Synthesis of (1R,7Z)-1-methyl-7-hexadecenyl acetate, the female sex pheromone of the honey locust gall midge

Article abstract of DOI:10.1271/bbb.120265

(1R,7Z)-1-Methyl-7-hexadecenyl acetate (1), the female sex pheromone of the honey locust gall midge (Dasineura gleditchiae), was synthesized from 6-hepten-1-ol in an 8.9% overall yield (eight steps). Hydrolytic kinetic resolution of (±)-1,2-epoxy-8-heptad

Full text of DOI:10.1271/bbb.120265

Biosci. Biotechnol. Biochem., 76 (7), 1419–1421, 2012
Note
Synthesis of (1R,7Z)-1-Methyl-7-hexadecenyl Acetate,
the Female Sex Pheromone of the Honey Locust Gall Midge
*
y
Yasumasa SHIKICHI and Kenji MORI
Photosensitive Materials Research Center, Toyo Gosei Co., Ltd., 4-2-1 Wakahagi, Inzai, Chiba 270-1609, Japan
Received April 6, 2012; Accepted April 20, 2012; Online Publication, July 7, 2012
[doi:10.1271/bbb.120265]
(1R,7Z)-1-Methyl-7-hexadecenyl acetate (1), the
female sex pheromone of the honey locust gall midge
(Dasineura gleditchiae), was synthesized from 6-hepten-
1-ol in an 8.9% overall yield (eight steps). Hydrolytic
kinetic resolution of (Æ)-1,2-epoxy-8-heptadecyne was
the key step in the synthesis.
(MCPBA) to give (ꢀ)-1,2-epoxy-8-heptadecyne (6).
HKR of (ꢀ)-6 was executed following Jacobsen’s
improved procedures by means of the (salen)Co(III)OTs
catalyst.6–8) Treatment of (ꢀ)-6 with (S,S)-
(salen)Co(III)OTs and 0.5 equivalents of water in
25
dichloromethane gave (S)-6, ½ꢀꢁD ꢂ7:00 (c 4.06,
hexane), in 42% yield based on (ꢀ)-6. The undesired
(R)-6 was hydrolyzed to diol (R)-7, which could be
removed easily by silica gel chromatography.
Key words: Dasineura gleditchiae; honey locust gall
midge; hydrolytic kinetic resolution; 1-
methyl-7-hexadecenyl acetate; pheromone
Reduction of (S)-6 with lithium aluminum hydride in
22
diethyl ether afforded (R)-8-heptadecyn-2-ol (8), ½ꢀꢁD
The chemical ecology of midges is an important
recent topic in insect pest control.2) In 1993 we reported
the method of synthesis of (1S,9E)-1-methyl-9-dode-
cenyl acetate, the female sex pheromone of the Hessian
fly, Mayetiola destructor, one such midge.3) Here we
report the method of synthesis of the pheromone of
another midge.
The honey locust gall midge, Dasineura gleditchiae
Osten, Sacken 1866 (Diptera: Cecidomyiidae), is the
most problematic pest of the honey locust tree (Gleditsia
triacanthos L.) in North America and its cultivars in
Europe. In order to monitor the flight of the midge by
ꢂ7:01 (c 4.00, hexane). Hydrogenation of (R)-8 over
Lindlar’s palladium catalyst in the presence of quinoline
in cyclohexane gave (2R,8Z)-8-heptadecen-2-ol (9),
21
½ꢀꢁD ꢂ6:47 (c 4.26, hexane). Finally, acetylation of
(2R,8Z)-9 with acetic anhydride and pyridine yielded the
pheromone, (1R,7Z)-1-methyl-7-hexadecenyl acetate
23
(1), ½ꢀꢁD ꢂ2:30 (c 4.01, hexane), the chemical purity
of which as checked by GC was 94.3%, including 4.3%
contaminating (E)-isomer and the saturated product
(0.7%). Its enantiomeric purity was 93.8% ee as
determined by enantioselective GC on a Chiramixꢀ
column.9) The overall yield of (1R,7Z)-1 is 8.9% based
on 2 (eight steps).
}
means of pheromone-based trapping, Szocs and co-
workers identified the female-emitted sex pheromone of
D. gleditchiae as (1R,7Z)-1-methyl-7-hexadecenyl ace-
tate (1) in 2009.4) The R absolute configuration at C-1
of 1 was determined by synthesis and bioassay of
the enantiomers of 1.4) Lipase-catalyzed asymmetric
hydrolysis of (ꢀ)-1 was employed as the key step in
their method of synthesis.
