chem. 1999, 64, 866−876.
(6) Ohtani, I.; Kusumi, T.; Kashman, Y.; Kakisawa, H. J. Am. Chem.
Soc. 1991, 113, 4092−4096.
(7) Manabe, Y.; Ebine, M.; Matsumori, N.; Murata, M.; Oishi, T. J.
Nat. Prod. 2012, 75, 2003−2006.
(8) Oishi, T.; Kanemoto, M.; Swasono, R.; Matsumori, N.; Murata,
M. Org. Lett. 2008, 10, 5203−5206.
(28) (a) Wang, Y.; O’Doherty, G. A. J. Am. Chem. Soc. 2013, 135,
9334−9337. (b) Kende, A. S.; Hernando, J. I. M.; Milbank, J. B.
Tetrahedron 2002, 58, 61−74.
(9) Ebine, M.; Kanemoto, M.; Manabe, Y.; Konno, Y.; Sakai, K.;
Matsumori, N.; Murata, M.; Oishi, T. Org. Lett. 2013, 15, 2846−2849.
(10) For a recent review, see: Bensoussan, C.; Rival, N.; Hanquet, G.;
Colobert, F.; Reymond, S.; Cossy, J. Nat. Prod. Rep. 2014, 31, 468−
488.
(29) Hashiguchi, S.; Fujii, A.; Takehara, J.; Ikariya, T.; Noyori, R. J.
Am. Chem. Soc. 1995, 117, 7562−7563.
(30) Sajiki, H.; Hattori, K.; Hirota, K. J. Org. Chem. 1998, 63, 7990−
(11) (a) BouzBouz, S.; Cossy, J. Org. Lett. 2001, 3, 1451−1454.
7992.
(b) Cossy, J.; Tsuchiya, T.; Ferrie,
́
L.; Reymond, S.; Kreuzer, T.;
I. E. Synlett 2007, 2286−2288.
(31) Corey, E. J.; Bakshi, R. K.; Shibata, S. J. Am. Chem. Soc. 1987,
109, 5551−5553.
(32) (a) Crimmins, M. T.; King, B. W. J. Am. Chem. Soc. 1998, 120,
9084−9085. (b) Bonini, C.; Chiummiento, L.; Lopardo, M. T.; Pullez,
M.; Colobert, F.; Solladie, G. Tetrahedron Lett. 2003, 44, 2695−2697.
(33) Scholl, M.; Ding, S.; Lee, C. W.; Grubbs, R. H. Org. Lett. 1999,
1, 953−956.
(34) Zhan, Z. J. US Patent No. US20070043180A1.
(35) Parikh, J. R.; Doering, W. E. J. Am. Chem. Soc. 1967, 89, 5505−
5507.
(36) Agrawal, D.; Sriramurthy, V.; Yadav, V. K. Tetrahedron Lett.
2006, 47, 7615−7618.
(37) (a) Kingsbury, J. S.; Harrity, J. P. A.; Bonitatebus, P. J.;
Hoveyda, A. H. J. Am. Chem. Soc. 1999, 121, 791−799. (b) Garber, S.
B.; Kingsbury, J. S.; Gray, B. L.; Hoveyda, A. H. J. Am. Chem. Soc.
2000, 122, 8168−8179.
(38) (a) Dess, D. B.; Martin, J. C. J. Org. Chem. 1983, 48, 4155−
4156. (b) Ireland, R. E.; Liu, L. J. Org. Chem. 1993, 58, 2899.
(c) Meyer, S. D.; Schreiber, S. L. J. Org. Chem. 1994, 59, 7549−7552.
(39) Sharpless, K. B.; Amberg, W.; Beller, M.; Chen, H.; Hartung, J.;
Colobert, F.; Jourdain, P.; Marko,
́
(c) Colobert, F.; Kreuzer, T.; Cossy, J.; Reymond, S.; Tsuchiya, T.;
Ferrie,
(d) Cossy, J.; Tsuchiya, T.; Reymond, S.; Kreuzer, T.; Colobert, F.;
Marko, I. E. Synlett 2009, 2706−2710. (e) Rival, N.; Hazelard, D.;
́ ́
L.; Marko, I. E.; Jourdain, P. Synlett 2007, 2351−2354.
́
Hanquet, G.; Kreuzer, T.; Bensoussan, C.; Reymond, S.; Cossy, J.;
Colobert, F. Org. Biomol. Chem. 2012, 10, 9418−9428. (f) Bensoussan,
C.; Rival, N.; Hanquet, G.; Colobert, F.; Reymond, S.; Cossy, J.
Tetrahedron 2013, 69, 7759−7770. (g) Rival, N.; Hanquet, G.;
Bensoussan, C.; Reymond, S.; Cossy, J.; Colobert, F. Org. Biomol.
Chem. 2013, 11, 6829−6840.
(12) (a) Paquette, L. A.; Chang, S.-K. Org. Lett. 2005, 7, 3111−3114.
(b) Chang, S.-K.; Paquette, L. A. Synlett 2005, 2915−2918. (c) Bedore,
M. W.; Chang, S.-K.; Paquette, L. A. Org. Lett. 2007, 9, 513−516.
(13) (a) Flamme, E. M.; Roush, W. R. Org. Lett. 2005, 7, 1411−1414.
(b) Hicks, J. D.; Flamme, E. M.; Roush, W. R. Org. Lett. 2005, 7,
5509−5512. (c) Hicks, J. D.; Roush, W. R. Org. Lett. 2008, 10, 681−
684.
(14) (a) de Vicente, J.; Betzemeier, B.; Rychnovsky, S. D. Org. Lett.
2005, 7, 1853−1856. (b) de Vicente, J.; Huckins, J. R.; Rychnovsky, S.
D. Angew. Chem., Int. Ed. 2006, 45, 7258−7262. (c) Huckins, J. R.; de
Vicente, J.; Rychnovsky, S. D. Org. Lett. 2007, 9, 4757−4760.
Kawanami, Y.; Lubben, D.; Manoury, E.; Ogino, Y.; Shibata, T.; Ukita,
̈
T. J. Org. Chem. 1991, 56, 4585−4588.
(40) Grieco, P. A.; Gilman, S.; Nishizawa, M. J. Org. Chem. 1976, 41,
1485−1486.
(15) Dubost, C.; Marko,
4005−4009.
́
I. E.; Bryans, J. Tetrahedron Lett. 2005, 46,
M
DOI: 10.1021/jo502322m
J. Org. Chem. XXXX, XXX, XXX−XXX