Stereoselective synthesis of the macrocyclic core of (-)-salicylihalamides A and B

Article abstract of DOI:10.1055/s-2007-965970

Stereoselective synthesis of the macrocyclic core of salicylihalamides A and B is described. The synthetic strategy features stereoselective iodolactonization, Sharpless asymmetric epoxidation, Mitsunobu esterification, and ring-closing metathesis. Georg

Full text of DOI:10.1055/s-2007-965970

1070
PAPER
Stereoselective Synthesis of the Macrocyclic Core of (–)-Salicylihalamides
A and B
S
tereosele
.
ctive
S
ynthe
S
sis of the Mac
r
ocyclic Cor
e
of (–)-Salicylihal
a
amides
A
a
d
ndB av,* P. Sundar Ram Reddy
Division of Organic Chemistry, Indian Institute of Chemical Technology, Hyderabad 500007, India
Fax +91(40)27160387; E-mail: yadavpub@iict.res.in
Received 7 September 2006; revised 15 December 2006
have proven useful.6 Our long-standing interest in the de-
velopment of strategies for the total synthesis of natural
products having cytotoxic properties prompted us to take
up the total synthesis of (–)-salicylihalamides A and B.6,7
Abstract: Stereoselective synthesis of the macrocyclic core of sal-
icylihalamides A and B is described. The synthetic strategy features
stereoselective iodolactonization, Sharpless asymmetric epoxida-
tion, Mitsunobu esterification, and ring-closing metathesis.
Key words: salicylihalamide, cytotoxicity, Sharpless epoxidation, Our retrosynthetic analysis revealed two key fragments,
metathesis
namely the functionalized benzoic acid derivative 2 and
the chiral aliphatic fragment 3, which would give the mac-
rolide core on simple Mitsunobu esterification and meta-
thesis reaction. Our synthetic strategy is mainly focused
on the synthesis of chiral aliphatic intermediate 3 contain-
ing three-stereogenic centers, the synthesis of aromatic
fragment 2 was reported earlier by our group. We envis-
aged that we would easily build the aliphatic intermediate
3 from readily available chiron moiety 6 using stereose-
lective iodolactonization, epoxide opening, Sharpless
asymmetric epoxidation, and sodium cyanoborohydride
mediated regioselective opening of the acetal as key steps.
The isolation and structural elucidation of cytotoxic sali-
cylihalamides A and B were reported by Boyd and co-
workers in 1997.1 These are novel secondary metabolites
produced by a marine sponge of the genus Haliclona
(south-western Australian coast). Since their discovery, a
number of other structurally similar bioactive metabolites
have been isolated and characterized, which include the
apicularens, lobatamides, and oximidines.2 Each of these
structures possesses a medium-sized macrolide ring en-
gendering a salicylate moiety and a dienyl enamide side
chain. Salicylihalamides displayed potent cytotoxicity
when screened against the NCI 60-cell human tumor line
assay, with a mean panel GI50 value of 15 nM.3 The mech-
anism of action of this compound has no correlation with
other known compounds and thus occupies an important
status. Thus, owing to the unique, potent cytotoxicity of
the salicylihalamides, as well as their scarcity and their
novel structural features, intense activity has been wit-
nessed in their synthetic chemistry.4,5 In particular, ring-
closing metathesis based syntheses of salicylihalamides
The macrolide synthesis started from commercially avail-
able citronellic acid (6). Acid 6 was converted into the
known iodolactone 7 as reported by Still et al.8 Treatment
of iodolactone 7 with potassium carbonate in methanol re-
sulted in the formation of epoxide 5 in good yield. Ep-
oxide 5 was opened with propargyl tetrahydropyranyl
ether employing the Yamaguchi protocol9 to produce the
homopropargyl alcohol 8. The ester group in compound 8
was reduced with lithium aluminum hydride in tetrahy-
drofuran to obtain the corresponding diol, which was, in
turn, subjected to monoprotection using tert-butylchlo-
HN
17
O
OMe
O
OH
O
OH
Me
OH
+
O
O
MPM
OH OMOM
3
2
1
COOH
HO
COOMe
OTBDPS
O
OMOM
5
4
6
Scheme 1 Retrosynthesis of (–)-salicylihalamide A (17E) and (–)-salicylihalamide B (17Z)
SYNTHESIS 2007, No. 7, pp 1070–1076
x
x
.
x
x
.2
0
0
7
Advanced online publication: 28.02.2007
DOI: 10.1055/s-2007-965970; Art ID: Z18506SS
© Georg Thieme Verlag Stuttgart · New York

PAPER
Stereoselective Synthesis of the Macrocyclic Core of (–)-Salicylihalamides A and B
1071
COOH
COOMe
COOMe
I
a
b
ref. 8
6 steps,
THPO
O
O
O
OH
46% overall yield
5
7
8
6
e,f
g
c,d
OTBDPS
OTBDPS
HO
THPO
OMOM
HO
10
OH
9
HO
HO
OTBDPS
OTBDPS
h
i
OTBDPS
O
OMOM
OH OMOM
OMOM
11
12
4
OH
OTBDPS
l,m
k
j
O
O
OMOM
O
O
OMOM
O
O
OMOM
Ar = 4-MeO6H4
Ar
15
Ar
Ar
13
14
n
MPM = 4-MeOC6H4CH2
MPM
O
OH OMOM
3
Scheme 2 Reagents and conditions: (a) K2CO3, MeOH, reflux, 1 h, 96%; (b) n-BuLi, propargyl tetrahydropyranyl ether, BF3·OEt2, THF,
–78 °C, 3 h, 87%; (c) LiAlH4, THF, 0 °C to r.t., 50 min; (d) TBDPSCl, Et3N, DMAP, CH2Cl2, 0 °C, 0.5 h, 96% (2 steps); (e) MOMCl, i-Pr2NEt,
DMAP, 0 °C to r.t., 6 h; (f) PPTS, EtOH, 60 °C, 1 h, 94% (2 steps); (g) LiAlH4, THF, 0 °C, 3 h, 93%; (h) Ti(Oi-Pr)4, (+)-DIPT, t-BuOOH,
CH2Cl2, 4 Å MS, –24 °C, 3 h, 89%; (i) Red-Al, THF, 0 °C to r.t., 2 h, 93%; (j) 4-methoxybenzaldehyde dimethyl acetal, CSA, CH2Cl2, 0 °C, 1
h, 95%; (k) TBAF, THF, 0 °C to r.t., 1 h, 96%; (l) SO3/py, Et3N, DMSO–CH2Cl2 (2:1.6), 0 °C, 0.5 h; (m) Ph3PCH3I, t-BuOK, THF, 0 °C, 3 h,
87% (2 steps); (n) NaBH3CN, TMSCl, MeCN, 4 Å MS, 0 °C, 15 min, 79%.
