An efficient synthesis of (±) solenopsin A

Article abstract of DOI:10.1515/hc-2011-0129

The efficient total synthesis of ( ± ) solenopsin A ( 9 ) was achieved in a series of eight steps starting from readily available N -Bn-N -Boc alanine derivative 1. Copyright by Walter de Gruyter.

Full text of DOI:10.1515/hc-2011-0129

Heterocycl. Commun., Vol. 18(2), pp. 61–65, 2012 • Copyright © by Walter de Gruyter • Berlin • Boston. DOI 10.1515/hc-2011-0129
An efficient synthesis of ( ) solenopsin A
Enzo B. Arévalo-García1,2
allyl adducts of N-protected amino aldehydes. Our synthe-
sis starts from an alanine adduct 1; multigram quantities of
this adduct are obtainable from alanine as described in the
experimental part. Compound 1 was subjected to hydrobo-
ration (BH3·THF) and a subsequent reaction with NaOH/
H2O2 affording alcohol 2 with good regioselectivity (>7:1).
1 EARTH University, 4442-1000, San Jose, Costa Rica
2 Department of Chemistry, C.W. Post. L.I.U. Long Island,
NY 11548, USA
e-mail: barevalo@excite.com
Treatment of 2 with MeSO2Cl/Et3N furnished mesylate 3
that was used in the next step without further purification.
Abstract
Catalytic hydrogenation (H2, 10% Pd/C, EtOH, RT) of the
benzyl group in 3 yielded the cyclic product 4. Employing
Beak-Wilkinson’s methodology (Wilkinson et al., 2000), the
side chain (at C-6) of 4 was introduced as follows. The treat-
ment of 4 with sec-BuLi/TMEDA at -30°C and reaction of
the carbanion formed with DMF (-78°C) afforded formylated
product 5 in 93:7 diastereoselectivity with 83% yield. Under
Wittig conditions aldehyde 5 was then allowed to react with
the ylide generated in situ from decyltriphenylphosphonium
bromide/n-BuLi/THF at -78°C to yield compound 6. In the
next step, a catalytic hydrogenation of product 6 afforded 7.
Then the silyl group in 7 (at the C-3 position) was cleaved
by the use of Bu4NF/THF affording 8 that was subjected to
selective reduction using NaBH3CN, followed by treatment
with TFA, to provide the final product 9 in 88% yield. The
physical and spectroscopic data of the synthesized compound
9 were in good agreement with those described in the litera-
ture (Leclerq et al., 1994; Chackalamannil and Wang, 1997;
Girard et al., 2004, 2005).
The efficient total synthesis of ( ) solenopsin A (9) was
achieved in a series of eight steps starting from readily avail-
able N-Bn-N-Boc alanine derivative 1.
Keywords: alanine; allyl; piperidine; solenopsin.
Introduction
The piperidine ring is a structural feature present in many
natural products of biological interest, as well as drugs and
drug candidates (Foder and Colasanti, 1985; Strunz and
Findlay, 1985; Wang and Wuonola, 1992; Schneider, 1996;
Laschat and Dickner, 2000; Weintraub et al., 2003). In the
past decade, there has been a growing interest in the synthesis
of compounds containing that ring in their structure due to
their biological activity, as well as for the increased impor-
tance of these heterocyclic compounds for the pharmaceutical
industry. Alkaloids bearing that ring are found abundantly in
nature; one of these alkaloids is solenopsin A (9 in Scheme
1). This substance, a constituent of a mixture secreted as
venom by fire ants from the Solenopsis species (Jones et al.,
1982; Leclercq et al., 1996) also exhibits cytotoxic, hemo-
lytic, necrotic, antibacterial, insecticidal, antifungal and anti-
biotical activities (Foder and Colasanti, 1985; Howell et al.,
2005). Although many elegant methods for its synthesis have
been published, the majority of these syntheses present long
and troublesome pathways (Fuji et al., 1979; Oppolzer, 1994;
Poerwono et al., 1998; Kumareswaran and Hassner, 2001;
Takahata et al., 2002; Amat et al., 2003; Dobbs and Guesné,
2005; Girard et al., 2005; Bandara Herath and Dhammika
Nanayakkara, 2008). Owing to the biological importance of
this compound as well as its structural characteristics, our goal
was to find a new method that could use available amino acid
derivatives and smooth conditions for the synthesis of 9.
