Enantioselective total synthesis of the proposed structure of macrolide iriomoteolide-1b

Article abstract of DOI:10.1016/j.tet.2011.06.025

An enantioselective total synthesis of the proposed structure of macrolide iriomoteolide-1b has been achieved by a convergent protocol, which was featured by an enantioselective organocatalytic transfer hydrogenation of enal, a Julia-Kocienski olefination

Full text of DOI:10.1016/j.tet.2011.06.025

Tetrahedron 67 (2011) 5979e5989
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Enantioselective total synthesis of the proposed structure of macrolide
iriomoteolide-1b
*
Zhengqing Ye, Tingyi Gao, Gang Zhao
Key Laboratory of Synthetic Chemistry of Natural Substances, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 29 April 2011
Received in revised form 1 June 2011
Accepted 10 June 2011
Available online 16 June 2011
An enantioselective total synthesis of the proposed structure of macrolide iriomoteolide-1b has been
achieved by a convergent protocol, which was featured by an enantioselective organocatalytic transfer
hydrogenation of enal, a JuliaeKocienski olefination to establish the C15eC16 E-olefin moiety, a Ku-
linkovich reaction associated with cyclopropyl-allyl rearrangement to produce allyl stannane and yt-
terbium triflate and carboxylic acid promoted allylation between allyl stannane and aldehyde with
tertiary alcohol at the a-position. The construction of macrolide 2 was realized by the successful im-
plementation of RCM utilizing 5 mol % Grubbs’s second generation catalyst at room temperature with E-
isomer as a single product.
Keywords:
Total synthesis
Iriomoteolide-1b
RCM
Ó 2011 Elsevier Ltd. All rights reserved.
Yamaguchi esterification
Allylation
Organocatalytic transfer hydrogenation
1. Introduction
the proposed structures of iriomoteolide-1a and iriomoteolide-1b
with a Sakurai reaction, JuliaeKocienski olefinations and a Yama-
Iriomoteolide-1a and 1b, two novel 20-membered macro-
lactones bearing almost the same carbon skeleton and chiral cen-
ters, were isolated from a benthic dinoflagellate Amphidinium
species, respectively, in 2007 by Tsuda and co-workers.1 The major
difference between these two analogues is that iriomoteolide-1a
(1) was featured a terminal double bond, which was isomerized
to the Z-internal alkene and herein a stable enone was formed in-
stead of hemiketal in iriomoteolide-1b (2).1b Iriomoteolide-1a ex-
hibits significant cytotoxicity against EpsteineBarr virus (EBV)-
infected human B lymphocyte Raji cells (IC50: 3 ng/mL) and human
B lymphocyte DG-75 cells (IC50: 2 ng/mL),1a which was more potent
guchi esterification as the key steps.3c Besides the synthesis of the
proposed structures, a (2E)-diastereomer of iriomoteolide-1a was
also described by Yang and co-workers.4 But unfortunately, none of
their final products were matched with the naturally occurring
iromoteolide-1a and iromoteolide-1b by comparison of their NMR
spectral data.3,4 In our efforts directed toward the total synthesis of
these macrolides, we have previously presented an efficient route
to the synthesis of the C15eC16 E-olefin moiety via
a JuliaeKocienski olefination.5 Herein, we would like to disclose
a concise, convergent and executable approach for preparing the
proposed structure of iriomoteolide-1b featured by the allylation
between allyl stannane and aldehyde promoted by both ytterbium
triflate and carboxylic acid, and Yamaguchi esterification accom-
panying with an unexpected double bond migration (Fig. 1).
than iriomoteolide-1b against DG-75 cells (IC50: 0.9
m
g/mL).1b
Considering their similar structure and distinct cytotoxicity,
iriomoteolide-1a and 1b have became attractive target moleculars
of many organic chemists.2ꢀ4 Horne and co-workers firstly ac-
complished the proposed structure of iriomoteolide-1a (1)
employing a Yamaguchi esterification and ring-closing metathesis
(RCM) reaction.3a Meanwhile, Xu and Ye group reported the syn-
thesis of the macrolactone core using Hoveyda-Grubbs’ second
generation catalyst to provide the product with sole E-configura-
tion at C15]C16.3b Then Ghosh and Yuan fulfilled the syntheses of
2. Results and discussion
We have previously reported the synthesis ofaldehyde 12 through
stereoselective reduction of the double bond in 8 with the NaBH4/
NiCl2$6H2O system to give the product in moderate selectivity
(dr>5:1).5 However, a more efficient and stereoselective protocol to
obtain saturated aldehyde 12 is still required and will be intriguing to
synthetic chemists. Inspired by the organocatalytic transfer hydro-
genation developed by Macmillan and List,6
was firstly reduced with diisobutylaluminumhydride (DIBAL-H)
a,b-unsaturated ester 8
* Corresponding author. Tel.: þ86 21 54925182; fax: þ86 21 64166128; e-mail
address: zhaog@mail.sioc.ac.cn (G. Zhao).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.06.025

5980
Z. Ye et al. / Tetrahedron 67 (2011) 5979e5989
Allylation
12
OH
23
OH
15
16
4
19
O
OTBS
SnBu3
OH
O
O
9
Esterification
H
6
5
2
7
OH
RCM
iriomoteolide-1a (1)
(proposed structure)
OTBDPS
OH
H
MOMO
O
Allylation
4
OH
OH
15
12
16
19
O
23
Esterification
O
OH
O
O
9
HO
6
2
4
OH
OTBS
7
6
RCM
iriomoteolide-1b (2)
(proposed structure)
Fig. 1. Retroanalysis of the proposed iriomoteolide-1a (1) and 1b (2).
followed by Swern oxidation to give enal 9, in which the double bond
was successfully hydrogenated by the ethyl Hantzsch ester 11 in the
presence of imidazolidinone catalyst 10. As expected, the desired al-
dehyde 12 could be obtained in 94% yield and with high selectivity
(dr>20:1). With the chiral aldehyde 12 in hand, the further synthesis
of fragment 4 was outlined in Scheme 1. Asymmetric Roush crotyla-
tion of the aldehyde 12 using the chiral trans-crotylboronate 13 pro-
ceededsmoothly to providethe corresponding alcohol 14 in95% yield
with good diastereoselectivity (dr>10:1).5,7 Protection of hydroxyl
group as a MOM ether followed by hydroborationeoxidation led to
the primary alcohol 15 in 78% yield. Subsequently, conversion of 15 to
Kocienski-type sulfone 16 was carried out smoothly by a two-step
sequence including a Mitsunobu reaction8 and an oxidation using
ammonium molybdate and hydrogenperoxide. Then JuliaeKocienski
olefinaton was carried out between sulfone 16 and the pre-prepared
aldehyde 175 affording the desired E-isomer 18 almost exclusively
(dr>20:1) in 91% yield. The high selectivity for E-olefin could be as-
cribed to the steric hindrance from the adjacent protected tertiary
alcohol.9 Next, a primary TBS group in 18 was selectively removed in
the presence of HF$Py and pyridine. Subsequent oxidation of the
resulting alcohol using DMP10 as an oxidant and removal of a tertiary
alcohol TBS group with TBAF at room temperature in 10e15 min
affordedaldehyde4in60%yieldoverthethreestepsfrom18. Itshould
benotedthatTBS groupon the tertiaryalcoholof4 wasdetrimentalto
the following allylation of the aldehyde due to the large steric hin-
drance, so it was favored to be removed before an allylation.
The synthesis of allyl stannane 5 (Scheme 2) commenced with
the known chiral ethyl (R)-(þ)-4-chloro-3-hydroxybutyrate 19,
OTBDPS
OTBDPS
OTBDPS
OTBDPS
c
ref.5
a, b
d
O
O
OHC
EtO2C
9
12
8
7
N
OTBDPS
N
OTBDPS
OTBDPS
OTBDPS
e, f
N
g, h
N
S
HO
O
OH
Ph
O
MOMO
MOMO
15
16
14
OTBDPS
TBSO
TBSO
OH
OTBS
j, k, l
i
H
TBSO
H
O
MOMO
MOMO
O
4
18
17
O
EtO2C
CO2Et
CO2iPr
CO2iPr
O
O
N
Bn
B
N
H
N
H
t-Bu
13
10
(R, R)-
11
Scheme 1. Reagents and conditions: (a) DIBAL-H, CH2Cl2, ꢀ78 ꢁC, 97%; (b) (COCl)2, DMSO, Et3N, CH2Cl2, ꢀ78 ꢁC, 92%; (c) 10 (20 mol %), 11 (1.5 equiv), TFA (20 mol %), CHCl3, ꢀ30 ꢁC,
94%, dr>20:1; (d) (R,R)-13, 4 A MS, toluene, ꢀ78 ꢁC, 95%; (e) DIPEA, MOMCl, TBAI, CH2Cl2, 40 ꢁC, 98%; (f) BH3$SMe2, THF, rt; then EtOH, 2.5 M NaOH, 30% H2O2, rt, 80%; (g) PTSH,
ꢀ
DIAD, PPh3, THF, rt, 96%; (h) (NH4)6Mo7O24$4H2O, 30% H2O2, EtOH, rt, 92%; (i) 16, LiHMDS, DMF/HMPA, ꢀ40 ꢁC, 10 min; then 17, ꢀ40 ꢁC to rt, 91%; (j) HF$Py, Py, THF, rt, 80%; (k) DMP,
NaHCO3, CH2Cl2, 90%; (l) TBAF, THF, rt, 50e84%. PTSH¼1-phenyl-1H-tetrazole-5-thiol, DMP¼DesseMartin periodinane.

Z. Ye et al. / Tetrahedron 67 (2011) 5979e5989
5981
OTBS
OTBS
OH
g, h
d, e, f
a, b, c
Cl
NC
Cl
CO2Et
OTs
OTs
19
20
21
OTBS
OTBS
OTBS
j, k
i
SnBu3
Br
OTs
5
22
23
Scheme 2. Reagents and conditions: (a) imidazole, DMAP, TBSCl, CH2Cl2, rt, 83%; (b) Ti(Oi-Pr)4, EtMgBr, Et2O, 94%; (c) imidazole, DMAP, TsCl, CH2Cl2, reflux, 95%; (d) TBAF, THF, rt,
80%; (e) NaCN, LiClO4, CH3CN, 70e75 ꢁC, 93%; (f) imidazole, DMAP, TBSCl, CH2Cl2, 40 ꢁC, 89%; (g) DIBAL-H, CH2Cl2, ꢀ78 ꢁC, 74%; (h) Ph3PþCH3Brꢀ, NaHMDS, THF, 0 ꢁC, 98%; (i)
MgBr2$Et2O, CH2Cl2, reflux, 1 h, 88%; (j) NaI, acetone, rt, 90%; (k) Bu3SnSnBu3, Pd2dba3 (5 mol %), THF, 55 ꢁC, 3 h, 100% conversion. NaHMDS¼sodium bis(trimethylsilyl)amide,
Pd2dba3¼tris(dibenzylideneacetone)dipalladium(0).
which was firstly transformed to TBS ether under basic conditions.
Then according to the method developed by Kulinkovich and
Meijere,11 1-substituted cyclopropanol was obtained followed by
treating with tosyl chloride to provide 20 in 89% yield over the two
steps. A TBAF promoted deprotectioneepoxidation gave the epox-
ide in 80% yield, which initially was supposed to be opened through
a copper-catalyzed addition of ethylmagnesium bromide to the
epoxy. However, no desired product was obtained with several
copper salts evaluated.12a Another method using NaCN as the nu-
cleophile in the presence of LiClO4 was herein introduced. Grati-
fyingly, it proceeded successfully followed by protection of the
resulting alcohol with TBSCl providing cyanide 21 in 83% yield over
the two steps.12b Reduction of cyanide 21 with DIBAL-H and sub-
sequent undergoing Wittig methylenation using Ph3PþCH3Brꢀ
provided an olefin 22 in 76% yield in two steps. Displacement of the
sulfonate group with bromide accompanying with a cyclopropyl-
allyl rearrangement of 22 took place efficiently to afford an allyl
bromide 23 in 88% yield,13 which was finally transformed to the
allyl stannane 5 through cross-coupling of the corresponding allyl
alcohol (not shown) in 91% yield with excellent diastereoselectivity
(dr>19:1), which was converted to the -unsaturated lactone 26
a,b
via acylation and subsequent ring-closing metathesis in 79% yield
over the three steps.15 The C3 methyl group in lactone 27 was then
introduced through 1,4-addition of Me2CuLi and PhSeCl mediated
dehydrogenation in 72% yield.16 After reductively opening of lac-
tone 27 under Luche’s conditions,17 the primary alcohol of the
resulted diol was selectively protected as a trityl ether and then
treated with TBAF to remove TBDPS group providing the novel diol
28 in 73% yield over three steps. Diol 28 was converted to the
corresponding olefin 30 in 88% yield in a four-step consequence
involving tosylation of the primary alcohol, formation of TBS silyl
ether, Finkelstein-type iodination and t-BuOK mediated
b-elimi-
nation.18 Acid 6 was finally obtained through trityl removal of 30,19
oxidation of the allyl alcohol with DMP, and further oxidation of the
resulting aldehyde with sodium chlorite in 74% yield over the three
steps.
