Stereoselective preparation of trisubstituted (Z)-alkenes; synthesis of the C17-C27 fragment of (-)-laulimalide

Article abstract of DOI:10.1016/j.tet.2005.01.002

A Ni-catalyzed cross-coupling reaction of (Z)-5-(tert-butyldiphenylsilyl) oxy-3-bromo-1-trimethylsilyl-3-penten-1-yne (1) with alkyl Grignard reagent gives (Z)-3-alkyl-5-(tert-butyldiphenylsilyl)oxy-1-trimethylsilyl-3-penten-1- ynes (2) stereospecifically

Full text of DOI:10.1016/j.tet.2005.01.002

Tetrahedron 61 (2005) 1971–1979
Stereoselective preparation of trisubstituted (Z)-alkenes;
synthesis of the C17–C27 fragment of (K)-laulimalide
*
Jun’ichi Uenishi, Masashi Ohmi, Katsuaki Matsui and Megumi Iwano
Kyoto Pharmaceutical University, Misasagi, Yamashina, Kyoto 607-8412, Japan
Received 2 December 2004; revised 28 December 2004; accepted 5 January 2005
Available online 21 January 2005
Abstract—A Ni-catalyzed cross-coupling reaction of (Z)-5-(tert-butyldiphenylsilyl)oxy-3-bromo-1-trimethylsilyl-3-penten-1-yne (1) with
alkyl Grignard reagent gives (Z)-3-alkyl-5-(tert-butyldiphenylsilyl)oxy-1-trimethylsilyl-3-penten-1-ynes (2) stereospecifically in good
yields. The (Z)-enyne 2a is transformed in four steps to (Z)-3-methyl-5-silyloxy-3-pentenal (3), which is coupled with ketophosphonate 4 to
give enone 13. The h-hydroxyallyl methanesulfonate derived from 13 is cyclized to 3,6-dihydro[2H]pyran by an intramolecular SN20
reaction stereoselectively, furnishing a C17–C27 carbon unit of (K)-laulimalide.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
zampanolide, haterumalide NA, and (C)-lasonolide A1 as
well as in acyclic marine natural products, such as (K)-
discodermolide, callystatin A and (K)-ratjadone.2
Stereocontrolled synthesis of tricarbon-substituted (Z)-
alkenes is important for the synthesis of organic molecules.
Since the configuration of the (Z)-structural unit in the
molecule can fix the shape, two substituted carbon branches
located in the cis relation of olefin play a specific role either
in the constitution of the macro-lactone ring structure or to
fix the conformation of acyclic structure, as shown in Figure
1. In fact, a methyl substituted (Z)-alkenyl unit can be
observed in the structures of biologically important natural
products, e.g. in macrolides, such as (K)-laulimalide, (K)-
Stepwise stereospecific cross-coupling of 1,1-dibromo-1-
alkene, as shown in Scheme 1, is a potential method for the
geometrically controlled synthesis of trisubstituted
alkenes.3 We reported carbon conjugated trisubstituted
alkenes by this method.4 More recently, we have reported
that Pd-catalyzed cross-coupling reaction of 3-bromo-3-en-
1-yne can afford both the (E)- or (Z)-trisubstituted alkenes
stereoselectively.5 In particular, isomerization of the (Z)-
alkenyl–palladium complex to the (E)-alkenyl–palladium
complex via cumulenyl–palladium complex intermediate
in CH2Cl2 or DMF and subsequent cross-coupling in
Sonogashira and Stille coupling is especially useful for
the synthesis of the tricarbon-substituted conjugated (Z)-
alkenyl unit, as shown in Scheme 2. After finding this
unique isomerization, we have reinvestigated our results
obtained previously by Ni-catalyzed Kumada–Tamao–
Corriu coupling reaction of bromoenyne,4a and have found
that the reaction proceeded completely with an inversion of
the stereochemistry and have made a correction of the
misassignment of the stereochemistry.6 In this paper, we
report the detail of this unique stereospecific synthesis of the
(Z)-alkenyl unit by Kumada–Tamao–Corriu cross-coupling
Figure 1.
Keywords: Bromoenyne; Trisubstituted (Z)-alkene; (K)-Laulimalide; SN20
reaction; 3,6-Dihydro[2H]pyran.
* Corresponding author. Tel.: C81 75 595 4665; fax: C81 75 595 4763;
e-mail: juenishi@mb.kyoto-phu.ac.jp
Scheme 1.
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.01.002

1972
J. Uenishi et al. / Tetrahedron 61 (2005) 1971–1979
careful reinvestigation of our previous results, this inversion
was found to occur exclusively in the Ni-catalyzed
Kumada–Tamao–Corriu coupling of 1 with ethylmagne-
sium bromide to give only (Z)-enyne. The coupling was
carried out either in THF, ether or benzene with alkyl-
magnesium halide in the presence of 5–10 mol% of
NiCl2(dppp). The yields were quite good with methyl and
trimethylsilylmethylmagnesium halide in 84 and 74% yields
for 2a and 2b, respectively. With ethylmagnesium bromide,
the yield of 2c was 61% along with a small amount of enyne
dimer and a reduced product by b-hydride elimination. The
reaction with phenylmagnesium bromide gave 2d poorly in
less than 20% yield. The stereochemistry of 2 was
confirmed by an NOE experiment after chemoselective
reduction of trimethylsilylethyne to trimethylsilylethane
with diimide,7 as shown in Scheme 3, and also conversion to
a dihydropyran ring in the later stage. It is interesting that
the isomerization by the 1,3-rearrangement can take place
depending on the solvent in the case of Pd catalyzed
reactions, although the corresponding rearrangement takes
place in most solvents in Ni-catalyzed cross-coupling
reaction to give an isomerized alkene. Since a geometrically
pure trisubstituted (Z)-alkene is an important functional
group in organic synthesis, this method will be useful not
only for the synthesis of the (Z)-enyne but also for that of a
trisubstituted alkene. In fact, a functionalization of the
trimethylsilylethynyl unit is possible such as to lead to other
functional groups including ethenyl, hydroxyethyl, formyl-
methyl, and carboxymethyl, which can be used for the
dihydropyran synthesis in Section 2.2.
Scheme 2.
of 3-bromo-3-en-1-yne and efficient access to the C17–C27
fragment of (K)-laulimalide by means of the (Z)-alkenyl
product.
