Stereoselective total syntheses of paecilomycins e and F through a protecting group directed diastereoselective intermolecular Nozaki-Hiyama-Kishi (NHK) reaction

Article abstract of DOI:10.1002/ejoc.201402133

An efficient and concise approach to the total syntheses of paecilomycins E (1) and F (2) is described. A protecting group directed intermolecular diastereoselective Nozaki-Hiyama-Kishi (NHK) reaction, a Julia-Kocienski olefination, a Sharpless asymmetric dihydroxylation, and De Brabander's lactonization protocol are used as the key steps.

Full text of DOI:10.1002/ejoc.201402133

FULL PAPER
DOI: 10.1002/ejoc.201402133
Stereoselective Total Syntheses of Paecilomycins E and F through a Protecting
Group Directed Diastereoselective Intermolecular Nozaki–Hiyama–Kishi
(NHK) Reaction
Debendra K. Mohapatra,*[a,b] D. Sai Reddy,[a,b] N. Arjunreddy Mallampudi,[a] and
Jhillu S. Yadav[a,b]
Keywords: Total synthesis / Natural products / C–C coupling / Dihydroxylation / Olefination / Cyclization
An efficient and concise approach to the total syntheses of
paecilomycins E (1) and F (2) is described. A protecting
group directed intermolecular diastereoselective Nozaki–
Hiyama–Kishi (NHK) reaction, a Julia–Kocienski olefination,
a Sharpless asymmetric dihydroxylation, and De Brabander’s
lactonization protocol are used as the key steps.
itol and dioxinone. Although the first total synthesis of
paecilomycin F (2), which proceeded through a ring-closing
metathesis (RCM) protocol, was reported by Srihari et
al.,[10] the synthesis of paecilomycin E (1) has not been re-
ported. Herein, we present a convergent approach for the
syntheses of paecilomycins E (1) and F (2) by using a pro-
tecting group directed intermolecular asymmetric Nozaki–
Hiyama–Kishi (NHK) reaction as the key step.
Introduction
Radicicol[1] was first isolated from the antifungal poly-
ketide metabolite of β-resorcylic acid lactone (RAL). Its
isolation and biological activity contributed to the discov-
ery of additional resorcyclic acid lactones, and, so far, more
than 30 naturally occurring RALs[2] have been reported.
These β-resorcylic acid lactones have been shown as cyto-
toxic,[3] antimalarial, antiviral, antiparasitic,[4] antifungal,[5]
protein tyrosine kinase ATPase inhibitory,[6] and nemato-
cidal[7] as well as contain a steroidic moiety with estrogenic
properties.[8] In 2010, Chen and co-workers[9a] isolated a re-
lated class of new RALs, the paecilomycins A–F (1–7),
along with other known RALs from the methanol extracts
of Paecilomyces fungus SC0924 (see Figure 1). Their struc-
tures were elucidated by extensive NMR analysis, single-
crystal X-ray determination, and chemical correlations.
Among them, paecilomycins E (1) and F (2) have shown
potent antiplasmodial activity against plasmodium falcipa-
rum lines 3D7 (IC50 values of 0.65 and 1.7 μm) and Dd2
(IC50 values of 20 nM and 8.8 μm), respectively. In 2012,
Chen and co-workers[9c] revised the assignment of the ste-
reochemistry at C-6Ј of paecilomycins E (1) and F (2) by
employing their total syntheses. The structural complexity
and potent biological activity against plasmodium species
as well as the revision of the assigned stereochemistry
prompted us to pursue the total syntheses of paecilomy-
cins E (1) and F (2) by using commercially available d-mann-
Figure 1. Structures of paecilomycins A–F (1–7).
For the retrosynthetic analysis (see Scheme 1), paecilo-
mycins E (1) and F (2) could be derived from compound 8
through a macrolactonization that followed De Brabander’s
protocol. The advanced fragment 8 could be generated from
coupling the two individual fragments 9 and 10 through a
Julia–Kocienski olefination reaction. Aldehyde 9 could be
smoothly obtained from 11 and 12 by using an intermo-
[a] Natural Products Chemistry Division, CSIR – Indian Institute
of Chemical Technology,
Hyderabad 500007, India
[b] Academy of Scientific and Innovative Research,
New Delhi 110001, India
E-mail: mohapatra@iict.res.in
www.iictindia.org
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201402133.
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FULL PAPER
Scheme 1. Retrosynthetic approach for paecilomycins E (1) and F (2).
lecular NHK reaction. Compounds 11 and 12 could be syn-
thesized from (S)-propylene oxide and d-mannitol. Frag-
ment 10 could be derived from dioxinone 13.
Results and Discussion
For the total synthesis of paecilomycins E and F, we
started with compound 15 (see Scheme 2), which was pre-
pared from commercially available 2,2,6-trimethyl-4H-1,3-
dioxin-4-one (13) by employing a known protocol.[11] Sub-
sequently, the phenolic hydroxy functionality was converted
into methyl ether 16 in 87% yield by using Mitsunobu[12]
conditions. Benzyl bromide 17 was prepared in 79% yield
through a bromination at the benzylic position of 16 with
N-bromosuccinimide (NBS) and benzoyl peroxide. The re-
sulting bromo compound 17 was treated with commercially
available 1-phenyl-1H-tetrazole-5-thiol and Et3N in tetra-
hydrofuran (THF) to obtain thioether 18, which was fur-
ther treated with meta-chloroperoxybenzoic acid (m-CPBA)
in CH2Cl2 to afford the corresponding sulfone fragment
10[13] in 88% yield over the two steps.
The synthesis of fragment 9 (see Scheme 3) was initiated
from compound 19, which was prepared from commercially
available d-mannitol (14) through a literature protocol.[14]
The treatment of 19 with a 1:1 ratio of MeOH and 4 n HCl
at 80 °C furnished the corresponding triol in 90% yield.
The primary hydroxy group was selectively protected as its
Scheme 2. Reagents and conditions: (a) MeOH, triphenylphos-
phine (TPP), diisopropyl azodicarboxylate (DIAD), THF, 0 °C–
r.t., 4 h, 87%; (b) NBS, benzoyl peroxide, CCl4, reflux, 6 h, 79%;
(c) 1-phenyl-1H-tetrazole-5-thiol, Et3N, THF, reflux, 6 h; (d) m-
CPBA, CH2Cl2, 0 °C to r.t., 24 h, 88%.
silyl ether by treatment with tert-butyldimethylsilyl chloride smoothly removed by treatment with tetra-n-butylammo-
(TBSCl) in the presence of imidazole to obtain 20 in 92% nium fluoride (TBAF) in THF to furnish primary alcohol
yield. Diol 20 was subsequently transformed into its aceton- 21 in 93% yield. The resulting primary hydroxy group was
ide derivative in 96% yield by using 2,2-dimethoxypropane treated with the Dess–Martin periodinane[15] reagent to af-
(2,2-DMP) and a catalytic amount of camphorsulfonic acid ford the corresponding aldehyde 12 in 88% yield. Vinyl iod-
(CSA). The tert-butyldimethylsilyl (TBS) group was ide fragment 11 was prepared from (S)-propylene oxide by
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Stereoselective Total Syntheses of Paecilomycins E and F
following a known protocol.[16] The combination of 11 with protected aldehyde afforded more than 95% of one isomer
aldehyde 12 under NHK[17] coupling conditions provided a in 61% yield.
mixture of diastereomeric allylic alcohols 22 and 23 (dr 7:3),
After studying the protecting group directed intermolec-
which were separated by chromatography on a silica gel col- uler NHK reaction, allylic alcohol 22 was protected as its
umn to give the diastereomers in 82% combined yield. Both MOM ether by using MOMCl to afford 30 in 96% yield.
isomers were used for the synthesis of paecilomycins E and The terminal double bond of 30 was then selectively dihy-
F. The newly created sterocenter at the allylic alcohol moi- droxylated under Sharpless dihydroxylation[20] conditions
ety of compound 23 was assigned by following a modified with K3Fe(CN)6, K2CO3, OsO4, tBuOH/H2O (1:1) to ob-
α-methoxy-α-trifluoromethylphenylacetic acid (MTPA) es- tain 31 in 84% yield. Treatment of the internal double bond
ter protocol[18] and determined to have the (S) configura- with Pd/C under hydrogen afforded 32 in 88% yield. The
tion. After assigning the newly created stereocenter in com- aliphatic key fragment 9 was prepared in 97% yield by the
pounds 22 and 23, we proceeded to determine the effect of oxidative cleavage of 32 with silicon dioxide supported
[21]
the protecting groups in 12 on the outcome of the inter- NaIO4
molecular NHK reaction, as similar experimental results
.
