An expeditious asymmetric synthesis of polyfunctional 1,7-dioxaspiro[5.5] undecanes

Article abstract of DOI:10.1002/ejoc.200400514

Quick access to polyfunctional spiroketal (3R)-4-[(2S,6R,8R,10S)-4,4- bis(ethylthio)-10-hydroxy-8-(2-hydroxy-ethyl)-1,7-dioxaspiro[5.5]undec-2-yl] butane-1,3-diol [(+)-19] is now available through the stereoselective functionalization of enantiomerically

Full text of DOI:10.1002/ejoc.200400514

FULL PAPER
An Expeditious Asymmetric Synthesis of Polyfunctional
1,7-Dioxaspiro[5.5]undecanes
Sandrine Gerber-Lemaire*[a] and Pierre Vogel[a]
Keywords: Bis(cyclohept-1-ene) derivatives / Ozonolysis / Polyfunctional spiroketals / Selective protection
Quick access to polyfunctional spiroketal (3R)-4-
1,1Ј-methylenebis[4-[(benzyloxy)methoxy]-6-[(triethylsilyl)-
[(2S,6R,8R,10S)-4,4-bis(ethylthio)-10-hydroxy-8-(2-hydroxy- oxy]cyclohept-1-ene [(−)-9], derived from 2,2Ј-methylenedif-
ethyl)-1,7-dioxaspiro[5.5]undec-2-yl]butane-1,3-diol [(+)-19]
is now available through the stereoselective functionalization
of enantiomerically pure protected tetrol (4R,4ЈR,6R,6ЈR)-
uran.
( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2004)
Introduction
theory, all possible pentadecan-1,3,5,7,9,11,13,15-octols can
be prepared from meso-5.[13] We have reported that threo-4
can be converted into the enantiomerically pure diacetate
(ϩ)-7 and diol (Ϫ)-6,[14] and we have shown that they can
be transformed in a few steps into enantiomerically pure,
long-chain polyketides.[15] We report here that (ϩ)-7 can be
converted into polyfunctional 1,7-dioxaspiro[5.5]undecanes
related to the spiroketal moieties of spongistatins.
A large variety of natural products of biological interest
contain the 1,7-dioxaspiro[5.5]undecane (6,6-spiroketal)
moiety.[1Ϫ4] Several synthetic approaches to spiroketals have
been proposed,[5] and the focus during the last decade has
been on the two AB and CD spiroketal units[6] of altohyrt-
ins (spongistatins),[7] highly promising anti-tumor agents[8]
isolated in minute amounts from rare marine sponges.[9Ϫ11]
Our group has developed a noniterative, asymmetric syn-
thesis of C15 polyketides, starting from the readily available
2,2Ј-methylenedifuran (3). Double [4ϩ3] cycloaddition of
halogenated 2-oxyallyl cations to 3 generates, after re-
Results and Discussion
As already reported, (ϩ)-7 can be transformed into the
ductive workup, a 55:45 mixture of diketones 4 and 5 semi-protected tetrol (Ϫ)-8 in 68% yield (Scheme 2).
(60%yield) that are readily separated (Scheme 1).[12] In Double silylation with Et3SiCl/imidazole provided (Ϫ)-9
Scheme 1
(92%). Ozonolysis of (Ϫ)-9 in an MeOH/CH2Cl2 (1:1) mix-
[a]
Institute of Chemical Sciences and Engineering, Swiss Institute
ture (Ϫ78 °C), followed by reductive treatment first with
of Technology (EPFL),
Me2S (Ϫ78 °C) and then with NaBH4 at 0 °C, afforded a
BCH, 1015 Lausanne, Switzerland
Fax: (internat.) ϩ 41-21-693-93-55
mixture of dihemiacetals 10 that was not isolated but was
E-mail: Sandrine.Gerber@epfl.ch
directly subjected to acidic treatment (40% aq. HF in
5040
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
DOI: 10.1002/ejoc.200400514
Eur. J. Org. Chem. 2004, 5040Ϫ5046

Polyfunctional 1,7-Dioxaspiro[5.5]undecanes
FULL PAPER
Scheme 2. Synthesis of protected tricyclic spiroketals
CH3CN, Ϫ50 °C). A mixture of tricyclic hemiacetal 11 and The (S) absolute configuration at C(3) and the confor-
β-hydroxyenone 12 was formed (1H NMR analysis of the mation of the spiroketal were established from the 2D-
crude product). When this mixture was treated with a cata- NOESY-1H NMR spectrum of (Ϫ)-16. The most stable spi-
lytic amount of camphorsulfonic acid in MeOH at 0 °C, roketal (two axial oxygen atoms, double anomeric effect,
spiroketal (Ϫ)-13 was obtained in 69% yield [based on (Ϫ)- conformation B) was not verified by the NOEs observed. In
9]. In the absence of MeOH, treatment of 11 and 12 under particular, two cross-peaks between the signals of C(4)-H2
the same catalytic conditions in CH2Cl2 (0 °C) provided (δH ϭ 1. 85 and 2.69 ppm) and C(3Ј)-H2 (δH ϭ 1.99 and
pure (ϩ)-11 in 72% yield. Silylation with 1 equiv. of (tBu)- 2.24 ppm) would be expected for this structure, and these
Me2SiOSO2CF3 in the presence of 2,6-lutidine at low tem- were not observed in the 2D-NOESY-1H NMR spectrum.
perature (Ϫ40 °C) was highly selective and resulted in the On the contrary, diagnostic NOEs required for confor-
formation of the semi-protected spiroketal (Ϫ)-14 in 90% mation A [C(6Ј)-H/C(4Ј)-H, C(4Ј)-H/C(1)-H, C(7)-H/C(9)-
yield. The reasons for the faster silylation of the tertiary H, C(9)-H/C(3Ј)-H] were observed. This established the for-
alcoholic moiety of the hemiacetal relative to the secondary mation of the kinetic spiroketal (axial/equatorial arrange-
alcohol group of (ϩ)-11 are not clear to us.[16] With the ment), which was trapped by the formation of an additional
use of 2 equiv. of (tBu)Me2SiOSO2CF3, a mixture of the hemiacetal at C(5). The structures of the (3R) enantiomer
disilylated derivative (Ϫ)-15 (60% yield) and (Ϫ)-14 (23% (kinetic or thermodynamic conformers) were not verified
yield) was observed.
Acetylation of alcohol (Ϫ)-14 under standard conditions
(Ac2O/pyridine, DMAP cat., 0 °C) gave acetate (Ϫ)-16
(91%), the structure of which was established by its spectro-
1
scopic data and especially its 2D-NOESY H NMR spec-
trum (Figure 1). Proton signal assignments were carried out
as follows. The most deshielded multiplet (δH ϭ 5.69 ppm)
was assigned to C(4Ј)-H. It showed cross-peaks with signals
at δH ϭ 2.24 and 1.99 ppm. These signals in turn did not
present any cross-peak with other protons adjacent to oxy-
gen atoms, and so were assigned to C(3Ј)-H2. The multiplet
at δH ϭ 1.86Ϫ1.95 ppm showed cross-peaks with the signal
of C(4Ј)-H and with a multiplet at δH ϭ 4.00 ppm [C(6Ј)-
H], and so was assigned to C(5Ј)-H2. The other multiplet
(δH ϭ 4.26 ppm) presenting cross peaks with the signal of
CH2CH2OBOM corresponds to C(7)-H, and the remaining
signal of a proton adjacent to an oxygen atom (δH
ϭ
4.85 ppm) was thus assigned to C(1)-H. The signals of C(4)-
H2 at δ ϭ 1.85 and 2.69 ppm and of C(9)-H2 at δ ϭ
1.79 ppm were then easily assigned from their multiplicities. spectrum
Figure 1. Representation of (Ϫ)-16 with indication of the proton
pairs presenting diagnostic NOEs in the 2D-NOESY 1H NMR
Eur. J. Org. Chem. 2004, 5040Ϫ5046
www.eurjoc.org
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
5041

S. Gerber-Lemaire, P. Vogel
FULL PAPER
by the cross-peaks observed. The 2D-NOESY-1H NMR Quick access to polyfunctional 1,7-dioxaspiro[5.5]unde-
spectrum of (Ϫ)-16 was thus consistent with a (3S)-config- canes is now available. The formation of a tricyclic structure
ured spiroketal.
[hemiacetal at C(5)] allows the trapping of the less energeti-
Attempts to oxidize the alcohol of (ϩ)-11 under cally favored kinetic spiroketal. Moreover, as various ster-
DessϪMartin,[17] Swern,[18] and Ley’s[19] conditions re- eoisomers of the starting diolefin (Ϫ)-9 can easily be ob-
sulted in decomposition of the starting material. Under the tained through the same methodology [meso and threo de-
same conditions, methyl acetal (Ϫ)-13 also decomposed and rivatives, C(6),C(6Ј)-exo and -endo diols], the transform-
the expected ketone could not be isolated in better yield ations reported here can generate a high diversity of
than 10%. Fortunately, silyl acetal (Ϫ)-14 was successfully stereoisomeric spiroketals on gram scale amounts. Studies
oxidized under Ley’s conditions (Pr4NRuO4 0.2 equiv., to obtain analogues of the spiroketals described here and
NMO, molecular sieves) to provide the desired ketone (Ϫ)- intermediates useful for the synthesis of natural products of
17 in 90% yield.
biological interest, including spongistatins, are underway in
If our methodology for the synthesis of 1,7-dioxaspiro- our laboratory.