2. Results and discussion
2.2. Synthetic plan for the C17–C27 fragment of (K)-
laulimalide
2.1. Kumada–Tamao–Corriu coupling of (Z)-3-bromo-1-
trimethylsilyl-3-penten-1-yne
(K)-Laulimalide is a marine natural product, possessing a
high degree of cytotoxicity in a number of human cancer
cell lines.8 Although several elegant total syntheses have
been achieved,9 the 4-methyl-3,6-dihydro[2H]pyran ring
located in the C23–C27 carbon chain, is prepared mostly by
ring closing metathesis9a,c,e–h and/or by hetero Diels–Alder
reaction.9b,d
Although the Pd-catalyzed cross-coupling reactions of (Z)-
5-(tert-butyldiphenylsilyl)oxy-3-bromo-1-trimethylsilyl-3-
penten-1-yne (1) with terminal alkyne, vinylboronic acid or
vinylstannane proceeded with retention of the configuration
in benzene under Sonogashira, Suzuki and Stille con-
ditions,4,5 we have recently reported the Sonogashira and
Stille reactions of 1 undergo with inversion of the
configuration in CH2Cl2 or DMF. We have proposed this
unusual isomerization mechanism by a 1,3-rearrangement
of the s-alkenyl–palladium complex through the cumu-
lenyl–palladium intermediate shown in Scheme 2.5 Upon
We planned to use the above (Z)-enyne unit for the
preparation of 4-methyl-3,6-dihydropyran. The structure
of (K)-laulimalide and its synthetic plan for the C17–C27
carbon skeleton including the pyran ring are outlined in
Scheme 3.

J. Uenishi et al. / Tetrahedron 61 (2005) 1971–1979
1973
Scheme 4.
Scheme 4. Reaction steps include a manipulation of
aldehyde 3 from trimethylsilyethynyl alkene 2a and the
Horner–Wadsworth–Emmons reaction of ketophosphonate
4 being derived from 5 with aldehyde 3 giving the a,b-
unsaturated ketone. The resultant enone will lead to
dihydropyran 7 in three steps via cyclization of allyl
methanesulfonate 6 by an intramolecular anti-SN20
reaction.
2.4. Preparation of ketophosphonate 4 and
Horner–Wadsworth–Emmons reaction
The synthesis of the C17–C20 carbon chain started from
a,b-unsaturated ester 5.11 Sharpless asymmetric dihydroxyl-
ation of 5 using AD-mix-a gave diol 11 in 96% yield with
99% ee after recrystallization.12 After a protection of the
diol as an acetonide by 2,2-dimethoxypropane in the
presence of CSA, the reaction of acetonide 12 with lithium
salt of dimethyl methylphosphonate gave ketophosphonate
4 in 80% yield in two steps. Horner–Wadsworth–Emmons
reaction of 4 with 3 in the presence of K2CO3 in THF and
water13 gave enone 13 in 70% yield (Scheme 6).
2.3. Preparation of aldehyde 3
Conversion of 2a to aldehyde 3 required four steps. First,
hydroboration of the terminal alkyne and successive
oxidation by Zweifel’s method10 gave carboxylic acid 8 in
72% yield. This acid was led to the methyl ester by
treatment with iodomethane in the presence of K2CO3 to
give 9 quantitatively. Reduction of the ester with LiBH4 in
THF afforded alcohol 10 in 79% yield. Oxidation of 10 with
Dess-Martin periodinane gave aldehyde 3 quantitatively
(Scheme 5).
2.5. Ring formation of 3,6-dihydro[2H]pyran
The precursors for the cyclization to 3,6-dihydro[2H]pyran
were prepared from 13. Although a reduction of ketone
with certain hydride reagents such as LiAl(OtBu)3H or
DIBAL-H gave a lower selectivity along with the 1,4-
reduction product, that with NaBH4 in the presence of CeCl3
Scheme 5.

1974
J. Uenishi et al. / Tetrahedron 61 (2005) 1971–1979
Scheme 6.
Mitsunobu reaction of 14b with benzoic acid in the presence
of diethyl diazodicarboxylate (DEAD) gave a 1:1 mixture of
15a (C21 benzoate) and 15a0 (C23 benzoate) in 81% yield,
which were separated by HPLC. The less polar compound
15a was obtained with a O10:1 diastereomeric ratio over
the other diastereomer 15b. Meanwhile, the regioisomer
15a0 contained its diastereomer 15b0 with a 20% diastereo-
meric ratio. Finally, methanolysis of 15a gave 14a in 97%
yield (Scheme 7).
Treatment of 14b with methanesulfonic anhydride in the
presence of triethylamine in CH2Cl2 at 0 8C gave the
corresponding methanesulfonate quantitatively. Without
purification, it was subjected to an SN20 reaction. When
the methanesulfonate was treated with TBAF in benzene,
(S)-dihydropyran 7 was obtained along with its diastereomer
70 in 60% yield with a 5.5:1 ratio. This reaction may be
explained as follows. As soon as the deprotection of the silyl
group with TBAF occurred, a generated oxygen nucleophile
attacks the C23 carbon from si-face to form the pyran ring
and simultaneous elimination of the methanesulfonate
produces the (E)-alkenyl bond and (S)-chiral center in an
anti-SN20 fashion. The undesired (R)-isomer was produced
via a SN10 type reaction in a 15% diastereomeric ratio. On
the other hand, the opposite stereochemistry took place in
the same reaction of 14a in which dihydropyran 70 was
obtained for the most part along with 7 in 61% yield with a
5:1 ratio. Tosylate or nosylate of 14a did not work well. In
Scheme 7.
at K78 8C gave b-allylic alcohol 14b in 80% yield
selectively, with a O10:1 ratio. An b-alcohol was
predominantly produced as was reported in the similar
function system.14 The other stereoisomer was prepared by
an inversion of this chiral alcohol using Mitsunobu reaction.
Scheme 8.

J. Uenishi et al. / Tetrahedron 61 (2005) 1971–1979
1975
Figure 2.
both cases, substitutions proceeded well in benzene in about
5:1 ratio but gave a lower ratio in THF (Scheme 8).
4.2. Kumada–Tamao–Corriu coupling of bromoenyne
with Grignard reagents
The stereochemistry of 3,6-dihydro[2H]pyran was con-
firmed after a conversion to the fragment that Wender et al.
used for their total synthesis of (K)-laulimalide.9d Func-
tionalization and two-carbon extension by seven-step
reactions from 7 reached a,b-unsaturated aldehyde 16.15
The proton NMR of the Wender’s a,b-unsaturated aldehyde
16 was exactly matched with that of the major isomer being
derived from 7. Its specific degree K94 (c 0.26, CHCl3) was
quite close to that of the Wender’s intermediate [K90
(c 1.86, CDCl3)]. On the other hand, the specific degree
of its diastereomer 160 derived from 70 was found to be K20
(c 0.11, CHCl3) (Fig. 2).
To a mixture of bromoenyne 1 (1.42 g, 3 mmol) and
NiCl2(dppp) (81 mg, 5 mol%) in THF (7.5 mL) was
dropped a THF solution of MeMgBr (0.93 M, 9.6 mL) at
0 8C. Then the cooling bath was removed and the mixture
was stirred at room temperature. After 1–4 h, the mixture
was quenched with water and extracted with hexane (two
times). The combined extracts were washed with satd
NH4Cl, water, and brine. The extract was dried over MgSO4
and concentrated under reduced pressure. The residual oil
was purified by silica gel column chromatography to give 2
as an oil. Reaction time; 4 h for 2a, 1 h for 2b, 1.5 h for 2c
and 1.0 h for 2d. Eluents for chromatography; 5% benzene
in hexane for 2a, 3% EtOAc in hexane for 2b, 2% EtOAc in
hexane for 2c and 10% benzene in hexane for 2c.
