An efficient synthesis of (-)-posticlure: The sex pheromone of Orgyia postica

Article abstract of DOI:10.1002/ejoc.200700449

An efficient multigram synthesis of (-)-posticlure, the first frans-epoxide sex pheromone found in Orgyia postica, from diethyl L-tartrate is described. The synthesis was completed in seven steps and 27 % overall yield. The synthetic strategy features double-Wittig olefination and a stereoselective one-pot conversion of diol to epoxide as the key steps. Wiley-VCH Verlag GmbH & Co. KGaA, 2007.

Full text of DOI:10.1002/ejoc.200700449

FULL PAPER
DOI: 10.1002/ejoc.200700449
An Efficient Synthesis of (–)-Posticlure: The Sex Pheromone of Orgyia postica
Rodney A. Fernandes*[a]
Keywords: Pheromones / Orgyia postica / Asymmetric synthesis / Epoxides / Diethyl -tartrate
An efficient multigram synthesis of (–)-posticlure, the first
trans-epoxide sex pheromone found in Orgyia postica, from
diethyl L-tartrate is described. The synthesis was completed
in seven steps and 27% overall yield. The synthetic strategy
features double-Wittig olefination and a stereoselective one-
pot conversion of diol to epoxide as the key steps.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2007)
Scheme 1. The target compound can be envisioned to be
easily derived from a cyclic orthoacetate 2, which, via the
acetoxonium ion, can be opened with bromide to give the
acetoxy bromide intermediate which upon hydrolysis would
produce the epoxide stereoselectively.[6] Compound 2 can
be derived from a vicinal diol. Hence the inherent chirality
of diethyl -tartrate (7) can be envisioned in compounds 2
and 5 and these can be derived (from diethyl -tartrate) by
successively attaching the corresponding side-chains by
Wittig olefination (route A). We planned to protect the di-
ethyl -tartrate hydroxy groups as a cyclic orthoacetate al-
Introduction
Orgyia postica is a tussock moth and a known pest to
mango and litchi in Okinawa, Japan.[1] Wakamura et al. in
2001 isolated the first trans-epoxide pheromone from
Orgyia postica and identified it as (6Z,9Z,11S,12S)-trans-
11,12-epoxyhenicosa-6,9-diene.[2] It was named “posticlure”
(1, Figure 1) in reference to the species name.[3] The coup-
ling constant of J = 2.2 Hz between the epoxide protons
confirmed the trans-oxirane structure. In the same report,
Wakamura described a short synthesis of natural posticlure
and its optical antipode employing the Sharpless asymmet-
ric epoxidation reaction with 59% ee. The optically pure
samples were obtained by preparative HPLC for field study.
Enantioselective synthesis of both (–)- and (+)-posticlure
employing the Sharpless asymmetric dihydroxylation pro-
cedure has also been reported.[4,5] No chiral pool synthesis,
which could give highly optically pure material, has been
reported. Herein a short, multigram stereoselective synthe-
sis of (–)-posticlure (1) starting from diethyl -tartrate is
described. The keys steps are double-Wittig olefination and
a stereoselective one-pot conversion of diol to epoxide.
Figure 1. (–)-Posticlure (1), the first trans-epoxide pheromone.
Results and Discussion
The various strategic considerations for the synthesis of
(–)-posticlure (1) from diethyl -tartrate (7) are shown in
[a] Departamento Organica Sintesis, Instituto de Quimica, Uni-
versidad Nacional Autonoma de Mexico, Circuito Exterior,
Ciudad Universitaria,
Coyoacan, 04510 Mexico D.F., Mexico
Fax: +52-55-56162217
E-Mail: fernandr@servidor.unam.mx
Supporting information for this article is available on the
WWW under http://www.eurjoc.org/ or from the author.
Scheme 1. Strategic considerations for the synthesis of (–)-post-
iclure (1).
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© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2007, 5064–5070

An Efficient Synthesis of (–)-Posticlure
though the stability of this cyclic orthoacetate was of much
concern. An alternative route would be to use the acetonide
which is more stable (route B, Scheme 1). Thus, compound
2 could also be derived from 3 (although this involves an
additional step of acetonide deprotection and orthoacetate
formation). Further, 3 can be obtained (via 6) from diethyl
-tartrate (7) by acetonide protection.[7] While this strategy
involves first attaching the diene side-chain and then install-
ing the epoxide in the final step, an alternative strategy
could be to first install the epoxide 4 from 6 and then attach
the diene side-chain in the final step.
At the onset, the reaction of diethyl -tartrate (7) with
trimethyl orthoacetate and catalytic pTsOH gave compound
8[8] in quantitative yield (Scheme 2). The LiAlH4 reduction
of 8 was a messy reaction. Even reverse addition, when Li-
AlH4 was added in portions to the solution of 8 in dry THF
at 0 °C, failed to give 9.[9] Changing the reducing agent to
DIBAl-H also failed to deliver 9. This could be due to the
poor stability of the cyclic orthoacetate, which is probably
hydrolyzed or decomposes during the reaction or work up.
Hence we planned to synthesize first compound
5
(Scheme 2) by acetonide protection so that we could probe
the stability of the cyclic orthoacetate towards subsequent
reaction conditions. Acetonide protection of diethyl -tar-
trate with 2,2-dimethoxypropane and catalytic pTsOH gave
10.[10] LiAlH4 reduction of 10 and further monohydroxy
protection with benzyl bromide afforded 11 in 82% yield.[11]
Swern oxidation of 11 and subsequent Wittig reaction with
n-C7H15CH=PPh3 afforded the Z isomer 6 (1H NMR indi-
cated a 97:3 Z/E mixture, however this is of no consequence
since this double bond needs to be saturated at a later stage)
in 80% yield. Further deprotection of the acetonide in 6
gave the corresponding diol 12 which, when treated with
trimethyl orthoacetate and catalytic pTsOH, failed to de-
liver the cyclic orthoacetate 5. However, a mixture of re-
gioisomeric monoacetoxy diols 13 and 14 was obtained in
78% yield.[12] Thus, the cyclic orthoacetate could not be
prepared and we opted to complete the synthesis of the tar-
get by acetonide protection.[13]
Scheme 2. Attempted synthesis of cyclic orthoacetate 5. Reagents
and conditions: (a) CH3C(OCH3)3 (1.5 equiv.), pTsOH (cat.),
CH2Cl2, room temp., 12 h, quant.; (b) (CH3)2C(OCH3)2
(1.5 equiv.), pTsOH (cat.), benzene, reflux, 8 h, quant.; (c) LiAlH4
(2.5 equiv.), THF, 0 °C, 12 h; (d) i. LiAlH4 (2.5 equiv.), THF, reflux,
4 h; ii. NaH (1.1 equiv.), DMF, –15 °C, 30 min, BnBr (1 equiv.),
1 h, room temp., 1 h, 82% from 10; (e) i. (COCl)2 (1.5 equiv.),
DMSO (3.0 equiv.), –78 °C, 20 min, 11, 45 min, Et3N (5 equiv.),
–78 °C, 30 min, to room temperature, 1 h; ii. n-C7H15CH2P+Ph3Br–
(1.1 equiv.), nBuLi (1.1 equiv.), room temp., 30 min, –80 °C, alde-
hyde (from 11), 2 h, room temp., overnight, 80% from 11; (f) 4 
HCl, MeOH, room temp., 8 h, 93%; (g) CH3C(OCH3)3 (1.2 equiv.),
pTsOH (cat.), CH2Cl2, 0 °C, 1.5 h, 78% (13+14).