rodiphenylsilane and triethylamine in dichloromethane to acetal 13 and then the silyl ether was deprotected with tet-
furnish secondary alcohol derivative 9. Protection of the rabutylammonium fluoride to give primary alcohol 14.
alcohol 9 as its methoxymethyl ether followed by depro- Sulfur trioxide/pyridine oxidation of alcohol 14 followed
tection of the tetrahydropyranyl moiety afforded propar- by one-carbon Wittig alkenation gave alkene 15, which on
gylic alcohol 10, which was subsequently reduced to reductive opening11 of the acetal with sodium cyanoboro-
allylic alcohol 4 using lithium aluminum hydride in tet- hydride and chlorotrimethylsilane furnished the required
rahydrofuran. Sharpless asymmetric epoxidation10 of al- aliphatic fragment 3.
lylic alcohol 4 yielded epoxy alcohol 11, which on
The synthesis of 2-allyl-6-methoxybenzoic acid, the aro-
reductive opening with sodium bis(2-methoxyethoxy)alu-
matic fragment of salicylihalamide was reported earlier
minum hydride (Red-Al) produced 1,3-diol 12 regioselec-
tively. Diol 12 was protected as its 4-methoxybenzylidene
by our group.12 Mitsunobu reaction13 between chiral ali-
OMPM
OMPM
OMe
O
OMe
O
OMOM
OMOM
O
O
a
b
c
2 + 3
16
17
OH
OMe
O
ref. 6e
OMOM
O
1
18
Scheme 3 Reagents and conditions: (a) DEAD, Ph3P, benzene, 10 °C to r.t., 1 h, 91%; (b) Grubb’s I catalyst, CH2Cl2, reflux, 3 h, 85%; (c)
DDQ, CH2Cl2–H2O (19:1), 0 °C to r.t., 94%.
Synthesis 2007, No. 7, 1070–1076 © Thieme Stuttgart · New York

1072
J. S. Yadav, P. S. R. Reddy
PAPER
Methyl (3S,4R)-4-Hydroxy-3-methyl-8-(tetrahydro-2H-pyran-
2-yloxy)oct-6-ynoate (8)
phatic alcohol 3 and benzoic acid 2 produced the ester 16,
which set the stage for a ring-closing metathesis reac-
tion.14
Under an atmosphere of N2, 1.6 M n-BuLi in hexane (45 mL, 72
mmol) was added to a soln of propargyl tetrahydropyran-2-yl ether
(7.45 g, 54 mmol) in THF (45 mL) at –78 °C and the mixture was
stirred for 15 min. Then, BF3·OEt2 (5.65 mL, 45 mmol) was added
to the soln, and the stirring was continued for 15 min at the same
temperature. Finally a soln of 5 (6.48 g, 45 mmol) in anhyd THF (40
mL) was added. The mixture was stirred at –78 °C for 3 h and then
the reaction was quenched by addition of sat. aq NH4Cl (30 mL).
Then the mixture was extracted with EtOAc and dried (anhyd
Na2SO4). Evaporation of the solvents resulted in crude alcohol,
which was purified by column chromatography (silica gel, 30–33%
EtOAc–petroleum ether) to afford pure 8 as colorless liquid; yield:
11.12 g (87%); Rf = 0.5 (silica gel, 50% EtOAc–petroleum ether).
Ring-closing metathesis with first generation Grubb’s cat-
alyst furnished the desired E-intermediate 17 as the pre-
dominant diastereomer (E/Z = 9:1). Deprotection of the 4-
methoxyphenylmethyl ether furnished the known alcohol
18,6e unequivocally proving the structure assigned to 17.
Compound 18 has been converted into the target molecule
1 by Furstner et al.6e thus the present strategy completes
the formal total synthesis.
In conclusion, our synthesis allowed easy access for the
preparation of intermediate 18 in greater than 100-mg
quantities, like many previous reports, thereby paving an
easy way for the total synthesis of salicylihalamides A and
B by introducing appropriate side chains. The synthetic
route includes very versatile reactions like iodolactoniza-
tion, epoxide opening, Sharpless asymmetric epoxidation,
Mitsunobu esterification, and metathesis.
[a]D25 +2.3 (c 2.0, CHCl3).
IR (neat): 3457, 2945, 2873, 1735, 1438, 1352, 1263, 1201, 1174,
1117, 1078, 1021, 948, 901, 870, 813, 757 cm–1.
1H NMR (200 MHz, CDCl3): d = 4.80–4.76 (m, 1 H), 4.21–4.19 (m,
2 H), 3.91–3.67 (m, 2 H), 3.66 (s, 3 H), 3.60–3.40 (m, 1 H), 2.80–
2.08 (m, 5 H), 1.90–1.30 (m, 6 H), 0.96 (d, J = 6.8 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 175.44, 96.58, 85.29, 80.05, 72.01,
61.80, 53.95, 51.11, 37.82, 36.57, 34.4, 30.01, 25.03, 25.00, 18.80.
Unless otherwise noted, materials were obtained from commercial
sources and used without further purification. All solvents were pu-
rified and dried by standard procedures before use. Organic solns of
the products were dried over anhyd Na2SO4. All reactions involving
organometallic reagents were conducted under an inert atmosphere.
Optical rotations were measured with a Jasco DIP-360 polarimeter.
IR spectra were obtained on a Thermo Nicolet Nexus 670 FTIR
spectrophotometer. NMR spectra were measured on Varian Gemini
200 or Varian Unity 400 or Varian Inova 500 MHz or Bruker
Avance 300 MHz spectrometers (1H) and 75 or 50 MHz spectrom-
eters (13C), in CDCl3 with TMS as an internal standard. MS spectra
were recorded using EI, liquid secondary ion mass spectrometric
(LSIMS), ESI, and HRMS techniques. The progress of all the reac-
tions was monitored by TLC using glass plates precoated with silica
gel 60F254 (0.5 mm, Merck). Column chromatography using silica
gel 60–120 mesh (EtOAc–hexane).
MS (EI): m/z = 284 [M+].
HRMS (EI): m/z [M+] calcd for C15H24O5: 284.1702; found:
284.1691.