Conclusions
An efficient, mild synthesis of ( ) solenopsinA(9) was devel-
oped. By the use of a series of well-known reactions it was
demonstrated that ( ) solenopsin A can be readily accessed.
The synthetic strategy presented in this article could be used
for the synthesis of other similar alkaloids.
Experimental section
All reagents were obtained from Aldrich, Fluka or Acros and were
used without further purification Solvents were dried using common
laboratory methods (Armarego and Perrin, 1996). Evaporation of
solvents was performed in a rotary evaporator under reduced pres-
sure. Analytical thin-layer chromatography (TLC) was performed
on precoated Merck silica gel 60 F254 TLC plates. Purification was
performed by flash column chromatography (Still et al., 1978) on
silica gel (Kieselgel-60, Merck, 200–400 mesh). NMR spectra were
recorded in CDCl3 with a Varian Gemini spectrometer at 200 MHz
(1H NMR) and 50 MHz (13C NMR). IR spectra were obtained on
a Perkin-Elmer 1640 FTIR spectrophotometer. Yields refer to chro-
matographically and spectroscopically pure compounds, unless
otherwise stated.
Results and discussion
Here, we report the application of a novel methodology for
the synthesis of ( ) solenopsin A (9), based on the use of
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62 E.B. Arévalo-García
Boc
N
Bn
Boc
Bn
N
BH3,THF then
MsCl,Et3N
CH2Cl2
H2O2,NaOH, 72%
OH
OTBS
Bn
2
OTBS
1
OTBS
Boc
N
H2/Pd-C
89%
1) s-BuLi, TMEDA
2) DMF, 83%
N
OMs
4
Boc
3
OTBS
P+Ph3Br-
OTBS
OTBS
OTBS
n-C9H19
H2/Pd-C
100%
n-BuLi, 70%
N
N
N
Boc
C10H21 Boc
Boc
5
6
7
O
C9H19
OH
1) NaBH3CN,AcOH
2) TFA, 88%
Bu4NF/THF
N
N
H
8
Boc
C10H21
C10H21
9
Scheme 1 Synthesis of ( ) solenopsin A (9).
General procedures
then increased to room temperature and the mixture was
stirred until the phases were completely separated. After sepa-
ration, the organic layer was washed with brine (5 mL), dried
(MgSO4) and concentrated yielding the desired N-Bn-N-Boc
alanine aldehyde. To a stirred suspension of this amino alde-
hyde (1 mmol, 0.26 g), zinc powder (2 mmol, 0.13 g), and
saturated aqueous solution of ammonium chloride (0.5 mL)
in THF (10 mL) was added allyl bromide (4.2 mmol, 0.36
mL). After stirring at room temperature for several hours,
until the substrate disappeared (by TLC), the reaction mixture
was extracted with Et2O (2×10 mL), the combined extracts
were dried (MgSO4), and concentrated in vacuo. The final
allylamino product is obtained as a mixture of syn (major)
and anti (minor) adducts that could be separated by column
chromatography after protection of the resulting hydroxyl
moiety with the TBS group, as follows. To a mixture of crude
adducts (from previous part, 1 mmol, 0.42 g) in DMF (4 mL)
at ambient temperature was sequentially added imidazole (4
mmol, 0.27 g) and TBSCl (1.5 mmol, 0.28 mL) in CH2Cl2
(5 mL). The mixture was stirred for 2 h. Saturated aque-
ous NH4Cl (30 mL) was added and the aqueous layer of the
mixture was extracted with ether (2×100 mL). The organic
layer was dried (MgSO4) and concentrated under reduced
pressure. The product was purified by flash column chroma-
tography (EtOAc/hexanes, 1:9) to afford 1 (0.36 g, 85%) as
Compound 1 A solution of alanine methyl ester hydrochlo-
ride (1 mmol, 0.14 g) and triethylamine (1 mmol, 0.14 mL)
in methanol (1 mL) at 0°C was treated with benzaldehyde
(1 mmol, 0.1 mL). The reaction mixture was stirred at room
temperature for 1.5 h and then cooled to 0°C and treated with
sodium borohydride (2 mmol, 0.076 g) portionwise. After
stirring at 0°C for 2 h the solution was partitioned between
4 m hydrochloric acid (2 mL) and Et2O (5 mL). The organic
layer was extracted with 4 m hydrochloric acid (2×1 mL).
