Stereoselective total synthesis of verbalactone

Article abstract of DOI:10.1007/s00706-014-1272-z

A simple and efficient route for the stereoselective total synthesis of verbalactone from commercially available inexpensive starting material d-mannitol using Barbier allylation, α-aminoxylation, and Yamaguchi macrolactonization as key steps is reported.

Full text of DOI:10.1007/s00706-014-1272-z

Monatsh Chem (2014) 145:2019–2024
DOI 10.1007/s00706-014-1272-z
ORIGINAL PAPER
Stereoselective total synthesis of verbalactone
Gurrala Alluraiah
Indraganti Sreenivasa Murthy
•
Reddymasu Sreenivasulu
•
•
Rudraraju Ramesh Raju
Received: 7 March 2014 / Accepted: 22 June 2014 / Published online: 4 September 2014
Ó Springer-Verlag Wien 2014
Abstract A simple and efficient route for the stereose-
lective total synthesis of verbalactone from commercially
available inexpensive starting material D-mannitol using
Barbier allylation, a-aminoxylation, and Yamaguchi mac-
rolactonization as key steps is reported.
The interesting biologically active nature and stereo-
chemical complexity of verbalactone attracted scientists
from worldwide toward the total synthesis of this lactone.
The first total synthesis of verbalactone was reported by
Barua and co-workers in 2004 using Barbier–Grignard and
Sharpless asymmetric dihydroxylation reactions as key
steps [7]. Further Sharma and Reddy reported another route
from L-malic acid [8]. Subsequently, Allais and Louvel
reported a different strategy for the synthesis of verbalac-
tone with commercially available hexanal as a starting
material using highly diastereo- and enantioselective al-
lylmetalations and Yamaguchi macrolactonization [9].
Meanwhile, several scientists reported with either chiral
pool starting material or stereoselective methods to install
stereogenic centers and consequent Yamaguchi macrol-
actonization to construct the lactone [10–14] (Fig. 1).
The reported synthetic routes to verbalactone mainly
associated with the long reaction sequences, lower yields,
and dependence on the chiral pool resources are some of
the disadvantages in the earlier reported methods. To
overcome the problems associated with the earlier
approaches, herein, we reported an alternative route for the
synthesis of verbalactone. In this context, we would like to
report an efficient and high-yielding enantioselective syn-
thesis of verbalactone employing an entirely different
approach. This strategy involves a concise divergent syn-
thesis of the target molecule 1 from inexpensive starting
material, i.e., D-mannitol, and subsequent Yamaguchi
macrolactonization to achieve the cyclic ring.
Keywords D-Mannitol Á Barbier allylation Á
a-Aminoxylation Á Yamaguchi macrolactonization Á
Verbalactone
Introduction
A 12-membered C symmetric dilactone, verbalactone (1),
2
is the first example for which a 1,7-dioxacyclododecane
moiety was reported as the ring system of a natural prod-
uct. Verbalactone (1) was isolated from the roots of
Verbascum undulatum Lam., a biennial plant of the genus
Verbascum that belongs to the family Scrophulariaceae by
Mitaku et al. [1], and exhibits antibacterial activity against
3
various Gram-positive (MIC 62.5 mg/cm ) and Gram-
3
negative bacteria (MIC 125 mg/cm ) [2]. The absolute
stereochemistry of verbalactone structure, 4R,6R,10R,12R,
were determined by spectroscopic methods, chemical cor-
relation and is similar to the NMR profile of (3R,5R)-
dihydroxydecanoic acid [3–6].
Electronic supplementary material The online version of this
article (doi:10.1007/s00706-014-1272-z) contains supplementary
material, which is available to authorized users.
G. Alluraiah Á R. Sreenivasulu Á I. Sreenivasa Murthy Á
R. Ramesh Raju (&)
Results and discussion
Department of Chemistry, Acharya Nagarjuna University,
Nagarjuna Nagar, Guntur 522510, Andhra Pradesh, India
e-mail: rrraju1@gmail.com
The retrosynthesis route for the synthesis of verbalactone is
outlined in Scheme 1. The target molecule 1 could be
123

2
020
G. Alluraiah et al.
synthesized through Yamaguchi’s macrolactonization of a
([97 % de). Selective mono-tosylation of diol 9 in the
presence of Bu SnO and Et N in CH Cl furnished 9a.
hydroxyl acid 2 which in turn could be obtained from ester
3
2
3
2
2
. The ester 3 could be prepared from the chiral aldehyde 4,
which in turn is derived from commercially available D-
mannitol.