3. Conclusion
4.2.1. (Z)-5-(tert-Butyldiphenylsilyl)oxy-3-methyl-1-tri-
methylsilyl-3-penten-1-yne (2a). Oil, 84% yield. RfZ0.5
(20% benzene in hexane); H NMR (300 MHz, CDCl3) d
0.08 (9H, s), 1.06 (9H, s), 1.83 (3H, q, JZ1.3 Hz), 4.42 (2H,
dq, JZ6.2, 1.3 Hz), 5.88 (1H, td, JZ6.2, 1.3 Hz), 7.34–7.42
(6H, m), 7.67–7.70 (4H, m). 13C NMR (75 MHz, CDCl3) d
K0.13, 19.2, 22.7, 26.9, 63.2, 103.4, 118.7, 127.6, 127.7,
129.5, 133.9, 135.5, 137.8. IR (film) cmK1: 2137. MS (EI)
m/z: 406 (MC). HR-MS (EI) m/z: 406.2144 (calcd for
C25H34OSi2: 406.2148).
A Ni-catalyzed cross-coupling reaction of 1 with alkyl
Grignard reagent gave alkylated (Z)-enyne 2 with inversion
of the initial configuration stereospecifically. A ring
construction of 3,6-dihydro[2H]pyran was achieved by an
intramolecular SN20 reaction of h-hydroxyallyl methane-
sulfonate. The substitution reaction accompanied with
chirality transfer effectively gave the C17–C27 carbon
unit of (K)-laulimalide.
1
4. Experimental
4.1. General
4.2.2. (Z)-5-(tert-Butyldiphenylsilyl)oxy-5-trimethylsilyl-
1-(trimethylsilyl)methyl-3-penten-1-yne (2b). Oil, 74%
yield. RfZ0.53 (3% tBuOMe in hexane). 1H NMR
(300 MHz, CDCl3) d 0.05 (9H, s), 0.05 (9H, s), 1.05 (9H,
s), 1.60 (2H, s), 4.43 (2H, d, JZ6.3 Hz), 5.70 (1H, t, JZ
6.3 Hz), 7.34–7.41 (6H, m), 7.67–7.70 (4H, m). 13C NMR
(75 MHz, CDCl3) d K1.5, K0.2, 19.3, 26.9, 27.3, 63.3,
104.2, 121.1, 127.6, 128.3, 129.5, 134.0, 134.8, 135.5. MS
(EI) m/z: 478 (MC). HR-MS (EI) m/z: 478.2539 (calcd for
C28H42OSi3: 478.2544).
1H NMR and 13C NMR spectra were recorded at 300 or
400 MHz and at 75 or 100 MHz, respectively. Melting
points were obtained on a melting point apparatus and were
uncorrected. Mass spectra were recorded using electron
impact (EI) ionization at 70 or 20 eV or chemical ionization
(CI) with isobutene gas. Silica gel (70–230 mesh) was used
for flash chromatography. Analytical thin-layer chromato-
graphy (TLC) was performed on glass pre-coated with
silica gel (0.25 mm thickness). High performance liquid
chromatography (HPLC) was carried out on a UV spectro-
photomeric detector (254 nm) to which a 20!250 mm size
column packed with silica gel was attached. All experiments
were carried out under an argon atmosphere. THF and ether
were dried over sodium/benzophenone ketyl, and CH2Cl2
was dried over P2O5, and they were distilled prior to use.
The solvent extracts were dried over MgSO4, and the
solutions were evaporated under reduced pressure. AD-mix-a
was purchased from Sigma-Aldrich chemical company.
4.2.3. (Z)-5-(tert-Butyldiphenylsilyl)oxy-3-ethyl-1-tri-
methylsilyl-3-penten-1-yne (2c). Oil, 61% yield. RfZ
0.53 (20% benzene in hexane); 1H NMR (300 MHz,
CDCl3) d 0.09 (9H, s), 1.06 (9H, s), 1.06 (3H, t, JZ
7.7 Hz), 2.11 (2H, q, JZ7.3 Hz), 4.46 (2H, d, JZ6.2 Hz),
5.88 (1H, t, JZ6.2 Hz), 7.37–7.42 (6H, m), 7.67–7.70 (4H,
m). 13C NMR (75 MHz, CDCl3) d 0.0, 12.9, 19.3, 27.0, 29.8,
63.3, 99.8, 125.2, 128.0, 128.4, 129.6, 134.0, 135.7, 136.3.
IR (film) cmK1: 2141. MS (EI) m/z: 420 (MC). HR-MS (EI)
m/z: 420.2300 (calcd for C26H36OSi2: 420.2305).

1976
J. Uenishi et al. / Tetrahedron 61 (2005) 1971–1979
4.2.4. (Z)-5-(tert-Butyldiphenylsilyl)oxy-3-phenyl-1-tri-
methylsilyl-3-penten-1-yne (2d). Oil, 17% yield. RfZ
0.34 (2% EtOAc in hexane); 1H NMR (300 MHz, CDCl3) d
0.13 (9H, s), 1.09 (9H, s), 4.68 (2H, d, JZ6.2 Hz), 6.58 (1H,
t, JZ6.2 Hz), 7.25–7.45 (9H, m), 7.53–7.59 (2H, m), 7.68–
7.75 (4H, m). 13C NMR (75 MHz, CDCl3) d K0.10, 19.3,
26.8, 63.9, 101.0, 123.0, 126.1, 127.7, 127.9, 128.3, 129.6,
133.7, 135.6, 137.0, 137.9. IR (film) cmK1: 2141. MS (EI)
m/z: 468 (MC). HR-MS (EI) m/z: 468.2298 (calcd for
C30H36OSi2: 468.2305).
m), 7.64–7.70 (4H, m). 13C NMR (100 MHz, CDCl3) d 19.1,
23.9, 26.8, 37.5, 51.8, 60.8, 127.6, 128.4, 129.6, 130.0,
133.8, 135.6, 171.5. IR (neat) cmK1: 3071, 3049, 2932,
2857, 1741, 1429, 1110, 1057. MS (EI) m/z: 382 (MC), 325,
213, 199, 105, 95. HR-MS (EI): m/z 382.1967 (calcd for
C23H30O3Si: 382.1964).
4.3.3. (Z)-5-(tert-Butyldimethylsilyl)oxy-3-methyl-3-pen-
ten-1-ol (10). LiBH4 (1.25 g, 57 mmol) was added to a
solution of 9 (7.28 g, 19 mmol) in THF (100 mL) at 0 8C by
several portions, and the reaction was continued for 15 h at
room temperature. Then, water was added and the mixture
was extracted with ether several times. The combined
extracts were washed with water, brine and dried over
MgSO4, and concentrated. The residual oil was purified by
column chromatography on silica gel eluted with 20%
EtOAc in hexane to give 10 (5.36 g) in 79% yield. Colorless
oil, RfZ0.60 (20% EtOAc in hexane). 1H NMR (400 MHz,
CDCl3) d 1.04 (9H, s), 1.74–1.76 (3H, m), 2.24 (2H, t, JZ
6.2 Hz), 3.61 (2H, t, JZ6.2 Hz), 4.15 (2H, d, JZ7.1 Hz),
5.58 (1H, t, JZ7.1 Hz), 7.36–7.44 (6H, m), 7.68–7.72 (4H,
m). 13C NMR (100 MHz, CDCl3) d 19.1, 23.5, 26.8, 35.2,
59.9, 60.1, 126.8, 127.7, 128.3, 129.7, 133.6, 135.6. IR
(neat) cmK1: 3392, 3071, 3048, 2931, 2857, 1472, 1428,
1112, 1062. MS (EI) m/z: 354 (MC), 297, 267, 219, 199,
152, 78. HR-MS (EI): m/z 354.2020 (calcd for C22H30O2Si:
354.2015).
