Total Synthesis of the Proposed Structures of the Novel Antimalarial Pyranone Cryptorigidifoliol e

Article abstract of DOI:10.1055/s-0035-1562778

The total syntheses of the proposed structures of the antimalarial lactone cryptorigidifoliol E are described. The synthetic sequence notably features a Bartlett-Smith halocyclization to give a chiral epoxide, followed by its regioselective ring-opening r

Full text of DOI:10.1055/s-0035-1562778

SYNTHESIS
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
© Georg Thieme Verlag Stuttgart · New York
2016, 48, A–H
paper
A
G. Manikanta et al.
Paper
Synthesis
Total Synthesis of the Proposed Structures of the Novel Antimalarial
Pyranone Cryptorigidifoliol E
Gembali Manikanta
Tumula Nagaraju
CBS reduction
O
Palakodety Radha Krishna*
OH
13'
OH
O
Still–Gennari olefination
D-211, Discovery Laboratory, Organic and Biomolecular
Chemistry Division, CSIR–Indian Institute of Chemical
Technology, Hyderabad-500007, India
prkgenius@iict.res.in
6
2'
5
8
olefin cross-metathesis
Cryptorigidifoliol E
Received: 14.06.2016
Accepted after revision: 16.06.2016
Published online: 02.08.2016
epoxide ring cleavage of epoxide 9, which might in turn be
prepared from the known homoallylic alcohol 10.4 Because
the configuration of the C13′ stereogenic carbon had not
been assigned, we proposed to synthesize both epimers of
the target molecule. Accordingly, the pivotal enantiomeric
olefins 7a and 7b, the other olefinic partners, might be syn-
thesized from ynone 11, and the lone stereogenic center
might be generated by Corey–Bakshi–Shibata (CBS) reduc-
tion. Advantageously, both enantiomers might be obtain-
able merely by changing the catalyst. The silyl-protected
ynone 11 might be prepared from commercially available
octane-1,8-diol.
DOI: 10.1055/s-0035-1562778; Art ID: ss-2016-z0281-op
Abstract The total syntheses of the proposed structures of the anti-
malarial lactone cryptorigidifoliol E are described. The synthetic se-
quence notably features a Bartlett–Smith halocyclization to give a chiral
epoxide, followed by its regioselective ring-opening reaction, Still–
Gennari olefination, Corey–Bakshi–Shibata (CBS) ynone reduction, and
olefin cross-metathesis.
Key words total synthesis, cryptorigidifoliol E, lactones, Bartlett–
Smith halocyclization, Corey–Bakshi–Shibata reduction, cross-meta-
thesis
To begin our synthesis, we prepared the known optical-
ly active homoallylic alcohol 104 from commercially avail-
able propane-1,3-diol (Scheme 2). Next, alcohol 10 was
The δ-lactone moiety is a privileged scaffold, widely
distributed among natural products. In particular, pyra-
nones are extremely important because of their bioactivi-
ties, which include antifungal, antibacterial, antitumor, and
antimalarial activities.1 Five new antimalarial α,β-unsatu-
rated δ-lactones were recently isolated from the root wood
of Cryptocarya rigidifolia and were named cryptorigidifoli-
ols A–E (Figure 1).2 Inspired by the biological activity of
these compounds and by the synthetic challenges offered
by their structures, and because of our interest in this class
of natural products,3 we set out to synthesize cryptorigidi-
foliol E. As the absolute stereochemistry at C13′ had not
been determined, we attempted to synthesize both epimers
of the target molecule.
Our retrosynthetic analysis of compound 5 is shown in
Scheme 1. Compounds 5a and 5b might be obtained from
the two pairs of intermediates 6 and 7a (for 5a) and 6 and
7b (for 5b) by Grubbs catalyst assisted olefin cross-meta-
thesis. The key lactone fragment 6 might in turn be ob-
tained from enoate 8 by an acid-catalyzed one-pot aceton-
ide deprotection, followed by lactonization. Enoate 8 might
be prepared by Still–Gennari olefination and regioselective
O
O
OH
O
OH
O
12
14
Cryptorigidifoliol A
OH
1
Cryptorigidifoliol B
OH
2
O
O
O
O
7
7
7
5
Cryptorigidifoliol D
O
4
Cryptorigidifoliol C
3
2
3
OH
13'
OH 1O
4'
4
6
2'
5
1'
8
5
3'
Cryptorigidifoliol E
5
Figure 1 Structures of cryptorigidifoliols A–E
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–H

B
G. Manikanta et al.
Paper
Synthesis
O
O
OH
OH
OH
O
OH
O
+
5
8
5
8
7a: 7R
7b: 7S
6
5a: 13'R
5b: 13'S
O
O
O
5
OTBDPS
O
7
11
O
8
OH
OH
octane-1,8-diol
O
PMBO
PMBO
10
9
Scheme 1 Retrosynthetic analysis of cryptorigidifoliol E
treated with di-tert-butyl dicarbonate in the presence of
DMAP to give the homoallylic tert-butyl carbonate 12 in
90% yield. Bartlett–Smith halocyclization5 of carbonate 12
with N-iodosuccinimide (NIS) or iodine in MeCN at 0 °C, fol-
lowed by treatment of the crude mixture with K2CO3 in
methanol, delivered the epoxy alcohol 96 in 66% yield. All
the spectral data for this compound agreed with reference
data, but the optical rotation had the opposite sign. Conse-
quently, the stereochemistry of the epoxide-bearing carbon
was initially assigned as R, on the basis of chemical correla-
tion. Next, regioselective ring-opening of 9 with trimethyl-
sulfonium iodide and BuLi in THF at –10 °C to 0 °C gave the
corresponding diol 13 in 75% yield. The stereochemistry of
the newly created stereogenic center in 13 was assigned by
examination of the 13C NMR spectra of the acetonide 14, ob-
tained from 13 by treatment with 2,2-dimethoxypropane
in the presence of PPTS in CH2Cl2 at room temperature
(90% yield). The 13C NMR of 14 showed signals assigned to
the acetonide methyl group at δ = 19.8 and 30.1 ppm, in ac-
cordance with Rychnovsky’s model for a 1,3-syn relation-
ship between the acetonide-attached carbons.7 Thus the
relative stereochemistry of the newly created stereogenic
center was unequivocally assigned as syn to the existing
one, and its absolute stereochemistry was confirmed as R.
In the next stage, deprotection of the PMB group in 14
with DDQ in CH2Cl2/H2O (9:1) gave enol 15 in 87% yield.