In conclusion, a new synthesis of the female sex
pheromone of Dasineura gleditchiae was accomplished,
employing Jacobsen’s HKR of (ꢀ)-epoxide 6 as the
key step.
We became interested in developing a new method of
synthesis of (1R,7Z)-1 based on retrosynthetic analysis,
as shown in Scheme 1. Pheromone (1R,7Z)-1 is pre-
pared by semi-hydrogenation and acetylation of (R)-8-
heptadecyn-2-ol (A), which is prepared by reductive
cleavage of (S)-epoxide B. Synthesis of (S)-B can be
achieved by hydrolytic kinetic resolution (HKR) of (ꢀ)-
B following Jacobsen and co-workers.5) The epoxide
(ꢀ)-B is readily available from commercially available
building blocks C and D.
Scheme 2 summarizes our method of synthesis of
(1R,7Z)-1. 6-Hepten-1-ol (2 = C) was converted to the
corresponding iodide 4 in a conventional manner via
tosylate 3. Alkylation of 1-decyne with 4 and n-
butyllithium yielded 1-heptadecen-8-yne (5), which
was epoxidized with m-chloroperbenzoic acid
Scheme 1. Retrosynthetic Analysis of (1R,7Z)-1.
*
y
Pheromone Synthesis, Part 251, See ref. 1 for Part 250.
To whom correspondence should be addressed. Fax: +81-3-3813-1516; E-mail: kjk-mori@arion.ocn.ne.jp

1420
Y. SHIKICHI and K. MORI
Scheme 2. Synthesis of (1R,7Z)-1.
Reagents: (a) TsCl, C5H5N (92%); (b) NaI, DMF (79%); (c) 1-decyne, n-BuLi, THF, HMPA (86%); (d) MCPBA, CH2Cl2 (58%); (e) (S,S)-
(Salen)Co(III)OTs, CH2Cl2, H2O (0.5 eq) (42%); (f) LiAlH4, Et2O (65%); (g) H2, Lindlar’s Pd cat., quinoline, cyclohexane (94%); (h) Ac2O,
C5H5N (96%).
Experimental
was washed with hexane. The filtrate and washings were diluted with
hexane and washed successively with a dil. Na2S2O3 solution, water,
an Na2CO3 solution, and brine, dried (MgSO4), and concentrated
in vacuo. The residue (14.0 g) was chromatographed over SiO2 (200 g).
Elution with hexane/EtOAc (100:1) gave 3.26 g (27%) of recovered 5.
Subsequent elution with hexane/EtOAc (20:1) gave 6.46 g of (ꢀ)-6.
The recovered 5 (3.26 g, 13.9 mmol) in CH2Cl2 (30 mL) was treated
with MCPBA (3.83 g, 15.3 mmol) again to give 1.65 g of (ꢀ)-6. The
combined (ꢀ)-6 (8.11 g) was distilled to give 7.54 g (58%) of (ꢀ)-6 as
All boiling point (bp) data are uncorrected values. Refractive indices
(nD) were measured with a DR-M2 refractometer (Atago, Tokyo,
Japan), and optical rotation values were measured with a P-1020
polarimeter (Jasco, Tokyo, Japan). IR spectra were measured with a
FT/IR-410 spectrometer (Jasco, Tokyo, Japan), and 1H-NMR spectra
(400 MHz, TMS at ꢁ ¼ 0:00 as internal standard) and 13C-NMR spectra
(100 MHz, CDCl3 at ꢁ ¼ 77:0 as internal standard) were recorded with
a JNM-AL 400 spectrometer (Jeol, Tokyo, Japan). GC-MS data were
measured with a 5975 Inert XL instrument (Agilent Technologies,
California, United States), and HRMS data were recorded on a 6530
Accurate Mass Q-TOF LC/MS instrument (Agilent Technologies,
California, United States). Column chromatography was carried out on
Kieselgel 60 Art. 1.07734 (Merck, Darmstadt, Germany).
18
a colorless oil, bp 134–136 ꢃC at 1.5 Torr; nD 1.4586; IR ꢂmax (film)
cmꢂ1: 2929 (s), 2856 (s), 1464 (m), 1259 (w), 1128 (w); 1H-NMR ꢁH
(400 MHz, CDCl3): 0.88 (3H, t, J ¼ 6:8 Hz, CH3), 1.20–1.66 (20H,
m), 2.10–2.25 (4H, m, CH2Cꢄ ꢅ2), 2.44–2.51 (1H, m), 2.73–2.80
(1H, m), 2.88–2.97 (1H, m). HRMS of (ꢀ)-6 [same conditions as for
4]: calcd. for C17H31O [ðM þ HÞþ], 251.2369: found, 251.2362.