4.3. Preparation of the C23–C27 carbon chain
4.3.1. (Z)-5-(tert-Butyldimethylsilyl)oxy-3-methyl-3-pen-
tenoic acid (8). To a THF solution of borane (70 mmol) in
THF (75 mL) was added 2-methyl-2-butene (14.8 mL,
140 mmol) dropwise at K15 8C and the mixture was stirred
at 0 8C for 2 h. This mixture was recooled to K40 8C, and a
THF (20 mL) solution of 2a (9.43 g, 23.2 mmol) was
dropped. The mixture was allowed to warm up to K3 8C
gradually during 3 h, and then quenched with MeOH
(30 mL) carefully at K10 8C. The whole mixture was
further stirred for an additional 30 min at K10 8C. Aq
sodium hydroxide (70 mL of 3 M solution) and hydrogen
peroxide (24 mL of 30% solution) were added to the
mixture at the same temperature. After stirring for 30 min,
the mixture was acidified with aq HCl (1 M solution) at the
same temperature and allowed to warm up to room
temperature. The reaction mixture was extracted with
EtOAc three times, and the extracts were washed with aq
sodium thiosulfate, water, and brine successively. After
drying over MgSO4, the extract was condensed and the
residual oil was purified by column chromatography on
silica gel eluted with EtOAc to give carboxylic acid 8
(6.15 g) in 72% yield as a colorless oil. RfZ0.61 (40%
EtOAc in hexane).
4.3.4. (Z)-5-(tert-Butyldimethylsilyl)oxy-3-methyl-3-pen-
ten-1-al (3). To a solution of 10 (2.76 g, 7.75 mmol) in
CH2Cl2 (75 mL) was added Dess-Martin periodinate
(4.94 g, 11.65 mmol) in an ice bath. After the addition,
the bath was removed and the mixture was stirred for 30 min
at room temperature. Then the mixture was quenched with
satd sodium thiosulfate and satd NaHCO3, and the whole
mixture was extracted with ether three times. The combined
extracts were washed with water and brine and dried over
MgSO4. Solvent was removed under a reduced pressure to
give a crude aldehyde 3 which was used for the next
Hornor–Wadsworth–Emonns reaction without further puri-
fication. RfZ0.86 (20% EtOAc in hexane). 1H NMR
(300 MHz, C6D6) d 1.26 (9H, s), 1.55 (3H, s), 2.54 (2H,
d, JZ2.0 Hz), 4.23 (2H, d, JZ6.3 Hz), 5.73 (1H, t, JZ
6.3 Hz), 7.30–7.40 (6H, m), 7.85–7.92 (4H, m), 9.10 (1H, t,
JZ2.0 Hz).
1H NMR (400 MHz, CDCl3) d 1.04 (9H, s), 1.80 (3H, d, JZ
1.3 Hz), 2.93 (2H, s), 4.19 (2H, dd, JZ6.4, 1.1 Hz), 5.63
(1H, t, JZ6.4 Hz), 7.36–7.44 (6H, m), 7.66–7.70 (4H, m).
13C NMR (100 MHz, CDCl3) d 19.1, 23.9, 26.8, 37.8, 60.7,
127.7, 128.4, 129.7, 130.6, 133.5, 135.6, 176.0. IR (neat)
cmK1: 3071, 3049, 2931, 2858, 1712, 1428, 1111, 1057.
CI-MS (CI) m/z: 369 (MCCH), 367, 311, 233, 199, 189,
113. HR-MS (CI): m/z 369.1877 (calcd for C22H29O3Si:
369.1886).
4.4. Preparation of the C17–C27 ketophosphonate
4.3.2. Methyl (Z)-5-(tert-butyldimethylsilyl)oxy-3-
methyl-3-pentenoate (9). To a mixture of 8 (6.79 g,
18.4 mmol) and iodomethane (3.44 mL, 55.3 mmol) in
anhydrous acetone (100 mL) was added anhydrous pow-
dered potassium carbonate (12.7 g, 92 mmol), and the
mixture was stirred for 5 h at room temperature. Then, it
was quenched with satd NH4Cl (10 mL) and the whole was
condensed to a half volume under a reduced pressure. The
mixture was extracted with ether and the extract was washed
with brine, and dried over MgSO4. Solvent was removed
and the residual oil was chromatographed on silica gel
eluted with 5% EtOAc in hexane to give 9 (7.0 g) as a
colorless oil in quantitative yield. RfZ0.22 (5% EtOAc in
4.4.1. Ethyl (2R,3S)-2,3-dihydroxy-5-(4-methoxybenzyl)
oxypentanoate (11). A suspension of AD-mix-a (25.1 g,
1.40 g/mol) in a 1:1 mixture of tBuOH and water (180 mL)
was stirred for 15 min at room temperature, and then
MeSO2NH2 (1.70 g, 17.9 mmol) and unsaturated ester 5
(4.73 g, 17.9 mmol) were added to the mixture at 0 8C. After
being stirred for 1 day at the same temperature, the reaction
mixture was quenched with satd sodium thiosulfate and
extracted with EtOAc three times. The extracts were
combined and washed with dil. HCl, water and brine. The
organic extract was dried over MgSO4, and concentrated.
The residue was purified by flash column chromatography
on silica gel eluted with 40% EtOAc in hexane to give
11 (5.14 g) in 96% yield which was recrystallized by
isopropyl ether to give pure colorless crystals over 99% ee.
1
hexane). H NMR (400 MHz, CDCl3) d 1.04 (9H, s), 1.77
(3H, d, JZ1.3 Hz), 2.87 (2H, s), 3.59 (3H, s), 4.21 (2H, d,
JZ6.4 Hz), 5.58 (1H, td, JZ6.4, 1.3 Hz), 7.35–7.44 (6H,

J. Uenishi et al. / Tetrahedron 61 (2005) 1971–1979
1977
Mp 39–40 8C (from diisopropyl ether) lit. mp 40 8C.12 RfZ
4.5. Preparation of the C17–C27 carbon chain
0.22 (50% EtOAc in hexane). [a]2D2 K2.0 (c 1.19, CHCl3).