The synthesis of (–)-posticlure (1) from 6 was completed
as shown in Scheme 3. We had two different strategies avail-
able from 6 to the target molecule 1: 1) to install the epoxide
stereoselectively first and then to attach the cis,cis-diene [Pd(OH)2/C (20%)][15] gave the epoxy alcohol 4[16] in 94%
side-chain and 2) to attach the cis,cis-diene side-chain first yield. Further oxidation of the alcohol with PCC under
followed by installation of the trans-epoxide. Both strategies buffered conditions with NaHCO3 followed by condensa-
involve the same number of steps to the target molecule and tion of the aldehyde with (Z)-n-C5H11CH=CHCH2-
were executed as follows. The diol 12 was easily trans- CH=PPh3 at –80 °C afforded (–)-posticlure (1) in 77%
formed into the epoxide using the Sharpless one-pot yield, [α]2D0 = –11.2 (c = 0.4, CHCl3) {ref.[5] [α]D20 = –10.8 (c
method.[6] Thus, the treatment of diol 12 with trimethyl or- = 1.07, CHCl3); ref.[4] [α]D20 = –11.1 (c = 1, CHCl3)}. The
thoacetate and catalytic pTsOH at room temperature fol- spectroscopic and analytical data of 1 matched well with
lowed by removal of volatiles afforded the intermediate cy- those reported.[4,5] The overall yield for this seven-step
clic orthoacetate which, without isolation, was immediately strategy was 27%.
treated with acetyl bromide to afford the regioisomeric
Alternatively, hydrogenation of the double bond and de-
halohydrin acetates.[14] Treatment of these with K2CO3 in benzylation of 6 with Pearlman’s catalyst [Pd(OH)2/C
MeOH resulted in hydrolysis of the acetate and subsequent (20%)] afforded the acetonide alcohol 15 in an excellent
oxirane formation affording stereoselectively the epoxide 16 yield of 95%. Further Swern oxidation of 15 and subse-
in 90% yield from 12. Subsequent hydrogenation of the quent Wittig reaction following a similar approach to that
double bond and debenzylation with Pearlman’s catalyst described in the literature[4] with (Z)-n-C5H11CH=CHCH2-
Eur. J. Org. Chem. 2007, 5064–5070
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5065

R. A. Fernandes
FULL PAPER
starting from chiral pool material, diethyl -tartrate, in
seven steps and 27% overall yield. The inherent chirality of
diethyl -tartrate is realized in the target pheromone and
the required side-chains were easily attached through suc-
cessive Wittig olefination reactions. The required trans-oxir-
ane structure was installed through a one-pot stereoselec-
tive conversion of diol to epoxide. The synthesis of the un-
natural antipode (+)-posticlure can also be visualized by
employing diethyl -tartrate. This alternative route will pro-
vide an easy excess to both (–)- and (+)-posticlure in
multigram quantities for field study and pest control.
Experimental Section
Solvents were purified and dried by standard procedures before use.
Commercially available reagents were used as procured. Melting
points are uncorrected. Optical rotations were measured using the
sodium D line at 589 nm with a Perkin–Elmer Model 343 polarime-
ter at 20 °C. IR spectra were recorded with a Bruker TENSOR 27
spectrometer as neat thin films or CHCl3 solution for solids. 1H
and 13C NMR were recorded with an Eclipse 300 MHz JEOL, a
Bruker Avance 300 MHz or a Gemini 200 MHz spectrometer with
TMS (δ = 0.00 ppm) and CHCl3 (δ = 77.00 ppm) as internal stan-
dards for 1H and 13C NMR, respectively. Mass spectra were re-
corded with a JEOL AX505HA spectrometer. The Wittig salts were
prepared by refluxing an equimolar mixture of the corresponding
alkyl halide and PPh3 in CH3CN solvent with a pinch of NaHCO3
for 18 h. The solvent was removed by rotary evaporation and the
white sticky solids were dried under high vacuum and handled un-
der argon.
Scheme 3. Synthesis of (–)-posticlure (1) from 6. Reagents and con-
ditions: (a) 4  HCl, MeOH, room temp., 8 h, 93%; (b) i.
CH3C(OCH3)3 (1.2 equiv.), pTsOH (cat.), CH2Cl2, room temp.,
30 min; ii. CH3COBr (1.24 equiv.), CH2Cl2, room temp., 1.5 h; iii.
K2CO3 (1.5 equiv.), MeOH, room temp., 2.5 h, 90% overall; (c)
Pd(OH)2/C (20%), H2 (80 psi), MeOH/EtOAc (1:5), room temp.,
12 h, 94%; (d) i. PCC (1.5 equiv.), NaHCO3 (1.5 equiv.), CH2Cl2,
0 °C, 4 h; ii. (Z)-n-C5H11CH=CHCH2CH2P+Ph3I– (1.1 equiv.),
nBuLi (1.1 equiv.), room temp., 30 min, –80 °C, aldehyde (from 4),
1 h, room temp., overnight, 77%; (e) Pd(OH)2/C (20%), H2 (80 psi),
MeOH/EtOAc (1:5), room temp., 12 h, 95%; (f) i. (COCl)2
(1.5 equiv.), DMSO (3 equiv.), –78 °C, 20 min, 15, 45 min, Et3N
(5 equiv.), –78 °C, 30 min, to room temperature, 1 h; ii. (Z)-n-
C5H11CH=CHCH2CH2P+Ph3I– (1.1 equiv.), nBuLi (1.1 equiv.),
room temp., 30 min, –80 °C, aldehyde (from 15), 1 h, room temp.,
overnight, 79%; (g) 4  HCl, MeOH, room temp., 8 h, 92%; (h)
i. CH3C(OCH3)3 (1.2 equiv.), pTsOH (cat.), CH2Cl2, room temp.,
20 min; ii. CH3COBr (1.2 equiv.), CH2Cl2, room temp., 1.5 h; iii.
K2CO3 (1.5 equiv.), MeOH, room temp., 2.5 h, 89% overall.
