Efficient total synthesis of (-)-(3S,6R)-3,6-dihydroxy-10-methylundecanoic acid

Article abstract of DOI:10.1002/ejoc.200600690

An efficient enantioselective synthesis of (-)-(3S,6R)-3,6-dihydroxy-10- methylundecanoic acid (1) from epichlorohydrin is described. The key steps include Jacobsen's HKR, Sharpless asymmetric dihydroxylation, regioselective opening of epoxide and cyclic

Full text of DOI:10.1002/ejoc.200600690

FULL PAPER
DOI: 10.1002/ejoc.200600690
Efficient Total Synthesis of (–)-(3S,6R)-3,6-Dihydroxy-10-methylundecanoic
Acid
Satyendra Kumar Pandey[a] and Pradeep Kumar*[a]
Keywords: Jacobsen’s hydrolytic kinetic resolution (HKR) / Grignard reaction / Hydroboration–oxidation / Dihydrox-
ylation / Regioselectivity / Cyclic sulfate
An efficient enantioselective synthesis of (–)-(3S,6R)-3,6-di-
hydroxy-10-methylundecanoic acid (1) from epichlorohydrin
is described. The key steps include Jacobsen’s HKR,
Sharpless asymmetric dihydroxylation, regioselective open-
ing of epoxide and cyclic sulfate.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2007)
the key steps.[3] As part of our continuing interest towards
asymmetric synthesis of naturally occurring compounds,[4]
we have accomplished the total synthesis of (–)-(3S,6R)-3,6-
dihydroxy-10-methylundecanoic acid (1) from commercially
available epichlorohydrin using Jacobsen’s HKR, Sharpless
asymmetric dihydroxylation and regioselective opening of
epoxide and cyclic sulfate as the key steps.
Introduction
(–)-(3S,6R)-3,6-Dihydroxy-10-methylundecanoic acid (1)
and its trimer 2 were isolated from the aerial parts of
Lafuentea rotundifolia Lag.[1] The original structure of 1
was assigned on the basis of the spectroscopic methods and
absolute configuration of chiral centre by Mosher’s analysis
(Figure 1).[2]
Results and Discussions
The synthesis of (–)-(3S,6R)-3,6-dihydroxy-10-methylun-
decanoic acid (1) started from the commercially available
epichlorohydrin (3) as shown in Scheme 1. Epichlorohydrin
(3) was subjected to Jacobsen’s HKR using the (R,R)-
(salen)CoIII·OAc complex (Figure 2) as catalyst to give (R)-
Scheme 1. Reagents and conditions: (i) (R,R)-(salen)CoIII·OAc
(0.5 mol-%), distd. H2O (0.55 equiv.), 0 °C, 14 h, (46% for 3a, 45%
for 3b).
Figure 1. (–)-(3S,6R)-3,6-dihydroxy-10-methylundecanoic acid (1)
and its trimer (2).
Compound 1 has been a synthetic target of considerable
interest due to its β-hydroxy acid skeleton and unique 1,4-
dihydroxy structure with an array of functionalities. Very
recently, Li et al. reported the first total synthesis of 1 in 11
steps using asymmetric allylboration by B-allyldiisopino-
campheylborane and hydroboration–oxidation reactions as
[a] Division of Organic Chemistry, Technology, National Chemical
Laboratory,
Pune 411008, India
Fax: +91-20-25902629
E-mail: pk.tripathi@ncl.res.in
Figure 2. Jacobsen’s hydrolytic kinetic resolution (HKR) catalyst.