1H NMR (400 MHz, CDCl3) d 1.30 (3H, t, JZ7.1 Hz),
1.79–1.87 (1H, m), 1.99–2.07 (1H, m), 2.90–3.02 (1H, br),
3.18–3.24 (1H, br), 3.62–3.74 (2H, m), 3.80 (3H, s), 4.06
(1H, brs), 4.14–4.19 (1H, m), 4.24–4.32 (2H, m), 4.46 (2H,
s), 6.88 (2H, d, JZ6.6 Hz), 7.25 (2H, d, JZ6.6 Hz). 13C
NMR (100 MHz, CDCl3) d 14.1, 33.2, 55.3, 61.9, 67.8,
71.6, 73.0, 73.6, 113.8, 129.4, 129.9, 159.3, 173.2.
4.5.1. (2E,5Z)-7-(tert-Butyldiphenylsilyl)oxy-1-{(4R,5S)-
2,2-dimethyl-5-[2-(4-methoxybenzyl)oxyethyl]-[1,3]-
dioxolan-4-yl}-5-methyl-hepta-2,5-dien-1-one (13). A
mixture of ketophosphonate 4 (1.94 g, 4.66 mmol), crude
aldehyde 3 (3.1 mmol), and anhydrous powdered K2CO3
(856 mg, 6.2 mmol) was stirred in a 1:1 mixture of THF–
water (40 mL) at room temperature. After 3 h, the reaction
was quenched with satd NH4Cl, and extracted with EtOAc.
The extract was washed with water and brine and dried over
MgSO4. Solvent was removed and the residue was purified
by flash column chromatography on silica gel eluted with
10% EtOAc in hexane to give 13 (1.4 g) in 70% yield. A
colorless oil. RfZ0.30 (15% EtOAc in hexane). [a]2D9 2.6 (c
4.4.2. Ethyl (4R,5S)-2,2-dimethyl-5-[2-(4-methoxybenzyl)
oxyethyl]-[1,3]dioxolan-4-carboxylate (12). A mixture of
diol 11 (4.4 g, 14.7 mmol) and CSA (1.13 g, 4.42 mmol)
was stirred in 2,2-dimethoxypropane at rt for 3 h. After an
addition of aq NaHCO3, the reaction mixture was diluted
with EtOAc and washed with water and brine. The organic
layer was dried over MgSO4 and the solvent was
evaporated. The residual oil was chromatographed on silica
gel eluted with 10% EtOAc in hexane to give acetonide 12
(4.03 g) in 80% yield. A colorless oil, RfZ0.48 (20%
1
1.20, CHCl3). H NMR (400 MHz, CDCl3) d 1.04 (9H, s),
1.34 (3H, s), 1.43 (3H, s), 1.68 (3H, d, JZ1.3 Hz), 1.87–
1.96 (1H, m), 1.98–2.07 (1H, m), 2.74 (2H, d, JZ6.8 Hz),
3.49–3.62 (2H, m), 3.78 (3H, s), 4.15–4.18 (4H, m), 4.39
(2H, s), 5.54 (1H, td, JZ6.4, 1.3 Hz), 6.44 (1H, dt, JZ15.8,
1.6 Hz), 6.83 (1H, dt, JZ15.8, 6.8 Hz), 6.84 (2H, d, JZ
8.8 Hz), 7.21 (2H, d, JZ8.8 Hz), 7.35–7.44 (6H, m), 7.65–
7.69 (4H, m). 13C NMR (100 MHz, CDCl3) d 19.1, 23.5,
26.1, 26.8, 27.2, 33.6, 35.4, 55.3, 60.6, 66.3, 72.5, 75.7,
84.1, 110.2, 113.7, 125.7, 127.2, 127.7, 129.2, 129.6, 130.4,
1
EtOAc in hexane). [a]2D5 K19.1 (c 1.23, CHCl3). H NMR
(400 MHz, CDCl3) d 1.27 (3H, t, JZ7.1 Hz), 1.44 (3H, s),
1.46 (3H, s), 1.96 (1H, dddd, JZ14.1, 7.7, 5.9, 5.7 Hz), 2.10
(1H, dddd, JZ14.1, 7.7, 6.6, 4.4 Hz), 3.54–3.66 (2H, m),
3.80 (3H, s), 4.13–4.32 (4H, m), 4.43 (2H, s), 6.87 (2H, d,
JZ8.8 Hz), 7.25 (2H, d, JZ8.8 Hz). 13C NMR (100 MHz,
CDCl3) d 14.1, 25.7, 27.1, 33.6, 55.3, 61.3, 66.3, 72.6, 76.5,
79.1, 110.7, 113.7, 129.2, 130.4, 159.1, 170.7. IR (neat)
cmK1: 2988, 2936, 2866, 1757, 1736, 1613, 1586, 1513,
1372, 1249, 1099, 1036. MS (EI) m/z: 338 (MC), 323, 280,
262, 233, 177, 189, 136. HR-MS (EI): m/z 338.1727 (calcd
for C18H26O6: 338.1729).
133.0, 133.7, 135.6, 146.7, 159.1, 197.5. IR (neat) cmK1
:
3070, 2932, 2857, 1692, 1617, 1587, 1513, 1248, 1110. MS
(EI) m/z: 642 (MC), 585, 459, 433, 199, 143. HR-MS (EI):
m/z 642.3380 (calcd for C39H50O6Si: 642.3376).
4.5.2. (2E,5Z)-(1R)-7-(tert-Butyldiphenylsilyl)oxy-1-
{(4R,5S)-2,2-dimethyl-5-[2-(4-methoxybenzyl)oxyethyl]-
[1,3]dioxolan-4-yl}-5-methyl-hepta-2,5-dien-1-ol (14b).
To a stirred mixture of 13 (1.75 g, 2.72 mmol) and CeCl3
heptahydrate (1.52 g, 4.08 mmol) in methanol (28 mL),
NaBH4 (154 mg, 4.08 mmol) was added at K78 8C by
several portions during 1 h. Then, the cooling bath was
removed and the mixture was allowed to warm up to room
temperature. Water was added and the mixture was
extracted with EtOAc. The organic extract was washed
with water and brine and dried over MgSO4. After removal
of solvent, the residue was purified by flash chromatography
on silica gel eluted with 20% EtOAc in hexane. Alcohol
14b (1.41 g) was obtained in 80% yield with a O10:1
diastereomeric ratio. A colorless oil, RfZ0.29 (20% EtOAc
in hexane). [a]D24 K9.4 (c 1.56, CHCl3). 1H NMR
(400 MHz, CDCl3) d 1.05 (9H, s), 1.39 (6H, s), 1.67 (3H,
d, JZ1.1 Hz), 1.73–1.91 (2H, m), 2.59 (2H, t, JZ6.5 Hz),
3.48–3.58 (2H, m), 3.63 (1H, dd, JZ7.7, 4.8 Hz), 3.80 (3H,
s), 3.97 (1H, dd, JZ7.9, 4.0 Hz), 3.98 (1H, dd, JZ7.9,
4.8 Hz), 4.20 (2H, d, JZ6.4 Hz), 4.41 (2H, s), 5.37 (1H, dd,
JZ15.3, 6.8, 1.1 Hz), 5.46 (1H, t, JZ6.4 Hz), 5.54 (1H, dtd,
JZ15.3, 6.5, 1.1 Hz), 6.87 (2H, d, JZ8.8 Hz), 7.23 (2H, d,
JZ8.8 Hz), 7.36–7.42 (6H, m), 7.67–7.71 (4H, m). 13C
NMR (100 MHz, CDCl3) d 19.2, 23.4, 26.8, 27.1, 27.4,
33.6, 35.1, 55.2, 60.6, 66.8, 72.3, 72.7, 75.0, 83.7, 108.9,
113.7, 125.7, 127.6, 129.2, 129.6, 129.7, 130.4, 131.1,
133.9, 135.1, 135.6, 159.1. IR (neat) cmK1: 3466, 3070,
2932, 2857, 1613, 1514, 1248, 1109, 1039. MS (EI) m/z:
644 (MC), 629, 587, 443, 388, 313, 295, 213, 199. HR-MS
(EI): m/z 644.3541 (calcd for C39H52O6Si: 644.3533).
