Chemo-enzymatic synthesis of both enantiomers of rugulactone

Article abstract of DOI:10.1016/j.tetasy.2010.01.016

The synthesis of both the (R)- and (S)-enantiomers of the natural product rugulactone has been achieved. Candida rugosa lipase hydrolyzes the butyrate ester of the protected 3-hydroxy homoallylic alcohol with very high enantioselectivity (E = 244) and pro

Full text of DOI:10.1016/j.tetasy.2010.01.016

Tetrahedron: Asymmetry 21 (2010) 320–324
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Chemo-enzymatic synthesis of both enantiomers of rugulactone
*
Gowrisankar Reddipalli, Mallam Venkataiah, Nitin W. Fadnavis
Biotransformation Laboratary, Indian Institute of Chemical Technology, Uppal Road, Habsiguda, Hyderabad 500 007, India
a r t i c l e i n f o
a b s t r a c t
Article history:
The synthesis of both the (R)- and (S)-enantiomers of the natural product rugulactone has been achieved.
Candida rugosa lipase hydrolyzes the butyrate ester of the protected 3-hydroxy homoallylic alcohol with
very high enantioselectivity (E = 244) and provides the key intermediates with high enantiomeric purity
(ee 98–99%) and excellent yields.
Received 18 December 2009
Accepted 26 January 2010
Available online 1 March 2010
Ó 2010 Elsevier Ltd. All rights reserved.
1. Introduction
obtained in excellent yield and enantiomeric purity. The interme-
diates so obtained are converted to the (R)- and (S)-enantiomers
The synthesis of biologically active natural products is of great
interest because of their medicinal use. Recently, rugulactone 1
isolated from the plant Cryptocarya rugulosa1 extract has been
reported to exhibit the inhibition of constitutive nuclear factor
of rugulactone 1 (Scheme 1).
2. Results and discussion
NF-jB activity in human lymphoma cell lines. This observation
Enantiomerically pure rugulactone was prepared in the follow-
ing manner. The monosilyl ether of 1,3-propanediol 2 was prepared
by selective protection with tert-butyldimethylsilyl chloride to ob-
tain compound 3 in 85% yield. The primary alcohol was oxidized
by Swern oxidation to the corresponding aldehyde and allylated
by Barbier’s procedure to obtain the racemic homoallylic alcohol 4
(92% over two steps). This was esterified with butyric acid to obtain
racemic 5. The enantioselective hydrolysis of 5 was carried out with
seven different lipases to screen and identify the most useful biocat-
alyst (Table 1). Typically, the lipase (50 mg) was dissolved in
Tris–HCl buffer (50 mM, pH 7.5, 10 mL) and the racemic ester
(100 mg) was added as an ethanolic solution with vigorous stirring.
The contents were stirred in vials on a magnetic stirrer for 24 h
and then extracted with n-hexane. The hexane extracts were ana-
lyzed by chiral HPLC to determine the enantiomeric purity of the
unreacted ester. The homoallylic alcohol, which was obtained as
the product of the enzymatic hydrolysis, was separated by column
chromatography and converted to its butyrate derivative again to
determine its enantiomeric purity. It was observed that the li-
pases from Rhizopus arrhizus, Rhizopus niveus, and wheat germ
showed very little selectivity. The lipases from porcine pancreas,
Pseudomonas cepacia, and Candida antarctica displayed a reason-
able enantioselectivity toward the (R)-enantiomer (E = 14–25),
but were not enough to be of preparative interest. The best
enantioselectivity was displayed by a lipase from Candida rugosa
(E = 244) and enzymatic hydrolysis provided the (S)-alcohol with
ee 98% at approximately 45% conversion. When the reaction was
allowed to proceed for a longer period, the reaction virtually
stopped at 50–52% conversion and provided the unreacted ester
with ee >99%.