With coupling partners 9 and 10 in hand, the synthesis
have been reported by our group with regard to intramolec- of fragment 33 was undertaken by using a Julia–Kocienski
ular NHK reactions.[19] Hence, we changed the protecting olefination protocol.[22] When the reaction was conducted
groups of aldehyde 12, which ranged from the smaller meth- in the presence of potassium hexamethyldisilazide
oxymethyl (MOM) group to the larger TBS group, and the (KHMDS) with THF as a solvent at –78 °C, the product
results are depicted in Table 1. Of the outcomes, the TBS- was obtained in poor yield with less selectivity. To improve
both the selectivity and yield, the reaction was performed
with KHMDS in presence of 18-crown-6 ether in 1,2-di-
methoxyethane (DME) at –78 °C to afford the desired ole-
fin 33 exclusively in 87% yield (see Scheme 4). The silyl
group in 33 was smoothly removed by treatment with
TBAF to obtain 8 in 91% yield. Macrolactone core 34 was
prepared in 78% yield through a one-pot acetonide depro-
tection and intramolecular macrolactonization under
De Brabander’s conditions[23] by using NaH and THF at
0 °C. Finally, a global deprotection of the MOM and acet-
Scheme 3. Reagents and conditions: (e) MeOH/4 n HCl (1:1),
80 °C, 12 h, 90%; (f) TBSCl, imidazole, CH2Cl2, 0 °C, 0.5 h, 92%;
(g) 2,2-DMP, CSA, CH2Cl2, 0 °C to r.t., 1 h, 96% (h) TBAF, THF,
0 °C–r.t., 10 h, 93% (i) Dess–Martin periodinane, NaHCO3,
CH2Cl2, 0 °C–r.t., 3 h, 88%; (j) 11, CrCl2, NiCl2, N,N-dimethyl-
formamide (DMF), r.t., 24 h, 82%; (k) MOMCl, N,N-diisopropyl-
Scheme 4. Reagents and conditions: (o) KHMDS, 10, 18-crown-6,
ethylamine (DIPEA), CH2Cl2, 0 °C–r.t., 10 h, 96%; (l) K2CO3, DME, –78 to –10 °C, 12 h, 87%; (p) TBAF, THF, 0 °C–r.t., 10 h,
K3[Fe(CN)6], OsO4, tBuOH/H2O (1:1), r.t., 24 h, 84%; (m) H2, Pd/
C, THF, r.t., 2 h, 88%; (n) NaIO4, SiO2, CH2Cl2, r.t., 1 h, 97%.
91%; (q) NaH, THF, 0 °C–r.t., 4 h, 78%; (r) HCl (2 n), THF, r.t.,
12 h, 88%.
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D. K. Mohapatra, D. S. Reddy, N. A. Mallampudi, J. S. Yadav
FULL PAPER
Table 1. Selectivity in the intermolecular Nozaki–Hiyama–Kishi reaction.
[a] Isolated ratio of the mixture. [b] Determined by 1H and 13C NMR analysis of the crude mixture. [c] Determined by HPLC analysis of
the crude mixture. [d] Combined yield of the mixture.
onide groups was achieved in one-pot by employing 2 n efficient manner by utilizing De Brabander’s protocol for
HCl to afford paecilomycin E (1) in 88% yield. The struc- the macrolactonization, a Julia–Kocienski olefination, a
ture of synthetic paecilomycin E (1) was determined by Sharpless dihydroxylation, and a protecting group directed
comparing its spectral (1H and 13C NMR) and analytical intermolecular asymmetric Nozaki–Hiyama–Kishi (NHK)
data {[α]2D5 = –103.5 (c = 0.35, MeOH); ref.[9] [α]2D4 = –106.4 reaction as the key steps. The spectroscopic and analytical
(c = 0.28, MeOH)}, and these were in good agreement with data of synthetic paecilomycins E and F were in good
the values reported for the natural product.[9a,9c]
agreement with the revised stereochemical assignments of
To accomplish the synthesis paecilomycin F (2), com- the isolated compounds that were reported by Chen et al.
pound 23 was employed by following the same sequence of A considerable amount of 1 and 2 were prepared from the
reactions and conditions as reported in Schemes 3 and 4. commercially available starting materials d-mannitol and
Paecilomycin F (2) was furnished in good overall yield (see dioxinone 13. By following the same protocol, the syntheses
Scheme 5). The spectroscopic (1H and 13C NMR) and ana- of other related molecules are in progress and will be re-
lytical data {[α]D25 = –94.5 (c = 0.8, MeOH); ref.[9] [α]2D4
=
ported in due course.
–96.4 (c = 0.28, MeOH)} were in good agreement with the
values reported for the natural product.[9a,9c]
Experimental Section
General Methods: All reactions that were performed under argon
are noted. All employed glassware for the reactions were oven- and
flame-dried. Anhydrous solvents were distilled prior to use. THF
was distilled from Na and benzophenone. CH2Cl2 and DMF were
distilled from CaH2, and MeOH was distilled from a Mg cake.
Commercial reagents were used without purification. Column
chromatography was carried out by using silica gel (60–120 mesh),
unless otherwise mentioned. Analytical thin layer chromatography
was performed on silica gel 60 F254 precoated plates (250 μm
thickness). Optical rotations [α]D were measured on a polarimeter
and reported in degreescm2 g–1. Infrared spectra were recorded
with the sample dissolved in CHCl3, and the data are reported in
wavenumbers (cm–1). Mass spectrometry data were obtained by
Scheme 5. Synthesis of paecilomycin F (2).
Conclusions
In summary, the total syntheses of paecilomycins E (1)
and F (2) have been achieved in a highly convergent and using MS (EI of ESI) and HRMS mass spectrometers. The 1H
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Stereoselective Total Syntheses of Paecilomycins E and F
NMR spectroscopic data were recorded at 300, 400, 500 MHz, and
the 13C NMR spectroscopic data were recorded at 75 and
125 MHz, CDCl3 was used as the NMR solvent, unless otherwise
mentioned. The chemical shifts are reported in ppm downfield
from tetramethylsilane, and the coupling constants (J) are reported
in Hertz (Hz). The abbreviations used to designate the multiplicity
of the signals are s (singlet), d (doublet), t (triplet), q (quartet), m
(multiplet), and br. (broad).
7-Methoxy-2,2-dimethyl-5-[(1-phenyl-1H-tetrazol-5-ylsulfonyl)-
methyl]-4H-benzo[d][1,3]dioxin-4-one (10): m-CPBA (70% w/w,
2.9 g, 12.21 mmol) was added in small portions to a solution of
thioether 18 (1.5 g, 3.48 mmol) in CH2Cl2 (30 mL) at 0 °C, and the
reaction mixture was stirred at room temperature for 24 h. It was
then quenched with a saturated Na2SO3 solution (30 mL), and the
resulting mixture was extracted with CH2Cl2 (3 ϫ 20 mL). The
combined organic layers were washed with saturated NaHCO3
solution (75 mL) and dried with anhydrous Na2SO4, and the sol-
vent was removed under reduced pressure. The residue was purified
by chromatography on a silica gel column (ethyl acetate/hexane,
1:6) to afford compound 9 (1.4 g, 88%) as a light yellow solid; m.p.
7-Methoxy-2,2,5-trimethyl-4H-benzo[d][1,3]dioxin-4-one (16): Com-
pound 15 (3.5 g, 16.8 mmol) was dissolved in THF (40 mL), and
MeOH (1.0 mL, 25.25 mmol) was added followed by Ph3P (6.6 g,
25.25 mmol) at 0 °C. After the mixture was stirred at the same
temperature for 5 min, diisopropyl azodicarboxylate (4.9 mL,
25.25 mmol) was added dropwise, and the resulting mixture was
stirred at room temperature for an additional 4 h. The mixture was
concentrated in vacuo, and the residue was purified by chromatog-
raphy on a silica gel column (ethyl acetate/hexane, 1:20) to give 16
102–104 °C. IR (neat): ν
= 3074, 2999, 2926, 2854, 1720, 1613,
˜
max
1582, 1355, 1291, 1065, 761 cm–1. H NMR (500 MHz, CDCl3): δ
= 7.68–7.49 (m, 5 H), 6.80 (d, J = 2.5 Hz, 1 H), 6.45 (d, J = 2.5 Hz,
1 H), 5.63 (s, 2 H), 3.86 (s, 3 H), 1.68 (s, 6 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 164.8, 160.6, 159.2, 153.2, 132.9, 131.2,
130.1, 129.3, 125.6, 116.1, 106.0, 105.7, 102.7, 59.2, 55.8, 25.4 ppm.
HRMS (ESI): calcd. for C19H18O6N4SNa [M + Na]+ 453.0839;
found 453.0840.
1
(3.2 g, 87%) as a white solid; m.p. 147–149 °C. IR (neat): ν
=
˜
max
2927, 2852, 1730, 1614, 1559, 1454, 1205, 1160 cm–1. 1H NMR
(300 MHz, CDCl3): δ = 6.41 (d, J = 2.3 Hz, 1 H), 6.23 (d, J =
2.3 Hz, 1 H), 3.82 (s, 3 H), 2.63 (s, 3 H), 1.69 (s, 6 H) ppm. 13C
NMR (75 MHz, CDCl3): δ = 164.7, 160.4, 158.8, 145.3, 112.7,
104.9, 99.2, 98.1, 55.4, 25.6, 22.2 ppm. MS (ESI): m/z = 245 [M +
Na]+. HRMS (ESI): calcd. for C12H14O4Na [M + Na]+ 245.0784;
found 245.0803.
