Transformation of esters into allyl halides via substituted cyclopropanols. Application in the synthesis of (2S,3R,7R/S)-3,7-dimethyltridec-2-yl acetate and propionate, sex attractants of pine sawfly Diprion pini

Article abstract of DOI:10.1016/j.tetlet.2004.05.022

A convenient new approach to the synthesis of the acetate and the propionate of (2S,3R,7R/S)-3,7-dimethyltridecan-2-ol, sex attractants of Diprion pini L., using the cyclopropanation of the ethoxycarbonyl group in O-THP protected ethyl (S)-lactate with ethylmagnesium bromide in the presence of titanium(IV) isopropoxide followed by C-2-C-3 cyclopropane ring opening as the key steps has been performed.

Full text of DOI:10.1016/j.tetlet.2004.05.022

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 5253–5255
Transformation of esters into allyl halides via substituted
cyclopropanols. Application in the synthesis of (2S,3R,7R/S)-3,7-
dimethyltridec-2-yl acetate and propionate, sex attractants of
pine sawfly Diprion pini
Andrey V. Bekish, Konstantin N. Prokhorevich and Oleg G. Kulinkovich*
Department of Organic Chemistry, Belarusian State University, Fr. Scaryny Av. 4, 220050 Minsk, Belarus
Received 5 March 2004; revised 26 April 2004; accepted 6 May 2004
Abstract—A convenient new approach to the synthesis of the acetate and the propionate of (2S,3R,7R/S)-3,7-dimethyltridecan-2-ol,
sex attractants of Diprion pini L., using the cyclopropanation of the ethoxycarbonyl group in O-THP protected ethyl (S)-lactate with
ethylmagnesium bromide in the presence of titanium(IV) isopropoxide followed by C-2–C-3 cyclopropane ring opening as the key
steps has been performed.
Ó 2004 Elsevier Ltd. All rights reserved.
Pine sawfly Diprion pini L. is a widely spread severe pest
on conifers, the sex pheromone of which has been
identified as the acetate (1-COMe) and the propionate
(1-COEt) of (2S,3R,7R)-3,7-dimethyltridecan-2-ol 1.1
Enantiomerically pure (2S,3R,7R)-3,7-dimethyltridecan-
2-ol 1 was synthesized starting from (3R,4R)-3,4-di-
methyl-c-butyrolactone, which was obtained in 10 steps
from (2R,3R)-tartaric acid.1 (2S,3R,7R/S)-3,7-Dimethyl-
tridecan-2-ol 1 is also of practical interest, because esters
of (2S,3R,7S)-3,7-dimethyltridecan-2-ol 1 do not inhibit
the biological activity of the natural pheromone.2
Recently, Hedenstrom et al. have performed a synthesis
cyclopropanol precursor.4 Thus, C-1–C-3 bond cleav-
ages in the three-membered cycle of 1,2-disubstituted
cyclopropanols leading to the corresponding a-methyl
ketones, were successfully used in short syntheses of
racemic pheromones of the German cockroach Blattella
germanica and mixobacterium Stigmatella aurantiaca.5;6
In the present work, to create the methyl-branched
skeleton of (2S,3R,7R/S)-3,7-dimethyltridecan-2-ol 1,
we have used an alternative approach based on the
transformation of mesylates of cyclopropanols into 2-
substituted allyl halides accompanied by C-2–C-3 bond
cleavage of a three-membered ring.7
of (2S,3R,7R/S)-3,7-dimethyltridecan-2-ol
1
using
stereoselective enzymatic acylation of racemic threo-3,7-
dimethyltridecan-2-ol 1 to create the required stereo-
chemistry at C-2and C-3 carbon atoms. In the present
work a new convenient approach to the synthesis of 1
starting from ethyl (S)-lactate has been performed.