has led to the possibility of its application in cancer chemotherapy
and as an antiviral agent1–3, and already two approaches to its ster-
eoselective synthesis have been reported.2,3 In the first approach
by Venkateswarlu et al.,3 the key intermediate homoallylic alcohol
(R)-6-(benzyloxy)-1-hexen-4-ol has been synthesized via asym-
metric allylation using (R)-BINOL and Ti(OiPr)4 while the second
approach of Yadav et al.2 employs the Jacobsen’s hydrolytic kinetic
resolution of an epoxide which is then converted to homoallylic
alcohol. The intermediate is also useful in the synthesis of
polycavernoside A,4 obolactone,5 spongistatin 16, and others. The
approaches involving asymmetric synthesis provide a single enan-
tiomer, for example, (R)-enantiomer, in the reaction sequence. In
order to obtain the (S)-enantiomer, the reaction needs to be re-
peated with the chiral catalyst of the opposite configuration. It is
generally argued that the synthesis of a single enantiomer with
the possibility of >90% yield is preferred over a kinetic resolution
with a maximum yield of 50%. However, it is well known that
the biological activity of the two enantiomers can differ widely
and it is important to synthesize and study the biological activity
of both the enantiomers. In such a situation, the resolution of a
racemic mixture to obtain both the enantiomers with high enan-
tiomeric purity and yields nearing 45% (90% of theoretical) is pref-
erable since some of the steps preceding the resolution need not be
repeated. Herein we report the resolution of the racemic homoal-
lylic alcohol 4 via lipase-catalyzed enantioselective hydrolysis of
the corresponding butyrate ester 5. Both (R)-5 and (S)-4 are
* Corresponding author. Fax: +91 40 27160512.
E-mail addresses: fadnavis@iict.res.in, fadnavisnw@yahoo.com (N.W. Fadnavis).
0957-4166/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2010.01.016

G. Reddipalli et al. / Tetrahedron: Asymmetry 21 (2010) 320–324
321
OH
OCOCH2CH2CH3
OCOCH2CH2CH3
OTBDMS
Candida rugosa lipase
OTBDMS
OTBDMS
(S)- e.e. 98%
+
Tris-HCl buffer, pH 7.5
5
(R)- e.e. > 99%
( )-5
4
E = 244
O
O
O
O
O
O
(S)-rugulactone (S)-1
(R)-rugulactone (R)-1
Scheme 1.
Table 1
Hydrolysis of ( )-5 with various lipasesa
Enzyme
ee (%)
Selectivity
Conversion c (%)
Enantioselectivity E
Lipase from Candida rugosa
Lipase from Candida antarctica
Lipase from Pseudomonas cepacia
Lipase from porcine pancreas
Lipase from wheat germ
85
50
30
30
15
14
12
(S)
(R)
(R)
(R)
(R)
(R)
(R)
45
37
24
25
33
51
26
244
14
16
25
2
Lipase from Rhizopus arrhizus
Lipase from Rhizopus niveus
1.5
2.2
a
Reaction conditions: [Substrate] = 100 mg in 10 mL Tris–HCl buffer, 0.05 M, pH 7.5; lipase 50 mg. Reaction period 24 h. Product configuration was assigned on the basis of
the specific rotation and comparison with the literature.
The two products were easily separated by column chromatog-
raphy. The (R)-butyrate ester was hydrolyzed with K2CO3 in meth-
anol to obtain alcohol (R)-4 without racemization, which was
treated with PTSA in methanol to obtain the diol (R)-6.
tems, USA). HPLC analyses were carried out on a Hewlett Packard
HP1090 unit with diode array detector and HP Chem Station soft-
ware. Chiral HPLC columns were obtained from Daicel, Japan.