[5.5]undecanes is to be applied to the formation of spongi-
statins, the tricyclic system will have to be opened (Scheme
3). This operation can be achieved in good yield by desilyl-
Experimental Section
ation of (Ϫ)-16 in the presence of aqueous HF at Ϫ40 °C
(98% crude yield), followed by a subsequent thioacetaliz-
ation step in a mixture of EtSH/CH2Cl2 (1:10) in the pres-
ence of BBr3 (2 equiv., 0 °C). This acidic treatment induced
the opening of the silyl acetal at the C(5) position, allowing
protection of the resulting ketone as a dithioacetal and
equilibration of the spiroketal to the most stable conformer
(axial/axial arrangement). This sequence provided (ϩ)-19 in
67% yield [based on (Ϫ)-16]. Selective functionalization of
each ring of these spiroketals should thus be possible
through derivatization of the ketone at C(4Ј) position of
(Ϫ)-17 or at C(4Ј) position of (ϩ)-19.
General: Commercial reagents (Fluka, Aldrich) were used without
purification. Solvents were distilled prior to use: MeOH from Mg
and I2, DMF from P2O5, and CH2Cl2 from CaH2. Light petroleum
ether used refers to the fraction boiling at 40Ϫ60 °C. Solutions
after reactions and extractions were concentrated in a rotary evap-
orator under reduced pressure. Liquid/solid flash chromatography
(FC): columns of silica gel (0.040Ϫ0.63 mm, Merck No.9385 silica
gel 60, 240Ϫ400 mesh). TLC for reaction monitoring: Merck silica
gel 60F254 plates; detection by UV light; Pancaldi reagent
[(NH4)6MoO4, Ce(SO4)2, H2SO4, H2O] or KMnO4. IR spectra:
1
PerkinϪElmer 1420 spectrometer. H NMR spectra: Bruker ARX
400 spectrometer (400 MHz); δ(H) in ppm relative to the solvent’s
residual 1H signal (CHCl3: δ ϭ 7.27 ppm; CH3OD: δ ϭ 3.34 ppm;
1
C6H6: δ ϭ 7.3 ppm) as internal reference; all H assignments were
confirmed by 2D-COSY-45 and 2D-NOESY spectra. 13C NMR
spectra: Same instrument as above (100.6 MHz); δ(C) in ppm rela-
tive to solvent’s 13C signal (CDCl3: δ ϭ 77.0 ppm; CD3OD: δ ϭ
48.5 ppm; C6D6: δ ϭ 128.5 ppm) as internal reference; coupling
constants J in Hz. MS: Nermag R-10-10C, chemical ionization
(NH3) mode m/z (amu) [% relative base peak (100%)]. MALDI-
TOF mass spectra were obtained from the Swiss Institute of Tech-
nology Mass Spectral Facility. Elemental analyses: Ilse Beetz, 96301
Kronach, Germany.
(4R,4ЈR,6R,6ЈR)-4,4Ј-Bis(benzyloxy)methoxy-6,6Ј-bis(triethylsilyl)-
oxy-1,1Ј-methylenebis(cyclohept-1-ene) [(؊)-9]: Imidazole (5 equiv.,
2.34 g, 34.41 mmol) and chlorotriethylsilane (3 equiv., 3.5 mL, 20
64 mmol) were added at 0 °C to a solution of (Ϫ)-8[15] (3.5 g,
6.881 mmol) in DMF (70 mL). After stirring at 0 °C for 45 min,
the mixture was poured into H2O (150 mL) and extracted with di-
ethyl ether (100 mL, 3 times). The combined organic extracts were
dried (MgSO4) and concentrated in vacuo. The residue was purified
by flash chromatography on silica gel (EtOAc/PE, 1:6) to afford
(Ϫ)-9 as a colorless oil (4.66 g, 92%). Rf ϭ 0.55 (EtOAc/EP, 1:6).
20
20
20
20
[α]2D0 ϭ Ϫ38, [α]
ϭ Ϫ42, [α]
ϭ Ϫ46, [α]
ϭ Ϫ83, [α]
ϭ
577
546
435
405
Ϫ105 (c ϭ 0.66, CHCl3). IR (film): ν˜ ϭ 3030, 2955, 2910, 2875,
1740, 1500, 1455, 1415, 1375, 1240, 1165, 1080, 1040, 1030, 870,
745 cmϪ1. UV (MeCN): λmax. (ε [dm3·molϪ1·cmϪ1]) ϭ 218 (15230)
nm. 1H NMR (CDCl3, 400 MHz, 25 °C): δ ϭ 0.58, 0.60 [2 q,
3JH,H ϭ 6.5, 6.7 Hz, 12 H, 6 CH2 (TES)], 0.96 [m, 18 H, 6 CH3
Scheme 3. Preparation of the polyfunctional spiroketal (ϩ)-19
Conclusion
2
(TES)], 1.97 [ddd, JH,H ϭ 13.5, 3JH,H ϭ 8.4, 3.3 Hz, 2 H, C(5)-H,
C(5Ј)-H], 2.07Ϫ2.10 [m, 2 H, C(5)-H, C(5Ј)-H], 2.15 [br. d, 2JH,H ϭ
14.8 Hz, 2 H, C(7)-H, C(7Ј)-H], 2.28Ϫ2.40 [m, 4 H, C(3)-H2, C(3Ј)-
H2], 2.72 [s, 2 H, C(8)-H2], 3.91Ϫ4.00 [m, 4 H, C(4)-H, C(6)-H,
The chemistry disclosed in this report demonstrates the
versatility of our noniterative approach to the preparation
of C15 polyketides and to spiroketals derived from them. C(4Ј)-H, C(6Ј)-H], 4.62 [s, 4 H, 2CH2Ph], 4.78 [AB system, 4 H, 2
5042  2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim www.eurjoc.org
Eur. J. Org. Chem. 2004, 5040Ϫ5046

Polyfunctional 1,7-Dioxaspiro[5.5]undecanes
FULL PAPER
3
CH2 (BOM)], 5.46 [t, JH,H ϭ 6.2 Hz, 2 H, C(2)-H, C(2Ј)-H], 1325, 1210, 1165, 1040, 815, 740, 700 cmϪ1. UV (MeCN): λmax. (ε
7.38Ϫ7.28 (m, 10 H, Harom..) ppm. 13C NMR (CDCl3, 100.6 MHz, [dm3·molϪ1·cmϪ1]) ϭ 254 (18250), 198 (8790) nm. 1H NMR
25 °C): δ ϭ 4.75 [t, 1JC,H ϭ 117, 6 CH2 (TES)], 6.9 [q, 1JC,H ϭ 121, ([D4]MeOH, 400 MHz, 25 °C): δ ϭ 1.61 [dd, 2JH,H ϭ 9.6, 3JH,H
ϭ
1
1
2
3
6 CH3 (TES)], 32.8 [t, JC,H ϭ 128, C(7), C(7Ј)], 40.3 [t, JC,H
ϭ
3.4 Hz, 1 H, C(3Ј)-H], 1.62 [dd, JH,H ϭ 10.9, JH,H ϭ 3.4 Hz, 1
129, C(3), C(3Ј)], 46.4 [t, 1JC,H ϭ 125, C(5), C(5Ј)], 51.5 [t, JC,H ϭ H, C(8)-H], 1.60Ϫ1.93 [m, 7 H, C(7)-CH2, C(9)-H2, C(3Ј)-H, C(6Ј)-
1
1
1
2
3
125, C(8)], 66.0 [d, JC,H ϭ 140, C(6), C(6Ј)], 69.3 [t, JC,H ϭ 144,
CH2], 1.94 [d, JH,H ϭ 11.0 Hz, 1 H, C(4)-H], 1.99 [dm, JH,H ϭ
1
1
2
4
2 CH2Ph], 71.6 [d, JC,H ϭ 146, C(4), C(4Ј)], 92.6 [t, JC,H ϭ 162, 10.9 Hz, 1 H, C(8)-H], 2.85 [dd, JH,H ϭ 11.0, JH,H ϭ 2.7 Hz, 1
1
3
2 CH2 (BOM)], 123.1 [d, JC,H ϭ 156, C(2), C(2Ј)], 127.6, 127.8, H, C(4)-H], 3.69 [t, JH,H ϭ 6.6 Hz, 4 H, 2 CH2-OBOM],
1
128.4 [3 d, JC,H ϭ 160, 158, 161, 10 Carom.], 138.0 (s, 2 Carom.), 3.99Ϫ4.14 [m, 3 H, C(7)-H, C(4Ј)-H, C(6Ј)-H], 4.48Ϫ4.55 [m, 1 H,
2
138.1 [s, C(1), C(1Ј)] ppm. CI-MS: m/z (%) ϭ 754 (57) [M ϩ
C(1)-H], 4.66 (s, 2 H, CH2Ph), 4.67, 4.72 (2 d, 2 H, JH,H
ϭ
NH4ϩ], 600 (2), 467 (5), 377 (10), 245 (11), 132 (16), 91 (100) 12.0 Hz, CH2Ph), 4.86 [s, 4 H, 2 CH2 (BOM)], 7.28Ϫ7.40 (m, 10
[PhCH2ϩ]. C43H68O6Si2 (737.176): calcd. C 70.06, H 9.30; found C
70.01, H 9.16.