To obtain the key (2S)-3-(bromomethyl)but-3-en-2-ol 2
we used ethyl (S)-lactate 3, which was transformed into
the corresponding THP derivative 4 (Scheme 1). The
ester 4 was reacted with ethylmagnesium bromide in the
3
8
presence of Ti(Oi-Pr)4 to form cyclopropanol 5 in a
high yield.9 The latter was transformed into mesylate 6
by a standard procedure. When treated with MgBr2, the
crude mesylate 6 underwent cationic cyclopropyl–allyl
isomerization with C-2–C-3 bond cleavage of the
cyclopropane ring.7 This reaction was performed in a
diethyl ether/chloroform mixture, and was accompanied
by removal of the THP protecting group10 to form (2S)-
3-(bromomethyl)but-3-en-2-ol 2.11;12 Protection of the
hydroxy group in the latter and subsequent reaction of 7
with 3-methylnonylmagnesium bromide13 catalyzed by
copper(I) iodide led to allylic alcohol derivative 8 in 91%
For the preparation of organic compounds with methyl
or methylene substituents, it is sometimes convenient to
use a three-membered ring cleavage in an appropriate
Keywords: Cyclopropanols; Titanacyclopropanes; (S)-Lactic acid;
Pheromones; Pine sawfly.
* Corresponding author. Tel.: +375-17-2095459; fax: +375-17-22656-
09; e-mail: kulinkovich@bsu.by
0040-4039/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.05.022

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A. V. Bekish et al. / Tetrahedron Letters 45 (2004) 5253–5255
OR
OTHP
OR
CO2Et
e
d
b
Br
91%
59% (based on 4)
OR
3: R= H
2: R= H
5: R= H
c
89%
a
a
96%
4: R= THP
7: R= THP
6: R= Ms
OR
OH
h, i, j, k
33%
g
86%
(2S, 3R/S, 7R/S)-1
8: R= THP
9: R= H
f
95%
OR
OH
l
85-90%
(2S, 3R, 7R/S)-1-COMe: R=COMe
(2S, 3R, 7R/S)-1-COEt: R=COEt
(2S, 3R, 7R/S)-1
Scheme 1. Reagents and conditions: (a) DHP, PPTS (5 mol %), CH2Cl2; (b) EtMgBr, Ti(Oi-Pr)4, Et2O/THF; (c) MsCl, Et3N, Et2O; (d) MgBr2,
CHCl3/Et2O; (e) 3-methylnonylmagnesium bromide, CuI (5 mol %); (f) MeOH, PPTS (5 mol %.); (g) NaBH4, NiCl2Æ6H2O, MeOH; (h) phthalic
anhydride, Et3N, C6H6; (i) (S)-())-1-phenylethylamine, acetone; (j) four recrystallizations from acetone; (k) KOH, MeOH; (l) CH3COCl or
C2H5COCl, Et3N, Et2O.
yield.14 Removal of the THP group in 8 by acid-cata-
lyzed methanolysis gave alcohol 9.15 Based on 1H NMR
spectra of the (þ)- and (À)-MTPA-esters16 of 9, we
found that the stereoisomeric purity of 9 at C-2was
more than 98%.17 Smooth reduction of double bond in
9, which led to a mixture of erythro- and threo-diaste-
reomeric alcohols 1 in a nearly equimolar ratio (GLC
analysis) in 86% total yield, was performed by the action
of NaBH4 in the presence of NiCl2Æ6H2O in metha-
nol.18;19
References and notes
1. Bergstrom, G.; Wassegren, A.-B.; Anderbrant, O.; Fager-
hag, J.; Edlund, H.; Hedenstrom, E.; Hogberg, H.-E.;
Geri, C.; Auger, M. A.; Varama, M.; Hansson, B. S.;
Lofqvist, J. Experientia 1995, 51, 370–380.
2. Anderbrant, O.; Hansson, B. S.; Hallberg, E.; Geri, C.;
Varama, M.; Hedenstrom, E.; Hogberg, H.-E.; Fagerhag,
J.; Edlund, H.; Wassgren, A.-B.; Bergstrom, G.; Lofqvist,
J. J. Insect Physiol. 1995, 41, 395–401.
3. Hedenstrom, E.; Edlund, H.; Lund, S.; Abersten, M.;
Persson, D. J. Chem. Soc., Perkin Trans. 1 2002, 1810–1817.