The diol (R)-6 was selectively oxidized with TEMPO and BAIB to
give the aldehyde (R)-7, which was used without purification for
olefination to obtain the unsaturated ester (R)-8 via the Still–Gen-
nari modification of the Horner–Emmons olefination reaction7 (Z/E
ratio of 95:5). The isomers were separated by column chromatog-
raphy to obtain the pure Z-isomer (71% over two steps). Upon
treatment with PTSA in benzene, the ester cyclized to the lactone
(R)-9 (95%). The cross-metathesis8 reaction of the lactone with 5-
phenyl-pent-1-en-3-one9 in the presence of a Grubbs’s second-
generation catalyst gave enantiomerically pure (R)-rugulactone
1a (Scheme 2) (75%). (S)-Rugalactone 1b was also synthesized in
a similar manner starting with the (S)-homoallylic alcohol.
4.1.1. 3-(tert-Butyldimethylsilanyloxy)-propan-1-ol 3
Sodium hydride (60% dispersion in mineral oil, 1.61 g, 40.3
mmol) was suspended in dry DME (30 mL). 1,3-Propanediol 2
(2.04 g, 26.8 mmol) dissolved in dry DME (8 mL) was added and
the reaction mixture was cooled in an ice bath. tert-Butyldimethyl-
silyl chloride (4.05 g, 26.8 mmol) was added slowly at 0 °C, after
which cooling was removed and the reaction mixture was stirred
at room temperature overnight. The reaction was quenched with
saturated NH4Cl solution (5 mL) under cooling. The solvent was
evaporated under reduced pressure. The residue was extracted with
EtOAc (2 ꢀ 30 mL) and dried with anhydrous Na2SO4. After evapora-
tion of ethyl acetate, the residue was chromatographed over silica
gel (60–120 mesh, EtOAc/hexane, 2:8) yielding 3 (4.34 g, 85%) as a
colorless oil. IR(neat) m .
max = 758, 1089, 1215, 1470, 3019 cmꢁ1 1H
3. Conclusion
NMR (300 MHz, CDCl3): d 0.07 (s, 6H), 0.90 (s, 9H), 1.77 (qn,
J = 5.82 Hz, 2H), 3.80 (t, J = 5.82 Hz, 2H), 3.82 (t, J = 5.82 Hz, 2H).
13C NMR (75 MHz, CDCl3): d ꢁ5.4, 18.3, 25.9, 34.2, 62.36, 62.9. ESI-
MS: m/z = 191 (M+1).
The lipase-catalyzed resolution provides an efficient route to the
synthesis of both the enantiomers of a biologically active natural
products as shown by the synthesis of (R)- and (S)-rugulactone.
4.1.2. 1-(tert-Butyldimethylsilyloxy)hex-5-en-3-ol 4
4. Experimental
4.1. General
At first, DMSO (3.21 g, 41.1 mmol) was added dropwise to a
solution of oxalyl chloride (2.6 g, 20.5 mmol) in dry CH2Cl2
(20 mL) at ꢁ78 °C. The reaction mixture was stirred for 25 min,
then the mono-protected alcohol 3 (2.6 g, 13.7 mmol) was added
and the contents were stirred for 1 h. The reaction was quenched
with triethylamine (8.3 g, 82.2 mmol) at ꢁ78 °C. The solvent was
then evaporated under reduced pressure, after which the residue
was extracted with CH2Cl2 (2 ꢀ 30 mL), and dried over anhydrous
Na2SO4. After the evaporation of DCM, the crude aldehyde obtained
was used as such without purification (2.51 g, 96%).