With all the building blocks in hand, development of a reliable
assembly process became the next goal. The completion of the
synthesis of the proposed structure of iriomoteolide-1b (2) was
shown in Scheme 4. Since the Barbier reaction between the allyl
bromide 23 and aldehyde 4 has been proved to be fruitless, a careful
survey of the conditions for the crucial coupling reaction between
allyl stannane 5 and aldehyde 4 was carried out. It was found that
the allylation did not proceed in the presence of ytterbium triflate
iodide with bis(tributyltin) using
a
catalytic amount of
Pd2dba3$CHCl3 (5 mol %). Due to the easy decomposition in the
silica gel column, the allyl stannane 5 was used as the crude
product for the following allylation without further purification.14
Synthesis of the last fragment (Z)-diene acid 6 was depicted in
Scheme 3. Asymmetric crotylation of the aldehyde 24 produced
O
O
O
O
a, b, c
d, e
TBDPSO
TBDPSO
TBDPSO
f, g, h
O
24
26
27
OTr
OTr
OTr
i, j
k, l
HO
TsO
OTBS
OH
OTBS
29
30
28
O
OH
CO2iPr
CO2iPr
m, n, o
O
B
O
OTBS
6
25
(S, S)-
Scheme 3. Reagents and conditions: (a) (S,S)-25, 4 A MS, toluene, ꢀ78 ꢁC, 91%; (b) Acryloyl chloride, Et3N, DMAP, CH2Cl2, rt, 95%; (c) Grubbs Cat. second (5 mol %), CH2Cl2, reflux,
91%; (d) (CH3)2CuLi, Et2O, ꢀ20 ꢁC to 0 ꢁC, 85%; (e) LDA, TMSCl, PhSeCl, THF, ꢀ78 ꢁC, 3 h; then NaHCO3, 30% H2O2, THF/EtOAc (v/v, 1:2), 3 h, 85%; (f) NaBH4, CeCl3$7H2O, MeOH, 0 ꢁC to
rt, overnight, 54% (81% br s, m); (g) TrCl, imidazole, DMAP, CH2Cl2, 0 ꢁC to rt, 90%; (h) TBAF, THF, rt, 100%; (i) TsCl, Et3N, DMAP, CH2Cl2, 99%; (j) TBSOTf, 2,6-lutidine, CH2Cl2, 0 ꢁC, 95%;
(k) NaI, acetone, rt, 97%; (l) t-BuOK, THF, 0 ꢁC to rt, 97%; (m) 1.0 M HCl (saturated with NaCl), CHCl3, rt, 2 days, 86%; (n) DMP, NaHCO3, CH2Cl2, rt, 93%; (o) NaClO2, Na2HPO4, 2-methyl-
2-butene, t-BuOH/H2O, 0 ꢁC, 40 min, 92%.
ꢀ

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Z. Ye et al. / Tetrahedron 67 (2011) 5979e5989
OTBDPS
OH
OTBDPS
OH
a
b, c
4
+
5
MOMO
OH
OH
O
TBSO
TBSO
32
31
OTBDPS
OH
OTBDPS
OH
d
O
O
O
OTBS
O
O
O
6
+
32
+
TBSO
2.5-3.0 : 1
OTBS
33
OTBS
33'
OH
OH
OH
OH
f
e
O
O
O
O
O
O
HO
HO
OH
OH
34
2
Scheme 4. Reagents and conditions: (a) Yb(OTf)3 (20 mol %), p-NO2PhCO2H (2 equiv), THF, rt, 91%; (b) IBX, DMSO, rt, 90%; (c) B-Bromocatecholborane, CH2Cl2, ꢀ78 ꢁC, 10e15 min,
78%; (d) 6, 2,4,6-Cl3C6H2COCl, Et3N, 0 ꢁC to rt, 2 h; then 32, DMAP, toluene, 0 ꢁC to rt, 23 h, 90%; (e) HF$Py, THF, rt, 6 days, 60e70%; (f) Grubbs Cat. second (5 mol %), CH2Cl2, rt,
overnight, 90%. IBX¼2-iodoxybenzoicacid.
or carboxylic acid,20b respectively, and aldehyde 4 was prone to
decomposing under above conditions. However, by the combina-
tion of ytterbium triflate and carboxylic acid in the reaction, the
allylation proceeded smoothly at room temperature to give 31 as
a pair of diastereoisomers up to 91% yield.20a although 20 mol % of
ytterbium triflate was required. Critical to our success was the
development of this mild and convergent method for the allylation
toward the total synthesis of iriomoteolide-1a in order to correct
the proposed structure are currently ongoing in our laboratory.
4. Experimental section
4.1. General
of allyl stannane 5 with aldehyde 4 with tertiary alcohol at the a-
All reactions were conducted under Ar atmosphere unless
stated otherwise and monitored by TLC on precoated silica gel
HSGF254 plates (Yantai Chemical Co., Ltd). Column chromatogra-
phy was performed on silica gel 300e400 mesh (Yantai Chemical
Co., Ltd) and eluted with hexanes and diethyl ether or ethyl acetate
mixtures. All solvents were refluxed and distilled from sodium
benzophenone ketyl (THF, Et2O, toluene) or CaH2 (CH2Cl2, DMF,
DMSO). The NMR spectra (1H: 400 MHz, 13C: 100 MHz) are reported
position of the carbonyl group. Oxidation of 31 using IBX and
subsequent removal of MOM group with B-Bromocatecholborane
at ꢀ78 ꢁC delivered the key intermediate 32 in 70% yield over the
two steps. Next, Yamaguchi esterification was employed to com-
bination of the key intermediate 32 and acid 6. However, an un-
expected migration of the double bond occurred and we got the
enone products Z-33 and E-330 as mixtures with a ratio of
2.5e3.0:1.21 The Mukaiyama and CoreyeNicolaou esterification
conditions were also investigated to avoid the migration of the
double bond but both proved to be unsuccessful.22 Ultimately, after
in
d units (parts per million) and J values (hertz) with Me4Si as the
internal standard. Infrared (IR) spectra are reported in wave num-
bers (cmꢀ1). Optical rotations are reported in units of
global deprotection of
a,b-unsaturated ketone 33 with excess
10ꢀ1 deg cm3 gꢀ1
.
HF$Py (200 equiv) at room temperature for about 6 days, the
macrolide 2 was assembled by the RCM reaction using 5 mol %
Grubbs’s second generation catalyst at room temperature with E-
isomer as a sole product23 in 63% yield over the two steps. However,
the spectral data of synthetic iriomoteolide-1b (2) did not match
with that reported for natural iriomoteolide-1b.1b That the major
difference of 1H and 13C shifts at C4 (3.80 ppm and 40.5 ppm for
synthetic iriomoteolide-1b compared to 2.62 ppm and 48.7 ppm for
the natural product), along with many other minor inconsistencies
throughout the spectra, suggests that the structure of natural
iriomoteolide-1b has been assigned incorrectly.24
4.2. (S,E)-4-((tert-Butyldiphenylsilyl)oxy)-3-methylpent-2-
enal (9)
To a solution of a,b-unsaturated ester 8 (1.68 g, 4.24 mmol) in
CH2Cl2 (20 mL) was added DIBAL-H (1.0 M in toluene, 10.6 mL,
10.6 mmol) at ꢀ78 ꢁC. The reaction mixture was stirred at ꢀ78 ꢁC
for 1 h before it was quenched by aqueous Rochelle salt solution
and stirred at room temperature for 2 h. The layers were separated
and the aqueous layer was extracted with CH2Cl2. The combined
organic layers were washed with brine, dried over Na2SO4, filtered,
and concentrated. Purification on silica gel (EtOAc/hexanes 1:20)
3. Conclusion
provided allyl alcohol (1.46 g, 97%) as a colorless oil.
25
In summary, we have presented herein a concise, efficient, and
highly stereoselective total synthesis of the proposed structure of
iriomoteolide-1b (2). The macrolide 2 was synthesized successfully
in 19 steps from the known methyl ketone 7 with 10.2% overall
yield. This convergent route was featured an organocatalytic
enantioselective transfer hydrogenation, ytterbium triflate and
carboxylic acid promoted allylation between allyl stannane and
[
a
]
D
ꢀ13.3 (c 3.45, CHCl3); IR (film): 3375, 3071, 2931, 2890,
2858, 1589, 1367, 1188, 838, 740 cmꢀ1
7.70e7.65 (m, 4H), 7.46e7.34 (m, 6H), 5.33 (t, J¼6.8 Hz, 1H), 4.22
(t, J¼6.3 Hz, 1H), 4.07e3.98 (m, 2H), 1.64 (s, 3H), 1.19 (d, J¼6.5 Hz,
3H), 1.09 (s, 9H); 13C NMR (100 MHz, CDCl3)
142.0, 136.0, 135.9,
134.5, 134.4, 129.6, 129.6, 127.5, 127.4, 123.1, 74.3, 59.1, 27.0, 23.0,
19.2, 11.5; MS (ESI): m/z 377.2, [MþNa]þ; HRMS (MALDI) calcd for
C22H30O2SiNaþ [MþNa]þ: 377.1907, found: 377.1921.
;
1H NMR (400 MHz, CDCl3)
d
d
aldehyde with tertiary alcohol at the a-position. Efforts directed

Z. Ye et al. / Tetrahedron 67 (2011) 5979e5989
5983
To a cooled (ꢀ78 ꢁC) flask containing 10 mL of CH2Cl2 was added
oxallylchloride (0.70 mL, 8.21 mmol) under argon, followed by
dropwise addition of DMSO (1.17 mL, 16.4 mmol) dissolved in 5 mL
of CH2Cl2. After 15 min, the above allyl alcohol dissolved in 5 mL of
CH2Cl2 was added to the reaction solution at ꢀ78 ꢁC. After 1 h, Et3N
(9.8 mL, 70.1 mmol) was added, and the reaction vessel was
maintained at ꢀ78 ꢁC for 20 min before the cooling bath was re-
moved. After the reaction had warmed to room temperature for
20 min, aq NaHCO3 was added and the layers were separated. The
aqueous layer was extracted with CH2Cl2 and the combined organic
layers were washed with brine, dried over Na2SO4. After filtration,
the organic phase was concentrated and purified by flash chro-
matography (Et2O/hexanes 1:20) to afford enal 9 (1.34 g, 92%) as
13C NMR (100 MHz, CDCl3)
d
140.3, 136.0, 136.0, 135.9, 134.8, 134.1,
129.6, 129.5, 127.6, 127.4, 115.9, 73.3, 72.5, 44.2, 37.1, 36.8, 27.1, 19.3,
19.1, 16.6, 16.4; MS (ESI): m/z 411.0, [MþH]þ; HRMS (MALDI) calcd
for C26H38O2SiNaþ [MþNa]þ: 433.2544, found: 433.2533.
4.5. (3S,4R,6S,7S)-7-((tert-Butyldiphenylsilyl)oxy)-4-
(methoxymethoxy)-3,6-di methyloctan-1-ol (15)
To a solution of the above alcohol 14 (808 mg, 1.97 mmol) and
TBAI (363 mg, 0.984 mmol) in CH2Cl2 (12 mL) was added DIPEA
(2.74 mL, 15.73 mmol) and the mixture was cooled to 0 ꢁC. MOMCl
(0.60 mL, 7.87 mmol) was added dropwise, and the mixture was
warmed to 40 ꢁC and stirred for 24 h. The reaction was quenched by
satd NaHCO3, extracted with CH2Cl2 and washed with brine. The
combined organic layers were dried over Na2SO4 and concentrated
under reduced pressure. The residue was purified by flash chro-
matography (Et2O/hexanes 1:40) to afford MOM ether (880 mg,
a colorless oil.
25
[
a]
ꢀ41.6 (c 1.55, CHCl3); IR (film): 3071, 2931, 2893, 2858,
D
1679, 1472, 1428, 1112, 822, 740 cmꢀ1 1H NMR (400 MHz, CDCl3)
;
d
9.97 (d, J¼8.1 Hz, 1H), 7.68e7.66 (m, 2H), 7.60e7.59 (m, 2H),
7.47e7.33 (m, 6H), 6.02 (d, J¼8.0 Hz, 1H), 4.24 (t, J¼6.5 Hz, 1H), 2.01
98%) as a colorless oil.
24
(s, 3H),1.19 (d, J¼6.5 Hz, 3H),1.08 (s, 9H); 13C NMR (100 MHz, CDCl3)
[a
]
ꢀ20.7 (c 1.50, CHCl3); IR (film): 3071, 2930, 2822, 1462,
D
d
191.6, 165.2, 135.8, 135.8, 133.8, 133.3, 129.9, 129.9, 127.7, 125.0,
1428, 1379, 1104, 1038, 955, 822, 739 cmꢀ1
;
1H NMR (400 MHz,
73.4, 27.0, 22.8, 19.2, 13.4; MS (ESI): m/z 375.2, [MþNa]þ; HRMS
CDCl3) 7.70e7.67 (m, 4H), 7.43e7.35 (m, 6H), 5.86e5.69 (m, 1H),
d
(ESI) calcd for C22H28O2SiNaþ [MþNa]þ: 375.1751, found: 375.1751.
5.04e4.99 (m, 2H), 4.59 (s, 2H), 3.84e3.78 (m, 1H), 3.49e3.44 (m,
1H), 3.34 (s, 3H), 2.42e2.37 (m, 1H), 1.77e1.71 (m, 1H), 1.64e1.58
(m, 1H), 1.37e1.33 (m, 1H), 1.05 (s, 9H), 1.04 (d, J¼7.7 Hz, 3H), 0.94
(d, J¼6.3 Hz, 3H), 0.91 (d, J¼7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3)
4.3. (3S,4S)-4-((tert-Butyldiphenylsilyl)oxy)-3-methylpenta-
nal (12)
d
140.2, 136.0, 136.0, 135.1, 134.3, 129.5, 129.4, 127.5, 127.3, 115.0,
A colorless solution of enal 9 (905 mg, 2.57 mmol) dissolved in
10 mL of chloroform was cooled to ꢀ30 ꢁC. To this solution was
96.1, 80.5, 72.5, 55.7, 40.9, 37.0, 33.8, 27.1, 20.0, 19.4, 15.4, 15.3; MS
(ESI): m/z 477.3, [MþNa]þ; HRMS (ESI) calcd for C28H42O3SiNaþ
[MþNa]þ: 477.2795, found: 477.2782.
added
(2R,5R)-5-benzyl-2-(tert-butyl)-3-methylimidazolidin-4-
one 10 (126 mg, 0.51 mmol), the ethyl Hantzsch ester 11 (975 mg,
3.85 mmol) and trifluoroacetic acid (58 mg, 0.51 mmol). The
resulting yellow suspension was stirred at ꢀ30 ꢁC for 3 days. The
reaction mixture was then diluted with Et2O and passed though
a short pad of silica gel. The solution was concentrated and purified
by flash chromatography (Et2O/hexanes 1:20) to afford aldehyde 12
(856 mg, 94%) as a colorless oil.
