A concise stereoselective total synthesis of diplodialide C

Article abstract of DOI:10.1007/s00706-015-1464-1

An asymmetric total synthesis of diplodialide C has been achieved starting from commercially available homoallylic alcohol. Regioselective opening of the chiral epoxide, cross-metathesis reaction, and Yamaguchi macrolactonization were used as the key step

Full text of DOI:10.1007/s00706-015-1464-1

Monatsh Chem
DOI 10.1007/s00706-015-1464-1
ORIGINAL PAPER
A concise stereoselective total synthesis of diplodialide C
Bommareddy Pratapareddy1 Reddymasu Sreenivasulu2
•
•
Islavathu Hatti2 Mandava Venkata Basaveswara Rao1
•
•
Rudraraju Ramesh Raju2
Received: 1 October 2014 / Accepted: 22 March 2015
Ó Springer-Verlag Wien 2015
Abstract An asymmetric total synthesis of diplodialide C
has been achieved starting from commercially available
homoallylic alcohol. Regioselective opening of the chiral
epoxide, cross-metathesis reaction, and Yamaguchi
macrolactonization were used as the key steps in this
synthesis.
various biological activities, in particular, diplodialide A(1)
displays significant inhibitory activity against progesterone
11a-hydroxylase in vegetable cell cultures of Rhizopus
stolonifer at 125 ppm. The absolute stereochemistry of
diplodialides were (9R)-1, (3S,9R)-2, and (3R,9R)-3 and
determined by Wada and Ishida [3].
Graphical Abstract
The interesting biological activity combined with simple
stereochemistry of diplodialides attracted scientists and re-
searchers worldwide. The first total synthesis of ( )-
diplodialide C was reported by Wakamatsu and co-workers
[4] in 1977. Further, the total synthesis of diplodialide C was
reported by Takeshi and co-workers [5] in 1979 using Bar-
bier-Grignard and Sharpless asymmetric dihydroxylation
reactions as key steps. Sharma and Reddy [6] reported the
stereoselective synthesis of diplodialides including diplodi-
alide C, by the combination of Jacobsen’s hydrolytic kinetic
resolution and sharpless epoxidation followed by ring-clos-
ing metathesis strategy. The stereoselective total syntheses
of natural products (-)-curvularin, curvulin, and (-)-
diplodialide C were reported by Tadross and co-workers [7]
using Grubbs’ second-generation catalyst, Grubbs-Hoveyda
third-generation catalyst and utilizing an aryne acyl-alkyla-
tion reaction followed by ring-closing metathesis.
Keywords Homoallylic alcohol Á
Cross-metathesis reaction Á Yamaguchi
macrolactonization Á Diplodialide C
Introduction
The first 10-membered lactone pentaketides are diplodialide
structures A(1), B(2), C(3), and D(4) (Fig. 1), which were
isolated from the plant pathogenic fungus Diplodiapinea
(IFO 6472) by Wada and Ishida [1, 2]. Diplodialides exhibit
The reported synthetic routes to diplodialide C mainly
associated with hard reaction conditions and low yields. To
overcome these disadvantages with the earlier approaches,
herein we reported an alternative route for the synthesis of
diplodialide C. In this context, we would like to report an
efficient and high yielding enantioselective synthesis of
diplodialide C employing an entirely different approach.
This strategy involves a concise divergent synthesis of the
target molecule 3 from inexpensive starting material, i.e.,
homoallylic alcohol, and subsequent cross-metathesis re-
action followed by Yamaguchi macrolactonization to form
the cyclic ring.