Further oxidation of the resulting alcohol 15 with Dess–
Martin periodinane in CH2Cl2 at 0 °C gave the correspond-
ing aldehyde, which was directly subjected to a Still–
Gennari reaction8 with methyl [bis(2,2,2-trifluoroeth-
OH
OBoc
b
a
c
propane-1,3-diol
PMBO
PMBO
PMBO
10
12
O
O
OH
OH OH
(R)
O
f
d
e
PMBO
PMBO
(R)
9
14
13
O
O
OH
g
O
O
O
O
h
O
HO
O
15
8
6
Scheme 2 Reagents and conditions: (a) Ref. 3; (b) (Boc)2O, DMAP, CH2Cl2, r.t., 5 h, 90%; (c) NIS, MeCN, –40 to 0 °C, 20 h, then K2CO3, MeOH, 0 °C to r.t.,
2 h, 66 % (two steps); (d) TMSI, BuLi, THF, –20 °C, 75%; (e) Me2C(OMe)2, PPTS, 0 °C to r.t., 6 h, 90%; (f) DDQ, CH2Cl2/H2O (19:1), 0 °C to r.t., 1 h, 87%; (g)
Dess–Martin periodinane, anhyd CH2Cl2, 0 °C, then MeO2CCH2P(O)(OCH2CF3)2, NaH, THF, –78 °C, 1 h, 75% (two steps); (h) 3 N HCl, THF, r.t., 12 h, 79%.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–H

C
G. Manikanta et al.
Paper
Synthesis
oxy)phosphoryl]acetate in THF at –78 °C for one hour to af-
ford the chromatographically separable α,β-unsaturated es-
ter 8 as the major Z-isomer (Z/E = 92:8) in 75% yield. Subse-
quent acetonide deprotection and cyclization of ester 8
with 3 N HCl gave the required fragment 6 in 79% yield.
Next, we shifted our focus to the synthesis of the olefin
fragments 7a and 7b. Selective protection of octane-1,8-
diol by treatment with TBDPSCl and imidazole in CH2Cl2
gave the monoprotected derivative 16 in 80% yield. The pri-
mary alcohol group in compound 16 was oxidized under
Swern conditions to afford the corresponding aldehyde,
which upon Corey–Fuchs reaction9 with CBr4 and PPh3 in
CH2Cl2 at 0 °C gave a dibromo alkene; this was dehydrobro-
minated with BuLi at –78 °C to 0 °C to give the alkyne 17 in
68% yield over the three steps. Deprotonation of terminal
alkyne 17 with BuLi, followed by addition of heptanal, gave
the racemic propargylic alcohol 18 in 78% yield.
TBDPS ether group of 19a and 19b with TBAF gave the re-
quired diols 20a and 20b, respectively, in 80% yield. These
were subjected to hydrogenation independently in the
presence of palladium on charcoal to give the saturated di-
ols 21a and 21b (92% yield), respectively. Selective oxida-
tion of the primary alcohol of the chiral diols 21a and 21b
with TEMPO and [bis(acetoxy)iodo]benzene in CH2Cl2 gave
the intermediate aldehydes, which on further one-carbon
Wittig olefination with methylene(triphenyl)phosphorane
[prepared in situ by treating methyl(triphenyl)phosphoni-
um iodide with BuLi at –78 °C] gave the desired products 7a
and 7b, respectively, in 66% yield over two steps. The spec-
tral data of both the compounds were similar, except for the
20
sign of rotation. Whereas [α]D for 7a was –7.8 (c 0.23,
CHCl3), that of 7b was +9.0 (c 0.58, CHCl3).
Finally, having successfully prepared the required lac-
tone 6 and the olefin fragments 7a and 7b, we coupled lac-
The ynol 18 was oxidized with Dess–Martin perio-
dinane to afford the ynone 11 in 90% yield. Asymmetric re-
duction of the ynone by using the CBS reagent (R)-(–)-2-
Me-CBS-oxazaborolidine and BH3·Me2S gave the chiral
propargylic alcohol 19a in 90% yield and 96% ee [by chiral
HPLC: ChiralPak IA 250 × 4.6 mm, 2% i-PrOH–hexane (flow
rate: 1 mL/min), 205 nm; tR = 10.129 min (2.05%), 10.558
min (97.94%)].10 Similarly, reduction of ynone 11 with the
O
OH
OH
O
7a
5
8
5a
Grubbs II catalyst
anhyd CH2Cl2, r.t.
O
6
CBS
reagent
(S)-(+)-2-Me-CBS-oxazaborolidine
and
OH
OH
O
BH3·SMe2 gave the other isomer 19b in 87% yield and 98%
ee [by chiral HPLC: ChiralPak IA 250 × 4.6 mm, 2% i-PrOH–
hexane (flow rate: 1 mL/min), 205 nm, tR = 10.154 min
(99.32%), 10.583 min (0.68%)].10 Next, deprotection of the
5
8
7b
5b
Scheme 4
b
OH
a
TBDPSO
TBDPSO
17
11
16
18
OH
O
c
5
5
d
OTBDPS
OTBDPS
OTBDPS
OH
7
OH
10
f
5
5
e
OH
19a: 7R
19b: 7S
20a: 10R
20b: 10S
OH
10
OH
7
g
OH
5
5
7a: 7R
7b: 7S
21a: 10R
21b: 10S
Scheme 3 Reagents and conditions: (a) (ClCO)2, DMSO, Et3N, CH2Cl2, –78 °C, 1 h, then CBr4, PPh3, CH2Cl2, 0 °C, then BuLi, THF, –78 °C to –20 °C, 68%
(three steps); (b) heptanal, BuLi, THF, –78 °C to 0 °C, 78%; (c) Dess–Martin periodinane, anhyd CH2Cl2, 0 °C, 90%; (d) [(R)-methyloxazaborolidine CBS
catalyst for 19a]/[(S)-methyloxazaborolidine CBS catalyst for 19b], BH3·SMe2, THF, –30 °C, 2–3 h, 90% (87% for 19b); (e) TBAF, anhyd THF, 0 °C to r.t., 3
h, 80%; (f) H2, Pd/C, EtOAc, r.t., 92%; (g) TEMPO, PhI(OAc)2, anhyd CH2Cl2, r.t., 1 h; then MePPh3+Br–, BuLi, anhyd THF, –78 °C to r.t., 2 h, 66% (two steps).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–H