A solution of borane-dimethyl sulfide (2.0 M solution in THF,
3.52 mL, 7.04 mmol) was added to a solution of the above MOM
ether (200 mg, 0.38 mmol) in dry THF (15 mL) at 0 ꢁC. After being
warmed to room temperature and stirred for 6 h, the mixture was
again cooled to 0 ꢁC and carefully quenched by successively addi-
tion of EtOH (2 mL), aq NaOH (2 mL, 2.5 M), and 30% H2O2 (2 mL).
The mixture was stirred for 2 h at room temperature. The aqueous
phase was extracted with EtOAc, and the combined organic phases
were washed with brine, dried over Na2SO4 and concentrated un-
der reduced pressure. The residue was purified by flash chroma-
tography (EtOAc/hexanes 1:10) to afford alcohol 15 (665 mg, 80%)
[
a]
28 þ3.6 (c 1.25, CHCl3); IR (film): 3071, 3049, 2961, 2931, 2889,
D
2858, 2715, 1726, 1587, 1472, 1427, 1382, 1110, 1043, 822, 740,
703 cmꢀ1
;
1H NMR (400 MHz, CDCl3)
d
9.72(t, J¼2.2 Hz, 1H),
7.68e7.66 (m, 4H), 7.45e7.36 (m, 6H), 3.86e3.81 (m, 1H), 2.71e2.64
(m, 1H), 2.25e2.18 (m, 2H), 1.06 (s, 9H), 0.96 (d, J¼6.3 Hz, 3H), 0.85
as a colorless oil.
27
(d, J¼6.6 Hz, 3H); 13C NMR (100 MHz, CDCl3)
d
202.8, 135.9, 135.9,
[a
]
ꢀ19.1 (c 2.55, CHCl3); IR (film): 3446, 3065, 2936, 2887,
D
134.5, 134.0, 129.7, 129.6, 127.7, 127.5, 72.2, 46.3, 35.0, 27.1, 19.3, 18.5,
15.7; MS (ESI): m/z 409.2, [MþMeOHþNa]þ; HRMS (ESI) calcd for
C22H30O2SiNaþ [MþNa]þ: 377.1904, found: 377.1907.
1464, 1430, 1379, 1105, 1040, 954, 822, 741 cmꢀ1
;
1H NMR
(400 MHz, CDCl3) 7.71e7.67 (m, 4H), 7.43e7.35 (m, 6H), 4.59 (s,
d
2H), 3.87e3.83 (m, 1H), 3.69e3.63 (m, 1H), 3.57e3.51 (m, 1H),
3.46e3.42 (m, 1H), 3.35 (s, 3H), 1.86e1.76 (m, 2H), 1.59e1.33 (m,
5H), 1.07 (s, 9H), 0.98 (d, J¼6.3 Hz, 3H), 0.95 (d, J¼6.8 Hz, 3H), 0.90
4.4. (3S,4R,6S,7S)-7-((tert-Butyldiphenylsilyl)oxy)-3,6-
dimethyloct-1-en-4-ol (14)5
(d, J¼7.0 Hz, 3H); 13C NMR (100 MHz, CDCl3)
d 136.0, 135.9, 134.9,
134.4, 129.6, 129.5, 127.6, 127.4, 96.0, 81.1, 72.6, 60.5, 55.7, 37.2, 34.3,
33.1, 32.6, 27.1, 19.7, 19.4, 15.5, 15.4; MS (ESI): m/z 495.3, [MþNa]þ;
HRMS (ESI) calcd for C28H44O4SiNaþ [MþNa]þ: 495.2901, found:
495.2888.
A solution of aldehyde 12 (1.23 g, 3.47 mmol) in toluene (5 mL)
was added dropwise to a mixture of crotylboronate (R,R)-13
(0.80 M stock solution in toluene, 6.5 mL, 5.20 mmol) and pow-
ꢁ
ꢀ
dered activated 4 A MS (600 mg) in toluene (25 mL) at ꢀ78 C. After
3 h at ꢀ78 ꢁC, the reaction mixture was quenched by satd K2CO3
solution and stirred at room temperature for 2 h. The layers were
separated and the aqueous phase was extracted with EtOAc and
washed with brine. The combined organic extracts were dried over
Na2SO4, filtered, and concentrated under reduced pressure. The
residue was purified by flash chromatography (Et2O/hexanes 1:20)
4.6. Sulfone 16
Triphenylphosphine (272 mg, 1.04 mmol), 1-phenyl-1H-tetra-
zole-5-thiol (PTSH, 185 mg, 1.04 mmol) and 15 (245 mg,
0.518 mmol) were dissolved in 6 mL of THF, to which was added
DIAD (0.20 mL, 1.04 mmol) at 0 ꢁC. After stirring at room temper-
ature for 19 h, the reaction was diluted by the addition of brine and
extracted with EtOAc. The combined organic layers were dried over
Na2SO4, filtered, and concentrated. Purification on silica gel (Et2O/
to afford 1.35 g (95%) of 14 as a colorless oil.
29
[
a]
ꢀ8.1 (c 1.50, CHCl3); IR (film): 3405, 3070, 2957, 2926,
D
2855, 1462, 1419, 1371, 1110, 1026, 958, 821, 739 cmꢀ1
;
1H NMR
(400 MHz, CDCl3) 7.70e7.67 (m, 4H), 7.44e7.37 (m, 6H), 5.82e5.73
d
hexanes 1:10) provided sulfide (316 mg, 96%) as a colorless oil.
29
(m, 1H), 5.11e5.06 (m, 2H), 3.90e3.84 (m, 1H), 3.50 (m, 1H),
2.20e2.12 (m,1H),1.87e1.74 (m, 2H),1.39e1.07 (m, 2H),1.07 (s, 9H),
1.02 (d, J¼6.8 Hz, 3H), 0.95 (d, J¼6.3 Hz, 3H), 0.89 (d, J¼6.8 Hz, 3H);
[a
]
ꢀ29.6 (c 2.15, CHCl3); IR (film): 3070, 2962, 2931, 2857,
D
1597, 1500, 1462, 1427, 1385, 1108, 1038, 955, 822, 761 cmꢀ1
;
1H
NMR (400 MHz, CDCl3) 7.66e7.65 (m, 4H), 7.57e7.53 (m, 5H),
d

5984
Z. Ye et al. / Tetrahedron 67 (2011) 5979e5989
25
7.42e7.31 (m, 6H), 4.54 (s, 2H), 3.84e3.79 (m, 1H), 3.55e3.48 (m,
1H), 3.41e3.37 (m, 1H), 3.28 (s, 3H), 3.27e3.23 (m, 1H), 1.85e1.78
(m, 2H), 1.73e1.67 (m, 1H), 1.64e1.56 (m, 3H), 1.02 (s, 9H), 0.99 (d,
J¼6.8 Hz, 3H), 0.95 (d, J¼6.3 Hz, 3H), 0.90 (d, J¼6.7 Hz, 3H); 13C NMR
[
a
]
D
ꢀ2.64 (c 1.35, CHCl3); IR (film): 3489, 3074, 2956, 2931,
2857, 1472, 1379, 1253, 1105, 1038, 836, 775 cmꢀ1
(400 MHz, CDCl3) 7.69e7.66 (m, 4H), 7.43e7.33 (m, 6H),
;
1H NMR
d
5.60e5.53 (m, 1H), 5.45 (d, J¼15.8 Hz, 1H), 4.56 (s, 2H), 3.84e3.79
(m, 1H), 3.43e3.39 (m, 1H), 3.33 (s, 3H), 3.29e3.25 (m, 1H),
2.13e2.09 (m, 1H), 2.03e2.00 (m, 1H), 1.83e1.72 (m, 3H), 1.60e1.57
(m, 1H), 1.30e1.26 (m, 1H), 1.28 (s, 3H), 1.05 (s, 9H), 0.95 (d,
J¼6.3 Hz, 3H), 0.93e0.89 (m, 15H), 0.10 (s, 3H), 0.08 (s, 3H); 13C
(100 MHz, CDCl3)
d 154.4, 136.0, 135.9, 134.9, 134.3, 133.8, 130.0,
129.8, 129.6, 129.5, 127.6, 127.4, 123.9, 96.1, 80.9, 72.4, 55.7, 37.3,
35.5, 33.1, 31.8, 31.1, 27.1, 19.8, 19.4, 15.4, 15.0; MS (ESI): m/z 655.3,
[MþNa]þ; HRMS (ESI) calcd for C35H48O3N4SSiNaþ [MþNa]þ:
655.3109, found: 655.3109.
NMR (100 MHz, CDCl3)
d 136.0, 135.9, 135.5, 135.0, 134.3, 129.6,
To a solution of the above sulfide (520 mg, 0.822 mmol) in EtOH
(15 mL) was added mixed 30% aq H2O2 (0.93 mL, 8.22 mmol) and
ammonium molybdate (206 mg, 0.164 mmol) at room temperature.
The mixture was stirred for 24 h and diluted by the addition of
brine. The combined organic layers were extracted with EtOAc,
dried over Na2SO4, filtered, and concentrated. Purification on silica
gel (EtOAc/hexanes 1:10) provided sulfone 16 (500 mg, 92%) as
129.6, 129.5, 127.6, 127.4, 95.9, 81.0, 75.8, 72.6, 71.4, 65.9, 55.7, 37.3,
36.3, 34.8, 33.0, 27.1, 25.9, 23.8, 19.7, 19.4, 18.2, 15.5, 15.3, ꢀ2.2; MS
(ESI): m/z 679.5, [MþNa]þ; HRMS (ESI) calcd for C38H64O5Si2Naþ
[MþNa]þ: 679.4185, found: 679.4172.
To a solution of the above alcohol (250 mg, 0.380 mmol) in
CH2Cl2 (10 mL) was added DMP (323 mg, 0.761 mmol) and NaHCO3
(128 mg, 1.52 mmol). The reaction was stirred at room temperature
for 1 h before it was quenched with satd NaHCO3 and satd Na2S2O3.
The mixture was extracted with CH2Cl2, washed with brine, dried
over Na2SO4, concentrated and purified by flash chromatography
(Et2O/hexanes 1:20e1:10) to afford aldehyde (225 mg, 90%) as
a colorless oil.
27
[a
]
ꢀ25.3 (c 2.10, CHCl3); IR (film): 3071, 2960, 2931, 2858,
D
1594, 1498, 1463, 1428, 1342, 1107, 1037, 956, 822, 762 cmꢀ1
;
1H
NMR (400 MHz, CDCl3) 7.70e7.59 (m, 9H), 7.43e7.34 (m, 6H), 4.49
d
(dd, J¼16.1, 6.8 Hz, 2H), 3.90e3.80 (m, 2H), 3.68e3.60 (m, 1H),
3.39e3.35 (m, 1H), 3.31 (s, 3H), 2.05e1.98 (m, 1H), 1.86e1.79 (m,
2H), 1.71e1.65 (m, 1H), 1.57e1.53 (m, 1H), 1.38e1.32 (m, 1H), 1.03 (s,
9H), 0.99 (d, J¼7.3 Hz, 3H), 0.97 (d, J¼6.7 Hz, 3H), 0.91 (d, J¼6.7 Hz,
a colorless oil.
25
[
a
]
D
ꢀ16.2 (c 1.20, CHCl3); IR (film): 3074, 2958, 2931, 2857,
1676, 1472, 1379, 1254, 1105, 1037, 837, 739 cmꢀ1
;
1H NMR
(400 MHz, CDCl3) 9.33 (s, 1H), 7.68e7.65 (m, 4H), 7.44e7.34 (m,
d
3H); 13C NMR (100 MHz, CDCl3)
d
153.5, 136.0, 135.9, 134.9, 134.2,
6H), 5.77e5.70 (m, 1H), 5.24 (d, J¼15.3 Hz, 1H), 4.56 (s, 2H),
3.83e3.78 (m, 1H), 3.41e3.37 (m, 1H), 3.33 (s, 3H), 2.14e2.10 (m,
1H),1.83e1.70 (m, 3H),1.58e1.54 (m, 1H),1.38 (s, 3H),1.32e1.26 (m,
1H), 1.05 (s, 9H), 0.95 (d, J¼6.3 Hz, 3H), 0.93 (s, 9H), 0.90 (d,
J¼7.0 Hz, 3H), 0.86 (d, J¼6.8 Hz, 3H), 0.11 (s, 3H), 0.10 (s, 3H); 13C
133.2, 131.4, 129.7, 129.7, 129.5, 127.6, 127.4, 125.1, 96.2, 80.7, 72.4,
55.8, 54.5, 37.1, 35.2, 33.9, 27.1, 23.8, 20.0, 19.3, 15.6, 15.2; MS (ESI):
m/z 687.3, [MþNa]þ; HRMS (MALDI) calcd for C35H48N4O5SSiNaþ
[MþNa]þ: 687.3007, found: 687.3000.
NMR (100 MHz, CDCl3)
d 200.5, 136.0, 135.9, 135.0, 134.3, 132.7,
4.7. Olefin 18
131.1, 129.6, 129.5, 127.6, 127.4, 96.0, 80.9, 80.4, 72.5, 55.7, 37.3, 36.2,
34.8, 33.1, 27.1, 25.8, 22.9, 19.7, 19.4, 18.3, 15.4, 15.1, ꢀ2.2, ꢀ2.3; MS
(ESI): m/z 677.4, [MþNa]þ; HRMS (ESI) calcd for C38H62O5Si2Naþ
[MþNa]þ: 677.4028, found: 677.4042.