(2R,3S)-1-(tert-Butyldimethylsilyloxy)hex-5-ene-2,3-diol (20): To a
solution of 19 (10.0 g, 47.17 mmol) in MeOH (20 mL) was added
HCl (4 n, 20 mL), and the reaction mixture was stirred at 80 °C for
12 h. Upon completion (monitored by TLC), the reaction mixture
was quenched by the addition of aqueous NaHCO3 (100 mL), and
the MeOH was removed under reduced pressure. The residue was
extracted with ethyl acetate (3ϫ 150 mL), and the combined or-
ganic layers were washed with brine (2ϫ 150 mL) and dried with
anhydrous Na2SO4. The solvent was removed under reduced pres-
sure, and purification of the crude product by chromatography on
a silica gel column (MeOH/CHCl3, 1:19) furnished the desired triol
(5.6 g, 90%) as a viscous, colorless liquid, which was immediately
used in the next step. To a stirred stirred solution of the triol (4.5 g,
34.09 mmol) in CH2Cl2 (60 mL) were added imidazole (3.5 g,
51.1 mmol) and TBSCl (5.1 g, 34.09 mmol) at 0 °C, and the reac-
tion mixture was stirred at the same temperature for 30 min. Upon
completion (monitored by TLC), the reaction mixture was
quenched by the addition of water (50 mL), and the resulting solu-
tion was extracted with CH2Cl2 (3ϫ 50 mL). The combined or-
ganic layers were dried with anhydrous Na2SO4, and the solvent
was removed under reduced pressure. The crude mass was purified
by chromatography on a silica gel column (ethyl acetate/hexane,
2:5) to afford 20 (7.7 g, 92%) as a colorless liquid. [α]2D5 = +6.2 (c
5-(Bromomethyl)-7-methoxy-2,2-dimethyl-4H-benzo[d][1,3]dioxin-4-
one (17): To a solution of 16 (2.5 g, 11.26 mmol) in CCl4 (40 mL)
were added NBS (1.2 g, 6.75 mmol) and benzoyl peroxide (30 mg),
and the reaction mixture heated at reflux. After 3 h, an additional
portion of NBS (1.2 g, 6.75 mmol) and benzoyl peroxide (30 mg)
were added, and the resulting mixture was heated at reflux for an
additional 3 h. The reaction was cooled to room temperature, and
the solid succinimide was removed by filtration. The solvent was
removed under reduced pressure, and the resulting orange oil was
purified by flash chromatography on a silica gel column (ethyl acet-
ate/hexane, 1:19) to afford compound 17 (2.6 g, 79%) as a white
solid; m.p. 89–92 °C. IR (neat): ν
= 2992, 2920, 2850, 1728,
˜
max
1612, 1580, 1435, 1205, 1163 cm–1. 1H NMR (500 MHz, CDCl3):
δ = 6.69 (s, 1 H), 6.37 (s, 1 H), 4.96 (s, 2 H), 3.83 (s, 3 H), 1.68 (s,
6 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 164.9, 159.6, 159.2,
143.3, 113.5, 105.5, 101.4, 98.2, 55.8, 31.1, 25.5 ppm. HRMS (ESI):
calcd. for C12H14O4Br [M + H]+ 301.0070; found 301.0065.
= 13.8, CHCl ). IR (neat): ν
= 3450, 2927, 2856, 1636, 1465,
˜
3
max
1372, 1252 cm–1. H NMR (500 MHz, CDCl3): δ = 5.85 (m, 1 H),
5.19–5.08 (m, 2 H), 3.75 (m, 2 H), 3.81–3.65 (m, 3 H), 3.54 (m, 1
H), 2.79 (br. s, 1 H), 2.51 (br. s, 1 H), 2.37 (m, 1 H), 2.26 (m, 1 H),
0.89 (s, 9 H), 0.007 (s, 6 H) ppm. 13C NMR (75 MHz, CDCl3): δ
= 134.5, 117.9, 72.9, 71.7, 63.9, 37.7, 25.7, 18.1, –5.5, –5.54 ppm.
MS (ESI): m/z = 269 [M + Na]+. HRMS (ESI): calcd. for C12H26-
O3SiNa [M + Na]+ 269.1543; found 269.1566.
1
7-Methoxy-2,2-dimethyl-5-[(1-phenyl-1H-tetrazol-5-ylthio)methyl]-
4H-1,3-benzodioxin-4-one (18): To a solution of 1-phenyl-1H-
tetrazole-5-thiol (1.8 g, 10.0 mmol) in dry THF (30 mL) was added
Et3N (1.4 mL, 10.0 mmol), and the mixture was stirred at room
temperature. After 40 min, compound 17 (2.0 g, 6.6 mmol) was
added, and the reaction mixture was heated at reflux for 6 h and
then diluted with water (30 mL). The resulting mixture was ex-
tracted with ethyl acetate (3ϫ 20 mL). The combined organic lay-
ers were dried with anhydrous Na2SO4 and evaporated under re-
duced pressure to give the crude thioether, which was purified by
flash chromatography on a silica gel column (ethyl acetate/hexane,
1:7) to afford compound 18 (1.9 g, 90%) as a white solid; m.p. 144–
(4R,5S)-5-(Allyl-2,2-dimethyl-1,3-dioxolan-4-yl)methanol (21): To a
stirred solution of TBS ether 20 (7.0 g, 28.46 mmol) and 2,2-di-
methoxypropane (17.4 mL, 142.3 mmol) in CH2Cl2 (50 mL) was
added camphorsulfonic acid (0.66 g, 2.84) at 0 °C, and the resulting
solution was stirred at ambient temperature for 1 h. Upon comple-
tion (monitored by TLC), the reaction mixture was quenched by
146 °C. IR (neat): νmax = 3068, 3000, 2924, 2853, 1717, 1611, 1579,
˜
1499, 1386, 1289 cm–1. 1H NMR(500 MHz, CDCl3): δ = 7.59–7.45 the addition of aqueous NaHCO3 (40 mL), and the resulting mix-
(m, 5 H), 7.13 (d, J = 2.5 Hz, 1 H), 6.33 (d, J = 2.5 Hz, 1 H), 4.96
(s, 2 H), 3.87 (s, 3 H), 1.68 (s, 6 H) ppm. 13C NMR (75 MHz,
CDCl3): δ = 165.1, 160.6, 159.0, 154.8, 142.7, 133.5, 129.9, 129.7,
ture was extracted with CH2Cl2 (2ϫ 100 mL). The combined or-
ganic layers were washed with brine (100 mL), dried with anhy-
drous Na2SO4, and concentrated under reduced pressure. Purifica-
123.7, 113.5, 105.6, 103.6, 101.6, 55.8, 35.8, 25.5 ppm. HRMS tion of the crude product by chromatography on a silica gel column
(ESI): calcd. for C19H19O4N4S [M + H]+ 399.1121; found 399.1124.
(ethyl acetate/hexane, 1:20) furnished the desired acetonide com-
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D. K. Mohapatra, D. S. Reddy, N. A. Mallampudi, J. S. Yadav
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pound (7.8 g, 96%) as a colorless liquid, which was immediately
used in the next step. To a solution the acetonide (6.5 g,
22.73 mmol) in THF (80 mL) was added TBAF (1 m in THF,
34.1 mL, 34.1 mmol) at 0 °C. The resulting mixture was stirred at
room temperature for an additional 10 h. Upon completion (moni-
tored by TLC), the reaction mixture was quenched by the addition
of water (60 mL), and the resulting mixture was extracted with
ethyl acetate (3 ϫ 100 mL). The combined organic layers were
washed with brine (100 mL), dried with anhydrous Na2SO4, and
concentrated under reduced pressure to afford a yellowish liquid.
Purification of the crude product by chromatography on a silica
gel column (ethyl acetate/hexane, 1:4) furnished compound 21
(3.6 g, 93%) as a colorless liquid. [α]2D5 = +10.8 (c = 0.6, CHCl3).
4.32 mmol), and the resulting mixture was stirred at 0 °C for 30 min
under argon. Methoxymethyl chloride (0.25 mL, 3.25 mmol) in
CH2Cl2 (10 mL) was added at same temperature, and the resulting
mixture was stirred at room temperature for an additional 10 h.
Upon completion (monitored by TLC), the reaction mixture was
quenched by the addition of water (20 mL), and the mixture was
extracted with CH2Cl2 (3ϫ 30 mL). The combined organic layers
were dried with anhydrous Na2SO4, and the solvent was removed
under reduced pressure. The crude mass was purified by
chromatography on a silica gel column (ethyl acetate/hexane, 1:24)
to afford MOM ether 30 (429 mg, 96%) as a colorless oil. [α]2D5
–49.9 (c = 1.0, CHCl ). IR (neat): ν = 2929, 2857, 1724, 1643,
=
˜
3
max
1376, 1216 cm–1. H NMR (500 MHz, CDCl3): δ = 5.9 (m, 1 H),
1
IR (neat): ν
= 3446, 2929, 1725, 1606, 1572, 1377, 1278, 5.74 (m, 1 H), 5.41 (m, 1 H), 5.16–5.08 (m, 2 H), 4.75 (d, J =
˜
max
1159 cm–1. H NMR (500 MHz, CDCl3): δ = 5.82 (m, 1 H), 5.16– 6.7 Hz, 1 H), 4.49 (d, J = 6.7 Hz, 1 H), 4.24 (m, 1 H), 4.10–4.06
5.08 (m, 2 H), 4.24 (m, 1 H), 4.17 (q, J = 5.7 Hz, 1 H), 3.65–3.62 (m, 2 H), 3.88 (m, 1 H), 3.37 (s, 3 H), 2.53–2.35 (m 2 H), 2.30–
(t, J = 5.7 Hz, 2 H), 2.38 (m, 1 H), 2.28 (m, 1 H), 1.48 (s, 3 H), 2.18 (m, 2 H), 1.44 (s, 3 H), 1.33 (s, 3 H), 1.12 (d, J = 6.1 Hz, 3
1.37 (s, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 134.1, 117.2, H), 0.87 (s, 9 H), 0.04 (s, 6 H) ppm. 13C NMR (125 MHz, CDCl3):
1
108.1, 77.7, 76.1, 61.4, 33.5, 27.9, 25.3 ppm. MS (ESI): m/z = 195
δ = 135.3, 133.3, 116.7, 108.1, 93.3, 78.9, 77.2, 75.4, 68.2, 56.2,
[M + Na]+. HRMS (ESI): calcd. for C9H16O3Na [M + Na]+ 42.6, 34.1, 27.7, 25.8, 25.5, 23.2, 18.1, –4.5, –4.7 ppm. HRMS
195.0992; found 195.1002.