The combined aqueous layers were extracted with Et2O (2×1
mL) and the ethereal phases were discarded. The aqueous
phase was neutralized with solid NaHCO3 and extracted with
Et2O (3×2 mL). The organic layer was dried (MgSO4) and
concentrated under reduced pressure producing the desired
N-benzyl alanine methyl ester (1.1 mmol, 0.21 g). A solu-
tion of this product in dry Et2O (3 mL) was treated with
di-tert-butyl dicarbonate (1 mmol, 0.23 mL). The mixture
was stirred overnight at room temperature, then washed with
0.1 m hydrochloric acid (2×3 mL) and with saturated aqueous
NaHCO3 (3 mL). Standard workup of the ethereal phase gave
the desired N-Bn-N-Boc derivative. This product (1 mmol,
0.29 g) was dissolved in anhydrous ether (6 mL) under argon
and the solution was cooled to -78°C, stirred, and treated
dropwise with a cold solution of DIBAL-H (1.5 m in tolu-
ene, 1.3 mL, 2 mmol). Stirring was continued at -78°C for
1 h. Then methanol (2 mL) and aqueous solution of sodium-
potassium tartrate (5 mL) were added. The temperature was
1
a pale green oil. H NMR: δ 7.4–7.15 (m, 5H), 5.75 (dd t,
J = 15.8 Hz, 10.1 Hz, 6.6 Hz, 1H), 4.9 (m, 2H), 4.25 (m, 2H),
3.81 (m, 1H), 3.54 (m, 1H), 2.38 (m, 2H), 1.32 (s, 9H), 1.26
(d, J = 7.0 Hz, 3H), 0.85 (s, 9 H), 0.07 (bs, 6H); 13C NMR:
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Synthesis of ( ) solenopsin A 63
δ 156.7, 141.0, 137.0, 128.2, 128.0, 127.8(2C), 126.7, 115.4,
74.2, 71, 54.7, 51.6, 37.4, 28.5(3C). 20.6(3C), 16.1, 13, -5.8,
-5.1; IR: ν 3080, 2850, 1750, 1445, 1300, 1140, 905 cm-1.
Anal. Calcd for C24H43NO3Si: C, 68.70; H, 11.45; N, 3.35.
Found: C, 68.80; H, 11.52; N, 3.43.
Calcd for C17H35NO3Si: C, 61.96; H, 10.70; N, 4.25. Found:
C, 61.89; H, 10.81; N, 4.15.
Compound 5 A solution of 4 (1 mmol, 0.33 g) in dry ether
(10 mL) was cooled to -78°C and treated with TMEDA (1.5
mmol, 0.22 mL) and s-BuLi (1.3 m in heptane, 0.9 mL, 1.2
mmol) The mixture was warmed to -25°C, stirred at that tem-
perature for 30 min, and then recooled to -78°C and treated
dropwise with DMF (1.9 mmol, 0.15 mL) in dry ether (1 mL).
