Ethyl-Branched Aldehydes and Ketones from Caimans
Journal of Natural Products, 2006, Vol. 69, No. 6 869
7.5 Hz, H-7); 13C NMR (CDCl3, 100 MHz) δ 211.3 (C, C-2), 55.2
(CH, C-3), 28.9 (CH3, C-1), 27.4 (CH2), 24.7 (CH2), 21.2 (CH2), 20.9
(CH2), 13.6 (CH3, C-5a), 11.9 (CH3, C-7); EIMS m/z (%) 142 [M]+
(4), 151 (1), 127 (1), 113 (4), 99 (11), 86 (100), 85 (22), 71 (47), 69
(9), 57 (29), 55 (13), 43 (62), 41 (26); HREIMS m/z 142.1349 (calcd
for C9H18O, 142.1358).
29.56 (CH2), 29.4 (CH2), 29.3 (CH2), 28.5 (CH2), 27.1 (CH2), 22.7
(CH2), 21.9 (CH2), 14.1 (CH3), 11.4 (CH3); HREIMS m/z of the
respective 2,4-dinitrophenylhydrazone 392.2420 (calcd for C20H32N4O4,
392.2418).
General Procedure for the Synthesis of Diketones. The â-keto
ester (1 equiv) was dissolved in a 4:1 mixture of Et2O and EtOH and
added to a previously prepared solution of magnesium ethanolate (1
equiv). Then the respective acid chloride (1 equiv) was added carefully,
and the reaction mixture was stirred for 16 h. The reaction was quenched
with ice and diluted H2SO4, and the phases were separated. The aqueous
layer was extracted with Et2O three times, and the combined organic
phases were washed with water. After drying (MgSO4) and removal
of the solvent, the crude product was used in the Krapcho decarb-
ethoxylation.19 The crude product was dissolved in a suspension of
aqueous DMSO and sodium chloride. The reaction mixture was heated
to reflux for 12 h. After cooling to room temperature the mixture was
diluted with water and extracted twice with EtO2. The organic layer
was washed with brine and dried over MgSO4. The solvent was
evaporated under reduced pressure, and the crude product was purified
by flash column chromatography on silica.
5-Ethylnonane-2,4-dione (33). This compound was obtained from
ethyl acetoacetate (1.3 g, 10 mmol) and 2-ethylhexanoyl chloride (1.62
g, 10 mmol) as a brownish liquid (1.14 g, yield 62%): IR νmax 2984,
2942, 2882, 1714, 1609, 1459, 1352 cm-1; 1H NMR (CDCl3, 400 MHz)
δ 15.5 (br s, OH), 5.48 (s, H-3), 3.58 (s, H-3), 2.36 (tt, J ) 8.1 Hz, 5.6
Hz, H-5), 2.24 (tt, J ) 5.8 Hz, 8.4 Hz, H-5), 2.11 (3H, s, H-1), 1.19-
1.65 (8H, m, H-6, H-6a, H-7, H-8), 0.84-0.91 (6H, m, H-7a, C-9);
13C NMR (CDCl3, 100 MHz) δ 213.1 (C, C-4), 196.7 (C, C-4), 192.2
(C, C-2), 176.5 (C, C-2), 99.9 (CH, C-3), 59.7 (CH2, C-3), 49.8 (CH,
C-5), 47.1 (CH, C-5), 28.5 (CH3, C-1), 25.1 (CH3, C-1), 25.4 (CH2),
24.2 (CH2), 23.2 (CH2), 22.1 (CH2), 13.8 (CH3), 13.7 (CH3), 11.7 (CH3),
11.6 (CH3); EIMS m/z 184 [M]+ (3), 169 (1), 155 (1), 141 (3), 128
(29), 114 (7), 113 (8), 100 (10), 86 (5), 85 (100), 71 (6), 70 (5), 57
(15), 55 (9), 43 (39), 41 (16); HREIMS m/z 184.1449 (calcd for
C11H20O2, 184.1464).
7-Ethylundecane-4,6-dione (38). This compound was obtained from
ethyl 3-oxohexanoate (1.58 g, 10 mmol) and 2-ethylhexanoyl chloride
(1.62 g, 10 mmol) as a light brown liquid (0.32 g, yield 15%): 1H
NMR (CDCl3, 400 MHz) δ 5.46 (s, H-5), 3.55 (s, H-5), 2.27 (2H, t, J
) 7.3 Hz, H-3), 2.03-2.09 (1H, m, H-7), 1.68-2.00 (10H, m, H-2,
H-8, H-8a, H-9, H-10), 0.96 (3H, t, J ) 7.4 Hz, H-9a), 0.85-0.92
(6H, m, H-1, H-11); 13C NMR (CDCl3, 100 MHz) δ 197.1 (C, C-4),
194.8 (C, C-6), 99.5 (CH2, C-5), 50.2 (CH, C-7), 40.5 (CH2, C-3), 32.2
(CH2, C-9), 29.7 (CH2, C-8), 25.9 (CH2, C-10), 22.8 (CH2, C-8a), 19.2
(CH2, C-2), 13.9 (CH3), 13.7 (CH3), 11.9 (CH3, C-9a); EIMS m/z 212
[M]+ (3), 169 (11), 156 (24), 142 (6), 128 (6), 113 (100), 97 (9), 71
(31), 57 (24), 43 (29); HREIMS m/z 212.1771 (calcd for C13H24O2,
212.1776).