(ESI): calcd. for C22H42O5SiNa [M + Na]+ 437.2675; found
437.2693.
(1R,5S,E)-1-[(4R,5S)-5-Allyl-2,2-dimethyl-1,3-dioxolan-4-yl]-5-
(tert-butyldimethylsilyloxy)hex-2-en-1-ol (22): To a solution of pri-
mary alcohol 21 (2.5 g, 14.51 mmol) and solid anhydrous NaHCO3
(1.5 g, 18.1 mmol) in CH2Cl2 (30 mL) at 0 °C was added Dess–
Martin periodinane (9.2 g, 21.76 mmol). The resulting mixture was
stirred at the same temperature for 3 h. Upon completion (moni-
tored by TLC), the reaction mixture was filtered through a bed of
Celite, and the filtrate was washed with saturated NaHCO3 (2ϫ
20 mL). The organic layer was separated and extracted with
CH2Cl2 (2ϫ 50 mL). The combined organic layers were dried with
anhydrous Na2SO4 and concentrated under reduced pressure. Puri-
fication of the crude mass by flash chromatography on a silica gel
column (ethyl acetate/hexane, 1:10) afforded the corresponding al-
dehyde 12 (2.1 g, 88%) as a pale yellow liquid, which was immedi-
ately used in the next step. A mixture of anhydrous CrCl2 (28.9 g,
235.2 mmol) and NiCl2 (0.3 g, 2.352 mmol) was added to a mixture
of aldehyde 12 (2.0 g, 11.76 mmol) and vinyl iodide 11 (5.3 g,
16.46 mmol) in degassed DMF (30 mL + 2ϫ 10 mL rinse) at ambi-
ent temperature. The resulting mixture was stirred at ambient tem-
perature for 24 h and then quenched by the addition of saturated
3-{(4S,5S)-2,2-Dimethyl-5-[(5R,9S,E)-9,11,11,12,12-pentamethyl-
2,4,10-trioxa-11-silatridec-6-en-5-yl]-1,3-dioxolan-4-yl}propane-1,2-
diol (31): To a 100 mL round-bottomed flask were added tBuOH
(2.5 mL), water (2.5 mL), K3[Fe(CN)]6 (835 mg, 2.54 mmol),
K2CO3 (347 mg, 2.52 mmol), and OsO4 (7.6 mg, 0.03 mmol). The
reaction mixture was stirred at room temperature for approximately
15 min, and then compound 30 (350 mg, 0.85 mmol) was added at
0 °C. The reaction mixture was stirred at room temperature for an
additional 24 h. Upon completion (monitored by TLC), the reac-
tion mixture was quenched by the addition of a saturated aqueous
solution of sodium sulfite (10 mL) at room temperature. The re-
sulting solution was extracted with ethyl acetate (3ϫ 20 mL), and
the combined organic extracts were washed with brine (40 mL).
The solvent was removed under reduced pressure. The crude mass
was purified by chromatography on a silica gel column (ethyl acet-
ate/hexane, 2:3) to give diol 31 (319 mg, 84 %, 1:1 ratio of dia-
stereomers) as a colorless liquid. [α]2D5 = –32.3 (c = 1.5, CHCl3). IR
(neat): ν
= 3541, 3396, 2928, 2856, 1693, 1464, 1217 cm–1. 1H
˜
max
NMR (300 MHz, CDCl3): δ = 5.72 (m, 1 H), 5.36 (m, 1 H), 4.74
NH4Cl (100 mL) at 0 °C. The resulting solution was stirred at room (d, J = 6.8 Hz, 1 H), 4.51–4.39 (m, 2 H), 4.10–4.03 (m, 2 H), 3.99–
temperature for 15 min and then extracted with diethyl ether (3ϫ
100 mL). The organic layer was washed with a saturated solution
of NaCl (150 mL), dried with anhydrous Na2SO4, and concentrated
under reduced pressure. Purification of the residue by flash
chromatography on a silica gel column (ethyl acetate/hexanes, 1:15)
afforded the separated diastereomers 22 and 23 (3.5 g, 82% com-
bined yield; 22/23, 7:3) as a colorless liquid. Data for major isomer
3.83 (m, 2 H), 3.65 (m, 1 H), 3.55 (m, 1 H), 3.36 (d, J = 6.4 Hz, 3
H), 2.28–2.18 (m, 2 H), 1.95–1.75 (m, 2 H), 1.45 (s, 1.5 H), 1.41 (s,
1.5 H), 1.34 (s, 3 H), 1.11 (d, J = 6.0 Hz, 3 H), 0.87 (s, 9 H), 0.005
(s, 6 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 133.6, 133.5,
128.7, 128.6, 108.7. 107.9, 93.3, 78.9, 78.7, 77.4, 75.5, 75.4, 74.7,
71.8, 69.9, 68.1, 67.0, 66.5, 56.4, 56.3, 42.6, 42.5, 32.4, 32.3, 27.9,
27.8, 25.8, 25.7, 25.6, 23.2, 23.1, 18.1, –4.6, –4.7 ppm. HRMS
(ESI): calcd. for C22H44O7SiNa [M + Na]+ 471.2725; found
471.2748.
22: [α]2D5 = –7.1 (c = 2.2, CHCl ). IR (neat): ν
= 3469, 2926,
˜
3
max
2854, 1642, 1463, 1376, 1253 cm–1. 1H NMR (300 MHz, CDCl3):
δ = 5.98–5.60 (m, 3 H), 5.67 (m, 2 H), 4.29–4.16 (m, 2 H), 3.95 (m,
1 H), 3.86 (q, J = 5.8 Hz, 1 H), 2.52 (m, 1 H), 2.41 (m, 1 H), 2.26–
2.14 (m, 2 H), 1.66 (br. s, 1 H), 1.44 (s, 3 H), 1.33 (s, 3 H), 1.12 (d,
J = 6.0 Hz, 3 H), 0.87 (s, 9 H), 0.04 (s, 6 H) ppm. 13C NMR
(125 MHz, CDCl3): δ = 135.4, 132.2, 130.1, 116.8, 108.1, 79.9, 77.3,
70.8, 68.3, 42.5, 34.4, 27.9, 25.8, 25.5, 23.4, 18.3, –4.5, –4.7 ppm.
HRMS (ESI): calcd. for C20H38O4SiNa [M + Na]+ 393.2431; found
393.2443. See below for data of minor isomer 23.
3-{(4S,5R)-2,2-Dimethyl-5-[(5R,9S)-9,11,11,12,12-pentamethyl-
2,4,10-trioxa-11-silatridecan-5-yl]-1,3-dioxolan-4-yl}propane-1,2-
diol (32): Compound 31 (280 mg, 0.63 mmol) was dissolved in THF
(5 mL), and commercial Pd/C (10% w/w, 50 mg) was added in one
portion. The resulting suspension was stirred under H2 for 2 h until
the starting material was complete consumed (indicated by TLC).
The suspension was filtered through a pad of Celite, which was
washed with ethyl acetate (20 mL). The combined filtrates were
washed with brine (1ϫ 10 mL), dried with anhydrous Na2SO4, and
concentrated under reduced pressure. The crude product was puri-
fied by chromatography on a silica gel column (hexane/ethyl acet-
(5R,9S,E)-5-[(4S,5S)-5-Allyl-2,2-dimethyl-1,3-dioxolan-4-yl]-
9,11,11,12,12-pentamethyl-2,4,10-trioxa-11-silatridec-6-ene (30): To
a stirred solution of compound 22 (400 mg, 1.08 mmol) in CH2Cl2
(10 mL) was added N,N-diisopropylethylamine (0.76 mL,
ate, 3:2) to afford 32 (249 mg, 88%) as a colorless liquid. [α]2D5
=
5028
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© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2014, 5023–5032

Stereoselective Total Syntheses of Paecilomycins E and F
–12.4 (c = 2.7, CHCl ). IR (neat): ν = 3611, 3397, 2928, 2856, H), 1.62–1.45 (m, 7 H), 1.36 (s, 3 H), 1.21 (d, J = 6.0 Hz, 3 H) ppm.
˜
3
max
1693, 1513, 1462, 1219 cm–1. 1H NMR (500 MHz, CDCl3): δ =
13C NMR (125 MHz, CDCl3): δ = 164.7, 160.2, 158.6, 143.7, 131.3,
4.47–4.61 (m, 2 H), 4.40 (m, 1 H), 4.07 (m, 2 H), 3.93 (m, 1 H), 130.2, 108.2, 107.9, 104.9, 103.6, 100.3, 96.0, 77.8, 77.3, 75.9, 67.7,
3.78 (m, 1 H), 3.69–3.60 (m, 2 H), 3.51 (m, 1 H), 3.36 (s, 3 H), 56.1, 55.6, 39.2, 33.8, 30.8, 27.9, 25.6, 25.7, 23.4, 20.0 ppm. HRMS
1.82–1.61 (m, 4 H), 1.50–1.36 (m, 7 H), 1.32 (s, 3 H), 1.10 (d, J =
(ESI): calcd. for C27H40O9SiNa [M + Na]+ 531.2537; found
6.1 Hz, 3 H) 0.87 (s, 9 H), 0.03 (s, 6 H) ppm. 13C NMR (75 MHz, 531.2546.
CDCl3): δ = 107.6, 95.7, 77.8, 77.7, 77.3, 75.7, 75.6, 74.4, 71.7,
(3aR,4R,8S,17aS,E)-11-Hydroxy-13-methoxy-4-(methoxymethoxy)-
69.5, 68.5, 67.0, 66.3, 56.0, 39.9, 32.6, 32.4, 31.2, 27.9, 27.8, 25.8,
25.5, 23.8, 20.1, 20.0, 18.0, –4.5, –4.8 ppm. HRMS (ESI): calcd. for
C22H46O7SiNa [M + Na]+ 473.2880; found 473.2905.