4. (a) Kulinkovich, O. G. Chem. Rev. 2003, 103, 2597–2632;
(b) Gibson, D. H.; De Puy, C. H. Chem. Rev. 1974, 74,
605–623.
5. Epstein, O. L.; Kulinkovich, O. G. Tetrahedron Lett. 1998,
39, 1823–1826.
6. Epstein, O. L.; Kulinkovich, O. G. Tetrahedron Lett. 2001,
42, 3757–3758.
7. Kozyrkov, Yu. Yu.; Kulinkovich, O. G. Synlett 2002, 3,
443–446.
8. (a) Kulinkovich, O. G.; Sviridov, S. V.; Vasilevskii, D. A.;
Pritytskaya, T. S. Zh. Org. Khim. 1989, 25, 2244–2245; (b)
Kulinkovich, O. G.; Sviridov, S. V.; Vasilevskii, D. A.
Synthesis 1991, 234.
Separation of (2S,3R/S,7R/S)-3,7-dimethyltridecan-2-ol
1 into (2S,3R,7R/S)- and (2S,3S,7R/S)-diastereomers
was performed by its transformation into acid phthalate
esters by reaction with phthalic anhydride20 followed by
salt formation with (S)-(À)-1-phenylethylamine in ace-
tone. The (S)-(À)-1-phenylethylamine salt was recrys-
tallized four times from acetone and then hydrolyzed by
potassium hydroxide to give (2S,3R,7R/S)-dimethyl-
tridecan-2-ol 1, which contained 4% of diastereomeric
(2S,3S,7R/S)-dimethyltridecan-2-ol 1 in 66% of the
1
1
theoretical yield.2 H and 13C NMR spectral data of
1
(2S,3R,7R/S)-3,7-dimethyltridecan-2-ol 1, as well as H
9. Esposito, A.; Taddei, M. J. Org. Chem. 2000, 65, 9245–
9248.
10. For deprotection of tetrahydropyranyl ethers with mag-
nesium bromide see: Sunggak, K.; Park, J. H. Tetrahedron
Lett. 1987, 28, 439–440.
NMR spectral data of its acetate (1-COMe) and pro-
pionate (1-COEt) were in accordance with the data re-
ported in the literature.1;2
11. Using ether as the only solvent in this transformation
resulted in a low conversion of 6 to a mixture of 2 and 7.
12. THP protected ethyl (S)-lactate (13.10 g, 64.9 mmol) 4 was
converted into mesylate 6 via cyclopropanol 5 according
to published procedures9 without purification of 5. A
solution of MgBr2, prepared from magnesium (5.52g,
227 mmol) and 1,2-dibromoethane (42.70 g, 227 mmol) in
Acknowledgements
We are grateful for financial support from the Ministry
of Forest of the Republic of Belarus and INTAS Pro-
gram of the European Union.

A. V. Bekish et al. / Tetrahedron Letters 45 (2004) 5253–5255
5255
diethyl ether (170 mL), was added in one portion to a
solution of crude mesylate 6 in chloroform (170 mL). The
reaction mixture was refluxed for 3 h under an argon
atmosphere. After cooling in ice, the reaction mixture was
treated with water (200 mL). The organic layer was
separated, and the aqueous layer was extracted with
dichloromethane (5 Â 40 mL). The combined organic
extracts were dried over Na2SO4, concentrated under
reduced pressure and distilled under reduced pressure,
giving 12.58 g of a fraction which boiled at 70–120 °C
(6 mm). 2-Substituted allyl bromide 2 (6.31 g, 59%) was
isolated by column chromatography on silica gel (eluent:
cyclohexane/ethyl acetate). 1NMR (400 MHz, CDCl3): d
5.28–5.31 (m, 2H), 4.54 (q, J ¼ 6:5 Hz, 1H), 4.11 (d,
J ¼ 10:2Hz, 1H), 3.99 (d, J ¼ 10:2Hz, 1H), 1.87 (br s,
1H), 1.37 (d, J ¼ 6:5 Hz, 3H). 13C NMR (100 MHz,
CDCl3): 149.0, 115.1, 68.1, 32.8, 22.1.