To a stirred solution of sulfone 16 (490 mg, 0.737 mmol) in 3 mL
of DMF/HMPA (3:1 v/v) was added LiHMDS (1.0 M in THF, 1.11 mL,
1.11 mmol) at ꢀ40 ꢁC. This was stirred for 10 min and followed by
the addition of aldehyde 17 (316 mg, 0.952 mmol) in 1.0 mL of DMF/
HMPA (3:1 v/v) via cannula. The reaction was allowed to warm
slowly to room temperature and stirred for 24 h before it was
quenched by the addition of satd NH4Cl solution. The layers were
separated and the aqueous layer was extracted with EtOAc. The
combined organic layers were washed with brine, dried over
Na2SO4, filtered, and concentrated. Purification on silica gel (hex-
anes) provided 18 (520 mg, 91%) as a colorless oil.
To
a stirred solution of the above aldehyde (196 mg,
0.299 mmol) in THF (5 mL) was added TBAF (1.0 M in THF, 0.36 mL,
0.36 mmol). The reaction was stirred at room temperature for
20 min before it was diluted with brine. The mixture was extracted
with EtOAc, dried over Na2SO4, concentrated and purified by flash
chromatography (EtOAc/hexanes 1:10e1:5) to afford 4 (136 mg,
84%) as a colorless oil.
26
[
a
]
D
ꢀ59.8 (c 1.85, CHCl3); IR (film): 3445, 3065, 2932, 1733,
1462, 1377, 1104, 1039, 821, 741 cmꢀ1
;
1H NMR (400 MHz, CDCl3)
[a
]
29 ꢀ1.2 (c 2.15, CHCl3); IR (film): 3073, 2956, 2927, 2857, 1462,
d 9.37 (s, 1H), 7.69e7.66 (m, 4H), 7.44e7.35 (m, 6H), 5.78e5.70 (m,
D
1378, 1254, 1108, 1039, 835, 775 cmꢀ1
;
1H NMR (400 MHz, CDCl3)
1H), 5.35 (d, J¼15.6 Hz, 1H), 4.56 (s, 2H), 3.87e3.80 (m, 1H),
3.42e3.38 (m, 1H), 3.33 (s, 3H), 3.31e3.27 (m, 1H), 2.18e2.15 (m,
1H), 1.86e1.71 (m, 3H), 1.58 (m, 1H), 1.38 (s, 3H), 1.41e1.33 (m, 1H),
1.06 (s, 9H), 0.96 (d, J¼6.3 Hz, 3H), 0.93 (s, 9H), 0.90 (d, J¼7.1 Hz,
3H), 0.86 (d, J¼6.8 Hz, 3H), 0.11 (s, 3H), 0.10 (s, 3H); 13C NMR
d
7.71e7.68 (m, 4H), 7.45e7.36 (m, 6H), 5.59e5.52 (m, 1H), 5.45 (d,
J¼15.5 Hz, 1H), 4.58 (s, 2H), 3.86e3.81 (m, 1H), 3.42e3.40 (m, 1H),
3.37 (m, 2H), 3.35 (s, 3H), 2.13e2.09 (m, 1H), 1.79e1.73 (m, 3H),
1.62e1.60 (m, 1H), 1.31e1.28 (m, 3H), 1.07 (s, 9H), 0.97 (d, J¼6.3 Hz,
3H), 0.93 (d, J¼6.8 Hz, 3H), 0.89 (m, 21H), 0.09 (s, 6H), 0.08 (s, 3H),
(100 MHz, CDCl3)
d 200.1, 136.0, 135.9, 134.9, 134.3, 133.3, 129.6,
0.05 (s, 3H); 13C NMR (100 MHz, CDCl3)
d
136.8, 136.0, 135.9, 135.1,
129.6, 129.5, 127.6, 127.4, 96.0, 80.9, 78.1, 72.6, 55.7, 37.3, 36.0, 34.7,
32.9, 27.1, 22.6, 19.6, 19.4, 15.5, 15.2; MS (ESI): m/z 563.4, [MþNa]þ;
HRMS (ESI) calcd for C32H48O5SiNaþ [MþNa]þ: 563.3163, found:
563.3144.
134.3, 129.6, 129.4, 127.9, 127.6, 127.4, 95.9, 81.2, 75.7, 72.5, 71.6,
55.6, 37.4, 36.5, 35.0, 33.1, 27.1, 25.9, 24.5, 19.9, 19.4, 18.3, 18.2, 15.5,
14.9, ꢀ2.1, ꢀ5.4; MS (ESI): m/z 793.5, [MþNa]þ; HRMS (ESI) calcd
for C44H79O5Si3þ [MþH]þ: 771.5230, found: 771.5256.
4.8. Aldehyde 4
4.9. (R)-1-(2-((tert-Butyldimethylsilyl)oxy)-3-chloropropyl)
cyclopropyl 4-methyl benzenesulfonate (20)
To a stirred solution of compound 18 (520 mg, 0.674 mmol) in
THF (15 mL) was added pyridine (1.35 mL, 13.5 mmol) and HF$Py
(0.334 mL, 13.5 mmol). The mixture was stirred at room temper-
ature for 3 days before it was quenched with satd NaHCO3. The
reaction mixture was extracted with EtOAc, washed with brine,
dried over Na2SO4, concentrated and purified by flash chroma-
tography (EtOAc/hexanes 1:20) to afford alcohol (354 mg, 80%) as
a colorless oil.
To a solution of compound 13 (1.28 g, 7.68 mmol) in CH2Cl2
(20 mL) was added imidazole (784 mg, 11.52 mmol) and TBSCl
(1.51 g, 9.99 mmol) at 0 ꢁC. The reaction was stirred at room tem-
perature for 15 h before it was quenched with aq NaHCO3. The
mixture was extracted with CH2Cl2, washed with brine, dried over
Na2SO4, concentrated and purified by flash chromatography (Et2O/
hexanes 1:40) to afford TBS ether (2.0 g, 83%) as a colorless oil.

Z. Ye et al. / Tetrahedron 67 (2011) 5979e5989
5985
26
[
a]
þ21.6 (c 1.16, CHCl3); 1H NMR (300 MHz, CDCl3)
[a
]
23 ꢀ1.6 (c 2.40, CHCl3); IR (film): 3527, 3065, 3017, 2927, 2251,
D
D
d
4.34e4.26 (m, 1H), 4.18e4.09 (m, 2H), 3.56e3.49 (m, 2H), 2.65
1598, 1496, 1366, 1158, 1094, 815 cmꢀ1; 1H NMR (400 MHz, CDCl3)
(dd, J¼15.5, 5.0 Hz, 1H), 2.47 (dd, J¼15.2, 7.3 Hz, 1H), 1.24 (t,
d
7.73 (d, J¼8.3 Hz, 2H), 7.33 (d, J¼8.0 Hz, 2H), 4.35 (m, 1H), 3.02 (m,
J¼7.0 Hz, 3H), 0.87 (s, 9H), 0.11 (s, 3H), 0.07 (s, 3H).
1H), 2.60 (dd, J¼16.8, 4.8 Hz, 1H), 2.51 (dd, J¼16.8, 6.0 Hz, 1H), 2.44
(s, 3H), 2.19 (dd, J¼16.1, 5.3 Hz, 1H), 1.84 (dd, J¼15.1, 8.8 Hz, 1H),
1.22e1.15 (m, 1H), 1.10e1.05 (m, 1H), 0.87e0.81 (m, 1H), 0.68e0.62
To a solution of TBS ether (2.10 g, 7.48 mmol) in Et2O (30 mL)
was added Ti(Oi-Pr)4 (1.11 mL, 3.74 mmol) and cooled to 0 ꢁC. A
solution of EtMgBr (3.0 M in Et2O, 7.48 mL, 22.43 mmol) was then
added dropwise over 1 h to the stirred solution. After 1 h at 0 ꢁC, the
reaction mixture was quenched with aq NH4Cl. The organic layer
was extracted with EtOAc, washed with brine, dried over Na2SO4,
concentrated and purified by flash chromatography (Et2O/hexanes
1:10) to afford cyclopropanol (1.86 g, 94%) as a colorless oil.
(m,1H); 13C NMR (100 MHz, CDCl3)
d 145.3,134.6,130.0,127.6,117.5,
65.1, 64.0, 42.7, 25.8, 21.7, 12.0, 11.1; MS (ESI): m/z 318.2, [MþNa]þ;
HRMS (ESI) calcd for C14H17NO4SNaþ [MþNa]þ: 318.0771, found:
318.0781.
To a solution of the above alcohol (720 mg, 2.44 mmol) in CH2Cl2
(15 mL) was added imidazole (332 mg, 4.88 mmol), DMAP (60 mg,
0.488 mmol) and TBSCl (552 mg, 3.66 mmol) at 0 ꢁC. The reaction
was stirred at room temperature for 1 h and then warmed to 40 ꢁC
overnight before it was quenched with aq NaHCO3. The mixture
was extracted with CH2Cl2, washed with brine, dried over Na2SO4,
concentrated and purified by flash chromatography (EtOAc/hex-
[
a]
26 þ7.3 (c 1.37, CHCl3); IR (film): 3439, 3086, 2956, 2930,1472,
D
1257, 1098, 838, 778 cmꢀ1
;
1H NMR (400 MHz, CDCl3)
d
4.25e4.19
(m, 1H), 3.65 (dd, J¼11.0, 7.0 Hz, 1H), 3.56 (dd, J¼11.0, 5.0 Hz, 1H),
3.27 (br, 1H), 2.02 (dd, J¼14.8, 4.5 Hz, 1H), 1.79 (dd, J¼14.8, 5.1 Hz,
1H), 0.92 (s, 9H), 0.84e0.78 (m, 1H), 0.74e0.68 (m, 1H), 0.59e0.54
(m, 1H), 0.44e0.39 (m, 1H), 0.16 (s, 6H); 13C NMR (100 MHz, CDCl3)
anes 1:4) to obtain 21 (889 mg, 89%) as a colorless oil.
24
d
72.9, 53.8, 47.4, 40.7, 25.7, 17.9, 13.7, 11.9, ꢀ4.6, ꢀ4.8; MS (ESI): m/z
[a
]
þ5.6 (c 2.40, CHCl3); IR (film): 3016, 2956, 2930, 2858,
D
287.2, [MþNa]þ; HRMS (ESI) calcd for C12H25ClO2SiNaþ [MþNa]þ:
2250, 1598, 1496, 1366, 1155, 1096, 779 cmꢀ1
CDCl3)
1H), 2.61 (dd, J¼16.8, 4.5 Hz, 1H), 2.51 (dd, J¼16.8, 4.5 Hz, 1H), 2.45
(s, 3H), 2.15e2.04 (m, 2H), 1.08e1.01 (m, 2H), 0.90 (s, 9H),
0.74e0.66 (m, 2H), 0.12 (s, 3H), 0.09 (s, 3H); 13C NMR (100 MHz,
;
1H NMR (400 MHz,
287.1205, found: 287.1213.
d
7.73 (d, J¼8.3 Hz, 2H), 7.33 (d, J¼8.3 Hz, 2H), 4.36e4.30 (m,
To a solution of the above cyclopropanol (1.38 g, 5.21 mmol) in
CH2Cl2 (20 mL) was added Et3N (1.45 mL, 10.42 mmol), DMAP
(127 mg, 0.104 mmol) and TsCl (1.49 g, 7.82 mmol) at 0 ꢁC. The
reaction was stirred at room temperature for 2 h and then warmed
to 40 ꢁC for additional 28 h before it was quenched with aq NaHCO3.
The reaction mixture was extracted with CH2Cl2, washed with
brine, dried over Na2SO4, concentrated and purified by flash chro-
matography (Et2O/hexanes 1:10) to afford 20 (2.08 g, 95%) as
a colorless oil.
CDCl3)
d 145.1, 134.9, 129.9, 127.6, 117.4, 65.4, 63.6, 43.0, 26.4, 25.7,
21.7, 17.8, 11.8, 11.4, ꢀ4.6, ꢀ4.9; MS (ESI): m/z 432.2, [MþNa]þ;
HRMS (ESI) calcd for C20H31NO4SSiNaþ [MþNa]þ: 432.1635, found:
432.1648.
4.11. (S)-1-(2-((tert-Butyldimethylsilyl)oxy)pent-4-en-1-yl)
cyclopropyl 4-methyl benzenesulfonate (22)
[
a]
27 þ1.7 (c 1.82, CHCl3); IR (film): 3015, 2956, 2930, 2857, 1599,
D
1496, 1472, 1254, 1096, 778 cmꢀ1; 1H NMR (400 MHz, CDCl3)
d
7.75
(d, J¼8.3 Hz, 2H), 7.32 (d, J¼8.0 Hz, 2H), 4.27e4.22 (m, 1H),
3.59e3.50 (m, 2H), 2.44 (s, 3H), 2.23 (dd, J¼15.0, 5.5 Hz, 1H), 1.84
(dd, J¼15.0, 7.5 Hz, 1H), 1.13e1.01 (m, 2H), 0.88 (s, 9H), 0.75e0.65
(m, 2H), 0.09 (s, 3H), 0.07 (s, 3H); 13C NMR (100 MHz, CDCl3)
To a stirred solution of 21 (794 mg,1.94 mmol) in CH2Cl2 (20 mL)
was DIBAL-H (1.0 M in toluene, 2.91 mL, 2.91 mmol) at 0 ꢁC. The
reaction mixture was stirred at 0 ꢁC for 1 h before it was quenched
by aqueous Rochelle salt solution and stirred at room temperature
for 2 h. The layers were separated and the aqueous layer was
extracted with CH2Cl2. The combined organic layers were washed
with brine, dried over Na2SO4, filtered, and concentrated. Purifi-
cation on silica gel (EtOAc/hexanes 3:20) provided aldehyde
(590 mg, 74%) as a white solid.
d
144.8,135.2,129.8,127.6, 68.9, 65.9, 64.0, 49.3, 41.2, 25.8, 21.7,18.0,
15.3, 12.1, 11.1, ꢀ4.6, ꢀ4.7; MS (ESI): m/z 441.2, [MþNa]þ; HRMS
(ESI) calcd for C19H31ClO4SSiNaþ [MþNa]þ: 441.1293, found:
441.1303.
