Efficient asymmetric synthesis of long-chain polyketides containing up to ten contiguous stereogenic centres by double chain elongation

Article abstract of DOI:10.1002/ejoc.201100196

The 2,3-anti-3,4-syn-stereotriad (1Z,2S,3R,4S)-1-ethylidene-2,4-dimethyl-3- [(1S)-1-phenylethoxy]-5-oxopent-1-yl isobutyrate {(-)-8, obtained in a one-pot operation from the trimethylsilyl (Z)-enol ether derived from pentan-3-one and (1E,3Z)-1[(1S)-phenyl

Full text of DOI:10.1002/ejoc.201100196

FULL PAPER
DOI: 10.1002/ejoc.201100196
Efficient Asymmetric Synthesis of Long-Chain Polyketides Containing up to
Ten Contiguous Stereogenic Centres by Double Chain Elongation
Maris Turks,[a] Kelly A. Fairweather,[b] Rosario Scopelliti,[b] and Pierre Vogel*[b]
Keywords: Aldol reactions / Aldol reduction / Polyketides / Polypropionates / Umpolung
The 2,3-anti-3,4-syn-stereotriad (1Z,2S,3R,4S)-1-ethylidene-
2,4-dimethyl-3-[(1S)-1-phenylethoxy]-5-oxopent-1-yl isobut-
yrate {(–)-8, obtained in a one-pot operation from the tri-
methylsilyl (Z)-enol ether derived from pentan-3-one and
(1E,3Z)-1[(1S)-phenylethoxy]-2-methylpenta-1,3-dien-3-yl
isobutyrate through SO2 umpolung} contains an ethyl ketone
(Z)-enol isobutyrate units remained intact were obtained. Af-
ter suitable protection, these were converted into their corre-
sponding lithium (Z)-enolates, which could react with isopro-
pylidene D-glyceraldehyde [(+)-9] to give aldol products that
were reduced to various stereodecads (polyketides with ten
contiguous stereogenic centres). The disclosed chemistry
moiety that undergoes diastereoselective cross-aldol reac- represents
a quick, asymmetric, diastereoselective and
tions with acetaldehyde. After subsequent reductions, vari-
ous diastereomeric stereohexads (polypropionate fragments
containing six contiguous stereogenic centres) in which the
stereodivergent construction of long-chain polyketides and
analogues by a double-chain-elongation strategy.
Diels–Alder (HDA) additions with SO2 to afford the six-
membered sultines 2, which are subsequently broken down
Introduction
Polypropionates are characterized by their alternating to the zwitterionic species 3 by acid-assisted heterolysis.
methyl- and hydroxy-substituted alkyl chains. They are
found in diverse classes of natural products and are of bio-
logical and medicinal interest.[1] Most applied synthetic ap-
proaches to polypropionates have been reviewed re-
cently.[2–4] They all are multistep syntheses once functional
group construction, semi-protection steps and stereogenic
centre installation are taken into account. For practical, en-
vironmental and economic reasons it is desirable to reduce
numbers of chemical operations to a minimum. Employ-
ment of one-step two-directional chain extension strategies
provides convenient and simple access to longer chain frag-
ments. In order to maintain stereodiversity, an easy desym-
metrization step has to be applied to these fragments for
the diastereoselective generation of multifunctional com-
pounds.[5]
Nucleophilic attack by the enoxysilanes 4 leads to the
formation of new C–C bonds and generates the silyl sulfin-
ates 5, which are converted in situ into the corresponding
sulfinic acids 6 through Pd-catalysed[10] or buffer-medi-
ated[11] desilylation. The sulfinic acids 6 are then desulfin-
ylated through retro-ene reactions, giving stereotriads of
type 7. We have thus developed one-pot access to 2,3-anti-
3,4-syn[8] and 2,3-anti-3,4-anti stereotriads[12] that have per-
mitted short and efficient syntheses of the cyclohexanone
subunit of baconipyrones A and B[13] and of β-hydroxy-δ-
lactones.[14] The first total asymmetric synthesis of dolabri-
ferol and its stereoisomers[12] has also been achieved by this
approach. Aldol reactions of ketones of type 7 have permit-
ted expeditious asymmetric syntheses of the C(19)–C(27)
stereoheptad of the rifamycins[15] and of Koert’s C(16)–
C(28) fragment of apoptolidin A.[16]
The stereotriads 7, each with an alkenyl ester, in fact each
contain two structural motifs for direct two-directional
chain elongation through two successive aldol reactions. On
one hand, the ketone moiety can be used directly in a first
aldol reaction (Scheme 2). The enol ester, at the other ter-
minus, can be transformed into an enolate for use in stereo-
selective aldol reactions, thus permitting dissymmetric two-
directional chain elongation, as illustrated in this report. We
chose the isobutyrate (–)-8 {(1Z,2S,3R,4S)-1-ethylidene-
2,4-dimethyl-3[(1S)-1-phenylethoxy-5-oxohept-1-yl isobut-
yrate]}, an anti,syn stereotriad, as starting material, with
acetaldehyde for the first aldol reaction and isopropylidene
d-glyceraldehyde [(+)-9] for the second. Conditions for dia-
We have reported one-pot syntheses of the stereotriads 7
through oxyallylation reaction cascades in which the elec-
tron-rich dienes 1 and the enoxysilanes 4 are coupled
through SO2 umpolung (Scheme 1).[6–8] The dienes 1, each
containing a 1-arylethyl chiral auxiliary,[9] undergo hetero-
[a] Faculty of Material Science and Applied Chemistry, Riga
Technical University,
1048 Riga, Latvia
[b] Swiss Federal Institute of Technology (EPFL),
1015 Lausanne, Switzerland
Fax: +41-216-939-375
E-mail: pierre.vogel@epfl.ch
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201100196.
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M. Turks, K. A. Fairweather, R. Scopelliti, P. Vogel
FULL PAPER
Scheme 1. One-pot syntheses of the stereotriads 5 through SO2-induced oxyallylation of the C-nucleophiles 3. A = acid catalyst; R =
alkyl; R1 = H, Me, R2 = alkyl, phenyl; for Z = O: R3, R4 = H, Me, alkyl; for Z = CH2: R3 = CH2TMS, CH2OAc, R4 = H. The opposite
enantiomers are obtained by using the (R)- instead of the (S)-arylethoxy moiety in 1.
stereoselective aldol reactions and subsequent reduction of column chromatography on silica gel. A second fraction
the obtained aldols have been found. The chemistry devel- (18%) contained two inseparable diastereomeric aldols 16
oped allows the preparation of long-chain polyketides con- + 17. Reduction of (+)-15 under Narasaka’s conditions[19]
taining ten contiguous stereogenic centres in a few steps.
gave a 4:1 mixture of diols, the major one being the ex-
pected syn-diol 18.
On treatment with MeLi·LiBr complex in anhydrous di-
ethyl ether at –78 °C, this mixture provided the hemiacetal
(+)-19 (Scheme 3), isolated in 61% yield. The 1H NMR
spectrum of (+)-19 confirmed the (6R) configuration, and
NOEs in this spectrum were consistent with the proposed
structure for this compound. The 13C NMR spectroscopic
data (syn-acetonide:[21] δMe = 19.0 and 22.8 ppm, δCquat.
=
98.3 ppm) for the acetonide (–)-20 confirmed the
(5R,6S,7R) configuration of the stereohexad 18.
Scheme 2. Double chain elongation through two succession aldol
reactions.
Evans–Tishchenko reduction of the aldol (+)-15 with
1 equiv. of SmI2 in CH3CHO (0 °C, 4 h) gave a low yield
(6%) of the expected anti-hydroxy acetate (+)-21
(Scheme 3). With 7 equiv. of SmI2 (–20 °C, 4 h) a 1:1 mix-
ture of (+)-21 and the rearranged product (–)-22 was ob-
tained in 86% yield. After a prolonged reaction time
Results and Discussion
Applying Paterson’s method[17] for direct formation of (–20 °C, 18 h) exclusive formation of (–)-22 (90% yield) was
enoxyboranes, we treated (–)-8 with (c-Hex)2BCl and Et3N observed. The acidic medium promotes intramolecular
at –15 °C (Scheme 3). Acetaldehyde was then added at transetherification, leading to the more stable phenylethyl
–78 °C, to give a mixture of 11 (21%) and the aldol 12 ether (–)-22. The 13C NMR spectrum of (–)-22 suggested
(42%). The borate 11 also provided 12 upon oxidation with partial racemisation about the phenylethyl centre. Treat-
H2O2/NaHCO3. The 1,5-anti diastereoselectivity was ex- ment of (–)-22 with TiCl4 cleaved the 1-phenylethyl ether
pected[18] and was confirmed by X-ray single-crystal radio- moiety to give a diol, which was converted into its aceto-
crystallography (see below). A syn reduction of the aldol 12 nide (+)-23 upon treatment with Me2C(OMe)2 and
under Narasaka’s conditions[19] (Et2BOMe/NaBH4/MeOH, TsOH·H2O (catalyst). The overall yield of the conversion
–78 °C) gave the diol 13 in 82% yield. A one-pot conversion (–)-22 Ǟ (+)-23 did not surpass 28%, so a more economical
of (–)-8 into the diol 13, which furnished 13 in 68% yield, (SmI2 in large excess!) and higher-yielding route was
was also developed. Treatment of 13 with (MeO)2CMe2 sought. We found a one-pot procedure in which the aldol
(TsOH·H2O cat., 20 °C, 1 h) gave the acetonide (+)-14, the (+)-15 was converted directly into (+)-23 in 50% yield. The
13C NMR spectrum of which confirmed[20] [δMe(acetonide) process started with esterification of the aldol (+)-15 (Ac2O/
= 19.3 and 30.4 ppm, δCquat. = 97.8 ppm] the syn-1,3-diol pyr/CH2Cl2, DMAP, 0 °C). Subsequent additions of
relative configuration of 13.
TiCl4·BH3·pyridine cleaved the phenethyl group, giving an
On application of Evans’[21] methodology for the Mukai- intermediate trichlorotitanate chelating the ketone moiety.
yama cross-aldol reaction between (–)-8 and acetaldehyde a This was then diastereoselectively reduced with borane/pyr-
mixture of β-hydroxy ketones was obtained, from which the idine complex.[22] The obtained syn-diol was directly con-
syn-aldol (+)-15 (Scheme 3) was isolated in 68% yield after verted into its acetonide (+)-23 under standard conditions.
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Asymmetric Synthesis of Long-Chain Polyketides
Interestingly, treatment of (+)-23 with LiEt3BH in THF at
–78 °C allowed the selective reduction of its acetate moiety,
with slower reduction of the enol isobutyrate moiety, lead-
ing to the alcohol (+)-24 in 75% yield.
A Mitsunobu reaction[23] with 18 was faster for the 7-
hydroxy group than for the 5-hydroxy group and provided
the p-nitrobenzoate (+)-25 (Scheme 3) in 67% yield. The
structures of (+)-25 and its precursors 18 and (+)-15 were
confirmed by single-crystal X-ray radiocrystallography of
(+)-25 (see the Supporting Information). Dess–Martin
periodinane oxidation[24] of (+)-25 gave the ketone (+)-26
(99%), which was treated with TiCl4·BH3/pyridine and then
with Me2C(OMe)2 (TsOH·H2O catalyst) to furnish the ste-
reohexad (+)-27 [50% based on (+)-25].
After having shown that 2,3-anti-3,4-syn-4,5-anti-5,6-
anti-6,7-anti [e.g. (+)-14], -4,5-anti-5,6-syn-6,7-syn [e.g. (–)-
20], -4,5-syn-5,6-anti-6,7-syn [e.g. (+)-23], -4,5-anti-5,6-syn-
6,7-anti [e.g. (+)-25] and 2,3-anti-3,4-syn-4,5-anti-5,6-anti-
6,7-anti [e.g. (+)-28] stereoisomeric stereohexads can be ob-
tained quickly with preservation of their enol isobutyric es-
ter moieties, we investigated conditions for the conversion
of these into lithium (Z)-enolates and their use in diastereo-
selective aldol reactions with 2,3-isopropylidene-d-glyceral-
dehyde [(+)-9].[25] The fully protected stereohexad (+)-14 re-
acted with MeLi·LiBr complex at –78 °C in diethyl ether to
afford the enolate 29[26] (Scheme 4), which was quenched
with (+)-9 to provide the single diastereomeric aldol (+)-30,
isolated in 74% yield. Debenzylation [H2/Pd(OH)2/C] and
subsequent reduction of the aldol with Me4NBH(OAc)3/
AcOH[27] afforded (–)-31 in 67% yield. Its structure was
established by single-crystal X-ray radiocrystallography (see
the Supporting Information), thus verifying the relative
configurations of the precursors 12, 13 and (+)-14. The triol
(–)-31 is a 12-carbon-chain polyketide containing ten con-
tiguous stereogenic centres. The diastereoselectivity of the
aldol reaction between (+)-9 and 29 is consistent with the
Cornforth model[28] for nucleophilic additions to 2-substi-
tuted aldehydes (see 32, Scheme 4). Consistently with the
above, the reaction between (–)-20 and (+)-9 under similar
conditions gave the aldol (–)-33 [64% and 16% of recovered
(–)-20].