D
G. Manikanta et al.
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Synthesis
Table 1 1H and 13C NMR Dataa for the Natural Product and for the Synthetic Compounds 5a and 5b
Position
Natural Product
Synthetic product 5a
δ (13C)
Synthetic product 5b
δ (13C)
1H (J Hz)
1H (J Hz)
δ (13C)
1H (J Hz)
2
163.5
121.3
145.0
29.2
164.1
121.3
145.1
29.2
164.1
121.3
145.1
29.3
3
6.03 br d (9.8)
6.90 m
6.02 dt (1.6, 9.7)
6.89 m
6.03 dt (1.6, 9.7)
4
6.89 m
5
2.44 m
2.44–2.40 m
4.56 m
2.46–2.40 m
4.57 m
6
72.5
4.69 m
75.9
75.9
1′, 5′
43.8, 32.9
1.79 m, 1.73 m
2.03 m
41.9, 32.0
1.79 m, 2.07–1.99 m
2.12 m
41.9, 32.1
1.79 m, 2.08–1.99 m
2.12 m
2′
3′
63.3
4.63 m
69.7
4.37 q (6.8)
69.8
4.37 q (6.7)
131.4
5.49 dd (7.0, 15.3)
131.6
5.46 tdd (1.3, 7.3,
15.2)
131.6
5.46 tdd (1.3, 7.3,
15.4)
4′
132.6
5.68 m
133.6
5.72 m
133.7
5.73 m
6′–11′
15–16′
28.0, 29.6
29.6, 29.6
29.6, 29.6
29.6, 29.6
1.61–1.22 m
25.6, 25.6
28.9, 29.0
29.3, 29.4
29.4, 29.6
1.48–1.24 m
25.6, 25.6
29.0, 29.1
29.4, 29.5
29.5, 29.6
1.49–1.22 m
12′
13′
14′
17′
18′
19′
42.1
64.4
42.1
32.0
22.8
14.2
1.61–1.49 m
4.15 m
37.5
71.9
37.4
31.8
22.6
14.0
1.48–1.24 m
3.59 m
37.5
72.0
37.4
31.8
22.6
14.1
1.49–1.22 m
3.58 m
1.61–1.49 m
1.33–1.22 m
1.33–1.22 m
0.88 t (7.0)
1.8–1.24 m
1.8–1.24 m
1.8–1.24 m
0.88 t (6.8)
1.49–1.22 m
1.49–1.22 m
1.49–1.22 m
0.89 t (6.7)
a 1H NMR in CDCl3, 500 MHz; 13C NMR in CDCl3, 125 MHz.
20
tone 6 with the appropriate olefin fragment 7a or 7b by us-
ing Grubbs II catalyst11 to afford the target C-13′ epimers 5a
and 5b, respectively (Scheme4).
The specific rotation for synthetic 5a was [α]D –4.8 (c
0.28, MeOH) and that of 5b was [α]D20 –10.0 (c 0.13, MeOH),
20
compared with the reported value of [α]D –25.0 (c 0.4,
NMR analysis of the synthetic products 5a and 5b
showed some differences from the reported NMR data. In
particular, differences in the 1H NMR spectra were observed
with respect to the chemical shifts of the H-2′ and H-13′
MeOH) for the natural product. It is pertinent to mention
that the absolute stereochemistry of the two stereogenic
carbons C6-OH and C2′-OH, were unequivocally assigned
by Kingston et al.2 and confirmed by us in the current study.
However, because the configuration of the C13′ stereogenic
center was not assigned, we synthesized both intermedi-
ates (7a and 7b) by an unambiguous method and we ob-
tained the epimeric targets 5a and 5b; nevertheless, the
spectral data for the two synthetic compounds 5a and 5b
did not match the reported data for the natural compound.
In conclusion, we have completed a synthesis of the two
proposed structures of cryptorigidifoliol E: 5a and 5b. Note-
worthy steps included an NIS- or I2-assisted Bartlett–Smith
halocyclization, a stereoselective ring-opening reaction, a
Still–Gennari olefination, an acid-catalyzed one-pot depro-
tection–lactonization procedure, a CBS reduction, and, fi-
nally, an olefin cross-metathesis. The stereocontrolled syn-
thesis of 5a and 5b suggests that a revision of the structure
of natural cryptorigidifoliol E might be necessary.
1
protons (Table 1). The H NMR chemical shifts of H-2′ and
H-13′ of the natural product were reported to occur at δ =
4.43 and 4.15 ppm as multiplets, whereas those of H-2′ and
H-13′ of the synthetic 5a appeared as multiplets at δ = 4.37
and 3.59 ppm, respectively, and those of 5b appeared as
multiplets at δ = 4.37 and 3.58 ppm, respectively. Likewise,
significant differences were noted in the 13C chemical shifts
of the chiral carbon atoms C6, C2′, and C13′. The 13C chemi-
cal shifts of C6, C2′, and C13′ in the natural product oc-
curred at δ = 72.5, 63.3, and 64.4 ppm, respectively, where-
as the resonances of the same carbon atoms appeared at δ =
75.9, 69.7, and 71.9 ppm, respectively, for synthetic 5a and
at δ = 75.9, 69.8, and 72.0 ppm, respectively, for 5b. Addi-
tionally, the 13C chemical shifts for C12′ and C14′ also
showed different chemical shifts for the natural and syn-
thetic compounds.
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E
G. Manikanta et al.
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Synthesis
(3R,5R)-7-[(4-Methoxybenzyl)oxy]hept-1-ene-3,5-diol (13)
NMR spectra were recorded on Bruker Avance spectrometers with
CDCl3 as solvent. 1H NMR spectra were recorded at 300, 400, or 500
MHz, and 13C NMR spectra were recorded at 100 or 125 MHz, as spec-
ified. Reactions were carried out under N2 in anhydrous solvents. All
reactions were monitored by TLC on silica-coated plates that were vi-
sualized by exposure to UV radiation and/or by α-naphthol charring.
Organic solutions were dried (Na2SO4) and concentrated below 40 °C
under reduced pressure. All column chromatographic separations
were performed on silica gel (60–120 mesh) with EtOAc and hexane
as eluents. Yields refer to chromatographically and spectroscopically
(1H and 13C NMR) homogeneous materials. Air-sensitive reagents
were transferred by syringe and double-ended needle. Optical rota-
tions were measured on an Anton Paar MCP-200 polarimeter. High-
resolution mass spectra were recorded by using a Thermo Scientific
Orbitrap.