Preparation of 5-Ethylnon-2-en-4-one (20). 20 was prepared from
9 (0.170 g, 1 mmol) by oxidation with iodosobenzoic acid according
to the method of Nicolaou et al.7 Compound 20 was obtained as a
colorless oil (0.063 g, yield 38%): IR νmax 3037, 2949, 2937, 2881,
1
1691, 1634, 1457, 1291 cm-1; H NMR (CDCl3, 400 MHz) δ 6.89
(1H, dq, J ) 15.6 Hz, 6.8 Hz, H-3), 6.21 (1H, dq, J ) 15.6 Hz, 1.6
Hz, H-2), 2.58 (1H, tt, J ) 5.5 Hz, 8.2 Hz, H-5), 1.90 (3H, dd, J ) 1.6
Hz, 6.8 Hz, H-1), 1.15-1.66 (8H, m, H-6, H-6a, H-7, H-8), 0.87 (3H,
t, J ) 7.1 Hz, H-7a), 0.84 (3H, t, J ) 7.3 Hz, H-9); 13C NMR (CDCl3,
100 MHz) δ 204.0 (C, C-4), 142.0 (CH, C-3), 131.1 (CH, C-2), 51.1
(CH, C-5), 31.1 (CH2), 29.5 (CH2), 24.7 (CH2, C-6a), 22.6 (CH2, C-8),
18.1 (CH3, C-1), 13.7 (CH3), 11.7 (CH3); EIMS m/z 168 [M]+, 153
(2), 139 (1), 125 (3), 113 (3), 112 (30), 111 (3), 98 (3), 97 (31), 70
(6), 69 (100), 57 (12), 55 (7), 43 (7), 41 (28), 39 (12); HREIMS m/z
168.1479 (calcd for C11H20O, 168.1515).
Preparation of 5-Ethylundec-2-en-4-one (22). 22 was prepared
from 10 (0.198 g, 1 mmol) by oxidation with iodosobenzoic acid
according to the method of Nicolaou et al.7 Compound 22 could only
be obtained as an unseparable mixture with the starting material 10
(0.158 g, yield 81%): 1H NMR (CDCl3, 400 MHz) δ 6.92 (1H, dq, J
) 15.2 Hz, 6.6 Hz, H-3), 6.24 (1H, m, J ) 15.2 Hz, H-2); 13C NMR
(CDCl3, 100 MHz) δ 206.4 (C, C-4), 144.1 (CH, C-3), 133.2 (CH,
C-2); EIMS m/z 196 [M]+ (2), 181 (3), 167 (2), 153 (2), 181 (2), 112
(27), 97 (18), 69 (100), 55 (14), 41 (55); HREIMS m/z 196.1842 (calcd
for C13H24O, 196.1827).
(E)-7-Ethylundec-4-en-6-one (27). Dry aluminum chloride (2.67
g, 20 mmol) was added to a solution of 2-ethylhexanoyl chloride (3.25
g, 20 mmol) in dry CH2Cl2 (17 mL) in portions at 0 °C and stirred
until all solid was dissolved. Then 1-pentene (2.81 g, 40 mmol) was
added dropwise at the same temperature.15 After stirring at room
temperature for 24 h, the mixture was poured onto an ice-diethyl ether
mixture, the ether layer was separated, and the aqueous layer was
repeatedly extracted with ether. The combined ether extracts were
washed with 15% potassium carbonate solution and with water and
dried with MgSO4. The solvent was removed and the residue was
purified by flash chromatography (SiO2, 2.5% diethyl ether in pentane).
Pure 27 was isolated as a colorless oil (0.43 g, yield 11%): 1H NMR
(CDCl3, 400 MHz) δ 6.86 (1H, dt, J ) 15.7, 7.0 Hz, H-4), 6.18 (1H,
dt, J ) 15.7, 1.5 Hz, H-5), 2.60 (1H, m, H-7), 2.20 (2H, m, H-3), 1.46
(10H, m, H-2, H-8, H-9, H-10, H-1′), 0.94 (3H, t, J ) 7.4 Hz, CH3),
0.86 (6H, m, 2 × CH3); 13C NMR (CDCl3, 100 MHz) δ 204.2 (C,
C-6), 146.9 (CH, C-4), 129.9 (CH, C-5), 51.2 (CH, C-7), 34.4 (CH2,
C-3), 31.3 (CH2), 29.7 (CH2), 25.0 (CH2), 22.8 (CH2), 21.4 (CH2), 13.9
(CH3), 13.6 (CH3), 11.8 (CH3); HREIMS m/z 196.1851 (calcd for
C13H24O, 196.1827).
