Tetrahedron Letters
3
cis-2-butene-1,4-diol (24)12 (Scheme 4). Silylether 24 was
oxidized by treating with pyridinium chlorochromate (PCC) and
Celite to provide E-enal 25 in 78% yeild.13 The resulting
aldehyde 25 underwent asymmetric aldol reaction14 with the
known chiral auxiliary (S)-4-benzyl-3-propionyloxazolidin-2-one
(26) to furnish hydroxyimide 27 in 76% yield as single
diastereomer. Protection of hydroxyl group in compound 27
using TESOTf afforded compound 28 in 88% yield. Reductive
cleavage of the chiral auxiliary in compound 28 using NaBH4 in
MeOH produced corresponding primary alcohol in 87% yield.
Oxidation of the resulting alcohol with Dess-Martin periodinane
(DMP) gave required aldehyde 29 in 72% yield.
°C, 1 h; ii) I2, THF, −78 to 0 °C, 30 min, 72%; f) i) TBAF, THF, 0
o
oC-rt, 4 h, 86%; ii) 21, PPh3, DIAD, THF, 0 C-rt, 6 h, 87%; g)
(NH4)6Mo7O24, H2O2, EtOH, rt, 12 h, 77%.
silyl protected Roche ester 31.16 Controlled reduction of ester 31
o
with DIBAL-H at −78 C afforded corresponding aldehyde,16
which was immediately treated with (ethoxycarbonylmethylene)
triphenylphosphorane in benzene at room temperature to furnish
α,ß-unsaturated ester 32 with E-configuration in 80% yield over
two steps. The ester group in compound 32 was reduced with
DIBAL-H to provide the corresponding allylic alcohol in 87%
yield. The Sharpless asymmetric epoxidation17 of resulting allylic
alcohol using (−)-DET and Ti(OiPr)4 in CH2Cl2 at −20 oC
furnished epoxy alcohol 33 in 85% yield (≥98% de). Epoxy
alcohol 33 was converted to the corresponding (chloromethyl)
oxirane using CCl4-Ph3P under reflux conditions followed by
base-induced elimination reaction18 to afford the chiral
propargylic alcohol 9 in 81% yield over two steps.
Propargyl alcohol 9 was protected as its p-methoxybenzyl
(PMB) ether with p-methoxybenzyl bromide (PMB-Br) and NaH
to afford corresponding alkyne 34 in 87% yield. The terminal
alkyne of 34 was subjected to a hydrozirconation-iodination
sequence by treatment with Schwartz reagent19 (Cp2ZrHCl)
prepared from Cp2ZrCl2 and DIBAL-H in situ followed by
exposure to an electrophilic iodine source to incorporate trans-
vinyl iodide 35 in 72% yield. Vinyl iodide 35 was next
transformed into sulfide 36 in 74% yield by a two-step sequence
involving removal of the tert-butyldiphenylsilyl (TBDPS)
protecting group using tetrabutylammonium fluoride (TBAF) and
Mitsunobu reaction of the resulting primary alcohol with 1-
phenyl-1H-tetrazole-5-thiol (21), triphenylphosphine (TPP) and
with ammonium heptamolybdate and H2O2 afforded sulfone
fragment 6 in 77% yield.11
Scheme 5. Coupling of aldehyde 29 and sulphone 22
With both the coupling partners aldehyde 29 and sulfone 22 in
hand, we then carried out Julia-Kocienski olefination11,15 (Scheme
5) under different reaction conditions (Table 1), but failed to
isolate required coupling product 30.
Table 1: Different conditions for Julia-Kocienski olefination
entry
reagent
conditions
time
yielda
1
2
3
4
LHMDS
KHMDS
LHMDS
KHMDS
THF/HMPA, –78 oC-rt
THF/HMPA, –78 oC-rt
DME, –78 oC-rt
12
12
12
12
NR
NR
NR
NR
DME, –78 oC-rt
Now, the stage is set to couple the sulphone 6 and aldehyde 5
aStarting material recovered
through Julia–Kocienski olefination.11,15 Aldehyde
5 was
prepared from alcohol 19 by oxidation with Dess-Martin
periodinane (DMP) in 91% y−ield. Coupling of sulfone 6 with
aldehyde 5 in presence of LiHMDS and HMPA/THF (1:4) at −78
oC for 2 h and stirring at room temperature over 5 h, furnished
To circumvent the above problem, we changed the strategy.
Accordingly, we planned to prepare sulfone 6 (Scheme 6) as one
of the coupling partner and earlier sulfone fragment became
aldehyde fragment in this case. The synthesis started from the
1
coupled product 4 with (E)-olefin (E/Z ≥ 9:1 as per H NMR) in
70% yield. The coupling product was assigned on the basis of its
1H NMR in which four peaks appeared due the resonance of
olefinic protons at δ 6.44, 6.21, and 5.33 ppm, benzylic methyle
protons at δ 4.56 ppm and methoxy methyl protons of PMB
group at δ 3.80 ppm, respectively. Furthermore, 13C NMR and
mass spectral data were in good agreement with the product.
Scheme 6. Synthesis of sulphone 6
Reagents and conditions: a) i) DIBAL-H, −78 oC, 30 min; ii)
Ph3P=CHCOOEt, C6H6, rt, 5 h, 80% (over 2 steps); b) i) DIBAL-H,
CH2Cl2, −20 oC, 30 min, 87%; ii) (−)-DET, Ti(OiPr)4, TBHP,
o
Scheme 6. Synthesis of the C3 to C15 fragment of callyspong-
iolide (1)
CH2Cl2, −20 C, 10 h, 85%; c) i) PPh3, NaHCO3, CCl4, reflux, 5 h;
o
ii) n-BuLi, THF, −78 C, 3 h, 81% (over 2 steps); d) PMBBr, NaH,
o
TBAI, THF, 0 C-rt, 6 h, 87%; e) i) Cp2ZrCl2, DIBAL-H, THF, 0