A 2.5 M soln of BuLi in THF (7.56 mL, 19.01 mmol) was added to a
stirred mixture of trimethylsulfonium iodide (3.88 g, 19.01 mmol) in
THF (25 mL) at –10 °C. The solution was stirred for 30 min, then a
solution of epoxide 9 (1.6 g, 6.34 mmol) in THF (10 mL) was added
and the mixture was stirred for 2 h at r.t. until the reaction was com-
plete. The reaction was cautiously quenched with sat. aq NH4Cl (5
mL), and the mixture was extracted with EtOAc (2 × 30 mL). The com-
bined organic extracts were washed with brine (30 mL), dried
(Na2SO4), and concentrated under reduced pressure. The crude prod-
uct was purified by column chromatography [silica gel, hexane–EtOAc
20
(1:1)] to a colorless liquid; yield: 1.26 g (75%); [α]D –12.7 (c 0.5,
CHCl3).
1H NMR (400 MHz, CDCl3): δ = 7.24 (d, J = 8.6 Hz, 2 H), 6.88 (d, J = 8.6
Hz, 2 H), 5.86 (ddd, J = 5.8, 10.5, 17.1 Hz, 1 H), 5.25 (dt, J = 1.3, 17.1 Hz,
1 H), 5.08 (dt, J = 1.3, 10.3 Hz, 1 H), 4.45 (s, 2 H), 4.37 (m, 1 H), 4.09 (s,
1 H), 3.80 (s, 3 H), 3.72–3.60 (m, 2 H), 1.85–1.56 (m, 4 H).
tert-Butyl (1S)-1-{2-[(4-Methoxybenzyl)oxy]ethyl}but-3-en-1-yl
Carbonate (12)
13C NMR (125 MHz, CDCl3): δ = 159.2, 140.6, 129.8, 129.3, 114.1,
Di-tert-butyl dicarbonate (5.83 g, 25.42 mmol), DMAP (0.77 g, 6.35
mmol), and Et3N (3.53 mL, 25.42 mmol) were added to a stirred solu-
tion of alcohol 10 (3.0 g, 12.71 mmol) in CH2Cl2 (30 mL) at 0 °C, and
the mixture was stirred at 0 °C to r.t. for 20 h. The mixture was then
diluted with 3% aq HCl (30 mL) and extracted with CH2Cl2 (3 × 30 mL).
The organic fractions were dried (Na2SO4), filtered, and concentrated,
and the crude product was purified by column chromatography [sili-
ca gel, hexane–EtOAc (9:1)] to give a colorless oil; yield: 3.84 g (90%);
[α]D20 +27.2 (c 1.5, CHCl3).
1H NMR (400 MHz, CDCl3): δ = 7.25 (d, J = 8.8 Hz, 2 H), 6.87 (d, J = 8.8
Hz, 2 H), 5.78 (m, 1 H), 5.14–5.04 (m, 2 H) 4.88 (quint, J = 6.2 Hz, 1 H),
4.41 (s, 2 H), 3.79 (s, 3 H), 3.53–3.46 (m, 2 H), 2.40–2.33 (m, 2 H), 1.88
(q, J = 6.4 Hz, 2 H), 1.47 (s, 9 H).
113.8, 73.1, 73.0, 72.0, 68.4, 55.2, 43.1, 36.8.
HRMS: m/z [M + Na]+ calcd for C15H22NaO4: 289.1412; found:
289.1410.
(4R,6R)-4-{2-[(4-Methoxybenzyl)oxy]ethyl}-2,2-dimethyl-6-vinyl-
1,3-dioxane (14)
2,2-Dimethoxypropane (1.05 mL, 8.64 mmol) and PPTS (0.217 g, 0.84
mmol) were added to a solution of diol 13 (1.15 g, 4.32 mmol) in an-
hyd CH2Cl2 (15 mL) at 0 °C, and the mixture was stirred at r.t. for 3 h.
The crude product was then mixed with CH2Cl2 (5 mL) and sat. aq
NaHCO3 (5 mL). The organic phase was separated, and the aqueous
phase was extracted with CH2Cl2 (2 × 25 mL). The combined organic
phases were dried (Na2SO4) and concentrated, and the residue was
purified by chromatography [silica gel, hexane–EtOAc (9:1)] to give a
colorless oil; yield: 1.18 g (90%); [α]D20 +12.6 (c 0.68, CHCl3).
1H NMR (400 MHz, CDCl3): δ = 7.25 (d, J = 8.5 Hz, 2 H), 6.87 (d, J = 8.5
Hz, 2 H), 5.81 (ddd, J = 5.8, 10.5, 16.5 Hz, 1 H), 5.24 (dt, J = 1.3, 17.2 Hz,
1 H), 5.11 (dt, J = 1.3, 10.5 Hz, 1 H), 4.42 (d, J = 1.7 Hz, 2 H), 4.34 (m, 1
H), 4.07 (m, 1 H), 3.80 (s, 3 H), 3.60–3.47 (m, 2 H), 1.84–1.65 (m, 2 H),
1.53 (dt, J = 2.5, 12.8 Hz, 1 H), 1.46 (s, 3 H), 1.41 (s, 3 H), 1.32 (m, 1 H).
13C NMR (100 MHz, CDCl3): δ = 159.0, 153.1, 133.3, 130.3, 129.2,
117.8, 113.6, 82.8, 73.8, 72.6, 66.1, 55.1, 38.8, 33.8, 27.7.
HRMS: m/z [M + NH4]+ calcd for C19H32NO5: 354.2279; found:
354.2275.
(2R)-4-[(4-Methoxybenzyl)oxy]-1-[(2R)-oxiran-2-yl]butan-2-ol (9)
NIS (4.66 g, 20.8 mmol) was slowly added to a solution of carbonate
12 (3.5 g, 10.41 mmol) in anhyd MeCN (30 mL) at –40 °C. The mixture
was then warmed to 0 °C and stirred for about 12h. When the reac-
tion was complete (TLC), it was quenched with sat. aq Na2S2O3 (20
mL). Sat. aq NaHCO3 (20 mL) was added, and the mixture was extract-
ed with Et2O (3 × 30 mL), dried (Na2SO4), and concentrated by evapo-
ration.
13C NMR (125 MHz, CDCl3): δ = 159.1, 138.7, 130.5, 129.2, 115.2,
113.7, 98.6, 72.6, 70.2, 65.7, 55.2, 36.7, 36.4, 30.1, 19.8.
HRMS: m/z [M + Na]+ calcd for C18H26NaO4: 329.1724; found:
329.1723.