H, Harom.) ppm. 13C NMR ([D4]MeOH, 100.6 MHz, 25 °C): δ ϭ
1
39.7, 40.2 [2 t, JC,H ϭ 125, 126, C(7)-CH2, C(6Ј)-CH2], 43.6 [t,
1JC,H ϭ 125, C(9)], 42.8 [t, 1JC,H ϭ 127, C(8)], 44.3 [t, 1JC,H ϭ 125,
C(5Ј)], 45.4 [t, 1JC,H ϭ 127, C(3Ј)], 45.6 [t, 1JC,H ϭ 128, C(4)], 60.2,
(1S,3S,4ЈS,5R,6ЈR,7R)-6Ј,7-Bis{2-[(benzyloxy)methoxy]ethyl}-tetra-
hydrospiro[2,6-dioxabicyclo[3.3.1]nonane-3,2Ј-pyran]-4Ј,5-diol [(؉)-
11]: A stream of ozone was passed at Ϫ78 °C through a solution
of (Ϫ)-9 (1.5 g, 2.035 mmol) in CH2Cl2/MeOH (25 mL/25 mL) for
5 min. A stream of O2 was passed through the mixture for 2 min,
and Me2S (4equiv., 645 µL, 8.139 mmol) was added dropwise. After
the mixture had been stirred at Ϫ78 °C for 5 min, NaBH4 (4 equiv.,
308 mg, 8.139 mmol) was added and the mixture was warmed to 0
°C for 30 min. Acetic acid (500 µL) was added, and the solution
was stirred at 0 °C for an additional 5 min. The mixture was poured
into a satd. aq. solution of NaHCO3 (80 mL) and extracted with
EtOAc (80 mL, 3 times). The combined organic extracts were dried
(MgSO4) and concentrated in vacuo to afford a pale yellow oil
(1.6 g, 98%). HF (40% in water, 4.5 mL) was added dropwise at
Ϫ50 °C to a solution of the crude bis(hemiketals) 10 (1.6 g,
1.987 mmol) in MeCN (45 mL). After stirring at Ϫ50 °C for 20
min, the mixture was poured, with vigorous stirring, into a satd.
aq. solution of NaHCO3 (100 mL), cooled to 0 °C. After 5 min,
solid NaHCO3 was added to reach pH ϭ 8 and the solution was
extracted with EtOAc (80 mL, 3 times). The combined organic ex-
tracts were dried (MgSO4) and concentrated in vacuo. The residue
(mixture of 11 and 12) was taken up in CH2Cl2 (20 mL), cooled to
0 °C, and treated with camphorsulfonic acid (30 mg). After stirring
at 0 °C for 30 min, the mixture was directly purified by flash chro-
matography on silica gel (CH2Cl2/MeOH, 15:1) to afford (ϩ)-11 as
a colorless oil [818 mg, 72% from (Ϫ)-9].
1
1
60.3 [2 t, JC,H ϭ 141, 2 CH2-OBOM], 66.3 [d, JC,H ϭ 144, C(1)],
69.9 [d, 1JC,H ϭ 148, C(4Ј)], 71.6, 71.7 (2 t, 1JC,H ϭ 142, 2 CH2Ph),
1
74.2, 75.3 [2 d, JC,H ϭ 140, 142, C(7), C(6Ј)], 96.0, 96.6 [2 t,
1JC,H ϭ 159, 162, 2 CH2 (BOM)], 110.8, 111.3 [2 s, C(3,2Ј), C(5)],
1
129.5, 129.8, 130.3 (3 d, JC,H ϭ 160, 159, 160, 10 Carom.), 141.9 (s,
2 Carom.) ppm. CI-MS: m/z (%) ϭ 576 (2) [M ϩ NH4ϩ], 516 (1),
391 (6), 312 (20), 205 (44), 91 (100) [PhCH2ϩ]. C31H42O9 (558.663):
calcd. C 66.65, H 7.58; found C 66.34, H 7.57.
(1S,3S,4ЈS,5R,6ЈR,7R)-6Ј,7-Bis{2-[(benzyloxy)methoxy]ethyl}-5-
methoxy-tetrahydrospiro[2,6-dioxabicyclo[3.3.1]nonane-3,2Ј-pyran]-
4Ј-ol [(؊)-13]: The same procedure as above was applied on (Ϫ)-9
(500 mg, 0.678 mmol). The crude mixture of 11 and 12 was taken
up in MeOH (8 mL) at 0 °C and treated with camphorsulfonic acid
(5 mg). After stirring at 0 °C for 15 min, the solution was poured
into a satd. aq. solution of NaHCO3 (20 mL) and extracted with
EtOAc (20 mL, 3 times). The combined organic extracts were dried
(MgSO4) and concentrated in vacuo. Purification by flash chroma-
tography on silica gel (CH2Cl2/MeOH, 20:1) afforded (Ϫ)-13 as a
pale yellow oil [268 mg, 69% from (Ϫ)-9]. Rf ϭ 0.22 (CH2Cl2/
20
20
MeOH, 15:1). [α]2D0 ϭ Ϫ18, [α] ϭ Ϫ30, [α] ϭ Ϫ41 (c ϭ 0.15,
435
405
CH2Cl2). IR (film): ν˜ ϭ 3355, 3030, 2920, 1590, 1420, 1370, 1325,
1210, 1120, 1030, 770 cmϪ1
.
UV (MeCN): λmax. (ε
[dm3·molϪ1·cmϪ1]) ϭ 197 (8670) nm. H NMR (C6D6, 400 MHz,
1
25 °C): δ ϭ 1.60 [dd, 2JH,H ϭ 12.7, 3JH,H ϭ 11.1 Hz, 1 H, C(8)-H],
2
1.72 [m, 2 H, C(9)-H2], 1.73 [d, JH,H ϭ 10.8 Hz, 1 H, C(4)-H],
1.80 [m, 2 H, C(5Ј)-H2], 1.75Ϫ1.96 [m, 4 H, CH2-C(7), CH2-C(6Ј)],
1.91 [dd, JH,H ϭ 12.9, JH,H ϭ 2.8 Hz, 1 H, C(3Ј)-H], 2.10 [dd,
Data for Intermediate (3R,5S,11S,13R)-1,15-Bis[(benzyloxy)meth-
oxy]-3,5,9,11,13-pentahydroxypentadec-8-en-7-one (12): Rf ϭ 0.3
(CH2Cl2/MeOH, 10:1). IR (film): ν˜ ϭ 3385, 2940, 1650, 1600, 1495,
1435, 1430, 1405, 1380, 1165, 1035 cmϪ1. UV (MeCN): λmax. (ε
[dm3·molϪ1·cmϪ1]) ϭ 208 (10180), 197 (10150) nm. 1H NMR
([D4]MeOH, 400 MHz, 25 °C): δ ϭ 1.68 [m, 2JH,H ϭ 13.0 Hz, 1 H,
C(4)-H], 1.72Ϫ1.89 [m, 6 H, C(2)-H2, C(12)-H2, C(14)-H2], 2.04
2
3
3
2
2JH,H ϭ 12.9, JH,H ϭ 8.9 Hz, 1 H, C(3Ј)-H], 2.11 [dm, JH,H
ϭ
2
4
12.7 Hz, 1 H, C(8)-H], 2.63 [dd, JH,H ϭ 10.8, JH,H ϭ 2.7 Hz, 1
H, C(4)-H], 3.30 [s, 3 H, OCH3], 3.72Ϫ3.88 [m, 4 H, 2 CH2-
OBOM], 3.97 (s, OH), 4.27 [m, 1 H, C(7)-H], 4.36Ϫ4.38 [m, 2 H,
2
C(4Ј)-H, C(6Ј)-H], 4.68, 4.71 (2 d, JH,H ϭ 11.8 Hz, 2 H, CH2Ph),
2
3
[ddd, JH,H ϭ 13.0, JH,H ϭ 9.8, 3.2 Hz, 1 H, C(4)-H], 2.40 [m, 2
4.75, 4.79 (2 d, 2JH,H ϭ 12.1 Hz, 2 H, CH2Ph), 4.82Ϫ4.86 [m, 1 H,
H, C(6)-H, C(10)-H], 2.49 [d, 2JH,H ϭ 13.8 Hz, 1 H, C(10)-H], 2.52
2
C(1)-H], 4.90, 4.93 [2 d, JH,H ϭ 7.1 Hz, 2 H, CH2 (BOM)], 4.95,
2
3
[d, JH,H ϭ 15.9, 1 H, C(6)-H], 3.69, 3.70 [2 t, JH,H ϭ 6.6 Hz, 4
H, C(1)-H2, C(15)-H2], 4.04 [m, 1 H, C(3)-H], 4.13 [m, 2 H, C(11)-
H, C(13)-H], 4.63, 4.64 [2 s, 4 H, 2CH2Ph], 4.66 [m, 1 H, C(5)-H],
4.84, 4.85 [2 s, 4 H, 2 CH2 (BOM)], 5.38 [s, 1 H, C(8)-H], 7.27Ϫ7.39
(m, 10 H, Harom.) ppm. 13C NMR ([D4]MeOH, 100.6 MHz, 25 °C):
δ ϭ 40.1, 40.2 [2 t, C(2), C(14)], 42.2 [t, C(4)], 44.8 [t, C(12)], 42.8,
45.5 [2 t, C(6), C(10)], 60.1, 60.3 [2 t, C(1), C(15)], 67.6 [d, C(11)],
71.7, 71.9 [2 t, 2CH2Ph], 74.6, 75.3 [2 d, C(3), C(13)], 78.5 [d, C(5)],
96.6, 96.7 [2 t, 2CH2 (BOM)], 107.2 [d, C(8)], 129.6, 129.8, 130.3
(3 d, 10 Carom.), 140.0, 140.1 (2 s, 2 Carom.), 178.4 [s, C(9)], 196.7
[s, C(7)] ppm.