15. NMR (400 MHz, CDCl3): d 5.02–5.04 (m, 1H), 4.79–4.82
(m, 1H), 4.25 (q, J ¼ 6:5 Hz, 1H), 1.92–2.12 (m, 2H), 1.56
(br s, 1H), 1.04–1.52(m, 18H), 1.29 (d, J ¼ 6:5 Hz), 0.88
(t, J ¼ 6:6 Hz, 3H), 0.85 (d, J ¼ 6:3 Hz, 3H). 13C NMR
(100 MHz, CDCl3): d 153.5, 107.9, 70.9, 70.9, 37.0, 37.0,
36.9, 36.9, 32.6, 32.0, 31.9, 29.6, 27.0, 25.4, 25.4, 22.7, 22.1,
19.6, 19.6, 14.1.
16. Dale, J. A.; Dull, D. L.; Mosher, H. S. J. Org. Chem. 1969,
34, 2543–2549.
17. The signals of the protons of the methoxy groups at 3.53
and 3.58 ppm were used to determine stereoisomeric
purity.
18. Toshio, S.; Kenryo, N.; Shuichi, S. Chem. Pharm. Bull.
1971, 19, 817–820.
19. NaBH4 (0.50 g, 13.2mmol) was added in small portions to
a solution of allylic alcohol 9 (1.50 g, 6.64 mmol) and
NiCl2Æ6H2O (0.39 g, 6.64 mmol) in methanol (30 mL) at
À20 °C over 5 min. The reaction mixture was stirred at
À20 °C for 15 min and then for 1 h at room temperature.
After solvent removal under reduced pressure, the residue
was diluted with diethyl ether and washed with brine. The
organic layer was separated, and the aqueous layer was
extracted with diethyl ether (4 Â 5 mL). The combined
organic extracts were dried over Na2SO4 and concentrated
under reduced pressure. Compound 1 (1.30 g, 86%) was
isolated by column chromatography on silica gel (eluent:
cyclohexane/ethyl acetate). 1NMR (400 MHz, CDCl3): d
3.61–3.73 (m, 1H), 2.00 (br s, 1H), 1.00–1.54 (m, 21H),
1.15 (d, J ¼ 6:3 Hz), 1.12(d, J ¼ 6:3 Hz), 0.80–0.90 (m,
9H).
13. Kletzke, P. G. J. Org. Chem. 1964, 29, 1363–1366.
14. Copper(I) iodide (0.19 g, 1.0 mmol) was added in one
portion to a solution of 3-methylnonylmagnesium bromide
(prepared
from
1-bromo-3-methylnonane
(8.90 g,
40.3 mmol) and magnesium (0.82g, 33.7 mmol) in diethyl
ether (40 mL)) cooled to À20 °C. After stirring for 3–5 min,
allyl bromide 7 (4.90 g, 19.7 mmol) in THF (15 mL) was
added drop wise to the reaction mixture over 5 min and
stirring was continued at À20 °C for 30 min and then 4 h at
room temperature. The reaction mixture was quenched
with 25 mL of saturated aqueous solution of NH4Cl. The
organic layer was separated, and the aqueous layer was
extracted with diethyl ether (4 Â 15 mL). The combined
organic extracts were washed with brine, dried over
Na2SO4 and concentrated under reduced pressure. Com-
pound 8 (5.55 g, 91%) was isolated by column chromato-
graphy on silica gel (eluent: cyclohexane/ethyl acetate).
20. Kantor, S. W.; Hauser, Ch. R. J. Am. Chem. Soc. 1953, 75,
1744.
21. Ratio of diastereomeric alcohols 1 was found on the basis
1
of it H NMR spectrum.1;2