2-[(4R,6R)-2,2-Dimethyl-6-vinyl-1,3-dioxan-4-yl]ethanol (15)
The residue was dissolved in MeOH (25 mL) and the solution was
cooled to 0 °C. K2CO3 (3.36 g, 24.74 mmol) was added and the mixture
was stirred at r.t. for 1 h. The solvent MeOH was removed under re-
duced pressure, and the crude residue was washed with H2O (3 × 20
mL) and extracted with EtOAc (2 × 50 mL). The organic layer was
dried (Na2SO4), concentrated, and purified by column chromatogra-
phy [silica gel, hexane–EtOAc (1:1)] to give a colorless oil; yield: 1.74
g (66%, two steps); [α]D20 –4.3 (c 1.0, CHCl3).
1H NMR (500 MHz, CDCl3): δ = 7.25 (d, J = 8.6 Hz, 2 H), 6.88 (d, J = 8.6
Hz, 2 H), 4.45 (s, 2 H), 4.05 (m, 1 H), 3.80 (s, 3 H), 3.70 (m, 1 H), 3.63
(m, 1 H), 3.24 (m, 1 H), 3.09 (m, 1 H), 2.77 (m, 1 H), 2.50 (dd, J = 2.7,
4.8 Hz, 1 H), 1.91–1.58 (m, 4 H).
DDQ (1.63 g, 7.18 mmol) was added to a solution of dioxane 14 (1.1 g,
3.59 mmol) in 19:1 H2O/CH2Cl2 (10 mL) at 0 °C, and the mixture was
stirred at r.t. for 1 h. When the reaction was complete, sat. aq NaHCO3
(25 mL) was added and the mixture was filtered. The filter was
washed with CH2Cl2 (3 × 30 mL), and the combined filtrates were
washed sequentially with H2O (10 mL) and brine (10 mL), dried
(Na2SO4), and evaporated under reduced pressure. The residue was
purified by column chromatography [silica gel, hexane–EtOAc (7:3)]
to give a colorless oil; yield: 0.58 g (87%); [α]D20 +15.5 (c 0.89, CHCl3).
1H NMR (400 MHz, CDCl3): δ = 5.82 (m, 1 H), 5.27 (dq, J = 1.3, 17.2 Hz,
2 H), 5.14 (m, 1 H), 4.39 (m, 1 H), 4.17 (m, 1 H), 3.83–3.73 (m, 2 H),
1.81–1.70 (m, 2 H), 1.55 (dt, J = 2.6, 12.9 Hz, 1 H), 1.51 (s, 3 H), 1.48–
1.38 (m, 4 H).
13C NMR (100 MHz, CDCl3): δ = 159.1, 129.8, 129.2, 113.7, 72.9, 69.4,
68.5, 55.2, 49.9, 46.5, 39.7, 36.2.
HRMS: m/z [M + Na]+ calcd for C14H20NaO4: 275.1255; found:
275.1253.
13C NMR (125 MHz, CDCl3): δ = 138.4, 115.4, 98.7, 70.3, 68.7, 60.5,
38.0, 36.4, 30.1, 19.7.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–H

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G. Manikanta et al.
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Synthesis
MS: m/z = 209 [M + Na]+.
tracted with CH2Cl2 (3 × 50 mL). The combined organic layers were
washed sequentially with H2O (20 mL) and brine (20 mL), dried
(Na2SO4), filtered, and concentrated in vacuo. The residue was puri-
fied by flash chromatography [silica gel, hexane–EtOAc (8:2)] to give a
colorless liquid.
Methyl (2Z)-4-[(4R,6R)-2,2-Dimethyl-6-vinyl-1,3-dioxan-4-yl]but-
2-enoate (8)
A solution of alcohol 15 (0.5 g, 2.68 mmol) in anhyd CH2Cl2 (10 mL)
was cooled to 0 °C, Dess–Martin periodinane (1.36 g, 3.2 mmol) was
added, and the mixture was stirred at r.t. for 2 h. The reaction was
then quenched with sat. aq Na2S2O3 and NaHCO3 (10 mL). The mixture
was diluted with CH2Cl2 (20 mL) and extracted with CH2Cl2 (2 × 20
mL). The extracts were washed sequentially with H2O (10 mL) and
brine (10 mL), dried (Na2SO4), and concentrated in vacuo to give the
corresponding aldehyde, which was used in the next step without
further characterization.
CBr4 (7.74 g, 23.38 mmol) was added to a solution of PPh3 (12.26 g,
46.79 mmol) in CH2Cl2 (60 mL) at 0 °C, and the mixture was stirred for
30 min. A solution of the aldehyde prepared above (4.47 g, 11.7
mmol) in CH2Cl2 (10 mL) was added, and the mixture was stirred for 1
h at 0 °C. Hexane (150 mL) was added to the mixture to precipitate a
solid. The mixture was filtered through a pad of silica and the sol-
vents were evaporated under reduced pressure to give the crude di-
bromoalkene, which was dissolved in THF. The solution was cooled to
–78 °C and a 2.5 M solution of BuLi in hexane (8.37 mL, 0.93 mmol)
was added dropwise. The mixture was allowed to warm to –20 °C and
stirred at –20 °C for 1 h. The reaction was then quenched by addition
of sat. aq NH4Cl (15 mL), and the mixture was warmed to r.t. The two
phases were separated, and the aqueous layer was extracted with
EtOAc (3 × 30 mL). The organic layers were combined, dried (Na2SO4),
filtered, and concentrated in vacuo. The residue was purified by col-
umn chromatography [silica gel, hexane–EtOAc (9:1)] to give a color-
less oil; yield: 3.32 g (68%, three steps).
Methyl [bis(2,2,2-trifluoroethoxy)phosphoryl]acetate (1.11 g, 3.49
mmol) was added to a stirred suspension of NaH (0.11 g, 4.58 mmol)
in anhyd THF (10 mL) at 0 °C, and the resulting solution was stirred
for 45 min at 0 °C then cooled to –78 °C. A solution of the aldehyde
(0.43 mg, 2.33 mmol) in anhyd THF (5 mL) was added dropwise over 5
min and the resulting mixture was stirred at –78 °C for 1 h. The reac-
tion was then quenched by adding NH4Cl (10 mL), and the mixture
was extracted with EtOAc (3 × 30 mL). The organic extracts were
washed with brine (10 mL), dried (Na2SO4), and concentrated under
reduced pressure. The crude material was purified by column chro-
matography [silica gel, hexane–EtOAc (9:1)] to give a colorless liquid;
yield: 0.42 g (75%); [α]D20 +32.9 (c 0.8, CHCl3).
