Versatile amine-promoted mild methanolysis of 3,5-dinitrobenzoates and its application to the synthesis of Colorado potato beetle pheromone

Article abstract of DOI:10.1248/cpb.c17-00462

A mild deacylation method for 3,5-dinitrobenzoates using methanolic solutions of amines, such as dialkylamines, was developed. The method’s versatility was confirmed by applying it to synthesizing a key intermediate for Colorado potato beetle pheromone.

Full text of DOI:10.1248/cpb.c17-00462

940
Chem. Pharm. Bull. 65, 940–944 (2017)
Vol. 65, No. 10
Regular Article
Highlighted Paper selected by Editor-in-Chief
Versatile Amine-Promoted Mild Methanolysis of 3,5-Dinitrobenzoates
and Its Application to the Synthesis of Colorado Potato Beetle
Pheromone
Yumiko Yamano,* Haruna Sasaki, and Akimori Wada
Department of Organic Chemistry for Life Science, Kobe Pharmaceutical University; Motoyamakita-machi,
Higashinada-ku, Kobe 658–8558, Japan.
Received June 7, 2017; accepted July 10, 2017
A mild deacylation method for 3,5-dinitrobenzoates using methanolic solutions of amines, such as
dialkylamines, was developed. The method’s versatility was confirmed by applying it to synthesizing a key
intermediate for Colorado potato beetle pheromone.
Key words 3,5-dinitrobenzoate; amine-promoted methanolysis; selective deacylation; Colorado potato beetle
pheromone
3,5-Dinitrobenzoates are typically crystalline compounds triethylamine, 4-dimethylaminopyridine (DMAP) followed
and are often used to confirm the structures of alcohols by in this order. Methanolysis of 3 with 0.2eq of diethylamine
X-ray crystallography.1–3) Some alcohols can be dinitrobenzo- completed with a bit slower rate (99%: 4h) than that of 0.5eq
ylated to improve their diastereomeric or enantiomeric purities (99%: 1.5h). Interestingly, the rate of ethanolysis of 3 was
by recrystallization.4–8) The resulting dinitrobenzoates are much lower than that of methanolysis. A 1-mmol-scale metha-
usually deacylated by alkaline solvolysis (a methanolic solu- nolysis of 3 with 0.5eq of diethylamine provided alcohol 2 in
tion of K2CO3 or aqueous KOH).4–8) 3,5-Dinitrobenzoic acid nearly quantitative isolated yield. This methanolysis procedure
has been used as a pro-nucleophile in the original Mitsunobu was convenient because extraction was not necessary and
reaction9) and the catalytic Mitsunobu reaction.10,11) Thus, a most of the methyl dinitrobenzoate by-product was removed
mild deacylation method for dinitrobenzoates would be useful by diluting the concentrated reaction mixture with ether and
for synthesizing compounds such as natural products and bio- hexane followed by filtration.
logically active compounds.
Chloroacetates can be cleaved in the presence of other
Recently, we found that methanolysis of the 3,5-dinitro- esters, such as acetates and benzoates, because of the large
benzoate quickly proceeds in the presence of triethylamine difference in the solvolysis rates.16) Thus, the time course of
in the total synthesis of lycopene-5,6-diols.8) Kobayashi and triethylamine-mediated (0.2, 0.5eq) methanolysis of chloro-
Acharya,12) and Tonoi et al.13) reported that the dinitroben- acetate 4 was examined. The times for 50% conversion of
zoates obtained by the Mitsunobu inversion of a secondary 3,5-dinitrobenzoate 3 and chloroacetate 4 into deacylated
alcohols bearing macrocyclic lactone moieties were deacyl- product 2 showed that the reactivity of 3 was comparable to
ated by treatment with a methanolic solution of triethylamine. that of 4 (Table 1). Compound 8 was prepared and we exam-
These reports encouraged us to investigate versatility of this ined the selective cleavage of the dinitrobenzoyl group in the
reaction. In the present work, we investigated the alcoholysis presence of the acetyl (Ac) group on the primary allylic hy-
of dinitrobenzoates in the presence of various amines. Then, droxyl group (Chart 2). A methanolic solution of 8 was treated
we applied our mild deacylation method in the efficient asym- with diethylamine to provide chemoselectively deacylated
metric synthesis of Colorado potato beetle (CPB) pheromone14) alcohol 7 in high yield. Successful deacetylation of 3,5-dini-
and its enantiomer.
torobenzoate 10 of α-hydroxy ketone 917) without racemization
reinforces the versatility of the reaction.