Diethyl (4R,5R)-2-Methoxy-2-methyl-1,3-dioxolane-4,5-dicarboxyl-
ate (8): Trimethyl orthoacetate (1.75 g, 14.56 mmol, 1.5 equiv.) was
added to a solution of diethyl -tartrate (7, 2 g, 9.7 mmol) and
pTsOH (25 mg) in dry CH2Cl2 (30 mL) and the mixture stirred for
12 h at room temperature. After adding a pinch of NaHCO3, the
reaction mixture was stirred for 15 min and water (50 mL) was
added. The organic layer was separated and washed with water,
brine, dried (Na2SO4) and concentrated to give virtually pure 8
(2.53 g, quantitative) as a colourless oil. [α]2D0 = –22.8 (c = 1.12,
CHCl3) {ref.[8] –22.19 (c = 0.96, CHCl )}. IR (neat): ν = 2986,
˜
3
2948, 2840, 1754, 1467, 1384, 1274, 1218, 1160, 1101, 1052, 892,
861 cm–1. 1H NMR (300 MHz, CDCl3/TMS): δ = 1.32 (t, J =
6.9 Hz, 3 H, CH3CH2O), 1.33 (t, J = 6.9 Hz, 3 H, CH3CH2O), 1.67
(s, 3 H, C-CH3), 3.33 (s, 3 H, OCH3), 4.27 (q, J = 6.9 Hz, 2 H,
CH3CH2O), 4.26–4.33 (m, 2 H, CH3CH2O), 4.73 (d, J = 5.4 Hz, 1
H, CH-O), 4.97 (d, J = 5.4 Hz, 1 H, CH-O) ppm. 13C NMR
(75 MHz, CDCl3/CHCl3): δ = 13.93 (2 C), 20.99, 50.35, 61.82,
61.84, 76.23, 76.63, 124.53, 168.75, 168.91 ppm. MS (EI): m/z (%)
= 247 (5.1) [M – 15]+, 231 (24.2), 217 (5.7), 189 (100), 115 (9.3),
75 (8.1), 59 (4.3), 43 (26.6).
CH=PPh3 at –80 °C afforded the Z isomer 3[4] (1H NMR
indicated a 97:3 Z/E ratio at the newly formed double bond
at C-9) in 79% yield. Deprotection of the acetonide was
achieved using 4  HCl in MeOH to give the diol 17 in 92%
yield. The diol 17 was easily transformed into the epoxide
by employing the one-pot procedure described for the syn-
thesis of 16 to afford stereoselectively the trans-epoxide (–)-
posticlure (1) in 89% yield, [α]2D0 = –11.3 (c = 0.48, CHCl3).
The overall yield for this alternative strategy was also 27%.
Diethyl (2R,3R)-2,3-O-Isopropylidenetartrate (10): 2,2-Dimeth-
oxypropane (18.94 g, 22.4 mL, 181.9 mmol, 1.5 equiv.) was added
to a solution of diethyl -tartrate (7, 25 g, 121.25 mmol) and
pTsOH (250 mg) in dry benzene (300 mL) and the reaction mixture
refluxed for 8 h with Dean–Stark removal of MeOH. After cooling
to room temperature, NaHCO3 (3 g) was added and the mixture
was stirred for 15 min. Water (200 mL) was added and the organic
layer separated. The aqueous layer was extracted with EtOAc
(2ϫ50 mL). The combined organic layers were washed with water,
brine, dried (Na2SO4) and concentrated to give 10 (29.8 g, quanti-
Conclusions
In summary
a highly efficient and stereoselective
multigram synthesis of (–)-posticlure has been achieved tative) as a pale yellow oil. IR (neat): ν = 2989, 2943, 1752, 1445,
˜
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Eur. J. Org. Chem. 2007, 5064–5070

An Efficient Synthesis of (–)-Posticlure
1378, 1259, 1213, 1162, 1112, 1023, 858, 703 cm–1. 1H NMR (12.2 mL, 2.5  in hexane, 30.5 mmol, 1.1 equiv.) at room tempera-
(200 MHz, CDCl3/TMS): δ = 1.32 (t, J = 7.2 Hz, 6 H, CH3CH2O),
ture. After stirring for 30 min, the mixture was cooled to –80 °C
1.50 (s, 6 H, C-CH3), 4.30 (q, J = 7.2 Hz, 4 H, CH3CH2O), 4.76– and a solution of the above aldehyde in THF (15 mL) was added.
4.83 (m, 2 H, CH-O) ppm. MS (EI): m/z (%) = 246 (1.8) [M]+, 231 The mixture was stirred for another 2 h and then at room tempera-
(77.2), 217 (100), 203 (40.2), 173 (39.8), 159 (32.6), 104 (23.3), 76
(14.8), 59 (28.1), 43 (68.9). An ester exchange was observed with
approximately 25% mixed ester formed [in the 1H NMR with a
peak at δ = 3.83 (s, 3 H) ppm, corresponding to an OMe group].[10]
However this is of no consequence as the compound will be re-
duced in the next step.
ture overnight. It was then quenched with a saturated aq. NH4Cl
solution and THF removed on a rotavapor at low pressure. Water
(100 mL) was added and the mixture extracted with EtOAc
(3ϫ50 mL). The combined organic layers were washed with water,
brine, dried (Na2SO4) and concentrated. The residue was purified
by flash chromatography using hexane/EtOAc (95:5) as eluent to
afford 6 (7.68 g, 80% from 11) as a colourless oil (1H NMR indi-
cated 97:3 Z/E mixture). [α]2D0 = +1.9 (c = 6, CHCl3). IR (neat):
(2S,3S)-4-Benzyloxy-2,3-(isopropylidenedioxy)butan-1-ol (11):
A
suspension of LiAlH4 (11.56 g, 304.6 mmol, 2.5 equiv.) in dry THF
(400 mL) was cooled with ice/water and a solution of 10 (30 g,
121.82 mmol) in dry THF (50 mL) was added dropwise over
15 min. The reaction mixture was refluxed for 4 h. It was then co-
oled to 0 °C and quenched with 10% aq. NaOH (30 mL), water
(10 mL) and EtOAc (100 mL). The white precipitate was filtered
through a pad of silica gel and washed with a mixture of MeOH/
EtOAc (1:3, 400 mL). The filtrate was concentrated to give the cor-
responding acetonide diol as a colourless syrup (18.9 g). IR (neat):
ν = 3057, 2985, 2927, 2856, 1716, 1587, 1457, 1435, 1374, 1242,
˜
1215, 1167, 1086, 1027, 912, 861, 743, 697 cm–1. 1H NMR
(300 MHz, CDCl3/TMS): δ = 0.88 (t, J = 6.7 Hz, 3 H, 12-H), 1.22–
1.39 (m, 10 H, 11-, 10-, 9-, 8-, 7-H), 1.44 (s, 6 H, C-CH3), 1.94–
2.15 (m, 2 H, 6-H), 3.51–3.62 (m, 2 H, 1-H), 3.83–3.88 (m, 1 H, 2-
H), 4.59 (s, 2 H, CH2Ph), 4.56–4.67 (m, 1 H, 3-H), 5.38 (ddt, J =
10.8, 9.8, 1.5 Hz, 1 H, 4-H), 5.68 (dt, J = 10.8, 7.6 Hz, 1 H, 5-H),
7.28–7.34 (m, 5 H, Ph) ppm. 13C NMR (75 MHz, CDCl3/CHCl3):
δ = 14.04, 22.59, 26.94, 27.14, 27.69, 29.08, 29.13, 29.54, 31.74,
69.19, 73.40, 73.51, 80.40, 109.11, 127.55, 128.26, 128.41, 128.51,
128.78, 133.55, 133.81, 136.39 ppm. MS (EI): m/z (%) = 346 (4.1)
[M]+, 331 (7.2), 277 (67.8), 262 (76.2), 196 (27.3), 183 (46.1), 97
(48.3), 91 (100), 83 (18.1), 69 (14.9), 43 (17.1). HRMS: calcd. for
C22H34O3 [M] 346.2509; found 346.2513.