1H NMR (500 MHz, CDCl3): δ = 7.69–7.64 (m, 4 H), 7.44–7.34 (m, 6 H),
3.65 (t, J = 6.4 Hz, 2 H), 2.17 (td, J = 2.5, 7.0 Hz, 2 H), 1.93 (t, J = 2.7 Hz,
1 H), 1.60–1.47 (m, 4 H), 1.41–1.23 (m, 6 H), 1.05 (s, 9 H).
13C NMR (100 MHz, CDCl3): δ = 135.5, 134.1, 129.4, 127.5, 84.7, 68.0,
63.9, 32.4, 28.8, 28.7, 28.4, 26.8, 25.6, 19.2, 18.3.
HRMS: m/z [M + H]+ calcd for C25H35OSi: 379.2457; found: 379.2462.
1H NMR (400 MHz, CDCl3): δ = 6.38 (dt, J = 7.9, 11.4 Hz, 1 H), 5.90–
5.77 (m, 2 H), 5.25 (dt, J = 1.3, 17.2 Hz, 1 H), 5.12 (dt, J = 1.3, 10.5 Hz, 1
H), 4.35 (m, 1 H), 4.01 (m, 1 H), 3.71 (s, 3 H), 2.94 (m, 1 H), 2.76 (m, 1
H), 1.57 (dt, J = 2.5 Hz, 1 H), 1.47 (s, 3 H), 1.43 (s, 3 H), 1.34 (m, 1 H).
13C NMR (125 MHz, CDCl3): δ = 166.6, 145.9, 138.5, 120.6, 115.4, 98.7,
16-{[tert-Butyl(diphenyl)silyl]oxy}hexadec-8-yn-7-ol (18)
70.0, 68.1, 51.0, 36.2, 35.4, 30.1, 19.7.
HRMS: m/z [M + Na]+ calcd for C13H20NaO4: 263.1254; found:
263.1253.
Alkyne 17 (3.2 g, 8.46 mmol) was dissolved in THF (25 mL), and the
solution was cooled to –78 °C. A 2.5 M solution of BuLi in hexane
(4.06 mL, 10.15 mmol) was added slowly and the mixture was stirred
for 30 min while the temperature was gradually increased to –10 °C.
Heptanal (1.17 g, 10.08 mmol) was added dropwise, and the mixture
was stirred for 1 h at r.t. The reaction was then quenched with sat. aq
NH4Cl (10 mL), and the mixture was extracted with EtOAc (3 × 30 mL).
The combined organic layers were washed with brine (20 mL), dried
(Na2SO4), and concentrated by rotary evaporation. The residue was
purified by chromatography [silica gel, hexane–EtOAc (9:1)] to give a
colorless liquid; yield: 3.24 g (78%).
(6R)-6-[(2R)-2-Hydroxybut-3-en-1-yl]-5,6-dihydro-2H-pyran-2-
one (6)
A stirred solution of enoate 8 (0.3 g, 1.25 mmol) in THF (5 mL) was
treated by dropwise addition of 3 M aq HCl (2 mL), and the solution
was stirred for 12 h at r.t. When the reaction was complete, the mix-
ture was carefully neutralized with sat. aq NaHCO3 (20 mL) at 0 °C
then extracted with EtOAc (3 × 30 mL). The organic extracts were
dried (Na2SO4), concentrated, and purified by column chromatogra-
phy [silica gel, hexane–EtOAc (1:1)] to give a colorless oil; yield: 0.165
g (79%); [α]D20 +96.7 (c 0.6, CHCl3).
The spectral data (1H and 13C NMR and HRMS) for 18 were identical to
those of 19a.
1H NMR (400 MHz, CDCl3): δ = 6.91 (m, 1 H), 6.02 (dt, J = 1.8, 9.9 Hz, 1
H), 5.89 (m, 1 H), 5.31 (dt, J = 1.3, 17.2 Hz, 1 H), 5.17 (dt, J = 1.2, 10.3
Hz, 1 H), 4.60 (m, 1 H), 4.42 (q, J = 6.3, 13.0 Hz, 1 H), 2.47–2.41 (m, 2
H), 2.12 (m, 1 H), 1.84 (dt, J = 5.3, 14.3 Hz, 1 H).
13C NMR (100 MHz, CDCl3): δ = 164.1, 145.2, 139.8, 121.1, 115.8, 75.8,
69.8, 41.1, 29.4.
16-{[tert-Butyl(diphenyl)silyl]oxy}hexadec-8-yn-7-one (11)
A solution of alcohol 18 (3.1 g, 6.3 mmol) in anhyd CH2Cl2 (30 mL)
was cooled to 0 °C, Dess–Martin periodinane was added (3.2 g, 7.54
mmol), and the mixture was stirred at r.t. for 2 h. The reaction was
then quenched with sat. aq Na2S2O3 and NaHCO3 (20 mL), and the
mixture was extracted with CH2Cl2 (3 × 50 mL). The organic phase
was washed with brine (20 mL), dried (Na2SO4), filtered, and concen-
trated. Purification of the crude product by column chromatography
[silica gel, hexane–EtOAc (9:1)] gave a colorless liquid; yield: 2.77 g
(90%).
HRMS: m/z [M + H]+ calcd for C9H13O3: 169.0861; found: 169.0859.
tert-Butyl(non-8-yn-1-yloxy)diphenylsilane (17)
DMSO (3.06 mL, 38.46 mmol) was added dropwise to a solution of ox-
alyl chloride (1.72 mL, 19.62 mmol) in CH2Cl2 (50 mL) at –78 °C under
N2. After 30 min, a solution of pyranone 16 (5.0 g, 13.08 mmol) in
CH2Cl2 was added dropwise. After 1 h, Et3N (10.92 mL, 78.51 mmol)
was added, and the mixture was allowed to warm to r.t. over 1 h. The
reaction was quenched with H2O (20 mL) and the mixture was ex-
1H NMR (300 MHz, CDCl3): δ = 7.70–7.64 (m, 4 H), 7.44–7.34 (m, 6 H),
3.69–3.64 (m, 2 H), 2.54–2.49 (m, 2 H), 2.34 (t, J = 7.1, Hz, 2 H), 1.70–
1.62 (m, 2 H), 1.60–1.51 (m, 4 H), 1.44–1.24 (m, 12 H), 1.05 (s, 9 H),
0.88 (t, J = 6.7 Hz, 3 H).
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G. Manikanta et al.