(3S,4R)-1-(tert-Butyldiphenylsiloxy)-3-methyl-8-(tetrahydro-
2H-pyran-2-yloxy)oct-6-yn-4-ol (9)
To a suspension of LiAlH4 (1.273 g, 33.5 mmol) in anhyd THF (30
mL) under an atmosphere of N2 at 0 °C was added 8 (9.514 g, 33.5
mmol) in anhyd THF (70 mL) and the mixture was stirred at r.t. for
1 h. It was then cooled to 0 °C, diluted with wet Et2O, and the excess
LiAlH4 was quenched by the addition of sat. Na2SO4. When the ef-
fervescence had subsided, the mixture was filtered through a pad of
Celite and washed with CHCl3 and hot EtOAc. The filtrate was
evaporated in vacuo and the residue was used directly in the next
step.
The residue was dissolved in anhyd CH2Cl2 (80 mL) under an atmo-
sphere of N2. Et3N (6.78 mL, 48.75 mmol) and TBDPSCl (9.16 mL,
35.75 mmol) were added sequentially at 0 °C. Next, a catalytic
amount of DMAP (0.397 g, 3.25 mmol) was added. The mixture
was stirred at r.t. for 0.5 h and then quenched by the addition of sat.
aq NH4Cl and extracted with CH2Cl2. The combined organic ex-
tracts were dried (Na2SO4) and concentrated in vacuo. Purification
by column chromatography (silica gel, 10–12% EtOAc–petroleum
ether) gave pure 9 as a clear oil; yield: 15.91 g (96% over 2 steps);
Rf = 0.7 (silica gel, 30% EtOAc–petroleum ether).
Methyl (3S)-3-[(2S)-Oxiran-2-yl]butanoate (5)
A 250-mL round-bottomed flask equipped with a magnetic stirring
bar, dry N2 inlet, reflux condenser and septum was flushed with N2
and charged with 7 (14.88 g, 62 mmol) and finely powdered K2CO3
(17.13 g, 124 mmol) in MeOH (120 mL). The mixture was refluxed
for 1 h; progress of the reaction was monitored by TLC. The result-
ing soln was allowed to cool to r.t., concentrated under reduced
pressure and partitioned between H2O (60 mL) and Et2O (60 mL).
The organic layer was washed with brine and H2O, dried (Na2SO4),
and evaporated to give the crude product. The residue was subjected
to column chromatography (silica gel, 8–10% EtOAc–petroleum
ether) to provide pure 5 as a clear oil; yield: 8.57 g (96%); Rf = 0.6
(silica gel, 20% EtOAc–petroleum ether).
[a]D25 –5.52 (c 2.0, CHCl3).
IR (neat): 3455, 3069, 2935, 2859, 1710, 1465, 1427, 1387, 1262,
1201, 1111, 1022, 939, 901, 870, 820, 739, 704, 613 cm–1.
1H NMR (200 MHz, CDCl3): d = 7.67–7.60 (m, 4 H), 7.42–7.31 (m,
6 H), 4.82–4.73 (m, 1 H), 4.23–4.16 (m, 2 H), 3.86–3.62 (m, 4 H),
3.57–3.44 (m, 1 H), 2.44–2.34 (m, 2 H), 1.96–1.76 (m, 2 H), 1.75–
1.40 (m, 7 H), 1.04 (s, 9 H), 0.88 (d, J = 6.8 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 135.42, 133.44, 129.54, 125.55,
96.72, 83.38, 77.88, 73.78, 72.84, 61.85, 54.54, 35.98, 34.3, 30.16,
26.70, 25.22, 24.87, 18.96, 15.88, 13.14.
[a]D25 +3.8 (c 2.0, CHCl3).
IR (neat): 2964, 1738, 1437, 1316, 1258, 1196, 1093, 1009, 936,
833 cm–1.
1H NMR (200 MHz, CDCl3): d = 3.67 (s, 3 H), 2.82-2.64 (m, 2 H),
2.52 (m, 1 H), 2.44-2.14 (m, 2 H), 2.02-1.80 (m, 1 H), 1.07 (d,
J = 7.0 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 172.36, 55.46, 51.36, 45.93, 37.41,
32.49, 16.40.
MS (ESI): m/z = 495 [M + H]+, 517 [M + Na]+.
HRMS (ESI): m/z [M + H]+ calcd for C30H43O4Si: 495.2931; found:
MS (ESI): m/z = 145 [M + H]+, 167 [M + Na]+.
495.2947.
Synthesis 2007, No. 7, 1070–1076 © Thieme Stuttgart · New York

PAPER
Stereoselective Synthesis of the Macrocyclic Core of (–)-Salicylihalamides A and B
1073
(5R,6S)-8-(tert-Butyldiphenylsiloxy)-5-(methoxymethoxy)-6-
methyloct-2-yn-1-ol (10)
HRMS (ESI): m/z [M + H]+ calcd for C27H41O4Si: 457.2774; found:
457.2761.
To a cold (0 °C) soln of 9 (12.63 g, 25.55 mmol) in CH2Cl2 (150
mL) were added i-Pr2NEt (44.4 mL, 255.5 mmol), MOMCl (9.64
mL, 127.7 mmol), and TBAI (0.943 g, 2.55 mmol). The mixture
was immediately allowed to warm to r.t. and protected from light.
After 6 h, sat. aq NaHCO3 was added together with Et2O. The or-
ganic layer was washed with brine and the aqueous layer was ex-
tracted with Et2O. The combined extracts were dried (Na2SO4) and
concentrated in vacuo to yield the crude product. The residue was
used directly in the next step.
{(2S,3R)-3-[(2R,3S)-5-(tert-Butyldiphenylsiloxy)-2-(methoxy-
methoxy)-3-methylpentyl]oxiran-2-yl}methanol (11)
To a suspension of activated powdered 4 Å molecular sieves (1.06
g, 20 wt%) in CH2Cl2 (25 mL), Ti(Oi-Pr)4 (0.626 mL, 2.106 mmol)
and (+)-DIPT (0.487 mL, 2.316 mmol) were added sequentially
at –24 °C. The mixture was stirred for 20 min and then 4.2 M
t-BuOOH in toluene (6.27 mL, 26.33 mmol) was added, and stirring
was continued at the same temperature for a further 30 min. To the
above soln, 4 (4.8 g, 10.53 mmol) in CH2Cl2 (10 mL) was added,
and stirred at –24 °C for 3 h. The mixture was quenched with H2O
(60 mL), warmed to r.t. and stirred for 1 h and then re-cooled to
0 °C. 30% Aq NaOH (w/v, 16 mL) saturated with NaCl was added
and the mixture was stirred at 0 °C for 10 min. CH2Cl2 was removed
under reduced pressure, the compound was extracted with Et2O,
washed with brine, dried (Na2SO4), filtered and concentrated in vac-
uo. Purification by column chromatography (silica gel, 24–27%
EtOAc–petroleum ether) afforded pure 11 as a colorless oil; yield:
4.42 g (89%); Rf = 0.5 (silica gel, 50% EtOAc–petroleum ether).