We then turned to the stereohexad (+)-28 as a potential
lithium enolate for a cross-aldol reaction with the aldehyde
(+)-9. Treatment of (+)-28 with MeLi·LiBr in diethyl ether
produced an enolate that was quenched with (+)-9 at
–78 °C to give, after aqueous workup, a 2:5 mixture of anti-
aldols after column chromatography on silica gel. The
major aldol (+)-35 (Scheme 5) was reduced with
Me4NBH(OAc)3/AcOH/MeCN to a 1:3 mixture (76%) of
the anti-diol (–)-36 and the syn-diol 37. The syn-diol 37 was
converted into its acetonide (–)-38 under standard condi-
tions.
The minor anti-aldol (+)-34 was reduced more stereose-
lectively with Me4NBH(OAc)3/AcOH/MeCN to afford the
major diol (+)-39, isolated in 70% yield. The structure of
(+)-39 was established by single-crystal X-ray radiocrystal-
lography, thus also confirming the relative configurations of
Scheme 3. Diastereoselective cross-aldol reactions between the
ethyl ketone (–)-8 and acetaldehyde and stereoselective preparation
of four stereohexads with preservation of the (Z)-enol ester moiety. the precursors (+)-34 and (+)-28.
Eur. J. Org. Chem. 2011, 3317–3328
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M. Turks, K. A. Fairweather, R. Scopelliti, P. Vogel
FULL PAPER
35. When the reduction of (+)-35 with Me4NBH(OAc)3 was
followed by treatment with Ac2O/pyridine and 4-(dimeth-
ylamino)pyridine (cat.), the diacetates (+)-40 and (+)-41
were isolated in 11 and 34% yields, respectively, after col-
umn chromatography on silica gel. The results collected in
Scheme 5 were surprising, because the diastereoselectivity
of these cross-aldol reactions is opposite to expectations
(Cornforth model, Scheme 4).[28,29] Also surprising was the
syn diastereoselectivity of the reduction of the aldol (+)-35
with Me4NBH(OAc)3.[27]
Conclusions
We have demonstrated for the first time that the anti,syn-
stereotriad (–)-8,[13] obtained in a one-pot operation from
the readily available trimethylsilyl (Z)-enol ether derived
from pentan-3-one and (1E,3Z)-1-[(1S)-phenylethyl]-2-
methylpenta-1,3-dien-3-yl isobutyrate[9] and possessing an
ethyl ketone unit on one terminus and a (Z)-enol ester on
the other, can be used in two successive cross-aldol reac-
tions, thus permitting the rapid construction of long-chain
polyketides and polypropionates by two-directional chain
elongation. With use of acetaldehyde, conditions for the
stereoselective synthesis of several protected stereohexads
were found. Two of them were used in cross-aldol reactions
with 2,3-O-isopropylidene-d-glyceraldehyde [(+)-9] with ex-
ploitation of their enol butyrate units as lithium (Z)-enolate
precursors. In one case the cross-aldol reaction was highly
diastereoselective and followed the Cornforth model. Sub-
sequent reduction of the aldols can also be highly diastereo-
selective, although the rules generally applied for the dia-
stereoselectivity of these reactions might not be followed,
depending on the configuration and nature of the poly-
ketide protecting groups. Long-chain polyketides contain-
ing ten contiguous stereogenic centres were obtained and
fully characterized. Because we have demonstrated that the
anti,anti diastereomer of (–)-8[12] can also be obtained in a
one-pot operation from the trimethylsilyl (E)-enol ether of
pentan-3-one[12] and because these stereotriads are available
in both their enantiomerically pure forms,[9] our chemistry
constitutes a combinatorial approach to the asymmetric
synthesis of long-chain polyketides and polypropionates. It
should be applicable to the generation of libraries (parallel
synthesis) of analogues and stereoisomers of natural anti-
biotics and antitumour agents.[30]
Scheme 4. Diastereoselective preparation of stereodecad (–)-31.
Experimental Section
General: All commercially available reagents and solvents (Fluka,
Aldrich, Acros) were used without further purification. For reac-
tions requiring anhydrous conditions, dry solvents were bought
(Fluka, Aldrich). Unless otherwise noted, experiments were carried
out under argon. Reactions were monitored by TLC (Merck silica
gel 60F254 plates) with detection by use of UV light, KMnO4 or
Pancaldi reagents [(NH4)6MoO4, Ce(SO4)2, H2SO4, H2O]. Purifica-
tions were performed by flash chromatography (FC) on silica gel
(Merck no. 9385 silica gel 60, 240–400 mesh). 1H NMR spectra
Scheme 5. Less diastereoselective cross-aldol reactions and aldol
reductions.
The structure of the minor anti-diol (–)-36 [derived from
(+)-35] was also established by single-crystal X-ray radio-
crystallography, thus also confirming the structure of (+)- were recorded with Bruker ARX 400 and DPX 400 spectrometers
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Asymmetric Synthesis of Long-Chain Polyketides
at 400 MHz and Bruker AVOO 800 spectrometers at 800 MHz.
Chemical shifts are given in ppm relative to the residual 1H solvent
signal (MeOD: δ = 3.34 ppm; CDCl3: δ = 7.27 ppm; C6D6: δ =
7.30 ppm) as the internal reference. 1H NMR assignments were
confirmed by 2D COSY spectra. The multiplicities given reflect
apparent signal patterns. 13C NMR spectra were recorded with the
same instruments as above at 101 MHz. Chemical shifts are given
in ppm relative to the residual 13C solvent signal (MeOD: δ =
49 ppm; CDCl3: δ = 77 ppm; C6D6: δ = 128.5 ppm). 13C NMR
assignments were confirmed by 2D HSQC spectra. Coupling con-
stants (J) are given in Hz for all NMR spectroscopic data. IR spec-
tra were recorded with a Perkin–Elmer Paragon 1000 FT-IR spec-
trometer. Mass spectra were recorded with the following instru-
ments: MALDI-TOF: Axima-CFR+ spectrometer, Kratos; ESI-Q:
Finnigan SSQ 710C spectrometer, Thermoquest; ESI-HRMS: Q-
Tof Ultima spectrometer, Micromass. Elemental analyses were per-
formed at Ilse Beets, 96301 Kronach, Germany, or with an EPFL-
ISIC-LCS instrument. Optical rotations were determined at 25 °C
with a Jasco P1020 polarimeter. [α] values are given in units of
10–1 degcm2 g–1.
lowed by NEt3 (2.46 mL, 17.6 mmol, 2 equiv.) and a solution of
the ethyl ketone (–)-8 (3.3 g, 8.8 mmol, 1 equiv.) in Et2O (11 mL),
was added under Ar at –15 °C to a solution of (c-hex)2BCl in hex-
anes (1 m, 14.1 mL, 14.1 mmol, 1.6 equiv.). The resulting suspen-
sion was stirred at –15 °C for 2 h. The temperature was lowered to
–78 °C, and acetaldehyde (2 mL, 35.2 mmol, 4 equiv.) was added.
The reaction mixture was stirred at –78 °C for 16 h. MeOH (20 mL)
was added, followed by solid NaBH4 (2.0 g, 52.8 mmol, 6 equiv.).
The resulting reaction mixture was stirred at –78 °C for 5 h. It was
carefully quenched by addition of MeOH (60 mL) at –78 °C, fol-
lowed by addition of satd. aq. Na/K tartrate (50 mL) and aq. H2O2
(30%, 14 mL). The resulting suspension was stirred (mechanical
stirrer) at –5 °C for 14 h. EtOAc (200 mL) was added, and the or-
ganic layer was washed with brine (3 ϫ 30 mL) and satd. aq.
Na2S2O3 (3ϫ10 mL), dried (Na2SO4) and filtered, and the solvents
were evaporated. The resulting oil was purified by FC (petroleum
ether/EtOAc, 8:2) to yield 13 (2.52 g, 68%). Colourless oil, Rf =
1
0.30 (petroleum ether/EtOAc, 8:2). H NMR (CDCl3, 400 MHz):
3
δ = 0.51 [d, J = 6.4 Hz, 3 H, CH3-C(6)], 1.03 [d, 3J = 6.4 Hz, 3
H, CH3-C(4)], 1.11, 1.10 [2ϫd, 3J = 7.0 Hz, 6 H, (CH3)2CHCOO-
C(1)], 1.17 [d, 3J = 7.0 Hz, 1 H, H-C(8)], 1.18 [d, 3J = 7.0 Hz, 3 H,
CH3-C(2)], 1.37 [m, 1 H, H-C(6)], 1.47 [2ϫd, 3J = 6.4 Hz, 6 H,
CCDC-822851 [(+)-25], -822852 [(–)-31], -822853 [(–)-36], and
-822854 [(+)-39] contain the supplementary crystallographic data.
The data can be obtained free of charge from the Cambridge Crys-
tallographic Data Centre via http://www.ccdc.cam.ac.uk/.
3
C(2-HЈ), C(2Ј-HЈ)], 1.89 [m, 1 H, H-C(4)], 2.54 [sept, J = 7.0 Hz,
1 H, (CH3)2CHCOO-C(1)], 2.95 [dq, 3J = 7.7, 3J = 7.0 Hz, 1 H,
3
3
H-C(2)], 3.17 [m, 1 H, H-C(5)], 3.63 [dq, J = 7.2, J = 5.8 Hz, 1
3
3
H, H-C(7)], 3.74 [dd, J = 6.4, J = 1.3 Hz, 1 H, H-C(3)], 4.57 [q,
3J = 6.4 Hz, 1 H, H-C(1ЈЈ)], 5.26 [q, 3J = 7.0 Hz, 1 H, H-C(1Ј)],
7.36–7.33 [m, 5 H, H-C(Ph)] ppm. MALDI-HRMS: calcd. for
C25H40O5Na+ 443.2773; found 443.2795.