Results and Discussion
Amine-Promoted Methanolysis of 3,5-Dinitrobenzo-
ates The time course of the methanolysis in the presence of
triethylamine (0.2–1.0eq) of 3,5-dinitrobenzoate 3, which was
prepared from previously synthesized compound 115) (Chart
1), was monitored by HPLC (Fig. 1(a)). The conversions (%)
of starting dinitrobenzoate 3 into alcohol 2 were calculated
based on the peak areas and molar absorbance coefficients (ε)
of 2 (2550) and 3 (9970) at a detection wavelength of 254nm.
The reaction proceeded even in the presence of a catalytic
amount of triethylamine and the reaction rate increased with
the molar equivalents of the amine. Next, we investigated the
methanolysis of 3 in the presence of 0.5eq of other amines
(Fig. 1(b)). Reaction rates of ethylamine, diethylamine and di-
isopropylamine were almost identical, and those of ammonia,
Chart 1. Synthesis of 3,5-Dinitrobenzoate 3
*To whom correspondence should be addressed. e-mail: y-yamano@kobepharma-u.ac.jp
© 2017 The Pharmaceutical Society of Japan

Vol. 65, No. 10 (2017)
Chem. Pharm. Bull.
941
Fig. 1. Time Course of Alcoholysis of 3,5-Dinitrobenzoate 3
All experiments were conducted at room temperature (23–25°C) in a 0.02M solution of 3 (0.1mmol) in MeOH (—) or EtOH (-----). (a) Treatment of 3 with 0.2–1.0eq
of Et3N; (b) treatment of 3 with 0.5eq of amine.
Table 1. Methanolysis of Compounds 3 and 4
Time for 50% conversion (h)
Substrate
Et3N (0.2eq)
Et3N (0.5eq)
3
4
5.1
3.4
2.0
1.6
Synthesis of CPB Pheromone The CPB, Leptinotarsa
decemlineata, is a severe defoliator of potatoes and related
solanaceous plants worldwide.18) The heavy use of synthetic
insecticides for CPB control has led to insecticide resistance.
The identification of the male-produced aggregation phero-
mone in CPBs, (3S)-1,3-dihydroxy-3,7-dimethyl-6-octen-2-one
(13a), has made insecticide-free pest management of CPB
Chart 2. Preparation and Deacylation of Compounds 8 and 10
possible. Preliminary bioassays revealed that (S)-13a at- opening and improved the enantiomeric purities of products
tracted both sexes of L. decemlineata, whereas (R)-13b was 11a, b by making them easy to crystallize.
inactive.14) Thus, several enantioselective synthetic methods
In the present work, we prepared CPB pheromone 13a and
of the CPB pheromone have been developed.19–22) In most its enantiomer 13b from 11a, b in two steps without triols 14.
cases, target compound 13 was derived through triol 14 by 11a, b was oxidized by 2-iodoxybenzoic acid (IBX) to provide
selective protection of the primary alcohol using tert-butyl- ketones 12a, b in high yields, which were then treated with
diphenylsilyl chloride, oxidation with dimethyl sulfoxide, and diethylamine in methanol to give desired compounds 13a, b
deprotection.19,20,22) The most recent synthesis22) derived 13 in high yields. When benzoate 12a was treated with aqueous
from triol 14, which was prepared from geraniol in four steps KOH in methanol, deacylated compound 13a was not obtained
by Sharpless asymmetric epoxidation, acetylation, treatment because of decomposition, indicating that dihydroxyketone 13
with aqueous perchloric acid in N,N-dimethylformamide, and was unstable under the strongly basic conditions. The specific
deacylation using K2CO3 in methanol. To improve the enantio- rotation values of 13a and b were so small {13a: [α]D26 +3.6
meric purity, the CPB pheromone was converted into the crys- (c=1.00, CHCl3), 13b: [α]D27 −2.4 (c=1.00, CHCl3); lit.19,20,22)
:
talline 4-bromobenzoate derivative, recrystallized, and then [α]D25 3.2 to 4.0 (c=0.4 to 1.08, CHCl3)} that their enantio-
hydrolyzed. However, the repeated protection and deprotection meric purities (13a: 97% enantiomeric excess (ee), 13b: 98%
of the hydroxyl group is inefficient.