The residual compound (13.20 g, 24.51 mmol) was dissolved in
EtOH (60 mL) and stirred along with catalytic amount of PPTS
(0.307 g, 1.23 mmol) at 60 °C for 1 h. The mixture was quenched
by addition of sat. aq NaHCO3 (10 mL). EtOH was evaporated un-
der reduced pressure, and the aqueous phase was extracted with
EtOAc (2 × 30 mL). The organic extracts were washed with brine
(1 × 30 mL) and dried (anhyd Na2SO4). The solvent was evaporated
and the product was purified by column chromatography (silica gel,
13–15% EtOAc–petroleum ether) to afford pure 10 as a colorless
liquid; yield: 10.92 g (94% over 2 steps); Rf = 0.7 (silica gel, 30%
EtOAc–petroleum ether).
[a]D25 –24.65 (c 2.0, CHCl3).
[a]D25 –2.74 (c 2.0, CHCl3).
IR (neat): 3438, 2933, 2888, 1467, 1427, 1386, 1105, 1038, 916,
822, 740, 704, 612 cm–1.
IR (neat): 3455, 2931, 2858, 1466, 1427, 1386, 1106, 1037, 899,
822, 739, 704 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.67–7.59 (m, 4 H), 7.42–7.31 (m,
6 H), 4.60 (s, 2 H), 3.80 (dd, J = 12.4, 2.3 Hz, 1 H), 3.77–3.57 (m,
4 H), 3.31 (s, 3 H), 2.99 (td, J = 6.2, 1.6 Hz, 1 H), 2.88 (q, J = 3.1
Hz, 1 H), 2.04–1.91 (br s, 1 H, OH), 1.86–1.74 (m, 2 H), 1.73–1.64
(m, 1 H), 1.60–1.50 (m, 2 H), 1.04 (s, 9 H), 0.83 (d, J = 7.1 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 135.5, 133.8, 129.54, 127.6, 96.1,
79.2, 62.02, 61.7, 59.04, 55.57, 53.94, 34.38, 33.28, 32.59, 26.80,
19.12, 14.96.
1H NMR (200 MHz, CDCl3): d = 7.67–7.59 (m, 4 H), 7.41–7.30 (m,
6 H), 4.67 (d, J = 6.8 Hz, 1 H), 4.55 (d, J = 6.8 Hz, 1 H), 4.13 (s, 2
H), 3.78–3.62 (m, 2 H), 3.59–3.48 (m, 1 H), 3.32 (s, 3 H), 2.49–2.36
(m, 2 H), 2.17–1.98 (m, 1 H), 1.83–1.64 (m, 2 H), 1.04 (s, 9 H), 0.86
(d, J = 7.5 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 135.56, 133.99, 129.56, 127.61,
96.25, 83.27, 79.77, 61.84, 55.63, 51.24, 35.67, 32.46, 26.86, 22.25,
19.19, 15.88, 13.97.
MS (ESI): m/z = 473 [M + H]+, 495 [M + Na]+.
MS (ESI): m/z = 455 [M + H]+, 477 [M + Na]+.
HRMS (ESI): m/z [M + H]+ calcd for C27H41O5Si: 473.2723; found:
473.2711.
HRMS (ESI): m/z [M + H]+ calcd for C27H39O4Si: 455.2618; found:
455.2631.
(3R,5R,6S)-8-(tert-Butyldiphenylsiloxy)-5-(methoxymethoxy)-
6-methyloctane-1,3-diol (12)
(E,5R,6S)-8-(tert-Butyldiphenylsiloxy)-5-(methoxymethoxy)-6-
methyloct-2-ene-1-ol (4)
To a stirred soln of 11 (2.5 g, 5.3 mmol) in anhyd THF (15 mL) un-
der an atmosphere of N2 was added Red-Al [4.42 mL, 15.9 mmol,
70% (w/w)] dropwise at 0 °C and the mixture was stirred at r.t. for
2 h. Then it was cooled to 0 °C, diluted with wet Et2O and the excess
Red-Al was quenched by the addition of sat. NH4Cl soln. When the
effervescence subsided, the mixture was filtered through a pad of
Celite and washed with CHCl3 and hot EtOAc. The filtrate was
washed with brine, dried (Na2SO4), and concentrated in vacuo. The
residue was purified by column chromatography (silica gel, 42–
45% EtOAc–petroleum ether) to furnish 12 as a viscous liquid;
yield: 2.33 g (93%); Rf = 0.4 (silica gel, 60% EtOAc–petroleum
ether).
To a suspension of LiAlH4 (0.610 g, 16 mmol) in anhyd THF (16
mL) under an atmosphere of N2 at 0 °C was added 10 (7.26 g, 16
mmol) in anhyd THF (32 mL) and the mixture was stirred at r.t. for
3 h. It was then was cooled to 0 °C, diluted with wet Et2O and the
excess of LiAlH4 was quenched by the addition of sat. Na2SO4.
When the effervescence subsided, the mixture was filtered through
a pad of Celite and washed with CHCl3 and hot EtOAc. The filtrate
was washed with brine, dried (Na2SO4), evaporated in vacuo, and
the residue was purified by column chromatography (silica gel, 15–
17% EtOAc–petroleum ether) to furnish 4 as a viscous liquid; yield:
6.78 g (93%); Rf = 0.5 (silica gel, 30% EtOAc–petroleum ether).
[a]D25 –28.75 (c 2.0, CHCl3).
[a]D25 –7.75 (c 2.0, CHCl3).
IR (neat): 3413, 2933, 2859, 1467, 1427, 1385, 1149, 1106, 1037,
915, 821, 739, 704 cm–1.
IR (neat): 3435, 2931, 2859, 1723, 1589, 1471, 1427, 1387, 1259,
1108, 1036, 898, 822, 739, 704, 613 cm–1.