2-Ethyldodecanal (16). Methyl dodecanoate was alkylated with ethyl
iodide using a modified published procedure.16,17 Thus, diisopropyl-
amine (3.04 g, 30 mmol) in dry THF (12 mL) was added dropwise to
a solution of n-butyllithium in hexane (1.6 M, 12.5 mL, 20 mmol).
After stirring for 10 min all solvents and volatile compounds were
evaporated in vacuo and the residue was dissolved in dry THF (20
mL). The resulting 1 M LDA solution was cooled to -78 °C. At this
temperature, methyl dodecanoate (4.29 g, 20 mmol) was added slowly
and the mixture was stirred for 20 min. Then a solution of ethyl iodide
(3.43 g, 22 mmol) in DMPU (0.73 mL) was added. The mixture was
allowed to warm to -40 °C and then quenched with saturated NH4Cl
solution. The mixture was acidified with 2 N HCl and extracted
repeatedly with ether. The combined ether extracts were washed with
saturated NaHCO3 solution and brine, dried with MgSO4, and concen-
trated in vacuo. Thus, methyl 2-ethyldodecanoate (4.61 g, yield 95%)
was obtained as a colorless oil. Reduction with LiAlH4 according to
known procedures furnished 2-ethyldodecan-1-ol (yield 90%). 2-Eth-
yldodecanal was finally obtained by oxidation with PDC in CH2Cl2
(yield 55%).18 This compound is rapidly oxidized to the corresponding
acid in air: 1H NMR (CDCl3, 400 MHz) δ 9.57 (1H, d, J ) 3.0 Hz,
H-1), 2.17 (1H, m, H-2), 1.55 (4H, m, H-3, H-1′), 1.26 (16H, br s,
H-4, H-5, H-6, H-7, H-8, H-9, H-10, H-11), 0.91 (3H, t, J ) 7.5 Hz,
CH3), 0.88 (3H, t, J ) 6.3 Hz, CH3); 13C NMR (CDCl3, 100 MHz) δ
205.7 (CH, C-1), 53.4 (CH, C-2), 31.9 (CH2), 29.7 (CH2), 29.58 (CH2),
Preparation of 3-Ethylnonane-2,4-dione (42). Nonane-2,4-dione
was obtained from ethyl acetoacetate (1.3 g, 10 mmol) and hexanoyl
chloride (1.34 g, 10 mmol) as a light brown liquid (1.14 g, yield
62%): 1H NMR (CDCl3, 400 MHz) δ 15.6 (br s, OH), 5.48 (s, H-3),
3.61 (s, H-3), 2.35 (tt, J ) 8.1 Hz, 5.7 Hz, H-5), 2.26 (tt, J ) 5.9 Hz,
8.3 Hz, H-5), 2.12 (1H, s, H-1), 1.19-1.65 (6H, m, H-6, H-7, H-8),
0.89 (3H, t, H-9); 13C NMR (100 MHz) δ 193.4 (C, C-4), 191.5 (C,
C-2), 99.7 (CH2, C-3), 57.9 (CH2, C-3), 38.2 (CH2, C-5), 31.4 (CH,
C-1), 25.4 (CH2), 25.0 (CH2), 22.4 (CH2, C-8), 13.8 (CH3, C-9); EIMS
m/z 156 [M]+ (5), 141 (8), 114 (11), 113 (23), 100 (52), 86 (4), 85
(100), 71 (6), 70 (5), 57 (11), 55 (13), 43 (64), 41 (21). A solution of
nonane-2,4-dione (0.78 g, 5 mmol) in THF was treated with potassium
carbonate (0.69 g, 5 mmol). After being stirred for 1.5 h at room
temperature, ethyl iodide (1.56 g, 10 mmol) was added. The reaction
mixture was stirred for another 16 h and then quenched with water.
The aqueous layer was extracted three times with EtO2. After washing
the combined ether phases with water and drying over MgSO4, the
solvent was evaporated under reduced pressure. The crude product was
purified by flash column chromatography on silica (0.386 g, yield
1
42%): IR νmax 2967, 2923, 2887, 1717, 1609, 1458 cm-1; H NMR
(400 MHz) δ 3.44 (1H, t, J ) 7.5 Hz, H-3), 2.39 (2H, t, J ) 7.2 Hz,
H-5), 2.23 (3H, s, H-1), 1.19-1.82 (8H, m, H-4a, H-6, H-7, H-8), 0.93
(3H, t, J ) 7.2 Hz, H-5a), 0.89 (3H, t, J ) 7.4 Hz, H-9); 13C NMR
(100 MHz) δ 204.5 (C, C-4), 199.7 (C, C-2), 67.2 (CH, C-3), 38.2
(CH2, C-5), 30.3 (CH3, C-1), 25.4 (CH2), 25.2 (CH2), 22.4 (CH2), 21.3
(CH2), 13.8 (CH3, C-9), 11.9 (CH3, C-5a); 184 [M+] (22), 155 (18),
141 (13), 128 (100), 127 (24), 113 (72), 109 (13), 99 (15), 85 (21), 57