ee) were directly confirmed by HPLC analysis (CHIRALPAK
Recently, during the total synthesis of lycopene-5,6-diols,8) ID, Daicel; EtOH–hexane, 15:85).
we prepared enantiomerically pure 2,3-dihydroxyneryl 3,5-di-
In conclusion, the mild deacylation method of 3,5-dinitro-
nitrobenzoate 11a, b via Sharpless asymmetric epoxidation of benzoates described here is promising as a versatile method
nerol followed by acidic hydrolysis (Chart 3). The dinitroben- for the synthesis of complex compounds such as natural prod-
zoyl group controlled the stereoselectivity in the epoxide ring ucts.

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Chem. Pharm. Bull.
Vol. 65, No. 10 (2017)
Chart 3. Synthesis of CPB Pheromone 13a and Its Enantiomer 13b
compound 2 (1.43g, 6.87mmol), Et3N (1.44mL, 10.4mmol)
Experimental
General UV spectra were recorded on a JASCO V-650 and DMAP (42mg, 0.34mmol) in dry CH2Cl2 (35mL) was
instrument. IR spectra were measured on a Perkin-Elmer added 3,5-dinitrobenzoyl chloride (1.59g, 6.89mmol) at 0°C
spectrum 100 Fourier transform (FT)-IR spectrometer. 1H- and the mixture was stirred at 0°C for a further 60min. After
and 13C-NMR spectra were determined on a Varian Gemi- the reaction was quenched by addition of saturated aqueous
ni-300 superconducting FT-NMR spectrometer. The chemi- NH4Cl, CH2Cl2 was evaporated off. The resulting mixture was
cal sifts are expressed in ppm relative to tetramethylsilane diluted with AcOEt and washed with brine. The organic layer
1
(δ=0) as internal standard for H-NMR and CDCl3 (δ=77.0) was dried and evaporated to give a residue, which was puri-
for 13C-NMR. Mass spectra were taken on a Thermo Fisher fied by flash CC (AcOEt–hexane–CH2Cl2, 1:5:3) to provide
Scientific Exactive spectrometer. Optical rotations were mea- compound 3 (2.48g, 90%) as a colorless solid: mp 102–105°C.
sured on a JASCO P-2200 polarimeter.
[α]D23 −56.9 (c=1.00, CHCl3). IR (CHCl3) cm−1: 1729 and
Flash column chromatography (CC) was performed on 1670 (CO), 1628 and 1607 (C=C), 1549 and 1345 (NO2). UV
using Kanto Silica Gel 60N. HPLC analyses were performed λmax (MeOH) nm (ε): 209 (37000), 285 (11300). 1H-NMR
on GL Sciences-GL7400 instrument with a photodiode array (300MHz, CDCl3) δ: 1.19 and 1.24 (each 3H, s, gem-CH3),
detector.
1.83 (3H, s, 3-CH3), 1.84 (1H, t, J=12Hz, 6-H), 2.02 (1H, ddd,
All operations were carried out under nitrogen or argon. J=12, 4, 2Hz, 6-H), 2.34 (3H, s, CH3CO), 2.40 (1H, brdd,
Evaporation of the extract or the filtrate was carried out under J=17.5, 10Hz, 2-H), 2.68 (1H, brdd, J=17.5, 5.5Hz, 2-H), 5.42
reduced pressure. In solvent extraction procedure, organic (1H, m, 1-H), 6.16 (1H, d, J=16.5Hz, 2′-H), 7.22 (1H, brd,
layer was dried over anhydrous Na2SO4. Ether refers to diethyl J=16.5Hz, 1′-H), 9.16 (2H, d, J=2.5Hz, ArH), 9.24 (1H, t,
ether, and hexane to n-hexane.