The mixture was stirred for 15 min at -78°C and then quenched
with saturated aqueous NH4Cl (5 mL). The organic layer was
separated. The aqueous layer was extracted with ether (3×5
mL), and the combined organic phases were washed with
brine (5 mL), dried over anhydrous Na2SO4, filtered, and
concentrated under reduced pressure. Flash chromatographic
purification (EtOAc/hexanes, 1:10) provided 5 (0.30 g, 83%)
Compound 2 A solution of compound 1 (1 mmol, 0.42 g)
in THF (5 mL) was treated with BH3·THF (2.5 mL of 1 m
in THF, 2.5 mmol) and the mixture was stirred at room tem-
perature overnight. Aqueous NaOH (3 m, 3 mL) was added
to the mixture followed by H2O2 (30%, 3 mL). Stirring was
continued for another 1 h before the addition of EtOAc
(15 mL). The layers were separated and the aqueous layer
was extracted with EtOAc (2×10 mL). The organic layer was
dried (MgSO4) and concentrated under reduced pressure.
The product was purified by flash column chromatography
(EtOAc/hexanes, 1:7) to afford compound 2 (0.32 g, 72%)
1
as a pale yellow oil. H NMR: δ 9.6 (s, 1H), 4.15 (m, 1 H),
1
as a pale yellow oil. H NMR: δ 7.3–7.1 (m, 5 H), 4.3–4.2
3.46 (m, 1 H), 2.87 (m, 1H), 1.81 (m, 2 H), 1.66 (m, 1 H), 1.51
(m, 1 H), 1.43 (s, 9 H), 1.22 (d, J = 7.1 Hz, 3 H), 0.9 (s, 9 H),
0.08 (s, 3 H), 0.06 (s, 3 H); 13C NMR: δ 196.3, 155.9, 80.4,
72.1, 67.8, 45.4, 30.2, 28.3, 26(3C), 16.6, 10, -5.3(2C); IR:
ν 2890, 2800, 1720, 1695, 1481, 1355, 1250, 1150, 890 cm-1.
Anal. Calcd for C18H35NO4Si: C, 60.50; H, 9.87; N, 3.92.
Found: C, 60.55; H, 9.79; N, 3.98.
(m, 2 H), 3.91 (m, 2 H), 3.7 (m, 1 H), 3.48 (br s, 1 H), 2.4
(m, 2H), 1.98 (br s, 1 H), 1.7 (m, 2 H), 1.4 (s, 9 H), 1.20 (d,
J = 7.1 Hz, 3 H), 0.82 (s, 9 H), 0.09 (brs, 6 H); 13C NMR:
δ 156.3, 134.9, 128.7, 128.6, 128.0, 127.9, 73.5, 68.8, 60.1,
58.1, 51.8, 28.6, 28.5, 26.5, 25.8, 18.4, 14.8, -5.5, -5.8; IR: ν
3520, 2800, 1755, 1480, 1320, 1248, 1142, 855 cm-1 . Anal.
Calcd for C24H43NO4Si: C, 65.85; H, 9.90; N, 3.21. Found:
C, 65.96; H, 9.79; N, 3.17.
Compound 6 To a cooled (0°C) solution of n-decyltriph-
enylphosphonium bromide (1.5 mmol, 0,73 g) in dry THF (3
mL) was added dropwise n-BuLi (2.5 m, 0.62 mL, 1.55 mmol)
under N2 atmosphere. After being stirred at room temperature
for 10 min, the mixture was cooled to -78°C and stirred for 15
min. To this mixture was added aldehyde 5 (1 mmol, 036 g) in
THF (5 mL). The solution was stirred for 1.5 h at -78°C and
warmed to room temperature. The reaction was partitioned
between water (5 mL) and CH2Cl2 (8 mL). The aqueous layer
was extracted with CH2Cl2 (3×5 mL), and the combined
organic phases were washed with brine (5 mL), dried over
anhydrous Na2SO4, filtered, and concentrated under reduced
pressure. Flash chromatographic purification (5:95, EtOAc/
hexanes) afforded 4 (0.34 g, 70%) as a colorless oil. 1H NMR:
δ 5.35–5.05 (m, 2H), 4.52 (m, 1 H), 3.50 (m, 1 H), 2.70 (qd,
J1 = 7.2, J2 = 7.0 Hz, 1 H), 1.91 (m, 2 H), 1.81–1.65 (m, 4
H),1.56 (s, 9 H), 1.48 (d, J = 7.2 Hz, 3 H), 1.35 (m, 2H), 1.28
(s, 12 H), 0.9 (s, 9 H), 0.7 (t, J = 6.9 Hz, 3H), 0.06 (s, 3 H),
0.04 (s, 3 H); 13C NMR: δ 155.5, 142, 135.3, 79.1, 48.8, 46.3,
33.1, 30.1(7C), 28.7(3C), 25.2, 23(3C), 20, 17.6, 14.2, 10.4,
-5.4(2C); IR: ν 3030, 2900, 1710, 1487, 1350, 1250, 1155,
910 cm-1. Anal. Calcd for C28H55NO3Si: C, 69.80; H, 11.51;
N, 2.91. Found: C, 69.91; H, 11.50; N, 2.79.