2,2,8-trimethyl-5,6,7,8,17,17a-hexahydro-3aH-benzo[c][1,3]dioxolo-
[4,5-h][1]oxacyclotetradecin-10(4H)-one (34): To a suspension of
NaH [washed with hexane (2ϫ) to remove mineral oil and then
dried, 64 mg, 1.6 mmol] in dry THF (5 mL) was slowly added
alcohol 8 (0.1 g, 0.2 mmol) in THF (2 mL) at 0 °C under argon,
and the suspension was stirred at room temperature for 4 h. Upon
completion (monitored by TLC), the reaction mixture was
quenched by the addition of ice pieces at 0 °C. The organic layer
was separated, and the aqueous layer was extracted with ethyl acet-
ate (3 ϫ 5 mL). The combined organic layers were dried with anhy-
drous Na2SO4, and the solvent was removed under reduced pres-
sure. The crude mass was purified by chromatography on a silica
gel column (ethyl acetate/hexane, 1:10) to afford 34 (70 mg, 78%)
as a colorless semisolid. [α]2D5 = –61.5 (c = 0.6, CHCl3). IR (neat):
5-[(E)-3-{(4S,5R)-2,2-Dimethyl-5-[(5R,9S)-9,11,11,12,12-penta-
methyl-2,4,10-trioxa-11-silatridecan-5-yl]-1,3-dioxolan-4-yl}prop-1-
enyl]-7-methoxy-2,2-dimethyl-4H-benzo[d][1,3]dioxin-4-one (33): To
a solution of diol 32 (230 mg, 0.51 mmol) in CH2Cl2 (10 mL) was
added sodium periodate on a silica gel support (1.02 g). The re-
sulting mixture was stirred at room temperature for 1 h. Upon com-
pletion (monitored by TLC), the reaction mixure was filtered, and
the solvent was removed under reduced pressure. The residue was
purified by flash chromatography on a silica gel column (ethyl acet-
ate/hexane, 1:10) to afford aldehyde 9 (206 mg, 97%), which was
immediately used in the next step. To a stirred solution of 10
(232 mg, 0.54 mmol) and 18-crown-6 (142 mg, 0.54 mmol) in DME
(10 mL) was added KHMDS (0.5 m in toluene, 1.08 mL,
0.54 mmol) at –78 °C. After 20 min, a solution of 9 (150 mg,
0.36 mmol) in DME (6 mL) was added, and the mixture was stirred
at –78 °C for 1 h. The reaction was then gradually warmed to
–10 °C. After stirring overnight at –10 °C, the mixture was
quenched by the addition of saturated NH4Cl (10 mL), and the
resulting solution was extracted with ethyl acetate (3ϫ 15 mL). The
combined extracts were washed with brine (25 mL), dried with an-
hydrous Na2SO4, and concentrated in vacuo. The residue was puri-
fied by chromatography on a silica gel column (ethyl acetate/hex-
ane, 1:19) to give 33 (194 mg, 87%) as a colorless oil. [α]2D5 = –24.9
ν
max = 2982, 2933, 1647, 1608, 1574, 1445, 1376, 1357, 1319, 1257,
˜
1211, 1159, 1103 cm–1. H NMR (500 MHz, CDCl3): δ = 12.05 (s,
1 H), 7.09 (d, J = 15.0 Hz, 1 H), 6.43 (d, J = 2.6 Hz, 1 H), 6.40 (d,
J = 2.6 Hz, 1 H), 5.82 (m, 1 H), 5.35 (m, 1 H), 4.73 (d, J = 6.9 Hz,
1 H), 4.62 (d, J = 6.9 Hz, 1 H), 4.39 (m, 1 H), 4.17 (m, 1 H), 3.82
(s, 3 H), 3.76 (m, 1 H), 3.36 (s, 3 H), 2.98 (m, 1 H), 2.67 (m, 1 H),
2.01–1.85 (m, 3 H), 1.72–1.60 (m, 3 H), 1.50 (s, 3 H), 1.42 (d, J =
6.4 Hz, 3 H), 1.35 (s, 3 H) ppm. 13C NMR (125 MHz, CDCl3): δ
= 171.3, 165.4, 163.9, 142.7, 133.5, 123.7, 108.5, 106.9, 103.9, 100.2,
97.4, 80.2, 77.2, 76.7, 73.0, 55.7, 55.4, 35.4, 33.6, 31.5, 27.2, 24.7,
21.7, 19.3 ppm. HRMS (ESI): calcd. for C24H34O8Na [M + Na]+
473.2151; found 473.2151.
1
(c = 1.8, CHCl ). IR (neat): ν
= 3448, 2925, 2854, 1733, 1605,
˜
3
max
1574, 1277, 1158 cm–1. H NMR (300 MHz, CDCl3): δ = 7.54 (d,
J = 15.7 Hz, 1 H), 6.80 (d, J = 2.5 Hz, 1 H), 6.33 (d, J = 2.5 Hz,
1 H), 6.28 (m, 1 H), 4.72–4.65 (m, 2 H), 4.29 (m, 1 H), 4.11 (m, 1
H), 3.84 (s, 3 H), 3.82–3.70 (m, 2 H), 3.41 (s, 3 H), 2.71–2.43 (m,
2 H), 1.74–1.63 (m, 8 H), 1.51–1.30 (m, 10 H), 1.13 (d, J = 6.1 Hz,
3 H), 0.88 (s, 9 H), 0.04 (s, 6 H) ppm. 13C NMR (75 MHz, CDCl3):
δ = 164.7, 160.4, 158.6, 143.8, 131.5, 130.2, 108.3, 107.9, 104.9,
103.6, 100.3, 95.9, 77.9, 75.9, 68.5, 56.1, 55.6, 40.0, 33.9, 31.5, 29.7,
27.9, 25.9, 25.7, 25.6, 25.5, 23.8, 20.3, 18.1, –4.4, –4.7 ppm. HRMS
(ESI): calcd. for C33H54O9SiNa [M + Na]+ 645.3411; found
645.3429.
1
Paecilomycin E (1): A solution of compound 34 (40 mg, 0.09 mmol)
in THF (5 mL) was treated with HCl (2 n, 5 mL), and the resulting
mixture was stirred at room temperature for 15 h. Upon comple-
tion of the reaction (monitored by TLC), ethyl acetate (5 mL) and
H2O (5 mL) were added. The layers were separated, and the aque-
ous phase was extracted with ethyl acetate (2ϫ 5 mL). The com-
bined organic portions were washed with a saturated sodium
hydrogen carbonate solution (2ϫ 15 mL) and then a brine solution
(15 mL), dried with anhydrous Na2SO4, and concentrated under
reduced pressure. The residue was purified by chromatography on
a silica gel column (ethyl acetate/hexane, 2:3) to give paecilomy-
cin E (1, 28 mg, 88%) as a white solid; m.p. 167–169 °C. [α]2D5
=
5-[(E)-3-{(4S,5R)-5-[(1R,5S)-5-Hydroxy-1-(methoxymethoxy)-
hexyl]-2,2-dimethyl-1,3-dioxolan-4-yl}prop-1-enyl]-7-methoxy-2,2-di-
methyl-4H-benzo[d][1,3]dioxin-4-one (8): To a stirred solution of
solution of 33 (160 mg, 0.26 mmol) in dry THF (5.0 mL) was added
TBAF (1 m in THF, 0.39 mL, 0.39 mmol) at 0 °C. The resulting
mixture was stirred at room temperature for an additional 10 h and
then quenched by the addition of water (5 mL). The resulting mix-
ture was extracted with ethyl acetate (3ϫ 5 mL), and the combined
organic layers were washed with brine (10 mL), dried with anhy-
drous Na2SO4, and concentrated to afford a yellowish liquid. Puri-
fication of the crude residue by chromatography on a silica gel col-
umn (ethyl acetate/hexane, 2:3) furnished 8 (120 mg, 91%) as a col-
–103.5 (c = 0.35, MeOH). IR (neat): νmax = 3448, 2926, 1616, 1595,
˜
1508, 1367, 1264, 1153 cm–1. 1H NMR (500 MHz, CDCl3): δ =
12.02 (s, 1 H), 7.2 (dd, J = 15.3, 1.5 Hz, 1 H), 6.38 (s, 2 H), 5.76
(ddd, J = 15.4, 10.6, 3.2 Hz, 1 H), 5.02 (m, 1 H), 4.16 (m, 1 H),
3.94 (q, J = 6.4 Hz, 1 H), 3.79 (s, 3 H), 3.67 (br. d, J = 3.5 Hz, 1
H), 2.77 (dt, J = 14.9, 10.6 Hz, 1 H), 2.62 (m, 1 H), 1.85–1.72 (m,
4 H), 1.40 (d, J = 6.1 Hz, 3 H), 1.32–1.27 (m, 2 H) ppm. 13C NMR
(125 MHz, CDCl3): δ = 171.3, 165.6, 164.0, 142.9, 134.5, 128.3,
108.6, 103.9, 100.2, 75.8, 74.0, 71.5, 55.4, 38.9, 35.7, 33.6, 21.0,
20.4 ppm. HRMS (ESI): calcd. for C19H26O7Na [M + Na]+
389.1576; found 389.1564.
orless viscous liquid. [α]2D5 = –29.5 (c = 1.3, CHCl ). IR (neat): ν
(1S,5S,E)-1-[(4R,5S)-5-Allyl-2,2-dimethyl-1,3-dioxolan-4-yl]-5-(tert-
butyldimethylsilyloxy)hex-2-en-1-ol (23): The earlier procedure af-
forded 23 as the minor isomer. Rf = 0.5 (ethyl acetate/hexane, 1:19).