Nucleophilic cyclization of the tosylate 9a in the presence
of K CO in MeOH afforded epoxide 10. Opening of
2
3
epoxide 10 with CuI and n-BuLi gave secondary alcohol 11
(72 %) and subsequent silylation of the secondary alcohol
11 with TBSCl and imidazole in CH Cl gave 12 in 70 %
The total synthesis of 1 was initiated with the known
chiral aldehyde 4 as illustrated in Scheme 2. Accordingly,
2
2
4
[15] on zinc-mediated Barbier allylation gave the allylic
yield. Silyl ether 12 was oxidized with RuCl /NaIO in
3 4
alcohol 5. Here anti selectivity in Barbier allylation can be
explained by the Felkin–Anh chelation model as shown in
Fig. 2. Due to chelation of ZnBr to the aldehyde carbonyl,
the nucleophile approaches from less-hindered side, thus
resulting in the formation of anti isomer predominantly.
The treatment of alcohol 5 with BnBr and sodium
hydride in dry THF at 25 to 30 °C for 6 h yielded 6, which
on hydrolysis with 70 % aq. acetic acid gave diol 7. Oxi-
dative cleavage of 7 followed by Wittig olefination of the
resultant aldehyde afforded the ester 3. The reduction of 3
with LAH in dichloromethane at -78 °C for 2 h gave
alcohol 8 (88 %). Oxidation of 8 under Swern condition
gave the corresponding aldehyde 8a. This aldehyde was
subjected to a-aminoxylation [16–18] catalyzed by L-pro-
CCl /MeCN/H O to furnish acid 13 in 72 % yield. Acid 13
4 2
was subjected to esterification under Yamaguchi reaction
conditions [19] to give lactone 14 in 77 % yield. Finally,
since deprotection of the benzyl groups in 14 has already
been reported in the literature [8], the synthesis of 14
formally constitutes the synthesis of verbalactone 1. The
1
13
optical rotation value, IR, mass, H and C NMR data of
the synthetic 14 were in good agreement with the data
reported by Sharma et al. [8].
Conclusion
In conclusion, a simple and efficient route for the stereo-
selective total synthesis of verbalactone (1) is reported
utilizing Barbier allylation, a-aminoxylation, and Yamag-
uchi macrolactonization as key steps.
line, followed by in situ reduction using NaBH to furnish
4
the required a-amino-substituted diol 8b. The reductive
hydrogenation of a-amino-substituted diol using 10 % Pd–
C in methanol afforded the chiral diol 9 in 72 % yield
Experimental
O
HO
H
H
All chemicals and solvents were purchased from Sigma–
Aldrich and Merck and used without further purification.
All reactions were monitored by thin-layer chromatogra-
phy (TLC) on silica Merck 60 F254 precoated aluminum
H
O
O
H
OH
O
1
13
plates. H and C NMR spectra were recorded with 500,
00, 150, and 75 MHz Bruker spectrometer. Chemical
Verbalactone (1)
3
Fig. 1 Structure of verbalactone (1)
shifts are reported in d units (ppm) with tetramethylsilane
Scheme 1
O
H
HO
H
H
COOH
O
O
H
OH OBn
OH
O
2
1
O
O
O
D-Mannitol
O
CHO
OBn
4
3
1
23

Synthesis of verbalactone
2021
Scheme 2
O
a
O
OH
O
c
d
O
HO
O
O
CHO
HO
OBn
OR
R = H
R = Bn
OBn
4
7
3
5
6
b
f(i)
OHC
f(ii)
e
f(iii)
HO
OBn
OBn
O
OBn
HN
Ph
8
8a
8
b
j
g
h
HO
OR OBn
OH OBn
O
OBn
0
9
11 R = H
1
i
12 R = TBS
k
l
COOH
COOH
TBSO
OBn
OH OBn
1
3
2
O
O
H
BnO
H
O
OBn
Ref [8]
H
HO
H
H
O
O
O
H
H
H
OH
O
O
1
1
4
3
2
equiv) in 100 cm THF at 0 °C followed by the addition
H
O
3
of 72 cm sat. NH Cl solution. After 6 h, the reaction
4
3
mixture was diluted with 50 cm sat. NH Cl solution and
O
4
Nu
3
extracted with ethyl acetate (2 9 100 cm ). The organic
H
3
3
layers were washed with water (2 9 50 cm ) and 50 cm
brine, dried over Na SO , concentrated under reduced
O
2
4
Zn
pressure and the residue was purified by column chroma-
tography (silica gel 60–120 mesh, 5 % EtOAc in pet. ether)
Br
to furnish 5 (17.5 g, 78 %) as a yellow liquid. [a] = ?1.7
D
Fig. 2 Barbier allylation by the Felkin–Anh chelation model
(
c = 2.5, CHCl3).