(1Z,2S,3R,4S,6R,7R)-1-Ethylidene-7-hydroxy-2,4,6-trimethyl-5-oxo-
3-[(1S)-1-phenylethoxy]octyl Isobutyrate (12): Et2O (1 mL), fol-
lowed by NEt3 (0.78 mL, 0.56 mmol, 1.61 equiv.) and a solution
of the ethyl ketone (–)-8 (0.13 g, 0.35 mmol, 1 equiv.)[13] in Et2O
(0.5 mL), was added under Ar at –15 °C to a solution of (c-hex)
2BCl in hexanes (1 m, 0.52 mL, 0.52 mmol, 1.5 equiv.). The re-
sulting suspension was stirred at –15 °C for 2 h. The temperature
was lowered to –78 °C, and a solution of acetaldehyde (0.04 mL,
0.73 mmol, 2.1 equiv.) in Et2O (2 mL) was added. The reaction
mixture was stirred at –78 °C for 16 h. It was carefully quenched
by addition of MeOH (2 mL) at –78 °C, followed by addition of
satd. aq. NaHCO3 (1.5 mL) and aq. H2O2 (30% , 0.5 mL). The
resulting suspension was stirred at 0 °C for 3 h. Satd. aq. Na2S2O3
(10 mL) was added at 0 °C. The mixture was extracted with EtOAc
(4ϫ10 mL). The combined organic layers were washed with brine,
dried (Na2SO4) and filtered, and the solvents were evaporated. The
resulting oil was purified by FC (petroleum ether/EtOAc, 8:2) to
yield 12 (60 mg, 42%) together with (–)-8 (ca. 40 mg, 21%). Data
(1Z,2S,3S,4R,5R,6R,7R)-1-Ethylidene-5,7-isopropylidenedioxy-
2,4,6-trimethyl-3-[(1S)-1-phenylethoxy]octyl Isobutyrate [(+)-14]:
pTsOH·H2O (45 mg, 0.24 mmol, 0.05 equiv.) was added at +5 °C
to a solution of the diol 13 (2.0 g, 4.76 mmol, 1 equiv.) in dimeth-
oxypropane (20 mL). The reaction mixture was stirred at 20 °C for
1 h, neutralized with solid NaHCO3 and filtered, and the solvents
were evaporated. The residue was purified by FC (petroleum ether/
EtOAc, 20:1). Yield 1.95 g, 89% of (+)-14. Colourless oil, Rf = 0.57
25
25
(petroleum ether/EtOAc, 9:1). [α]2D5 = +4.0. [α] = +4.3. [α]
=
577
435
25
+13.4. [α]
= +18.3 (c = 0.35, CHCl3). 1H NMR (CDCl3,
400 MHz): δ = 0.66 [d, J = 6.4 Hz, 3 H, CH3-C(6)], 0.94 [d, J =
7.0 Hz, 3 H, CH3-C(4)], 1.12 [d, J = 7.0 Hz, 3 H, CH3-C(2)], 1.18
[d, J = 5.8 Hz, 3 H, H-C(8)], 1.26, 1.25 [2ϫd, J = 7.0 Hz, 6 H,
405
3
3
3
3
3
3
(CH3)2CHCOO-C(1)], 1.30 [m, 1 H, H-C(6)], 1.34 [d, J = 7.0 Hz,
3 H, H-C(2ЈЈ)], 1.35, 1.34 [2ϫs, 6 H, (CH3)2CO-C(5,7)], 1.47 [dd,
1
for 12: Colourless oil, Rf = 0.35 (petroleum ether/EtOAc, 8:2). H
3J = 7.0, 5J = 1.3 Hz, 3 H, H-C(2Ј)], 1.92 [qt, 3J = 7.0, 3J = 1.9 Hz,
NMR (CDCl3, 400 MHz): δ = 0.95 [d, 3J = 7.4 Hz, 3 H, CH3-
3
1 H, H-C(4)], 2.64 [sept, J = 7.0 Hz, 1 H, (CH3)2CHCOO-C(1)],
3
3
C(6)], 1.06 [d, J = 6.8 Hz, 3 H, CH3-C(4)], 1.08 [d, J = 6.2 Hz, 3
2.66 [m, 1 H, H-C(2)], 3.22 [dd, 3J = 10.6, 3J = 2.0 Hz, 1 H, H-
H, H-C(8)], 1.14 [d, 3J = 7.4 Hz, 3 H, CH3-C(2)], 1.21, 1.20 [2ϫd,
3
3
3
C(5)], 3.52 [dq, J = 9.9, J = 6.1 Hz, 1 H, H-C(7)], 3.86 [dd, J =
3J = 7.4 Hz, 6 H, (CH3)2CHCOO-C(1)], 1.39 [d, J = 6.8 Hz, 3 H,
3
4.5, 3J = 1.9 Hz, 1 H, H-C(3)], 4.85 [q, 3J = 6.4 Hz, 1 H, H-C(1ЈЈ)],
5.22 [dq, J = 7.0, J = 1.3 Hz, 1 H, H-C(1Ј)], 7.21 [t, J = 7.0 Hz,
1 H, H-C(Ph)], 7.30 [t, J = 7.0 Hz, 2 H, H-C(Ph)], 7.36 [d, J =
7.0 Hz, 2 H, H-C(Ph)] ppm. 13C NMR (CDCl3, 100.6 MHz): δ =
10.8, 12.3, 12.6, 14.9, 19.1, 19.3, 19.3, 20.2, 23.1, 30.4, 34.4, 35.1,
37.4, 43.7, 70.8, 73.6, 74.6, 78.3, 97.8, 111.7, 126.2, 126.6, 128.0,
H-C(2ЈЈ)], 1.47 [d, 3J = 6.8 Hz, 3 H, H-C(2Ј)], 2.53 [quint, 3J =
3
4
3
7.4 Hz, 1 H, H-C(6)], 2.57 [d, 3J = 4.3 Hz, 1 H, HO-C(7)], 2.61
3
3
3
3
[sept, J = 7.4 Hz, 1 H, (CH3)2CHCOO-C(1)], 2.76 [dq, J = 6.8,
3J = 6.2 Hz, 1 H, H-C(2)], 2.86 [dq, J = 7.4, J = 3.7 Hz, 1 H, H-
C(4)], 3.77 [m, 1 H, H-C(7)], 3.81 [t, 3J = 4.3 Hz, 1 H, H-C(3)],
4.49 [q, 3J = 6.2 Hz, 1 H, H-C(1ЈЈ)], 5.27 [q, 3J = 6.8 Hz, 1 H,
H-C(1Ј)], 7.36–7.23 [m, 5 H, H-C(Ph)] ppm. 13C NMR (CDCl3,
100.6 MHz): δ = 10.9, 12.2, 12.8, 14.1, 19.0, 20.4, 23.8, 34.2, 41.4,
48.5, 52.0, 69.3, 74.5, 76.3, 112.6, 126.6, 127.5, 128.3, 143.8, 149.7,
3
3
145.4, 150.7, 174.5 ppm. IR (film): ν = 2970, 2935, 1750, 1695,
˜
1455, 1380, 1265, 1140 cm–1. MALDI-HRMS: calcd. for
C28H44O5Na+ 483.3086; found 483.3079. C28H44O5 (460.65): calcd.
C 73.01, H 9.63; found C 73.21, H 9.53.
174.7, 217.0 ppm. IR (film): ν = 3530, 2975, 2880, 1750, 1690, 1455,
˜
1385, 1135 cm–1. MALDI-HRMS: calcd. for C25H38O5K+
457.2356; found 457.2355.
(1Z,2S,3R,4S,6S,7R)-1-Ethylidene-7-hydroxy-2,4,6-trimethyl-5-oxo-
3-[(1S)-1-phenylethoxy]octyl Isobutyrate [(+)-15]: tert-Butyldime-
thylsilyl trifluoromethanesulfonate (0.88 mL, 4.56 mmol) was
added dropwise under argon at –20 °C to the ketone (–)-8 (1.42 g,
(1Z,2S,3S,4R,5R,6R,7R)-1-Ethylidene-5,7-dihydroxy-2,4,6-trimeth-
yl-3-[(1S)-1-phenylethoxy]octyl Isobutyrate (13): Et2O (28 mL), fol- 3.80 mmol)[13] and Et3N (1.32 mL, 9.49 mmol) in CH2Cl2 (40 mL).
Eur. J. Org. Chem. 2011, 3317–3328
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3321

M. Turks, K. A. Fairweather, R. Scopelliti, P. Vogel
FULL PAPER
The resulting solution was stirred for 2 h, with the reaction mixture
being allowed to warm gradually to 20 °C. The reaction mixture
was then diluted with cold (–50 °C) pentane, washed consecutively
with aq. citric acid (10 mL), satd. aq. NaHCO3 and brine and dried
(MgSO4). Concentration of the organic phase in vacuo gave the
corresponding silyl (Z)-enol ether, which was used directly in the
next step without purification. BF3·Et2O (0.62 mL, 4.94 mmol) was
added dropwise at –78 °C under Ar to a solution of the crude silyl
(2S,3S,4S,5S,6R)-2-Ethyl-6-[(2S,3R)-3Ј-hydroxybut-2-yl]-3,5-di-
methyl-4-[(S)-1-phenylethoxy]tetrahydro-2H-pyran-2-ol [(+)-19]:
The diol 18 (0.06 g, 0.14 mmol) in (MeOCH2)2 (3 mL) was added
at –78 °C under Ar to a solution of MeLi·LiBr complex (0.32 mL
of a 2.2 m solution in diethyl ether, 0.71 mmol) in diethyl ether
(3 mL). The reaction mixture was stirred for 5 h and was then
quenched with satd. aq. NH4Cl and allowed to warm to 20 °C. The
organic layer was separated, and the aq. layer was further extracted
enol ether (1.69 g, 3.80 mmol) and MeCHO (0.24 mL, 4.18 mmol) with diethyl ether (3ϫ10 mL). The combined organic extracts were
in CH2Cl2 (50 mL). The reaction mixture was stirred for 1.5 h and
then poured into a satd. solution of NaHCO3 (20 mL). The organic
phase was separated, and the aq. phase was further extracted with
CH2Cl2 (2ϫ50 mL). The combined organic extracts were dried
(MgSO4) and concentrated in vacuo to give a yellow oil. Purifica-
tion by FC (EtOAc/petroleum ether, 1:9) gave a first fraction as a
mixture of two isomeric products 16 + 17 (0.25 g, 16%), and then
(+)-15 (1.08 g, 68%), colourless oil. [α]2D5 = +1.9 (c = 0.10, CHCl3).
1H NMR (400 MHz, CDCl3): δ = 0.89 (d, J = 7.0 Hz, 3 H), 1.06
(d, J = 7.0 Hz, 3 H), 1.07 (d, J = 6.4 Hz, 3 H), 1.16 (d, J = 7.0 Hz,
3 H), 1.22 (d, J = 7.0 Hz, 3 H), 1.23 (d, J = 7.0 Hz, 3 H), 1.41 (d,
washed with brine, dried (MgSO4) and concentrated in vacuo to
give a yellow oil. Purification by FC (EtOAc/petroleum ether, 1:9)
gave (+)-19 as a colourless oil (0.030 g, 61%). [α]2D5 = +29.0 (c =
0.10, CHCl ). IR (thin film): ν = 3355, 2970, 2930, 2880, 1455,
˜
3
1375, 1155, 1110 cm–1. H NMR (400 MHz, CDCl3): δ = 0.71 (d,
1
J = 6.8 Hz, 3 H, 5-CH3), 0.90 (d, J = 6.8 Hz, 3 H, 3-CH3 or 1Ј-
CH3), 0.91 (t, J = 6.8 Hz, 3 H, 2Ј-CH3), 0.95 (d, J = 6.8 Hz, 3 H,
3-CH3 or 1Ј-CH3), 1.10 (d, J = 6.2 Hz, 3 H, 3Ј-CH3), 1.46 (d, J =
6.2 Hz, 3 H, 1ЈЈ-CH3), 1.58 (m, 1 H, H1Ј), 1.49–1.83 (m, 2 H, H1Ј),
1.74–1.81 (m, 1 H, H5), 2.21 (m, 1 H, H3), 3.46 (dd, J = 10.5,
4.3 Hz, 1 H, H4), 3.58 (m, 1 H, -OH), 3.65 (dd, J = 10.5, 1.9 Hz,
J = 6.4 Hz, 3 H), 1.49 (d, J = 7.7 Hz, 3 H), 2.53–2.61 (m, 1 H), 1 H, H6), 3.89 (m, 1 H, H3Ј), 4.48 (q, J = 6.8 Hz, 1 H, H1ЈЈ), 7.31–
2.63 (quint, J = 7.0 Hz, 1 H), 2.76 (m, 1 H), 2.88 (m, 1 H), 3.82 (t,
J = 4.5 Hz, 1 H), 3.90 (m, 1 H), 4.51 (q, J = 6.4 Hz, 1 H), 5.24 (q,
J = 7.0 Hz, 1 H), 7.25–7.35 (m, 5 H) ppm. 13C NMR (100.6 MHz,
7.35 (m, 5 H) ppm. 13C NMR (100.6 MHz, CDCl3): δ = 4.4, 6.8,
8.3, 12.9, 20.8, 24.3, 32.0, 32.7, 35.4, 38.2, 72.5, 73.7, 75.2, 79.9,
100.7, 126.8, 127.5, 128.2, 143.5 ppm. ESI-HRMS: calcd. for
CDCl3): δ = 10.8, 12.4, 13.1, 18.9, 19.1, 19.9, 23.7, 34.2, 41.1, 46.8, C21H34O4Na 373.2355; found 373.2357.
49.1, 67.4, 75.0, 76.5, 112.5, 126.6 (2ϫ Ar), 127.5 (Ar), 128.2 (2ϫ
(1Z,2S,3S,4R,5R,6S,7R)-1-Ethylidene-5,7-isopropylidenedioxy-
Ar), 143.6, 149.7, 174.4, 217.1 ppm. IR (thin film): ν = 3505, 2975,
˜
2,4,6-trimethyl-3-[(1S)-1-phenylethoxy]octyl Isobutyrate [(–)-20]:
pTsOH·H2O (1 mg, 0.008 mmol) was added at 0 °C under Ar to 18
(0.067 g, 0.16 mmol) in 2,2-dimethoxypropane (5 mL). The reac-
tion mixture was allowed to warm to 20 °C and stirred for 1.5 h,
after which NaHCO3 was added until the pH was neutral. The
mixture was then filtered, washed with CH2Cl2 and dried (MgSO4).