˜
3
max
= 3448, 3078, 2987, 2934 1643, 1447, 1376, 1219 cm–1. 1H NMR
(300 MHz, CDCl3): δ = 7.55 (d, J = 15.9 Hz, 1 H), 6.80 (d, J =
2.3 Hz, 1 H), 6.34 (d, J = 2.3 Hz, 1 H), 6.28 (m, 1 H), 4.74–4.66
[α]2D5 = –5.8 (c = 3.8, CHCl ). IR (neat): ν
= 3469, 2926, 2854,
˜
3
max
(m, 2 H), 4.32 (m, 1 H), 4.18–4.08 (m, 2 H), 3.88–3.83 (s, 3 H), 1642, 1463, 1376, 1253 cm–1. 1H NMR (500 MHz, CDCl3): δ =
3.78 (m, 1 H), 3.42 (s, 3 H), 2.68–2.46 (m, 2 H), 4.79–1.66 (m, 8
5.88–5.75 (m, 2 H), 5.48 (dd, J = 7.1, 15.4 Hz, 1 H), 5.14–5.07 (m,
5029
Eur. J. Org. Chem. 2014, 5023–5032
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org

D. K. Mohapatra, D. S. Reddy, N. A. Mallampudi, J. S. Yadav
FULL PAPER
2 H), 4.18 (m, 1 H), 4.11 (m, 1 H), 3.98 (t, J = 6.1 Hz, 1 H), 3.84
(q, J = 6.1 Hz, 1 H), 2.46–2.31 (m, 2 H), 2.22 (m, 1 H), 2.14 (m, 1
H), 1.50 (s, 3 H), 1.36 (s, 3 H), 1.11 (d, J = 6.1 Hz, 3 H), 0.87 (s,
9 H), 0.03 (s, 6 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 134.7,
131.4, 130.7, 117.1, 108.1, 80.1, 76.6, 70.5, 68.1, 42.6, 34.4, 27.7,
25.8, 25.2, 23.3, 18.01, –4.5, –4.8 ppm. HRMS (ESI): calcd. for
C20H38O4NSiNa [M + Na]+ 393.2431; found 393.2443.
3-{(4R,5R)-2,2-Dimethyl-5-[(5S,9R)-9,11,11,12,12-pentamethyl-
2,4,10-trioxa-11-silatridecan-5-yl]-1,3-dioxolan-4-yl}propane-1,2-
diol (32a): Compound 31a (250 mg, 0.56 mmol) was dissolved in
THF (5 mL), and commercial Pd/C (10% w/w, 45 mg) was added
in one portion. The resulting suspension was stirred under H2 for
2 h until the starting material was completely consumed (indicated
by TLC). The suspension was filtered through a pad of Celite,
which was washed with ethyl acetate (20 mL). The combined fil-
trates were washed with brine (1ϫ 10 mL), dried with anhydrous
Na2SO4, and concentrated under reduced pressure. The crude
product was purified by chromatography on a silica gel column
(hexane/ethyl acetate, 3:2) to afford product 32a (0.219 g, 87%) as
(5S,9S,E)-5-[(4S,5S)-5-Allyl-2,2-dimethyl-1,3-dioxolan-4-yl]-
9,11,11,12,12-pentamethyl-2,4,10-trioxa-11-silatridec-6-ene (30a):
To a stirred solution of compound 23 (380 mg, 1.03 mmol) in
CH2Cl2 (10 mL) was added N,N-diisopropylethylamine (0.72 mL,
4.108 mmol), and the resulting mixture was stirred at 0 °C for
30 min under argon. Methoxymethyl chloride (0.24 mL,
3.09 mmol) in CH2Cl2 (8 mL) was added at the same temperature,
and the resulting mixture was stirred at room temperature for an
additional 10 h. Upon completion (monitored by TLC), the reac-
tion mixture was quenched by the addition of water (20 mL), and
the resulting solution was extracted with CH2Cl2 (3ϫ 30 mL). The
combined organic layers were dried with anhydrous Na2SO4, and
the solvent was removed under reduced pressure. The crude mass
was purified by chromatography on a silica gel column (ethyl acet-
ate/hexane, 1:24) to afford MOM ether 30a (405 mg, 95%) as a
a colorless liquid. [α]2D5 = –52.4 (c = 1.9, CHCl ). IR: ν
= 3611,
˜
3
max
3397, 2928, 2856, 1693, 1513, 1462, 1219 cm–1 1H NMR
.
(300 MHz, CDCl3): δ = 4.86 (t, J = 6.80 Hz, 1 H), 4.64 (dd, J =
1.9 Hz, J = 6.8 Hz, 1 H), 4.29 (m, 1 H), 4.11 (m, 1 H), 3.96 (m, 1
H), 3.76 (m, 1 H), 3.68–3.57 (m, 2 H), 3.49 (m, 1 H), 3.39 (s, 3 H),
1.88–1.36 (m, 11 H), 1.34 (s, 3 H), 1.10 (d, J = 6.1 Hz, 3 H), 0.85
(s, 9 H), 0.03 (s, 6 H) ppm. 13C NMR (125 MHz, CDCl3): δ =
108.9, 108.5, 96.7, 96.6, 80.5, 74.9, 74.8, 73.7, 71.5, 69.2, 68.6, 68.5,
67.0, 66.4, 55.9, 55.8, 39.8, 32.7, 32.5, 32.1, 32.0, 28.3, 28.0, 25.9,
25.8, 25.7, 23.8, 21.6, 21.5, 18.1, –4.3, –4.7 ppm. HRMS (ESI):
calcd. for C22H46O7SiNa [M + Na]+ 473.2880; found 473.2905.
light yellow liquid. [α]2D5 = +7.1 (c = 0.6, CHCl ). IR: νmax = 2929,
˜
3
5-[(E)-3-{(4S,5R)-2,2-Dimethyl-5-[(5S,9S)-9,11,11,12,12-penta-
methyl-2,4,10-trioxa-11-silatridecan-5-yl]-1,3-dioxolan-4-yl}prop-1-
enyl]-7-methoxy-2,2-dimethyl-4H-benzo[d][1,3]dioxin-4-one (33a):
To a solution of diol 32a (160 mg, 0.36 mmol) in CH2Cl2 (10 mL)
was added sodium periodate on a silica gel support (0.72 g). The
resulting mixture was stirred at room temperature for 1 h. Upon
complection (monitored by TLC), the reaction mixture was filtered,
and the filtrate was removed under reduced pressure. The residue
was purified by flash chromatography on a silica gel column (ethyl
acetate/hexane, 1:10) to afford aldehyde 9a (146 mg. 97%), which
was used immediately in the next step. To a stirred solution of 10
(219 mg, 0.51 mmol) and 18-crown-6 (134 mg, 0.51 mmol) in DME
(10 mL) was added KHMDS (0.5 m in toluene, 1.02 mL,
0.51 mmol) at –78 °C. After 20 min, a solution of 9 (142 mg,
0.34 mmol) in DME (6 mL) was added, and the mixture was stirred
at –78 °C for 1 h. The reaction mixture was then gradually warmed
to –10 °C. After stirring overnight at –10 °C, the mixture was
quenched by the addition of saturated NH4Cl (10 mL), and the
resulting mixture was extracted with ethyl acetate (3ϫ 15 mL). The
combined extracts were washed with brine (25 mL), dried with an-
hydrous Na2SO4, and concentrated in vacuo. The residue was puri-
fied by chromatography on a silica gel column (ethyl acetate/hex-
ane, 1:19) to give 33a (0.179 g, 85%; inseparable mixture of E/Z,
9:1) as a colorless liquid, the isomers of which were separated in
the final step of the synthesis. [α]2D5 = –25.0 (c = 1.4, CHCl3). IR:
2857, 1724, 1643, 1376, 1216 cm–1. 1H NMR (500 MHz, CDCl3):
δ = 5.88–5.76 (m, 2 H), 5.36 (dd, J = 6.8, 15.4 Hz, 1 H), 5.10–5.05
(d, 2 H), 4.73 (m, J = 6.5 Hz, 1 H), 4.61 (m, J = 6.5 Hz, 1 H),
4.14–4.05 (m, 3 H), 3.86 (q, J = 6.1 Hz, 1 H), 3.39 (s, 3 H), 2.37–
2.22 (m, 3 H), 2.17 (m, 1 H), 1.47 (s, 3 H), 1.35 (s, 3 H), 1.10 (d, J
= 6.10 Hz, 3 H), 0.86 (s, 9 H), 0.03 (s, 6 H) ppm. 13C NMR
(125 MHz, CDCl3): δ = 134.9, 133.9, 127.7, 116.9, 108.4, 93.1, 79.7,
76.7, 74.5, 67.9, 55.4, 42.6, 34.6, 27.9, 25.9, 25.8, 23.2, 18.1, –4.5,
–4.8 ppm. HRMS (ESI): calcd. for C22H42O5NSiNa [M + Na]+
437.2675; found 437.2693.