(
R)-2-((S)-1-(Benzyloxy)but-3-enyl)-1,4-dioxaspi-
(
TMS) as a reference. All coupling constants (J) are
ro[4.5]decane (6) [21]
NaH (2.41 g, 103.7 mmol, 2 equiv) was added to a cooled
reported in Hertz. Multiplicity is indicated as s (singlet), d
(
(
doublet), dd (double doublet), t (triplet), q (quartet), m
multiplet). FT-IR spectra were taken on IR spectropho-
3
(0 °C) solution of 11.0 g 5 (51.8 mmol, 1 equiv) in 50 cm
3
dry THF, stirred for 30 min, and treated with 6.9 cm BnBr
57.1 mmol, 1.1 equiv). After stirring at room temperature
tometer using NaCl optics. Mass spectra were performed
on direct inlet system or LC by MSD trap SL. Optical
rotation values are recorded on digital polarimeter at
(
3
for 6 h, the reaction mixture was quenched with 8 cm sat.
NH Cl solution and extracted with ethyl acetate
4
2
5 °C.
S)-1-((R)-1,4-Dioxaspiro[4.5]decan-2-yl)but-3-en-1-ol (5)
20]
3
2 9 40 cm ). The organic layers were washed with water
(
3
3
(
(2 9 10 cm ), 30 cm brine, dried (Na SO ), evaporated
2 4
[
under reduced pressure; the residue was purified by column
chromatography (silica gel 60-120 mesh, 3 % EtOAc in
pet. ether) to furnish 6 (12 g, 83 %) as a yellow liquid.
[a] = ?41.7 (c = 1.5, CHCl ).
3
Allyl bromide (10.7 cm , 126.30 mmol, 1.2 equiv) was
added over 15 min to a mixture of 18 g aldehyde 4
(
105.26 mmol, 1 equiv) and 13.7 g dry zinc (210.50 mmol,
D
3
123

2
022
G. Alluraiah et al.
(2R,3S)-3-(Benzyloxy)hex-5-ene-1,2-diol (7) [22]
A solution of 11.6 g 6 (38.41 mmol, 1 equiv) in 120 cm
EtOAc in pet. ether) gave 8 (4.04 g, 88 %) as a colorless
1
3
liquid. [a] = -30.6 (c = 1.07, CHCl3);
H NMR
D
7
1
0 % aq. acetic acid was stirred at room temperature for
2 h. After the completion of reaction, it was quenched
(CDCl , 300 MHz): d = 7.44–7.28 (m, 5H, –C H ),
3
6 5
5.79–5.67 (m, 1H, olefinic), 5.07–4.94 (m, 2H olefinic),
4.51 (d, 1H, J = 10.8 Hz, benzylic), 4.41 (d, 1H,
J = 10.8 Hz, benzylic), 3.76 (t, 2H, J = 5.8 Hz, –
with NaHCO and adjusted its pH to 2–3. The reaction
3
3
mixture was extracted with ethyl acetate (3 9 100 cm )
and dried over Na SO followed by the evaporation of
2
OCH ), 3.48–3.38 (m, 1H, –OCH), 2.32–2.11 (m, 2H,
3
4
solvent under reduced pressure. Further purification of the
residue was done by column chromatography (silica gel
allylic), 1.92 (br.s, 1H, –OH), 1.59–1.22 (m, 4H, 2 9 –
1
3
CH ) ppm; C NMR (75 MHz, CDCl ): d = 139.6, 133.9,
2
3
6
0–120 mesh, 40 % EtOAc in pet. ether) furnishing 7
6.2 g, 73 %) as a yellow liquid. [a] = ?41.9 (c = 1.0,
129.1, 128.8, 128.5, 116.3, 78.4, 72.2, 63.4, 36.2, 31.3,
-
1
(
28.4 ppm; IR: mꢀ = 3,363, 2,926, 2,856, 1,496, 1,443 cm
;
MS (ESI): m/z = 243 ([M ? Na] ), 221 ([M ? H] ).