4.10. (S)-1-(2-((tert-Butyldimethylsilyl)oxy)-3-cyanopropyl)
cyclopropyl 4-methyl benzenesulfonate (21)
Mp¼68e70 ꢁC; [
a
]
24 þ1.8 (c 0.55, CHCl3); IR (film): 3544, 2955,
D
2926, 2855, 1732, 1693, 1598, 1456, 1362, 1176, 1095, 932, 814 cmꢀ1
;
1H NMR (400 MHz, CDCl3)
d
9.78 (t, J¼1.7 Hz, 1H), 7.75 (d, J¼8.3 Hz,
To a stirred solution of 20 (930 mg, 2.22 mmol) in THF (15 mL)
was added TBAF (1.0 M in THF, 4.44 mL, 4.44 mmol). The reaction
was stirred at room temperature for 14 h before it was quenched
with brine. The mixture was extracted with EtOAc, dried over
Na2SO4, concentrated and purified by flash chromatography
(EtOAc/hexanes 1:5) to afford epoxide (479 mg, 80%) as a colorless
2H), 7.33 (d, J¼8.1 Hz, 2H), 4.60e4.54 (m, 1H), 2.73 (dd, J¼5.3,
2.0 Hz, 1H), 2.71e2.47 (m, 1H), 2.45 (s, 3H), 2.12 (dd, J¼14.5, 6.5 Hz,
1H), 1.94 (dd, J¼14.9, 6.8 Hz, 1H), 1.10e1.01 (m, 2H), 0.86 (s, 9H),
0.70e0.62 (m, 2H), 0.09 (s, 6H); 13C NMR (100 MHz, CDCl3)
d 202.0,
144.9, 135.1, 129.9, 127.6, 65.9, 63.9, 50.6, 43.8, 25.7, 21.7, 17.8, 11.9,
11.7, ꢀ4.4, ꢀ4.8; MS (ESI): m/z 435.1, [MþNa]þ; HRMS (ESI) calcd for
C20H32O5SSiNaþ [MþNa]þ: 435.1598, found: 435.1620.
oil.
25
[
a]
þ5.4 (c 1.70, CHCl3); IR (film): 3050, 2955, 2925, 2854,
To a stirred suspension of Ph3PþCH3Brꢀ (961 mg, 2.69 mmol) in
THF (8 mL) was added NaHMDS (2.0 M in THF, 1.26 mL, 2.51 mmol)
at 0 ꢁC for 30 min. A solution of the above aldehyde (370 mg,
0.897 mmol) in THF (4 mL) was then added to the stirred solution.
After 30 min at 0 ꢁC, the reaction mixture was quenched with aq
NH4Cl and extracted with EtOAc. The combined organic layers were
washed with brine, dried over Na2SO4, concentrated and purified
by flash chromatography (Et2O/hexanes 1:10) to afford olefin 22
(360 mg, 98%) as a white solid.
D
1598, 1460, 1376, 1171, 1095, 813 cmꢀ1 1H NMR (400 MHz, CDCl3)
;
d
7.76 (d, J¼2.1 Hz, 2H), 7.31 (d, J¼2.0 Hz, 2H), 3.12e3.08 (m, 1H),
2.77e2.75 (m, 1H), 2.49e2.47 (m, 1H), 2.47 (s, 3H), 2.32e2.27 (m,
1H), 1.85e1.80 (m, 1H), 1.19e1.15 (m, 2H), 0.79e0.67 (m, 2H); 13C
NMR (100 MHz, CDCl3)
d 144.8, 135.3, 129.8, 127.6, 64.4, 49.3, 46.5,
39.1, 21.6, 11.3, 11.1; MS (ESI): m/z 291.2, [MþNa]þ; HRMS (ESI) calcd
for C13H16O4SNaþ [MþNa]þ: 291.0662, found: 291.0667.
To a solution of the above epoxide (622 mg, 2.32 mmol) in
CH3CN (15 mL) was added NaCN (568 mg, 11.59 mmol) and LiClO4
(1.86 g, 11.59 mmol). The reaction was stirred at 70 ꢁC for 7 h before
it was quenched with brine. The mixture was extracted with EtOAc,
dried over Na2SO4, concentrated and purified by flash chromatog-
raphy (EtOAc/hexanes 1:2) to afford alcohol (639 mg, 93%) as
a colorless oil.
Mp¼78e80 ꢁC; [
a
]
24 þ6.7 (c 1.10, CHCl3); IR (film): 3075, 3015,
D
2955, 2929, 2857, 1641, 1599, 1472, 1364, 1178, 1096, 931, 776 cmꢀ1
;
1H NMR (400 MHz, CDCl3)
2H), 5.81e5.71 (m, 1H), 5.04e5.00 (m, 2H), 4.11e4.05 (m, 1H), 2.44
(s, 3H), 2.34e2.27 (m, 1H), 2.21e2.12 (m, 2H), 1.58e1.54 (m, 1H),
1.12e1.06 (m, 1H), 1.02e0.96 (m, 1H), 0.87 (s, 9H), 0.74e0.70 (m,
d
7.74 (d, J¼8.3 Hz, 2H), 7.31 (d, J¼8.0 Hz,

5986
Z. Ye et al. / Tetrahedron 67 (2011) 5979e5989
1H), 0.69e0.55 (m, 1H), 0.05 (s, 3H), 0.04 (s, 3H); 13C NMR
(100 MHz, CDCl3) 144.6, 135.6, 134.5, 129.7, 127.6, 117.2, 68.5, 64.7,
42.8, 42.1, 25.9, 21.6, 17.9, 12.2, 11.0, ꢀ4.5, ꢀ4.5; MS (ESI): m/z 433.3,
[MþNa]þ; HRMS (ESI) calcd for C21H34O4SSiNaþ [MþNa]þ:
433.1839, found: 433.1844.
15.8; MS (ESI): m/z 391.2, [MþNa]þ; HRMS (ESI) calcd for
C23H32O2SiNaþ [MþNa]þ: 391.2064, found: 391.2073.
d
To a solution of the above alcohol (720 mg, 1.95 mmol) was
added DIPEA (1.0 mL, 5.86 mmol) and DMAP (24 mg, 0.195 mmol).
Then acryloyl chloride (0.24 mL, 2.93 mmol) was added dropwise at
0 ꢁC. The reaction was stirred at room temperature for 18 h before it
was quenched with satd NaHCO3. The mixture was extracted with
CH2Cl2, washed with brine, dried over Na2SO4, concentrated and
purified by flash chromatography (Et2O/hexanes 1:40) to obtain
diene (784 mg, 95%) as a colorless oil.
4.12. (S)-((2-(Bromomethyl)hepta-1,6-dien-4-yl)oxy)(tert-
butyl)dimethylsilane (23)
To a solution of 22 (400 mg, 0.974 mmol) in CH2Cl2 (10 mL) was
added MgBr2$Et2O (754 mg, 2.92 mmol) at room temperature. The
reaction was refluxed at argon for 1 h and then cooled to room
temperature. The mixture was quenched with brine, extracted with
EtOAc, dried over Na2SO4, concentrated and purified by flash
chromatography (hexanes) to afford allyl bromide 23 (274 mg, 88%)
[
a
]
D
26 ꢀ7.1 (c 2.00, CHCl3); IR (film): 3072, 3050, 2931, 2858,1725,
1472, 1295, 1110, 823, 738 cmꢀ1
;
1H NMR (400 MHz, CDCl3)
d
7.68e7.64 (m, 4H), 7.43e7.35 (m, 6H), 6.33 (dd, J¼17.3, 1.5 Hz, 1H),
6.04 (dd, J¼17.4, 10.8 Hz, 1H), 5.80e5.71 (m, 2H), 5.19e5.16 (m, 1H),
5.15e5.01 (m, 2H), 3.66 (t, J¼6.0 Hz, 2H), 2.53e2.46 (m, 1H),
1.87e1.77 (m, 2H), 1.05 (s, 9H), 1.00 (d, J¼7.0 Hz, 3H); 13C NMR
as a colorless oil.
24
[a
]
þ2.7 (c 1.20, CHCl3); IR (film): 3079, 2955, 2929, 2857,
(100 MHz, CDCl3) d 165.8, 139.4, 135.6, 135.6, 133.8, 133.7, 130.3,
D
1640, 1471, 1362, 1210, 1089, 835, 775 cmꢀ1
;
1H NMR (400 MHz,
129.6, 128.9, 127.7, 115.6, 74.1, 60.4, 41.4, 34.0, 26.8, 19.2, 15.6; MS
(ESI): m/z 445.3, [MþNa]þ; HRMS (ESI) calcd for C26H34O3SiNaþ
[MþNa]þ: 445.2169, found: 445.2175.
CDCl3) 5.87e5.77 (m, 1H), 5.25 (s, 1H), 5.08e5.03 (m, 2H), 5.00 (s,
d
1H), 4.04 (d, J¼10.0 Hz, 1H), 3.98 (d, J¼10.0 Hz, 1H), 3.91e3.86 (m,
1H), 2.40 (dd, J¼14.3, 5.5 Hz, 1H), 2.29 (dd, J¼14.0, 6.5 Hz, 1H),
2.27e2.18 (m, 2H), 0.89 (s, 9H), 0.06 (s, 3H), 0.05 (s, 3H); 13C NMR
To a stirred solution of diene (710 mg, 1.68 mmol) in CH2Cl2
(50 mL) was added second generation Grubbs catalyst (71 mg,
0.084 mmol) at room temperature. The resulting solution was
refluxed under argon for 12 h. The solvent was evaporated and the
residue was purified by flash chromatography (EtOAc/hexanes
(100 MHz, CDCl3)
d 142.8, 134.9, 118.1, 117.3, 70.9, 41.6, 40.6, 37.4,
25.9, 18.1, ꢀ4.5; HRMS (þTOF EI): m/z [Mþeallyl] calcd for
C11H22OSi81Br: 279.0603; found: 279.0587. HRMS (þTOF EI): m/z
[Mþeallyl] calcd for C11H22OSi79Br: 277.0623; found: 277.0605.
1:10) to afford lactone 26 (604 mg, 91%) as a colorless oil.
25
[
a
]
D
ꢀ14.4 (c 1.10, CHCl3); IR (film): 3071, 3049, 2930, 2857,
4.13. (S)-tert-Butyldimethyl((2-((tributylstannyl)methyl)
1729, 1471, 1247, 1111, 822, 704 cmꢀ1 1H NMR (400 MHz, CDCl3)
;
hepta-1,6-dien-4-yl)oxy) silane (5)
d
7.68e7.64 (m, 4H), 7.45e7.37 (m, 6H), 6.33 (dd, J¼9.7, 2.5 Hz, 1H),
5.94 (dd, J¼9.8, 2.5 Hz, 1H), 3.97 (dt, J¼9.5, 3.0 Hz, 1H), 3.97e3.92
(m, 1H), 3.88e3.83 (m, 1H), 2.58e2.49 (m, 1H), 2.01e1.93 (m, 1H),
1.91e1.83 (m, 1H), 1.13 (d, J¼7.2 Hz, 3H), 1.05 (s, 9H); 13C NMR
To a solution of 23 (274 mg, 0.858 mmol) in acetone (10 mL) was
added NaI (1.29 g, 8.58 mmol) at room temperature. The reaction
mixture was stirred for 1 day and diluted with brine. The mixture
was extracted with EtOAc, dried over Na2SO4, filtered, concentrated
and purified by flash chromatography (hexanes) to afford allyl io-
dide (282 mg, 90%) as a colorless oil.
(100 MHz, CDCl3)
d 164.0, 151.4, 135.6, 135.5, 133.7, 133.5, 129.7,
127.8, 127.8, 120.2, 80.5, 59.4, 35.8, 33.3, 26.9, 19.2, 16.5; MS (ESI):
m/z 417.2, [MþNa]þ; HRMS (ESI) calcd for C24H30O3SiNaþ [MþNa]þ:
417.1856, found: 417.2047.
The corresponding allyl iodide (282 mg, 0.770 mmol) was dis-
solved in THF (8 mL) and treated with bis(tributyltin) (0.58 mL,
1.16 mmol) followed by Pd2dba3$CHCl3 (35 mg, 0.0385 mmol).
Argon was bubbled through the solution for 25 min and it was then
heated to 55 ꢁC for 3 h. Brine was added and the mixture was
extracted with EtOAc. The combined organic layers were dried over
Na2SO4, filtered and concentrated in vacuo to provide allyl stannane
5 without flash column chromatography in 100% conversion.
4.15. (5R,6S)-6-(2-((tert-Butyldiphenylsilyl)oxy)ethyl)-4,5-
dimethyl-5,6-dihydro-2H-pyran-2-one (27)
A
solution of methyllithium (3.0 M in ether, 4.24 mL,
12.72 mmol) was added to a suspension of CuI (1.21 g, 6.36 mmol)
in Et2O (15 mL) at 0 ꢁC, and the resulting mixture was stirred at 0 ꢁC
for 20 min to form a clear solution. A solution of lactone 26 (837 mg,
2.12 mmol) in Et2O (5 mL) was added, and the mixture was stirred
at 0 ꢁC for 5 h. The reaction was quenched with satd NH4Cl solution
and extracted with EtOAc. The combined organic extracts were
washed with brine, dried over Na2SO4, concentrated and purified
by flash chromatography (EtOAc/hexanes 1:10) to obtain mixtures
(738 mg, 85%).