ν = 3410, 2988, 2935, 2881, 1457, 1377, 1251, 1219, 1166, 1109,
˜
1054, 986, 907, 845, 733, 681 cm–1. 1H NMR (200 MHz, CDCl3/
TMS): δ = 1.43 (s, 6 H, C-CH3), 2.91 (br. s, 2 H, OH), 3.67–3.83
(m, 4 H, CH2OH), 3.97–4.01 (m, 2 H, CH-O) ppm.
Oil-free NaH (3.22 g, 134.1 mmol, 1.1 equiv.) was added in por-
tions over 20 min to a solution of the above acetonide diol in dry
DMF (200 mL) at –15 °C. The reaction mixture was stirred at
–15 °C for 30 min and BnBr (20.83 g, 121.8 mmol, 1 equiv.) in dry
(2S,3S,4Z)-1-Benzyloxydodec-4-ene-2,3-diol (12): A 4  solution of
HCl (25 mL) was added to a solution of 6 (8 g, 23.08 mmol) in
DMF (20 mL) was added. After 1 h the reaction mixture was MeOH (150 mL) and the mixture stirred at room temperature for
warmed to room temperature and stirred for another 1 h. It was
quenched with ice/water and the aqueous layer extracted with
EtOAc (4ϫ50 mL). The combined organic layers were washed with
water (2ϫ50 mL), brine, dried (Na2SO4) and concentrated. The
residue was purified by flash chromatography using hexane/EtOAc
(7:3) as eluent to afford 11 (25.18 g, 82% from 10) as a colourless
oil. [α]2D0 = +9.1 (c = 1, CHCl3) {ref.[11b] +9.0 (c = 0.99, CHCl3)}.
8 h. Solid NaHCO3 (6 g) was added and stirred for 15 min. MeOH
was partly removed on a rotavapor under reduced pressure, water
(150 mL) was added and the mixture extracted with CH2Cl2
(2ϫ30 mL). The combined organic layers were washed with water,
brine, dried (Na2SO4) and concentrated. The residue was purified
by flash chromatography using hexane/EtOAc (3:2) as eluent to
give 12 (6.58 g, 93%) as a colourless oil. [α]2D0 = +4.5 (c = 2,
IR (neat): ν = 3464, 3031, 2987, 2932, 2872, 1496, 1454, 1375, 1251,
CHCl ). IR (neat): ν = 3400, 3064, 3029, 3010, 2955, 2925, 2856,
˜
˜
3
1215, 1166, 1082, 991, 907, 847, 741, 700, 608 cm–1. 1H NMR
1722, 1659, 1495, 1455, 1363, 1307, 1276, 1208, 1116, 1033, 912,
(300 MHz, CDCl3/TMS): δ = 1.40 (s, 3 H, C-CH3), 1.41 (s, 3 H, 738, 698 cm–1. H NMR (300 MHz, CDCl3/TMS): δ = 0.88 (t, J =
1
C-CH3), 2.62 (s, 1 H, OH), 3.55 (dd, J = 10.2, 5.4 Hz, 1 H, 4-H),
3.62–3.68 (m, 2 H, 1-H), 3.75 (dd, J = 11.9, 4.1 Hz, 1 H, 4Ј-H),
6.8 Hz, 3 H, 12-H), 1.2–1.38 (m, 10 H, 11-, 10-, 9-, 8-, 7-H), 1.94–
2.18 (m, 2 H, 6-H), 2.88 (br. s, 2 H, OH), 3.46 (dd, J = 9.6, 6.0 Hz,
3.90–3.96 (m, 1 H, 2-H), 4.04 (dt, J = 8.4, 5.4 Hz, 1 H, 3-H), 4.57 1 H, 2-H), 3.54–3.65 (m, 2 H, 1-H), 4.42 (ddd, J = 8.9, 6.5, 1.0 Hz,
(s, 2 H, CH2Ph), 7.29–7.36 (m, 5 H, Ph) ppm. 13C NMR (75 MHz,
CDCl3/CHCl3): δ = 26.85, 26.88, 62.38, 70.38, 73.56, 76.52, 79.57,
109.23, 127.59 (2 C), 127.67, 128.31 (2 C), 137.59 ppm. MS (EI):
m/z (%) = 252 (1.8) [M]+, 251 (6.2) [M – 1]+, 237, (24.8), 194 (16.2),
176 (12.3), 131 (37.1), 105 (14.8), 91 (100), 59 (52.9), 43 (14.1).
HRMS: calcd. for C14H19O4 [M – H] 251.1283; found 251.1288.
1 H, 3-H), 4.52 (s, 2 H, CH2Ph), 5.39 (ddt, J = 10.9, 9.0, 1.5 Hz, 1
H, 4-H), 5.60 (ddt, J = 10.8, 7.6, 0.9 Hz, 1 H, 5-H), 7.28–7.35 (m, 5
H, Ph) ppm. 13C NMR (75 MHz, CDCl3/CHCl3): δ = 14.00, 22.56,
27.86, 29.08, 29.20, 29.48, 31.73, 68.21, 71.25, 73.51, 73.63, 127.69
(2 C), 127.76, 127.83, 128.38 (2 C), 134.91, 137.64 ppm. MS (EI):
m/z (%) = 289 (1.8) [M – 17]+, 277 (1.5), 263 (1.7), 245 (6.3), 197
(1.9), 181 (5.4), 155 (17.4), 107 (15.5), 95 (16.4), 91 (100), 81 (16.8),
57 (27.9), 43 (13.1), 41 (14.2). HRMS: calcd. for C19H31O3 [M +
H] 307.2274; found 307.2279.
(2S,3S,4Z)-1-Benzyloxy-2,3-(isopropylidenedioxy)dodeca-4-ene (6):
Dimethyl sulfoxide (6.51 g, 6.0 mL, 83.32 mmol, 3 equiv.) in
CH2Cl2 (15 mL), was added to a solution of (COCl)2 (5.28 g,
3.5 mL, 41.6 mmol, 1.5 equiv.) in CH2Cl2 (100 mL) at –78 °C. After
20 min, a solution of 11 (7 g, 27.74 mmol) in CH2Cl2 (15 mL) was
added and the mixture stirred for 45 min. Et3N (14.04 g, 19.4 mL,
138.7 mmol, 5 equiv.) in CH2Cl2 (15 mL) was added and the re-
sulting mixture was stirred for another 30 min and then warmed to
room temperature over 1 h. It was then quenched with water and
extracted with CH2Cl2 (2ϫ50 mL). The combined organic layers
were washed with water, brine, dried (Na2SO4) and concentrated
to give the corresponding aldehyde, which was used directly in the
next reaction.