D
?
?
CHCl3).
(
S,E)-Methyl 4-(benzyloxy)hepta-2,6-dienoate
3, C H O )
NaIO4 (8.6 g, 40.54 mmol, 1.5 equiv) was added to a
(
2S,4S)-4-(Benzyloxy)hept-6-ene-1,2-diol (9) [23]
3
Dry DMSO (2.7 cm , 36.36 mmol, 2 equiv) was added
(
1
5
18
3
3
dropwise to a solution of 2.2 cm oxalyl chloride
3
25.45 mmol, 1.5 equiv) in 15 cm dry CH Cl at
cooled (0 °C) solution of 6 g 7 (27.02 mmol, 1 equiv) in
6
(
2
2
3
0 cm CH Cl , followed by the addition of 4 cm sat.
3
2 2
-78 °C and stirred the reaction mixture for 20 min. Now
a solution of 4.0 g 8 (18.18 mmol, 1 equiv) in 15 cm dry
3
NaHCO and stirred at room temperature for 5 h. Further
3
the reaction mixture was dried over Na SO , filtered and
2
4
CH Cl was added to the above reaction mixture and
2
2
evaporated the solvent under reduced pressure gave the
corresponding aldehyde, which was used directly for the
next step.
stirred for 2 h at -78 °C. Then it was quenched with
3
2 cm Et N (90.90 mmol, 5 equiv) and diluted with
1
3
3
0 cm CH Cl . Further, the reaction mixture was washed
5
2
2
3
with 50 cm water, 50 cm brine, dried over Na SO
3
2
4
(
Methoxycarbonylmethylene)triphenylphosphorane
followed by solvent evaporation. The obtained residue was
purified by column chromatography (silica gel 60–120
mesh, 10 % EtOAc in pet. ether) to furnish the corre-
sponding aldehyde 8a as a yellow liquid.
(
13.5 g, 40.54 mmol, 1.5 equiv) was added to the above-
3
obtained aldehyde which was already dissolved in 80 cm
benzene and the reaction mixture was allowed for reflux.
After 2 h, solvent was evaporated and the residue was
purified by column chromatography (silica gel 60–120
mesh, 10 % EtOAc in pet. ether) furnishing 3 (6.04 g,
One portion of 0.42 g L-proline (3.63 mmol, 20 mol%,
0.2 equiv) was added to a stirred solution of 3.9 g aldehyde
9
1 %) as a yellow liquid. E isomer: [a] = ? 74.6
D
(18.12 mmol, 1 equiv) and 1.94 g nitrosobenzene
1
3
(
c = 1.0, CHCl ); H NMR (CDCl , 300 MHz): d = 7.36–
3
3
(18.12 mmol, 1 equiv) in 20 cm DMSO at 25 °C. After
24 h, the temperature was lowered to 0 °C, followed by
dilution with 30 cm anhydrous MeOH and the careful
7
.24 (m, 5H, –C H ), 6.59 (dd, 1H, J = 6.6, 15.8 Hz,
6 5
3
olefinic), 5.89 (d, 1H, J = 15.8 Hz, olefinic), 5.79–5.61
m, 1H, olefinic), 4.99–4.91 (m, 2H olefinic), 4.54 (s, 2H,
benzylic), 3.73 (s, 3H, –OCH ), 3.57–3.49 (m, 1H, –OCH),
(
addition of excess NaBH (1.45 g, 36.33 mmol, 2 equiv).