2
4.97 [2 d, JH,H ϭ 6.8 Hz, 2 H, CH2 (BOM)], 7.20Ϫ7.25 (m, 2 H,
3
Harom.), 7.35Ϫ7.30 (m, 4 H, Harom.), 7.46, 7.51 (2 d, JH,H ϭ 8.6,
7.4 Hz, 4 H, Harom.) ppm. 13C NMR (C6D6, 100.6 MHz, 25 °C):
δ ϭ 38.5, 39.0 [2 t, CH2-C(7), CH2-C(6Ј)], 41.6 [t, C(9)], 42.5 [t,
C(8)], 43.4 [t, C(3Ј)], 43.9 [t, C(5Ј)], 44.6 [t, C(4)], 50.8 (q, OCH3),
59.5, 59.6 (2 t, 2 CH2-OBOM), 65.5 [d, C(4Ј)], 69.0 [d, C(1)], 70.4,
70.5 (2 t, 2CH2Ph), 73.4 [d, C(7)], 74.8 [d, C(6Ј)], 95.0, 95.4 [2 t, 2
CH2 (BOM)], 109.2, 110.2 [2 s, C(3,2Ј), C(5)], 128.3, 128.6, 129.1
(3 d, 10 Carom.), 139.0 (s, 2 Carom.) ppm. MALDI-TOF: m/z ϭ 611
[M ϩ Kϩ]. C32H44O9 (572.691): calcd. C 67.11, H 7.74; found C
66.32, H 7.68.
Data for (؉)-11: Rf ϭ 0.13 (CH2Cl2/MeOH, 15:1). [α]2D0 ϭ ϩ11,
20
20
20
[α] ϭ ϩ12, [α] ϭ ϩ23, [α] ϭ ϩ26 (c ϭ 0.36, CH2Cl2). IR (1S,3S,4ЈS,5S,6ЈR,7R)-6Ј,7-Bis{2-[(benzyloxy)methoxy]ethyl}-5-
577
435
405
(film): ν˜ ϭ 3445, 3030, 2945, 2895, 1655, 1635, 1555, 1455, 1375, [(tert-butyldimethylsilyl)oxy]-tetrahydrospiro[2,6-dioxabicyclo-
Eur. J. Org. Chem. 2004, 5040Ϫ5046
www.eurjoc.org  2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim 5043

S. Gerber-Lemaire, P. Vogel
FULL PAPER
[3.3.1]nonane-3,2Ј-pyran]-4Ј-ol [(؊)-14]: 2,6-Lutidine (2.5 equiv.,
115 µL, 0.984 mmol) and tert-butyldimethylsilyl trifluoromethanes-
2
CH2Ph), 4.91 [m, 1 H, C(1)-H], 4.95, 5.00 [2 d, JH,H ϭ 7.0 Hz, 2
H, CH2 (BOM)], 4.99 [s, 2 H, CH2 (BOM)], 7.22 (m, 2 H, Harom.),
ulfonate (0.1  in CH2Cl2, 1 equiv., 3.94 mL, 0.394 mmol) were 7.31 (m, 4 H, Harom.), 7.51 (m, 4 H, Harom.) ppm. 13C NMR (C6D6,
added to a solution of (ϩ)-11 (220 mg, 0.394 mmol) in anhydrous 100.6 MHz, 25 °C): δ ϭ Ϫ5.5, Ϫ5.4, Ϫ4.3, Ϫ4.1 [4 q, 2 Si(CH3)2],
CH2Cl2 (1.2 mL), cooled to Ϫ40 °C. After stirring at Ϫ40 °C for
1 h, the mixture was poured into a satd. aq. solution of NaHCO3
(20 mL) and extracted with CHCl3 (20 mL, 3 times). The combined
organic extracts were dried (MgSO4) and concentrated in vacuo.
Purification by chromatography on silica gel (EtOAc/PE, 1:5) af-
18.0 [s, C(CH3)3], 25.9 (q, tBu), 38.6, 39.3 [2 t, C(7)-CH2, C(6Ј)-
CH2], 41.6 [t, C(5Ј)], 42.0 [t, C(8)], 43.3 [t, C(3Ј)], 44.1 [t, C(9)],
44.4 [t, C(4)], 59.7 (t, 2 CH2-OBOM), 66.5 [d, C(4Ј)], 68.1 [d, C(1)],
69.4, 69.5 (2 t, 2 CH2Ph), 72.2 [d, C(7)], 73.9 [d, C(6Ј)], 94.1, 94.2
[2 t, 2 CH2 (BOM)], 108.4, 108.5 [2 s, C(3,2Ј), C(5)], 127.0, 128.1,
forded (Ϫ)-14 as a colorless oil (239 mg, 90%). Rf ϭ 0.48 (EtOAc/ 128.6 (3 d, 10 Carom.), 138.4, 138.6 (2 s, 2 Carom.) ppm. C43H70O9Si2
20
20
petroleum ether, 1:4). [α]2D0 ϭ Ϫ6, [α]
ϭ Ϫ7, [α]
ϭ Ϫ14, (787.189): calcd. C 65.61, H 8.96, Si 7.14; found C 65.69, H 8.92,
577
435
20
[α] ϭ Ϫ17 (c ϭ 0.25, CH2Cl2). IR (film): ν˜ ϭ 3485, 3045, 3030, Si 7.17.
405
2925, 1495, 1470, 1385, 1255, 1095, 835, 775, 735, 695, 665 cmϪ1
.
UV (MeCN): λmax. (ε [dm3·molϪ1·cmϪ1]) ϭ 207 (4600), 194 (10490)
(1S,3S,4ЈS,5S,6ЈR,7R)-6Ј,7-Bis{2-[(benzyloxy)methoxy]ethyl}-5-
[(tert-butyldimethylsilyl)oxy]-tetrahydrospiro[2,6-dioxabicyclo-
[3.3.1]nonane-3,2Ј-pyran]-4Ј-yl Acetate [(؊)-16]: 4-(Dimethyl-
amino)pyridine (5 mg) was added at 0 °C to a solution of alcohol
(Ϫ)-14 (380 mg, 0.565 mmol) in pyridine/acetic anhydride (2.5 mL/
2.5 mL). The mixture was stirred at 0 °C for 45 min and the sol-
vents were evaporated in vacuo. Purification by flash chromatogra-
phy on silica gel (EtOAc/PE, 1:5) afforded (Ϫ)-16 as a pale yellow
oil (367 mg, 91%). Rf ϭ 0.56 (EtOAc/pentane, 1:4). [α]2D0 ϭ Ϫ4,
1
nm. H NMR (C6D6, 400 MHz, 25 °C): δ ϭ 0.20, 0.21 [2 s, 6 H,
Si(CH3)2], 1.13 (s, 9 H, tBu), 1.63 [dd, JH,H ϭ 11.9, JH,H
2
3
ϭ
2
3
11.2 Hz, 1 H, C(8)-H], 1.69 [dd, JH,H ϭ 12.1, JH,H ϭ 3.2 Hz, 1
H, C(5Ј)-H], 1.74 [d, 2JH,H ϭ 10.7 Hz, 1 H, C(4)-H], 1.77Ϫ1.84 [m,
2
3
3 H, C(9)-H2, C(5Ј)-H], 1.87 [dd, JH,H ϭ 12.9, JH,H ϭ 2.1 Hz,
C(3Ј)-H], 1.91Ϫ2.06 [m, 4 H, C(7)-CH2, C(6Ј)-CH2], 2.15 [dd,
2JH,H ϭ 12.9, JH,H ϭ 9.6 Hz, 1 H, C(3Ј)-H], 2.17 [dm, JH,H
ϭ
3
2
2
4
11.9 Hz, 1 H, C(8)-H], 2.73 [dd, JH,H ϭ 10.7, JH,H ϭ 2.7 Hz, 1
H, C(4)-H], 3.76Ϫ3.88 [m, 4 H, 2 CH2-OBOM], 4.29 [m, 1 H, C(7)-
H], 4.40Ϫ4.43 [m, 2 H, C(4Ј)-H, C(6Ј)-H], 4.79 [s, 2 H, CH2Ph],
4.71, 4.88 [2 d, 2 H, JH,H ϭ 12.3 Hz, CH2Ph], 4.94 [m, 1 H, C(1)-
H], 4.95, 4.98 [2 s, 4 H, 2CH2 (BOM)], 7.20Ϫ7.26 (m, 2 H, Harom.),
20
20
[α]
ϭ Ϫ5, [α]
ϭ Ϫ38 (c ϭ 0.25, CH2Cl2). IR (film): ν˜ ϭ
577
435
3065, 3035, 2930, 1740, 1610, 1495, 1470, 1370, 1330, 1255, 1115,
835, 775, 735, 635, 665 cmϪ1
.