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim 369
Eur. J. Org. Chem. 2007, 369–373

S. Kumar Pandey, P. Kumar
FULL PAPER
Scheme 2. Reagents and conditions: (a) Me2CH(CH2)2MgBr, CuI, dry Et2O, –78 °C, 12 h, 98%; (b) KOH, Et2O, 0 °C to room temp.,
6 h, 96%; (c) C2H3MgBr, CuI, THF, –78 °C to room temp., 12 h, 95%; (d) BnBr, TBAI, NaH, DMF, 0 °C to room temp., 1.5 h, 97%;
(e) (i) BH3.SMe2, THF, 0 °C to room temp., 4 h; (ii) 3  NaOH, H2O2, 0 °C to room temp., 6 h, 88%; (f) (COCl)2, DMSO, CH2Cl2,
–78 °C, 1.5 h, Et3N, –60 °C, 1 h (ii) Ph3P=CHCO2Et, THF, room temp., 24 h, 93%; (g) (DHQ)2PHAL (1 mol-%), 0.1  OsO4 (0.5 mol-
%), K2CO3, K3Fe(CN)6, MeSO2NH2, tBuOH/H2O, 1:1, 0 °C, 24 h, 96%; (h) (i) SOCl2, Et3N, CH2Cl2, 0 °C, 30 min; (ii) RuCl3, NaIO4,
CCl4/MeCN/H2O; 2:2:3, 0 °C, 1 h, 98%; (i) NaBH4, DMAC, 25 °C, 30 min, then 20% aq. H2SO4, overnight, 86%; (j) 20% Pd(OH)2/C,
H2, EtOAc, room temp., 10 h, 81%.
epichlorohydrin (3a) as a single isomer [α]2D5 = –32.5 (c = fate 11 reacted with 1 equiv. of NaBH4 with apparent com-
1.25, MeOH); {ref.[5] [α]2D6 = –32.8 (c = 1.27, MeOH)}, plete selectivity for attack at C-2 position to furnish the
which was easily isolated from the more polar diol 3b by intermediate sulfate ester which, without further isolation
distillation (Scheme 1).[5]
was subjected to acidic hydrolysis using 4  H2SO4 to give
With enantiomerically pure epichlorohydrin (3a) in hand, 12 in excellent yield. Finally, benzyl deprotection with 20%
we then subjected it to copper-catalysed (CuI) regioselective Pd(OH)2/H2 led to 1 as a white powder in 81% yield. The
ring-opening with isoamylmagnesium bromide (3aǞ4) fol- physical and spectroscopic data were in full agreement with
lowed by treatment with base to give the epoxide 5 the literature.[3]
(Scheme 2). Subsequent reaction with vinylmagnesium bro-
mide furnished 6 in overall 89% yield. The hydoxyl protec-
tion of 6 with benzyl bromide in the presence of NaH gave
7 in 97% yield, which was then subjected to hydroboration–
Conclusions
In conclusion, a practical and enantioselective synthesis
of (–)-(3S,6R)-3,6-dihydroxy-10-methylundecanoic acid has
been achieved from epichlorohydrin in 10 steps and 46.5%
overall yield, employing Jacobsen’s HKR, Sharpless asym-
metric dihydroxylation, regioselective opening of epoxide
and cyclic sulfate as the key steps. The merits of this synthe-
sis are high diastereoselectivity and high yielding reaction
steps. The synthetic strategy described has significant po-
tential for further extension to other analogues of β-hy-
droxy carboxylic acid with no substituents at Cα.
oxidation reaction to afford the alcohol 8 in 88% yield.
Our next aim was to carry out the two carbon homologa-
tion of 8 by means of Wittig reaction. To this end, com-
pound 8 was oxidised to the aldehyde under Swern condi-
tions,[6] the product was subsequently treated with (ethoxy-
carbonylmethylene)triphenylphosphorane in dry THF at
room temperature to furnish the trans-Wittig product 9 in
93% yield. The dihydroxylation of olefin 9 with osmium
tetroxide and potassium ferricyanide as co-oxidant in the
presence of (DHQ)2PHAL under the Sharpless asymmetric
conditions[7] gave the diol 10 in 96% yield with 94% de.
Treatment of the diol 10 with thionyl chloride and triethyl-
amine in CH2Cl2 gave the cyclic sulfite, which was further
oxidised using NaIO4 and a catalytic amount of ruthenium
trichloride to furnish the corresponding cyclic sulfate 11[8]
in quantitative yield. The synthetic strategy shown in
Scheme 2 was based on the presumption that the nucleo-
philic opening of the cyclic sulfate 11 would occur in a re-
Experimental Section
Solvents were purified and dried by standard procedures before
use. Petroleum ether of boiling range 60–80 °C was used. Optical
rotations were measured using sodium D line on JASCO-181 digi-
tal polarimeter. Infrared spectra were recorded with a Perkin–El-
mer model 683 grating Infrared spectrometer. Mass spectrum was
giospecific manner at the α-carbon.[9] Indeed, the cyclic sul- obtained with a TSQ 70, Finningen MAT mass spectrometer. 1H
370
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© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2007, 369–373

Total Synthesis of (–)-(3S,6R)-3,6-Dihydroxy-10-methylundecanoic Acid
FULL PAPER
NMR (200 MHz) and 13C (50 MHz) NMR spectra were recorded
in CDCl3 solution with residual CHCl3 (= 7.27 ppm) and (= 77.00
ppm) respectively as internal standard. Elemental analyses were
carried out with a Carlo Erba CHNS-O analyzer. Diastereomeric
was then stirred at room temperature for 30 min after which it was
again cooled to 0 °C. Benzyl bromide (2.49 g, 15.49 mmol) and
tetra-n-butylammonium iodide (262 mg, 0.71 mmol) was slowly
added thereto with further stirring for 1 h at the same temperature.