4
3
Now the reaction mixture was quenched after 10 min by
pouring the reaction mixture into a vigorously stirred
1
3
2
1
1
.48–2.31 (m, 2H, allylic) ppm;
C NMR (CDCl3,
50 MHz): d = 166.8, 147.1, 139.8, 134.1, 129.2, 128.9,
28.6, 119.2, 113.4, 82.3, 70.8, 52.2, 39.6 ppm; IR
biphasic solution of Et O and aqueous HCl (1 M). Then the
2
organic layer was separated and the aqueous phase was
3
extracted with EtOAc (3 9 30 cm ). Further, the combined
(
neat): mꢀ = 3,390, 2,902, 1,722, 1,612, 1,512, 1,448, 1,386,
-
1
?
,164, 1,037 cm ; MS (ESI): m/z = 247 ([M ? H] ).
1
organic phase was dried over anhydrous Na SO , concen-
2
4
trated, and purified by column chromatography over silica
gel using EtOAc/pet. ether (40:60) as eluent, which gave
the pure aminoxy alcohol 8b as a pure diastereomer. At this
time, 4.9 g aminoxy alcohol (14.98 mmol, 1 equiv) was
(
R)-4-(Benzyloxy)hept-6-en-1-ol (8, C H O )
14 20 2
3
DIBAL-H (30.0 cm , 42.27 mmol, 20 mol% in toluene, 2
equiv) was added to a stirred solution of 5.2 g ester 3
3
(
21.13 mmol, 1 equiv) in 30 cm dry CH Cl at -78 °C
2
2
3
dissolved in 30 cm EtOAc and 0.25 g 10 % Pd/C was
and the reaction mixture was stirred at the same temper-
added to this solution. Now the reaction mixture was
allowed for stirring at 1 bar hydrogen pressure for 12 h.
After completion of the reaction (monitored by TLC), it
was filtered through Celite pad. Further, the filtrate was
dried over Na SO , concentrated, and the residue was
ature for 2 h. Further the reaction mixture was quenched
3
with few drops of MeOH and 5 cm aq. sodium potassium
tartrate, and filtered through Celite. It was dried over
Na SO followed by the evaporation of solvent under
2
4
2
4
reduced pressure. Finally, the residue was purified by
column chromatography (silica gel 60–120 mesh, 30 %
purified by column chromatography using 40 % EtOAc in
1
23

Synthesis of verbalactone
2023
pet. ether as eluent to give the pure diol 9 (2.9 g, 69 %) as a
2
(neat): mꢀ = 3,351, 3,052, 2,931, 2,855, 1,732, 1,611, 1,509,
1,461, 1,247, 1,106, 1,036, 823, 701 cm ; MS (ESI): m/
5
-1
yellow liquid. [a] = ?6.8 (c = 0.5, CHCl3).
D
?
z = 299 ([M ? Na] ).
(S)-2-((S)-2-(Benzyloxy)pent-4-enyl)oxirane (10) [23]
p-TsCl (2.2 g, 11.86 mmol, 1 equiv) was added portion
((4S,6R)-4-(Benzyloxy)undec-1-en-6-yloxy)(tert.-butyl)-
wise at 0 °C to a cooled (0 °C) stirred solution of 2.8 g diol
dimethylsilane (12, C24H O Si)
42 2
3
(11.86 mmol, 1 equiv), DMAP (cat.), and 3.3 cm Et N
9
The stirred solution of alcohol 1.5 g 11 (5.43 mmol, 1
equiv) and 1.1 g imidazole (16.30 mmol, 3 equiv) in
3
3
23.72 mmol, 2 equiv) in 20 cm CH Cl and the reaction
(
2
2
3
20 cm dry CH
mixture was stirred at room temperature for 14 h. Work-up
as described for 15 and purification by column chroma-
tography (silica gel 60–120 mesh, 10 % EtOAc in pet.
ether) gave mono-tosylate 9a (4.2 g, 88 %) as a yellow
syrup.