J=2.5Hz, ArH). 13C-NMR (75MHz, CDCl3) δ: 21.41, 27.46,
(E)-4-[(R)-4-Hydroxy-2,6,6-trimethylcyclohex-1-enyl]- 28.35, 29.85, 36.72, 38.42, 43.85, 71.07, 122.33, 129.35 (C×2),
but-3-en-2-one (2) HF·Pyridine (Py) (4mL) was added 130.36, 132.89, 134.19, 136.01, 141.47, 148.65 (C×2), 162.07,
in several portions to a solution of compound 115) (987mg, 198.22. HR-MS (ESI) m/z Calcd for C20H22O7N2Na [M+Na]+
3.06mmol) in tetrahydrofuran (THF) (10mL) at 0°C. After 425.1319. Found 425.1320.
being stirred at 0°C for 40min, the reaction mixture was
Time Course of Alcoholysis of 3,5-Dinitrobenzoate 3
diluted with AcOEt, washed successively with brine, satu- (Fig. 1) Each amine (1.0M in MeOH; 20µL, 0.02mmol to
rated aqueous NaHCO3, and then brine. Evaporation of the 100 µL, 0.1mmol) was added to a stirred solution of com-
dried solution gave a residue, which was purified by flash CC pound 3 (40.0mg, 0.1mmol) in MeOH or EtOH (5.0mL). The
(acetone–hexane, 3:7) to afford compound 2 (638mg, quant.) reaction was monitored by HPLC [LiChrosorb CN 0.46×25cm
as a coreless oil: [α]D23 −87.8 (c=1.01, CHCl3). IR (CHCl3) (Merck), AcOEt–hexane (3:7), 1.0mL/min, 254nm (detect.);
cm−1: 3606 and 3460 (OH), 1668 (CO), 1605 (C=C). UV λmax methyl and ethyl 3,5-dinitrobenzoate: 4.0min, 3: 5.1min, 2:
1
(MeOH) nm (ε): 291 (9560). H-NMR (300MHz, CDCl3) δ: 6.1min]. Conversions (%) of compound 3 into compound 2
1.11 and 1.12 (each 3H, s, gem-CH3), 1.49 (1H, t, J=12Hz, were calculated as shown in the following equation.
5′-H), 1.71 (1H, d, J=4.5Hz, OH), 1.77 (3H, s, 2′-CH3), 1.78
Conversion (%)
(1H, ddd, J=12, 3.5, 2Hz, 5′-H), 2.09 (1H, brdd, J=17, 9.5Hz,
peak area of 3
9970 (ε at 254 nm of 3)
3′-H), 2.30 (3H, s, CH3CO), 2.43 (1H, brdd, J=17, 5.5Hz,
3′-H), 4.00 (1H, m, 4′-H), 6.10 (1H, d, J=16.5Hz, 3-H), 7.19
(1H, brd, J=16.5Hz, 4-H). 13C-NMR (75MHz, CDCl3) δ:
21.55, 27.27, 28.53, 30.04, 36.87, 42.73, 48.37, 64.45, 132.28,
132.32, 135.58, 142.33, 198.55. High resolution (HR)-MS (elec-
trospray ionization (ESI)) m/z Calcd for C13H20O2Na [M+Na]+
231.1356. Found 231.1354.
=
×100
peak area of 3
peak area of 2
2550 (ε at 254 nm of 2)
+
9970
Et2NH-Promoted Methanolysis of 3,5-Dinitrobenzoate
To a stirred solution of compound 3 (402mg, 1.00mmol)
3
(R)-3,5,5-Trimethyl-4-[(E)-3-oxobut-1-enyl]cyclohex- in THF (1mL) and MeOH (30mL) was added Et2NH (1.0M
3-enyl 3,5-Dinitrobenzoate (3) To a stirred solution of in MeOH; 0.5mL, 0.5mmol) at room temperature (r.t.). After

Vol. 65, No. 10 (2017)
Chem. Pharm. Bull.