The reaction mixture was quenched with addition of cold water at
0 °C. The two phases were separated and the aqueous phase was
extracted with EtOAc (3ϫ30 mL). The combined organic layers
were washed with water (3ϫ20 mL), brine, dried (Na2SO4) and
concentrated. The residual oil was purified by silica gel column
chromatography (Rf = 0.45, EtOAc/petroleum ether, 1:50) to fur-
nish the benzyl-protected alcohol 7 (3.36 g, 97%) as a colourless
1
excess was determined using H and 13C NMR spectroscopy. Col-
umn chromatography was performed on silica gel (60–120 and 230–
400 mesh) using a mixture of petroleum ether and ethyl acetate as
eluent.
(R)-1-Chloro-6-methylheptan-2-ol (4): A solution of isoamylmagne-
sium bromide prepared form isoamyl bromide (9.8 g, 64.85 mmol)
and Mg turnings (1.58 g, 64.85 mmol) in dry Et2O was added drop-
wise to a stirred solution of (R)-epichlorohydrin (3a) (Ͼ99% ee,
3.00 g, 32.43 mmol) and CuI (1.24 g, 6.49 mmol) in dry Et2O
(50 mL) at –78 °C. The mixture was warmed to –20 °C within 12 h
and poured into a saturated NH4Cl solution. The layers were sepa-
rated and the aqueous layer was extracted with Et2O (3ϫ50 mL).
The combined ethereal extracts were dried with Na2SO4. The ex-
tracts were concentrated to near dryness and purified on silica gel
column chromatography (Rf = 0.40, EtOAc/petroleum ether, 1:9)
to give 4 as a colourless oil (5.23 g, 98%). [α]2D5 = +6.07 (c = 1,
CHCl ). IR (neat): ν = 3409, 2955, 1467, 1216 cm–1. 1H NMR
oil. [α]2D5 = +9.44 (c = 1.0, CHCl ). IR (neat): ν = 2867, 1640, 1454,
˜
3
1095 cm–1. 1H NMR (200 MHz, CDCl3): δ = 0.88 (d, J = 6.82 Hz,
6 H), 1.11–1.60 (m, 7 H), 2.34 (t, J = 6.37 Hz, 2 H), 3.40–3.51
(quint, 1 H), 4.50 (d, J = 11.62 Hz, 1 H), 4.59 (d, J = 11.62 Hz, 1
H), 5.04–5.06 (m, 1 H) 5.09–5.11 (m, 1 H), 5.14–5.15 (m, 1 H),
7.30–7.41 (m, 5 H) ppm. 13C NMR (50 MHz, CDCl3): δ = 22.6,
23.1, 27.9, 34.0, 38.3, 39.0, 70.9, 78.5, 116.7, 127.4, 127.7, 128.2,
135.1, 138.9 ppm. C17H26O (246.39): calcd. C 82.87, H 10.64; found
C 82.91, H 10.59.
˜
3
(R)-4-(Benzyloxy)-8-methylnonan-1-ol (8): BH3·DMS (1.09 g,
6.58 mL, 14.29 mmol, 2  solution in THF) was added to a solu-
tion of 7 (3.2 g, 12.99 mmol) in dry THF (35 mL) at 0 °C under
argon, and the reaction mixture was warmed to room temperature
and stirred for 4 h. The reaction flask was cooled to 0 °C and then
a solution of NaOH (1.04 g, 25.98 mmol) in EtOH/H2O (2:1,
15 mL), followed by H2O2 (4.41 mL, 38.96 mmol, 30% w/v solu-
tion in water) were added dropwise within 30 min. It was then
stirred at room temperature for 6 h. The product was taken up in
EtOAc and the aqueous layer extracted with EtOAc (3ϫ25 mL).