2
Cl
2
was treated with 0.91 g TBSCl
(5.93 mmol, 1.1 equiv) at 0 °C under nitrogen atmosphere
and stirred at room temperature for 4 h. The reaction
3
mixture was quenched with 10 cm aq. NH
Cl solution and
4
3
extracted with CH Cl (2 9 50 cm ). The combined
2 2
3
3
extracts were washed with 30 cm water, 30 cm brine,
dried over Na SO , and concentrated. The residue was
A solution of 4.2 g of the above crude tosylate 9a
3
11.5 mmol, 1 equiv) in 25 cm MeOH was treated with
2
4
(
purified by column chromatography (silica gel 60–120
4
.0 g K CO (28.84 mmol, 2.5 equiv) and stirred at room
2 3
mesh, 5 % EtOAc in pet. ether) to furnish 12 (2.0 g, 91 %)
1
temperature for 1 h. After, the reaction mixture was treated
3
with 10 cm aq. NH Cl solution and MeOH was evapo-
as a colorless liquid. [a] = ?57.4 (c = 0.76, CHCl ); H
D
3
4
NMR (CDCl , 300 MHz): d = 7.34–7.22 (m, 5H, –C H ),
3
6 5
rated below 40 °C under reduced pressure. Further the
residue was extracted with ether (3 9 25 cm ) and com-
5.82–5.69 (m, 1H, olefinic), 5.08–4.97 (m, 2H olefinic),
4.61 (q, 2H, J = 11.1 Hz, benzylic), 3.61 (m, 1H, –OCH),
3.49 (p, 1H, J = 6.1, 9.2 Hz, –OCH), 2.39–2.12 (m, 2H,
3
3
bined organic layers were washed with 25 cm water,
3
5 cm brine, dried over Na SO followed by evaporation.
2
2
4
allylic), 1.56 (t, 2H, J = 8.1 Hz, –CH ), 1.40–1.11 (m, 8H,
2
Finally, the residue was purified by column chromatogra-
4
9 –CH ), 1.02 (s, 9H, t-butyl), 0.91 (t, 3H, J = 7.5 Hz, –
2
phy (silica gel 60–120 mesh, 10 % EtOAc in pet. ether) to
2
1
3
CH ), 0.21 (s, 6H, 2 9 –CH ) ppm; C NMR (75 MHz,
5
3
3
afford 10 (1.7 g, 68 %) as a colorless liquid. [a]D = ?23.1
CDCl ): d = 138.6, 136.8, 128.8, 128.5, 128.3, 116.4,
3
(
c = 3.1, CHCl3).
76.9, 74.2, 73.1, 44.6, 38.3, 34.3, 26.8, 26.1, 23.2, 19.1,
1
3.8, -4.9 ppm; IR (neat): mꢀ = 2,959, 2,854, 1,477, 1,368,
(
4S,6R)-4-(Benzyloxy)undec-1-en-6-ol (11, C H O )
1
8
28
2
-1
1,264, 1,128, 1,049, 996 cm ; MS (ESI): m/z = 413
3
n-Butyllithium (14 cm , 29.35 mmol, 2 M solution in n-
?
[M ? Na] ), 391 ([M ? H] ).
?
(
hexane, 4 equiv) was added at -20 °C to a stirred mixture
of 2.7 g copper(I) iodide (14.67 mmol, 2 equiv) in 20 cm
3
(3R,5R)-3-(Benzyloxy)-5-(tert.-butyldimethylsilyloxy)-
dry ether and stirred for 0.5 h. A solution of 1.6 g 10
(
decanoic acid (13, C H O Si)
2
3 40 4
3
7.33 mmol, 1 equiv) in 10 cm dry ether was added to the
NaIO4 (3.95 g, 18.46 mmol, 4 equiv) was added to a
above mixture and stirred for 1 h. The reaction mixture was
3
quenched with 10 cm aq. NH Cl solution and allowed to
solution of 1.8 g olefin 12 (4.61 mmol, 1 equiv) in a
3
3
3
4
mixture of 6 cm CCl , 6 cm CH CN, and 9 cm H O
4 3 2
stir for 15 min. Organic layer was separated and the
followed by the addition of 0.02 g RuCl (0.09 mmol, 0.05
3
aqueous layer was washed with ethyl acetate
3
2 9 20 cm ). The combined organic layers were washed
equiv) and the entire mixture was stirred vigorously for 2 h
(
at room temperature. The reaction mixture was diluted with
3