1H NMR (200 MHz, CDCl3): d = 7.65–7.59 (m, 4 H), 7.41–7.30 (m,
6 H), 4.59 (ABq, J = 6.6 Hz, 2 H), 4.12–3.96 (m, 1 H), 3.80 (t,
J = 5.6 Hz, 2 H), 3.76–3.58 (m, 3 H), 3.40 (s, 3 H), 2.00–1.83 (m, 1
H), 1.82–1.55 (m, 4 H), 1.54–1.46 (m, 2 H), 1.04 (s, 9 H), 0.83 (d,
J = 6.9 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 135.45, 133.82, 129.48, 127.53,
96.8, 79.35, 68.18, 62.04, 61.67, 55.78, 38.44, 38.1, 34.4, 32.97,
26.76, 19.1, 15.24.
1H NMR (200 MHz, CDCl3): d = 7.67-7.60 (m, 4 H), 7.43–7.31 (m,
6 H), 5.69–5.63 (m, 2 H), 4.61-4.52 (m, 2 H), 4.04 (br d, J = 3.8
Hz, 2 H), 3.80–3.58 (m, 2 H), 3.48–3.38 (m, 1 H), 3.31 (s, 3 H),
2.33–2.14 (m, 2 H), 2.00–1.82 (m, 1 H), 1.81–1.66 (m, 1 H), 1.42
(br s, 1 H, OH), 1.38–1.28 (m, 1 H), 1.04 (s, 9 H), 0.84 (d, J = 7.5
Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 135.48, 133.84, 131.29, 129.50,
129.27, 127.56, 95.75, 80.98, 63.44, 61.86, 55.53, 35.26, 34.16,
32.04, 26.80, 19.14, 14.29.
MS (ESI): m/z = 475 [M + H]+, 497 [M + Na]+.
MS (ESI): m/z = 457 [M + H]+, 479 [M + Na]+.
Synthesis 2007, No. 7, 1070–1076 © Thieme Stuttgart · New York

1074
J. S. Yadav, P. S. R. Reddy
PAPER
HRMS (ESI): m/z [M + H]+ calcd for C27H43O5Si: 475.2880; found:
475.2897.
sphere of N2. The mixture was stirred at 0 °C for 30 min and then
the reaction was quenched with sat. NH4Cl soln and extracted with
petroleum ether. The organic extract was dried (Na2SO4) and con-
centrated in vacuo. The resulting aldehyde was used directly in the
next step.
(3S,4R)-1-(tert-Butyldiphenylsiloxy)-4-(methoxymethoxy)-5-
[(4R)-2-(4-methoxyphenyl)-1,3-dioxan-4-yl]-3-methylpentane
(13)
To a mixture of methyltriphenylphosphonium iodide (3.15 g, 7.8
mmol) and t-BuOK (0.582 g, 5.2 mmol) in anhyd THF (15 mL) at
–78 °C was added 18-crown-6 (~5 mg) and the soln was stirred for
1 h. Then aldehyde (0.457 g, 1.3 mmol) in anhyd THF (6 mL) was
added to this soln and stirring was continued until the starting ma-
terial had been consumed. The mixture was quenched by the addi-
tion of H2O (6 mL) and the solvent was evaporated. The residue was
taken in EtOAc and the organic layer was washed with H2O (1 × 15
mL) followed by brine (1 × 15 mL) and dried (anhyd Na2SO4). The
solvent was evaporated under reduced pressure. Purification by col-
umn chromatography (silica gel, 7–9% EtOAc–petroleum ether) af-
forded pure 15 as a viscous liquid; yield: 0.469 g (87% over 2 steps);
Rf = 0.7 (silica gel, 30% EtOAc–petroleum ether).
To a soln of 12 (1.327 g, 2.8 mmol) in anhyd CH2Cl2 (10 mL), 4-
methoxybenzaldehyde dimethyl acetal (0.573 mL, 3.36 mmol) and
CSA (7 mg, 0.028 mmol) were added sequentially at 0 °C. The mix-
ture was stirred at the same temperature for 1 h and then the reaction
was quenched by the addition of sat. aq NaHCO3 soln. The mixture
was extracted with EtOAc, washed with brine, dried (Na2SO4), and
concentrated in vacuo. Purification by column chromatography (sil-
ica gel, 10–12% EtOAc–petroleum ether) gave 13 a as colorless oil;
yield: 1.57 g (95%); Rf = 0.7 (silica gel, 20% EtOAc–petroleum
ether).
[a]D25 –18.75 (c 2.0, CHCl3).
IR (neat): 2955, 2857, 1614, 1518, 1427, 1366, 1249, 1104, 1037,
917, 824, 740, 704, 612 cm–1.
[a]D25 –15.25 (c 2.0, CHCl3).
1H NMR (200 MHz, CDCl3): d = 7.72–7.59 (m, 4 H), 7.48–7.30 (m,
8 H), 6.85 (d, J = 9.1 Hz, 2 H), 5.43 (s, 1 H), 4.64 (ABq, J = 6.8 Hz,
2 H), 4.25 (dd, J = 11.3, 3.8 Hz, 1 H), 4.06–3.88 (m, 2 H), 3.80 (s,
3 H), 3.78–3.60 (m, 3 H), 3.34 (s, 3 H), 2.05–1.64 (m, 4 H), 1.63–
1.42 (m, 1 H), 1.40–1.22 (m, 2 H), 1.03 (s, 9 H), 0.83 (d, J = 7.6 Hz,
3 H).
13C NMR (75 MHz, CDCl3): d = 160.04, 135.56, 129.54, 127.62,
127.16, 113.55, 100.77, 96.2, 73.69, 67.1, 62.31, 55.27, 37.29,
34.24, 32.4, 31.88, 26.88, 19.2, 15.23.
IR (neat): 2925, 2852, 1713, 1613, 1516, 1461, 1370, 1249, 1215,
1100, 1036, 914, 827, 759, 668 cm–1.
1H NMR (200 MHz, CDCl3): d = 7.34 (d, J = 8.3 Hz, 2 H), 6.83 (dd,
J = 9.1, 2.3 Hz, 2 H), 5.84–5.64 (m, 1 H), 5.40 (s, 1 H), 5.05–4.94
(m, 2 H), 4.64 (q, J = 6.8 Hz, 2 H), 4.24 (dd, J = 11.3, 4.5 Hz, 1 H),
4.03–3.84 (m, 3 H), 3.79 (s, 3 H), 3.37 (s, 3 H), 2.4–2.2 (m, 1 H),
2.0–1.70 (m, 3 H), 1.69–1.52 (m, 2 H), 1.51–1.40 (m, 1 H), 0.88 (d,
J = 6.7 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 160.03, 137.72, 131.90, 127.19,
115.61, 113.42, 100.67, 96.66, 77.63, 73.62, 66.93, 55.61, 55.18,
37.63, 36.65, 36.18, 31.76, 14.70.