To a stirred solution of i-Pr2NH (0.136 mL, 0.968 mmol) in THF
(6 mL) was added n-BuLi (1.6 M in hexanes, 0.61 mL, 0.968 mmol) at
ꢀ78 ꢁC. After stirred at 0 ꢁC for 30 min, a solution of the above
mixtures (265 mg, 0.649 mmol) was added to the stirred solution at
ꢀ78 ꢁC. After 30 min, TMSCl (0.41 mL, 3.23 mmol) was added. After
additional 30 min, PhSeCl (371 mg, 1.94 mmol) was added to the
reaction system. The reaction mixture was stirred at ꢀ78 ꢁC for 3 h
before it was quenched with satd NH4Cl. Then it was extracted with
EtOAc, washed with brine and dried over Na2SO4. The combined
organic extracts were concentrated under reduced pressure and
dissolved in THF/EtOAc (2 mL/4 mL). NaHCO3 (545 mg, 6.49 mmol)
and 30% H2O2 (0.27 mL, 6.49 mmol) were added to the above solu-
tion at 0 ꢁC. After 40 min, the reaction mixture was warmed to room
temperature and stirred overnight. It was quenched with satd
NH4Cl, extracted with EtOAc, washed with brine, dried over Na2SO4,
4.14. (5R,6S)-6-(2-((tert-Butyldiphenylsilyl)oxy)ethyl)-5-
methyl-5,6-dihydro-2H-pyran-2-one (26)
To a solution of aldehyde 24 (1.25 g, 4.00 mmol) in toluene
ꢀ
(30 mL) was added powdered activated 4 A MS (600 mg) and cooled
to ꢀ78 ꢁC. Crotylboronate (S,S)-25 (0.80 M stock solution in toluene,
7.5 mL, 6.00 mmol) was then added to the stirred solution at ꢀ78 ꢁC.
After 2 h at ꢀ78 ꢁC, the reaction mixture was quenched by satd
K2CO3 solution and stirred at room temperature for additional 2 h.
The layers were separated and the aqueous phase was extracted
with EtOAc and washed with brine. The combined organic extracts
were dried over Na2SO4, filtered, and concentrated under reduced
pressure. The residue was purified by flash chromatography (EtOAc/
hexanes 1:20) to afford alcohol (1.34 g, 91%) as a colorless oil.
[a
]
26 þ2.7 (c 1.60, CHCl3); IR (film): 3517, 3071, 2929, 2857, 1729,
D
1640, 1471, 1390, 1111, 822 cmꢀ1
;
1H NMR (400 MHz, CDCl3)
d
7.74e7.66 (m, 4H), 7.47e7.39 (m, 6H), 5.89e5.80 (m, 1H),
5.10e5.06 (m, 2H), 3.93e3.82 (m, 2H), 3.79e3.75 (m, 1H), 3.01 (d,
J¼2.2 Hz, 1H), 2.30e2.23 (m, 1H), 1.74e1.64 (m, 2H), 1.07 (s, 9H),
1.05 (d, J¼1.8 Hz, 3H); 13C NMR (100 MHz, CDCl3)
d 140.7, 135.6,
134.9, 133.3, 133.2, 129.8, 127.8, 115.3, 63.4, 44.0, 35.7, 26.9, 19.1,

Z. Ye et al. / Tetrahedron 67 (2011) 5979e5989
5987
concentrated and purified by flash chromatography (EtOAc/hexanes
1:10) to afford lactone 27 (225 mg, 85%) as a colorless oil.
Na2SO4, concentrated and purified by flash chromatography
(EtOAc/hexanes 3:20) to provide tosylate (290 mg, 99%) as a color-
less oil.
27
4.16. (3S,4R,Z)-4,5-Dimethyl-7-(trityloxy)hept-5-ene-1,3-diol
(28)
[
a
]
ꢀ9.9 (c 1.20, CHCl3); IR (film): 3504, 3058, 3032, 2960,
D
2925, 2854, 1597, 1459, 1260, 1094, 802 cmꢀ1
CDCl3)
;
1H NMR (400 MHz,
d
7.82 (d, J¼8.2 Hz, 2H), 7.49e7.47 (m, 6H), 7.39e7.32 (m,
To a solution of lactone 27 (97 mg, 0.237 mmol) in MeOH (5 mL)
was added CeCl3$7H2O (265 mg, 0.712 mmol) and NaBH4 (27 mg,
0.721 mmol) at 0 ꢁC. The reaction mixture was stirred for 3 h at 0 ꢁC
before it was diluted with brine. The mixture was extracted with
EtOAc, dried over Na2SO4, concentrated and purified by flash chro-
matography (EtOAc/hexanes 1:10) to give diol (53 mg, 54%, 81% br s,
m) as a colorless oil with recovered starting material 27 (32 mg).
9H), 7.28 (d, J¼7.3 Hz, 2H), 5.67 (t, J¼6.8 Hz, 1H), 4.26e4.17 (m, 2H),
3.62 (dd, J¼10.7, 7.2 Hz, 1H), 3.45 (dd, J¼10.3, 7.2 Hz, 1H), 3.40 (t,
J¼9.5 Hz, 1H), 2.49 (s, 3H), 2.30e2.24 (m, 1H), 2.18 (d, J¼3.3 Hz, 1H),
2.01e1.93 (m, 1H), 1.72 (s, 3H), 1.67 (m, 1H), 0.89 (d, J¼6.8 Hz, 3H);
13C NMR (100 MHz, CDCl3)
d 144.6, 144.0, 141.7, 133.3, 129.8, 128.7,
127.9, 127.8, 127.0, 124.9, 87.1, 68.7, 68.3, 59.4, 41.2, 34.3, 21.6, 18.6,
15.0; MS (ESI): m/z 593.3, [MþNa]þ; HRMS (ESI) calcd for
C35H38O5SNaþ [MþNa]þ: 593.2332, found: 593.2324.
[a]
26 ꢀ1.5 (c 2.90, CHCl3); IR (film): 3409, 3049, 2959, 2929, 2857,
D
1740, 1471, 1240, 1109, 822, 737 cmꢀ1
;
1H NMR (400 MHz, CDCl3)
To a stirred solution of tosylate (273 mg, 0.478 mol) in CH2Cl2
(10 mL) was added 2,6-lutidine (0.22 mL, 1.91 mmol) and TBSOTf
(0.21 mL, 0.957 mmol) at 0 ꢁC. After stirred at 0 ꢁC for 1 h, the re-
action mixture was quenched with satd NaCHO3. It was extracted
with CH2Cl2, washed with brine, dried over Na2SO4, concentrated
and purified by flash chromatography (Et2O/hexanes 1:40) to afford
d
7.69e7.67 (m, 4H), 7.47e7.37 (m, 6H), 5.74 (t, J¼7.3 Hz,1H), 4.21 (dd,
J¼11.5, 8.3 Hz, 1H), 3.97e3.84 (m, 3H), 3.69 (t, J¼10.8 Hz, 1H),
2.81e2.74 (m, 1H), 1.83e1.80 (m, 1H), 1.73 (s, 3H), 1.69e1.62 (m, 1H),
1.05 (s, 9H), 0.93 (d, J¼7.0 Hz, 3H); 13C NMR (100 MHz, CDCl3)
d 142.6,
135.6, 135.6, 133.0, 132.8, 130.0, 129.9, 127.9, 127.8, 126.2, 72.8, 63.8,
57.2, 40.4, 35.9, 26.8, 19.0, 18.4, 15.3; MS (ESI): m/z 435.2, [MþNa]þ;
HRMS (ESI) calcd for C25H36O3SiNaþ [MþNa]þ: 435.2326, found:
435.2339.
TBS ether 29 (311 mg, 95%) as a colorless oil.
29
[a
]
ꢀ12.9 (c 2.20, CHCl3); IR (film): 3058, 3032, 2956, 2856,
D
1598, 1491, 1364, 1177, 838 cmꢀ1; 1H NMR (400 MHz, CDCl3)
d 7.75
To a solution of the above diol (273 mg, 0.662 mmol) in CH2Cl2
(8 mL) was added Et3N (0.19 mL, 1.32 mmol), DMAP (8 mg,
0.066 mmol) and TrCl (277 mg, 0.992 mmol) at 0 ꢁC. The reaction
mixture was stirred at room temperature overnight and quenched
with satd NaHCO3. It was extracted with CH2Cl2, washed with brine,
dried over Na2SO4, concentrated and purified by flash chromatog-
raphy (EtOAc/hexanes 1:20) to obtain Tr ether (390 mg, 90%) as
(d, J¼8.3 Hz, 2H), 7.51e7.49 (m, 6H), 7.36e7.32 (m, 9H), 7.28 (d,
J¼7.0 Hz, 2H), 5.53 (t, J¼6.1 Hz, 1H), 3.98 (t, J¼7.2 Hz, 2H), 3.65 (dd,
J¼11.3, 7.8 Hz, 1H), 3.56e3.48 (m, 2H), 2.49 (s, 3H), 2.41e2.35 (m,
1H), 1.77e1.69 (m, 2H), 1.74 (s, 3H), 0.92 (d, J¼7.0 Hz, 3H), 0.78 (s,
9H), ꢀ0.09 (s, 3H), ꢀ0.11 (s, 3H); 13C NMR (100 MHz, CDCl3)
d 144.6,
144.3, 139.5, 129.8, 128.7, 128.0, 127.9, 127.9, 127.8, 127.3, 127.0,
124.7, 86.8, 71.3, 67.7, 60.6, 39.5, 33.5, 25.8, 21.6, 20.5, 17.9, 14.3,
ꢀ4.4, ꢀ4.8; MS (ESI): m/z 707.3, [MþNa]þ; HRMS (ESI) calcd for
C41H52O5SSiNaþ [MþNa]þ: 707.3197, found: 707.3208.
a colorless oil.
27
[
a]
ꢀ8.9 (c 2.30, CHCl3); IR (film): 3515, 3057, 3023, 2928,
D
2855, 1490, 1427, 1109, 822, 742 cmꢀ1
;
1H NMR (400 MHz, CDCl3)
d
7.66e7.65 (m, 4H), 7.45e7.43 (m, 6H), 7.41e7.34 (m, 6H),
4.18. tert-Butyl(((3S,4R,Z)-4,5-dimethyl-7-(trityloxy)hepta-
7.28e7.21 (m, 6H), 7.19e7.17 (m, 3H), 5.57 (t, J¼6.5 Hz, 1H),
3.87e3.78 (m, 2H), 3.64e3.54 (m, 3H), 2.65 (s, 1H), 2.33e2.26 (m,
1H), 1.74 (s, 3H), 1.70e1.66 (m, 1H), 1.48e1.43 (m, 1H), 1.03 (s, 9H),
1,5-dien-3-yl)oxy) dimethylsilane (30)
To a solution of TBS ether 29 (313 mg, 0.457 mmol) in acetone
(8 mL) was added NaI (1.30 g, 9.14 mmol) at room temperature. The
reaction mixture was stirred for 2 days and diluted with brine. It
was extracted with EtOAc, dried over Na2SO4, concentrated and
purified by flash chromatography (Et2O/hexanes 1:40) to afford
0.86 (d, J¼6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3)
d 144.3, 141.7,
135.6, 135.6, 133.6, 133.5, 129.7, 128.8, 128.0, 127.8, 127.7, 126.9,
124.3, 86.9, 71.9, 62.6, 60.0, 41.0, 36.8, 26.9, 19.1, 19.0, 15.5; MS (ESI):
m/z 677.3, [MþNa]þ; HRMS (ESI) calcd for C44H50O3SiNaþ
[MþNa]þ: 677.3421, found: 677.3419.
iodide (284 mg, 97%) as a colorless oil.
27
To a stirred solution of Tr ether (336 mg, 0.513 mmol) in THF
(10 mL) was added TBAF (1.0 M in THF, 1.03 mL, 1.03 mmol) at room
temperature. The reaction mixture was stirred for 2 h and diluted
with brine. It extracted with EtOAc, dried over Na2SO4, concen-
trated and purified by flash chromatography (EtOAc/hexanes 1:4)
[a
]
ꢀ17.8 (c 1.40, CHCl3); IR (film): 3059, 3025, 2956, 2927,
D
2855, 1458, 1258, 1047, 834 cmꢀ1
;
1H NMR (400 MHz, CDCl3)
d
7.51e7.49 (m, 6H), 7.36e7.33 (m, 6H), 7.30e7.28 (m, 3H), 5.58 (t,
J¼6.3 Hz, 1H), 3.67 (dd, J¼11.3, 7.5 Hz, 1H), 3.57e3.49 (m, 2H), 2.97
(t, J¼6.3 Hz, 2H), 2.50e2.43 (m, 1H), 2.10e1.85 (m, 3H), 1.76 (s, 3H),
0.97 (d, J¼7.0 Hz, 3H), 0.85 (s, 9H), 0.13 (s, 3H), 0.02 (s, 3H); 13C NMR
to give diol 28 (213 mg, 100%) as a colorless oil.
23
[
a]
þ11.9 (c 0.70, CHCl3); IR (film): 3463, 3060, 3024, 2925,
(100 MHz, CDCl3) d 144.3, 140.0, 128.7, 127.8, 126.9, 124.4, 86.7, 75.0,
D
2854, 1712, 1491, 1446, 1157, 761 cmꢀ1
;
1H NMR (400 MHz, CDCl3)
60.5, 38.6, 38.6, 25.8, 20.6, 18.0, 14.7, 2.3, ꢀ4.4, ꢀ4.5; MS (ESI): m/z
633.3, [MþNa]þ; HRMS (ESI) calcd for C34H45IO2SiNaþ [MþNa]þ:
663.2126, found: 663.2154.