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Synthesis
13C NMR (100 MHz, CDCl3): δ = 188.4, 135.4, 134.0, 129.4, 127.5, 94.1,
80.8, 63.8, 45.5, 32.4, 31.4, 28.7, 28.7, 28.6, 27.6, 26.8, 25.5, 24.0, 22.4,
19.1, 18.8, 13.9.
(10R)-Hexadec-8-yne-1,10-diol (20b)
This was prepared by the same procedure as for 20a; yield: 0.43 g
20
(82%); [α]D –2.8 (c 0.2, CHCl3). Spectral data (1H and 13C NMR and
HRMS: m/z [M + H]+ calcd for C32H47O2Si: 491.3345; found: 491.3350.
MS) for 20b were identical to those of 20a.
(10R)-Hexadecane-1,10-diol (21a)
(7R)-16-{[tert-Butyl(diphenyl)silyl]oxy}hexadec-8-yn-7-ol (19a)
A solution of diol 20a (0.3 g, 1.18 mmol) in EtOAc (8 mL) was stirred
with 10% Pd/C (40 mg) under H2 (balloon) for 3 h at r.t. The mixture
was then filtered through Celite, which was washed with EtOAc (30
mL). The filtrate was evaporated in vacuo, and the residue was puri-
fied by column chromatography [silica gel, hexane–EtOAc (7:3)] to
give a white solid; yield: 0.28 g (92%); mp 64 °C; [α]D +6.8 (c 0.17,
CHCl3).
1H NMR (500 MHz, CDCl3): δ = 3.64 (t, J = 6.7 Hz, 2 H), 3.58 (m, 1 H),
1.62–1.53 (m, 4 H), 1.49–1.22 (m, 22 H), 0.89 (t, J = 6.8 Hz, 3 H).
A 1 M solution of (R)-CBS reagent in toluene (5.34 mL, 5.34 mmol)
was added to a stirred solution of ynone 11 (1.31 g, 2.65 mmol) in
anhyd THF (15 mL) at –30 °C. BH3·SMe2 (1.25 mL, 13.33 mmol) was
then added dropwise over 5 min, and the mixture was stirred for 1.5
h at –30 °C. The reaction was quenched by addition of MeOH (1 mL),
and the mixture was stirred for another 10 min then concentrated
under vacuum. The residue was purified by column chromatography
[silica gel, hexane–EtOAc (6:4)] to give a colorless oil; yield: 1.18 g
(90%, 96% ee); [α]D20 +1.6 (c 0.9, CHCl3).
20
13C NMR (125 MHz, CDCl3): δ = 72.0, 63.0, 37.5, 37.4, 32.7, 31.8, 29.6,
29.5, 29.3, 25.7, 25.6, 22.6, 14.0.
HPLC: Chiral Pak IA (250 × 4.6 mm), 2% i-PrOH–hexane (flow rate: 1
mL/min), 205 nm; tR = 10.129 min (2.05%), 10.558 min (97.94%).
1H NMR (500 MHz, CDCl3): δ = 7.69–7.64 (m, 4 H), 7.44–7.35 (m, 6 H),
4.34 (t, J = 5.7 Hz, 1 H), 3.65 (t, J = 6.5 Hz, 2 H), 2.19 (td, J = 1.9 Hz, 2 H),
1.72–1.60 (m, 2 H), 1.59–1.24 (m, 18 H), 1.05 (s, 9 H), 0.88 (t, J = 6.7
Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 135.4, 134.1, 129.4, 127.5, 85.4, 81.3,
63.9, 62.7, 38.2, 32.4, 31.7, 28.9, 28.8, 28.7, 28.6, 26.8, 25.6, 25.1, 22.5,
19.2, 18.6, 14.0.
MS: m/z = 281 [M + Na]+.
(S)-Hexadecane-1,10-diol (21b)
This was prepared by the same procedure as for 20a; yield: 0.27 g
20
(90%); [α]D –5.9 (c 0.3, CHCl3). The spectral data (1H and 13C NMR
and MS) and mp for 21b were identical to those of 21a.
MS: m/z = 515 [M + Na]+.
(7R)-Heptadec-16-en-7-ol (7a)
TEMPO (0.048 g, 0.307 mmol) and PhI(OAc)2 (0.74 g, 2.32 mmol) were
added to a solution of diol 21a (0.2 g, 0.775 mmol) in anhyd CH2Cl2 (3
mL), and the mixture was stirred for 1 h. The reaction was then
quenched with sat. aq Na2S2O3 (10 mL). The aqueous layer was sepa-
rated and extracted with CH2Cl2 (5 × 10 mL). The organic phases were
combined, dried (Na2SO4), and concentrated to give a crude product
that was used in the next step without purification.
(7S)-16-{[tert-Butyl(diphenyl)silyl]oxy}hexadec-8-yn-7-ol (19b)
A 1 M solution of (R)-CBS reagent in toluene (5.34 mL, 5.34 mmol)
was added to a stirred solution of ynone 11 (1.31 g, 2.65 mmol) in
anhyd THF (15 mL) at –30 °C. BH3·SMe2 (1.25 mL, 13.33 mmol) was
then added dropwise over 5 min, and the mixture was stirred for 1.5
h at –30 °C. The reaction was quenched by addition of MeOH (1 mL)
and the mixture was stirred for another 10 min, then concentrated
under vacuum. The residue was purified by column chromatography
[silica gel, hexane–EtOAc (6:4)] to give a colorless oil; yield: 1.14 g
(87%, 98% ee); [α]D20 –2.1 (c 0.17, CHCl3).
Methyltriphenylphosphonium bromide (0.62 g, 1.73 mmol) was dis-
solved in THF (8 mL) and the solution was cooled to –78 °C. A 2.5 M
solution of BuLi in hexane (0.68 mL, 1.71 mmol) was added dropwise
with stirring, and the solution was stirred for a further 30 min. A
solution of the crude aldehyde product (0.15 g, 0.58 mmol) in anhyd
THF (5 mL) was added, and the mixture was stirred for an additional 1
h. The reaction was then quenched with sat. aq NH4Cl (15 mL), and
the mixture was extracted with Et2O (3 × 20 mL). The combined or-
ganic extracts were washed sequentially with H2O (10 mL) and brine
(10 mL), dried (Na2SO4), and concentrated in vacuo. The crude prod-
uct was purified by column chromatography [silica gel, hexane–EtOAc
HPLC: Chiral Pak IA (250 × 4.6 mm), 2% i-PrOH–hexane (flow rate: 1
mL/min), 205 nm; tR = 10.154 min (99.32%), 10.583 min (0.68%).