MS (LSIMS): m/z = 593 [M + H]+, 615 [M + Na]+.
HRMS (LSIMS): m/z [M + Na]+ calcd for C35H48NaO6Si: 615.3118;
found: 615.3113.
MS (ESI): m/z = 351 [M + H]+, 373 [M + Na]+.
HRMS (ESI): m/z [M + H]+calcd for C20H31O5: 351.2171; found:
351.2193.
(3S,4R)-4-(Methoxymethoxy)-5-[(4R)-2-(4-methoxyphenyl)-
1,3-dioxan-4-yl]-3-methylpentan-1-ol (14)
To a soln of 13 (1.534 g, 2.6 mmol) in anhyd THF (10 mL) and 1 M
TBAF in THF (3.9 mL, 3.9 mmol) was added at 0 °C. The mixture
was warmed to r.t. and stirred for 1 h and then the reaction was
quenched by the addition of sat. aq NH4Cl. The mixture was extract-
ed with EtOAc, washed with brine, dried (Na2SO4), and concentrat-
ed in vacuo. Purification by column chromatography (silica gel, 32–
34% EtOAc–petroleum ether) afforded 14 as a clear oil; yield:
0.883 g (96%); Rf = 0.4 (silica gel, 50% EtOAc–petroleum ether).
(3R,5R,6S)-1-(4-Methoxybenzyloxy)-5-(methoxymethoxy)-6-
methylnon-8-en-3-ol (3)
To a soln of 15 (0.336 g, 0.96 mmol) in anhyd MeCN (20 mL), ac-
tivated and powdered 4 Å molecular sieves (124 mg) were added at
r.t. The mixture was stirred for 5 min, the mixture was cooled to
0 °C and NaBH3CN (0.362 g, 5.78 mmol) and TMSCl (0.74 mL,
5.78 mmol) were added sequentially. The resulting soln was stirred
for 15 min and then quenched by the addition of sat. aq NH4Cl. It
was extracted with EtOAc, washed with brine, dried (Na2SO4), fil-
tered, and concentrated in vacuo. Purification by column chroma-
tography (silica gel, 16–19% EtOAc–petroleum ether) provided 3
as a clear oil; yield: 0.267 g (79%); Rf = 0.4 (silica gel, 30% EtOAc–
petroleum ether).
[a]D25 –32.75 (c 2.0, CHCl3).
IR (neat): 3403, 2932, 1715, 1605, 1514, 1462, 1380, 1252, 1150,
1099, 1035, 915, 830, 759, 706 cm–1.
1H NMR (200 MHz, CDCl3): d = 7.33 (d, J = 8.5 Hz, 2 H), 6.83 (d,
J = 8.5 Hz, 2 H), 5.39 (s, 1 H), 4.67 (ABq, J = 6.9 Hz, 2 H), 4.23
(dd, J = 10.8, 3.9 Hz, 1 H), 4.01–3.81 (m, 3 H), 3.78 (s, 3 H), 3.73–
3.64 (m, 1 H), 3.62–3.53 (m, 1 H), 3.38 (s, 3 H), 2.02–1.88 (m, 1 H),
1.86–1.68 (m, 2 H), 1.67–1.58 (m, 2 H), 1.47 (br d, J = 12.4 Hz, 1
H), 1.41–1.28 (m, 1 H), 0.91 (d, J = 7.7 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 159.65, 131.20, 127.15, 113.42,
100.64, 96.46, 77.9, 73.42, 66.9, 61,43, 55.7, 55.14, 36.8, 34.64,
33.86, 31.7, 16.43.
[a]D25 +21.12 (c 2.3, CHCl3).
IR (neat): 3448, 2925, 2854, 1740, 1612, 1513, 1461, 1375, 1248,
1150, 1095, 1035, 913, 815 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.20 (br d, J = 8.3 Hz, 2 H), 6.82
(d, J = 8.3 Hz, 2 H), 5.82–5.64 (m, 1 H), 5.04–4.93 (m, 2 H), 4.64
(s, 2 H), 4.42 (s, 2 H), 4.01–3.83 (m, 1 H), 3.79 (s, 3 H), 3.75–3.50
(m, 3 H), 3.38 (s, 3 H), 3.15 (br s, 1 H, OH), 2.37–2.18 (m, 1 H),
2.12–1.95 (m, 1 H), 1.94–1.34 (m, 5 H), 0.87 (d, J = 6.8 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 159.08, 137.53, 130.14, 129.18,
115.77, 113.68, 97.12, 79.15, 72.26, 68.25, 66.84, 64.82, 55.79,
55.19, 38.59, 36.85, 36.40, 14.89.
MS (ESI): m/z = 355 [M + H]+, 377 [M + Na]+.
HRMS (ESI): m/z [M + H]+ calcd for C19H31O6: 355.2121; found:
355.2114.
(4S,5R)-5-(Methoxymethoxy)-6-[(4R)-2-(4-methoxyphenyl)-
1,3-dioxan-4-yl]-4-methylpent-1-ene (15)
To a soln of 14 (0.531 g, 1.5 mmol) in anhyd CH2Cl2 (3.9 mL) and
DMSO (4.5 mL), Et3N (1.04 mL, 7.5 mmol) and SO3/py complex
(1.19 g, 7.5 mmol) were added sequentially at 0 °C under an atmo-
MS (ESI): m/z = 375 [M + Na]+.
HRMS (ESI): m/z [M + Na]+ calcd for C20H32NaO5: 375.2147;
found: 375.2145.