Concentration of the organic phase in vacuo gave a yellow oil,
which was purified by FC (EtOAc/petroleum ether, 5:95–1:9) to
give (–)-20 (0.050 g, 68%) as a colourless oil. [α]2D5 = –108 (c =
0.100, CHCl3). 1H NMR (400 MHz, CDCl3): δ = 0.75 (d, J =
6.4 Hz, 3 H), 0.82 (d, J = 6.4 Hz, 3 H), 0.83 (s, 3 H), 1.04 (d, J =
7.0 Hz, 3 H), 1.06 (d, J = 6.4 Hz, 3 H), 1.24 (s, 3 H), 1.30 (d, J =
7.0 Hz, 3 H), 1.31 (d, J = 7.0 Hz, 3 H), 1.35 (d, J = 6.4 Hz, 3 H),
1.49 (d, J = 7.0 Hz, 3 H), 1.10–1.39 (m, 1 H), 1.64 (m, 1 H), 2.63
(quint, J = 7.0 Hz, 1 H), 2.72 (quint, J = 7.0 Hz, 1 H), 3.25 (dd, J
= 10.2, 1.9 Hz, 1 H), 3.71 (d, J = 7.0 Hz, 1 H), 3.74 (qd, J = 6.4,
1.9 Hz, 1 H), 4.48 (q, J = 6.4 Hz, 1 H), 5.25 (q, J = 7.0 Hz, 1 H),
7.30–7.34 (m, 5 H) ppm. 13C NMR (100.6 MHz, CDCl3): δ = 3.9,
9.0, 10.8, 13.7, 19.0, 19.1, 19.2, 19.4, 24.9, 29.9, 33.7, 34.4, 35.5,
42.1, 69.0, 74.1, 98.3, 111.4, 126.2 (2ϫ Ar), 126.5 (Ar), 127.0 (2ϫ
Ar), 145.7, 150.3, 174.6 (two carbon peaks obscured by CDCl3)
2935, 2880, 1745, 1700, 1495, 1450, 1370, 1240, 1135, 1080 cm–1.
ESI-HRMS: calcd. for C25H38O5Na 441.2617; found 441.2631.
(1Z,2S,3S,4R,5R,6S,7R)-1-Ethylidene-5,7-dihydroxy-2,4,6-trimeth-
yl-3-[(1S)-1-phenylethoxy]octyl Isobutyrate (18): Diethylmeth-
oxyborane (0.41 mL, 3.59 mmol) was added at 0 °C under Ar to
(+)-15 (0.5 g, 1.20 mmol) in THF (20 mL) and MeOH (4 mL). The
reaction mixture was then allowed to warm to 20 °C. After 1 h, the
resulting chelate was cooled to 0 °C, NaBH4 (0.18 g, 4.80 mmol)
was added portionwise, and the reaction mixture was stirred for
2.5 h. The reaction was quenched with AcOH (2 mL) and the mix-
ture poured into aq. satd. NaHCO3 (20 mL). The aq. phase was
then extracted with EtOAc (4ϫ20 mL). The combined organic ex-
tracts were washed with brine (20 mL), dried (MgSO4) and concen-
trated in vacuo to give the boronic ester as a yellow oil. The crude
boronate was dissolved in MeOH (20 mL) and concentrated under
reduced pressure, and the process was then repeated (5ϫ20 mL).
Purification by FC (EtOAc/petroleum ether, 1:9) gave recovered
boronate (0.09 g) and 18 as a colourless oil (0.34 g, 68 %). The
boronate ester was treated with MeOH (5 mL), water (1 mL), hy-
drogen peroxide (0.5 mL, 30% aq. solution) and satd. aq. NaHCO3
at 0 °C for 5 h. The reaction mixture was then poured into water
(5 mL) and extracted with EtOAc (3ϫ10 mL) to give the diol 18
ppm. IR (thin film): ν = 2975, 2940, 2880, 1740, 1695, 1455, 1380,
˜
1260, 1200, 1185, 1085, 1020 cm–1. ESI-HRMS: calcd. for
C28H44O5Na 483.3086; found 483.3085.
(0.084 g, 17%) as a colourless oil (combined yield of 18, 0.42 g, 4:1,
1
85%). H NMR (400 MHz, CDCl3): δ = 0.70 (d, J = 7.0 Hz, 3 H), (1Z,2S,3S,4R,5S,6R,7R)-7-Acetoxy-1-ethylidene-5-hydroxy-2,4,6-
0.73 (d, J = 7.0 Hz, 3 H), 0.98 (d, J = 7.0 Hz, 3 H), 1.66 (d, J = trimethyl-3-[(S)-1-phenylethoxy]octyl Isobutyrate [(+)-21]: SmI2
6.4 Hz, 3 H), 1.33 (d, J = 7.0 Hz, 3 H), 1.34 (d, J = 7.0 Hz, 3 H), (0.2 mL of a 0.1 m solution in THF, 0.02 mmol) was added at 0 °C
1.43 (d, J = 6.40 Hz, 3 H), 1.53 (d, J = 7.0 Hz, 3 H), 1.30–1.60 (m, under Ar and with exclusion of light to the aldol (+)-15 (0.043 g,
2 H), 2.60–2.68 (m, 1 H), 2.78 (quint, J = 7.0 Hz, 1 H), 3.09 (s, 1
H), 3.27 (dd, J = 9.6, 1.9 Hz, 1 H), 3.52 (dd, J = 9.0, 1.3 Hz, 1 H),
3.77 (m, 1 H), 4.51 (q, J = 6.4 Hz, 1 H), 5.36 (q, J = 7.0 Hz, 1 H),
0.10 mmol) and MeCHO (0.12 mL, 2.08 mmol) in THF (0.5 mL).
The reaction mixture was stirred for 1 h, after which no reaction
had occurred. More SmI2 (0.4 equiv.) was therefore added, and the
7.36–7.46 (m, 5 H) ppm. 13C NMR (100.6 MHz, CDCl3): δ = 3.7, reaction mixture was stirred for an additional 3 h. The reaction
10.0, 11.1, 14.8, 19.3 (2ϫ CH3), 21.0, 22.7, 34.3, 37.4, 38.8, 42.0,
72.5, 77.5, 77.8, 80.0, 112.3, 127.2 (2ϫ Ar), 128.4 (Ar), 128.7 (2ϫ
mixture was then diluted with diethyl ether and washed with a satd.
solution of NaHCO3. The organic phase was separated, and the
Ar), 143.5, 149.9, 174.4 ppm. IR (thin film): ν = 3435, 2970, 2935, aq. phase was further extracted with diethyl ether (3ϫ5 mL). The
˜
2880, 1750, 1695, 1455, 1385, 1120, 1075 cm–1. ESI-HRMS: calcd.
for C25H40O5Na 443.2773; found 443.2777.
combined organic extracts were washed with satd. aq. NaHCO3
and brine, dried (MgSO4) and concentrated in vacuo to give a yel-
3322
www.eurjoc.org
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2011, 3317–3328

Asymmetric Synthesis of Long-Chain Polyketides
low oil. FC (AcOEt/petroleum ether, 1:9 to 1:4) gave recovered (+)-
extracts were dried (MgSO4) and concentrated in vacuo to give a
yellow oil (0.09 g, 3,5-syn-diol). This was dissolved in 2,2-dimeth-
oxypropane and cooled to 0 °C, and p-toluenesulfonic acid mono-
hydrate (0.026 g, 0.14 mmol) was added. The reaction mixture was
stirred for 45 min, and solid NaHCO3 was then added until the pH
15 together with (+)-21 as a colourless oil (2.7 mg, 6%). [α]2D5
=
+1.0 (c = 0.100, CHCl3). 1H NMR (400 MHz, CDCl3): δ = 0.70
(d, J = 6.8 Hz, 3 H), 0.74 (d, J = 6.8 Hz, 3 H), 0.96 (d, J = 7.4 Hz,
3 H), 1.09 (d, J = 6.2 Hz, 3 H), 1.30 (d, J = 6.8 Hz, 3 H), 1.31 (d,
J = 7.4 Hz, 3 H), 1.38 (d, J = 6.2 Hz, 3 H), 1.50 (d, J = 6.8 Hz, 3 was neutral. The mixture was filtered, washed with CH2Cl2 and
H), 1.47–1.62 (m, 2 H), 2.00 (s, 3 H), 2.61 (m, 1 H), 2.76 (quint, J concentrated in vacuo to give a colourless oil, which was purified
= 6.8 Hz, 1 H), 3.20 (ddd, J = 9.9, 4.9, 1.2 Hz, 1 H), 3.72 (dd, J =
9.2, 1.9 Hz, 1 H), 4.54 (q, J = 6.8 Hz, 1 H), 4.73 (quint, J = 6.2 Hz,
1 H), 5.32 (q, J = 6.8 Hz, 1 H), 7.28–7.38 (m, 5 H) ppm. 13C NMR
(100.6 MHz, CDCl3): δ = 8.2, 9.7, 11.0, 14.5, 18.0, 21.3, 23.1, 29.7
by FC (AcOEt/petroleum ether, 5:95) to give (+)-23 as a colourless
oil (0.047 g, 42% over four steps). [α]2D5 = +5.0 (c = 0.10, CHCl3).
1H NMR (400 MHz, CDCl3): δ = 0.80 (d, J = 6.8 Hz, 3 H), 0.86
(d, J = 6.8 Hz, 3 H), 0.94 (d, J = 6.8 Hz, 3 H), 2.43 (d, J = 6.8 Hz,
(2ϫ CH3), 36.9, 39.2, 42.3, 70.1, 73.4, 76.8, 77.2, 112.5, 126.9 (2ϫ 3 H), 1.27 (d, J = 6.8 Hz, 6 H), 1.29 (s, 3 H), 1.35 (s, 3 H), 1.43 (d,
Ar), 127.8 (Ar), 128.7 (2ϫ Ar), 144.7, 150.4, 171.1, 174.5 ppm. IR
J = 6.8 Hz, 3 H), 1.49 (m, 1 H), 1.62 (m, 1 H), 2.03 (s, 3 H), 2.37
(m, 1 H), 2.69 (quint, J = 6.8 Hz, 1 H), 3.55 (dd, J = 9.9, 1.9 Hz,
1 H), 3.67 (dd, J = 9.9, 1.9 Hz, 1 H),5.13 (q, J = 6.8 Hz, 1 H), 5.34
(qd, J = 6.8, 1.9 Hz, 1 H) ppm. 13C NMR (100.6 MHz, CDCl3): δ
= 4.1, 7.6, 11.1, 13.7, 17.8, 18.6, 19.2, 21.2, 29.7, 30.2, 34.2, 39.1,
40.5, 40.6, 68.9, 73.4, 74.7, 98.9, 111.0, 149.7, 170.4, 174.2 ppm. IR
(thin film): ν = 3500, 2970, 2925, 2855, 1735, 1455, 1375, 1260,
˜
1140, 1080 cm–1. ESI-HRMS: calcd. for C27H42O6Na 485.2879;
found 485.2876.
(1Z,2S,3S,4S,5R,6S,7R)-7-Acetoxy-1-ethylidene-3-hydroxy-2,4,6-tri-
methyl-5-[(S)-1-phenylethoxy]octyl Isobutyrate [(–)-22]: SmI2
(1.7 mL of a 0.1 m solution in THF, 0.17 mmol) was added at
–20 °C under Ar with exclusion of light to (+)-15 (0.010 g,
0.024 mmol) and MeCHO (0.030 mL, 0.48 mmol) in THF
(0.5 mL). The reaction mixture was stirred for 18 h and was then
diluted with diethyl ether and washed with a satd. solution of
NaHCO3. The organic phase was separated, and the aq. phase was
further extracted with diethyl ether (3ϫ5 mL). The combined or-
ganic extracts were washed with satd. NaHCO3 and brine, dried
(MgSO4) and concentrated in vacuo to give a yellow oil. FC (Ac-
OEt/petroleum ether, 1:9) gave (–)-22 as a colourless oil (0.010 g,
90%). [α]2D5 = –14.5 (c = 0.10, CHCl3). 1H NMR (400 MHz,
CDCl3): δ = 0.71 (d, J = 6.8 Hz, 3 H), 0.83 (d, J = 7.4 Hz, 3 H),
(thin film): ν = 2975, 2935, 1750, 1735, 1460, 1375, 1240, 1130,
˜
1015 cm–1. ESI-HRMS: calcd. for C22H38O6Na 421.2566; found
421.2556.