5 cm CH Cl and the upper aqueous phase was extracted
3
with water (2 9 10 cm ), 10 cm brine, dried over
3
2
2
3
Na SO , and concentrated under reduced pressure. The
2
with CH Cl (2 9 10 cm ). The combined organic layers
2 2
4
crude product was purified by column chromatography
silica gel 60–120 mesh, 12 % EtOAc in pet. ether) to give
1 (1.56 g, 78 %) as a colorless liquid. [a] = ?31.6
were dried over Na SO and concentrated. The obtained
2 4
(
crude residue was purified by column chromatography
(silica gel 60–120 mesh, 25 % EtOAc in pet. ether) to
1
D
1
(
c = 0.7, CHCl ); H NMR (CDCl , 300 MHz): d = 7.37–
afford 13 (1.6 g, 85 %) as a liquid. [a] = ?22.24
3
3
D
1
H
7
4
4
.22 (m, 5H, –C H ), 5.83–5.69 (m, 1H, olefinic), 5.06–
6
(c = 0.42, CHCl3);
NMR (CDCl3, 300 MHz):
5
.97 (m, 2H olefinic), 4.61 (d, 1H, J = 10.9 Hz, benzylic),
.39 (d, 1H, J = 10.9 Hz, benzylic), 3.82–3.76 (m, 1H, –
d = 7.34–7.24 (m, 5H, –C H ), 4.49 (d, 1H,
6
5
J = 11.8 Hz, benzylic), 4.39 (d, 1H, J = 11.8 Hz, ben-
zylic), 3.57 (m, 1H, –OCH), 3.48–3.39 (m, 1H, –OCH),
2.61 (d, 2H, J = 6.3 Hz, –CH ), 1.54 (m, 2H, –CH ), 1.46–
OCH), 3.648–3.57 (m, 1H, –OCH), 2.32–2.22 (m, 2H,
allylic), 2.06 (br s, 1H, –OH), 1.57 (t, 2H, J = 8.1 Hz, –
CH ), 1.46–1.07 (m, 8H, 4 9 –CH ), 0.93 (t, 3H,
2
2
2
2
1.17 (m, 8H, 4 9 –CH ), 0.98 (s, 9H, t-butyl), 0.84 (t, 3H,
2
13
1
3
J = 7.6 Hz, –CH ) ppm; C NMR (75 MHz, CDCl3):
3
J = 7.5 Hz, –CH ), 0.33 (s, 6H, 2 9 –CH ) ppm;
3
C
3
d = 138.8, 136.3, 128.9, 128.5, 128.2, 114.1, 75.9, 72.2,
NMR (75 MHz, CDCl ): d = 175.8, 138.4, 129.3, 128.5,
3
7
0.1, 44.4, 38.6, 36.5, 33.2, 24.2, 23.8, 14.6 ppm; IR
128.3, 75.8, 74.7, 72.8, 45.3, 40.1, 33.8, 32.3, 28.8, 26.8,
123

2
024
G. Alluraiah et al.
3
with 40 cm 7 % aq NaHCO , 40 cm 2 M aqueous HCl,
3
2
3.2, 18.8, 13.8, -4.4, -4.1 ppm; IR (neat): mꢀ = 3,581,
3
-
,033, 2,953, 1,713, 1,606 cm . MS (ESI): m/z = 431
1
3
40 cm brine, and dried over Na SO . The separated
3
2
4
?
?
[M ? Na] ), 409 ([M ? H] ).
(
organic layer was evaporated under reduced pressure and
the obtained residue was purified by column chromatog-
raphy (silica gel 60–120 mesh, 15 % EtOAc in pet. ether)
(
3R,5R)-3-(Benzyloxy)-5-hydroxydecanoic acid
(
2, C H O )
1
7 26 4
to give 14 (0.48 g, 52 %) as a syrup. [a] = ?12.3
3
TBAF (1.1 cm , 4.11 mmol, 1.2 equiv) was added to a
D
(
c = 0.8, CHCl3).
cooled (0 °C) solution of 1.4 g 13 (3.43 mmol, 1 equiv) in
3
0 cm dry THF under nitrogen atmosphere and stirred for
1
Acknowledgments We are grateful to CSIR-IICT, Hyderabad for
providing analytical facilities
3
h. After completion of reaction, the reaction mixture was
3
diluted with 5 cm water and extracted with ethyl acetate
3
2 9 50 cm ). The combined organic layers were washed
3
with water (2 9 10 cm ), 10 cm brine, dried over
(
3
References
Na SO , evaporated, and the residue was purified by
4
2
1
2
3
4
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column chromatography (silica gel 60–120 mesh, 55 %
(
EtOAc in pet. ether) to give 2 (0.86 g, 86 %) as a liquid.