& Mandava Venkata Basaveswara Rao
professormandava@gmail.com
& Rudraraju Ramesh Raju
rrraju1@gmail.com
1
Department of Chemistry, Krishna University,
Machilipatnam 521 001, Andhra Pradesh, India
2
Department of Chemistry, Acharya Nagarjuna University,
Nagarjuna Nagar, Guntur 522510, Andhra Pradesh, India
123

B. Pratapareddy et al.
Fig. 1 Structures of
diplodialides
(E/Z 90:10) in 57 % yield, along with 12a in 21 % yield, a
homodimer of 7. The simultaneous reduction of olefin and
deprotection of the benzyl group with Pd/C in EtOAc
yielded saturated alcohol 13 in 91 % yield. Oxidation of
alcohol 13 with TEMPO and BIAB [15, 16] in aq. CH2Cl2
afforded acid 14 in 76 % yield, which on desilylation with
TBAF in dry THF gave hydroxyacid 5 in 88 % yield. The
resulting hydroxy acid 5 was subjected to macrolac-
tonization under the Yamaguchi [17, 18] protocol by using
2,4,6-trichlorobenzoyl chloride, followed by cyclization in
the presence of DMAP under high dilution conditions in
toluene afforded the lactone 15 in 63 % yield.
Results and discussion
The retrosynthesis route for the synthesis of diplodialide C
is outlined in Scheme 1. The target molecule 3 could be
synthesized through Yamaguchi’s macrolactonization of a
hydroxyl acid 5 which in turn could be obtained from
olefins 6 and 7 [14]. The olefin 6 could be prepared from
commercially available homoallylic alcohol (8) by simple
chemical transformations.
The total synthesis of 3 was initiated with commercially
available homoallylic alcohol (8) as illustrated in
Scheme 2. Accordingly, homoallylic alcohol (8) protected
as benzyl ether by treating with benzyl bromide and sodi-
um hydride in tetrahydrofuranat, 0–25 °C for 8 h yielded 9
in 94 % yield. Epoxidation of terminal olefin 9 was ac-
complished with m-CPBA in CHCl3 in 91 % yield as a
racemic mixture. The racemic epoxide 9a, on hydrolytic
kinetic resolution using Jacobsen’s (S,S)-catalyst [8] in the
presence of AcOH and H2O for 16 h stirring at 0–25 °C
afforded enantiopure (S)-epoxide 10 ([99 % ee) in 44 %
yield and R-diol 10a in 39 % yield. Regioselective opening
of the chiral epoxide 10, upon reaction with vinylmagne-
sium bromide in dry ether in the presence of CuI [9, 10]
gave alcohol 11 (88 %), which upon subsequent treatment
with TBDPSCl and imidazole in CH2Cl2 gave silyl ether 6
in 90 % yield. Further, silyl ether 6 was subjected to cross-
metathesis [11–13] with known olefin 7 [14] in the pres-
ence of 10 mol% Grubbs second-generation catalyst in
CH2Cl2, at reflux afforded cross-metathesis product 12
Finally, desilylation of lactone 15 with TBAF in dry
THF, afforded the diplodialide C in 84 % yield. The
spectral and analytical data of synthetic diplodialide C (3)
were in good agreement with the reported values in the
literature [6].
Conclusion
In conclusion, a concise stereoselective total synthesis of
diplodialide C (3) was accomplished. A combination of
regioselective opening of the chiral epoxide, cross-
metathesis reaction, and Yamaguchi macrolactonization
were used as key steps.
Experimental
All chemicals and solvents were purchased from Sigma
Aldrich and Merck, and used without further purification.
All reactions were monitored by thin layer chromatography
(TLC) on silica Merck 60 F254 percolated aluminum
plates. 1H and 13C NMR spectra were recorded in 500, 300,
150, and 75 MHz Bruker spectrometer. Chemical shifts are
reported in d units (ppm) with tetramethylsilane (TMS) as a
reference. All coupling constants (J) are 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 spectrophotometer by 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 25 °C.