(2S,3S,4Z)-1-Benzyloxy-3-(acetoxy)dodec-4-en-2-ol
(13)
and
(2S,3S,4Z)-1-Benzyloxy-2-(acetoxy)dodec-4-en-3-ol (14): Trimethyl
orthoacetate (0.377 g, 3.13 mmol, 1.2 equiv.) was added to a solu-
tion of 12 (0.8 g, 2.61 mmol) in CH2Cl2 (25 mL) and pTsOH
(10 mg) at 0 °C and the mixture was stirred for 1.5 h (TLC showed
consumption of polar material). NaHCO3 (500 mg) was added and
the mixture stirred for 5 min followed by the addition of water
(50 mL). The organic layer was separated, washed with brine, dried
(Na2SO4) and concentrated. The residue was purified by flash
chromatography using hexane/EtOAc (3:2) as eluent to give a mix-
ture of 13 and 14 (0.709 g, 78%) as a colourless oil (1H NMR
analysis indicated a 1:3 mixture of regioisomers). [α]2D0 = +5.6 (c =
To a solution of octyltriphenylphosphonium bromide (13.89 g,
30.50 mmol, 1.1 equiv.) in dry THF (150 mL) was added nBuLi
Eur. J. Org. Chem. 2007, 5064–5070
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5067

R. A. Fernandes
FULL PAPER
1, CHCl ). IR (neat): ν = 3462, 3064, 3028, 2955, 2926, 2856, 1740, 1.84 (br. s, 1 H, OH), 2.94–2.96 (m, 2 H, 1-H), 3.63 (ddd, J = 12.6,
˜
3
1659, 1496, 1455, 1370, 1238, 1180, 1108, 1026, 911, 817, 740, 700, 7.2, 4.1 Hz, 1 H, 3-H), 3.93 (ddd, J = 12.6, 5.2, 2.1 Hz, 1 H, 2-
606 cm–1. 1H NMR (300 MHz, CDCl3/TMS) major isomer:* δ =
0.88 (t, J = 6.8 Hz, 3 H), 1.2–1.38 (m, 10 H), 2.04 (s, 3 H), 2.01–
2.22 (m, 2 H), 2.5 (br. s, 1 H), 3.48 (dd, J = 9.8, 5.8 Hz, 1 H), 3.57
(dd, J = 9.9, 3.7 Hz, 1 H), 3.77–3.85 (m, 1 H), 4.52 (s, 2 H), 5.31–
H) ppm. 13C NMR (75 MHz, CDCl3/CHCl3): δ = 14.10, 22.60,
25.91, 29.33, 29.41, 29.55 (2 C), 31.61, 31.92, 56.20, 58.72,
61.91 ppm. MS (EI): m/z (%) = 169 (10.8) [M – 31]+, 157 (2.2), 109
(22.7), 97 (100), 95 (45.8), 83 (73.1), 81 (28.9), 71 (55.6), 69 (89.8),
5.40 (m, 1 H), 5.62–5.71 (m, 2 H), 7.25–7.36 (m, 5 H) ppm; charac- 57 (73), 43 (36.6), 41 (12.4). HRMS: calcd. for C12H23O2 [M – H]
teristic peaks for the minor isomer: δ = 3.62 (dd, J = 10.5, 5.1 Hz,
1 H), 3.68 (dd, J = 10.6, 4.1 Hz, 1 H), 4.54 (s, 2 H), 4.65–4.70 (m,
1 H), 4.95–5.00 (m, 1 H), 5.31–5.36 (m, 1 H), 5.55–5.63 (m, 1
H) ppm. 13C NMR (75 MHz, CDCl3/CHCl3) major isomer: δ =
14.02, 21.10, 22.55, 28.00, 29.07, 29.19, 29.32, 31.73, 70.65, 70.78,
72.20, 73.47, 123.86, 127.64 (2 C), 128.35 (2 C), 135.09, 136.73,
137.64, 170.23. MS (EI): m/z (%) = 349 (1.4) [M + 1]+, 331 (18.1)
[M+ – 17]+, 289 (10.5), 271 (8.2), 241 (10.3), 197 (17.3), 155 (33.4),
107 (19.5), 91 (100), 81 (17.8), 57 (17.9), 43 (69.1), 41 (18.5).
HRMS: calcd. for C21H33O4 [M + H] 349.2379; found 349.2386.
*Individual peaks are not assigned as we did not investigate which
is major and minor.
199.1698; found 199.1699.
(2S,3S)-2,3-(Isopropylidenedioxy)dodecan-1-ol (15): Pd(OH)2/C
(20%, 400 mg) was added to a solution of 6 (2 g, 5.77 mmol) in
MeOH/EtOAc (1:5, 30 mL). The mixture was pressurized to 80 psi
of H2 in an autoclave and stirred at room temperature for 12 h.
The catalyst was filtered through a pad of silica gel and washed
with EtOAc (50 mL). The filtrate was concentrated and the residue
purified by flash chromatography using hexane/EtOAc (4:1) as elu-
ent to afford 15 (1.42 g, 95%) as a colourless oil. [α]2D0 = –23.3
(c = 0.38, CHCl3) {ref.[4] –21.6 (c = 1, CHCl )}. IR (neat): ν =
˜
3
3466, 2986, 2927, 2856, 1462, 1375, 1246, 1219, 1168, 1103, 1051,
903, 854, 722 cm–1. 1H NMR (300 MHz, CDCl3/TMS): δ = 0.88
(t, J = 6.6 Hz, 3 H, 12-H), 1.22–1.38 (m, 14 H, 11-, 10-, 9-, 8-, 7-,
6-, 5-H), 1.40 (s, 3 H, C-CH3), 1.41 (s, 3 H, C-CH3), 1.44–1.61 (m,
2 H, 4-H), 2.44 (s, 1 H, OH), 3.60 (dd, J = 11.2, 4.0 Hz, 1 H, 3-
H), 3.70–3.81 (m, 2 H, 1-H), 3.82–3.89 (m, 1 H, 2-H) ppm. 13C
NMR (75 MHz, CDCl3/CHCl3): δ = 14.00, 22.58, 25.89, 26.95,
27.27, 29.21, 29.42 (2 C), 29.62, 31.79, 33.04, 62.08, 76.92, 81.56,
108.48 ppm. MS (EI): m/z (%) = 243 (100) [M – 15]+, 227 (22.2),
165 (3.8), 123 (9.2), 109 (22.3), 95 (39.1), 81 (23.1), 59 (68.9), 55
(19.8), 43 (36.2). HRMS: calcd. for C15H29O3 [M – H] 257.2117;
found 257.2121.
(2S,3S,4Z)-1-Benzyloxy-2,3-epoxydodec-4-ene (16): pTsOH (25 mg)
followed by trimethyl orthoacetate (1.89 g, 15.7 mmol, 1.2 equiv.)
was added to a solution of diol 12 (4 g, 13.05 mmol) in dry CH2Cl2
(50 mL) and the mixture stirred at room temperature for 30 min.