(S)-1,2-Epoxy-8-heptadecyne [(S)-6]. A mixture of (S,S)-N,N0-
bis(3,5-di-t-butylsalicylidene)-1,2-cyclohexanediamino cobalt(II) [(S,S)-
6-Heptenyl tosylate (3). In the manner described previously,8)
2
19
(5.30 g, 46.4 mmol) gave 11.5 g (92%) of 3 as a colorless oil, nD
1.5071; IR ꢂmax (film) cmꢂ1: 3074 (m), 2931 (s), 2860 (m),1639 (m),
1599 (m, arom. C=C), 1458 (m), 1362 (s, SO2), 1176 (s, SO2), 1097
(m), 949 (s), 816 (m), 665 (m), 555 (m); 1H-NMR ꢁH (400 MHz,
CDCl3): 1.22–1.39 (4H, m), 1.59–1.71 (2H, m), 1.92–2.06 (2H, m),
2.50 (3H, s, C6H4CH3), 4.02 (2H, t, J ¼ 6:4 Hz, CH2OTs), 4.87–5.01
(2H, m, CH2=CH), 5.67–5.81 (1H, m, CH2=CH), 7.34 (2H, d,
J ¼ 8:0 Hz, arom. H), 7.79 (2H, d, J ¼ 8:0 Hz, arom. H).
.
(salen)Co(II)] (54 mg, 0.089 mmol) and p-TsOH H2O (17 mg, 0.089
mmol) in dry CH2Cl2 (1.2 mL) was stirred for 1 h under air at room
temperature. The mixture was concentrated and dried for 1 h in vacuo.
(ꢀ)-6 (3.73 g, 14.9 mmol) and water (134 mL, 7.44 mmol) were added,
and the mixture was stirred vigorously at room temperature. After
20 min, the mixture solidified and could not be stirred easily. After a
further 2 h, it gradually turned to a paste-like suspension and stirring
became relatively easy. The mixture was stirred for 20 h at room
temperature. Then it was dissolved in a small amount of EtOAc and
chromatographed over SiO2 (30 g). Elution with hexane/EtOAc (50:1)
gave 1.82 g of (S)-6 as a dark oil. Subsequent elution with EtOAc gave
2.05 g of (R)-7 as a brown solid. Crude (S)-6 was distilled to give (S)-6
6-Heptenyl iodide (4). In the manner described previously,8)
(10.8 g, 40.2 mmol) gave 7.15 g (79%) of 4 as a colorless oil, nD
3
20
1.5084; IR ꢂmax (film) cmꢂ1: 3076 (m), 2929 (s), 2854 (m), 1639 (m),
1458 (m), 1207 (w), 991 (m), 910 (m), 723 (w); 1H-NMR ꢁH
(400 MHz, CDCl3): 1.33–1.52 (4H, m), 1.75–1.92 (2H, m), 1.98–2.15
(2H, m), 3.19 (2H, t, J ¼ 6:8 Hz, CH2I), 4.91–5.08 (2H, m, CH2=CH),
5.73–5.87 (1H, m, CH2=CH). HRMS of 4 [APCI ionization; positive
polarity; 6 mA corona current; N2 (35 psi) nebulizer; N2 (5 L/min,
350 ꢃC) drying gas; 350 ꢃC vaporizer; 3000 V capillary current; 0.01 M
HCO2H aq/MeOH (10/90) eluant]: calcd. for C7H14I [ðM þ HÞþ],
225.0135: found, 225.0129.
18
(1.56 g, 42%) as a colorless oil, bp 144–145 ꢃC at 1 Torr; nD 1.4597;
25
½ꢀꢁD ꢂ7:00 (c 4.06, hexane). Its IR and 1H-NMR spectra were
identical to those of (ꢀ)-6. HRMS of (S)-6 [same conditions as for 4]:
calcd for C17H31O [ðM þ HÞþ], 251.2369: found, 251.2368.