To a solution of iodide (284 mg, 0.443 mmol) in THF (8 mL) was
added t-BuOK (145 mg, 1.33 mmol) at 0 ꢁC. The reaction was stirred
for 5 h before it was quenched with satd NH4Cl. The mixture was
extracted with EtOAc, washed with brine, dried over Na2SO4, con-
centrated and purified by flash chromatography (Et2O/hexanes
d
7.51e7.49 (m, 6H), 7.37e7.33 (m, 6H), 7.30e7.26 (m, 3H), 5.71 (t,
J¼7.0 Hz, 1H), 3.80 (t, J¼5.8 Hz, 2H), 3.68e3.54 (m, 3H), 2.88 (br,
2H), 2.42e2.34 (m,1H),1.82e1.78 (m,1H),1.76 (s, 3H),1.71e1.56 (m,
1H), 0.90 (d, J¼6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3)
d 143.9,
142.5, 128.7, 127.9, 127.1, 124.5, 87.3, 73.5, 61.8, 59.3, 41.4, 36.2, 18.5,
15.0; MS (ESI): m/z 439.3, [MþNa]þ; HRMS (MALDI) calcd for
C28H32O3Naþ [MþNa]þ: 439.2244, found: 439.2257.
1:40) to afford olefin 30 (220 mg, 97%) as a colorless oil.
27
4.17. (3S,4R,Z)-3-((tert-Butyldimethylsilyl)oxy)-4,5-dimethyl-
7-(trityloxy)hept-5-en-1-yl 4-methyl benzenesulfonate (29)
[a
]
ꢀ19.9 (c 1.75, CHCl3); IR (film): 3060, 3023, 2956, 2927,
D
2856, 1491, 1253, 1067, 836 cmꢀ1
;
1H NMR (400 MHz, CDCl3)
d
7.53e7.52 (m, 6H), 7.37e7.32 (m, 6H), 7.30e7.28 (m, 3H),
To a solution of diol (213 mg, 0.511 mmol) in CH2Cl2 (10 mL) was
added Et3N (0.14 mL, 1.02 mmol), DMAP (6 mg, 0.051 mmol) and
TsCl (146 mg, 0.767 mmol) at 0 ꢁC. The reaction was stirred at room
temperature overnight. The mixture was quenched with satd
NaHCO3, extracted with CH2Cl2, washed with brine, dried over
5.68e5.55 (m, 2H), 5.09e5.02 (m, 2H), 3.85 (t, J¼7.3 Hz, 1H), 3.68
(dd, J¼11.0, 8.0 Hz, 1H), 3.61e3.57 (m, 1H), 2.48e2.41 (m, 1H), 1.76
(s, 3H), 0.97 (d, J¼6.8 Hz, 3H), 0.84 (s, 9H), ꢀ0.01 (s, 3H), ꢀ0.03 (s,
3H); 13C NMR (100 MHz, CDCl3)
d 144.5, 140.7, 140.1, 128.8, 127.7,
126.8, 123.9, 115.1, 86.6, 77.1, 60.7, 41.0, 25.8, 19.8, 18.1, 14.9,ꢀ4.1,

5988
Z. Ye et al. / Tetrahedron 67 (2011) 5979e5989
ꢀ5.1; MS (ESI): m/z 535.3, [MþNa]þ; HRMS (ESI) calcd for
C34H44O2SiNaþ [MþNa]þ: 535.3003, found: 535.3012.
(m, 6H), 5.86e5.78 (m, 1H), 5.69e5.63 (m, 1H), 5.50e5.44 (m, 1H),
5.06e5.02 (m, 2H), 4.93 (s, 2H), 4.56 (s, 2H), 3.86e3.80 (m, 2H),
3.53e3.50 (m, 1H), 3.42 (m, 1H), 3.33 (s, 3H), 2.35e2.21 (m, 6H),
2.15e1.98 (m,1H),1.85e1.74 (m, 3H),1.61 (m,1H),1.30e1.23 (m, 6H),
0.97 (s, 9H), 0.95 (d, J¼6.0 Hz, 3H), 0.90 (d, J¼6.7 Hz, 3H), 0.88 (s, 9H),
0.05e0.03 (m, 6H); MS (ESI): m/z 803.6, [MþNa]þ; HRMS (ESI) calcd
for C46H76O6Si2Naþ [MþNa]þ: 803.5073, found: 803.5087.
4.19. Acid 6
To a stirred solution of olefin 30 (192 mg, 0.374 mmol) in CHCl3
(10 mL) was added aq HCl (1.0 M in H2O saturated with NaCl,
0.75 mL, 0.749 mmol) at 0 ꢁC. The reaction was stirred at room
temperature for 2 days and quenched with satd NaHCO3. The
mixture was extracted with CH2Cl2, washed with brine, dried over
Na2SO4, concentrated and purified by flash chromatography (Et2O/
To a solution of the above alcohol 31 (124 mg, 0.159 mmol) in
DMSO (2 mL) was added IBX (178 mg, 0.635 mmol). The reaction
mixture was stirred at room temperature for 10 h. The mixture was
diluted with brine, extracted with EtOAc, dried over Na2SO4 and
concentrated under reduced pressure. The crude product was pu-
rified by flash chromatography (EtOAc/hexanes 1:20) to give ketone
hexanes 1:40e1:20) to afford alcohol (87 mg, 86%) as a colorless oil.
30
[a
]
ꢀ4.2 (c 1.45, CHCl3); IR (film): 3401, 2958, 2929, 2857,
D
1253, 1034, 836 cmꢀ1
;
1H NMR (400 MHz, CDCl3)
d
5.77e5.64 (m,
(111 mg, 90%) as a colorless oil.
25
2H), 5.15e5.11 (m, 2H), 4.14 (dd, J¼11.8, 7.0 Hz, 1H), 3.93e3.86 (m,
2H), 2.79e2.72 (m, 1H), 2.30 (br, 1H), 1.67 (s, 3H), 0.90 (d, J¼6.8 Hz,
3H), 0.85 (s, 9H), 0.04 (s, 3H), 0.02 (s, 3H); 13C NMR (100 MHz,
[
a
]
D
ꢀ32.9 (c 1.10, CHCl3); IR (film): 3445, 3073, 2928, 2856,
1691, 1582, 1466, 1296, 1105, 1039, 835, 737 cmꢀ1
;
1H NMR
(400 MHz, CDCl3) 7.69e7.66 (m, 4H), 7.45e7.35 (m, 6H),
d
CDCl3)
d
142.3, 140.6, 126.4, 116.3, 77.2, 57.7, 40.6, 25.8, 18.6, 18.2,
5.86e5.75 (m, 1H), 5.46 (d, J¼15.6 Hz, 1H), 5.06e5.02 (m, 2H), 5.00
(s, 1H), 4.88 (s, 1H), 4.57 (s, 2H), 3.84e3.81 (m, 1H), 3.41 (m, 1H),
3.34 (s, 3H), 2.28e2.16 (m, 5H), 1.84e1.69 (m, 3H), 1.58e1.55 (m,
1H), 1.45 (s, 3H), 1.34e1.29 (m, 3H), 1.06 (s, 9H), 0.95 (d, J¼6.3 Hz,
3H), 0.90 (d, J¼6.8 Hz, 3H), 0.88 (s, 9H), 0.85 (d, J¼6.8 Hz, 3H), 0.05
15.2, ꢀ4.2, ꢀ4.7; MS (ESI): m/z 293.3, [MþNa]þ; HRMS (ESI) calcd
for C15H30O2SiNaþ [MþNa]þ: 293.1907, found: 293.1915.
To a solution of the above alcohol (87 mg, 0.322 mmol) in CH2Cl2
(5 mL) was added DMP (273 mg, 0.643 mmol) and NaHCO3 (108 mg
1.29 mmol). The reactionmixturewasstirredatroom temperature for
30 min before it was quenched satd NaHCO3 and satd Na2S2O3. The
mixture was extracted with CH2Cl2, washed with brine, dried over
Na2SO4, concentrated and purified by flash chromatography (Et2O/
(s, 3H), 0.03 (s, 3H); 13C NMR (100 MHz, CDCl3)
d 209.7, 139.7, 136.0,
135.9, 134.9, 134.3, 133.3,131.9, 131.9,129.6, 129.5, 127.6, 127.4, 117.2,
117.1, 96.0, 81.0, 79.1, 72.6, 71.2, 55.7, 43.8, 43.3, 41.7, 37.3, 36.1, 34.5,
33.1, 27.1, 25.9, 24.9, 19.7, 19.4, 18.1, 15.5, 15.3, ꢀ4.4, ꢀ4.4; MS (ESI):
m/z 801.5, [MþNa]þ; HRMS (MALDI) calcd for C46H74O6Si2Naþ
[MþNa]þ: 801.4916, found: 801.4906.
hexanes 1:20) to afford aldehyde (80 mg, 93%) as a colorless oil.
25
[a
]
ꢀ32.4 (c 1.30, CHCl3); IR (film): 3075, 2958, 2929, 2857,
D
1735, 1691, 1638, 1258, 837, 776 cmꢀ1
;
1H NMR (400 MHz, CDCl3)
To a stirred solution of the above ketone (65 mg, 0.0834 mmol) in
CH2Cl2 (5 mL) was added a solution of B-Bromocatecholborane
(33 mg, 0.167 mmol) in CH2Cl2 (1 mL) at ꢀ78 ꢁC. The reaction mix-
ture was stirred at ꢀ78 ꢁC for 10 min. The mixture was quenched
with satd NaHCO3, extracted with EtOAc, washed with brine, dried
over Na2SO4 and concentrated under reduced pressure. The crude
product was purified by flash chromatography (EtOAc/hexanes
1:20e1:10) to give alcohol 32 (111 mg, 90%) as a colorless oil.
d
9.97 (d, J¼8.1 Hz, 1H), 5.90 (d, J¼8.1 Hz, 1H), 5.76e5.68 (m, 1H),
5.20e5.16 (m, 2H), 4.00 (t, J¼7.5 Hz, 1H), 3.47e3.39 (m, 1H), 1.92 (s,
3H),1.06 (d, J¼7.1 Hz, 3H), 0.83 (s, 9H), 0.01 (s, 3H), ꢀ0.01 (s, 3H); 13C
NMR (100 MHz, CDCl3)
d 190.8, 164.7, 140.0, 130.6, 116.7, 77.0, 41.4,
25.7, 20.8,18.1,15.4, ꢀ4.0, ꢀ5.1; MS (ESI): m/z 291.2, [MþNa]þ; HRMS
(ESI) calcd for C15H28O2SiNaþ [MþNa]þ: 291.1751, found: 291.1751.
To a solution of the above aldehyde (80 mg, 0.298 mmol) and 2-
methyl-2-butene (1 mL) in tert-butanol (4 mL) was added dropwise
a solution of NaClO2 (81 mg, 0.894 mmol) and NaH2PO4 (107 mg,
0.894 mmol) in H2O (1 mL) 0 ꢁC. Then the reaction mixture was
stirred at 0 ꢁC for 40 min, quenched with satd NH4Cl, extracted with
EtOAc, washed with brine, dried over Na2SO4 and concentrated
under reduced pressure. The crude product was purified by flash
chromatography (Et2O/hexanes 1:20) to give acid 6 (78 mg, 92%) as
[
a
]
D
25 ꢀ8.0 (c 1.10, CHCl3); IR (film): 3455, 3072, 2929, 2857,1680,
1614, 1463, 1251, 1108, 822, 737 cmꢀ1
;
1H NMR (400 MHz, CDCl3)
d
7.68e7.66 (m, 4H), 7.45e7.37 (m, 6H), 5.89e5.75 (m, 1H), 5.51 (d,
J¼15.6 Hz, 1H), 5.06e5.02 (m, 2H), 5.00 (s, 1H), 4.89 (s, 1H), 3.91 (m,
1H), 3.86e3.78 (m, 2H), 3.58e3.53 (m, 1H), 3.33 (AB d, J¼16.6 Hz,
1H), 3.27 (AB d, J¼16.3 Hz, 1H), 2.45e2.37 (m, 1H), 2.27e2.16 (m,
4H), 1.96e1.84 (m, 2H), 1.73e1.71 (m, 1H), 1.45 (s, 3H), 1.33e1.21 (m,
4H), 1.07 (s, 9H), 0.91 (d, J¼6.3 Hz, 3H), 0.88 (s, 9H), 0.85 (d,
J¼2.2 Hz, 3H), 0.83 (d, J¼2.0 Hz, 3H), 0.07e0.00 (m, 6H); 13C NMR
a colorless oil.
27
[a
]
ꢀ34.3 (c 1.55, CHCl3); IR (film): 3088, 2966, 2929, 2856,
D
1693, 1634, 1254, 836, 776 cmꢀ1
5.79e5.70 (m, 2H), 5.20e5.15 (m, 2H), 4.02 (t, J¼7.2 Hz, 1H),
3.71e3.64 (m, 1H), 1.85 (d, J¼1.0 Hz, 3H), 0.97 (d, J¼7.1 Hz, 3H), 0.87
(s, 9H), 0.06 (s, 3H), 0.04 (s, 3H); 13C NMR (100 MHz, CDCl3)
170.1,
;
1H NMR (400 MHz, CDCl3)
(100 MHz, CDCl3) d 209.7, 139.7, 136.0, 135.8, 134.9, 134.4, 133.8,
d
132.1, 131.9, 129.7, 129.7, 127.7, 127.5, 117.2, 117.1, 79.1, 73.9, 73.3,
71.2, 43.7, 43.3, 41.7, 39.1, 36.6, 36.4, 35.0, 31.9, 31.5, 30.2, 27.1, 25.9,
24.8, 22.7, 19.2, 18.1, 17.6, 15.8, 14.1, ꢀ4.4, ꢀ4.5; MS (ESI): m/z 757.5,
[MþNa]þ; HRMS (MALDI) calcd for C44H70O5Si2Naþ [MþNa]þ:
757.4654, found: 757.4667.
d
161.0, 139.6, 118.7, 116.2, 77.2, 41.0, 25.8, 20.7, 18.2, 14.7, ꢀ4.1, ꢀ5.0;
MS (ESI): m/z 307.2, [MþNa]þ; HRMS (ESI) calcd for C15H28O3SiNaþ
[MþNa]þ: 307.1700, found: 307.1708.