UV (MeCN): λmax. (ε
2
1
[dm3·molϪ1·cmϪ1]) ϭ 207 (9050) nm. H NMR (C6D6, 400 MHz,
3
25 °C): δ ϭ 0.10, 0.11 [2 s, 6 H, Si(CH3)2], 1.03 (s, 9 H, tBu), 1.61
7.31Ϫ7.36 (m, 4 H, Harom.), 7.47, 7.55 (2 d, JH,H ϭ 7.4, 4 H,
2
3
arom.) ppm. 13C NMR (C6D6, 100.6 MHz, 25 °C): δ ϭ Ϫ5.5 [q,
[dd, JH,H ϭ 12.8, JH,H ϭ 11.0 Hz, 1 H, C(8)-H], 1.79 [m, 2 H,
H
2
C(9)-H2], 1.85 [d, JH,H ϭ 10.6 Hz, 1 H, C(4)-H], 1.86 (s, 3 H,
Si(CH3)2], 18.2 [s, C(CH3)3], 25.9 (q, tBu), 37.9, 38.8 [2 t, C(7)-
CH2, C(6Ј)-CH2], 41.0 [t, C(3Ј)], 42.0 [t, C(5Ј)], 42.3 [t, C(9)], 43.5,
43.6 [2 t, C(4), C(8)], 59.6 [t, 2 CH2-OBOM], 64.7 [d, C(4Ј)], 68.1
[d, C(1)], 69.4, 69.5 (2 t, 2 CH2Ph), 71.9 [d, C(7)], 73.4 [d, C(6Ј)],
108.6, 109.6 [2 s, C(3,2Ј), C(5)], 127.3, 128.2, 128.3 (3 d, 10 Carom.),
138.4, 138.7 (2 s, 2 Carom.) ppm. MALDI-TOF: m/z ϭ 673 [M ϩ
Hϩ]. C37H56O9Si (672.926): calcd. C 66.04, H 8.39, Si 4.17; found
C 66.06, H 8.30, Si 4.12.
2
OAc), 1.86Ϫ1.95 [m, 2 H, C(5Ј)-H2], 1.99 [dd, JH,H ϭ 14.8,
3JH,H ϭ 4.8 Hz, 1 H, C(3Ј)-H], 1.70Ϫ2.00 [m, 4 H, C(7)-CH2,
2
3
C(6Ј)-CH2], 2.13 [ddd, JH,H ϭ 12.8, JH,H ϭ 4.3, 2.8 Hz, 1 H,
C(8)-H], 2.24 [dd, JH,H ϭ 14.8, JH,H ϭ 8.5 Hz, 1 H, C(3Ј)-H],
2.69 [dd, JH,H ϭ 10.6, JH,H ϭ 2.7 Hz, 1 H, C(4)-H], 3.66Ϫ3.81
(m, 2 H, CH2-OBOM), 3.82 (tm, JH,H ϭ 6.6 Hz, 2 H, CH2-
2
3
2
4
3
OBOM), 4.00 [m, 1 H, C(6Ј)-H], 4.26 [m, 1 H, C(7)-H], 4.67, 4.72
2
(2 d, JH,H ϭ 12.1 Hz, 2 H, CH2Ph), 4.73 (s, 2 H, CH2Ph), 4.85
2
(1S,3S,4ЈS,5S,6ЈR,7R)-6Ј,7-Bis{2-[(benzyloxy)methoxy]ethyl}-4Ј,5-
[(tert-butyldimethylsilyl)oxy]-tetrahydrospiro[2,6-dioxabicyclo-
[3.3.1]nonane-3,2Ј-pyran [(؊)-15]: 2,6-Lutidine (3 equiv., 63 µL,
0.537 mmol) and tert-butyldimethylsilyl trifluoromethanesulfonate
(2 equiv., 82 µL, 0.358 mmol) were added at Ϫ30 °C to a solution
[m, 1 H, C(1)-H], 4.86, 4.92 [2 d, JH,H ϭ 7.0 Hz, 2 H, CH2
2
(BOM)], 4.92, 4.97 [2 d, JH,H ϭ 7.0 Hz, 2 H, CH2 (BOM)], 5.69
[m, 1 H, C(4Ј)-H], 7.13Ϫ7.17 (m, 2 H, Harom.), 7.23Ϫ7.28 (m, 4
H, Harom.), 7.42Ϫ7.48 (m, 4 H, Harom.) ppm. 13C NMR (C6D6,
1
100.6 MHz, 25 °C): δ ϭ Ϫ5.5, Ϫ5.4 [2 q, JC,H ϭ 118, Si(CH3)2],
of (ϩ)-11 (100 mg, 0.179 mmol) in anhydrous CH2Cl2 (4 mL). 18.2 [s, C(CH3)3], 20.8 (q, 1JC,H ϭ 129, OAc), 25.9 (q, 1JC,H ϭ 125,
1
After stirring at Ϫ30 °C for 45 min, the mixture was poured into
a satd. aq. solution of NaHCO3 (10 mL) and extracted with CHCl3
(10 mL, 3 times). The combined organic extracts were dried
(MgSO4) and concentrated in vacuo. Purification by chromatogra-
phy on silica gel (EtOAc/PE, 1:10 to 1:4) afforded (Ϫ)-15 as a col-
orless oil (84 mg, 60%) and (Ϫ)-14 as a colorless oil (28 mg, 23%).
tBu), 38.4, 38.7 [2 t, JC,H ϭ 125, 127, C(7)-CH2, C(6Ј)-CH2], 40.1
1
1
[t, 1JC,H ϭ 126, C(3Ј)], 41.0 [t, JC,H ϭ 131, C(5Ј)], 41.7 [t, JC,H
ϭ
1
1
127, C(9)], 42.0 [t, JC,H ϭ 129, C(8)], 43.2 [t, JC,H ϭ 133, C(4)],
59.4, 59.7 [2 t, JC,H ϭ 141, 140, 2 CH2-OBOM], 67.1 [d, JC,H
1
1
ϭ
142, C(4Ј)], 68.1 [d, 1JC,H ϭ 145, C(1)], 69.4, 69.5 [2 t, 1JC,H ϭ 147,
2 CH2Ph], 72.1 [d, 1JC,H ϭ 141, C(7)], 72.7 [d, 1JC,H ϭ 141, C(6Ј)],
94.3, 94.4 [2 t, 1JC,H ϭ 159, 2 CH2 (BOM)], 108.7 [s, C(3,2Ј), C(5)],
127.3, 128.3, 128.5 (3 d, masked, 10 Carom.), 138.5, 138.7 (2 s, 2
Carom.), 169.7 (s, CϭO) ppm. MALDI-TOF: m/z ϭ 898 [M ϩ8
Na]. C39H58O10Si (714.963): calcd. C 65.51, H 8.18; found C 65.50,
H 8.16.
Data for (؊)-15: Rf ϭ 0.50 (EtOAc/petroleum ether, 1:8). [α]2D0
ϭ
Ϫ26 (c ϭ 0.38, CH2Cl2). IR (film): ν˜ ϭ 2955, 2930, 2885, 2855,
1470, 1460, 1385, 1360, 1330, 1255, 1170, 1100, 1045, 1005, 835,
775, 735, 700 cmϪ1. UV (MeCN): λmax. (ε [dm3·molϪ1·cmϪ1]) ϭ
193 (17400) nm. 1H NMR (C6D6, 400 MHz, 25 °C): δ ϭ 0.32, 0.22
[2 s, 12 H, 2 Si(CH3)2], 1.13, 1.15 (2 s, 18 H, tBu), 1.69 [dd, 2JH,H ϭ (1S,3S,5S,6ЈR,7R)-6Ј,7-Bis{2-[(benzyloxy)methoxy]ethyl}-5-[(tert-
3
14.7, JH,H ϭ 12.4 Hz, 1 H, C(8)-H], 1.89 [m, 2 H, C(9)-H2], 1.90 butyldimethylsilyl)oxy]-dihydrospiro[2,6-dioxabicyclo[3.3.1]nonane-
[d, JH,H ϭ 10.6 Hz, 1 H, C(4)-H], 1.97Ϫ2.01 [m, 2 H, C(5Ј)-H2],
2
˚
3,2Ј-pyran]-4Ј(3ЈH)-one [(؊)-17]: Activated molecular sieves (4 A,
2
2.02Ϫ2.12 [m, 4 H, C(7)-CH2, C(6Ј)-CH2], 2.24 [dd, JH,H ϭ 14.6, 45 mg, 500 mg/mmol), N-methylmorpholine N-oxide (2.5 equiv.,
3JH,H ϭ 7.7 Hz, 1 H, C(3Ј)-H], 2.30 [ddd, JH,H ϭ 14.7, JH,H
ϭ
30 mg, 0.224 mmol), and TPAP (0.2 equiv., 6.3 mg, 1.790.10Ϫ5 mol)
2
3
4.7, 2.9 Hz, 1 H, C(8)-H], 2.36 [dd, JH,H ϭ 14.6, JH,H ϭ 3.8 Hz, were added to a solution of (Ϫ)-14 (50 mg, 8.950.10Ϫ5 mol) in an-
2
3
2
4
1 H, C(3Ј)-H], 2.84 [dd, JH,H ϭ 10.6, JH,H ϭ 2.5 Hz, 1 H, C(4)-
H], 3.85Ϫ3.95 (m, 4 H, 2 CH2-OBOM), 4.23 [m, 1 H, C(6Ј)-H], min and filtered through a pad of silica gel (EtOAc, 50 mL). The
4.32 [m, 1 H, C(7)-H], 4.48 [m, 1 H, C(4Ј)-H], 4.77 (m, 4 H, 2 filtrate was concentrated in vacuo. Purification by flash chromatog-
hydrous CH2Cl2 (1.5 mL). The mixture was stirred at 25 °C for 50
5044
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2004, 5040Ϫ5046

Polyfunctional 1,7-Dioxaspiro[5.5]undecanes
FULL PAPER
raphy on silica gel (EtOAc/PE, 1:5) afforded (Ϫ)-17 as a colorless 14.7, 3JH,H ϭ 4.3 Hz, 1 H, C(3Ј)-H], 2.69 [dd, 2JH,H ϭ 12.4, 4JH,H ϭ
oil (45 mg, 90%). Rf ϭ 0.43 (EtOAc/petroleum ether, 1:6). [α]2D0
ϭ
2.6 Hz, 1 H, C(4)-H], 3.55Ϫ3.82 (m, 4 H, 2 CH2-OBOM), 4.01 [m,
20
20
20
2
Ϫ15, [α] ϭ Ϫ15, [α] ϭ Ϫ30, [α] ϭ Ϫ35 (c ϭ 0.4, CH2Cl2). 1 H, C(6Ј)-H], 4.22 [m, 1 H, C(7)-H], 4.68, 4.74 [2 d, JH,H
ϭ
577
435
405
IR (film): ν˜ ϭ 3030, 2930, 2855, 1715, 1500, 1470, 1385, 1255, 1095, 12.4 Hz, 2 H, CH2Ph], 4.74 (s, 2 H, CH2Ph), 4.83 [m, 1 H, C(1)-
2
1045, 835, 775, 735 cmϪ1
.