(R)-8-Heptadecyn-2-ol (8). After reduction with LiAlH4 (0.25 g,
6.6 mmol) in Et2O (8 mL), (S)-6 (2.95 g, 11.8 mmol) gave 1.93 g (65%)
1-Heptadecen-8-yne (5). In the manner described previously,8)
4
(7.07 g, 31.6 mmol) gave 6.34 g (86%) of 5 as a colorless oil, bp 121–
20
22
of 8 as a colorless oil, nD 1.4595; ½ꢀꢁD ꢂ7:01 (c 4.00, hexane); IR
ꢂmax (film) cmꢂ1: 3354 (s, O–H), 2929 (s), 2856 (s), 1464 (m), 1375
(w), 1128 (w, C–O), 1099 (w); 1H-NMR ꢁH (400 MHz, CDCl3): 0.88
(3H, t, J ¼ 6:8 Hz, CH3CH2), 1.19 (3H, d, J ¼ 6:0 Hz, CH3CH), 1.21–
1.74 (21H, m), 2.02–2.26 (4H, br, CH2Cꢄ ꢅ2), 3.70–3.88 (1H, br,
125 ꢃC at 3 Torr; nD 1.4564; IR ꢂmax (film) cmꢂ1: 3078 (w), 2929 (s),
20
2856 (s), 1641 (w), 1458 (m), 993 (w), 910 (m), 723 (w); 1H-NMR ꢁH
(400 MHz, CDCl3): 0.88 (3H, t, J ¼ 6:4 Hz, CH3), 1.15–1.65 (18H,
m), 1.95–2.09 (2H, m), 2.09–2.26 (4H, m, CH2Cꢄ ꢅ2), 4.87–5.07
(2H, m, CH2=CH), 5.74–5.88 (1H, m, CH2=CH). GC-MS [HP-5MS
column, 5% phenylmethylsiloxane, 30 m ꢅ 0:25 mm i.d.; 60.7 kPa
pressure; 50 ꢃC (10 min hold), 50–160 ꢃC (+10 ꢃC/min, 10 min hold),
160–220 ꢃC (+4 ꢃC/min) temperature]: tR19.9 min (99.4%). MS of 5
(70 eV, EI): m=z: 234 (0.2) [Mþ, C17H30], 219 (14), 205 (3), 191 (3),
177 (5), 163 (17), 149 (13), 136 (36), 121 (95), 107 (61), 95 (72), 93
(76), 81 (100), 79 (84), 67 (98), 55 (56), 41 (54).
CHOH). HRMS of 8 [same conditions as for 4]: calcd. for C17H33
[ðM þ HÞþ], 253.2526: found, 253.2526.
O
(2R,8Z)-8-Heptadecen-2-ol (9). Lindlar’s Pd catalyst on CaCO3
with Pb2þ (Aldrich, 20 mg) and quinoline (40 mL) were added to a
solution of 8 (1.00 g, 3.96 mmol) in cyclohexane (10 mL). The mixture
was stirred under an H2 atmosphere (gas cylinder, 1 atm) at room
temperature for 2 h. Then it was filtered through Celite, and the catalyst
and Celite were washed with Et2O. The filtrate was diluted with Et2O,
and washed successively with a dil. HCl solution, water, an NaHCO3
solution, and brine, dried (MgSO4), and concentrated in vacuo. The
residue (992 mg) was chromatographed over SiO2 (20 g). Elution with
(ꢀ)-1,2-Epoxy-8-heptadecyne [(ꢀ)-6]. MCPBA (69% purity,
14.5 g, 57.9 mmol) was added portionwise to a stirred and ice-cooled
solution of 5 (12.3 g, 52.5 mmol) in CH2Cl2 (120 mL) at 0–5 ꢃC. The
mixture was stirred for 30 min at 0–5 ꢃC and for 2.8 h at room
temperature. Then it was filtered to remove solid MCBA. The solid
19
hexane/EtOAc (10:1) gave 949 mg (94%) of 9 as a colorless oil, nD

Synthesis of the Pheromone of the Honey Locust Gall Midge
1421
21
1.4572; ½ꢀꢁD ꢂ6:47 (c 4.26, hexane); IR ꢂmax (film) cmꢂ1: 3347 (s,
(28), 43 (70), 41 (36). HRMS of 1 [same conditions as for 4]: calcd. for
19H37O2 [ðM þ HÞþ], 297.2788: found, 297.2789.
O–H), 3005 (m), 2925 (s), 2854 (s), 1654 (w), 1464 (m), 1375 (m),
1123 (m, C–O), 1096 (w); 1H-NMR ꢁH (400 MHz, CDCl3): 0.88 (3H, t,
J ¼ 6:8 Hz, CH3CH2), 1.19 (3H, d, J ¼ 6:4 Hz, CH3CH), 1.21–1.52
(21H, m), 1.92–2.09 (4H, m), 3.74–3.84 (1H, br, CHOH), 5.29–5.40
(2H, m, CH=CH). HRMS of 9 [same conditions as for 4]: calcd for
C17H35O [ðM þ HÞþ], 255.2682: found, 255.2680.