Scheme 1
123

A concise stereoselective…
Scheme 2
O
a
b
c
OBn
OH
OBn
8
9
9a
OR
OTBDPS
OTBS
O
d
f
OBn
OBn
OBn
10 (44%)
12 (57%)
11 R = H
e
+
6 R =TBDPS
+
OTBS
OH
HO
OBn
OTBS
j
12a (21%)
10a (39%)
OTBDPS
OH
OTBS
OTBDPS
OR
h
g
COOH
13
14 R = TBS
5 R = H
i
O
O
O
O
k
TBDPSO
HO
3
15
o
o
Reagents and conditions: (a) BnBr, NaH, THF, 0 oC to 25 C, 8 h; (b) m-CPBA, CHCl3, 25 C, 8 h;
(c) ( S,S)-Jacobsen’s catalyst, H2O, THF, 0 C to 25oC; (d) vinylMgBr, THF, −40 oC, 4 h; (e)
o
TBDPSCl, imidazole, CH2Cl2, 0 oC to 25 oC; (f)7, Grubbs II catalyst (10 mol %), CH2Cl2, reflux, 2 h;
(g) Pd/C, MeOH, 25 oC, 6 h; (h) TEMPO, BIAB, H2O:CH2Cl2, (1:1), 0 C, 1 h; (i) PPTS,
o
MeOH, 0 oC to 25 oC, 3 h; (j) (i)2,4,6-trichlorobenzoyl chloride, Et3N, dry THF, 0 ºC to 25 oC, 2 h;
(ii) DMAP, dry toluene, 70 ºC, 5 h; (k) TBAF, dry THF, 25oC, 1 h
[(But-3-enyloxy)methyl]benzene (9) [19]
(S)-2-[2-(Benzyloxy)ethyl]oxirane (10) [19]
To a suspension of 8.0 g NaH (333.32 mmol, 60 % w/v
dispersion in mineral oil, 4.0 eq) in 100 cm3, anhydrous
THF was added drop wise to a solution of 6.0 g 3-buten-1-
ol 8 (83.33 mmol, 1.0 eq) at 0 °C. To this mixture, 0.150 g
TBAI and 11.9 cm3 benzyl bromide (99.99 mmol, 1.2 eq)
were added, and stirring was continued for 2 h at the same
temperature and overnight at 25 °C. The reaction mixture
was quenched by small crushed ice flakes until a clear
solution (biphasic) had formed. The reaction mixture was
extracted with ether and the extract was washed with water
(1 9 100 cm3), brine (1 9 100 cm3) and dried over anhy-
drous Na2SO4. Evaporation of the solvents followed by
column chromatography (silica gel, 60–120 mesh, 5 %
EtOAc in pet. ether) afforded the pure product 9 (12.2 g,
91 % yield) as a colorless liquid.
Crude benzyl ether 9 (12.0 g, 74.07 mmol, 1.0 eq) was
dissolved in 100 cm3 dichloromethane and the solution was
cooled to 0 °C. NaHCO3 (15.2 g) was added, followed by
25.5 g m-CPBA (148.14 mmol, 70 % w/w, 4.0 eq). The
solution was stirred for 16 h before being filtered through a
pad of Celite and concentrated under reduced pressure. The
residue was then dissolved in 100 cm3 water and extracted
with Et2O (3 9 50 cm3). The combined organic extracts
were then washed with 3 M NaOH (3 9 50 cm3), followed
by brine (50 cm3), dried over Na2SO4, and evaporated.
Chromatography (silica gel, 60-120 mesh, 8 % EtOAc in
1
pet. ether) gave 9a, as a colorless oil (11.3 g, 89 %). H
NMR (CDCl3, 300 MHz): d = 7.32–7.23 (m, 5H), 4.50 (s,
2H), 3.62–3.56 (m, 2H), 3.14–2.99 (m, 1H), 2.74 (dd,
J = 5.84, 4.61 Hz, 1H), 2.47 (dd, J = 5.84, 2.92 Hz, 1H),
123

B. Pratapareddy et al.
1.91–1.85 (m, 1H), 1.77–1.71 (m, 1H) ppm; ESI–MS: m/z
= 201 ([M ? Na]?).