943
being stirred at r.t. for 1h, MeOH was evaporated off. Ether (C×2), 18.21, 21.00, 21.20, 25.91 (C×3), 28.25, 29.93, 36.64,
(10mL) and hexane (10mL) were added to the resulting 42.71, 48.56, 65.44, 65.52, 127.29, 127.65, 132.15, 136.02,
residue and the precipitates were filtered off. The filtrate was 170.84. HR-MS (ESI) m/z Calcd for C20H36O3NaSi [M+Na]+
concentrated to give a residue, which was purified by flash 375.2326. Found 375.2331.
CC (acetone–hexane–CH2Cl2, 1:2:2) to yield compound 2
(208mg, quant.) as a colorless oil.
(E)-3-[(R)-4-Hydroxy-2,6,6-trimethylcyclohex-1-enyl]-
allyl Acetate (7) In the same manner as described for
(R)-3,5,5-Trimethyl-4-[(E)-3-oxobut-1-en-1-yl]cyclohex- the preparation of compound 2, desilylation of compound 6
3-enyl 2-Chloroacetate (4) To a stirred solution of com- (1.20g, 3.40mmol) gave crude products, which were purified
pound 2 (823mg, 3.95mmol), Et3N (0.82mL, 5.89mmol) and by flash CC (acetone–hexane, 3:7) to provide compound 7
DMAP (24mg, 0.20mmol) in dry CH2Cl2 (15mL) was added (677mg, 83%) as a colorless oil: [α]D24 −116.3 (c=1.06, CHCl3).
1
slowly chloroacetyl chloride (0.38mL, 4.78mmol) at 0°C. IR (CHCl3) cm−1: 3606 and 3453 (OH), 1732 (CO). H-NMR
After being stirred at 0°C for 1h, the mixutre was quenched (300MHz, CDCl3) δ: 1.03 and 1.04 (each 3H, s, gem-CH3),
by addition of saturated aqueous NH4Cl and extracted with 1.44 (1H, t, J=12Hz, 5′-H), 1.46 (1H, brs, OH), 1.68 (3H,
AcOEt. The extracts were washed with brine, dried and s, 2′-CH3), 1.75 (1H, ddd, J=12, 3.5, 2Hz, 5′-H), 2.00 (1H,
evaporated to give a residue, which was purified by flash CC brdd, J=17, 9.5Hz, 3′-H), 2.07 (3H, s, CH3COO), 2.34 (1H,
(AcOEt–hexane, 1:2) to provide compound 4 (825mg, 73%) brdd, J=17, 5.5Hz, 3′-H), 3.97 (1H, m, 4′-H), 4.60 (2H, dd,
as a colorless solid: mp 75–77°C. [α]D20 −60.9 (c=0.98, CHCl3). J=6.5, 1Hz, 1-H2), 5.51 (1H, dt, J=16, 6.5Hz, 2-H), 6.11 (1H,
IR (CHCl3) cm−1: 1749, 1687sh and 1669 (CO), 1607 (C=C). brd, J=16Hz, 3-H). 13C-NMR (75MHz, CDCl3) δ: 21.00,
1
UV λmax (MeOH) nm (ε): 218 (7800), 287 (9700). H-NMR 21.18, 28.36, 29.95, 36.73, 42.17, 48.19, 64.96, 65.38, 126.64,
(300MHz, CDCl3) δ: 1.12 and 1.16 (each 3H, s, gem-CH3), 127.92, 131.94, 136.30, 170.87. HR-MS (ESI) m/z Calcd for
1.65 (1H, t, J=12Hz, 6-H), 1.77 (3H, s, 3-CH3), 1.85 (1H, ddd, C14H22O3Na [M+Na]+ 261.1461. Found 261.1463.
J=12, 3.5, 2Hz, 6-H), 2.21 (1H, brdd, J=17, 9.5Hz, 2-H),
(R)-4-[(E)-3-Acetoxyprop-1-enyl]-3,5,5-trimethylcyclo-
2.31 (3H, s, CH2CO), 2.54 (1H, brdd, J=17, 5.5Hz, 2-H), 5.15 hex-3-enyl 3,5-Dinitrobenzoate (8) In the same manner as
(1H, m, 1-H), 6.12 (1H, d, J=16.5Hz, 2′-H), 7.19 (1H, brd, described for the preparation of compound 3, benzoylation of
J=16.5Hz, 1′-H). 13C-NMR (75MHz, CDCl3) δ: 21.40, 27.42, compound 7 (614mg, 2.58mmol) gave crude products, which
28.30, 29.76, 36.49, 38.28, 41.09, 43.58, 70.04, 130.76, 132.68, were purified by flash CC (AcOEt–hexane–CH2Cl2, 1:5:3) to
135.75, 141.70, 166.93, 198.38. HR-MS (ESI) m/z Calcd for provide compound 8 (1.12g, quant.) as a pale yellow solid: mp
C15H22O3Cl [M+H]+ 285.1252 and 287.1223. Found 285.1252 77–80°C. [α]D24 −71.5 (c=1.02, CHCl3). IR (CHCl3) cm−1: 1729
1
and 287.1221.