The combined organic layers were washed with brine, water, dried
(Na2SO4) and concentrated. Purification by silica gel column
chromatography (Rf = 0.30, EtOAc/petroleum ether, 2:8) of the
crude product gave alcohol 8 as a colourless liquid (3.02 g, 88%).
(200 MHz, CDCl3): δ = 0.89 (d, J = 6.6 Hz, 6 H), 1.14–1.64 (m, 7
H), 2.09 (br. s, 1 H), 3.57 (ddd, J = 3.3, 8.0, 18.0 Hz, 2 H), 3.76–
3.87 (m, 1 H) ppm. 13C NMR (50 MHz, CDCl3): δ = 22.4, 23.2,
27.8, 34.4, 38.7, 50.3, 71.4 ppm. C8H17ClO (164.67): calcd. C 58.35,
H 10.41; found C 58.40, H 10.39.
(R)-2-(4-Methylpentyl)oxirane (5): Finely powdered KOH (5.21 g,
92.91 mmol) was added to a solution of 4 (5.10 g, 30.97 mmol) in
Et2O (50 mL). The mixture was stirred vigorously for 6 h between
0 °C and room temp. and poured into 20 mL water. After separa-
tion of the layers, the aqueous layer was extracted with Et2O
(3ϫ50 mL) and the combined organic layers were dried with
Na2SO4. Evaporation of the solvent and silica gel column chroma-
tographic purification (Rf = 0.70, EtOAc/petroleum ether, 1:49) of
the crude product gave 5 as a colourless liquid (3.81 g, 96%).
[α]2D5 = –6.37 (c = 1.0, CHCl ). IR (neat): ν = 3388, 2867, 1726,
˜
3
1454, 1063 cm–1. 1H NMR (200 MHz, CDCl3): δ = 0.88 (d, J =
7.0 Hz, 6 H), 1.11–1.74 (m, 11 H), 1.94 (br. s, 1 H), 3.39–3.50
(quint, 1 H), 3.64 (t, J = 6.9 Hz, 2 H), 4.49 (d, J = 11.50 Hz, 1 H),
4.57 (d, J = 11.50 Hz, 1 H), 7.30–7.37 (m, 5 H) ppm. 13C NMR
(50 MHz, CDCl3): δ = 22.5, 22.9, 27.8, 28.4, 30.1, 33.7, 38.9, 62.7,
70.7, 78.8, 127.4, 127.7, 128.2, 138.6 ppm. C17H28O2 (264.40):
calcd. C 77.22, H 10.67; found C 77.15, H 10.70
[α]2D5 = +5.96 (c = 1, CHCl ). IR (neat): ν = 3018, 2869, 1736, 1467,
˜
3
1216 cm–1. H NMR (200 MHz, CDCl3): δ = 0.89 (d, J = 6.7 Hz,
1
6 H), 1.16–1.63 (m, 7 H), 2.47 (dd, J = 3.1, 5.3 Hz, 1 H), 2.76 (t,
J = 4.5 Hz, 1 H), 2.87–2.96 (m, 1 H) ppm. 13C NMR (50 MHz,
CDCl3): δ = 22.4, 23.7, 27.9, 32.7, 38.6, 47.0, 52.2 ppm. C8H16O
(128.21): calcd. C 74.94, H 12.58; found C 74.84, H 12.49.