Compound 7 To a suspension of Pd/C (50 mg, 10% Pd) in
ethanol (10 mL) was added 6 (1 mmol, 0.48 g). The mixture
was stirred at room temperature under an atmospheric pres-
sure of H2 for 12 h (until complete by TLC). The mixture was
filtered through Celite. After concentration under reduced
pressure, the residue was chromatographed on a silica gel
column (EtOAc/hexanes, 5:95) to yield 7 (0.454 g, 94%) as
a colorless oil. 1H NMR: δ 4.09 (qd, J1 = 7.2, J2 = 7.0 Hz, 1
H), 3.50 (m, 1 H), 2.60 (m, 1 H), 1.68 (m, 1 H), 1.39 (m, 1
H), 1.4 (s, 9 H), 1.28 (s, 20 H), 1.25 (d, J = 7.2 Hz, 3 H), 0.91
(m, 3 H), 0.8 (s, 9 H), 0.05 (s, 3 H), 0.03 (s, 3 H); 13C NMR: δ
156.8, 76.5, 70.1, 52.3, 48.2, 33.6, 29.5(2C), 28.9, 28.6(5C),
Compound 3 A solution of alcohol 2 (1 mmol, 0.4373 g)
in CH2Cl2 (10 mL) was treated at 0°C with Et3N (1.5 mmol,
0.21 mL) and MeSO2Cl (1.3 mmol, 0.10 mL). The mixture
was stirred for 10 min at 0°C and then warmed to room tem-
perature and stirred for an additional 6 h. After completion of
the reaction as monitored by TLC, it was quenched by addi-
tion of saturated NH4Cl (6 mL) and H2O (3 mL). The aque-
ous layer was extracted with CH2Cl2 (3×10 mL), washed
with brine, and dried over anhydrous Na2SO4. The solvent
was then evaporated under reduced pressure. The residue
was purified by flash column chromatography (EtOAc/
hexanes, 1:10) to afford 3 (0.47 g, 91%) as a pale green oil.
1H NMR: δ 7.3–7.2 (m, 5 H); 4.2 (s, 2 H), 3.85 (bs, 1 H),
3.73 (m, 1 H), 3.5 (m, 2 H), 1.51 (m, 4 H), 1.43 (s, 9 H),
1.20 (d, J = 7.1 Hz, 3 H), 0.9 (s, 9 H), 0.07 (s, 3 H), 0.05
(s, 3 H); 13C NMR: δ 154.1, 136, 128.3, 127.9, 127.1, 81.2,
80, 71.5, 60.3, 38.1, 28.1(3C), 26.8(3C), 18.6, -5.4(2C);
IR: ν 2830, 1754, 1480, 1330, 1290, 1130, 850 cm-1. Anal.
Calcd for C25H45NO6SSi: C, 58.20; H, 8.90; N, 2.70. Found:
C, 58.10; H, 8.81; N, 2.83.