(S,Z)-4-{(4S,5R,6S)-6-[(2S,3R)-3-Hydroxybut-2-yl]-2,2,5-trimethyl-
1,3-dioxan-4-yl}pent-2-en-3-yl Isobutyrate [(+)-24]: Super-Hydride®
(LiEt3BH, 0.09 mL, 0.09 mmol) was added at –78 °C under Ar to
the acetate (+)-24 (0.018 g, 0.045 mmol) in THF (1 mL). The mix-
ture was stirred for 2.5 h, after which TLC revealed that all of the
starting material had been consumed. The reaction mixture was
then quenched with H2O (2 mL) and extracted with CH2Cl2
(3ϫ10 mL). The combined organic extracts were washed with H2O
(5 mL) and brine (5 mL), dried (MgSO4) and concentrated in vacuo
1.09 (d, J = 7.4 Hz, 3 H), 1.12 (d, J = 7.4 Hz, 3 H), 1.15 (d, J = to give (+)-24 as a colourless oil (12 mg, 75%). [α]2D5 = +9.0 (c =
6.8 Hz, 3 H), 1.17 (d, J = 6.8 Hz, 3 H), 1.42 (d, J = 7.4 Hz, 3 H), 0.10, CHCl3). 1H NMR (400 MHz, CDCl3): δ = 0.75 (d, J =
1.46 (d, J = 6.8 Hz, 3 H), 1.44–1.50 (m, 1 H), 1.76 (m, 1 H), 1.98
(s, 3 H), 2.57 (quint, J = 6.8 Hz, 1 H), 2.85 (m, 1 H), 3.02 (m, 1
H), 3.31 (d, J = 2.5 Hz, 1 H), 3.40 (dd, J = 5.6, 4.3 Hz, 1 H), 4.56
(q, J = 6.8 Hz, 1 H), 5.22 (q, J = 6.8 Hz, 1 H), 5.30 (qd, J =
6.8, 1.9 Hz, 1 H), 7.26–7.34 (m, 5 H) ppm. 13C NMR (100.6 MHz,
6.8 Hz, 3 H), 0.85 (d, J = 6.8 Hz, 3 H), 0.92 (d, J = 6.8 Hz, 3 H),
1.16 (d, J = 6.8 Hz, 3 H), 1.25 (d, J = 6.8 Hz, 6 H), 1.36 (s, 3 H),
1.42 (d, J = 6.8 Hz, 3 H), 1.43 (s, 3 H), 1.53–1.63 (m, 1 H), 1.98
(m, 1 H), 2.37 (m, 1 H), 2.68 (quint, J = 6.8 Hz, 1 H), 3.16 (d, J =
9.2 Hz, 1 H), 3.71 (d, J = 9.9 Hz, 1 H), 3.82 (m, 1 H), 3.89 (d, J =
CDCl3): δ = 7.2, 9.2, 10.8, 12.5, 18.1, 19.1, 21.3, 23.5, 29.7, 34.1, 9.9 Hz, 1 H), 5.12 (q, J = 6.8 Hz, 1 H) ppm. 13C NMR (100.6 MHz,
35.2, 39.3, 40.7, 69.8, 74.6, 75.4, 79.4, 111.4, 125.5 (2ϫ Ar), 126.6
(Ar), 128.3 (2ϫ Ar), 142.3, 150.3, 170.7, 174.2 ppm. IR (thin film):
CDCl3): δ = 4.2, 11.1, 11.7, 13.6, 18.1, 19.1, 19.2, 29.8, 30.4, 34.2,
38.9, 40.7, 71.0, 74.8, 75.6, 99.0, 111.3, 149.5, 174.1 ppm. IR (thin
ν = 3500, 2970, 2925, 2855, 1735, 1455, 1375, 1260, 1140,
film): ν = 3465, 2970, 2935, 2880, 1750, 1460, 1380, 1265, 1200,
˜
˜
1080 cm–1. ESI-HRMS: calcd. for C27H42O6Na 485.2879; found
485.2870.
1185, 1135 cm–1. ESI-HRMS: calcd. for C20H36O5Na 379.2460;
found 379.2477.
(S,Z)-4-{(4S,5R,6S)-6-[(2S,3R)-3-Acetoxybut-2-yl]-2,2,5-trimethyl- (1Z,2S,3S,4R,5R,6R,7S)-1-Ethylidene-5-hydroxy-7-(4-nitrobenzoyl-
1,3-dioxan-4-yl}pent-2-en-3-yl Isobutyrate [(+)-23]: Ac2O
(0.055 mL, 0.57 mmol) was added at 0 °C under Ar to (+)-15
oxy)-2,4,6-trimethyl-3-[(1S)-1-phenylethoxy]octyl Isobutyrate [(+)-
25]: DEAD (diethyl azodicarboxylate, 0.60 mL, 3.84 mmol) was
(0.12 g, 0.29 mmol) and pyridine (0.046 mL, 0.57 mmol) in CH2Cl2 added dropwise at 20 °C under Ar to a solution of the diol 18
(5 mL). A catalytic amount of 4-(dimethylamino)pyridine (2 mg) (0.53 g, 1.28 mmol), triphenylphosphane (1.00 g, 3.84 mmol) and
was then added, and the mixture was stirred for 2 h. The reaction
was quenched with H2O (5 mL), the organic phase was separated,
and the aq. phases were further extracted with CH2Cl2 (3ϫ10 mL).
The combined organic extracts were washed with aq. HCl (1 m),
satd. aq. NaHCO3 and brine, dried (MgSO4) and concentrated in
vacuo to give a colourless oil (0.13 g). This was dissolved in CH2Cl2
(7 mL) and cooled to –78 °C under Ar. Anhydrous TiCl4 (0.57 mL
of a 1 m solution in CH2Cl2, 0.57 mmol) was added, and the reac-
tion mixture was stirred for 1.5 h, after which TLC revealed that
all the starting material had been consumed. A solution of borane–
pyridine complex (0.028 mL, 0.28 mmol) in CH2Cl2 (3 mL) was
added dropwise, and the reaction mixture was stirred for 15 min,
then quenched with aq. HCl (1 m, 5 mL) and allowed to warm to
20 °C. The organic phase was separated, and the aq. phase was
further extracted with CH2Cl2 (3ϫ10 mL). The combined organic
p-nitrobenzoic acid (0.64 g, 3.84 mmol) in toluene (20 mL). The
yellow solution was stirred for 18 h and then concentrated in vacuo,
and the resulting residue was purified by FC (AcOEt/petroleum
ether, 0:100–5:95) to give (+)-25 as a colourless oil (0.48 g, 67%).
A sample was recrystallised from hexane to give white, needle-like
crystals (X-ray, see the Supporting Information); m.p. 85–88 °C.
[α]2D5 = +12.7 (c = 0.10, CHCl3). 1H NMR (400 MHz, CDCl3): δ =
0.77 (d, J = 7.4 Hz, 3 H), 0.79 (d, J = 7.4 Hz, 3 H), 0.95 (d, J =
7.4 Hz, 3 H), 1.27 (d, J = 6.2 Hz, 3 H), 1.29 (d, J = 6.2 Hz, 3 H),
1.30 (d, J = 6.2 Hz, 3 H), 1.31 (d, J = 6.8 Hz, 3 H), 1.49 (d, J =
6.8 Hz, 3 H), 1.46–1.58 (m, 1 H), 1.80 (m, 1 H), 2.61 (m, 1 H), 2.75
(quint, J = 6.8 Hz, 1 H), 3.26 (dd, J = 9.2, 5.5 Hz, 1 H), 3.62 (d, J
= 9.2 Hz, 1 H), 4.48 (q, J = 6.2 Hz, 1 H), 4.97 (quint, J = 6.8 Hz,
1 H), 5.33 (q, J = 6.8 Hz, 1 H), 7.12–7.17 (m, 5 H), 8.25 (d, J =
8.6 Hz, 2 H), 8.35 (d, J = 8.6 Hz, 2 H) ppm. 13C NMR (100.6 MHz,
Eur. J. Org. Chem. 2011, 3317–3328
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3323

M. Turks, K. A. Fairweather, R. Scopelliti, P. Vogel
CDCl3): δ = 8.0, 10.0, 11.1, 14.5, 17.9, 19.2, 19.3, 22.6, 34.3, 36.9, 74.7, 74.8, 98.9, 111.2, 123.5 (2ϫ Ar), 130.5 (2ϫ Ar), 136.5, 149.5,
FULL PAPER
39.4, 42.2, 70.4, 75.1, 76.2, 76.9, 112.2, 123.8 (2ϫ Ar), 127.1 (2ϫ
Ar), 127.7, 128.2 (2ϫ Ar), 130.6 (2 ϫ Ar), 136.3, 143.6, 150.0,
150.4, 163.9, 174.1 ppm. IR (thin film): ν = 2975, 2935, 2875, 1720,
˜
1530, 1460, 1380, 1340, 1280, 1100 cm–1. ESI-HRMS: calcd. for
C27H39NO8Na 528.2573; found 528.2452.
150.5, 164.1, 174.4 ppm. IR (thin film): ν = 3595, 2975, 2930, 1750,
˜
1720, 1605, 1530, 1455, 1345, 1280, 1120, 1100 cm–1. ESI-HRMS:
calcd. for C32H43NO8Na 592.2886; found 592.2878. C32H43NO8
(569.69): calcd. C 67.47, H 7.61; found C 67.36, H 7.55.
(S,Z)-4-{(4S,5R,6R)-6-[(2R,3S)-3-(tert-Butyldimethylsilyloxy)but-2-
yl]-2,2,5-trimethyl-1,3-dioxan-4-yl}pent-2-en-3-yl Isobutyrate [(+)-
28]: K2CO3 (0.10 g) was added at 0 °C under Ar to the p-nitroben-
(1Z,2S,3R,4S,6S,7S)-1-Ethylidene-7-nitrobenzoyloxy-2,4,6-trimeth- zoate (+)-27 (0.058 g, 0.11 mmol) in MeOH/THF/H2O (2:1:1,
yl-5-oxo-3-[(1S)-1-phenylethoxy]octyl Isobutyrate [(+)-26]: Dess–
10 mL). The reaction mixture was allowed to warm to 20 °C and
Martin periodinane (1.66 g, 3.91 mmol) was added at 0 °C under
stirred for 5 h and was then quenched with aq. HCl (1 m) until the
Ar to (+)-25 (0.89 g, 1.56 mmol) in CH2Cl2 (40 mL). After 1.5 h, pH was neutral. The MeOH was removed in vacuo, and the residue
the reaction mixture was stirred with aq. sodium thiosulfate (1 m,
10 mL) and satd. aq. NaHCO3 (10 mL) until the cloudiness disap-
peared. The organic phase was separated, and the aq. phase was
extracted with CH2Cl2 (3ϫ15 mL). The combined organic extracts
were dried (MgSO4) and concentrated in vacuo to give a colourless
oil. FC (AcOEt/hexane, 1:9) gave (+)-26 (0.87 g, 99%), colourless
oil. [α]2D5 = +42.0 (c = 0.20, CHCl3). 1H NMR (400 MHz, CDCl3):
was extracted with AcOEt (3ϫ10 mL). The combined organic ex-
tracts were washed with brine, dried with MgSO4 and concentrated
to give the corresponding alcohol as a colourless oil. This was then
dissolved in CH2Cl2 (5 mL) and cooled to 0 °C. Et3N (0.040 mL,
0.29 mmol) was added, followed by Me3SiOSO2CF3 (0.025 mL,
0.13 mmol), and the reaction mixture was stirred for 20 min. The
reaction was then quenched with H2O (5 mL), the organic layer
δ = 0.88 (d, J = 6.8 Hz, 3 H), 0.99 (d, J = 7.0 Hz, 3 H), 1.18 (d, J was separated, and the aq. phase was further extracted with
= 7.0 Hz, 3 H), 1.20 (d, J = 7.0 Hz, 6 H), 1.28 (d, J = 6.9 Hz, 3 CH2Cl2 (3ϫ10 mL). The combined organic extracts were washed
H), 1.37 (d, J = 6.2 Hz, 3 H), 1.48 (d, J = 7.0 Hz, 3 H), 2.61 (quint,
J = 6.8 Hz, 1 H), 2.75 (m, 1 H), 2.93 (m, 1 H), 2.99 (quint, J =
6.8 Hz, 1 H), 3.80 (t, J = 4.3 Hz, 1 H), 4.46 (q, J = 6.8 Hz, 1 H),
with brine (5 mL), dried (MgSO4) and concentrated in vacuo. FC
(AcOEt/petroleum ether, 5:95) gave (+)-28, colourless oil (0.04 g,
78% over two steps). [α]2D5 = +16.0 (c = 0.10, CHCl3). 1H NMR
5.26 (q, J = 6.8 Hz, 1 H), 5.31 (q, J = 6.8 Hz, 1 H), 7.18–7.25 (m, (400 MHz, CDCl3): δ = 0.04 (s, 3 H), 0.05 (s, 3 H), 0.75 (d, J =
5 H), 8.08 (d, J = 8.6 Hz, 2 H), 8.25 (d, J = 8.6 Hz, 2 H) ppm. 13C
NMR (100.6 MHz, CDCl3): δ = 10.8, 11.8, 12.2, 13.2, 16.7, 18.9,
19.1, 23.5, 34.1, 41.3, 47.4, 48.7, 73.3, 74.9, 76.4, 112.6, 123.5 (2ϫ
7.4 Hz, 3 H), 0.81 (d, J = 6.8 Hz, 3 H), 0.89 (s, 9 H), 0.92 (d, J =
7.4 Hz, 3 H), 0.98 (d, J = 6.2 Hz, 3 H), 1.26 (d, J = 6.8 Hz, 6
H),1.33 (s, 3 H), 1.34 (s, 3 H), 1.43 (d, J = 6.8 Hz, 3 H), 1.40–1.46
Ar), 126.6 (2ϫ Ar), 127.4, 128.2 (2ϫ Ar), 130.4 (2ϫ Ar), 135.7, (m, 1 H), 1.80 (m, 1 H), 2.37 (m, 1 H), 2.69 (quint, J = 6.8 Hz, 1
143.4, 149.8, 150.4, 163.5, 174.3, 212.3 ppm. IR (thin film): ν =
H), 3.48 (dd, J = 10.4, 1.9 Hz, 1 H), 3.66 (dd, J = 9.9, 1.9 Hz, 1
˜
2975, 2930, 2875, 1745, 1720, 1605, 1525, 1455, 1345, 1270, 1115,
H), 4.14 (m, 1 H), 5.13 (q, J = 6.8 Hz, 1 H) ppm. 13C NMR
1100 cm–1. ESI-HRMS: calcd. for C32H41NO8Na 590.2730; found (100.6 MHz, CDCl3): δ = –4.8, –4.5, 4.1, 7.9, 11.1, 13.7, 17.0, 18.1,
590.2733.