compound 7 (5.8, 90 %). [a]2D5 = -8.2 (c = 0.9, CHCl3);
1H NMR (300 MHz, CDCl3): d = 7.71–7.65 (m, 5H, Ar–
H), 7.42–7.18 (m, 10H, Ar–H), 5.81–5.64 (m, 1H, olefinic),
4.94–4.88 (m, 2H, olefinic), 4.33 (s, 2H, benzylic CH2),
3.96 (m, 1H, –OCH), 3.48 (t, J = 4.3 Hz, 2H, –OCH2),
2.28 (m, 2H, allylic CH2), 1.86–1.78 (m, 2H, –CH2), 1.05
(s, 9H, t-Bu) ppm; 13C NMR (75 MHz, CDCl3):
d = 137.1, 136.8, 135.1, 132.8, 128.9, 128.1, 127.9,
127.2, 126.9, 117.3, 82.2, 75.8, 69.2, 42.1, 38.3, 27.2,
18.9 ppm; ESI–MS: m/z = 467 ([M ? Na]?).
A
mixture of 0.21 g (S,S)-(-)-N,N1-bis(3,5-di-
tert-butylsalicyclidene)-1,2-cyclohexanediaminocobalt(II)
(0.31 mmol, 0.005 eq), toluene, and 0.04 cm3 AcOH
(0.63 mmol, 0.01 eq) was stirred while open to the air for
1 h at 25 °C. The solvent was removed under reduced
pressure and the brown residue was dried over high
vacuum. The oxirane 9a (11 g, 63.95 mmol, 1.0 eq) was
added in one portion, the stirred mixture was cooled in an
ice water bath. Water (0.63 cm3, 35.17 mmol, 0.55 eq)
was slowly added and the temperature of the reaction
mixture was maintained in such a way that it never rises
more than 20 °C. After completion of reaction within one
hour, removed the ice bath. Now the reaction mixture was
stirred for 22 h at room temperature and finally the residue
was purified by column chromatography to afford the
epoxide 10 (4.9 g, 44 %) as colorless oil [a]2D5 = -18.8
(c = 0.8, CHCl3).
(5S,11R)-5-[2-(4-Methoxybenzyloxy)ethyl]-
2,2,11,13,13,14,14-heptamethyl-3,3-diphenyl-4,12-dioxa-
3,13-disilapentadec-6-ene (12, C39H58O3Si2)
1.92 g olefin 7 (9.0 mmol, 2.0 eq) and 2nd Grubbs’
generation catalyst (10 mol %) were added to a solution
of 2.0 g olefin 6 (4.50 mmol, 1.0 eq) in 100 cm3 CH2Cl2
under N2 atmosphere at room temperature. The tem-
perature was raised to reflux and the reaction allowed
stirring for 48 h. The reaction mixture was directly
adsorbed on silica to perform the column chromatography
(silica gel, 60–120 mesh, 4 % EtOAc in pet. ether), to give
12 in 57 % yield as a colorless syrup. [a]2D5 = ?32.99
(c = 1.2, CHCl3); 1H NMR (200 MHz, CDCl3): d = 7.63–
7.54 (m, 4H, Ar–H), 7.40–7.28 (m, 6H, Ar–H), 7.24–7.16
(m, 5H, Ar–H), 5.15–5.02 (m, 2H, olefinic), 4.57 (d, 1H,
J = 11.7 Hz, benzylic), 4.53 (d, 1H, J = 11.7 Hz, ben-
(R)-1-(Benzyloxy)hex-5-en-3-ol (11) [20, 21]
Copper iodide (0.53 g, 2.79 mmol, 0.1 eq)was gently
heated under vacuum and slowly cooled under nitrogen
atmosphere, then 10 cm3 THF was added and the resulting
suspension was cooled to -20 °C and 55 cm3 vinyl
magnesium bromide (29.04 mmol, 1.1 eq) was added at
the same temperature while stirring. A solution of 4.8 g
epoxide 5 (27.90 mmol, 1.0 eq) in 20 cm3 dry THF was
added to the above reagent and the mixture was stirred at
-20 °C for 1 h. After completion of the reaction, the
reaction was quenched with saturated aqueous NH4Cl,
extracted into EtOAc (3 9 30 cm3), the combined organic
layer was washed with brine, dried over Na2SO4, and
concentrated, to give the crude product which was purified
by column chromatography (silica gel, 60–120 mesh, 15 %
EtOAc in pet. ether) to afford 11 (5.1 g, 88 %) as a
colorless liquid [a]2D5 = ?3.3 (c = 1, CHCl3).
