One-pot hydrogenation conditions for a sequential process to (+)-monomorine

Article abstract of DOI:10.1021/jo030083c

(+)-Monomorine has been synthesized under mild hydrogenation conditions initiating deprotection followed by intramolecular, sequential reductive amination reactions. The precursors could be prepared concisely using B-alkyl Suzuki cross coupling of a chiral homoallylamine and a vinyl iodide or an iodofuran derivative.

Full text of DOI:10.1021/jo030083c

SCHEME 1
On e-P ot Hyd r ogen a tion Con d ition s for a
Sequ en tia l P r ocess to (+)-Mon om or in e
Guncheol Kim,* Sung-do J ung, Eun-ju Lee, and
Nakjeong Kim
Department of Chemistry, College of Natural Science,
Chungnam National University, Taejon 305-764, Korea
guncheol@cnu.ac.kr
Received March 5, 2003
Abstr a ct: (+)-Monomorine has been synthesized under
mild hydrogenation conditions initiating deprotection fol-
lowed by intramolecular, sequential reductive amination
reactions. The precursors could be prepared concisely using
B-alkyl Suzuki cross coupling of a chiral homoallylamine and
a vinyl iodide or an iodofuran derivative.
SCHEME 2a
The indolizidine alkaloid monomorine, a trail phero-
mone of the Pharaoh’s ant, is a fused bicyclic tertiary
amine molecule isolated from Monomorium pharaonis L.
by Ritter.1 Many synthetic methods have been developed
for the skeleton with the correct arrangement of chiral
centers adjacent to the nitrogen atom.2 As we have been
interested in an intramolecular reductive amination
approach for the indolizidine skeleton,3 we wanted to
arrange an asymmetric sequential reductive pathway to
(+)-monomorine.
a
Key: (a) CbzCl, NaHCO3, MeOH/H2O, rt, 77%; (b) DIBAL-H,
toluene, -78 °C, 45%; (c) Ph3PdCH2, THF/DMF, HMPA, 0 °C,
67%.
SCHEME 3a
The previous results for the molecule have shown that
in the course of reductive reaction the stereocenter at C5
afforded high selectivity of the two developing C3 and
C9 centers, whereas the center at C3 gave poor selectiv-
ity.2 In Shawe’s racemic synthesis of monomorine, they
used the 1,5-dicarbonyl precursor in which the stereo-
center arranged at C3 should control the other ones in
the reductive amination, and actually the reaction yielded
1:1 diastereomeric mixture.2b Therefore, we considered
that intermediate 2a or 2b would be a proper precursor
in which N-Cbz and 1,4-dicarbonyl groups are arranged,
and hydrogenation conditions should trigger the desired
transformation selectively and consecutively.3 The pre-
cursors were considered to be prepared readily by B-alkyl
Suzuki coupling4 of homoallylamine 3 and the iodide
compound 4 or 5 (Scheme 1).
a
Key: (a) Ac2O, Et3N, DMAP, CH2Cl2, 97%; (b) TMSCl, NaI,
H2O, CH3CN, rt, 69%; (c) NaOMe, MeOH, rt, 81%; (d) PDC,
CH2Cl2, rt, 83%.
benzylamide.5 Protection of the amino ester 6 with CbzCl
(77% yield) was followed by DIBAL-H reduction to afford
aldehyde 7 in 45% yield, and the Wittig reaction of 7
provided 3 in 67% yield (Scheme 2).
The coupling partner, internal alkenyl iodide 4, was
made selectively via a four-step sequence; protection of
1-nonyn-5-ol with Ac2O (97% yield), treatment with HI,
generated in situ,6 affording internal iodoalkenyl acetate
9 as a major isomer in a 10:1 mixture of inseparable
regioisomers (69% yield), and deprotection (81% yield)
followed by PDC oxidation (83% yield) (Scheme 3).
The Suzuki cross coupling of 3 and 4 provided the
methylene compound 10 in 76% yield, and conversion of
10 to the carbonyl precursor 2a was achieved by oxidative
cleavage using OsO4 and Oxone in DMF in 58% yield
(Scheme 4).7 For the desired transformation of 2a , 1 atm
of H2 for 1 h at room temperature was indeed enough to
afford 50% of (+)-monomerine (1) as a main product after
The homoallylamine 3 was prepared from the chiral
â-amino methyl butanoate 6, which was made by the
known procedure using (S)-lithium N-benzyl-R-methy-
(1) Ritter, F. J .; Rotgans, I. E. M.; Talman, E.; Verwiel, P. E. J .;
Stein, F. Experiencia 1973, 29, 530.
(2) (a) J efford, C. W.; Tang, Q.; Zaslona, A. J . Am. Chem. Soc. 1991,
113, 3513. (b) Shawe, T. T.; Sheils, C. J .; Gray, S. M.; Conard, J . L. J .
Org. Chem. 1994, 59, 5841. (c) Munchhof, M. J .; Meyers, A. I. J . Am.
Chem. Soc. 1995, 117, 5399. (d) Berry, M. B.; Craig, D.; J ones, P. S.;
Ronlands, G. J . J . Chem. Soc., Chem. Commun. 1997, 2141. (e) Mori,
M.; Hori, M.; Sato, Y. J . Org. Chem. 1998, 63, 4832. (f) Riesinger, S.
W.; Lofstedt, J .; Petterson-Fasth, H.; Ba¨ckvall, J .-E. Eur. J . Org. Chem.
1999, 12, 3277. (g) Kel′in, A. V.; Sromek, A. W.; Gevorgyan, V. J . Am.
Chem. Soc. 2001, 123, 2074 and references therein.
(3) Kim, G.; J ung, S.-d.; Kim, W.-j. Org. Lett. 2001, 3, 2985.
(4) (a) Miyamura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457. (b)
Suzuki, A. J . Organomet. Chem. 1999, 576, 147. (c) Chemler, S. R.;
Trauner, D.; Danishefsky, S. J . Angew. Chem., Int. Ed. 2001, 40, 4544.
(5) (a) Davies, S. G.; Ichihara, O. Tetrahedron: Asymmetry 1991, 2,
183. (b) Davies, S. G.; Fenwick, D. R. J . Chem. Soc., Chem. Commun.
1995, 1109. For the amide reagent, we used the commercial (S)-(-)-
N-benzyl-R-methylbenzylamine (97+%ee). The optical purity of 6 was
determined to be >92% by 1H NMR using Eu(hfc)3 in CDCl3..
(6) Kamiya, N.; Chikami, Y.; Ishii, Y. Synlett 1990, 675.
(7) Trais, B. R.; Narayan, R. S.; Borhan, B. J . Am. Chem. Soc. 2002,
124, 3824.
10.1021/jo030083c CCC: $25.00 © 2003 American Chemical Society
Published on Web 05/21/2003
J . Org. Chem. 2003, 68, 5395-5398
5395