UV (MeCN): λmax. (ε H], 4.87, 4.91 [2 d, JH,H ϭ 7.1 Hz, 2 H, CH2 (BOM)], 4.90 [s, 2
1
[dm3·molϪ1·cmϪ1]) ϭ 206 (6830), 200 (6860) nm. H NMR (C6D6,
H, CH2 (BOM)], 5.65 [m, 1 H, C(4Ј)-H], 7.12Ϫ7.16 (m, 2 H,
Harom.), 7.25 (m, 4 H, Harom.), 7.44Ϫ7.49 (m, 4 H, Harom.) ppm.
400 MHz, 25 °C): δ ϭ 0.12, 0.13 [2 s, 6 H, Si(CH3)2], 1.05 (s, 9 H,
tBu), 1.57 [dd, JH,H ϭ 12.3, JH,H ϭ 11.3 Hz, 1 H, C(8)-H], 1.73 MALDI-TOF: m/z ϭ 601 [M ϩ Hϩ].
2
3
[m, 2 H, C(9)-H2], 1.79Ϫ1.92 [m, 4 H, C(7)-CH2, C(6Ј)-CH2], 2.00
Data for (؉)-19: Rf ϭ 0.27 (CH2Cl2/MeOH, 15:1). [α]2D0 ϭ ϩ28,
[d, 2JH,H ϭ 10.9 Hz, C(4)-H], 2.08 [dm, 2JH,H ϭ 12.3 Hz, 1 H, C(8)-
20
20
20
2
3
[α]
ϭ ϩ30, [α]
ϭ ϩ59, [α]
ϭ ϩ73 (c ϭ 0.2, MeOH). IR
577
435
405
H], 2.56 [dd, JH,H ϭ 15.8, JH,H ϭ 4.9, 1 H, C(5Ј)-H], 2.73 [dd,
(film): ν˜ ϭ 3375, 3030, 2945, 1660, 1460, 1435, 1115, 1025, 780,
2JH,H ϭ 10.9, 3JH,H ϭ 2.7 Hz, 1 H, C(4)-H], 2.53, 2.79 [2 d, 2JH,H ϭ
14.4 Hz, 2 H, C(3Ј)-H2], 2.82 [dd, JH,H ϭ 15.8, JH,H ϭ 7.1 Hz, 1
H, C(5Ј)-H], 3.76 (m, 4 H, 2 CH2-OBOM), 4.22 [m, 1 H, C(7)-H],
4.50 [m, 1 H, C(6Ј)-H], 4.57, 4.62 [2 d, JH,H ϭ 12.1 Hz, 2 H,
CH2Ph], 4.67, 4.78 [2 d, JH,H ϭ 12.3 Hz, 2 H, CH2Ph], 4.81 [m, 1
2
3
665 cmϪ1. UV (MeCN): λmax. (ε [dm3·molϪ1·cmϪ1]) ϭ 207 (11900)
1
nm. H NMR (C6D6, 400 MHz, 25 °C): δ ϭ 1.27 [m, 6 H, 2 CH3
2
(SEt)], 1.55Ϫ1.82 [m, 4 H, C(2)-H2, CH2-C(8Ј)], 2.08Ϫ2.20 [m, 6
2
3
2
H, C(4)-H2, C(9Ј)-H2, C(11Ј)-H2], 1.99 [dd, JH,H ϭ 10.8, JH,H
ϭ
2
2.6 Hz, 1 H, C(3Ј)-H], 2.07, 2.15 [2 d, 2JH,H ϭ 10.8 Hz, 2 H, C(5Ј)-
H2], 2.28 [dd, JH,H ϭ 10.8, JH,H ϭ 2.1 Hz, 1 H, C(3Ј)-H], 2.63
[q, JH,H ϭ 7.5 Hz, 2 H, CH2 (SEt)], 2.79 [q, JH,H ϭ 7.3 Hz, 2 H,
CH2 (SEt)], 3.66 [t, JH,H ϭ 6.5 Hz, 2 H, C(1)-H2], 3.69Ϫ3.77 [m,
H, C(1)-H], 4.79, 4.82 [2 d, JH,H ϭ 6.7 Hz, 2 H, CH2 (BOM)],
2
3
2
4.85, 4.88 [2 d, JH,H ϭ 7.0 Hz, 2 H, CH2 (BOM)], 7.13Ϫ7.39 (m,
3
3
6 H, Harom.), 7.41, 7.47 [2 d, 2JH,H ϭ 7.5 Hz, 4 H, Harom.] ppm. 13
C
3
1
NMR (C6D6, 100.6 MHz, 25 °C): δ ϭ Ϫ4.7 [q, JC,H ϭ 118,
1
2 H, CH2-OH], 4.03 [m, 1 H, C(8Ј)-H], 4.08Ϫ4.13 [m, 2 H, C(2Ј)-
H, C(10Ј)-H], 4.17 [m, 1 H, C(3)-H] ppm. 13C NMR ([D4]MeOH,
100.6 MHz, 25 °C): δ ϭ 13.4, 15.0 [2 q, 2 CH3 (SEt)], 24.0, 24.5 [2
t, 2 CH2 (SEt)], 35.7, 36.6 [2 t, C(2), CH2-C(8Ј)], 38.8, 39.4 [2 t,
C(2Ј), C(5Ј)], 41.1, 42.6 [2 t, C(9Ј), C(11Ј)], 43.4 [t, C(4)], 49.1 [s,
C(4Ј)], 59.0, 59.7 [2 t, C(1), CH2-OH], 66.3 [d, C(10Ј)], 69.0, 69.1
[2 d, C(2Ј), C(8Ј)], 70.4 [d, C(3)], 98.1 [s, C(6Ј)] ppm. MALDI-
TOF: m/z ϭ 406 [M Ϫ H2O]ϩ. C19H36O6S2 (424.619): calcd. C
53.75, H 8.55; found C 53.64, H 8.51.
Si(CH3)2], 18.9 [s, C(CH3)3], 26.6 [q, JC,H ϭ 125, tBu], 38.9, 39.0
[2 t, 1JC,H ϭ 126, CH2-C(7), CH2-C(6Ј)], 42.0 [t, 1JC,H ϭ 129, C(9)],
1
1
42.7 [t, JC,H ϭ 127, C(8)], 43.7 [t, JC,H ϭ 130, C(4)], 48.1 [t,
1JC,H ϭ 129, C(3Ј)], 50.7 [t, JC,H ϭ 128, C(5Ј)], 60.2, 60.3 [2 t,
1
1JC,H ϭ 142, 140, 2 CH2-OBOM], 69.0 [d, 1JC,H ϭ 145, C(1)], 70.1,
1
1
70.2 (2 t, JC,H ϭ 146, 2 CH2Ph), 72.0 [d, JC,H ϭ 141, C(7)], 72.2
[d, 1JC,H ϭ 142, C(6Ј)], 94.4, 95.0 [2 t, 1JC,H ϭ 158, 2 CH2 (BOM)],
1
108.2, 109.5 [2 s, C(3,2Ј), C(5)], 127.9 (d, JC,H ϭ 160, Carom.),
129.1, 129.7 (2 d, masked, Carom.), 139.1, 139.4 (2 s, 2 Carom.), 203.3
[s, C(4Ј)] ppm. MALDI-TOF: m/z ϭ 671 [M ϩ Hϩ], 613 [M Ϫ
tBu]ϩ. C37H54O9Si (670.911): calcd. C 66.24, H 8.11; found C
66.23, H 8.09.
Acknowledgments
This work was supported by the Swiss National Science Foun-
(3R)-4-[(2S,6S,8R,10S)-4,4-Bis(ethylthio)-10-hydroxy-8-(2-hydroxy-
ethyl)-1,7-dioxaspiro[5.5]undec-2-yl]butane-1,3-diol [(؉)-19]: HF
(40% in water, 0.5 mL) was added dropwise at Ϫ40 °C to a solution
of (Ϫ)-16 (87 mg, 0.122 mmol) in acetonitrile (3.5 mL). After stir-
ring at Ϫ40 °C for 30 min, the mixture was poured with vigorous
stirring into a satd. aq. solution of NaHCO3 (15 mL), cooled to 0
°C. After 5 min, solid NaHCO3 was added to reach pH ϭ 8 and the
solution was extracted with EtOAc (15 mL, 3 times). The combined
organic extracts were dried (MgSO4) and concentrated in vacuo.