1
[
a] = ?32.6 (c = 1.0, CHCl ); H NMR (CDCl3,
D
3
3
00 MHz): d = 7.37–7.25 (m, 5H, –C H ), 4.43 (d, 1H,
6
5
3
:533
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J = 11.7 Hz, benzylic), 4.39 (d, 1H, J = 11.7 Hz, ben-
zylic), 3.87–3.78 (m, 1H, –OCH), 3.51–3.43 (m, 1H, –
1
OCH), 2.58 (d, 2H, J = 6.5 Hz, –CH ), 1.54 (m, 2H, –
2
6
CH ), 1.46–1.27 (m, 8H, 4 9 –CH ), 0.94 (t, 3H,
2
2
1
3
J = 7.3 Hz, –CH ) ppm; C NMR (CDCl , 75 MHz):
3
3
8
9
. Sharma GVM, Reddy ChG (2004) Tetrahedron Lett 45:7483
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d = 175.6, 138.5, 129.2, 128.4, 128.2, 74.6, 72.3, 71.2,
4.2, 40.8, 38.4, 32.2, 25.8, 22.4, 14.3 ppm; IR (neat):
mꢀ = 3,481, 2,939, 2,851, 2,112, 1,723, 1,614, 1,512, 1,362,
4
10. Salunke GB, Shivakumar I, Gurjar MK (2009) Tetrahedron Lett
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2. Das B, Laxmminarayana K, Krishnaiah M, Nandan Kumar D
2009) Helv Chim Acta 92:1840
5
-
1
?
1
,041, 778 cm ; MS (ESI): m/z = 317 ([M ? Na] ), 295
1
?
[M ? H] ).
(
(
1
1
3. Sabitha G, Bhaskar V, Yadav JS (2008) Synth Commun 38:3129
4. Wu JZ, Gao J, Ren GB, Zhen ZB, Zhang YH, Wu YK (2009)
Tetrahedron 65:289
(
3R,5R,9R,11R)-3,9-Bis(benzyloxy)-5,11-
dipentylcyclododecane-1,7-dione (14) [8]
3
A solution of 0.4 cm 2,4,6-trichlorobenzoyl chloride
15. Chatopadyay A, Mamdapur VR (1995) J Org Chem 60:585
1
3
2.55 mmol, 2 equiv) in 2 cm dry THF was added to a
6. Hayashi Y, Yamaguchi J, Hibino K, Shoji M (2003) Tetrahedron
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7. List B (2002) Tetrahedron 58:5573
(
3
stirred solution of 0.5 g 2 (1.7 mmol, 1 equiv) and 0.7 cm
3
Et N (5.1 mmol, 4 equiv) in 3 cm dry THF. The resulting
1
3
18. Hayashi Y, Yamaguchi J, Sumiya T, Shoji M (2004) Angew
Chem Int Ed 43:1112
1
mixture was stirred for 2 h at room temperature under
nitrogen atmosphere and evaporated to afford the mixed
3
anhydride. Now, it was diluted with 10 cm toluene and
9. Inanaga J, Hirata K, Saeki H, Katsuki T, Yamaguchi M (1979)
Bull Chem Soc Jpn 52:1989
0. Vilanova C, S a´ nchez-P e´ ris M, Rold a´ n S, Dhotare B, Carda M,
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2
filtered quickly through Celite. The filtrate was added
dropwise to a stirred solution of 0.06 g DMAP (0.51 mmol,
3
.3 equiv) in 490 cm toluene (total volume used for this
21. Chandrasekhar S, Sreelakshmi
3:3233
22. Bujaranipalli S, Eppa G, Das S (2013) Synlett 24:1117
L (2012) Tetrahedron Lett
5
0
3
operation was 500 cm ) at 90 °C over a period of 8 h.
After the complete addition, the reaction mixture was
stirred at 100 °C for 2 h. Further, it was cooled, washed
2
3. Kamal A, Reddy PV, Prabhakar S, Balakrishna M (2009) Tet-
rahedron Asymm 20:2861
1
23