Spectral data (1H and 13C NMR and MS) for 19b were identical to
those of 19a.
(10R)-Hexadec-8-yne-1,10-diol (20a)
To a stirred solution of ynol 19a (1.0 g, 2.03 mmol) in anhyd THF (10
mL) was treated with a 1.0 M solution of TBAF in THF (3.04 mL, 3.04
mmol) at 0 °C, and the mixture was stirred for 1 h at r.t. The solvent
was then evaporated under reduced pressure and the residue was pu-
rified by column chromatography [silica gel, hexane–EtOAc (7:3)] to
give a colorless liquid; yield: 0.412 g (80%); [α]D20 +1.7 (c 0.5, CHCl3).
1H NMR (500 MHz, CDCl3): δ = 4.34 (tt, J = 1.8, 6.5 Hz, 1 H), 3.64 (t, J =
6.7 Hz, 2 H), 2.20 (td, J = 1.9, 7.0 Hz, 2 H), 1.73–1.61 (m, 2 H), 1.61–
1.47 (m, 4 H), 1.47–1.25 (m, 14 H), 0.89 (t, J = 6.5 Hz, 3 H).
20
(9:1)] to give a colorless liquid; yield: 0.13 g (66%, two steps); [α]D
–7.8 (c 0.23, CHCl3).
1H NMR (400 MHz, CDCl3): δ = 5.81 (m, 1 H), 5.04–4.90 (m, 2 H), 3.58
(m, 1 H), 2.09–1.98 (m, 2 H), 1.53–1.24 (m, 24 H), 0.89 (t, J = 6.6 Hz, 3
H).
13C NMR (125 MHz, CDCl3): δ = 139.1, 114.0, 72.0, 37.4, 33.7, 31.8,
29.6, 29.5, 29.4, 29.3, 29.0, 28.9, 25.6, 25.6, 22.6, 14.0.
MS: m/z = 277 [M + Na]+.
13C NMR (100 MHz, CDCl3): δ = 85.2, 81.4, 62.8, 62.6, 38.1, 32.5, 31.7,
28.9, 28.7, 28.6, 28.4, 25.5, 25.1, 22.5, 18.5, 14.0.
(S)-Heptadec-16-en-7-ol (7b)
This was prepared by the same procedure as for 7a; yield: 0.13 g
(67%); [α]D20 +9.0 (c 0.58, CHCl3).
MS: m/z = 277 [M + Na]+.
The spectral data (1H and 13C NMR and MS) for 7b were identical to
those of 7a.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–H

H
G. Manikanta et al.
Paper
Synthesis
(6R)-6-[(2R,3E,13R)-2,13-Dihydroxynonadec-3-en-1-yl]-5,6-dihy-
dro-2H-pyran-2-one (5a)
Supporting Information
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0035-1562779.
Grubbs II catalyst (0.01 g, 0.011 mmol) was added to a stirred solution
of enol 7a (0.03 g, 0.118 mmol) and lactone 6 (0.04 g, 0.238 mmol) in
anhyd CH2Cl2 (2 mL), and mixture was stirred at r.t. for 5 h. When the
reaction was complete, the solvent was removed under reduced pres-
sure and the residue was purified by column chromatography [silica
gel, hexane–EtOAc (1:1)] to give a colorless liquid; yield: 0.027 g
(60%); [α]D20 –4.8 (c 0.28, MeOH).
1H NMR (500 MHz, CDCl3): δ = 6.89 (m, 1 H), 6.02 (dt, J = 1.6, 9.7 Hz, 1
H), 5.72 (m, 1 H), 5.46 (tdd, J = 1.3, 7.3, 15.2 Hz, 1 H), 4.56 (m, 1 H),
4.37 (q, J = 6.8 Hz, 1 H), 3.59 (m, 1 H), 2.44–2.40 (m, 2 H), 2.12 (m, 1
H), 2.07–1.99 (m, 2 H), 1.79 (m, 1 H), 1.48–1.24 (m, 24 H), 0.88 (t, J =
6.8 Hz, 3 H).
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References
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28.9, 25.6 (2 C), 22.6, 14.0.
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417.2975.
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(6R)-6-[(2R,3E,13S)-2,13-Dihydroxynonadec-3-en-1-yl]-5,6-dihy-
dro-2H-pyran-2-one (5b)
Prepared from 7b (0.028 g, 0.11 mmol) and lactone 6 (0.037 g, 0.22
mmol) by the same method as for 5a as a colorless liquid; yield: 0.024
g (58%); [α]D20 –10.0 (c 0.13, MeOH).
1H NMR (500 MHz, CDCl3): δ = 6.89 (m, 1 H), 6.03 (dt, J = 1.6, 9.7 Hz, 1
H), 5.73 (m, 1 H), 5.46 (tdd, J = 1.3, 7.3, 15.4 Hz, 1 H), 4.57 (m, 1 H),
4.37 (q, J = 6.7 Hz, 1 H), 3.58 (m, 1 H), 2.46–2.40 (m, 2 H), 2.12 (m, 1
H), 2.08–1.99 (m, 2 H), 1.79 (m, 1 H), 1.49–1.22 (m, 24 H), 0.89 (t, J =
6.7 Hz, 3 H).
13C NMR (125 MHz, CDCl3): δ = 164.1, 145.1, 133.7, 131.6, 121.3, 75.9,
72.0, 69.8, 41.9, 37.5, 37.4, 32.1, 31.8, 29.6, 29.5 (2 C), 29.4, 29.3, 29.1,
29.0, 25.6 (2 C), 22.6, 14.1.
HRMS: m/z [M + Na]+ calcd for C24H42NaO4: 417.2977; found:
417.2975.
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Acknowledgment
Two of the authors (G.M. and T.N.) thank the UGC and the CSIR, New
Delhi for financial support in the form of fellowships. The authors
thank the CSIR, India for financial support as part of the XII Five Year
Plan program under the title TREAT (BSC-0116).
(11) (a) Chatterjee, A. K.; Grubbs, R. H. Angew. Chem. Int. Ed. 2002,
41, 3171. (b) Trost, B. M.; Aponick, A. J. Am. Chem. Soc. 2006, 128,
3931. (c) Grubbs, R. H. Tetrahedron 2004, 60, 7117. (d) Radha
Krishna, P.; Dayaker, G. Tetrahedron Lett. 2007, 48, 7279.
(e) Radha Krishna, P.; Shiva Kumar, E. Tetrahedron Lett. 2009,
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© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–H