The residue was taken up in CH2Cl2/ethanethiol (2 mL/0.2 mL)
and cooled to 0 °C. BBr3 (2 equiv., 1  in CH2Cl2, 0.244 mmol,
244 µL) was added dropwise. The solution was stirred at 0 °C for
15 min and poured into a satd. aq. solution of NaHCO3 (15 mL),
cooled to 0 °C. After the mixture had been stirred for 2 min, the
aqueous layer was extracted with CH2Cl2 (15 mL, 3 times). The
combined organic extracts were dried (MgSO4) and concentrated
in vacuo at Ϫ20 °C. Purification by flash chromatography on silica
gel (CH2Cl2/MeOH, 15:1) afforded (ϩ)-19 as a pale yellow oil
(34 mg, 67%).
`
dation. We thank Mr. Martial Rey, Mr. Francisco Sepulveda, and
Dr. Alain Razaname for technical help.
[1]
[2]
[1a]
For reviews, see, for example:
1987, 43, 3309.
T. L. B. Boivin, Tetrahedron
[1b]
F. Perron, K. F. Albizati, Chem. Rev. 1989,
89, 1617. [1c] V. Vaillancourt, N. E. Pratt, F. Perron, K. F. Albiz-
ati, Total Synth. Nat. Prod. 1992, 533. [1d] N. Haddad, Z. Abra-
movich, I. Ruhman, Recent Res. Dev. Org. Chem. 1997, 1, 35.
For examples of insect pheromones, see:
Herbert, Nat. Prod. Rep. 1984, 1, 299.
A. Lewis, M. T. Fletcher, R. A. I. Drew, C. J. Moore, W.
[2a]
R. Baker, R. H.
[2b]
W. M. Kitching, J.
Francke, J. Chem. Soc., Chem. Commun. 1986, 853 and refer-
[2c]
ences cited therein.
Y. Q. Tu, C. J. Moore, W. Kitching,
Tetrahedron: Asymmetry 1995, 6, 397.
For components of glandular secretions of higher insects, see,
for example: J. R. Aldrich, G. K. Waite, S. Schutz, W. Francke,
J. Org. Chem. 1994, 59, 6136.
For polyether ionophores, see, for example:
[3]
[4]
[4a]
H. Mishima,
M. Kurabayashi, C. Tamura, Tetrahedron Lett. 1975, 10, 711.
[4b]
R. W. Burg, B. M. Miller, J. Birnbaum, S. A. Currie, R.
Hartman, Y. L. Wong, R. L. Monaghan, G. Olson, L. Putter,
J. B. Tunac, H. Wallick, E. O. Stapley, R. Oiwa, S. Omura,
Data for Intermediate (1S,3S,4ЈS,5S,6ЈR,7R)-6Ј,7-Bis{2-[(benzyl-
oxy)methoxy]ethyl}-5-hydroxy-tetrahydrospiro[2,6-dioxabicyclo-
[3.3.1]nonane-3,2Ј-pyran]-4Ј-yl Acetate (18): IR (film): ν˜ ϭ 3440,
3060, 3035, 2935, 1740, 1610, 1490, 1375, 1320, 1250, 1110, 830,
785, 660 cmϪ1. UV (MeCN): λmax. (ε [dm3·molϪ1·cmϪ1]) ϭ 205
(10040) nm. 1H NMR (C6D6, 400 MHz, 25 °C): δ ϭ 1.61 [dd,
Antimicrob. Agents Chemother. 1979, 15, 361. [4c] H. Mrozik, P.
[4d]
Eskola, M. H. Fisher, Tetrahedron. Lett. 1982, 23, 2377.
S.
M. Kupchan, E. J. La Voie, A. R. Branfman, B. Y. Fei, W. M.
Bright, R. F. Bryan, J. Am. Chem. Soc. 1977, 99, 3199.
[5] [5a]
P. Deslongchamps, D. D. Rowan, N. Pothier, T. Sauve, J.
Saunders, Can. J. Chem. 1981, 59, 1105. [5b] P. Deslongchamps,
D. D. Rowan, N. Pothier, J. Saunders, Can. J. Chem. 1981, 59,
1122.
3
2JH,H ϭ 13.7, JH,H ϭ 11.4 Hz, 1 H, C(8)-H], 1.89 [m, 2 H, C(9)-
2
H2], 1.83 [d, JH,H ϭ 12.4 Hz, 1 H, C(4)-H], 1.87 (s, 3 H, OAc),
[5c]
D. A. Evans, H. P. Ng, D. L. Rieger, J. Am. Chem.
2
3
[5d]
1.88 [m, 2 H, C(5Ј)-H2], 2.01 [dd, JH,H ϭ 14.7, JH,H ϭ 7.9 Hz, 1
H, C(3Ј)-H], 1.80Ϫ2.12 [m, 4 H, C(7)-CH2, C(6Ј)-CH2], 2.15 [ddd,
Soc. 1993, 115, 11446.
D. A. Evans, S. W. Kaldor, T. K.
Jones, J. Clardy, T. J. Stout, J. Am. Chem. Soc. 1990, 112, 7001.
3
2
[5e]
2JH,H ϭ 13.7, JH,H ϭ 4.1, 2.6 Hz, 1 H, C(8)-H], 2.24 [dd, JH,H ϭ
J. D. White, G. L. Bolton, A. P. Dantanarayana, C. M. J.
Eur. J. Org. Chem. 2004, 5040Ϫ5046
www.eurjoc.org
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
5045

S. Gerber-Lemaire, P. Vogel
FULL PAPER
Fox, R. N. Hiner, R. W. Jackson, K. Sakuma, U. S. Warrier, J.
A. N. Tyler, Tetrahedron 1999, 55, 8671. [7e] J. Guo, K. J. Duffy,
Am. Chem. Soc. 1995, 117, 1908. [5f] M. T. Crimmins, R. O’Ma-
K. L. Stevens, P. I. Dalko, R. M. Roth, M. M. Hayward, Y.
[5g]
[7f]
hony, J. Org. Chem. 1989, 54, 1157.
Daub, J. Org. Chem. 1983, 48, 1303.
R. E. Ireland, J. P.
R. E. Ireland, J. P.
Kishi, Angew. Chem. Int. Ed. Engl. 1997, 36, 187.
M. M.
[5h]
Hayward, R. M. Roth, K. J. Duffy, P. I. Dalko, K. L. Stevens,
Daub, G. S. Mandel, N. S. Mandel, J. Org. Chem. 1983, 48,
J. Guo, Y. Kishi, Angew. Chem. Int. Ed. Engl. 1997, 36, 187.
[5i]
[7g]
1312.
S. L. Schreiber, Z. Wang, J. Am. Chem. Soc. 1985,
A. B. Smith III, V. A. Doughty, A. Lin, L. Zhuang, M. D.
107, 5303. [5j] N. L. Totah, S. L. Schreiber, J. Org. Chem. 1991,
McBriar, A. M. Boldi, W. H. Moser, N. Murase, K. Nakayama,
[7h]
56, 6255. [5k] B. Bernet, P. M. Bishop, M. Caron, T. Kawamata,
M. Sobukawa, Angew. Chem. Int. Ed. 2001, 40, 191.
A. B.
B. L. Roy, L. Ruest, G. Sauve, P. Soucy, P. Deslongchamps,
Can. J. Chem. 1985, 63, 2818.
hony, J. Org. Chem. 1990, 55, 5894.
Smith III, Q. Lin, V. A. Doughty, L. Zhuang, M. D. McBriar,
[5l]
M. T. Crimmins, R. OЈMa-
J. K. Kerns, C. S. Brook, N. Murase, K. Nakayama, Angew.
[5m]
[7i]
Y. Zhao, N. E. Pratt,
Chem. Int. Ed. 2001, 40, 196.
A. B. Smith III, V. A.
[5n]
M. J. Heeg, K. F. Albizati, J. Org. Chem. 1993, 58, 1300.
M. T. Crimmins, R. OЈMahony, J. Org. Chem. 1989, 54, 1157.
Doughty, C. Sfouggatakis, C. S. Bennett, J. Koyanagi, M. Take-
[7j]
uchi, Org. Lett. 2002, 4, 783.
A. B. Smith III, W. Zhu, S.
[5o]
M. T. Crimmins, D. M. Bankaitis-Davis, W. G. Hollis Jr.,
Shirakami, C. Sfouggatakis, V. A. Doughty, C. S. Bennett, Y.
[5p]
[7k]
J. Org. Chem. 1988, 53, 652.
M. F. Jacobs, B. D. Sothers,
Sakamoto, Org. Lett. 2003, 5, 761.
I. Paterson, D. Y. K.
A. Huebener, W. Kitching, J. Chem. Soc., Perkin Trans. 1 1995,
Chen, M. J. Coster, J. L. Acen˜a, J. Bach, K. R. Gibson, L.
901. [5q] M. T. Crimmins, R. S. Al-awar, I. M. Vallin, R. OЈMa-
E. Keown, R. M. Oballa, T. Trieselmann, D. J. Wallace, A. P.
hony, W. G. Hollis Jr., D. M. Bankaitis-Davis, J. G. Lever, J.
