Stereoselective synthesis of pear ester

Article abstract of DOI:10.1007/s10600-017-2191-0

A simple two-step synthesis of ethyl-(2E,4Z)-deca-2,4-dienoate based on Fe-catalyzed cross-coupling of ethyl-(2E,4Z)-5-chloropenta-2,4-dienoate, which was obtained via one-pot oxidation and olefination of readily available (2Z)-3-chloroprop-2-en-1-ol by n-pentylmagnesiumbromide, was developed.

Full text of DOI:10.1007/s10600-017-2191-0

DOI 10.1007/s10600-017-2191-0
Chemistry of Natural Compounds, Vol. 53, No. 6, November, 2017
STEREOSELECTIVE SYNTHESIS OF PEAR ESTER
*
R. N. Shakhmaev, A. Sh. Sunagatullina,
D. A. Akimova, and V. V. Zorin
A simple two-step synthesis of ethyl-(2E,4Z)-deca-2,4-dienoate based on Fe-catalyzed cross-coupling of
ethyl-(2E,4Z)-5-chloropenta-2,4-dienoate, which was obtained via one-pot oxidation and olefination of readily
available (2Z)-3-chloroprop-2-en-1-ol by n-pentylmagnesiumbromide, was developed.
Keywords: ethyl-(2E,4Z)-deca-2,4-dienoate, pear ester, Fe-catalyzed cross-coupling, barium permanganate.
Ethyl-(2E,4Z)-deca-2,4-dienoate (1) is commonly known as pear ester, was isolated from Bartlett pears (Pyrus
communis), and is responsible for the specific taste of this fruit [1]. Pear ester is widely used as a flavor in the food and
perfume industries [2] and is an effective attractant for battling the codling moth (Cydia pomonella) [3, 4].
Several approaches to the synthesis of 1 were based on a Wittig reaction [5–7], a Horner–Wadsworth–Emmons
reaction [8, 9], and stereoselective hydrogenation of acetylenic precursors [10]. However, their many steps, low overall
yields, and (or) low stereoselectivity hindered the development of a convenient and effective method for synthesizing pear
ester.
Herein, the development of a simple two-step method for synthesizing 1 using Fe-catalyzed cross-coupling of ethyl-
(2E,4Z)-5-chloropenta-2,4-dienoate (2) and n-pentylmagnesiumbromide is reported. Recently, Fe-based catalysts have
successfully replaced traditional platinum-group metal compounds in the syntheses of natural compounds and pharmaceutical
substances [11–15]. The main advantages of the iron salts usually used in cross-coupling [Fe(acac) , FeCl ] are the low cost,
3
3
availability, high catalytic-reaction rates, ability to be used as electrophilic partners of usually inactive aryl- and vinylchlorides,
lack of ligands, low toxicity, and ecological safety [16, 17].
O
O
1'
3
1'
a
b
Cl
R
Cl
1
OH
O
1
O
2'
5
5
3
2
1
1: R = n-C H
5
11
a. BaMnO , Ph P=CHCOOEt; b. n-C H MgBr, Fe(acac) , THF–NMP
4
3
5
11
3
The starting compound was (2Z)-3-chloroprop-2-en-1-ol (3) [18], which is easily prepared via hydrolysis of
(Z)-1,3-dichloropropene, a readily available multi-ton side product of allylchloride production [19]. The one-pot oxidation of
3 by barium manganate (BaMnO ) [20, 21] followed by Wittig olefination using (carboethoxymethylene)triphenylphosphorane
4
provided an efficient method for producing the new promising building block ethyl-(2E,4Z)-5-chloropenta-2,4-dienoate (2).
This strategy allowed problems with the preparation and isolation of the extremely labile, toxic, and difficultly handled
cis-3-chloroacrolein to be avoided. Furthermore, BaMnO is stable and convenient to use and reduces the amount of required
4
oxidant as compared with standard activated MnO (usually used in 10–50-fold excess [22]). Oxidation of 3 by BaMnO
2
4
(4 eq.) in the presence of (carboethoxymethylene)triphenylphosphorane in CH Cl at room temperature formed a mixture of
2
2
2 and its (2Z,4Z)-isomer in a 4:1 ratio that was easily and completely separated by ordinary column chromatography.
Fe-catalyzed cross-coupling of vinylchloride 2 with n-pentylmagnesiumbromide in the presence of catalytic amounts of Fe(acac)
3
in THF:N-methylpyrrolidone (NMP) at room temperature gave target 1 in good yield (77%) and isomeric purity (98%).
Ufa State Petroleum Technological University, 1 Kosmonavtov St., Ufa, 450062, e-mail: biochem@rusoil.net.
Translated from Khimiya Prirodnykh Soedinenii, No. 6, November–December, 2017, pp. 867–869. Original article submitted
February 17, 2017.
©
0009-3130/17/5306-1017 2017 Springer Science+Business Media New York
1017