All the reagents were purchased from Sigma–Aldrich. IR spectra
were recorded on a Perkin–Elmer RX-1 FT-IR system. 1H NMR
(300 MHz) and 13C NMR (75 MHz) spectra were recorded on a Bru-
ker Avance-300 MHz spectrometer. Optical rotations were mea-
sured with a Horiba-SEPA-300 digital polarimeter. Mass spectra
were recorded on a Q STAR mass spectrometer (Applied Biosys-

322
G. Reddipalli et al. / Tetrahedron: Asymmetry 21 (2010) 320–324
OH
a
b
HO
OH
OTBDMS
O
OTBDMS
OH
HO
4
2
3
O
O
O
c
d
+
OTBDMS
OTBDMS
OTBDMS
5
(R)-5 (e.e.>99%)
(S)-4 (e.e. 98%)
f
e
OH
OH
OH
e
OH
OTBDMS
OH
(R)-6
(R)-4
g
O
O
OH
O
O
(R)-7
h
(S)-1
OH
OMe
(R)-8
O
i
O
O
O
O
O
ArCH2CH2COCHCH2
j
(R)-9
(R)-1
Scheme 2. Reagents and conditions: (a) NaH, TBDMSCl, DME, rt overnight; (b) (i) (COCl)2, DMSO, DCM, ꢁ78 °C 1 h; (ii) Zn, allyl bromide, NH4Cl in THF 3 h; (c) DCC, DMAP,
butyric acid in DCM, 2 h; (d) Tris–HCl buffer, 0.05 M, pH 7.5; Candida rugosa lipase, 48 h; (e) PTSA, MeOH, 1 h; (f) K2CO3, MeOH, 4 h; (g) BAIB, TEMPO, DCM, 4 h; (h) Methyl
P,P-bis(2,2,2-trifluoroethyl)phosphonoacetate, NaH, THF, ꢁ78 °C; (i) PTSA, benzene reflux, 1 h; (j) ArCH2CH2COCHCH2, Grubbs’s second-generation catalyst, DCM, 50 °C, 5 h.
To a stirred solution of crude aldehyde in THF, zinc dust (1.74 g,
26.7 mmol) and allyl bromide (2.40 g, 20 mmol) were added at
room temperature. After stirring for 5 min in an ice bath, saturated
NH4Cl solution (4 mL) was added dropwise with cooling and then
the reaction mixture was stirred at 0–5 °C for 3 h. The reaction was
then quenched with an excess amount of saturated NH4Cl solution
(5 mL) and filtered through a pad of Celite. The filtrate was evapo-
rated under reduced pressure, after which the residue was
extracted with ethyl acetate, and dried over Na2SO4. After evapora-
tion of the ethyl acetate, the residue was chromatographed over
silica gel (60–120 mesh, EtOAc/hexane, 1:9) yielding 4 (2.90 g,
92% overall yield) as a colorless oil.
4.1.4. (R)-1-(tert-Butyldimethylsilyloxy)hex-5-en-3-yl butyrate
(R)-5 and (S)-1-(tert-butyldimethylsilyloxy)hex-5-en-3-ol (S)-4
4.1.4.1. Enzymatic hydrolysis. Racemic substrate
5 (1.44 g,
4.80 mmol) was dispersed into a mixture of Tris–HCl buffer
(20 mL, 5 mM, pH 7.5 containing 5 mM CaCl2) with sonication.
The lipase enzyme from C. rugosa (0.6 g) was added as a solution
in Tris–HCl buffer (5 mL) and the contents were stirred at room
temperature on a magnetic stirrer while maintaining the pH of
the reaction mixture at 7.5 with 0.2 M NaOH. The reaction was fol-
lowed by monitoring the amount of NaOH consumed. After 45%
conversion (consumption of 10.8 mL NaOH, 36 h), the reaction
mixture was extracted with hexane and dried with anhydrous
Na2SO4. After the evaporation of hexane, the residue was chro-
matographed over silica gel (60–120 mesh, EtOAc/hexane, 1:19)
yielding (S)-4 (0.65 g, 45%) as a colorless oil.