19.0, 19.2, 25.7, 25.9, 29.8, 30.3, 34.2, 40.5, 40.7, 67.4, 74.9, 75.0,
98.5, 111.0, 149.8, 174.1 ppm. IR (thin film): ν = 2930, 2855, 1745,
˜
(2S,3R)-3-{(4S,5R,6S)-6-[(S,Z)-3-(Isobutyryloxy)pent-3-en-2-yl]-
2,2,5-trimethyl-1,3-dioxan-4-yl}but-2-yl 4-Nitrobenzoate [(+)-27]:
The ketone (+)-26 (0.43 g, 0.76 mmol) was dissolved in CH2Cl2
(20 mL) and cooled to –78 °C under Ar. TiCl4 (1.52 mL of a 1 m
solution in CH2Cl2, 1.52 mmol) was added, and the reaction mix-
ture was stirred for 1 h, after which TLC revealed that all the start-
ing material had been consumed. A solution of borane–pyridine
complex (0.15 mL, 1.52 mmol) in CH2Cl2 (8 mL) was added drop-
wise, and the reaction mixture was stirred for 1 h and then
quenched with HCl (1 m, 10 mL) and allowed to warm to 20 °C.
The organic phase was separated, the aq. phase was further ex-
tracted with CH2Cl2 (3ϫ20 mL), and the combined organic ex-
tracts were dried (MgSO4) and concentrated in vacuo to give a
yellow oil. This was loaded onto a short column of silica gel, and
after 30 min eluted with AcOEt/petroleum ether (1:4) to give a 3,4-
anti-diol as a colourless oil. This diol (0.37 g) was dissolved in 2,2-
dimethoxypropane (20 mL), the mixture was cooled to 0 °C, and
p-toluenesulfonic acid monohydrate (0.014 g, 0.076 mmol) was = –1.0. [α]
1470, 1380, 1255, 1200, 1135 cm–1. ESI-HRMS: calcd. for
C26H51O5Si [M + H]+ 471.3506; found 471.3500.
(+)-(2R,3S,4S,6S,7S,8R,9R,10R,11R)-3-Hydroxy-1,2:9,11-bis(iso-
propylidenedioxy)-4,6,8,10-tetramethyl-7-[(1S)-1-phenylethoxy]dode-
can-5-one [(+)-30]: A solution of MeLi·LiBr complex in Et2O (2 m,
0.32 mL, 0.64 mmol, 3 equiv.) was diluted with Et2O (2 mL). It was
cooled to –78 °C, a solution of the enol isobutyrate (+)-14 (98 mg,
0.21 mmol, 1 equiv.) in Et2O (2 mL) was added, and the resulting
reaction mixture was stirred at –78 °C for 2 h. A solution of the
aldehyde (+)-9 (0.17 g, 1.28 mmol, 6 equiv.) in Et2O (0.5 mL) was
added at the same temperature, and stirring was continued for 16 h.
Satd. aq. NH4Cl (10 mL) was added, and the aq. layer was ex-
tracted with EtOAc (4ϫ10 mL). The combined organic layers were
washed with brine, dried (Na2SO4), filtered and concentrated in
vacuo. FC (petroleum ether/EtOAc, 8:2) gave (+)-30 (82 mg, 74%).
Colourless oil, Rf = 0.31 (hexane/EtOAc, 8:2). [α]2D5 = +1.3. [α]
25
577
25
25
= –2.7. [α]
= –4.3 (c = 0.30, CHCl3). 1H NMR
435
405
added. The reaction mixture was stirred for 1 h, and solid NaHCO3
was then added until the pH was neutral. The mixture was filtered,
washed with CH2Cl2 and concentrated in vacuo to give a colourless
oil. FC (AcOEt/petroleum ether, 5:95–1:9) gave (+)-27, colourless
oil (0.19 g, 50% over three steps). [α]2D5 = +22.0 (c = 0.10, CHCl3).
1H NMR (400 MHz, CDCl3): δ = 0.84 (d, J = 6.4 Hz, 3 H), 0.93
(d, J = 7.0 Hz, 3 H), 0.95 (d, J = 7.0 Hz, 3 H), 1.26 (d, J = 7.0 Hz,
9 H), 1.35 (s, 3 H), 1.37 (s, 3 H), 1.43 (d, J = 7.0 Hz, 3 H), 1.52
(m, 1 H), 2.18 (m, 1 H), 3.57 (m, 1 H), 2.69 (quint, J = 7.0 Hz, 1
H), 3.60 (dd, J = 10.2, 1.9 Hz, 1 H), 3.69 (dd, J = 9.6, 1.9 Hz, 1
H), 5.13 (q, J = 7.0 Hz, 1 H), 5.53 (m, 1 H), 8.19 (d, J = 9.0 Hz, 2
H), 8.28 (d, J = 9.0 Hz, 2 H) ppm. 13C NMR (100.6 MHz, CDCl3):
δ = 4.2, 8.7, 11.1, 13.4, 18.9, 19.2, 29.8, 30.2, 34.2, 37.7, 40.7, 73.0,
(CDCl3, 400 MHz): δ = 0.70 [d, 3J = 6.4 Hz, 3 H, CH3-C(10)], 0.92
[d, J = 7.0 Hz, 3 H, CH3-C(8)], 1.05 [d, 3J = 6.4 Hz, 3 H, CH3-
3
3
3
C(6)], 1.19 [d, J = 6.4 Hz, 3 H, H-C(12)], 1.22 [d, J = 7.0 Hz, 3
H, CH3-C(4)], 1.31 [d, 3J = 6.4 Hz, 3 H, H-C(2Ј)], 1.33 [s, 3 H,
(CH3)2CO-C(9,11)], 1.35 [m+s, 7 H, H-C(10)], (CH3)2CO-C(1,2),
(CH3)2CO-C(9,11), 1.42 [s, 3 H, (CH3)2CO-C(1,2)], 1.86 [ddq, 3J =
7.4, J = 4.2, 3J = 2.0 Hz, 1 H, H-C(8)], 2.97 [dq, J = 7.0, 3J =
2.0 Hz, 1 H, H-C(4)], 3.19 [dq, 3J = 9.6, 3J = 6.7 Hz, 1 H, H-C(6)],
3.24 [dd, 3J = 10.2, 3J = 3.8 Hz, 1 H, H-C(9)], 3.28 [d, 3J = 2.6 Hz,
1 H, HO-C(3)], 3.51 [dq, 3J = 9.6, 3J = 6.4 Hz, 1 H, H-C(11)], 3.80
[dt, 3J = 9.0, 3J = 1.9 Hz, 1 H, H-C(3)], 3.85 [dd, 3J = 8.3, 3J =
5.3 Hz, 1 H, Hb-C(1)], 3.95 [dt, 3J = 8.3, 3J = 5.7 Hz, 1 H, H-C(2)],
3
3
3
3
4.07 [t, 3J = 8.3 Hz, 1 H, Ha-C(1)], 4.08 [dd, J = 7.0, J = 2.0 Hz,
3324
www.eurjoc.org
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2011, 3317–3328

Asymmetric Synthesis of Long-Chain Polyketides
3
1 H, H-C(7)], 4.90 [q, J = 7.0 Hz, 1 H, H-C(1Ј)], 7.31–7.21 [m, 5
(d, J = 7.0 Hz, 3 H), 1.05 (d, J = 7.0 Hz, 3 H), 1.07 (d, J = 6.4 Hz,
H, H-C(Ph)] ppm. 13C NMR (CDCl3, 100.6 MHz): δ = 8.3, 13.3, 3 H), 1.19 (s, 3 H), 1.88 (d, J = 7.0 Hz, 3 H), 1.29 (d, J = 6.4 Hz,
13.5, 15.3, 19.5, 20.1, 20.9, 25.3, 27.1, 30.1, 37.8, 38.0, 48.2, 48.5,
67.7, 70.8, 72.5, 75.0, 75.5, 76.8, 77.8, 97.9, 109.3, 126.4, 127.1,
3 H), 1.35 (s, 3 H), 1.38 (s, 3 H), 1.45 (s, 3 H), 1.33–1.40 (m, 1 H),
1.57–1.65 (m, 1 H), 3.02 (qd, J = 7.0, 2.6 Hz, 1 H), 3.20 (m, 1 H),
3.22 (d, J = 3.2 Hz, 1 H), 3.37 (dd, J = 10.2, 1.9 Hz, 1 H), 3.77
(qd, J = 6.4, 1.9 Hz, 1 H), 3.89 (dt, J = 7.7, 2.6 Hz, 1 H), 3.95–
4.03 (m, 2 H), 4.11–4.19 (m, 2 H), 4.54 (q, J = 6.4 Hz, 1 H), 7.25–
7.35 (m, 5 H) ppm. 13C NMR (100.6 MHz, CDCl3): δ = 3.8, 8.2,
8.7, 14.4, 18.9, 19.9, 23.8, 25.2, 27.0, 29.9, 33.8, 36.6, 47.7, 47.8,
67.6, 68.9, 72.5, 73.8, 75.0, 78.1, 78.2, 98.7, 109.2, 125.8 (2ϫ Ar),
128.1, 144.5, 219.0 ppm. IR (film): ν = 3455, 2990, 2935, 1705,
˜
1455, 1380, 1260, 1205, 1070 cm–1. MALDI-HRMS: calcd. for
C30H48O7Na+ 540.3298; found 540.3252. C30H48O7 (520.70): calcd.
C 69.20, H 9.29; found C 69.05, H 9.27.
(–)-(2R,3S,4R,5R,6R,7R,8S,9R,10S,11S)-1,2:9,11-Bis(isopropylid-
enedioxy)-4,6,8,10-tetramethyldodecane-1,2,3,5,7,9,11-heptol [(–)-
31] [IUPAC Recommendation: (1S,2R,3R,4R,5R,6S)-1-[(4R)-2,2-Di-
methyl-1,3-dioxolan-4-yl]-2,4-dimethyl-6-[(4R,5S,6S)-2,2,5,6-tetra-
methyl-1,3-dioxan-4-yl]heptane-1,3,5-triol]: Pd(OH)2 on activated
charcoal (20%, 50% moistened with H2O, 20 mg) was added to a
solution of (+)-30 (52 mg, 0.10 mmol) in MeOH (3 mL). The re-
sulting suspension was stirred under H2 (1 bar) for 3 h. The reac-
tion mixture was filtered through Celite, and the solvents were
evaporated. The resulting oil was dissolved in MeCN (0.5 mL) and
added at –15 °C to a solution of Me4NBH(OAc)3 (0.39 g,
1.50 mmol, 15 equiv.) in AcOH (1 mL) and MeCN (0.5 mL). The
reaction mixture was stirred at –20 °C for 24 h. The reaction was
quenched with aq. potassium sodium tartrate (0.5 m, 5 mL) and the
mixture extracted with EtOAc (4ϫ 5 mL). The combined organic
layers were washed with aq. satd. NaHCO3 and brine, dried
(Na2SO4), filtered and concentrated in vacuo. FC (CH2Cl2/MeOH,
97:3) provided (–)-31 (28 mg, 67%), white solid. Crystals suitable
for X-ray analysis were obtained by recrystallization from hexane/
CHCl3; m.p. 153 °C, Rf = 0.29 (CH2Cl2/MeOH, 97:3). [α]2D5 = –5.
127.0 (Ar), 128.2 (2ϫ Ar), 144.9, 218.6 ppm. IR (thin film): ν =
˜
3460, 2980, 2935, 2880, 1700, 1455, 1380, 1370, 1260, 1200, 1185,
1065, 1020 cm–1. ESI-HRMS: calcd. for C30H48O7Na 543.3298;
found 543.3298.