3-{(4R,5S)-2,2-Dimethyl-5-[(5S,9R,E)-9,11,11,12,12-pentamethyl-
2,4,10-trioxa-11-silatridec-6-en-5-yl]-1,3-dioxolan-4-yl}propane-1,2-
diol (31a): To a 100 mL round-bottomed flask were added tBuOH
(2.5 mL), water (2.5 mL), K3[Fe(CN)]6 (809 mg, 2.46 mmol),
K2CO3 (339 mg, 2.52 mmol), and OsO4 (0.8 mg, 0.003 mmol). The
reaction mixture was stirred at room temperature for approximately
15 min, and then compound 30a (340 mg, 0.82 mmol) was added
at 0 °C. The reaction mixture was stirred at room temperature for
an additional 24 h. Upon completion (monitored by TLC), the re-
action mixture was quenched by the addition of a saturated aque-
ous solution of sodium sulfite (10 mL) at room temperature. The
resulting solution was extracted with ethyl acetate (3ϫ 15 mL), and
the combined organic extracts were washed with brine (30 mL).
The solvent was removed under reduced pressure to give the crude
mass, which was purified by chromatography on a silica gel column
(ethyl acetate/hexane, 2:3) to give diol 31a (0.312 g, 85%, 1:1 ratio
of diastereomers) as a colorless liquid. [α]2D5 = +6.4 (c = 1.5,
ν
= 2925, 2854, 1733, 1605, 1574, 1462, 1277, 1158 cm–1. 1H
˜
max
NMR (500 MHz, CDCl3): δ = 7.50 (d, J = 15.7 Hz, 1 H), 4.77 (s,
1 H), 6.32 (s, 1 H), 6.24 (m, 1 H), 4.89 (d, J = 6.8 Hz, 1 H), 4.68
(d, J = 6.8 Hz, 1 H), 4.17–4.09 (m, 2 H), 3.23 (s, 3 H), 3.76 (m, 1
H), 3.70 (m, 1 H), 3.41 (s, 3 H), 2.53 (m, 1 H), 2.36 (m, 1 H), 1.68
(s, 6 H), 1.64–1.55 (m, 2 H), 1.53–1.28 (m, 12 H), 1.10 (d, J =
6.1 Hz, 3 H), 0.86 (s, 9 H), 0.02 (s, 6 H) ppm. 13C NMR (75 MHz,
CDCl3): δ = 164.7, 164.5, 160.2, 158.9, 158.6, 143.6, 142.4, 130.7,
130.5, 130.3, 128.5, 123.1 108.5, 108.3, 105.2, 104.9, 103.5, 100.2,
99.7, 96.6, 96.5, 80.5, 80.2, 76.8, 75.3, 75.0, 68.6, 68.4, 55.8, 55.7,
55.5, 39.7, 39.6, 34.1, 32.2, 32.1, 28.2, 27.9, 25.9, 25.8, 25.5, 23.8,
21.7, 18.0, –4.4, –4.7 ppm. HRMS (ESI): calcd. for C33H54O9SiNa
[M + Na]+ 645.3411; found 645.3429.
CHCl ). IR: νmax = 3541, 3396, 2928, 2856, 1693, 1464, 1217 cm–1.
˜
3
1H NMR (300 MHz, CDCl3): δ = 5.81 (m, 1 H), 5.34 (m, 1 H),
4.72 (m, 1 H), 4.60 (m, 1 H), 4.36 (m, 1 H), 4.15 (t, J = 6.8 Hz, 1
H), 4.09 (q, J = 8.4 Hz, 1 H), 3.97–3.82 (m, 2 H), 3.63 (m, 1 H),
3.47 (m, 1 H), 3.38 (s, 3 H), 2.29–2.13 (m, 2 H), 1.85–1.60 (m, 2
H), 1.52 (s, 1.5 H), 1.46 (s, 1.5 H), 1.38 (m, 3 H), 1.10 (d, J =
6.1 Hz, 3 H), 0.87 (s, 9 H), 0.04 (s, 6 H) ppm. 13C NMR (125 MHz,
CDCl3): δ = 134.3, 134.1, 127.5, 127.4. 109.1, 108.5, 93.2, 93.1,
79.7, 79.6, 74.5, 74.2, 73.8, 71.7, 69.5, 68.0, 67.8, 66.9, 66.4, 55.5,
42.6, 42.5, 32.8, 32.6, 27.9, 27.8, 25.9, 25.83, 25.81, 25.7, 23.2, 23.1,
18.1, –4.5, –4.72, –4.75 ppm. HRMS (ESI): calcd. for C22H44O7Si
[M + Na]+ 471.2725; found 471.2748.
5-[(E)-3-{(4S,5R)-5-[(1S,5S)-5-Hydroxy-1-(methoxymethoxy)hexyl]-
2,2-dimethyl-1,3-dioxolan-4-yl}prop-1-enyl]-7-methoxy-2,2-di-
5030
www.eurjoc.org
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2014, 5023–5032

Stereoselective Total Syntheses of Paecilomycins E and F
methyl-4H-benzo[d][1,3]dioxin-4-one (8a): To a stirred solution of
–94.5 (c = 0.8, MeOH). IR: ν
= 3448, 2926, 1616, 1595, 1508,
˜
max
solution of 33a (100 mg, 0.16 mmol) in dry THF (5.0 mL) was 1367, 1264, 1153, 1087 cm–1. 1H NMR (500 MHz, CDCl3): δ =
added TBAF (1 m in THF, 0.24 mL, 0.24 mmol) at 0 °C. The re-
sulting mixture was stirred at room temperature for an additional
10 h and then quenched by the addition of water (5 mL). The mix-
ture was extracted with ethyl acetate (3ϫ 5 mL), and the combined
extracts were washed with brine (10 mL). The organic layer was
dried with anhydrous Na2SO4 and then concentrated to afford a
yellowish liquid. Purification of the crude mass by chromatography
on a silica gel column (ethyl acetate/hexane, 2:3) furnished 8a
(74 mg, 92%) as a light yellow liquid. [α]2D5 = –31.5 (c = 1.6,
12.29 (s, 1 H), 7.15 (d, J = 15.3 Hz, 1 H), 6.41 (s, 2 H), 5.69 (ddd,
J = 15.4, 11.4, 2.6 Hz, 1 H), 4.79 (m, 1 H), 4.19 (m, 2 H), 3.81 (s,
3 H), 3.54 (m, 1 H), 2.68 (m, 1 H), 2.49 (m, 1 H), 2.05–1.79 (m, 3
H) ppm. 13C NMR (125 MHz, CDCl3): δ = 171.4, 165.9, 164.0,
142.9, 134.2, 127.2, 109.0, 103.3, 100.2, 76.2, 73.7, 68.8, 66.9, 55.4,
38.7, 35.2, 30.9, 21.2, 20.9 ppm. HRMS (ESI): calcd. for
C19H26O7Na [M + Na]+ 389.1576; found 389.1571.
(5S,6R,E)-5-Allyl-6-(methoxymethoxy)-11,13,13,14,14-pentamethyl-
2,4,12-trioxa-13-silapentadec-8-en-7-ol (24): [α]2D5 = +25.6 (c = 1.3,
CHCl ). IR: ν
= 3448, 3078, 2987, 2934 1643, 1447, 1376,
˜
CHCl ). IR: ν
= 3457, 2953, 1739, 1641, 1442, 1218 cm–1. 1H
3
max
˜
3
max
1
1219 cm–1. H NMR (500 MHz, CDCl3): δ = 7.52 (d, J = 5.6 Hz,
1 H), 6.78 (d, J = 2.5 Hz, 1 H), 6.34 (s, J = 2.5 Hz, 1 H), 6.27 (m,
1 H), 4.91 (d, J = 6.8 Hz, 1 H), 4.74 (d, J = 6.8 Hz, 1 H), 4.19–
4.05 (m, 3 H), 3.84 (s, 3 H), 3.73 (m, 1 H), 3.42 (s, 3 H), 2.50 (m,
1 H), 2.41 (m, 1 H), 1.69 (s, 6 H), 1.56–1.22 (m, 14 H), 1.19 (d, J
= 6.1 Hz, 3 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 164.8,
164.5, 160.3, 158.9, 158.6 143.6, 142.4, 130.8, 130.4, 130.2, 128.4,
112.5, 108.6, 108.5, 108.3, 105.2, 104.9, 103.6, 100.3, 99.9, 96.8,
96.7, 80.7, 80.2, 77.2, 75.5, 75.3, 67.8, 55.9, 55.7, 55.6, 55.5, 38.98,
38.9, 34.2, 31.9, 31.8, 28.2, 27.9, 26.0, 25.8, 25.8, 25.7, 25.6, 25.5,
23.5, 23.3, 21.5, 21.421 ppm. HRMS (ESI): calcd. for C27H40O9-
SiNa [M + Na]+ 531.2537; found 531.2546.
NMR (500 MHz, CDCl3): δ = 5.87 (m, 1 H), 5.75 (m, 1 H), 5.61
(dd, J = 15.4, 6.7 Hz, 1 H), 5.13–5.06 (m, 2 H), 4.71–4.62 (m, 4
H), 4.26 (br. s, 1 H), 3.85 (q, J = 5.9 Hz, 1 H), 3.42 (s, 3 H), 3.38
(s, 3 H), 3.33 (br. d, J = 7.6 Hz, 1 H), 2.56 (m, 1 H), 2.39 (m, 1
H), 2.22 (m, 2 H), 1.12 (d, J = 5.9 Hz, 3 H), 0.87 (s, 9 H), 0.04 (s,
1 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 134.6, 134.5, 130.6,
130.3, 130.2, 130.1, 117.4, 117.3, 98.2, 98.1, 96.3, 96.2, 84.6, 83.4,
77.6, 77.1, 77.9, 71.8, 68.3, 56.1, 56.0, 55.9, 55.8, 42.7, 35.2, 35.1,
25.8, 23.3, 18.1, –4.5, –4.7 ppm. HRMS (ESI): calcd. for C21H42O6-
SiNa [M + Na]+ 441.2643; found 441.2679.