The enantiomeric purity of the butyrate ester was determined
directly by chiral HPLC analysis. Since the alcohol was difficult to
analyze, it was again converted to the butyrate derivative and ana-
lyzed for its enantiomeric purity. Thus the analysis of the recovered
products on chiral stationary phase provided the values for the
enantiomeric excesses of substrate (ees) and product (eep). The
enantioselectivity E was calculated according to Sih et al.10 Product
4.1.3. 1-(tert-Butyldimethylsilyloxy)hex-5-en-3-yl butyrate 5
To a stirred solution of 4 (2.60 g, 11.34 mmol), DCC (2.56 g,
12.42 mmol) and DMAP (catalytic amount, 15 mg) in 20 mL CH2Cl2
was added butyric acid (5.36 g, 60.74 mmol) at 0 °C. Cooling was
stopped and the contents were stirred at room temperature for
2 h. The solution was filtered and the solvent was removed under
reduced pressure. The residue was chromatographed over silica
gel (60–120 mesh, hexane) yielding 5 (3.26 g, 96%) as a colorless
oil.

G. Reddipalli et al. / Tetrahedron: Asymmetry 21 (2010) 320–324
323
configurations were assigned on the basis of their specific rotation
and comparison with the literature value.
added sodium hydride (80 mg, 2 mmol, 60% dispersion in mineral
oil) and the resulting ylide solution was stirred for 45 min at 0 °C
and then cooled to ꢁ78 °C . The crude aldehyde (R)-7, dissolved
in dry THF (3 mL) was added dropwise with stirring at ꢁ78 °C
and then stirring was continued for 3 h. The reaction was quenched
with saturated NH4Cl (2 mL) solution at 0 °C. The solvent was
evaporated under reduced pressure, after which the residue was
extracted with EtOAc (2 ꢀ 10 mL) and dried with anhydrous
Na2SO4. After evaporation of ethyl acetate, the residue was chro-
matographed (silica gel, 60–120 mesh, EtOAc/hexane, 2:98) to ob-
4.1.4.2. HPLC analysis with chiral stationary phase. The enan-
tiomeric purity was determined by HPLC analysis on a Chiralcel
AD-H column (250 ꢀ 5 mm), Daicel Chemical Industries, Japan.
Mobile phase 1% 2-propanol in hexane containing. Flow rate
0.5 mL/min. Detection wavelength 220 nm. Retention times (R)-
5: 6.6 min; (S)-5: 7.5 min.
(S)-4: ½a 2D5
ꢂ
¼ ꢁ6:9 (c 1, CHCl3), ee 98%; lit.11 = ꢁ4.8 (c 1, CHCl3),
ee 66%. IR(neat)
m
max = 777, 836, 914, 1001, 1255, 1471, 1643,
tain (R)-8 (169 mg, 71% overall yield) as a colorless oil. ½a D25
¼ þ4:5
ꢂ
2363, 2860, 2932, 3077, 3419 cmꢁ1
.
1H NMR (300 MHz, CDCl3): d
(c 1, CHCl3). IR(neat) mmax = 817, 920, 1046, 1173, 1439, 1645, 1723,
0.07 (s, 6H), 0.90 (s, 9H), 1.59–1.68 (m, 2H), 2.17–2.27 (m, 2H),
3.02 (s, 1H), 3.74–3.92 (m, 3H), 5.03–5.12 (m, 2H), 5.73–5.89
(m, 1H). 13C NMR (75 MHz, CDCl3): d ꢁ5.6, 18.1, 25.8, 37.7, 41.9,
62.5, 71.2, 117.2, 134.9. ESI-MS: m/z = 253 (M+Na).
2952, 3456 cmꢁ1 1H NMR (300 MHz, CDCl3): d 2.19–2.39 (m, 2H),
.
2.74–2.89 (m, 2H), 3.71 (s, 3H), 3.81 (br s, 1H), 4.40–4.56 (m, 1H),
5.05–5.19 (m, 2H), 5.72–5.86 (m, 1H), 5.90 (d, J = 11.33 Hz, 1H),
6.38 (dt, J = 3.77, 8.30 Hz, 1H), 13C NMR (75 MHz, CDCl3): d 35.8,
41.8, 51.2, 70.1, 118.3, 121.4, 134.4, 146.2. ESI-MS: m/z = 193
(M+Na).