zylic), 3.69–3.57 (m, 2H,
2 –OCH), 3.42(t, 1H,
J = 6.8 Hz, CH), 2.42–2.29 (m, 2H, allylic), 2.08–1.98
(m, 2H, allylic), 1.72–1.54 (m, 4H, 2 –CH2), 1.16 (d, 3H,
J = 6.8 Hz, –CH3), 1.02 (s, 9H, t-Bu), 0.87 (s, 9H, t-Bu),
0.22 (s, 6H, 2 –CH3) ppm; 13C NMR (75 MHz, CDCl3):
d = 136.8, 133.8, 132.9, 129.8, 128.3, 128.1, 127.8, 127.6,
76.1, 71.1, 68.2, 38.8, 36.6, 35.8, 30.9, 27.2, 26.1, 23.8,
ꢀ
19.6, 18.3, -4.2 ppm; IR (neat): m = 3010, 2940, 1610,
1190, 1100 cm-1; ESI–MS: m/z = 653 ([M ? Na]?).
(3R,9R)-9-(tert-Butyldimethylsilyloxy)-3-(tert-
butyldiphenylsilyloxy)decan-1-ol (13, C32H54O3Si2)
To a stirred solution of 1.5 g 12 (2.37 mmol, 1.0 eq) in 10
cm3 EtOAc, 10 % palladium adsorbed on carbon (Pd/C)
was added and stirred under H2 atmosphere for 12 h at
room temperature. The reaction mixture was filtered
through Celite and the filtrate was concentrated under
reduced pressure and purified by column chromatography
(silica gel, 60–120 mesh, 20 % EtOAc in pet. ether) to
furnish 13 (1.1 g, 91 %) as colorless syrup. [a]2D5 = ?9.9
(c = 0.8, CHCl3); 1H NMR (200 MHz, CDCl3): d = 7.68–
7.56 (m, 4H, Ar–H), 7.35–7.27 (m, 6H, Ar–H), 3.67–3.56
(m, 2H, 2 –OCH), 3.53 (t, 2H, J = 6.8 Hz, –OCH2), 2.04
(br.s, 1H, –OH), 1.78–1.52 (m, 2H, –CH2), 1.46–1.17 (m,
10H, 5 –CH2), 1.17 (d, 3H, J = 6.6 Hz, –CH3), 0.98 (s,
9H, t-Bu), 0.83 (s, 9H, t-Bu), 0.19 (s, 6H, 2 –CH3) ppm;
(R)-[1-(Benzyloxy)hex-5-en-3-yloxy](tert-butyl)diphenylsi-
lane (6, C29H36O2Si)
To a cooled (0 °C) solution of 3.0 g compound 11
(14.56 mmol, 1.0 eq) and 1.98 g imidazole (29.12 mmol,
2.0 eq) in 30 cm3 dry dichloromethane was added 4.8 g
tert-butyldiphenylsilylchloride (17.47 mmol, 1.2 eq) drop
wise and stirred for 4 h. After the completion of reaction,
the reaction mixture was diluted with 20 cm3 water and
extracted into dichloromethane (3 9 30 cm3). The com-
bined organic layer was washed with 10 cm3 brine
solution, dried over anhydrous Na2SO4, and concentrated
under vacuum to furnish the crude residue, which was
purified by column chromatography (silica gel, 60–120
mesh, 5 % EtOAc in pet. ether) to afford the pure
123

A concise stereoselective…
13C NMR (75 MHz, CDCl3): d = 137.1, 133.6, 129.8,
128.1, 78.3, 68.1, 61.3, 38.7, 32.3, 29.8, 27.2, 26.7, 26.1,
(4R,10R)-4-(tert-Butyldiphenylsilyloxy)-10-methyloxecan-
2-one (15, C16H36O3Si)
ꢀ
25.9, 24.1, 19.5, 18.2, -4.1 ppm; IR (neat): m = 3368,
A solution of 0.2 g hydroxy acid 5 (0.45 mmol, 1.0 eq) in 2
cm3 dry THF at 0 °C under an N2 atmosphere was treated
with 0.25 cm3 Et3N (1.80 mmol, 4.0 eq) and 0.21 mg
2,4,6-trichlorobenzoyl chloride (1.35 mmol, 3.0 eq) se-
quentially. After stirring at room temperature for 2 h, it
was diluted with 20 cm3 toluene. Next, this mixture was
added dropwise over 5 h, to a solution of 55 mg DMAP
(0.45 mmol) in 250 cm3 dry toluene preheated at 60 °C.