(R)-8-Methylnon-1-en-4-ol (6): Vinylmagnesium bromide (3.07 g,
23.40 mmol, 23.40 mL, 1  solution in THF) was added dropwise
to a stirred solution of 5 (2.00 g, 15.60 mmol) and CuI (594 mg,
3.12 mmol) in dry THF (30 mL) over 30 min at –78 °C and stirred
for 12 h. The mixture was warmed to 0 °C, before it was quenched
with a saturated NH4Cl solution (20 mL). The layers were sepa-
rated, the aqueous layer extracted with Et2O (3ϫ30 mL), the com-
bined ethereal extracts were washed with brine (20 mL) and dried
(Na2SO4). Evaporation of the solvent and purification by silica gel
column chromatography (Rf = 0.50, EtOAc/petroleum ether, 1:20)
of the crude product gave 6 as a colourless oil (2.32 g, 95%). [α]2D5
Ethyl (R,E)-6-(Benzyloxy)-10-methylundec-2-enoate (9): DMSO
(2.56 g, 2.33 mL, 32.83 mmol) in CH2Cl2 (5 mL) was added drop-
wise to a solution of oxalyl chloride (2.02 g, 15.89 mmol) in dry
CH2Cl2 (30 mL) at –78 °C within 15 min. The reaction mixture was
stirred for 30 min and a solution of 8 (2.8 g, 10.59 mmol) in CH2Cl2
(20 mL) was added dropwise within 15 min. The reaction mixture
was stirred for 30 min at –78 °C and 30 min at –60 °C and then
Et3N (4.72 g, 6.50 mL, 46.60 mmol) in CH2Cl2 (5.00 mL) was
added dropwise and stirred for 1 h. The reaction mixture was
poured into saturated solution of NaHCO3 (50 mL) and the or-
ganic layer separated. The aqueous layer was extracted with diethyl
ether (3ϫ20 mL) and the combined organic layers were washed
(brine), dried (Na2SO4) and concentrated to give the crude alde-
hyde. This was used for the next step without further purification.
= +2.80 (c = 1.0, CHCl ). IR (CHCl ): ν = 3421, 2955, 1640, 1467,
˜
3
3
1
1216 cm–1. H NMR (200 MHz, CDCl3): δ = 0.88 (d, J = 6.6 Hz,
6 H), 1.13–1.61 (m, 7 H), 2.06–2.38 (m, 2 H), 3.59–3.71 (m, 1 H),
5.08–5.12 (m, 1 H), 5.16–5.20 (m, 1 H), 5.74–5.94 (m, 1 H) ppm.
13C NMR (50 MHz, CDCl3): δ = 22.5, 23.4, 27.9, 37.0, 38.9, 41.9,
70.6, 117.8, 134.9 ppm. C10H20O (156.27): calcd. C 76.86, H 12.90;
found C 76.51, H 12.93.
A solution of the above aldehyde in dry THF (10 mL) was added
to a solution of (ethoxycarbonylmethylene)triphenylphosphorane
(4.06 g, 11.65 mmol) in dry THF (20 mL). The reaction mixture
was stirred at room temperature for 24 h. It was then concentrated
and purified by silica gel column chromatography (Rf = 0.60,
(R)-[(8-Methylnon-1-en-4-yloxy)methyl]benzene (7): NaH (60%,
0.85 g, 21.12 mmol) was added to
a solution of 6 (2.2 g,
14.07 mmol) in dry DMF (50 mL) at 0 °C. The reaction mixture EtOAc/petroleum ether, 1:9) to give olefin 9 as a pale yellow oil
Eur. J. Org. Chem. 2007, 369–373
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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371

S. Kumar Pandey, P. Kumar
FULL PAPER
(3.27 g, 93%). [α]2D5 = –11.45 (c = 1.0, CHCl ). IR (CHCl ): ν =
of the cyclic sulfate 11 (300 mg, 0.70 mmol) in dry DMAC (8 mL).
The reaction mixture was stirred under argon at room temperature
˜
3
3
2953, 1721, 1654, 1268, 1046 cm–1. 1H NMR (200 MHz, CDCl3):
δ = 0.88 (d, J = 6.4 Hz, 6 H), 1.15–1.74 (m, 12 H), 2.20–2.41 (m, for 30 min. The solvent was removed under reduced pressure and
2 H), 3.36–3.47 (quint, 1 H), 4.19 (q, J = 7.6, 14.5 Hz, 2 H), 4.46
(d, J = 11.50 Hz, 1 H), 4.55 (d, J = 11.50 Hz, 1 H) 5.82 (dt, J =
the reaction mixture was acidified with 4  H2SO4 (6 mL) and
stirred at room temperature overnight. The solvent was stripped off
1.70, 15.7 Hz, 1 H) 6.86–7.05 (m, 1 H), 7.29–7.37 (m, 5 H) ppm. under reduced pressure and the residue was purified by silica gel
13C NMR (50 MHz, CDCl3): δ = 14.2, 22.5, 27.8, 28.0, 32.1, 33.8,
39.0, 60.0, 70.8, 77.9, 121.3, 127.4, 127.7, 128.2, 138.7, 149.0, 166.5.