The solvent was evaporated and the residual methanol was re-
moved under high vacuum. CH2Cl2 (50 mL) and CH3COBr
(1.99 g, 1.2 mL, 16.2 mmol, 1.24 equiv.) was added to the residue
and the mixture stirred for 1.5 h at room temperature. It was then
concentrated and the residue diluted with MeOH (80 mL) and
treated with K2CO3 (2.71 g, 19.59 mmol, 1.5 equiv.). The mixture
was stirred for 2.5 h at room temperature and then poured into
water (100 mL) and extracted with CH2Cl2 (2ϫ50 mL). The com-
bined organic layers were washed with brine, dried (Na2SO4) and
concentrated. The residue was purified by flash chromatography
using hexane/EtOAc (9:1) as eluent to give 16 (3.39 g, 90%) as a
(6Z,9Z,11S,12S)-11,12-(Isopropylidenedioxy)henicosa-6,9-diene (3):
Dimethyl sulfoxide (3.63 g, 3.3 mL, 46.45 mmol, 3 equiv.) in
CH2Cl2 (10 mL), was added to a solution of (COCl)2 (2.95 g, 2 mL,
23.21 mmol, 1.5 equiv.) in CH2Cl2 (80 mL) at –78 °C. After 20 min,
a solution of 15 (4 g, 15.48 mmol) in CH2Cl2 (10 mL) was added
and the mixture stirred for 45 min. Et3N (7.83 g, 10.8 mL,
77.36 mmol, 5 equiv.) in CH2Cl2 (10 mL) was added and the re-
sulting mixture stirred for another 30 min and then warmed to
room temperature over 1 h. The reaction mixture was quenched
with water and extracted with CH2Cl2 (2ϫ50 mL). The combined
organic layers were washed with water, brine, dried (Na2SO4) and
concentrated to give the corresponding aldehyde which was used
directly for the next reaction.
colourless oil. [α]2D0 = –13.4 (c = 4, CHCl ). IR (CHCl ): ν = 3063,
˜
3
3
3027, 2955, 2926, 2855, 1718, 1665, 1496, 1456, 1382, 1359, 1308,
1245, 1206, 1103, 1058, 1027, 966, 902, 874, 738, 699 cm–1. 1H
NMR (300 MHz, CDCl3/TMS): δ = 0.88 (t, J = 6.8 Hz, 3 H, 12-
H), 1.2–1.32 (m, 8 H, 11-, 10-, 9-, 8-H), 1.33–1.43 (m, 2 H, 7-H),
2.10–2.29 (m, 2 H, 6-H), 3.06–3.11 (m, 1 H, 2-H), 3.48–3.56 (m, 2
H, 1-H), 3.77 (dd, J = 11.4, 3.0 Hz, 1 H, 3-H), 4.58 (d, J = 2.7 Hz,
2 H, CH2Ph), 5.06 (ddt, J = 10.4, 9.3, 1.2 Hz, 1 H, 4-H), 5.74 (dt,
J = 10.8, 7.5 Hz, 1 H, 5-H), 7.26–7.35 (m, 5 H, Ph) ppm. 13C NMR
(75 MHz, CDCl3/CHCl3): δ = 14.00, 22.55, 27.67, 29.06 (2 C),
29.47, 31.75, 51.59, 58.40, 69.90, 73.20, 126.02, 127.64 (3 C), 128.33
(2 C), 137.26, 137.84 ppm. MS (EI): m/z (%) = 288 (2.1) [M]+, 287
(2.2) [M – 1]+, 271 (3.8), 253 (4.2), 241 (4.3), 197 (4.5), 181 (8.2),
167 (5.1), 133 (15.1), 107 (18.8), 104 (38.1), 91 (100), 83 (10.2), 55
(12.3), 43 (11.3), 41 (18.0). HRMS: calcd. for C19H28O2 [M]
288.2090; found 288.2093.
nBuLi (6.9 mL, 2.5  in hexane, 17.2 mmol, 1.1 equiv.) was added
to a solution of (Z)-(non-3-enyl)triphenylphosphonium iodide
(8.76 g, 17.02 mmol, 1.1 equiv.) in dry THF (100 mL) at room tem-
perature. After stirring for 30 min, the mixture was cooled to
–80 °C and a solution of the above aldehyde in THF (10 mL) was
added. The mixture was stirred for another 1 h and then at room
temperature overnight. It was quenched with saturated aq. NH4Cl
and THF was removed on a rotavapor at low pressure. Water
(75 mL) was added and the mixture extracted with EtOAc
(3ϫ40 mL). The combined organic layers were washed with water,
brine, dried (Na2SO4) and concentrated. The residue was purified
by flash chromatography using hexane/EtOAc (9:1) as eluent to
afford 3 (4.46 g, 79% from 15) as a colourless oil (1H NMR indi-
cated 97:3 Z/E mixture). [α]2D0 = +1.5 (c = 4, CHCl3).[17] IR (neat):
(2S,3S)-2,3-Epoxydodecan-1-ol (4): Pd(OH)2/C (20%, 500 mg) was
added to a solution of 16 (2 g, 6.93 mmol) in MeOH/EtOAc (1:5,
50 mL). The mixture was pressurized to 80 psi of H2 in an auto-
clave and stirred at room temperature for 12 h. The catalyst was
filtered through a pad of silica gel and washed with EtOAc
(50 mL). The filtrate was concentrated and the residue purified by
flash chromatography using hexane/EtOAc (4:1) as eluent to afford
4 (1.302 g, 94%) as a white solid. M.p. 59–60 °C (ref.[16] 62.5–
63 °C). [α]2D0 = –31.9 (c = 3, CHCl3) {ref.[16] –29.4 (c = 6.8, CHCl3)}.