(4S,5R,10R,E)-4,5-Bis(benzyloxy)-10-(tert-butyldimethylsilyloxy)un-
deca-1,7-dien-6-ol (26): [α]2D5 = +5.5 (c = 2.0, CHCl ). IR: ν
=
˜
3
max
(3aR,4S,8S,17aS,E)-11-Hydroxy-13-methoxy-4-(methoxymethoxy)-
2,2,8-trimethyl-5,6,7,8,17,17a-hexahydro-3aH-benzo[c][1,3]dioxolo-
[4,5-h][1]oxacyclotetradecin-10(4H)-one (34a): To a suspension of
NaH [washed with hexane (2ϫ) to remove mineral oil and then
dried, 41 mg, 1.04 mmol] in dry THF (5 mL) was slowly added
alcohol 8a (0.066 g, 0.13 mmol) in THF (2 mL) at 0 °C under ar-
gon, and the suspension was stirred at room temperature for 4 h.
Upon completion (monitored by TLC), the reaction mixture was
quenched with ice pieces at 0 °C. The organic layer was separated,
and the aqueous layer extracted with ethyl acetate (3ϫ 5 mL). The
combined organic layers were dried with anhydrous Na2SO4, and
the solvent was removed under reduced pressure. The crude mass
was purified by chromatography on silica gel (ethyl acetate/hexane,
1:10) to afford product 34a (46 mg, 79%) as a colorless viscous
3470, 2929, 1729, 1452, 1250, 1217 cm–1 1H NMR (300 MHz,
.
CDCl3): δ = 7.39–7.27 (m, 10 H), 5.94 (m, 1 H), 5.75 (m, 1 H),
5.66 (dd, J = 15.5, 6.5 Hz, 1 H), 5.18–5.09 (m, 2 H), 4.75–4.47 (m,
4 H), 4.34 (t, J = 7.1 Hz, 1 H), 3.83 (m, 1 H), 3.67 (m, 1 H), 3.55
(t, J = 5.8 Hz, 1 H), 2.65–2.44 (m, 2 H), 2.26–2.11 (m, 2 H), 1.12
(d, J = 6.1 Hz, 3 H), 0.89 (s, 9 H), 0.05 (s, 6 H) ppm. 13C NMR
(125 MHz, CDCl3): δ = 138.3, 138.1, 137.9, 137.8, 134.8, 133.5,
131.5, 131.1, 129.9, 129.7, 128.9, 128.7, 128.4, 128.37, 128.33,
128.31, 128.17, 127.9, 127.8, 127.7, 127.6, 127.4, 126.1, 126.0,
117.3, 117.2, 83.2, 81.8, 79.7, 79.4, 73.8, 73.8, 73.7, 71.7, 71.5, 68.4,
68.3, 42.7, 42.4, 35.3, 34.7, 25.8, 23.4, 23.3, 18.1, –4.5, –4.7 ppm.
HRMS (ESI): calcd. for C31H46O4SiNa [M + Na]+ 533.3058; found
533.3087.
(5S,6R,11R,E)-5-Allyl-6-(tert-butyldimethylsilyloxy)-2,2,3,3,11,
13,13,14,14-nonamethyl-4,12-dioxa-3,13-disilapentadec-8-en-7-ol
liquid. [α]2D5 = –74.9 (c = 1.4, CHCl ). IR: νmax = 3417, 2925, 2853,
˜
3
1718, 1651, 1610, 1575, 1359, 1258 cm–1 1H NMR (500 MHz,
.
(28): [α]2D5 = +13.5 (c = 0.4, CHCl ). IR: ν
= 3445, 2893, 1730,
˜
3
max
CDCl3): δ = 12.13 (s, 1 H), 7.06 (d, J = 15.5 Hz, 1 H), 6.40 (s, 2
H), 5.80 (m, 1 H), 5.17 (m, 1 H), 4.84 (d, J = 6.9 Hz, 1 H), 4.74
(d, J = 6.9 Hz, 1 H), 4.25 (m, 1 H), 3.98 (t, J = 5.3 Hz, 1 H), 3.8
(s, 1 H), 3.72 (m, 1 H), 3.45 (s, 1 H), 2.81–2.60 (m, 2 H), 1.98–1.62
(m, 5 H), 1.51 (s, 3 H), 1.45–1.29 (m, 9 H) ppm. 13C NMR
(125 MHz, CDCl3): δ = 171.5, 170.4, 165.5, 164.2, 163.9, 143.1,
141.6, 133.9, 133.4, 129.7, 122.7, 109.3, 108.9, 107.9, 107.5, 103.8,
100.1, 99.9, 97.1, 95.8, 81.8, 80.2, 75.1, 74.6, 73.8, 73.7, 56.0, 55.9,
55.4, 33.5, 33.4, 32.8, 31.9, 31.2, 28.2, 27.0, 25.7, 25.6, 20.4, 20.3,
20.1, 19.8 ppm. HRMS (ESI): calcd. for C24H34O8Na [M + Na]+
473.2151; found 473.2151.
1647, 1362, 1219 cm–1. H NMR (300 MHz, CDCl3): δ = 5.81 (m,
1 H), 5.59–5.48 (m, 2 H), 4.99–4.92 (m, 2 H), 4.04 (m, 1 H), 3.87–
3.81 (m, 2 H), 3.71 (d, J = 5.0 Hz, 1 H), 2.25 (m, 1 H), 2.15 (m, 1
H), 1.11 (d, J = 6.1 Hz, 3 H), 0.95–0.85 (m, 27 H), 0.12–0.01 (m,
18 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 137.61, 131.9, 126.9,
115.6, 80.89, 75.3, 72.6, 68.3, 42.8, 37.9, 26.1, 25.9, 25.8, 23.1, 18.3,
18.2, 18.1, –4.2, –4.4, –4.5, –4.7, –4.8 ppm. HRMS (ESI): calcd. for
C29H62O4Si3Na [M + Na]+ 581.3848; found 581.3871.
1
(S)-(1S,5S,E)-1-[(4S,5S)-5-Allyl-2,2-dimethyl-1,3-dioxolan-4-yl]-5-
(tert-butyldimethylsilyloxy)hex-2-en-1-yl 3,3,3-Trifluoro-2-methoxy-
1
2-phenylpropanoate (23a): H NMR (300 MHz, CDCl3): δ = 7.61–
Paecilomycin F (2): A solution of compound 34a (0.27 mg,
0.055 mmol) in THF (5 mL) was treated with HCl (2 n, 4 mL), and
the mixture was stirred at room temperature for 15 h. Upon com-
pletion of the reaction (monitored by TLC), ethyl acetate (4 mL)
and H2O (4 mL) were added. The layers were separated, and the
aqueous phase was extracted with ethyl acetate (2ϫ 5 mL). The
combined organic portions were washed with a saturated sodium
hydrogen carbonate solution (2ϫ 15 mL) and then a brine solution
(15 mL), dried with anhydrous Na2SO4, and concentrated under
reduced pressure. The residue was purified by chromatography on
a silica gel column (ethyl acetate/hexane, 2:3) to give paecilo-
7.55 (m, 2 H), 7.40–7.33 (m, 3 H), 5.97–5.75 (m, 2 H), 5.50 (t, J =
7.9 Hz, 1 H), 5.38 (dd, J = 8.1, 15.4 Hz, 1 H), 5.16–5.08 (m, 2 H),
4.24 (m, 2 H), 3.81 (m, 1 H), 3.62 (s, 3 H), 2.44–2.01 (m, 4 H), 1.45
(s, 3 H), 1.33 (s, 3 H), 1.07 (d, J = 6.2 Hz, 3 H), 0.88 (s, 9 H), 0.04
(s, 3 H), 0.03 (s, 3 H) ppm.
(R)-(1S,5S,E)-1-[(4S,5S)-5-Allyl-2,2-dimethyl-1,3-dioxolan-4-yl]-5-
(tert-butyldimethylsilyloxy)hex-2-en-1-yl 3,3,3-Trifluoro-2-methoxy-
1
2-phenylpropanoate (23b): H NMR (500 MHz, CDCl3): δ = 7.58,
(d, J = 7.9 Hz, 2 H), 7.41–7.35 (m, 3 H), 6.01 (m, 1 H), 5.76 (m, 1
H), 5.59 (m, 2 H), 5.10–5.05 (m, 2 H), 4.17–4.09 (m, 2 H), 3.85 (q,
J = 6.1 Hz, 1 H), 3.54 (s, 1 H), 2.33–2.13 (m, 4 H), 1.41 (s, 3 H),
mycin F (2, 17 mg, 87%) as a white solid; m.p. 98–101 °C. [α]2D5
=
Eur. J. Org. Chem. 2014, 5023–5032
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5031

D. K. Mohapatra, D. S. Reddy, N. A. Mallampudi, J. S. Yadav
FULL PAPER
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H) ppm.
Supporting Information (see footnote on the first page of this arti-
cle): Experimental details and copies of the 1H and 13C NMR spec-
tra of new compounds.
Acknowledgments
[9]
The authors thank the Council of Scientific and Industrial Re-
search (CSIR), New Delhi, for financial support as part of the XII
Five Year Plan Programme under title ORIGIN (CSC-0108).
D. S. R. and N. A. M. thank the Council of Scientific and Indus-
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form of a research fellowship.
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Received: February 23, 2014
Published Online: July 11, 2014
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