4.4.3. Dimethyl 2-{(4R,5S)-2,2-dimethyl-5-(4-methoxy-
benzyl)oxyethyl-[1,3]dioxolan-4-yl}-2-oxo-ethyl-1-phos-
phonate (4). To a solution of lithium salt of dimethyl
methylphosphonate generated from dimethyl methylphos-
phonate (3.40 g, 27.4 mmol) with nBuLi (1.57 M in hexane
solution, 15.1 mL) at K78 8C in anhydrous THF (100 mL),
a THF (20 mL) solution of ester 12 (4.03 g, 11.9 mmol) was
added dropwise at K78 8C and the mixture was stirred for
30 min at the same temperature. Satd NH4Cl was added to
the mixture and it was extracted with EtOAc. The organic
extract was washed with water and brine and dried over
MgSO4. Solvent was removed and the residue was purified
by column chromatography on silica gel eluted with EtOAc
to give 4 (4.96 g) with a quantitative yield. A colorless oil.
1
RfZ0.65 (EtOAc). [a]2D5 C22.2 (c 1.54, CHCl3). H NMR
(400 MHz, CDCl3) d 1.41 (3H, s), 1.44 (3H, s), 1.88–1.99
(1H, m), 2.02–2.11 (1H, m), 3.25 (1H, dd, JZ21.8,
14.5 Hz), 3.44 (1H, dd, JZ22.5, 14.5 Hz), 3.53–3.64 (2H,
m), 3.77 (3H, d, JZ6.0 Hz), 3.79 (3H, d, JZ6.0 Hz), 3.80
(3H, s), 4.17 (1H, d, JZ7.7 Hz), 4.22 (1H, ddd, JZ11.7,
7.7, 7.5 Hz), 4.42 (2H, s), 6.86 (2H, d, JZ8.8 Hz), 7.24 (2H,
d, JZ8.8 Hz). 13C NMR (100 MHz, CDCl3) d 26.2, 27.1,
33.6, 35.8, 37.2, 52.9, 53.0 (d, JZ6.5 Hz), 53.2 (JZ6.1 Hz),
66.2, 72.6, 75.1, 84.8, 84.8, 110.5, 113.6, 113.7, 129.3,
130.4, 159.1, 201.6 (d, JZ7.2 Hz). IR (neat) cmK1: 3473,
2988, 2955, 2856, 1717, 1613, 1514, 1250, 1033. MS (EI)
m/z: 416 (MC), 350, 340, 272, 237, 222, 176. HR-MS (EI):
m/z 416.1601 (calcd for C19H29O8P: 416.1600).

1978
J. Uenishi et al. / Tetrahedron 61 (2005) 1971–1979
4.6. Mitsunobu reaction of 14b with benzoic acid;
preparation of 15a and 15a0
A mixture of benzoate 15a (120 mg, 0.16 mmol) and
powdered K2CO3 (111 mg, 0.8 mmol) in methanol (1.6 mL)
was stirred for 2 h at room temperature. The mixture was
poured into cold water and extracted with ether. The extract
was washed with water and brine and dried over MgSO4.
After solvent was removed, the residue was purified by flash
chromatography on silica gel eluted with 20% EtOAc in
hexane to give alcohol 14a (100 mg) in 97% yield. Colorless
oil, RfZ0.52 (30% EtOAc in hexane). [a]2D3 K8.3 (c 1.18,
To a mixture of 14b (926 mg, 1.44 mmol), benzoic acid
(352 mg, 2.88 mmol), and triphenylphosphine (755 mg,
2.88 mmol) in benzene, diethyl diazodicarboxylate
(1.25 mL, 40% in toluene solution) was dropped in an ice
bath. After the mixture was stirred for 1 h at the same
temperature, water was added and the mixture was extracted
with ether. The ethereal extract was washed with water, and
brine and dried over MgSO4. After the solvent was
removed, the crude product was purified by flash column
chromatography on silica gel eluted with 10% EtOAc in
hexane. A 1:1 mixture of C21 and C23 benzoates, 15a and
15a0 (871 mg) were obtained in 81% yield. They were
separated by HPLC with 15% EtOAc in hexane as an eluent
(12 mL/min).
1
CHCl3). H NMR (400 MHz, CDCl3) d 1.04 (9H, s), 1.36
(3H, s), 1.37 (3H, s), 1.67 (3H, d, JZ1.5 Hz), 1.75–1.84
(1H, m), 1.86–1.95 (1H, m), 2.59 (2H, d, JZ6.4 Hz), 3.50–
3.60 (2H, m), 3.68 (1H, dd, JZ8.1, 4.6 Hz), 3.79 (3H, s),
4.00 (1H, td, JZ8.1, 3.7 Hz), 4.15 (1H, td, JZ6.1, 0.9 Hz),
4.20 (2H, dd, JZ6.6, 1.2 Hz), 4.41 (2H, s), 5.39–5.48 (2H,
m), 5.54 (1H, dtd, JZ15.4, 6.6, 1.1 Hz), 6.86 (2H, d, JZ
8.6 Hz), 7.23 (2H, d, JZ8.6 Hz), 7.36–7.44 (6H, m), 7.66–
7.70 (4H, m). 13C NMR (100 MHz, CDCl3) d 19.2, 23.4,
26.8, 27.0, 27.3, 34.2, 35.1, 55.3, 60.7, 66.9, 71.8, 72.7,
74.8, 83.2, 108.6, 113.8, 125.7, 127.6, 128.9, 129.3, 129.6,
4.6.1. Compound 15a. Colorless oil (less polar isomer,
retention time 11.9 min), RfZ0.57 (20% EtOAc in hexane)
[a]2D5 K18.6 (c 0.93, CHCl3). 1H NMR (400 MHz, CDCl3) d
1.02 (9H, s), 1.30 (3H, s), 1.38 (3H, s), 1.63 (3H, d, JZ
1.1 Hz), 1.90–2.00 (2H, m), 2.60 (2H, d, JZ6.4 Hz), 3.50–
3.62 (2H, m), 3.77 (3H, s), 3.93 (1H, dd, JZ8.0, 3.5 Hz),
4.04 (1H, td, JZ8.0, 3.7 Hz), 4.17 (2H, dd, JZ6.4, 1.1 Hz),
4.39 (2H, s), 5.44 (1H, t, JZ6.4 Hz), 5.52–5.67 (3H, m),
6.82 (2H, d, JZ8.8 Hz), 7.19 (2H, d, JZ8.8 Hz), 7.33–7.44
(8H, m), 7.53–7.59 (1H, m), 7.64–7.68 (4H, m), 8.02–8.05
(2H, m). 13C NMR (100 MHz, CDCl3) d 19.1, 23.3, 26.8,
26.9, 27.4, 34.0, 35.1, 55.2, 60.6, 66.6, 72.5, 74.4, 75.2,
82.0, 109.3, 113.7, 125.3, 125.9, 127.6, 128.4, 129.1, 129.5,
129.7, 130.2, 130.5, 133.0, 133.6, 133.9, 134.8, 135.6,
159.1, 165.4. IR (neat) cmK1: 2932, 2857, 1722, 1613,
1514, 1249, 1110. MS (EI) m/z: 748 (MC), 733, 691, 634,
615, 313, 295, 199. HR-MS (EI): m/z 748.3788 (calcd for
C46H56O7Si: 748.3795).