(1S,2R,4S)-4-{(4S,5R,6R)-6-[(2R,3S)-3-(tert-Butyldimethylsilyloxy)-
but-2-yl]-2,2,5-trimethyl-1,3-dioxan-4-yl}-1-[(R)-2,2-dimethyl-1,3-di-
oxolan-4-yl]-1-hydroxy-2-methylpentan-3-one [(+)-34] and
(1R,2S,4S)-4-{(4S,5R,6R)-6-[(2R,3S)-3-(tert-Butyldimethylsilyloxy)-
but-2-yl]-2,2,5-trimethyl-1,3-dioxan-4-yl}-1-[(R)-2,2-dimethyl-1,3-di-
oxolan-4-yl]-1-hydroxy-2-methylpentan-3-one [(+)-35]: The enol iso-
butyrate (+)-28 (0.11 g, 0.23 mmol) in diethyl ether (3 mL) was
added at –78 °C under Ar to MeLi·LiBr complex in diethyl ether
(3 mL). The mixture was stirred for 4 h, a solution of freshly pre-
pared (+)-9 (0.18 g, 1.38 mmol) in diethyl ether (1 mL) was then
added, and the mixture was stirred for an additional 4 h. The reac-
tion was then quenched with satd. aq. NH4Cl (5 mL) and the mix-
ture allowed to warm to 20 °C before extraction with AcOEt
(4ϫ10 mL). The combined organic extracts were washed with
brine (5 mL), dried (MgSO4) and concentrated in vacuo to give a
colourless oil. FC (AcOEt/petroleum ether, 5:95 to 1:9 to 1:4) gave
the starting material (+)-28 (0.043 g), as well as (+)-34 (0.015 g,
20% based on recovered starting material) as a colourless oil and
(+)-35 as a colourless oil (0.037 g, 49% based on recovered starting
material).
[α]
577
= –1. [α]
= –9. [α]
= –8 (c = 0.1, CHCl3). 1H NMR
25
25
25
435
405
(CDCl3+D2O, 400 MHz): δ = 0.78 [d, 3J = 7.0 Hz, 3 H, CH3-
3
C(10)], 0.82 [d, 3J = 7.0 Hz, 3 H, CH3-C(6)],* 0.95 [d, J = 7.0 Hz,
3
3
3 H, CH3-C(4)],* 1.04 [d, J = 7.0 Hz, 3 H, CH3-C(8)], 1.21 [d, J
= 6.1 Hz, 3 H, H-C(12)], 1.39, 1.37 [2ϫs, 6 H, (CH3)2CO-C(9,11)],
1.43 [s, 6 H, (CH3)2CO-C(1,2)], 1.64–1.55 [m, 1 H, H-C(10)], 1.80
[dquint, 3J = 7.4, 3J = 2.8 Hz, 1 H, H-C(6)],* 1.91 [br q, 3J =
7.4 Hz, 1 H, H-C(8)], 2.06 [dquint, J = 7.4, J = 2.6 Hz, 1 H, H-
C(4)],* 3.61 [dd, J = 10.2, J = 1.6 Hz, 1 H, H-C(9)], 3.63 [dq, J
Data for (+)-34 (Minor: anti-Aldol): [α]2D5 = +23.0 (c = 0.10,
3
3
1
CHCl3). H NMR (400 MHz, CDCl3): δ = 0.05 (s, 3 H), 0.06 (s, 3
3
3
3
H), 0.77 (d, J = 7.0 Hz, 3 H), 0.88 (d, J = 7.0 Hz, 3 H), 0.91 (s, 9
H), 0.96 (d, J = 7.0 Hz, 3 H), 0.99 (d, J = 6.4 Hz, 3 H), 1.27 (d, J
= 7.6 Hz, 3 H),1.32 (s, 6 H), 1.36 (s, 3 H), 1.42 (s, 3 H), 1.46 (m, 1
H), 1.81 (m, 1 H), 2.99 (dq, J = 9.6, 7.0 Hz, 1 H), 3.11 (m, 1 H),
3.48 (m, 1 H), 3.55 (dd, J = 10.2, 1.9 Hz, 1 H), 3.97–4.16 (m, 5 H)
ppm. 13C NMR (100.6 MHz, CDCl3): δ = –4.8, –4.6, 4.3, 8.0, 11.9,
14.1, 17.1, 18.1, 19.1, 25.2, 25.9, 26.8, 29.3, 29.8, 40.5, 47.1, 48.6,
3
3
3
= 9.6, J = 6.1 Hz, 1 H, H-C(11)], 3.91 [dd, J = 7.7, J = 2.2 Hz,
3
1 H, H-C(3)], 3.93 [d, J = 9.9 Hz, 1 H, H-C(7)], 4.04–4.00 [m, 2
H, Hb-C(1), H-C(5)], 4.14 [dd, 2J = 8.0, 3J = 6.8 Hz, 1 H, Ha-C(1)],
3
3
4.18 [dt, J = 8.2, J = 6.4 Hz, 1 H, H-C(2)] ppm; * exchangeable
assignments. 13C NMR (CDCl3, 100.6 MHz): δ = 10.5, 11.2, 12.2,
12.4, 19.2, 19.8, 25.6, 27.0, 30.3, 33.6, 37.1, 37.6, 37.9, 67.9, 70.8,
72.1, 74.1, 74.6, 76.3, 81.0, 98.6, 109.0 ppm. IR (film): ν = 3480– 67.4, 67.4, 74.6, 76.1, 76.8, 76.9, 98.6, 109.2, 220.4 ppm. IR (thin
˜
3400 (br. s), 2985, 2935, 1385, 1205, 1175, 1060 cm–1. MALDI-
HRMS: calcd. for C22H42O7Na+ 441.2828; found 441.2821.
film): ν = 3485, 2930, 2880, 2855, 1695, 1460, 1375, 1255, 1205,
˜
1185, 1155 cm–1. ESI-HRMS: calcd. for C28H55O7Si [M + H]+
531.3717; found 531.3717.
(–)-(2R,3S,4S,7S,8R,9R,10R,11S)-3-Hydroxy-1,2:9,11-bis(isopropyl-
idenedioxy)-4,6,8,10-tetramethyl-7-[(1S)-1-phenylethoxy]dodeca-5-
one [(–)-33]: The enol isobutyrate (–)-20 (0.040 g, 0.087 mmol) was
dissolved in diethyl ether (1 mL) and added at –78 °C under Ar to
MeLi–LiBr complex (0.12 mL of a 2.2 m solution in diethyl ether,
0.26 mmol, 1 mL). The reaction mixture was stirred for 2 h, a solu-
tion of freshly prepared aldehyde (+)-9 (0.068 g, 0.52 mmol) in di-
ethyl ether (0.25 mL) was then added, and the mixture was stirred
at –78 °C for 20 h. The reaction was then quenched with satd. aq.
NH4Cl and the mixture allowed to warm to 20 °C. The organic
layer was separated, and the aq. layer was further extracted with
EtOAc (4ϫ10 mL). The combined organic extracts were washed
with brine, dried (MgSO4) and concentrated in vacuo to give a
colourless oil. FC (AcOEt/petroleum ether, 1:9 to 1.5:8.5) gave re-
covered enol isobutyrate (–)-20 (6.2 mg, 16%), together with (–)-33
as a colourless oil (0.029 g, 64%). [α]2D5 = –9.6 (c = 0.10, CHCl3).
1H NMR (400 MHz, CDCl3): δ = 0.75 (d, J = 7.0 Hz, 3 H), 0.79
Data for (+)-35 (Major: syn-Aldol): [α]2D5 = +8.4 (c = 0.10, CHCl3).
1H NMR (400 MHz, CDCl3): δ = 0.04 (s, 3 H), 0.04 (s, 3 H), 0.76
(d, J = 6.8 Hz, 3 H), 0.86 (d, J = 6.8 Hz, 3 H), 0.89 (s, 9 H), 0.95
(d, J = 6.8 Hz, 3 H), 0.98 (d, J = 6.2 Hz, 3 H), 1.20 (d, J = 7.4 Hz,
3 H), 1.28 (s, 3 H), 1.32 (s, 3 H), 1.35 (s, 3 H), 1.42 (s, 3 H), 1.46
(m, 1 H), 1.79 (m, 1 H), 2.91 (qd, J = 6.8, 2.5 Hz, 1 H), 3.01 (dq,
J = 9.9, 7.4 Hz, 1 H), 3.45 (d, J = 2.5 Hz, 1 H), 3.55 (dd, J = 10.5,
1.9 Hz, 1 H), 3.78 (m, 1 H), 3.92–4.02 (m, 2 H), 4.04–4.16 (m, 3
H) ppm. 13C NMR (100.6 MHz, CDCl3): δ = –4.8, –4.6, 4.3, 8.1,
12.4, 17.2, 18.1, 19.2, 25.3, 25.7, 26.9, 29.5, 29.8, 40.5, 45.6, 48.3,
67.4, 67.7, 73.0, 74.6, 74.9, 76.5, 98.7, 109.3, 219.3 ppm. IR (thin
film): ν = 3455, 2935, 2885, 2855, 1705, 1460, 1380, 1255, 1205,
˜
1075 cm–1. ESI-HRMS: calcd. for C28H55O7Si [M + H]+ 531.3717;
found 531.3712.
(1R,2S,3R,4R)-4-{(4R,5S,6R)-6-[(2R,3S)-3-(tert-Butyldimethylsilyl-
oxy)but-2-yl]-2,2,5-trimethyl-1,3-dioxan-4-yl}-1-[(R)-2,2-dimethyl-
Eur. J. Org. Chem. 2011, 3317–3328
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3325

M. Turks, K. A. Fairweather, R. Scopelliti, P. Vogel
FULL PAPER
1,3-dioxolan-4-yl]-2-methylpentane-1,3-diol [(–)-36]: AcOH
(1.5 mL) was added at room temp. under Ar to Me4NBH(OAc)3
(0.28 g, 1.05 mmol) in MeCN (0.5 mL). The solution was cooled
to –20 °C, a solution of ketone (+)-35 (0.033 g, 0.062 mmol) in ace-
give a diol mixture as a colourless oil (0.021 g, 70%). A sample of
this crude diol was purified by FC (AcOEt/petroleum ether, 1:9) to
give (+)-39 as a white solid. A sample of (+)-39 was recrystallised
from ether/hexane to give white needles; m.p. 124–125 °C. [α]2D5
=
1
tonitrile (1 mL) was then added, and the reaction mixture was +3.0 (c = 0.10, CHCl3). H NMR (400 MHz, CDCl3): δ = 0.04 (s,
stirred for 24 h. The reaction mixture was quenched with aq. so-
dium potassium tartrate (1 m , 5 mL) and extracted with EtOAc
(4ϫ10 mL). The combined organic extracts were washed with a
satd. solution of NaHCO3 and brine, dried (MgSO4) and concen-
trated in vacuo to give the diol mixture as a colourless oil [0.25 g;
(–)-36/37, 1:3; 76%]. FC of a sample (AcOEt/petroleum ether, 1:9)
gave the syn-diol 37 as a colourless oil, which was characterized as
its acetonide (–)-38, and the anti-diol (–)-36 as a white solid. A
sample of (–)-36 was recrystallised from diethyl ether/hexane to give
3 H), 0.05 (s, 3 H), 0.75 (d, J = 7.4 Hz, 3 H), 0.85 (d, J = 6.8 Hz,
3 H), 0.86 (d, J = 7.4 Hz, 3 H), 0.89 (s, 9 H), 0.98 (d, J = 6.2 Hz,
3 H), 1.06 (d, J = 7.4 Hz, 3 H), 1.34 (s, 3 H), 1.36 (s, 3 H), 1.39 (s,
3 H), 1.41 (s, 3 H), 1.47 (m, 1 H), 1.80 (m, 1 H), 1.93–2.05 (m, 2
H), 3.08 (br. d, J = 4.9 Hz, 1 H), 3.33 (br. d, J = 6.8 Hz, 1 H), 3.51
(dd, J = 10.5, 1.9 Hz, 1 H), 3.64 (m, 1 H), 3.84 (dd, J = 9.9, 1.9 Hz,
1 H), 3.94 (dd, J = 8.0, 6.8 Hz, 1 H), 4.03–4.18 (m, 4 H) ppm. 13C
NMR (100.6 MHz, CDCl3): δ = –4.8, –4.6, 4.3, 8.0, 11.0, 12.0,
17.1, 18.2, 19.6, 25.4, 25.9, 26.7, 29.9, 30.8, 36.9, 37.6, 40.4, 66.4,
67.4, 74.1, 75.0, 76.5, 77.2, 98.5, 108.9 (one peak obscured by
white, needle-like crystals; m.p. 108–110 °C. [α]2D5 = –9.0 (c = 0.10,
1
CHCl3). H NMR (400 MHz, CDCl3): δ = 0.04 (s, 3 H), 0.05 (s, 3 CDCl3 signal) ppm. IR (thin film): ν = 3415, 2930, 2855, 1460,
˜
H), 0.73 (d, J = 6.8 Hz, 3 H), 0.77 (d, J = 6.8 Hz, 3 H), 0.89 (s, 9
1380, 1250, 1200, 1070 cm–1. ESI-HRMS: calcd. for C28H57O7Si
H), 0.89 (d, J = 6.8 Hz, 3 H), 0.98 (d, J = 6.2 Hz, 3 H), 1.15 (d, J [M + H]+ 533.3868; found 533.3967.