Compound 4 A suspension of the mesylate 3 (1 mmol,
0.52 g) and Pd/C (50 mg, 10% Pd) in ethanol (10 mL) was
stirred overnight (until complete by TLC) at room tempera-
ture under an atmospheric pressure of H2. The mixture was
then filtered through Celite, and the solvent was removed
under reduced pressure. Flash chromatographic purification
on silica gel (EtOAc/hexanes, 1:9) provided 4 (0.31 g, 95%)
1
as a colorless oil. H NMR: δ 4.32 (m, 1H), 3.8 (m, 1H),
3.14 (m, 1H), 2.62 (ddd, J = 13.1 Hz, 13.0 Hz, 2.1 Hz), 1.71
(m, 2H),1.58 (m, 2H), 1.38 (s, 9H), 1.35 (d, J = 7 Hz, 3 H), 0.9
(s, 9 H), 0.04 (s, 3 H), 0.02 (s, 3 H); 13C NMR: δ 158.1, 80,
72.1, 50.5, 43.3, 31.2, 27.5(3C), 25(3C), 19.3, 10.8, -5.6, -5.1;
IR: ν 2910, 1695, 1474, 1360, 1248, 1145, 900 cm-1. Anal.
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64 E.B. Arévalo-García
quinolizidine alkaloids from a phenylglycinol-derived δ-lactam.
J. Org. Chem. 2003, 68, 1919–1928.
26.3, 25.9(2C), 23, 20.1, 19.6, 18.2, 14.8, 13.5, -5.0, -4.8;
IR: ν 2890, 1730, 1490, 1355, 1250, 1155, 915 cm-1. Anal.
Calcd for C28H57NO3Si: C, 69.50; H, 11.87; N, 2.89. Found:
C, 69.55; H, 11.93; N, 2.79.
Armarego, W. L. F.; Perrin, D. D. Purification of Laboratory
Chemicals, 4th Edition; Butterworth Heinmann: Oxford, 1996.
Bandara Herath, H. M. T.; Dhammika Nanayakkara, N. P. Synthesis
of enantiomerically pure fire ant venom alkaloids: solenopsins
and isosolenopsins A, B and C. J. Heterocycl. Chem. 2008, 45,
129–136.
Chackalamannil, S.; Wang, Y. An enantioselective route to trans-
2,6-disubstituted piperidines. Tetrahedron 1997, 53, 11203–
11210.
Dobbs, A. P.; Guesné, S. J. J. Rapid access to trans-2,6-disubstituted
piperidines: expedient total synthesis of (–)-solenopsin A and
(+)-epi-dihydropinidine. Synlett 2005, 13, 2101–2104.
Foder, G. B.; Colasanti, B. The pyridine and piperidine alkaloids:
chemistry and pharmacology. In Alkaloids: Chemical and
Biological Perspectives; Pelletier, S. W., Ed.; Wiley: New York,
1985, Vol. 3, pp. 1.
Fuji, K.; Ichikawa, K.; Fujita, E. Aversatile synthesis of ( )-solenop-
sin A. Chem. Pharm. Bull. 1979, 27, 3183–3185.
Girard, N.; Gautier, C.; Malassene, R.; Hurvois, J.-P.; Moinet, C.;
Touper, L. Dearomatization of N-phenyl-2,6-dialkylpiperidines:
practical synthesis of ( )-solenopsin A and ( )-dihydropinidine.
Synlett 2004, 11, 2005–2009.
Girard, N.; Hurvois, J.-P.; Toupet, L.; Moinet, C. Anodic cyana-
tion of (–)-N-phenyl-2-methylpiperidine: a short synthesis of
(+)-solenopsin A and (+)-isosolenpsin A. Synth. Comm. 2005,
35, 711–723.
Howell, G.; Butler, J.; Deshazo, R. D.; Farley, J. M.; Liu, H. L.;
Nanayakkara, N. P.; Yates, A.; Yi G. B.; Rockhold, R. W.