C21H32O3 (332.48): calcd. C 75.86, H 9.70; found C 75.88, H 9.69.
column chromatography (Rf = 0.50, EtOAc/petroleum ether, 1:1.5)
to give 12 as a colourless syrup (190 mg, 86%). [α]2D5 = +4.01 (c =
1.0, CHCl ). IR (CHCl ): ν = 3425, 2916, 1651, 1265 cm–1. 1H
˜
3
3
NMR (200 MHz, CDCl3): δ = 0.86 (d, J = 6.6 Hz, 6 H), 1.18–1.85
(m, 11 H), 2.33–2.56 (m, 3 H), 3.99–4.09 (m, 1 H), 4.12 (d, J =
11.40 Hz, 1 H), 4.20 (d, J = 11.40 Hz, 1 H), 5.12–5.24 (quint, 1 H),
7.33–7.61 (m, 3 H), 8.05 (d, J = 7.0 Hz, 2 H) ppm. 13C NMR
(50 MHz, CDCl3): δ = 13.7, 19.2, 19.7, 22.5, 22.6, 27.9, 30.5, 38.0,
65.5, 71.7, 72.5, 128.3, 128.8, 130.9, 132.3, 167.7 ppm. C19H30O4
(322.44): calcd. C 70.77, H 9.38; found C 70.84, H 9.41.
Ethyl (2R,3S,6R)-6-(Benzyloxy)-2,3-dihydroxy-10-methylundecano-
ate (10): Osmium tetroxide (0.22 mL, 0.1  solution in toluene,
0.5 mol-%) was added to
a mixture of K3Fe(CN)6 (4.46 g,
13.53 mmol), K2CO3 (1.87 g, 13.53 mmol), (DHQ)2PHAL (35 mg,
1 mol-%) in tBuOH/H2O (1:1, 20 mL) at 0 °C, followed by meth-
anesulfonamide (428 mg, 4.50 mmol). After stirring for 2 min at
0 °C, the olefin 9 (1.5 g, 4.51 mmol) was added in one portion. The
reaction mixture was stirred at 0 °C for 24 h and then quenched
with solid sodium sulfite (3 g). The stirring was continued for ad-
ditional 15 min and then the solution was extracted with EtOAc
(3ϫ20 mL). The combined extracts were washed with brine, dried
(Na2SO4) and concentrated. Purification by silica gel column
chromatography (Rf = 0.30, EtOAc/petroleum ether, 1:4) of the
crude product gave 10 as a colourless syrupy liquid (1.59 g, 96%,
(3S,6R)-3,6-Dihydroxy-10-methylundecanoic Acid (1): A catalytic
amount of 20% Pd(OH)2/C was added to a solution of 12 (51 mg,
0.16 mmol) in EtOAc (8 mL). The reaction mixture was hydroge-
nated using a H2 balloon for 10 h at room temperature. After this
time the reaction mixture was filtered through a pad of celite and
the pad was washed with additional EtOAc (30 mL). Purification
by silica gel column chromatography (Rf = 0.25, EtOAc/petroleum
ether, 8:2) of the crude product gave 1 as a white powder (30 mg,
81%). m.p. 150–151 °C {ref.[3] 149–151 °C}, [α]2D5 = –9.66 (c = 0.9
94% de). [α]2D5 = –15.08 (c = 1.0, CHCl ). IR (neat): ν = 3444, 2867,
˜
3
1737, 1454, 1275, 1206 cm–1. 1H NMR (200 MHz, CDCl3): δ =
0.86 (d, J = 6.5 Hz, 6 H), 1.14–1.79 (m, 14 H), 2.40 (br. s, 2 H),
3.38–3.50 (m, 1 H), 3.86–3.91 (m, 1 H), 4.06 (dd, J = 2.0, 4.1 Hz,
1 H), 4.30 (q, J = 7.1 Hz, 2 H), 4.49 (d, J = 11.75 Hz, 1 H), 4.56
CHCl3), {ref.[3] [α]2D5 = –7.00 (c = 0.9, CHCl )}. IR (CHCl ): ν =
˜
3
3
3386, 2957, 1685 cm–1. H NMR (200 MHz, CDCl3): δ = 0.88 (d,
1
J = 6.8 Hz, 6 H), 1.16–1.67 (m, 11 H), 1.84 (br. s, 2 H), 2.47–2.50
(d, J = 11.75 Hz, 1 H), 7.30–7.36 (m, 5 H) ppm. 13C NMR (m, 2 H), 3.60–3.69 (m, 1 H), 4.01–4.10 (m, 1 H) ppm. MS (ESI):
+
(50 MHz, CDCl3): δ = 14.0, 22.5, 22.9, 27.8, 29.3, 29.7, 33.7, 38.9,
61.7, 70.6, 72.5, 73.3, 78.6, 127.4, 127.7, 128.2, 138.6, 173.4 ppm.