= 7.4 Hz, 3 H), 1.38 (s, 3 H), 1.41 (s, 3 H), 1.44 (s, 3 H), 1.48 (s, 3
(1R,2S,3R,4S)-4-{(4S,5S,6R)-6-[(2R,3S)-3-(tert-Butyldimethylsilyl-
H), 1.21–1.56 (m, 2 H), 1.82 (m, 1 H), 2.04 (m, 1 H), 3.51–3.60 (m,
3 H), 3.82 (dd, J = 9.2, 1.9 Hz, 1 H), 3.96–4.03 (m, 2 H), 4.12 (m,
1 H), 4.21 (q, J = 8.0 Hz, 1 H), 4.37 (s, 1 H), 5.19 (s, 1 H) ppm.
13C NMR (100.6 MHz, CDCl3): δ = –4.9, –4.6, 4.5, 8.1, 11.5, 12.0,
17.2, 18.2, 19.5, 25.6, 25.9, 26.8, 29.8, 30.8, 35.4, 36.7, 40.4, 65.9,
oxy)but-2-yl]-2,2,5-trimethyl-1,3-dioxan-4-yl}-1-[(R)-2,2-dimethyl-
1,3-dioxolan-4-yl]-2-methylpentane-1,3-diyl Diacetate [(+)-41] and
(1R,2S,3S,4S)-4-{(4S,5S,6R)-6-[(2R,3S)-3-(tert-Butyldimethylsilyl-
oxy)but-2-yl]-2,2,5-trimethyl-1,3-dioxan-4-yl}-1-[(R)-2,2-dimethyl-
1,3-dioxolan-4-yl]-2-methylpentane-1,3-diyl Diacetate
[(+)-40]:
67.4, 72.4, 74.9, 78.3, 80.9, 83.3, 99.0, 109.6 ppm. IR (thin film): ν
˜
AcOH (1.5 mL) was added at 20 °C under Ar to Me4NBH(OAc)3
(0.28 g, 1.05 mmol) in MeCN (0.5 mL), The solution was cooled
to –20 °C, a solution of the ketone (+)-34 (0.033 g, 0.062 mmol) in
MeCN (1 mL) was then added, and the reaction mixture was
stirred for 24 h. The reaction mixture was quenched with aq. so-
dium potassium tartrate (1 m, 5 mL) and extracted with EtOAc
(4ϫ10 mL). The combined organic extracts were washed with satd.
aq. NaHCO3 and brine, dried (MgSO4) and concentrated in vacuo
to give a colourless oil (0.25 g), which was used directly in the next
step without purification. Ac2O (0.023 mL, 0.23 mmol) and pyr-
idine (0.019 mL, 0.23 mmol) in CH2Cl2 (2.5 mL) were added to the
crude diol mixture (0.25 g, 0.047 mmol) at 0 °C under Ar. A cata-
lytic amount of 4-(dimethylamino)pyridine was then added, and
the mixture was stirred for 18 h. The reaction was quenched with
water (5 mL), the organic phase was separated, and the aq. phase
was further extracted with CH2Cl2 (3ϫ10 mL). The combined or-
ganic extracts were washed with satd. aq. CuSO4 (5 mL), aq. citric
acid (10%, 5 mL), satd. aq. NaHCO3 (5 mL) and brine (5 mL),
dried (MgSO4) and concentrated in vacuo to give a colourless oil.
FC (AcOEt/petroleum ether, 5:95) gave the syn-diacetate (+)-41 as
a colourless oil (0.013 g, 34% over two steps). Further elution gave
the anti-diacetate (+)-40 as a colourless oil (0.004 g, 11% over two
steps).
Data for (+)-41: [α]2D5 = +17.0 (c = 0.10, CHCl3). 1H NMR
(400 MHz, CDCl3): δ = 0.04 (s, 3 H), 0.05 (s, 3 H), 0.74 (d, J =
7.4 Hz, 3 H), 0.79 (d, J = 6.8 Hz, 3 H), 0.84 (d, J = 6.8 Hz, 3 H),
0.89 (s, 9 H), 0.91 (d, J = 7.4 Hz, 3 H), 0.98 (d, J = 6.2 Hz, 3 H),
1.32–1.45 (m, 1 H), 1.35 (s, 6 H), 1.39 (s, 6 H), 1.80 (m, 1 H), 2.08
(s, 6 H), 2.15 (m, 1 H), 2.56 (m, 1 H), 3.49 (dd, J = 10.5, 1.8 Hz,
1 H), 3.74–3.81 (m, 2 H), 3.98 (dd, J = 8.0, 6.2 Hz, 1 H), 4.08–4.18
(m, 2 H), 4.88 (dd, J = 7.4, 2.5 Hz, 1 H), 5.18 (dd, J = 6.8, 3.1 Hz,
1 H) ppm. 13C NMR (100.6 MHz, CDCl3): δ = –4.8, –4.6, 4.4, 7.7,
10.4, 13.2, 17.0, 18.1, 19.1, 20.9, 21.0, 25.4, 25.9, 26.6, 29.9, 30.6,
35.5, 36.1, 40.5, 66.8, 67.3, 73.9, 74.7, 75.1, 75.2, 77.4, 98.2, 109.1,
= 3435, 2930, 2885, 2855, 1460, 1380, 1250, 1205, 1120, 1100,
1065 cm–1. ESI-HRMS: calcd. for C28H57O7Si [M + H]+ 533.3868;
found 533.3878.
tert-Butyl [(2S,3R)-3-{(4R,5S,6R)-6-[(S)-1-{(4R,5S,6R)-6-[(R)-2,2-
Dimethyl-1,3-dioxolan-4-yl]-2,2,5-trimethyl-1,3-dioxan-4-yl}ethyl]-
2,2,5-trimethyl-1,3-dioxan-4-yl}but-2-yloxy]dimethylsilane [(–)-38]:
The diol 37 (1 mg, 0.001 mmol) was dissolved in 2,2-dimethoxypro-
pane (1 mL), the mixture was cooled to 0 °C, and TsOH·H2O
(0.5 mg) was added. The reaction mixture was allowed to warm to
20 °C and stirred for 1 h. Solid NaHCO3 was then added until the
pH was neutral. The mixture was filtered, washed with CH2Cl2 and
concentrated in vacuo to give a colourless oil, which was purified
by FC (AcOEt/petroleum ether, 5:95) to give (–)-38, colourless oil
1
(1 mg, 91%). [α]2D5 = –9.0 (c = 0.10, CHCl3). H NMR (400 MHz,
CDCl3): δ = 0.03 (s, 3 H), 0.04 (s, 3 H), 0.72 (d, J = 6.8 Hz, 3 H),
0.86 (d, J = 6.8 Hz, 3 H), 0.88 (s, 9 H), 0.97 (d, J = 6.8 Hz, 3 H),
0.98 (d, J = 6.2 Hz, 3 H), 1.34 (s, 6 H), 1.36 (s, 3 H), 1.37 (s, 3 H),
1.39 (s, 3 H), 1.41 (s, 3 H), 1.48 (m, 1 H), 1.75–1.82 (m, 2 H), 2.07
(m, 1 H), 3.48 (dd, J = 10.5, 1.9 Hz, 1 H), 3.68 (dd, J = 8.6, 1.9 Hz,
1 H), 3.81–3.87 (m, 2 H), 3.91 (dd, J = 8.6, 1.9 Hz, 1 H), 4.00 (m,
1 H), 4.06 (m, 1 H), 4.12 (qd, J = 6.2, 3.0 Hz, 1 H) ppm. 13C NMR
(100.6 MHz, CDCl3): δ = –4.9, –4.4, 5.7, 6.6, 8.1, 10.0, 17.3, 18.2,
19.4, 19.7, 25.1, 25.9, 27.1, 29.8, 29.9, 30.3, 30.7, 37.5, 40.3, 67.6,
68.0, 73.6, 74.2, 74.4, 75.4, 75.8, 98.4, 98.9, 109.2 ppm. IR (thin
film): ν = 2985, 2930, 2855, 1460, 1380, 1255, 1200, 1105,
˜
1075 cm–1. ESI-HRMS: calcd. for C31H61O7Si [M + H]+ 573.4181;
found 573.4187.
(1S,2S,3S,4S)-4-{(4R,5S,6R)-6-[(2R,3S)-3-(tert-Butyldimethylsilyl-
oxy)but-2-yl]-2,2,5-trimethyl-1,3-dioxan-4-yl}-1-[(R)-2,2-dimethyl-
1,3-dioxolan-4-yl]-2-methylpentane-1,3-diol [(+)-39]: AcOH
(1.5 mL) was added at 20 °C under Ar to Me4NBH(OAc)3 (0.30 g,
1.13 mmol) in MeCN (0.5 mL). The solution was cooled to –20 °C,
a solution of the ketone (+)-34 (0.030 g, 0.057 mmol) in MeCN
(1 mL) was then added, and the reaction mixture was stirred for
24 h. The reaction mixture was quenched with aq. sodium potas-
sium tartrate (1 m, 5 mL) and extracted with EtOAc (4ϫ10 mL).
The combined organic extracts were washed with satd. aq.
NaHCO3 and brine, dried (MgSO4) and concentrated in vacuo to
170.5, 170.6 ppm. IR (thin film): ν = 2930, 2885, 2855, 1730, 1460,
˜
1370, 1250, 1075 cm–1. ESI-HRMS: calcd. for C32H60O9SiK
655.3644; found 655.3619.
Data for (+)-40: [α]2D5 = +21.0 (c = 0.10, CHCl3). 1H NMR
(400 MHz, CDCl3): δ = 0.03 (s, 3 H), 0.04 (s, 3 H), 0.73 (d, J =
3326
www.eurjoc.org
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2011, 3317–3328

Asymmetric Synthesis of Long-Chain Polyketides
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6.8 Hz, 3 H), 0.80 (d, J = 7.4 Hz, 3 H), 0.81 (d, J = 6.2 Hz, 3 H),
0.88 (s, 9 H), 0.97 (d, J = 6.8 Hz, 3 H), 0.99 (d, J = 6.8 Hz, 3 H),
1.29 (s, 3 H), 1.33 (s, 3 H), 1.37 (s, 3 H), 1.41 (s, 3 H), 1.78 (m, 1
H), 1.98–2.10 (m, 2 H), 2.04 (s, 3 H), 2.08 (s, 3 H), 2.39 (m, 1 H),
3.48 (dd, J = 10.5, 1.9 Hz, 1 H), 3.61 (dd, J = 8.6, 6.8 Hz, 1 H),
3.78 (dd, J = 9.9, 1.9 Hz, 1 H), 3.99 (dd, J = 8.0, 6.2 Hz, 1 H), 4.13
(m, 1 H), 4.19 (q, J = 6.2 Hz, 1 H), 4.71 (dd, J = 10.5, 1.2 Hz, 1
H), 5.07 (dd, J = 8.6, 1.9 Hz, 1 H) ppm. 13C NMR (100.6 MHz,
CDCl3): δ = –4.8, –4.6, 4.3, 7.8, 10.9, 14.7, 16.9, 18.1, 19.3, 21.1,
21.2, 25.5, 25.7, 26.3, 30.0, 30.6, 34.8, 37.0, 40.5, 66.0, 67.3, 72.0,
74.3, 75.3, 76.9, 77.2, 98.0, 109.8, 170.4, 170.9 ppm. IR (thin film):
ν = 2935, 2885, 2857, 1744, 1461, 1371, 1242, 1202, 1188,
˜
1078 cm–1. ESI-HRMS: calcd. for C32H61O9Si 617.4085; found
617.4037.
[6]
[7]
[8]
Supporting Information (see footnote on the first page of this arti-
cle): 1H and 13C NMR spectra of compounds 12–15, 19–28, 30, 31,
33–36, 38–41.
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S. Laclef, C. J. Exner, M. Turks, V. Videtta, P. Vogel, J. Org.
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the mass spectra, and to M. M. Rey for technical assistance. Single-
crystal X-ray diffraction studies were carried out by Dr. R. Scopel-
liti, EPFL.
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© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2011, 3317–3328