130.4, 130.7, 133.9, 135.2, 135.6, 159.2. IR (neat) cmK1
:
3450, 3033, 2932, 2857, 1613, 1514, 1428, 1249, 1110,
1040. MS (EI) m/z: 644 (MC), 629, 587, 388, 313, 295, 213,
199. HR-MS (EI): m/z 644.3528 (calcd for C39H52O6Si:
644.3533).
4.6.4. Stereoselective dihydropyran ring formation by
SN20 reaction; preparation of 7 and 70. A mixture of
alcohol 14 (a or b, 0.2 mmol), triethylamine (1.4 mmol) and
methanesulfonic anhydride (1 mmol) was stirred in CH2Cl2
(2 mL) at 0 8C for 1 h. A cold water was added to the
mixture, and it was extracted with ether. The ethereal layer
was quickly washed with aq NaHCO3, water, and brine and
dried over MgSO4. Evaporation of solvent and residue was
dissolved in benzene (1 mL). To this solution a THF
solution of tetrabutylammonium fluoride (1 M, 1 mL) was
added and the mixture was stirred for overnight at room
temperature. Then, the mixture was quenched with water
and extracted with ether. The extract was washed with water
and brine and dried over MgSO4. Solvent was removed and
the residue was purified by flash chromatography on silica
gel eluted with 20% EtOAc in hexane to give a colorless oil.
A 5.5:1 mixture of 7 and 70 was obtained from 14b in 60%
yield, and a 1:5 mixture was obtained from 14a in 61%
yield. The mixture of 7 and 70 were not separable by column
chromatography, TLC, and HPLC. A mixture of 7 and 70.
Colorless oil, RfZ0.36 (20% EtOAc in hexane). IR (neat)
cmK1: 2933, 2853, 1613, 1514, 1247, 1091, 1037. MS (EI)
m/z: 388 (MC), 370, 330, 312, 267, 209, 160, 136. HR-MS
(EI): m/z [M]C 388.2251 (calcd for C23H32O5: 388.2250).
1H NMR and 13C NMR are following; 7; 1H NMR
(400 MHz, CDCl3) d 1.40 (3H, s), 1.40 (3H, s), 1.69 (3H,
brs), 1.77–1.95 (3H, m), 1.99–2.08 (1H, m), 3.51–3.63 (2H,
m), 3.80 (3H, s), 3.83 (1H, td, JZ8.2, 4.0 Hz), 4.00–4.06
(1H, m), 4.06 (1H, dd, JZ8.2, 7.5 Hz), 4.11–4.22 (2H, m),
4.43 (2H, s), 5.41 (1H, brs), 5.70 (1H, ddd, JZ15.6, 7.5,
1.3 Hz), 5.87 (1H, ddd, JZ15.6, 5.4, 0.5 Hz), 6.86 (2H, d,
JZ8.8 Hz), 7.25 (2H, d, JZ8.8 Hz). 13C NMR (100 MHz,
CDCl3) d 22.9, 26.9, 27.2, 32.0, 35.6, 55.2, 65.6, 66.7, 72.6,
73.1, 77.8, 81.9, 108.6, 113.7, 119.6, 127.4, 129.2, 130.5,
131.3, 135.4, 159.1. 70; 1H NMR (400 MHz, CDCl3) d 1.40
(3H, s), 1.40 (3H, s), 1.69 (3H, brs), 1.78–1.94 (3H, m),
2.01–2.11 (1H, m), 3.51–3.64 (2H, m), 3.80 (3H, s), 3.79–
4.6.2. Compound 15a0. Colorless oil (polar isomer,
retention time 13.5 min), RfZ0.57 (20% EtOAc in hexane).
The diastereomeric ratio of (S)- and (R)-benzoates was 4:1.
The spectral data are described for only the major isomer.
1H NMR (400 MHz, CDCl3) d 1.03 (9H, s), 1.37 (3H, s),
1.38 (3H, s), 1.76 (3H, d, JZ1.1 Hz), 1.75–1.85 (2H, m),
2.13 (1H, dd, JZ13.9, 4.8 Hz), 2.45 (1H, dd, JZ13.9,
9.0 Hz), 3.44–3.57 (2H, m), 3.70–3.78 (1H, m), 3.79 (3H, s),
4.01 (1H, dd, JZ8.2, 6.4 Hz), 4.11 (1H, dd, JZ12.8,
5.7 Hz), 4.28 (1H, dd, JZ12.8, 7.3 Hz), 4.35 (2H, s), 5.47
(1H, dd, JZ7.3, 5.7 Hz), 5.54–5.60 (1H, m), 5.70 (1H, dd,
JZ15.5, 6.4 Hz), 5.77 (1H, dd, JZ15.5, 6.2 Hz), 6.84 (2H,
d, JZ8.8 Hz), 7.19 (2H, d, JZ8.8 Hz), 7.31–7.44 (8H, m),
7.47–7.53 (1H, m), 7.64–7.69 (4H, m), 7.88–7.93 (2H, m).
13C NMR (100 MHz, CDCl3) d 19.2, 24.0, 26.8, 26.9, 27.2,
32.0, 37.2, 55.3, 60.8, 66.6, 72.2, 72.6, 77.9, 81.3, 108.7,
113.7, 127.6, 128.3, 128.3, 129.2, 129.5, 129.6, 129.6,
130.1, 130.4, 132.2, 132.3, 132.9, 133.9, 135.6, 159.1,
165.4. IR (neat) cmK1: 3070, 2932, 2858, 1720, 1613, 1514,
1269, 1249, 1110. MS (EI) m/z: 748 (MC), 733, 691, 633,
615, 313, 295, 213. HR-MS (EI): m/z 748.3790 (calcd for
C46H56O7Si: 748.3795).
4.6.3. (2E,5Z)-(1S)-7-(tert-Butyldiphenylsilyl)oxy-1-
{(4R,5S)-2,2-dimethyl-5-[2-(4-methoxybenzyl)oxyethyl]-
[1,3]dioxolan-4-yl}-5-methyl-hepta-2,5-dien-1-ol (14a).