ν = 3013, 2985, 2957, 2927, 2850, 1712, 1462, 1373, 1338, 1170,
˜
1103, 1051, 914, 882, 725 cm–1. 1H NMR (300 MHz, CDCl3/TMS):
IR (CHCl ): ν = 3480, 2985, 2927, 2854, 1450, 1305, 1245, 1103, δ = 0.85–0.91 (m, 6 H, 1-, 21-H), 1.23–1.38 (m, 20 H, 20-, 19-,
˜
3
1090, 903, 840, 710, 685 cm–1. H NMR (300 MHz, CDCl3/TMS): 18-, 17-, 16-, 15-, 14-, 4-, 3-, 2-H), 1.41 (s, 3 H, C-CH3), 1.42 (s, 3
1
δ = 0.88 (t, J = 6.7 Hz, 3 H, 12-H), 1.21–1.38 (m, 12 H, 11-, 10-,
H, C-CH3), 1.47–1.58 (m, 2 H, 13-H), 2.05 (br. dd, J = 13.8, 7.2 Hz,
9-, 8-, 7-, 6-H), 1.41–1.45 (m, 2 H, 5-H), 1.56–1.58 (m, 2 H, 4-H), 2 H, 5-H), 2.89 (dt, J = 7.2, 1.2 Hz, 2 H, 8-H), 3.6–3.67 (m, 1 H,
5068
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© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2007, 5064–5070

An Efficient Synthesis of (–)-Posticlure
12-H), 4.38 (t, J = 8.7 Hz, 1 H, 11-H), 5.26–5.47 (m, 3 H, olefin- 7.4 Hz, 2 H, 8-H), 3.37 (ddd, J = 8.9, 2.2, 0.9 Hz, 1 H, 11-H), 5.06
H), 5.66 (ddt, J = 10.8, 7.4, 0.9 Hz, 1 H, olefin-H) ppm. 13C NMR
(ddt, J = 10.8, 8.7, 1.5 Hz, 1 H, 10-H), 5.37 (dtt, J = 10.8, 7.2,
(75 MHz, CDCl3/CHCl3): δ = 14.02, 14.07, 22.53, 22.65, 26.02, 1.5 Hz, 1 H, 7-H), 5.44 (dtt, J = 10.8, 7.2, 1.5 Hz, 1 H, 6-H), 5.67
26.19, 27.09, 27.25, 27.28, 29.23, 29.28, 29.49, 29.51, 29.74, 31.49,
(ddt, J = 10.8, 7.5, 0.9 Hz, 1 H, 9-H) ppm.[18] 13C NMR (75 MHz,
31.81, 31.87, 76.67, 80.91, 108.26, 126.67 (2 C), 131.04, CDCl3/CHCl3): δ = 14.00, 14.05, 22.53, 22.63, 25.90, 26.04, 27.20,
134.18 ppm. MS (EI): m/z (%) = 349 (4.8) [M – 15]+, 289 (6.2),
208, (11.8), 155 (16.1), 97 (88.3), 83 (9.3), 69 (34.9), 55 (100), 43
(7.1). HRMS: calcd. for C24H43O2 [M – H] 363.3264; found
363.3271.
29.21, 29.26, 29.43, 29.49, 29.52, 31.47, 31.86, 32.04, 54.27, 60.10,
126.75, 127.31, 131.07, 134.24 ppm. MS (EI): m/z (%) = 306 (3.1)
[M]+, 289 (2.4), 249 (2.1), 235 (3.2), 209 (3.3), 195 (34.4), 179 (8.7),
155 (15.3), 136 (8.8), 109 (18.1), 95 (28.3), 93 (28.4), 79 (88.5), 67
(53.9), 55 (70.1), 43 (73.3), 41 (100). HRMS: calcd. for C21H38O
306.2924; found 306.2927.
(6Z,9Z,11S,12S)-11,12-Dihydroxyhenicosa-6,9-diene (17):
A 4 
solution of HCl (12 mL) was added to a solution of 3 (4 g,
10.97 mmol) in MeOH (100 mL) and the mixture stirred at room
temperature for 8 h. Solid NaHCO3 (4 g) was added and the mix-
ture stirred for 15 min. MeOH was partly removed on a rotavapor,
the mixture diluted with water (50 mL) and extracted with EtOAc
(3ϫ50 mL). The combined organic layers were washed with water,
brine, dried (Na2SO4) and concentrated. The residue was purified
by flash chromatography using hexane/EtOAc (3:2) as eluent to
give 17 (3.28 g, 92%) as a colourless oil. [α]2D0 = +2.5 (c = 5,
(11S,12S)-(–)-Posticlure (1) from 17: pTsOH (12 mg) followed by
trimethyl orthoacetate (0.888 g, 7.39 mmol, 1.2 equiv.) was added
to a solution of diol 17 (2 g, 6.16 mmol) in dry CH2Cl2 (10 mL)
and the mixture stirred at room temperature for 20 min. The sol-
vent was evaporated and the residual methanol was removed under
high vacuum. CH2Cl2 (10 mL) and CH3COBr (0.910 g, 0.550 mL,
7.4 mmol, 1.2 equiv.) was added to the residue and the mixture
stirred for 1.5 h at room temperature. It was then concentrated, the
residue diluted with MeOH (15 mL) and treated with K2CO3
(1.28 g, 9.24 mmol, 1.5 equiv.). The mixture was stirred for 2.5 h at
room temperature, then poured into water (50 mL) and extracted
with CH2Cl2 (2ϫ30 mL). The combined organic layers were
washed with brine, dried (Na2SO4) and concentrated. The residue
was purified by flash chromatography using hexane/diethyl ether
CHCl3).[17] IR (neat): ν = 3370, 3011, 2956, 2925, 2855, 1712, 1462,
˜
1377, 1274, 1230, 1045, 1027, 723 cm–1. 1H NMR (300 MHz,
CDCl3/TMS): δ = 0.84–0.92 (m, 6 H, 1-, 21-H), 1.2–1.38 (m, 20 H,
20-, 19-, 18-, 17-, 16-, 15-, 14-, 4-, 3-, 2-H), 1.41–1.52 (m, 2 H, 13-
H), 2.0–2.1 (m, 2 H, 5-H), 2.53 (br. s, 2 H, OH), 2.81–2.92 (m, 2
H, 8-H), 3.39–3.5 (m, 1 H, 12-H), 4.22 (dt, J = 8.0, 0.9 Hz, 1 H,
11-H), 5.28–5.36 (m, 1 H, olefin-H), 5.37–5.47 (m, 2 H, olefin-H),
5.60 (ddt, J = 10.8, 7.5, 0.9 Hz, 1 H, olefin-H) ppm. 13C NMR
(75 MHz, CDCl3/CHCl3): δ = 14.00, 14.04, 22.52, 22.64, 25.71,
26.34, 27.24, 29.21, 29.28, 29.54 (2 C), 29.63, 31.47, 31.85, 32.78,
71.06, 74.99, 126.60, 128.77, 131.09, 132.98 ppm. MS (EI): m/z (%)
= 324 (1.3) [M]+, 307 (36.2) [M – 17]+, 306 (13.8), 289 (11.2), 213
(32.3), 157 (54.1), 112 (39.4), 97 (38.3), 83 (89.5), 69 (65.1), 57
(100), 55 (96.4), 43 (59.4), 41 (79.2). HRMS: calcd. for C21H40O2
[M] 324.3030; found 324.3034.
(9:1) as eluent to give 1 (1.68 g, 89%) as a colourless oil. [α]2D0
–11.3 (c = 0.48, CHCl3).
=
Supporting Information (see also the footnote on the first page of
this article): Spectra of relevant compounds.
Acknowledgments
R.A.F. thanks Dr. Raymundo Cea Olivares (Director, Instituto de
Química, UNAM) and Dr. Luis Demetrio Miranda for support
(11S,12S)-(–)-Posticlure (1) from 4: Epoxy alcohol 4 (1 g, 5 mmol) and encouragement. Financial support from the Instituto de Quím-
in CH2Cl2 (5 mL) was added to a stirred slurry of PCC (1.62 g,
7.5 mmol, 1.5 equiv.) and NaHCO3 (0.63 g, 7.5 mmol, 1.5 equiv.)
in dry CH2Cl2 (50 mL) at 0 °C and the mixture stirred for 4 h. It
was then warmed to room temperature, filtered through a pad of
silica gel and washed with CH2Cl2 (75 mL). The filtrate was con-
centrated to give the corresponding aldehyde which was used di-
rectly in the next reaction.
ica, UNAM is gratefully acknowledged.