4.20. Alcohol 32
4.21. Macrolactone 2
To a solution of aldehyde 4 (88 mg, 0.163 mmol) and allyl
stannane 5 (172 mg, 0.325 mmol) in THF (6 mL) was added Yb(OTf)3
(20 mg, 0.0325 mmol) and p-NO2PhCO2H (54 mg, 0.325 mmol). The
reaction mixture was stirred at room temperature for 24 h. The
mixture was quenched with satd NaHCO3, extracted with EtOAc,
washed with brine, dried over Na2SO4 and concentrated under
reduced pressure. The crude product was purified by flash chro-
matography (EtOAc/hexanes 1:20e1:10) to give alcohol 31 (116 mg,
91%) as a colorless oil.
To a stirred solution of acid 6 (36 mg, 0.128 mmol) in toluene
(2.5 mL) was added Et3N (0.071 mL, 0.511 mmol) and 2,4,6-
Cl3C6H2COCl (0.040 mL, 0.256 mmol) at 0 ꢁC. The reaction mix-
ture was stirred for 2 h and cooled to 0 ꢁC. A solution of alcohol 32
(47 mg, 0.064 mmol) and DMAP (31 mg, 0.256 mmol) in toluene
(1.5 mL) was then added to the above solution at 0 ꢁC. The resulting
mixture was stirred at room temperature for 23 h and quenched
with satd NaHCO3. The mixture was extracted with EtOAc, washed
with brine, dried over Na2SO4 and concentrated under reduced
pressure. The crude product was purified by flash chromatography
(Et2O/hexanes 1:20) to give 33 (58 mg, 90%) as a colorless oil.
IR (film): 3444, 3070, 2927, 2859, 1461, 1375, 1098, 1040,
816 cmꢀ1; 1H NMR (400 MHz, CDCl3)
d 7.69e7.66 (m, 4H), 7.43e7.34

Z. Ye et al. / Tetrahedron 67 (2011) 5979e5989
5989
IR (film): 3453, 3072, 2961, 2926, 2855, 1732, 1615, 1463, 1255,
836, 739 cmꢀ1 1H NMR (400 MHz, CDCl3)
7.68e7.66 (m, 4H),
Foundation of China for financial support (Nos. 21032006,
20172064, 203900502, 20532040), Shanghai Natural Science
Council, and Excellent Young Scholars Foundation of National
Natural Science Foundation of China (20525208).
;
d
7.41e7.34 (m, 6H), 6.22 (s, 1H), 5.93e5.75 (m, 3H), 5.64 (s, 1H),
5.47 (d, J¼15.3 Hz, 1H), 5.15e5.03 (m, 4H), 4.83 (m, 1H), 4.40e4.37
(m, 1H), 4.08e4.05 (m, 1H), 3.95e3.92 (m, 1H), 3.83 (m, 1H),
2.37e2.21 (m, 6H), 2.21 (m, 1H), 1.84 (s, 3H), 1.80e1.77 (m, 1H),
1.65e1.51 (m, 4H), 1.41 (s, 3H), 1.37e1.21 (m, 3H), 1.05 (s, 9H),
0.99e0.80 (m, 30H), 0.05e0.00 (m, 12H); MS (ESI): m/z 1023.6,
[MþNa]þ; HRMS (ESI) calcd for C59H96O7Si3Naþ [MþNa]þ:
1023.6356, found: 1023.6384.
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tet.2011.06.025.
To a stirred solution of 33 (38 mg, 0.0379 mmol) in THF (4 mL)
was added HF$Py (95
mL, 3.79 mmol) at room temperature. The
reaction was stirred for 3 days and the additional HF$Py (95
m
L,
References and notes
3.79 mmol) was then added. The reaction was stirred for additional
3 days. The mixture was quenched with satd NaHCO3, extracted
with EtOAc, washed with brine, dried over Na2SO4 and concen-
trated under reduced pressure. The crude product was purified by
flash chromatography (EtOAc/hexanes 1:5e1:2) to give 34 (14 mg,
1. (a) Tsuda, M.; Oguchi, K.; Iwamoto, R.; Okamoto, Y.; Kobayashi, J.; Fukushi, E.;
Kawabata, J.; Ozawa, T.; Masuda, A.; Kitaya, Y.; Omasa, K. J. Org. Chem. 2007, 72,
4469; (b) Tsuda, M.; Oguchi, K.; Iwamoto, R.; Okamoto, Y.; Fukushi, E.; Kawa-
bata, J.; Ozawa, T.; Masuda, A. J. Nat. Prod. 2007, 70, 1661.
2. For synthesis of fragments of iriomoteolide-1a, see: (a) Fang, L.; Xue, H.; Yang, J.
Org. Lett. 2008, 10, 4645; (b) Ghosh, A. K.; Yuan, H. Tetrahedron Lett. 2009, 50,
1416; (c) Xie, J.; Horne, D. A. Tetrahedron Lett. 2009, 50, 4485; (d) Xie, J.; Ma, Y.;
Horne, D. A. Org. Lett. 2009, 11, 5082; (e) Chin, Y.-J.; Wang, S.-Y.; Loh, T.-P. Org.
Lett. 2009, 11, 3674; (f) Wang, S.-Y.; Chin, Y.-J.; Loh, T.-P. Synthesis 2009, 3557;
(g) Paterson, I.; Rubenbauer, P. Synlett 2010, 571; (h) Liu, Y.; Wang, J.; Li, H.; Wu,
J.; Feng, G.; Dai, W.-M. Synlett 2010, 2184.
3. For synthetic studies toward the total synthesis of the proposed structures of
iriomoteolide-1a and -1b, see: (a) Xie, J.; Ma, Y.; Horne, D. A. Chem. Commun.
2010, 4770; (b) Li, S.; Chen, Z.; Xu, Z.; Ye, T. Chem. Commun. 2010, 46, 4773; (c)
Ghosh, A. K.; Yuan, H. Org. Lett. 2010, 12, 3120.
4. For synthetic studies toward the total synthesis of diastereomers of
iriomoteolide-1a, see: Fang, L.; Yang, J.; Yang, F. Org. Lett. 2010, 12, 3124.
5. Ye, Z.; Deng, L.; Qian, S.; Zhao, G. Synlett 2009, 2469.
70%) as colorless oil.
24
[a]
ꢀ54.0 (c 0.20, CHCl3); 1H NMR (400 MHz, CDCl3)
d 6.33
D
(s, 1H), 5.91e5.76 (m, 4H), 5.54 (d, J¼15.6 Hz, 1H), 5.30e5.26 (m,
1H), 5.21e5.19 (m, 1H), 5.16e5.12 (m, 2H), 4.98e4.94 (m, 1H),
4.42 (m, 1H), 3.91e3.87 (m, 2H), 3.81e3.78 (m, 1H), 3.74e3.68
(m, 1H), 2.40e2.25 (m, 3H), 2.22 (d, J¼0.8 Hz, 3H), 2.16e2.11 (m,
1H), 2.04e1.96 (m, 1H), 1.90 (s, 3H), 1.87e1.84 (m, 2H), 1.78e1.72
(m, 2H), 1.52e1.50 (m, 1H), 1.43 (s, 3H), 1.35e1.28 (m, 2H), 1.08
(d, J¼6.6 Hz, 3H), 0.98 (d, J¼6.8 Hz, 3H), 0.87 (d, J¼6.0 Hz, 3H),
0.85 (d, J¼7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3)
d 200.6, 167.5,
160.8, 159.6, 139.7, 134.2, 133.5, 130.1, 120.2, 119.1, 118.4, 116.7,
77.9, 75.9, 75.6, 69.5, 68.5, 48.9, 42.1, 41.0, 36.6, 35.9, 35.3, 32.9,
24.8, 20.1, 19.8, 19.8, 15.4, 15.3, 15.2; MS (ESI): m/z 557.3,
[MþNa]þ; HRMS (ESI) calcd for C31H50O7Naþ [MþNa]þ: 557.3449,
found: 557.3467.
6. (a) Ouellet, S. G.; Tuttle, J. B.; MacMillan, D. W. C. J. Am. Chem. Soc. 2005,
127, 32; (b) Yang, J. W.; Fonseca, M. T. H.; Vignola, N.; List, B. Angew. Chem.,
Int. Ed. 2005, 44, 108; (c) Mayer, S.; List, B. Angew. Chem., Int. Ed. 2006, 45,
4193.
7. Roush, W. R.; Ando, K.; Powers, D. B.; Palkowitz, A. D.; Halterman, R. L. J. Am.
Chem. Soc. 1990, 112, 6339.
8. Mitsunobu, O. Synthesis 1981, 1.
To a stirred solution of 34 (15 mg, 0.0281 mmol) in anhydrous
CH2Cl2 (28 mL) was added second generation Grubbs catalyst
(4.8 mg, 0.00561 mmol) at room temperature. The resulting solu-
tion was stirred under argon at room temperature for 12 h. The
solvent was filtered and evaporated. The crude product was puri-
fied by flash chromatography (EtOAc/hexanes 1:5e1:2e1:1) to af-
ford macrolactone 2 (13 mg, 90%) as a colorless oil.
9. (a) Blakemore, P. R.; Cole, W. J.; Kocienski, P. J.; Morley, A. Synlett 1998, 26; (b)
Liu, P.; Jacobsen, E. N. J. Am. Chem. Soc. 2001, 123, 10772; (c) Hayes, P. Y.;
Kitching, W. J. Am. Chem. Soc. 2002, 124, 9718; (d) Blakemore, P. R. J. Chem. Soc.,
Perkin Trans. 1 2002, 2563.
10. Dess, D. B.; Martin, J. C. J. Org. Chem. 1983, 48, 4155.
11. (a) Kulinkovich, O. G.; Meijere, A. Chem. Rev. 2000, 100, 2789; (b) Kulinkovich,
O. G. Chem. Rev. 2003, 103, 2597.
12. (a) These copper regents include CuI, Li2CuCl4, CuBr$SMe2, CuCN in addition
with non copper regent BF3$SMe2. (b) Chini, M.; Crotti, P.; Favero, L.; Macchia, F.
Tetrahedron Lett. 1991, 32, 4775.
13. Kulinkovich, O. G.; Kozyrkov, Y. Y.; Bekish, A. V.; Matiushenkov, E. A.; Lysenko, I.
L. Synthesis 2005, 1713.
[a]
25 ꢀ76.3 (c 0.14, CHCl3); IR (film): 3433, 2961, 2924, 2853,1686,
D
1612,1460,1378,1264,1158, 971, 737cmꢀ1;1HNMR (400 MHz,CDCl3)
d
6.32 (s,1H), 5.85e5.78 (m,1H), 5.82 (s,1H), 5.75e5.67 (m, 2H), 5.52
14. Burns, N. Z.; Baran, P. S. Angew. Chem., Int. Ed. 2008, 47, 205.
15. Deiters, A.; Martin, S. F. Chem. Rev. 2004, 104, 2199.
(d, J¼15.8 Hz, 1H), 4.97 (m, 1H), 4.53 (s, 1H), 4.16e4.11 (m, 1H),
3.92e3.85 (m, 1H), 3.83e3.80 (m, 1H), 3.78e3.74 (m, 1H), 2.30e2.19
(m, 4H), 2.26(s, 3H), 2.12e2.08(m, 2H),1.98 (s, 3H),1.98e1.90 (m, 2H),
1.69e1.63 (m,1H),1.49(s, 3H),1.42e1.35 (m, 1H), 1.19 (d, J¼7.1 Hz, 3H),
1.11 (d, J¼6.5 Hz, 3H), 0.94 (d, J¼6.3 Hz, 3H), 0.88 (d, J¼6.8 Hz, 3H); 13C
16. Barrero, A. F.; Arseniyadis, S.; Moral, J. F. Q.; Herrador, M. M.; Valdivia, M.;
ꢁ
Jimenez, J. J. Org. Chem. 2002, 67, 2501.
17. (a) Gemal, A. L.; Luche, J. L. J. Am. Chem. Soc. 1981, 103, 5454; (b) Hollenstein, M.;
Leumann, C. J. J. Org. Chem. 2005, 70, 3205.
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19. Michaelis, S.; Blechert, S. Org. Lett. 2005, 7, 5513.
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Li, G.; Zhao, G. J. Org. Chem. 2005, 70, 4272.
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Jpn. 1979, 52, 1989; (b) Parenty, A.; Moreau, X.; Campagne, J. M. Chem. Rev. 2006,
106, 911.
NMR (100 MHz, CDCl3) d 200.9,167.3, 160.4, 159.3, 136.1, 133.2,129.9,
126.7,120.7,118.7, 77.7, 75.6, 75.6, 69.5, 68.4, 48.4, 41.0, 40.5, 36.4, 35.8,
31.2, 29.7, 24.0, 21.6, 20.4, 20.2, 15.7, 15.0, 13.9; MS (ESI): m/z 529.3,
[MþNa]þ;HRMS (MALDI)calcd forC29H46O7Naþ [MþNa]þ: 529.3136,
found: 529.3112.
22. (a) Mukaiyama, T.; Usui, M.; Saigo, K. Chem. Lett. 1976, 49; (b) Coery, E. J.;
Nicolaou, K. C. J. Am. Chem. Soc. 1974, 96, 5614.
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Acknowledgements
€
T. M.; Grubbs, R. H. Acc. Chem. Res. 2001, 34, 18; (c) Furstner, A. Angew. Chem.,
Int. Ed. 2000, 39, 3012.
24. Our synthetic spectra data of
We are grateful to National Basic Research Program of China
(973 Program, 2010CB833200), National Natural Science
2 was in agreement with that of Ghosh’s
group.