After completion of addition, the reaction mixture was
allowed for stirring at 60 °C for 1 h. It was then cooled to
room temperature and concentrated under reduced pres-
sure. Purification of the residue by column chromatography
(silica gel, 60–120 mesh, 8 % EtOAc inpet. ether)
furnished lactone 15 (0.12 g, 63 %) as a colorless oil.
[a]2D5 = -19.7 (c = 0.6, CHCl3); 1H NMR (300 MHz,
CDCl3): d = 7.65–7.54 (m, 4H, Ar–H), 7.44–7.33 (m, 6H,
Ar–H), 4.94 (m, 1H, –CH), 4.16 (m, 1H, –CH), 2.71 (dd,
1H, J = 5.4, 15.4 Hz, –CH), 2.45 (dd, 1H, J = 8.3,
15.4 Hz, –CH), 1.79–1.33 (m, 10H, 5 –CH2), 1.23 (d,
3H, J = 6.5 Hz, –CH3) ppm; 13CNMR (75 MHz, CDCl3):
d = 172.4, 133.8, 133.6, 129.8, 128.0, 81.1, 67.8, 43.1,
34.3, 32.0, 29.8, 27.2, 26.1, 23.9, 22.1, 19.0 ppm; IR
2934, 2859, 1428, 1108, 1055 cm-1; ESI–MS: m/z = 543
([M ? H]?).
(3R,9R)-9-(tert-Butyldimethylsilyloxy)-3-(tert-
butyldiphenylsilyloxy)decanoicacid (14, C32H52O4Si2)
To a stirred solution of 1.1 g 13 (2.02 mmol, 1.0 eq) in
CH2Cl2:H2O (1:1, 1 cm3), 94 mg TEMPO (0.61 mmol,
0.3 eq), and 0.19 g BIAB (0.61 mmol, 0.3 eq) were added
at 0 °C and stirred for 1 h. The reaction mixture was
diluted with 5 cm3 water and extracted with CH2Cl2
(2 9 20 cm3). The organic layers were washed with
10 cm3 brine, dried (Na2SO4), evaporated, and the residue
purified by column chromatography (silica gel, 60–120
mesh, 30 % EtOAc in pet. ether) to give acid 14 (0.85 g,
76 %) as
a
colorless gummy oil. [a]2D5 = -105.3
(c = 0.25, CHCl3); 1H NMR (200 MHz, CDCl3):
d = 7.67–7.54 (m, 4H, Ar–H), 7.39–7.28 (m, 6H, Ar–H),
3.71–3.63 (m, 1H, –OCH), 3.61–3.53 (m, 1H, –OCH), 2.73
(dd, 1H, J = 8.6, 15.1 Hz, –CH–COOH), 2.64 (dd, 1H,
J = 5.8, 15.1 Hz, –CH–COOH), 1.69–1.52 (m, 2H, –CH2),
1.42–1.27 (m, 8H, 4 –CH2), 1.16 (d, 3H, J = 6.4 Hz,
–CH3), 0.99 (s, 9H, t-Bu), 0.81 (s, 9H, t-Bu), 0.21 (s, 6H, 2
–CH3) ppm; 13C NMR (75 MHz, CDCl3): d = 172.8,
136.9, 133.8, 129.9, 128.2, 81.3, 67.8, 44.2, 39.3, 33.2,
30.4, 27.1, 26.3, 25.8, 24.2, 20.3, 18.6, -4.6 ppm; IR
ꢀ
(neat): m = 2938, 1730,1646, 1377, 1207, 1096, 1044,
869 cm-1; ESI–MS: m/z = 425 ([M ? H]?).