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Compound 8 To a solution of 7 (1 mmol, 0.48 g) in dry
THF (20 mL) was added TBAF (1 m in THF, 20 mL, 20 mmol)
at room temperature. The solution was stirred overnight, and
then an aqueous NH4Cl solution (10 mL) and water (15 mL)
were added successively. The mixture was extracted with
CH2Cl2 (3×20 mL), and the combined organic layers were
washed with brine (15 mL), dried over anhydrous Na2SO4,
filtered, and concentrated under reduced pressure. The residue
was chromatographed (EtOAc/hexanes, 1:4) to yield 8 (0.34g,
91%) as a colorless oil. 1H NMR: δ 3.65 (m, 1H), 3.0 (m, 2H),
2.44 (m, 1H), 1.85 (m, 2H), 1.75 (m, 2H), 1.55 (m, 2H), 1.46
(s, 9H), 1.33 (d, J = 7.1 Hz, 3H), 1.28 (m, 18 H), 0.85 (t, J = 6.9
Hz, 3H); 13C NMR: δ 159.1, 71.2, 73, 55.4, 49.1, 34.4, 32(6C),
30.6, 27.1(3C), 23, 20.4, 18.2, 11.3; IR: ν 3405, 2900, 1720,
1490, 1355, 905 cm-1. Anal. Calcd for C22H43NO3: C, 71.5; H,
11.75; N, 3.78. Found: C, 70.9; H, 11.56; N, 3.83.
Compound 9 (solenopsin A) Compound 8 (1 mmol, 0.37
g) was suspended in acetic acid (25 mL), then NaBH3CN (15
mmol, 0.94 g) was carefully added to this suspension. Stirring
was continued until TLC showed the consumption of all start-
ing material (16 h at room temperature). Then the acetic acid
was evaporated and the residue was dissolved in CH2Cl2 (20
mL) and washed with saturated aqueous NaHCO3 (15 mL),
water (15 mL), and brine (15 mL), and dried over anhydrous
Na2SO4, filtered and concentrated under reduced pressure.
The crude N-Boc protected derivative thus obtained was dis-
solved in CH2Cl2 (10 mL) and the solution was treated slowly
at 0°C with TFA (10 mL). The mixture was stirred for 1 h
and then concentrated under reduced pressure. After addition
of dichloromethane (30 mL) and saturated aqueous Na2CO3
solution (20 mL), the mixture was extracted with ethyl acetate
(3×20 mL). The combined organic layers were concentrated
in vacuo to afford crude compound 9 (0.22 g, 88% in two
steps), that gave satisfactory spectroscopic data. Product 9
was obtained as a colorless oil. 1H NMR: δ 0.86 (t, J = 6.4 Hz,
3 H), 1.10 (d, J = 6.7 Hz, 3 H), 11.19 (br s, 18 H), 1.28–1.64
(m, 9H), 2.73–2.80 (m, 1 H), 2.91–3.06 (m, 1 H); 13C NMR: δ
56.5, 52, 37.5, 35.1, 34.3, 29.3(7C), 24.6, 22, 21.7, 20.5, 13.8;
IR: ν 2930, 2840, 1459, 1380, 1140, 1061 cm-1. The spectral
data for this compound matched that reported in the literature
(Girard et al., 2005). Anal. Calcd for C17H35N: C, 80.55; H,
13.90; N, 5.53. Found: C, 80.50; H, 13.96; N, 5.61.
Jones, T. H.; Blum, M. S.; Fales, H. Ant venom alkaloids from
Solenopsis and Monorium species: recent developments.
Tetrahedron 1982, 38, 1949–1958.
Kumareswaran, R.; Hassner, A. Asymmetric synthesis of
N-acetyl-(R)-coniine and N-Boc-(2R,6R)-solenopsin
A via
ring-closingmetathesis. Tetrahedron:Asymmetry2001, 12, 2269–
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Acknowledgments
The author is grateful to EARTH University, C.W. Post Long Island
and Wright State University Chemistry Departments for partial
support.
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Received December 15, 2011; accepted March 15, 2012
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