[1] N. Arakaki, K. Kawasaki, S. Yoshimatsu, Bull. Okinawa Agric.
Exp. Stn. 1977, 18, 29–38.
[2] S. Wakamura, N. Arakaki, M. Yamamoto, S. Hiradate, H. Ya-
sui, T. Yasuda, T. Ando, Tetrahedron Lett. 2001, 42, 687–689.
[3] For an excellent classification of pheromones, see: a) http://
www.nysaes.cornell.edu/pheronet; b) In February 2004 a new
pherolist was created by Peter Witzgall, Tobias Lindblom, Ma-
rie Bengtsson and Miklós Tóth: http://www-pherolist.slu.se/
pherolist.php.
[4] R. A. Fernandes, P. Kumar, Tetrahedron 2002, 58, 6685–6690.
[5] S.-E. Muto, K. Mori, Eur. J. Org. Chem. 2001, 4635–4638.
[6] For a one-pot vicinal-diol-to-epoxide conversion, see: H. C.
Kolb, K. B. Sharpless, Tetrahedron 1992, 48, 10515–10528.
[7] If diethyl -tartrate is protected as a cyclic orthoacetate and
carried forward (7 Ǟ 5 Ǟ 2, route A) then compound 2 can
be converted directly into 1. However, by acetonide protection
(7 Ǟ 6 Ǟ 3, route B), the conversion of compound 3 into 1
has to proceed via the orthoacetate 2, which is the intermediate
in the diol-to-epoxide conversion. This means one extra step
of acetonide deprotection. Similarly the conversion of 7 into 4
proceeds via compound 6.
nBuLi (2.2 mL, 2.5  in hexane, 5.5 mmol, 1.1 equiv.) was added to
a solution of (Z)-(non-3-enyl)triphenylphosphonium iodide (2.83 g,
5.5 mmol, 1.1 equiv.) in dry THF (50 mL) at room temperature.
After stirring for 30 min, the mixture was cooled to –80 °C and a
solution of the above aldehyde in THF (5 mL) was added. The
mixture was stirred for another 1 h and then at room temperature
overnight. It was quenched with saturated aq. NH4Cl and THF
was removed on a rotavapor at low pressure. Water (50 mL) was
added and the mixture extracted with diethyl ether (3ϫ20 mL).
The combined organic layers were washed with water, brine, dried
(Na2SO4) and concentrated. The residue was purified by flash
chromatography using hexane/diethyl ether (9:1) as eluent to afford
1 (1.18 g, 77% from 4) as a colourless oil. [α]2D0 = –11.2 (c = 0.4,
CHCl3) {ref.[5] –10.8 (c = 1.07, CHCl3); ref.[4] –11.1 (c = 1,
[8] L. Longobardo, G. Mobbili, E. Tagliavini, C. Trombini, A.
Umani-Ronchi, Tetrahedron 1992, 48, 1299–1316.
[9] The reduction of compound 8 to 9 is not known in the litera-
ture. For an example of cyclic orthoformate reduction with Li-
AlH4, see: K. C. Nicolaou, D. P. Papahatjis, D. A. Claremon,
R. L. Magolda, R. E. Dolle, J. Org. Chem. 1985, 50, 1440–
1456.
CHCl )}. IR (CHCl ): ν = 3013, 2957, 2926, 2855, 1718, 1462,
˜
3
3
1376, 1312, 1273, 1241, 1102, 1042, 968, 912, 878, 732 cm–1. 1H
NMR (300 MHz, CDCl3/TMS): δ = 0.88 (m, 6 H, 1-, 21-H), 1.2–
1.32 (m, 18 H, 20-, 19-, 18-, 17-, 16-, 15-, 14-, 3-, 2-H), 1.33–1.39
(m, 2 H, 4-H), 1.48–1.62 (m, 2 H, 13-H), 2.07 (dt, J = 7.2, 7.0 Hz,
2 H, 5-H), 2.82 (dt, J = 5.8, 2.2 Hz, 1 H, 12-H), 2.96 (dd, J = 7.5,
Eur. J. Org. Chem. 2007, 5064–5070
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5069

R. A. Fernandes
FULL PAPER
[10] M. Carmack, C. J. Kelley, J. Org. Chem. 1968, 33, 2171–2173.
[11] Compounds 10 and 11 were synthesized following literature
procedures, see: a) Z.-J. Yao, Y.-L. Wu, J. Org. Chem. 1995, 60,
1170–1176. In this reference there is a discrepancy in the sign
of the optical rotation. The enantiomer of 11, prepared from
-tartaric acid, is reported to have [α]2D0 = +9.0 (c = 4.1,
CHCl3). The same compound is reported to have [α]2D0 = –9.0
(c = 1.6, EtOAc) in D. T. Fox, C. D. Poulter, J. Org. Chem.
2005, 70, 1978–1985 and [α]2D0 = –8.0 (c = 0.975, CHCl3) in b)
E. Hungerbuhler, D. Seebach, Helv. Chim. Acta 1981, 64, 687–
702.
[13] If the cyclic orthoacetate was stable to multistep reactions we
could save one step in the synthetic strategy, that is, route A
vs. route B (see Scheme 1).
[14] The intermediates are shown below. The cyclic orthoacetate is
formed as exemplified by this conversion, though probably it
is not stable to isolation.
[12] The diol 12 was treated with trimethyl orthoacetate and cata-
lytic p-TsOH in dry CH2Cl2 at 0 °C. After complete consump-
tion of the starting material (TLC, 1.5 h) a fast-moving spot
was detected on a TLC sheet which we believed could be cyclic
orthoacetate 5. Also a polar spot corresponding to 13 and 14
was noticed. After aqueous work-up and column chromatog-
raphy 13 and 14 were isolated as a mixture. The integration of
the allylic proton (C-3) and also the acetyl (CH3) group indi-
cated that 13 and 14 were present in a 1:3 ratio. However, we
did not investigate which is the major isomer. Even avoiding
aqueous work-up, that is, quenching the reaction with solid
NaHCO3, filtration, concentration and column chromatog-
raphy, afforded the mixture in the same ratio. For a similar
conversion of vicinal diols to monoacetoxy products using tri-
methyl orthoacetate, see: M. Ikejiri, K. Miyashita, T. Tsunemi,
T. Imanishi, Tetrahedron Lett. 2004, 45, 1243–1246.
[15] For an example of debenzylation with Pearlman’s catalyst in
the presence of an epoxide, see: D.-G. Liu, B. Wang, G.-Q. Lin,
J. Org. Chem. 2000, 65, 9114–9119.
[16] W. R. Roush, K. Ando, D. B. Powers, A. D. Palkowitz, R. L.
Halterman, J. Am. Chem. Soc. 1990, 112, 6339–6348.
[17] The optical rotation value for this compound did not match
with that reported in ref.[4]
[18] Individual peaks are assigned in analogy with ref.[5]
Received: May 17, 2007
Published Online: August 7, 2007
5070
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Eur. J. Org. Chem. 2007, 5064–5070