Hodgson, R. D. Norcross, Angew. Chem. Int. Ed. 2001, 40,
[5r]
[7l]
Am. Chem. Soc. 1996, 119, 7513.
M. T. Crimmins, D.G.
Washburn, J. D. Katz, F. J. Zawacki, Tetrahedron Lett. 1998,
4055.
M. T. Crimmins, J. D. Katz, L. C. McAtee, E. A.
[7m]
Tabet, S. J. Kirincich, Org. Lett. 2001, 3, 949.
M. T. Crim-
39, 3439. [5s] H. Huang, C. Mao, S. T. Jan, F. M. Uckun, Tetra-
mins, J. D. Katz, D. G. Washburn, S. P. Allwein, L. F. McAtee,
C. H. Heathcock, M.
McLaughlin, J. Medina, J. L. Hubbs, G. A. Wallace, R. Scott,
[5t]
[7n]
hedron Lett. 2000, 41, 1699.
A. G. M. Barrett, D. C. Brad-
J. Am. Chem. Soc. 2002, 124, 5661.
dock, C. D. de Koning, A. J. P. White, D. J. Williams, J. Org.
Chem. 2000, 65, 375. [5u] R. Zemribo, K. T. Mead, Tetrahedron
M. M. Claffey, C. J. Hayes, G. R. Ott, J. Am. Chem. Soc. 2003,
[5v]
[7o]
´
Lett. 1998, 39, 3891.
G. Solladie, N. Huser, Tetrahedron:
125, 12844.
J. L. Hubbs, C. H. Heathcock, J. Am. Chem.
Asymmetry 1994, 5, 255. [5w] A. M. Doherty, S. V. Ley, B. Lygo,
Soc. 2003, 125, 12836.
T. Terauchi, T. Tanaka, T. Terauchi,
[7p]
[5x]
D. J. Williams, J. Chem. Soc., Perkin Trans. 1 1984, 1371.
M. Morita, K. Kimijima, I. Sato, W. Shoji, Y. Nakamura, T.
Tsukada, T. Tsunoda, C. Hayashi, N. Kanoh, M. Nakata,
Tetrahedron Lett. 2003, 44, 7747. [7q] T. Terauchi, T. Terauchi, I.
Sato, W. Shoji, T. Tsukada, T. Tsunoda, N. Kanoh, M. Nakata,
Tetrahedron Lett. 2003, 44, 7741.
[8]
S. Sauret, A. Cuer, J. G. Gouray, G. Jeminet, Tetrahedron:
[5y]
Asymmetry 1995, 6, 1995.
H. Nakamura, K. Sato, A. Mu-
[5z]
rai, Tetrahedron Lett. 1996, 37, 7267.
Brewer, Curr. Org. Chem. 2003, 7, 227.
K. T. Mead, B. N.
[6] [6a]
M. M. Claffey, C. H. Heathcock, J. Org. Chem. 1996, 61,
G. R. Pettit, J. Nat. Prod. 1996, 59, 812.
[9] [9a]
[6b]
7646.
hedron Lett. 1996, 37, 8581.
Tetrahedron Lett. 1997, 38, 5119.
I. Paterson, R. M. Oballa, R. D. Norcross, Tetra-
G. R. Pettit, Z. A. Cichacz, C. L. Herald, F. Gao, M. R.
[6c]
L. A. Paquette, A. Braun,
Boyd, J. M. Schmidt, E. Hamel, R. Bai, J. Chem. Soc., Chem.
[6d]
C. J. Hayes, C. H.
Commun. 1994, 1605. [9b] G. R. Pettit, C. L. Herald, Z. A. Cich-
[6e]
Heathcock, J. Org. Chem. 1997, 62, 2678.
M. Oballa, Tetrahedron Lett. 1997, 38, 8241.
I. Paterson, R.
acz, F. Gao, M. R. Boyd, N. D. Christie, J. M. Schmidt, Nat.
[6f]
[9c]
A. B. Smith
Prod. Lett. 1993, 3, 239.
G. R. Pettit, C. L. Herald, Z. A.
III, L. Zhuang, C. S. Brook, Q. Lin, W. H. Moser, R. E. L.
Trout, A. M. Boldi, Tetrahedron Lett. 1997, 38, 8671. [6g] A. B.
Smith III, Q. Lin, K. Nakayama, A. M. Boldi, C. S. Brook,
Cichacz, F. Gao, J. M. Schmidt, M. R. Boyd, N. D. Christie,
F. E. Boettner, J. Chem. Soc., Chem. Commun. 1993, 1805.
G. R. Pettit, Z. A. Cichacz, F. Gao, C. L. Herald, M. R. Boyd,
[9d]
[9e]
M. D. McBriar, W. H. Moser, M. Sobukawa, L. Zhuang, Tetra-
J. Chem. Soc., Chem. Commun. 1993, 1166.
G. R. Pettit, Z.
[6h]
hedron Lett. 1997, 38, 8675.
I. Paterson, D. J. Wallace, K.
A. Cichacz, F. Gao, C. L. Herald, M. R. Boyd, J. M. Schmidt,
J. N. A. Hooper, J. Org. Chem. 1993, 58, 1302.
N. Fusetani, K. Shinoda, S. Matsunaga, J. Am. Chem. Soc.
1993, 115, 3977.
[6i]
R. Gibson, Tetrahedron Lett. 1997, 38, 8911.
M. Nakata, Tetrahedron Lett. 1998, 39, 3795.
T. Terauchi,
[6j]
[10]
M. T. Crim-
[6k]
mins, D. G. Washburn, Tetrahedron Lett. 1998, 39, 7487.
I.
[11] [11a]
Paterson, D. J. Wallace, R. M. Oballa, Tetrahedron Lett. 1998,
M. Kobayashi, S. Aoki, I. Kitagawa, Tetrahedron Lett.
[6l]
[11b]
39, 8545.
M. M. Claffey, C. J. Hayes, C. H. Heathcock, J.
1994, 35, 1243.
M. Kobayashi, S. Aoki, H. Sakai, K. Ka-
[6m]
Org. Chem. 1999, 64, 8267.
D. Zuev, L. A. Paquette, Org.
M. T. Crimmins, J. D. Katz, Org. Lett.
T. Terauchi, T. Terauchi, I. Sato, T. Tsukada,
wazoe, N. Kihara, T. Sasaki, I. Kitagawa, Tetrahedron Lett.
1993, 34, 2795.
[12b]
[6n]
Lett. 2000, 2, 679.
[6o]
[12] [12a]
2000, 2, 957.
M. E. Schwenter, P. Vogel, Chem. Eur. J. 2000, 6, 195.
[6p]
N. Kanoh, M. Nakata, Tetrahedron Lett. 2000, 41, 2649.
A. B. Smith III, V. A. Doughty, C. Stouggatakis, C. S. Bennett,
K. T. Meilert, M. E. Schwenter, Y. Shatz, R. Dubbaka, P. Vo-
gel, J. Org. Chem. 2003, 68, 2964.
[6q]
[13]
[14]
[15]
[16]
J. Koyanagi, M. Takeuchi, Org. Lett. 2002, 4, 783.
I. Pater-
M. E. Schwenter, P. Vogel, J. Org. Chem. 2001, 66, 7869.
[6r]
´
son, M. J. Coster, Tetrahedron Lett. 2002, 43, 3285.
E. B.
A. G. Csaky¨, P. Vogel, Tetrahedron: Asymmetry 2000, 11, 4935.
Hulson, W. R. Roush, Org. Lett. 2002, 4, 3719. [6s] M. J. Gaunt,
D. F. Hook, H. R. Tanner, S. V. Ley, Org. Lett. 2003, 5, 4815.
S. Gerber-Lemaire, P. Vogel, Eur. J. Org. Chem. 2003, 2959.
Steric crowding about the equatorial alcohol at C(4Ј) is prob-
ably responsible for the faster silylation of the tertiary hydroxy
group of (ϩ)-11 at low temperature.
[6t]
M. J. Gaunt, A. S. Jessiman, P. Orsini, H. R. Tanner, D. F.
Hook, S. V. Ley, Org. Lett. 2003, 5, 4819.
For total syntheses of spongistatins: [7a] D. A. Evans, P. J. Col-
[17] [17a] D. B. Dess, J. C. Martin, J. Org. Chem. 1983, 48, 4155. [17b]
R. E. Ireland, L. Lin, J. Org. Chem. 1993, 58, 2899.
[7]
eman, L. C. Dias, Angew. Chem. Int. Ed. Engl. 1997, 36, 2738.
[7b]
D. A. Evans, B. W. Trotter, B. Cote, P. J. Coleman, Angew.
[18] [18a] A. J. Mancuso, S. L. Huang, D. Swern, J. Org. Chem. 1978,
ˆ ´
[7c]
[18b]
Chem. Int. Ed. Engl. 1997, 36, 2741. D. A. Evans, B. W.
Trotter, B. Cote, P. J. Coleman, L. C. Dias, A. N. Tyler, Angew.
Chem. Int. Ed. Engl. 1997, 36, 2744. D. A. Evans, B. W.
Trotter, P. J. Coleman, B. Cote, L. C. Dias, H. A. Rajapakse,
43, 2480.
T. T. Tidwell, Org. React. 1990, 39, 287.
[19]
ˆ ´
S. V. Ley, J. Norman, W. P. Griffith, S. P. Marsden, Synthesis
[7d]
1994, 639.
ˆ ´
Received July 22, 2004
5046
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2004, 5040Ϫ5046