(R)-5: ½a 2D5
ꢂ
¼ ꢁ10:2 (c 1, CHCl3), ee >99%. IR(neat)
m
max = 758,
1H
d 0.02 (s, 6H), 0.88 (s, 9H), 0.95
836, 920, 1095, 1216, 1255, 1727, 2358, 2959, 3020 cmꢁ1
.
NMR (300 MHz, CDCl3):
(t, J = 7.55 Hz, 3H), 1.64 (qt, J = 7.55 Hz, 2H), 1.69–1.79 (m, 2H),
2.23 (t, J = 7.55 Hz, 2H), 2.33 (qt, J = 7.55 Hz, 2H), 3.56–3.65 (m,
2H), 4.97–5.10 (m, 3H), 5.65–5.80 (m, 1H). 13C NMR (75 MHz,
CDCl3): d ꢁ5.5, 13.7, 18.3, 18.5, 25.9, 36.5, 36.6, 38.8, 59.4, 70.3,
117.6, 133.6, 173.1. ESI-MS: m/z = 323 (M+Na).
4.1.8. (R)-6-Allyl-5,6-dihydro-2H-pyran-2-one (R)-9
Compound (R)-8 (123 mg, 0.72 mmol) was stirred with a solu-
tion of PTSA (7.5 mg, 0.03 mmol) in benzene (3 mL) and refluxed
for 1 h. Benzene was removed by evaporation under reduced pres-
sure, after which sodium carbonate solution (0.5 mL, 10%) was
added, and the product was extracted with ethyl acetate
(3 ꢀ 5 mL). The ethyl acetate layer was dried over anhydrous
Na2SO4 and evaporated. The residue was chromatographed over
silica gel (60–120 mesh, EtOAc/hexane, 6:4) yielding (R)-9
4.1.5. (R)-1-(tert-Butyldimethylsilyloxy)hex-5-en-3-ol (R)-4
The recovered butyrate ester (0.75 g, ee 80%) from enzymatic
hydrolysis was re-suspended in Tris–HCl buffer containing the en-
zyme as described above and the reaction mixture was stirred for
24 h. The enantiomeric purity of the ester was monitored by chiral
HPLC analysis. The ee of the product reached >99% in 24 h. The
reaction was then stopped and the product (R)-5 was recovered
as described in Section 4.1.4 (0.63 g, 44%).
(95 mg, 95%) as a colorless oil. ½a D25
ꢂ
¼ ꢁ114:1 (c 1, CHCl3). IR(neat)
m
max = 815, 920, 1045, 1248, 1389, 1728, 2920 cmꢁ1 1H NMR
.
(300 MHz, CDCl3): d 2.29–2.39 (m, 2H), 2.40–2.62 (m, 2H), 4.40–
4.53 (m, 1H), 5.05–5.21 (m, 2H), 5.74–5.92 (m, 1H), 5.96–6.05
(dt, J = 1.70, 6.42 Hz, 1H), 6.79–6.88 (m, 1H). 13C NMR (75 MHz,
CDCl3): d 28.5, 38.9, 77.0, 118.7, 121.1, 132.1, 145.0, 164.2. ESI-
MS: m/z = 139 (M+1).