Diplodialide C (3)
ꢀ
(neat): m = 3450, 2928, 2855, 1737, 1639, 1438, 1363,
To a cooled (0 °C) solution of 0.11 g 15 (0.25 mmol,
1.0 eq) in 1 cm3 dry THF under nitrogen atmosphere, 0.4
cm3 of a solution of TBAF in THF (1.0 M, 0.38 mmol,
1.5 eq) was added and stirred for 1 h. The reaction was
diluted with 5 cm3 water and extracted with EtOAc
(2 9 20 cm3). The combined organic layers were washed
with water (2 9 10 cm3), brine (10 cm3), dried (Na2-
SO4), evaporated, and purified the residue by column
chromatography (silica gel, 60–120 mesh, 20 % EtOAc
in pet. ether) to afford 3 (40 mg, 84 %) as a colorless
1277, 1075, 1040, 921, 699 cm-1; ESI–MS: m/z = 557
([M ? H]?).
(3R,9R)-3-(tert-Butyldiphenylsilyloxy)-9-hydroxydecanoic
acid (5, C26H38O4Si)
To a cooled (0 °C) solution of 0.8 g 14 (1.43 mmol,
1.0 eq) in 5 cm3 methanol, 36 mg PPTS (0.14 mmol,
0.1 eq) was added and stirred for 6 h. After completion of
the reaction, methanol was removed and extracted with
EtOAc (2 9 20 cm3). The combined organic layers were
washed with water (2 9 20 cm3), brine (10 cm3), dried
(Na2SO4), evaporated, and purified the residue by column
chromatography (silica gel, 60–120 mesh, 35 % EtOAc in
pet. ether) to afford 5 (0.63 g, 88 %) as a colorless liquid.
liquid. [a]2D5
= -38.9 (c = 0.7, CHCl3) (Ref. [6]
[a]2D5 = -41.0 (c = 0.61, CHCl3)); spectral data were
in good agreement with the reported values in the
literature [6].
1
[a]2D5 = -89.81 (c = 0.55, CHCl3); H NMR (300 MHz,
Acknowledgments We are grateful to CSIR-IICT, Hyderabad for
providing analytical facilities.
CDCl3): d = 7.66–7.57 (m, 4H, Ar–H), 7.42–7.31 (m, 6H,
Ar–H), 3.81–3.73 (m, 2H, 2 –OCH), 2.78 (dd, 1H, J = 8.8,
15.3 Hz, –CH–COOH), 2.63 (dd, 1H, J = 6.1, 15.3 Hz,
–CH–COOH), 1.73–1.32 (m, 10H, 5 –CH2), 1.19 (d, 3H,
J = 6.2 Hz, –CH3), 0.94 (s, 9H, t-Bu) ppm; 13CNMR
(75 MHz, CDCl3): d = 173.6, 136.8, 134.1, 130.1, 128.2,
81.3, 68.1, 43.3, 40.4, 32.2, 30.4, 27.1, 26.2, 25.3, 23.8,
19.1 ppm; IR (neat): mꢀ = 3425, 2927, 2856, 1653, 1512,
1456, 1378, 1249, 1025, 699 cm-1; ESI–MS: m/z = 465
([M ? Na]?).
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