Synthesis 2007, No. 7, 1070–1076 © Thieme Stuttgart · New York

PAPER
Stereoselective Synthesis of the Macrocyclic Core of (–)-Salicylihalamides A and B
1075
(1S,3R,4S)-1-[2-(4-Methoxybenzyloxy)ethyl]-3-(methoxy-
methoxy)-4-methylhept-6-enyl 2-Allyl-6-methoxybenzoate (16)
To a soln of 3 (0.169 g, 0.48 mmol) and 2 (0.092 g, 0.48 mmol), in
anhyd benzene (10 mL) was cooled to 10 °C, treated with Ph3P
(0.629 g, 2.4 mmol), and stirred for 5 min at 10 °C. DEAD (0.437
mL, 2.4 mmol) was added dropwise via microsyringe, and the mix-
ture was stirred 20 min further, diluted with hexanes (15 mL),
washed with H2O (20 mL), dried (Na2SO4), filtered, and concentrat-
ed. Flash column chromatography (silica gel, 5–7% EtOAc–petro-
leum ether) afforded pure 16 as a viscous colorless oil; yield: 0.230
g (91%); Rf = 0.7 (silica gel, 20% EtOAc–petroleum ether).
with EtOAc (4 × 20 mL). The combined organic layers were dried
(Na2SO4) and concentrated in vacuo. The residue was purified by
flash column chromatography (silica gel, 50% EtOAc–petroleum
ether) to give colorless alcohol 18 as a clear oil; yield: 0.117 g
(94%); Rf = 0.6 (silica gel, 70% EtOAc–petroleum ether).
[a]D25 –31.3 (c 0.5, CHCl3) [Lit.6e [a]D25 –34.5 (c 1.0, CHCl3)].
IR (neat): 3470, 2927, 1721, 1583, 1466, 1274, 1117, 1074, 1037,
973, 839, 799, 758, 665 cm–1.
1H NMR (500 MHz, CDCl3): d = 7.29–7.23 (m, 1 H), 6.81 (t,
J = 8.6 Hz, 2 H), 5.49–5.40 (m, 1 H), 5.35–5.27 (m, 1 H), 5.20–5.12
(m, 1 H), 4.56 (d, J = 6.8 Hz, 1 H), 4.45 (d, J = 6.8 Hz, 1 H), 3.91–
3.82 (m, 1 H), 3.79 (s, 3 H), 3.72 (q, J = 10.3 Hz, 2 H), 3.63 (dd,
J = 11.9, 2.6 Hz, 1 H), 3.29 (s, 3 H), 3.18 (dd, J = 11.9, 2.6 Hz, 1
H), 2.91 (br s, 1 H, OH), 2.03–1.52 (m, 7 H), 0.96 (d, J = 6.8 Hz, 3
H).
13C NMR (75 MHz, CDCl3): d = 167.7, 157.2, 139.7, 133.24,
130.65, 128.74, 124.6, 123.3, 109.85, 95.89, 78.7, 73.7, 58.78, 55.9,
55.34, 38.34, 38.26, 37.47, 34.79, 14.5.
[a]D25 –9.44 (c 1.60, CHCl3).
IR (neat): 2930, 1720, 1585, 1512, 1466, 1375, 1253, 1096, 1036,
915, 759 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.36–7.22 (m, 3 H), 6.92–6.73 (m,
4 H), 6.05–5.65 (m, 2 H), 5.52–5.27 (m, 1 H), 5.13–4.94 (m, 4 H),
4.64 (s, 2 H), 4.45 (s, 2 H), 3.81 (s, 3 H), 3.78 (s, 3 H), 3.70–3.52
(m, 3 H), 3.42–3.30 (m, 5 H), 2.40–2.14 (m, 1 H), 2.12–1.73 (m, 6
H), 0.88 (d, J = 6.5 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 167.6, 159.2, 156.3, 138.2, 137.6,
136.3, 130.5, 130.2, 129.3, 124.2, 121.7, 116.3, 115.7, 113.9, 108.8,
96.2, 78.1, 72.9, 70.7, 66.5, 55.8, 55.5, 37.9, 37.3, 36.2, 35.8, 35.3,
34.5, 13.8.
HRMS (ESI): m/z [M + Na]+ calcd for C21H30NaO6: 401.1940;
found: 401.1943.
Acknowledgment
HRMS (LSIMS): m/z [M + Na]+ calcd for C31H42NaO7: 549.2828;
found: 549.2846.
P.S.R.R. thanks CSIR, New Delhi for financial assistance.
(3S,5R,6S)-14-Methoxy-3-[2-(4-methoxybenzyloxy)ethyl]-5-
(methoxymethoxy)-6-methyl-3,4,5,6,7,10-hexahydro-1H-2-
benzoxacyclododecin-1-one (17)
References
(1) Erickson, K. L.; Beutler, J. A.; Cardellina, J. H. II; Boyd, M.
R. J. Org. Chem. 1997, 62, 8188; corrigendum: J. Org.
Chem. 2001, 66, 1532.
To a flask charged with degassed CH2Cl2 (30 mL) was added simul-
taneously a soln of the Grubbs’ catalyst RuCl2(=CHPh)[P(Cy)3]3
(0.035 g, 0.04 mmol) in CH2Cl2 (20 mL) and a soln of 16 (0.210 g,
0.4 mmol) in CH2Cl2 (20 mL) over a 1 h period via addition funnels.
When the addition was complete, the mixture was refluxed for 3 h.
The resulting soln was brought to r.t., the solvent was evaporated
and the residue purified by flash column chromatography (silica
gel, 15% EtOAc–petroleum ether) to give 17 as a light brown col-
ored viscous liquid; yield: 0.169 g (85%); ratio E/Z 9:1; Rf = 0.4 (sil-
ica gel, 30% EtOAc–petroleum ether).
(2) Lobatamides: (a) McKee, T. C.; Galinis, D. L.; Pannell, L.
K.; Cardellina, J. H. II; Laakso, J.; Ireland, C. M.; Murray,
L.; Capon, R. J.; Boyd, M. R. J. Org. Chem. 1998, 63, 7805 .
Lobatamide A is identical to the structure of YM–75518,
see: (b) Suzumura, K.-I.; Takahashi, I.; Matsumoto, H.;
Nagai, K.; Setiawan, B.; Rantiatmodjo, R. M.; Suzuki, K.-I.;
Nagano, N. Tetrahedron Lett. 1997, 38, 7573. (c) Dekker,
K. A.; Aiello, R. J.; Hirai, H.; Inagaki, T.; Sakakibara, T.;
Suzuki, Y.; Thompson, J. F.; Yamauchi, Y.; Kojima, N. J.
Antibiot. 1998, 51, 14 . Apicularens: (d) Kunze, B.;
Jansen, R.; Sasse, F.; Hofle, G.; Reichenbach, H. J. Antibiot.
1998, 51, 1075. (e) Jansen, R.; Kunze, B.; Reichenbach, H.;
Hofle, G. Eur. J. Org. Chem. 2000, 913 . Oximidines:
(f) Kim, J. W.; Shin-Ya, K.; Furihata, K.; Hayakawa, Y.;
Seto, H. J. Org. Chem. 1999, 64, 153.