(CO), 1548 and 1345 (NO2). H-NMR (300MHz, CDCl3) δ:
Time Course of Et3N-Promoted Methanolysis of Chlo- 1.12 and 1.17 (each 3H, s, gem-CH3), 1.75 (3H, s, 3-CH3), 1.80
roacetate 4 (Table 1) In the same manner as described for (1H, t, J=12Hz, 6-H), 1.97 (1H, ddd, J=12, 3.5, 1.5Hz, 6-H),
time course of alcoholysis of 3,5-dinitrobenzoate 3, a solu- 2.10 (3H, s, CH3COO), 2.34 (1H, brdd, J=16.5, 9.5Hz, 2-H),
tion of compound 4 (28.5mg, 0.1mmol) in MeOH (5.0mL) 2.59 (1H, brdd, J=16.5, 6Hz, 2-H), 4.65 (2H, d, J=6.5Hz,
was treated with Et3N. The reaction was monitored by HPLC 3′-H2), 5.41 (1H, m, 1-H), 5.59 (1H, dt, J=16, 6.5Hz, 2′-H),
[LiChrosorb CN 0.46×25cm (Merck), AcOEt–hexane (3:7), 6.16 (1H, brd, J=16Hz, 1′-H), 9.16 (2H, d, J=2Hz, ArH),
1.0mL/min, 254nm (detect.); 4 (ε at 254nm: 3080): 4.2min, 2 9.23 (1H, t, J=2Hz, ArH). 13C-NMR (75MHz, CDCl3) δ:
(ε at 254nm: 2550): 6.1min].
20.94, 21.04, 28.12, 29.69, 36.54, 37.84, 43.63, 65.13, 71.63,
(E)-3-[(R)-4-tert-Butyldimethylsilyloxy(TBS)-2,6,6- 122.22, 125.46, 128.56, 129.33 (C×2), 131.16, 134.34, 136.71,
trimethylcyclohex-1-enyl]allyl Acetate (6) To a solution of 148.59 (C×2), 162.08, 170.77. HR-MS (ESI) m/z Calcd for
compound 515) (1.50g, 4.43mmol) in dry ether (30mL) was C21H24O8N2Na [M+Na]+ 455.1425. Found 455.1427.
added diisobutylaluminium hydride (DIBAL-H) (1.0M in
Et2NH-Promoted Methanolysis of 3,5-Dinitrobenzoate 8
hexane; 9.8mL, 9.8mmol) at 0°C and the mixture was stirred In the same manner as described for Et2NH-promoted metha-
at 0°C for 10min. Excess DIBAL-H was destroyed by the nolysis of 3,5-dinitrobenzoate 3, methanolysis of compound
addition of moist silica gel (SiO2–H2O, 5:1) and the mixture 8 (200mg, 0.46mmol) gave the crude products, which were
was filtered through Celite. The filtrate was dried and evapo- purified by flash CC (acetone–hexane–CH2Cl2, 2:9:9) to yield
rated to give the crude alcohol, which was dissolved in dry compound 2 (98mg, 89%) as a colorless oil.