The structure, stereochemical configuration and isomeric purity of the obtained compounds were confirmed by
high-performance GC, IR and NMR spectroscopy, and GC-MS. The vinylic H SSCCs J 15.2–15.6 Hz and J = 7.3 Hz that
2,3
4,5
were characteristic of the (E)- and (Z)-configurations and the strong-field shift by 4 ppm of the allyl C resonance of 1 as
compared with the (2E,4E)-analogs provided reliable proof of the (2E,4Z)-structures of synthesized dienes (1 and 2) [23].
The advantages of the developed method are the use of industrially available (Z)-1,3-dichloropropene (side product
of allylchloride production), small number of steps, high yield, isomeric purity of the target product, and lost cost of
the Fe-catalyst.
EXPERIMENTAL
13
1
PMR and C NMR spectra were recorded in CDCl on an AV-500 instrument (500 MHz for H and 125 MHz
3
13
13
for C). Chemical shifts in PMR spectra were measured vs. TMS; in C NMR spectra, relative to the solvent resonance
(ꢀ 77.0 ppm). GC-MS analysis used a Shimadzu GCMS-QP2010S instrument [electron-impact ionization at 70 eV, detected
C
mass range 33–350 Da, HP-1ms capillary column (30 m ꢁ 0.25 mm ꢁ 0.25 ꢂm), vaporizer temperature 280°C, ionization-
chamber temperature 200°C, temperature programmed from 50 to 300°C at 10°C/min, He carrier gas (1.1 mL/min)].
The reported mass spectra include peaks for the 10 strongest fragments plus the molecular ion.
Ethyl-(2E,4Z)-5-chloropenta-2,4-dienoate (2). A suspension of (2Z)-3-chloroprop-2-en-1-ol (3, 1.85 g, 2 mmol),
BaMnO (2.05 g, 8 mmol), and (carboethoxymethylene)triphenylphosphorane (0.697 g, 2 mmol) in anhydrous CH Cl
4
2
2
(8 mL) was stirred vigorously at room temperature until the substrate was fully converted (GC monitoring). The solid was
separated by centrifugation (the yield was slightly lowered if the precipitate was filtered). The organic phase was filtered
through a layer of silica gel and concentrated. The precipitate was separated by column chromatography (SiO , hexane–Et O,
2
2
1
9:1ꢃ8:2) to afford 2 (0.196 g, 61%) and the (2Z,4Z)-isomer (0.041 g, 13%). Í NMR spectrum (500 MHz, CDCl , ꢀ, ppm,
3
J/Hz): 1.31 (3H, t, J = 7, H -2ꢄ), 4.24 (2H, q, J = 7, Í-1ꢄ), 6.03 (1H, d, J = 15.6, H-2), 6.37 (1H, d, J = 7.3, H-5), 6.45 (1H,
3
13
dd, J = 11, 7.3, H-4), 7.68 (1H, dd, J = 15.6, 11, H-3). C NMR spectrum (125 MHz, CDCl , ꢀ, ppm): 14.19 (Ñ-2ꢄ), 60.58
(C-1ꢄ); 124.53, 126.14, 127.66, 136.57 (4 ꢁꢅCH=), 166.36 (C-1). Mass spectrum, m/z (I , %): 160 ([M] , 17), 125 (29),
3
+
rel
117 (25), 115 (76), 97 (100), 89 (18), 87 (55), 52 (10), 51 (62), 50 (11).
Ethyl-(2E,4Z)-deca-2,4-dienoate (1). A solution of 2 (0.1 g, 0.62 mmol) and Fe(acac) (7 mg, 0.02 mmol) in THF
3
(1 mL) and NMP (0.64 mL) under Ar at 0°C was treated slowly and dropwise with a solution of n-pentylmagnesiumbromide
(0.7 mL, 1 M) in THF, stirred for 0.5 h at room temperature, and treated with HCl solution (10%, 10 mL) and EtOAc (8 mL).
The organic layer was separated. The aqueous layer was extracted with hexane (3 ꢁ 3 mL). The combined organic phases
were washed with saturated NaHCO solution, dried over MgSO , and concentrated. The product was purified by column
3
4
1
chromatography (SiO , hexane–EtOAc, 9:1). Yield 0.094 g (77%), oily compound. Í NMR spectrum (500 MHz, CDCl , ꢀ,
2
3
ppm, J/Hz): 0.89 (3Í, t, J = 7, Í-10), 1.27–1.34 (7Í, m, Í-2ꢄ, 2ÑÍ ), 1.39–1.45 (2Í, m, Í-7), 2.30 (2Í, q, J = 7.6, Í-6), 4.21
2
13
(2Í, q, J = 7, Í-1ꢄ), 5.82–5.88 (2Í, m, Í-2, 5), 6.12 (1Í, t, J = 11.6, Í-4), 7.61 (1Í, dd, J = 15.2, 11.6, Í-3). C NMR
spectrum (125 MHz, CDCl , ꢀ, ppm): 13.93 (Ñ-10), 14.25 (Ñ-2ꢄ), 22.44 (Ñ-9), 28.18 (Ñ-6), 29.00 (Ñ-7), 31.33 (Ñ-8), 60.20
3
+
(Ñ-1ꢄ), 121.11 (Ñ-2), 126.37 (Ñ-4), 139.47 (Ñ-3), 141.61 (Ñ-5), 167.31 (Ñ-1). Mass spectrum, m/z (I , %): 196 ([M] , 21), 125
rel
(67), 98 (50), 97 (75), 81 (100), 79 (38), 67 (88), 66 (31), 55 (41), 53 (29), 41 (53).
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