(3) Boyd, M. R.; Farina, C.; Belfiore, P.; Gagliardi, S.; Kim, J.-
W.; Hayakawa, Y.; Beutler, J. A.; McKee, T. C.; Bowman,
B. J.; Bowan, E. J. J. Pharmacol. Exp. Ther. 2001, 297, 114.
(4) For an extensive review, see: Forgac, M. Adv. Mol. Cell.
Biol. 1998, 23B, 403.
(5) For a therapeutic focus, see: Farina, C.; Gagliardi, S. Drug
Discovery Today 1999, 4, 163.
(6) Subsequent total syntheses have appeared: (a) Wu, Y.;
Esser, L.; De Brabander, J. K. Angew. Chem. Int. Ed. 2000,
39, 4308. (b) Labrecque, D.; Charron, S.; Rej, R.; Blais, C.;
Lamothe, S. Tetrahedron Lett. 2001, 42, 2645. (c) Snider,
B. B.; Song, F. Org. Lett. 2001, 3, 1817. (d) Smith, A. B.;
Zheng, J. Synlett 2001, 1019. (e) Furstner, A.; Dierkes, T.;
Thiel, O. R.; Blanda, G. Chem. Eur. J. 2001, 7, 5286.
(f) Wu, Y.; Liao, X.; Wang, R.; Xie, S. S.; De Brabander, J.
K. J. Am. Chem. Soc. 2002, 124, 3245. (g) Larry, Y. Chem.
Rev. 2003, 103, 4283. (h) Christian, H.; Frank, D.; Martin,
E. M. Eur. J. Org. Chem. 2005, 728. (i) Haack, T.; Haack,
K.; Diederich, W. E.; Blackman, B.; Roy, S.; Pusuluri, S.;
Georg, G. I. J. Org. Chem. 2005, 70, 7592.
[a]D25 –27.53 (c 1.30, CHCl3).
IR (neat): 2924, 2853, 1726, 1513, 1464, 1375, 1253, 1096, 1036,
760 cm–1.
1H NMR (500 MHz, CDCl3): d = 7.32–7.21 (m, 3 H), 6.87 (d,
J = 8.6 Hz, 2 H), 6.78 (dd, J = 8.3, 3.8 Hz, 2 H), 5.52–5.40 (m, 1
H), 5.34–5.25 (m, 1 H), 5.19–5.10 (m, 1 H), 4.56 (d, J = 6.8 Hz, 1
H), 4.50 (d, J = 11.2 Hz, 1 H), 4.44 (d, J = 6.8 Hz, 1 H), 4.41 (d,
J = 11.2 Hz, 1 H), 4.32 (q, J = 6.8 Hz, 1 H), 3.80 (s, 3 H), 3.76–3.68
(m, 4 H), 3.67–3.58 (m, 2 H), 3.29 (s, 3 H), 3.17 (dd, J = 14.6, 2.6
Hz, 1 H), 2.07–1.79 (m, 4 H), 1.71 (td, J = 11.2, 2.6 Hz, 1 H), 1.63–
1.50 (m, 2 H), 0.94 (d, J = 6.8 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 167.7, 159.1, 157.2, 139.55,
133.48, 130.57, 130.3, 129.35, 128.3, 123.64, 122.87, 113.74,
109.77, 95.8, 79.7, 73.87, 72.79, 66.26, 55.79, 55.35, 55.24, 38.38,
37.42, 37.35, 35.7, 34.53, 14.1.
HRMS (ESI): m/z [M + Na]+ calcd for C29H38NaO7: 521.2515;
found: 521.2508.
(3S,5R,6S)-3-(2-Hydroxyethyl)-14-methoxy-5-(methoxy-
methoxy)-6-methyl-3,4,5,6,7,10-hexahydro-1H-2-benzoxa-
cyclododecin-1-one (18)
To a soln of benzolactone 17 (0.165 g, 0.33 mmol) in CH2Cl2 (10
mL) and H2O (~0.5 mL) was added DDQ (0.091 g, 0.40 mmol). The
mixture was stirred at r.t. for 1.5 h and then the yellow slurry was
poured into sat. NaHCO3 (15 mL) and H2O (30 mL) and extracted
Synthesis 2007, No. 7, 1070–1076 © Thieme Stuttgart · New York

1076
J. S. Yadav, P. S. R. Reddy
PAPER
(7) Partial syntheses and model studies: (a) George, G. I.; Ahn,
Y. M.; Blackman, B.; Farokhi, F.; Flaherty, P. T.; Mossman,
C. J.; Roy, S.; Yang, K. L. Chem. Commun. 2001, 255.
(b) Wu, Y.; Seguil, O. R.; De Brabander, J. K. Org. Lett.
2000, 2, 4241. (c) Bhattacharjee, A.; De Brabander, J. K.
Tetrahedron Lett. 2000, 41, 8069. (d) Feutrill, J. T.;
Holloway, G. A.; Hilli, F.; Hugel, H. M.; Rizzacasa, M. A.
Tetrahedron Lett. 2000, 41, 8569. (e) Furstner, A.; Oliver,
R. T.; Blanda, G. Org. Lett. 2000, 2, 3731. (f) Scheufler, F.;
Maier, M. E. Synlett 2001, 1221. (g) Bauer, M.; Maier, M.
E. Org. Lett. 2002, 4, 2205. (h) Lebreton, S.; Xie, X.;
Ferguson, D.; De Brabander, K. Tetrahedron 2004, 60,
9635.
(8) David, B. C.; John, H. M.; Clark, W. S. J. Am. Chem. Soc.
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(9) Yamaguchi, M.; Hirao, I. Tetrahedron Lett. 1983, 24, 391.
(10) Gao, Y.; Hanson, R. M.; Klunder, J. M.; Ko, S. Y.;
Masamune, H.; Sharpless, K. B. J. Am. Chem. Soc. 1987,
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(11) Johansson, R.; Samuelsson, B. J. Chem. Soc., Chem.
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(12) Yadav, J. S.; Srihari, P. Tetrahedron: Asymmetry 2004, 15,
81.
(13) Mitsunobu, O. Synthesis 1981, 1.
(14) (a) Grubbs, R. H.; Chang, S. Tetrahedron 1998, 54, 4413.
(b) Trnka, T. M.; Grubbs, R. H. Acc. Chem. Res. 2001, 34,
18.
Synthesis 2007, No. 7, 1070–1076 © Thieme Stuttgart · New York