J. Uenishi et al. / Tetrahedron 61 (2005) 1971–1979
1979
5. Uenshi, J.; Matsui, K.; Ohmi, M. Tetrahedron Lett. 2005, 46,
225–228.
3.84 (1H, m), 3.98–4.03 (1H, m), 4.07 (1H, t, JZ7.7 Hz),
4.12–4.23 (2H, m), 4.43 (2H, s), 5.41 (1H, brs), 5.69 (1H,
ddd, JZ15.7, 7.2, 1.5 Hz), 5.90 (1H, ddd, JZ15.7, 5.1,
0.9 Hz), 6.87 (2H, d, JZ8.8 Hz), 7.25 (2H, d, JZ8.8 Hz).
13C NMR (100 MHz, CDCl3) d 22.9, 27.0, 27.3, 32.1, 35.6,
55.3, 65.7, 66.8, 72.7, 72.9, 78.0, 81.8, 108.6, 113.8, 119.7,
127.1, 129.3, 130.5, 131.4, 135.0, 159.1.
6. The correction was made in Tetrahedron Lett. 2005, 46, 359.
7. Uenishi, J.; Matsui, K.; Ohmiya, H. Orgnometallic Chem.
2002, 653, 141–149.
8. (a) Corley, D. G.; Herb, R.; Moore, R. E.; Scheuer, P. J.; Paul,
V. J. J. Org. Chem. 1988, 53, 3644–3646. (b) Tanaka, J.-I.;
Higa, T.; Bernardinelli, G.; Jefford, C. W. Chem. Lett. 1996,
255–256. (c) Mooberry, S. L.; Tien, G.; Hernandez, A. H.;
Plubrukarn, A.; Davidson, B. S. Cancer Res. 1999, 59,
653–660. (d) Pryor, D. E.; O’Brate, A.; Bilcer, G.; Diaz,
J. F.; Wang, Y.; Kabaki, M.; Jung, M. K.; Andreu, J. M.;
Ghosh, A. K.; Giannakakou, P.; Hamel, E. Biochemistry 2002,
41, 9109–9115.
Acknowledgements
This work was financially supported by a Special Grant for
Cooperative Research administered by the Japan Private
School Promotion Foundation. This research was supported
(in part) by the 21st Century Center of Excellence Program
‘Development of Drug Discovery Frontier Integrated from
Tradition to Proteome’ from the Ministry of Education,
Culture, Sports, Science and Technology, Japan.
9. An excellent full review for (K)-laulimalide; see, Mulzer, J.;
Ohler, E. Chem. Rev. 2003, 103, 3753–3786. Total syntheses
see, (a) Ghosh, A. K.; Wang, Y. J. Am. Chem. Soc. 2000, 122,
11027–11028. (b) Paterson, I.; De Savi, C.; Tudge, M. Org.
Lett. 2001, 3, 3149–3152. (c) Mulzer, J.; Ohler, E. Angew.
Chem. Int. Ed. 2001, 40, 3842–3846. (d) Wender, P. A.;
Hedge, S. G.; Hubbard, R. D.; Zhang, L. J. Am. Chem. Soc.
2002, 124, 4956–4957. (e) Crimmins, M. T.; Stanton, M. G.;
Allwein, S. P. J. Am. Chem. Soc. 2002, 124, 5958–5959. (f)
Williams, D. R.; Mi, L.; Mullins, R. J.; Stites, R. E.
Tetrahedron Lett. 2002, 43, 4841–4844. (g) Nelson, S. G.;
Cheung, W. S.; Kassick, A. J.; Hilfiker, M. A. J. Am. Chem.
Soc. 2002, 124, 13654–13655. (h) Gallagher, B. M., Jr.; Fang,
F. G.; Johannes, C. W.; Pesant, M.; Tremblay, M. R.; Zhao, H.;
Akasaka, K.; Li, X.; Liu, J.; Littlefield, B. A. Bioorg. Med.
Chem. Lett. 2004, 14, 575–579.
References and notes
1. Macrolide containing trisubstituted (Z)-alkenyl unit; (a) (K)-
Zampanolide; Tanaka, J.; Higa, T. Tetrahedron Lett. 1996, 37,
5535–5538. (b) (C)-Lasonolide A; Horton, P. A.; Koehn,
F. E.; Longley, R. E.; McConnel, O. J. J. Am. Chem. Soc. 1994,
116, 6015–6016. (c) Haterumalide NA; Takada, N.; Sato, H.;
Suenaga, K.; Arimoto, H.; Yamada, K.; Ueda, K.; Uemura, D.
Tetrahedron Lett. 1999, 40, 6309–6312. (d) Leucascandrolide
B; D’Ambrosio, M.; Tato, M.; Pocsfalvi, G.; Debitus, C.;
Pietra, F. Helv. Chim. Acta 1999, 82, 347–354.
10. Zweifel, G.; Backlund, S. J. J. Am. Chem. Soc. 1977, 99,
3184–3185.
11. Chakraborty, T. K.; Purkait, S.; Das, S. Tetrahedron 2003, 59,
9127–9135.
2. Acyclic polyene marine natural product containing trisubsti-
tuted (Z)-alkenyl unit; (a) (K)-Discodermolide; Gunasekera,
S. P.; Gunasekera, M.; Longley, R. E.; Schulte, G. K. J. Org.
Chem. 1990, 55, 4912–4915. (b) Callystatin A; Kobayashi, M.;
Higuchi, K.; Murakami, N.; Tajima, H.; Aoki, S. Tetrahedron
Lett. 1997, 38, 2859–2862. (c) (K)-Ratjadone; Schummer, D.;
Gerth, K.; Reichenbach, H.; Hoefle, G. Liebigs Ann. 1995,
685–688.
12. The enantiomer purity was determined by Chiral-cel AD-RH
column (Daicel Co. Ltd) eluting with CH3CN:water (3:7).
Compound 11 is less polar than its enontiomer. Ueno, T.;
Oikawa, M.; Oikawa, H.; Ichihara, A. Biosci. Biotech.
Biochem. 1995, 59, 2104–2110.
13. Horner–Wadsworth–Emmons reaction; Zhang, Y.; Xu, C.; Li,
J.; Yuan, C. Tetrahedron: Asymmetry 2003, 14, 63–70.
14. Chida, N.; Tobe, T.; Ogawa, S. Tetrahedron Lett. 1991, 32,
1063–1066.
3. (a) Minato, A.; Suzuki, K.; Tamao, K. J. Am. Chem. Soc. 1987,
109, 1257–1258. (b) Shi, J.; Zeng, X.; Negishi, E. Org. Lett.
2003, 5, 1825–1828 and references cited therein.
15. The diastereomers can be separated at the later stage by
chromatography and the details will be published in a full
account for the total synthesis of (K)-laulimalide in due course.
4. (a) Uenishi, J.; Matsui, K. Tetrahedron Lett. 2001, 42,
4353–4355. (b) Uenishi, J.; Matsui, K.; Wada, A. Tetrahedron
Lett. 2003, 44, 3093–3096.