C
Acknowledgment
We thank Mr. M. Kimura (President, Toyo Gosei Co.,
Ltd.) for his support.
(1R,7Z)-1-Methyl-7-hexadecenyl acetate (1). In the usual manner, 9
(299 mg, 1.18 mmol) in dry pyridine (1.5 mL) was treated with acetic
anhydride (484 mg, 4.74 mmol) to give 334 mg (96%) of 1 as a
colorless oil. A portion of this oil was distilled to give an analytical
References
sample, bp 146–147 ꢃC at 2 Torr; nD 1.4473; ½ꢀꢁD ꢂ2:30 (c 4.01,
1) Shikichi Y, Akasaka K, Tamogami S, Shankar S, Yew JY, and
Mori K, Tetrahedron, 68, 3750–3760 (2012).
21
23
22
hexane), ½ꢀꢁD þ0:15 (c 4.12, CHCl3); IR ꢂmax (film) cmꢂ1: 3005 (m),
2926 (s), 2855 (s), 1739 (s, C=O), 1654 (w), 1462 (m), 1372 (m), 1244
(s); 1H-NMR ꢁH (400 MHz, CDCl3): 0.88 (3H, t, J ¼ 6:8 Hz,
CH3CH2), 1.20 (3H, d, J ¼ 6:4 Hz, CH3CH), 1.22–1.65 (20H, m),
1.93–2.11 (4H, br), 2.03 (3H, s, CH3C=O), 4.84–4.92 (1H, m,
CHO2CCH3), 5.29–5.40 (2H, m, CH=CH); 13C-NMR ꢁC (100 MHz,
CDCl3): 14.1, 19.9, 21.4, 22.7, 25.3, 27.1, 27.2, 29.1, 29.3, 29.5,
29.6, 29.7, 31.9, 35.9, 71.0, 129.5, 129.9, 170.6. Enantioselective GC
of 1: [GC-2014 instrument (Shimadzu, Kyoto, Japan), InartCap
CHIRAMIXꢀ column, 30 m ꢅ 0:25 mm i.d.; 60.7 kPa pressure; 40–
180 ꢃC (þ0:7 ꢃC/min) temperature, He (0.7 mL/min) carrier gas]: tR
229.1 min [(S)-1, 3.1%], tR 305.4 min [(R)-1, 96.9%, 93.8% ee]. GC-
MS [same conditions as for 5]: tR 31.5 min [(2R,8Z)-1, 94.3%], tR
31.7 min [(2R,8E)-1, 4.3%], tR 32.2 min [saturated product of 1, 0.7%]
MS of 1 (70 eV, EI): m=z: 296 (0.04) [Mþ, C19H36O2], 295 (0.2)
½M ꢂ 1ꢁþ, 236 (25), 194 (11), 166 (10), 152 (10), 138 (15), 137 (11),
125 (5), 124 (27), 123 (21), 111 (13), 110 (66), 109 (42), 97 (26), 96
(100), 95 (64), 83 (31), 82 (84), 81 (77), 68 (50), 67 (71), 55 (57), 54
2) Hall DR, Amarawardana L, Cross JV, Francke W, Boddun T, and
Hillbur Y, J. Chem. Ecol., 38, 2–22 (2012).
3) Takeuchi Y and Mori K, Biosci. Biotechnol. Biochem., 57, 1967–
1968 (1993).
´
4) Molnar B, Karpati Z, Szocs G, and Hall DR, J. Chem. Ecol., 35,
´
´
}
706–714 (2009).
5) Schaus SE, Brandes BD, Larrow JF, Tokunaga M, Hansen KB,
Gould AE, Furrow ME, and Jacobsen EN, J. Am. Chem. Soc.,
124, 1307–1315 (2002).
6) Nielsen LPC, Stevenson CP, Blackmond DG, and Jacobsen EN,
J. Am. Chem. Soc., 126, 1360–1362 (2004).
7) Stevenson CP, Nielsen LPC, and Jacobsen EN, Org. Synth., 83,
162–169 (2006).
8) Mori K, Shikichi Y, Shankar S, and Yew JY, Tetrahedron, 66,
7161–7168 (2010).
9) Tamogami S, Awano K, Amaike M, Takagi Y, and Kitahara T,
Flavour Frag. J., 16, 349–352 (2001).