C21H34O5 (366.24): calcd. C 68.82, H 9.35; found C 68.64, H 9.43.
m/z = 232 [M]
.
Acknowledgments
(2R,3S,6R)-5-(3-Benzyloxy-7-methyloctyl)-4-ethoxycarbonyl-1,3,2-
dioxathiolane 2,2-Dioxide (11): Et3N (290 mg, 0.4 mL, 2.87 mmol)
was added to a solution of diol 10 (500 mg, 13.65 mmol) in dry
CH2Cl2 (15 mL). The mixture was cooled in an ice bath and thionyl
chloride (180 g, 0.11 mL, 15.02 mmol) was added dropwise at 0 °C.
The reaction mixture was stirred for 30 min and then quenched by
adding water (10 mL). The phases were separated and aqueous
phase extracted with CH2Cl2 (3ϫ10 mL). The combined organic
phases were dried with Na2SO4 and concentrated. Then the solu-
tion was cooled with an ice-water bath and diluted with CH3CN
(10 mL) and CCl4 (10 mL). RuCl3·H2O (15 mg, 0.07 mmol) and
NaIO4 (518 mg, 2.43 mmol) were added, followed by water
(15 mL). The resulting orange mixture was stirred at room tem-
perature for 1 h. The mixture was then diluted with diethyl ether
(20 mL), and the two phases separated. The organic layer was
washed with water (20 mL), saturated with aq. NaHCO3 (20 mL),
brine, dried with Na2SO4, and concentrated. Purification by silica
gel column chromatography (Rf = 0.60, EtOAc/petroleum ether,
1:5) of the crude product gave the sulfate 11 as a colourless liquid
S. K. P. thanks CSIR New Delhi for a research fellowship. We are
grateful to Dr. M. K. Gurjar for his support and encouragement.
Financial support from DST, New Delhi (Project Grant No. SR/
S1/OC-40/2003) is gratefully acknowledged. This is NCL communi-
cation No. 6696.
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(573 mg, 98%). [α]2D5 = –1.27 (c = 1.0, CHCl ). IR (neat): ν = 2954,
˜
3
1765, 1739, 1454, 1217 cm–1. 1H NMR (200 MHz, CDCl3): δ =
0.89 (d, J = 6.3 Hz, 6 H), 1.16–1.23 (m, 14 H), 3.40–3.51 (quint, 1
H), 4.30 (q, J = 7.6, 11.4 Hz, 2 H), 4.47 (d, J = 11.74 Hz, 1 H),
4.56 (d, J = 11.74 Hz, 1 H), 4.59–4.73 (m, 1 H), 5.00–5.20 (m, 1
H), 7.30–7.36 (m, 5 H) ppm. 13C NMR (50 MHz, CDCl3): δ =
13.9, 22.5, 27.8, 29.5, 30.2, 33.7, 38.9, 62.4, 70.8, 81.3, 82.5, 86.64,
127.5, 127.7, 128.3, 138.6, 166.8 ppm. C21H32O7S (428.54): calcd.
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(3S,6R)-6-(Benzyloxy)-3-hydroxy-10-methylundecanoic Acid (12):
NaBH4 (26 mg, 0.70 mmol) was added under argon to a solution
372
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Eur. J. Org. Chem. 2007, 369–373

Total Synthesis of (–)-(3S,6R)-3,6-Dihydroxy-10-methylundecanoic Acid
FULL PAPER
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Received: August 8, 2006
Published Online: October 27, 2006
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Eur. J. Org. Chem. 2007, 369–373
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