CH2Cl2 (10mL) and Et3N (3.1mL, 22.3mmol), DMAP (54mg,
(S)-4-Ethynyl-3,5,5-trimethyl-2-oxocyclohex-3-enyl
0.44mmol) and Ac2O (0.84mL, 8.89mmol) were added to it. 3,5-Dinitrobenzoate (10) In the same manner as described
After being stirred at r.t. for 20min, the reaction mixture was for the preparation of compound 3, benzoylation of compound
diluted with AcOEt and washed with brine. The organic layer 9 (1.23g, 6.90mmol) gave crude products, which were puri-
was dried and evaporated to give a residue, which was puri- fied by flash CC (AcOEt–hexane, 3:7) to provide compound
fied by flash CC (AcOEt–hexane, 15:85) to give compound 10 (2.21g, 86%) as a colorless solid: mp 133–134°C. [α]D25
6 (1.31g, 84% from 5) as a colorless oil: [α]D25 −77.5 (c=0.94, −166.3 (c=0.93, CHCl3). IR (CHCl3) cm−1: 3302 (≡C−H),
1
CHCl3). IR (CHCl3) cm−1: 1733 (CO). H-NMR (300MHz, 2092 (C≡C), 1742 and 1689 (CO), 1628 (C=C), 1549 and 1345
1
DCl3) δ: 0.78 (6H, s, SiCH3×2), 0.90 (9H, s, tert-Bu), 1.01 and (NO2). H-NMR (300MHz, CDCl3) δ: 1.41 and 1.47 (each
1.03 (each 3H, s, gem-CH3), 1.47 (1H, t, J=12Hz, 5′-H), 1.65 3H, s, gem-CH3), 2.03 (3H, s, 3-CH3), 2.27 (1H, dd, J=13,
(1H, ddd, J=12, 3.5, 2Hz, 5′-H), 1.67 (3H, s, 2′-CH3), 2.04 7Hz, 6-H), 2.33 (1H, t, J=13Hz, 6-H), 3.88 (1H, s, ≡C–H),
(1H, brdd, J=17, 9.5Hz, 3′-H), 2.07 (3H, s, CH3COO), 2.20 5.82 (1H, dd, J=13, 7Hz, 1-H), 9.20 (2H, d, J=2.5Hz, ArH),
(1H, brdd, J=17, 5.5Hz, 3′-H), 3.93 (1H, m, 4′-H), 4.61 (2H, 9.25 (1H, t, J=2.5Hz, ArH). 13C-NMR (75MHz, CDCl3) δ:
dd, J=6.5, 1Hz, 1-H2), 5.52 (1H, tt, J=16, 6.5Hz, 2-H), 6.13 14.37, 25.91, 30.48, 36.87, 41.20, 73.24, 79.66, 93.37, 122.59,
(1H, brd, J=16Hz, 3-H). 13C-NMR (75MHz, CDCl3) δ: −4.60 129.68 (C×2), 133.44, 137.44, 145.19, 148.63 (C×2), 161.87,

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Chem. Pharm. Bull.
Vol. 65, No. 10 (2017)
191.79. HR-MS (ESI) m/z Calcd for C18H16O7N2Na [M+Na]+ ddd, J=14, 9.5, 5.5Hz, 4-H2), 1.84–2.16 (2H, m, 5-H2), 2.97
395.0850. Found 395.0850. (1H, s, OH), 2.97 (1H, t, J=5Hz, OH), 4.46 and 4.53 (each
Et2NH-Promoted Methanolysis of 3,5-Dinitrobenzoate 1H, d, J=20, 5Hz, 1-H2), 5.04 (1H, tsept, J=7, 1Hz, 6-H).
10 In the same manner as described for Et2NH-promoted 13C-NMR (75MHz, CDCl3) δ: 17.66, 22.15, 25.63, 26.12,
methanolysis of 3,5-dinitrobenzoate 3, methanolysis of com- 39.92, 64.65, 78.46, 122.95, 133.31, 214.15. HR-MS (ESI) m/z
pound 10 (372mg, 1.00mmol) gave the crude products, which Calcd for C10H18O3Na [M+Na]+ 209.1148. Found 209.1147.
were purified by flash CC (acetone–hexane–CH2Cl2, 1:6:3) to
yield compound 9 (176mg, 99%) as a colorless solid. H-NMR
(R)-13b
1
In the same manner as described above, compound 11b
data were identical with those previously reported.17) The en- (683mg, 1.80mmol) was converted into (R)-13b (308mg, 92%)
antiomeric purity was confirmed (>99% ee) by chiral HPLC as a colorless oil. The enantiomeric purity was confirmed
[CHIRALPAK IC 0.46×25cm (Daicel), EtOH–hexane (5:95), (98% ee) by chiral HPLC: [α]D27 −2.4 (c=1.00, CHCl3). HR-MS
1.0mL/min, 27°C, 267nm (detect.); 9: 11.13min, enantiomer (ESI) m/z Calcd for C10H18O3Na [M+Na]+ 209.1148. Found
of 9: 12.69min]; HR-MS (ESI) m/z Calcd for C11H14O2Na 209.1149.