Compound (R)-5 (670 mg, 2.23 mmol) was stirred with a solu-
tion of K2CO3 (616 mg, 4.47 mmol) in methanol (10 mL) for 4 h at
room temperature and the solvent was then evaporated under re-
duced pressure. The residue was extracted with ethyl acetate
(3 ꢀ 15 mL); the ethyl acetate layer was dried over anhydrous
Na2SO4 and evaporated to obtain (R)-4 (504 mg, 98%) as a colorless
4.1.9. (R,E)-6-(4-Oxo-6-phenylhex-2-enyl)-5,6-dihydro-2H-pyran-
2-one (R)-rugulactone (R)-1
To a stirred solution of (R)-9 (42 mg, 0.3 mmol) and 5-phenyl-
pent-1-en-3-one (145 mg, 0.91 mmol) in dry 1.5 mL CH2Cl2 was
added Grubbs’ second-generation catalyst (2.6 mg, 10 mol %), and
the reaction mixture was stirred at 50 °C for 5 h. After completion
of the reaction, the solvent was removed under reduced pressure
and the residue was chromatographed over silica gel (60–120
mesh, EtOAc/hexane, 4:5) to yield 1a (62 mg, 75%) as a colorless
oil. ½a 2D5
¼ þ7:8 (c 1, CHCl3).
ꢂ
4.1.6. (R)-Hex-5-ene-1,3-diol (R)-6
Compound (R)-4 (441 mg, 1.91 mmol) was stirred with a solu-
tion of PTSA (13 mg, 0.05 mmol) in methanol (10 mL) for 1 h at
room temperature. Methanol was removed by evaporation under
reduced pressure, after which sodium carbonate solution (1 mL,
10%) was added and the product was extracted with ethyl acetate
(3 ꢀ 15 mL). The ethyl acetate layer was dried over anhydrous
Na2SO4 and evaporated, yielding (R)-6 (241 mg, 96%) as a colorless
oil. ½a 2D5
ꢂ
¼ ꢁ46:9 (c 1, CHCl3), lit.2
½
a 2D5
ꢂ
¼ ꢁ46:5 (c 1, CHCl3). IR(-
neat) mmax = 761, 816, 962, 1046, 1191, 1247, 1385, 1671, 1727,
2556, 2879, 3027, 3452 cmꢁ1 1H NMR (300 MHz, CDCl3): d 2.29–
.
2.36 (m, 2H), 2.59–2.69 (m, 2H), 2.85–2.98 (m, 4H), 4.49–4.60
(m, 1H), 6.04 (dt, J = 1.51, 6.04 Hz, 1H), 6.20 (dt, J = 1.51,
14.35 Hz, 1H), 6.75–6.84 (m, 1H), 6.85–6.92 (m, 1H), 7.15–7.23
(m, 3H), 7.25–7.31 (m, 2H). 13C NMR (75 MHz, CDCl3): d 28.8,
29.62, 29.85, 37.44, 41.63, 76.0, 121.3, 126.0, 128.3, 128.4, 133.4,
140.0, 140.9, 144.7, 163.7, 199.0. ESI-MS: m/z = 293 (M+Na).
oil. ½a 2D5
ꢂ
¼ þ9:1 (c 1, CHCl3). IR(neat)
mmax = 917, 997, 1054, 1432,
1643, 2935, 3079, 3352 cmꢁ1
.
1H NMR (300 MHz, CDCl3): d
1.57–1.77 (m, 2H), 2.18–2.32 (m, 2H), 2.95 (br, 2H), 3.71–3.93
(m, 3H), 5.05–5.16 (m, 2H), 5.71–5.87 (m, 1H). 13C NMR (75 MHz,
CDCl3): d 37.8, 42.1, 61.0, 70.5, 118.0, 134.5. ESI-MS: m/z = 139
(M+Na).
References
4.1.7. (R,Z)-Methyl 5-hydroxyocta-2,7-dienoate (R)-8
To a stirred solution of (R)-6 (162 mg, 1.3 mmol) in dry CH2Cl2
(5 mL), BAIB (675 mg, 2.09 mmol) and TEMPO (13 mg, catalytic
amount) were added at room temperature and stirred for 4 h.
The reaction was then quenched with saturated Na2S2O3 solution
(2 mL), extracted with CH2Cl2 (2 ꢀ 8 mL), dried over anhydrous
Na2SO4,, and concentrated under reduced pressure to obtain crude
aldehyde (R)-7 (151 mg, 93%).
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