[M+Na]+ 201.0886. Found 201.0885.
(S)-3-Hydroxy-3,7-dimethyl-2-oxooct-6-enyl 3,5-Dinitro-
Conflict of Interest The authors declare no conflict of
benzoate (12a) To a solution of the compound 11a8) (1.00g, interest.
2.62mmol) in dry THF (7.7mL) and dry dimethylsulfoxide
(7.7mL) was added IBX (2.20g, 7.86mmol) in one portion and
the reaction mixture was heated at 50°C for 1h under stirring.
After cooling, water (15mL) was added to the mixture and
the precipitates were filtered off and washed with AcOEt. The
filtrate was washed with brine, dried and evaporated to give a
residue, which was purified by flash CC (AcOEt–hexane, 3:7)
to yield the ketone 12a (908mg, 91%) as a pale yellow viscous
oil: [α]D22 −23.1 (c=0.99, CHCl3). IR (CHCl3) cm−1: 3605 and
3510 (OH), 1749 and 1732 (split.) (CO), 1550 and 1345 (NO2).
1H-NMR (300MHz, CDCl3) δ: 1.46 (3H, s, 3-CH3), 1.65 and
1.71 (each 3H, s, gem-CH3), 1.74 and 1.91 (each 1H, ddd,
J=14, 9.5, 6Hz, 4-H2), 1.99–2.22 (2H, m, 5-H2), 2.78 (1H,
s, OH), 5.12 (1H, tsept, J=7, 1Hz, 6-H), 5.34 and 5.41 (each
1H, d, J=17.5Hz, 1-H2), 9.22 (2H, d, J=2Hz, ArH), 9.26 (1H,
t, J=2Hz, ArH). 13C-NMR (75MHz, CDCl3) δ: 17.73, 22.15,
25.68, 26.01, 39.69, 67.36, 79.53, 122.69, 123.04, 129.71 (C×2),
133.03, 133.49, 148.65 (C×2), 162.00, 200.26. HR-MS (ESI)
m/z Calcd for C17H19O8N2 [M−H]− 379.1147. Found 379.1151.
(R)-12b
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In the same manner as described above, compound 11b8)
(1.00g, 2.62mmol) was converted into (R)-12b (949mg, 95%)
as a pale yellow viscous oil; [α]D24 +17.6 (c=1.02, CHCl3).
HR-MS (ESI) m/z Calcd for C17H19O8N2 [M−H]− 379.1147.
Found 379.1151.
(S)-1,3-Dihydroxy-3,7-dimethyloct-6-en-2-one
(CPB
Pheromone) (13a) To a solution of compound 12a (591mg,
1.56mmol) in MeOH (16mL) was added Et2NH (85µL,
0.78mmol) at r.t. After being stirred at r.t. for 10min, the
mixture was concentrated. The resulting residue was puri-
fied by flash CC (AcOEt–hexane, 1:2) to provide compound
1
13a (274mg, 95%) as a colorless oil. H- and 13C-NMR data
were identical with those reported.22) The enantiomeric pu-
rity was confirmed (97% ee) by chiral HPLC [CHIRALPAK
ID 0.46×25cm (Daicel), EtOH–hexane (15:85), 1.0mL/min,
30°C, 210nm (detect.); 13a: 5.66min, 13b: 6.73min]; [α]D26
+3.6 (c=1.00, CHCl3). IR (CHCl3) cm−1: 3607 and 3610 (OH),
1
1712 (CO). H-NMR (300MHz, CDCl3) δ: 1.37 (3H, s, 3-CH3),
1.58 and 1.67 (each 3H, s, gem-CH3), 1.71 and 1.80 (each 1H,