SCHEME 4a
consecutive reductive amination reactions. However, it
is not still clear whether 2a and 2b converged to a
common intermediate prior to providing the product.
Further application of this strategy for related com-
pounds is under study.
Exp er im en ta l Section
All reactions were performed in oven-dried glassware with
magnetic stirring. Commercial grade reagents were used without
further purification except for chlorotrimethylsilane (TMSCl),
which was distilled from calcium hydride. Anhydrous THF was
distilled from Na/benzophenone. The melting points are uncor-
rected. TLC analysis was performed using glass plate precoated
with silica gel 60F254. Flash column chromatography was
performed with 230-400 mesh silica gel. 1H NMR spectra were
obtained on 300 and 500 MHz spectrometers. NMR spectra were
recorded in parts per million (δ) relative to the peak for
tetramethylsilane (δ ) 0.00) as an internal standard. Optical
rotations were obtained on a digital polarimeter.
(3S)-3-(N-Ben yloxyca r bon yla m in o)bu tyl Ald eh yd e (7).
To a solution of amino ester 6 (0.260 g, 2.20 mmol) in 10 mL of
50% aqueous MeOH were added NaHCO3 (0.460 g, 5.50 mmol)
and CbzCl (0.560 g, 3.30 mmol) at 0 °C, the mixture was stirred
for 5 h at rt, extra CbzCl (0.560 g, 3.30 mmol) was added, and
the mixture was stirred for an additional 4 h. To the resulting
mixture were added saturated NH4Cl solution and NaHCO3
solution, and the solution was extracted with EtOAc (5 mL ×
3). The organic layer was dried over MgSO4, filtered, and
concentrated under vacuum. The crude product was purified by
column chromatography of silica gel (50 g, elution with hexane/
EtOAc ) 2:1) to provide 0.420 g (77%) of N-Cbz ester intermedi-
ate: 1H NMR (300 MHz, CDCl3) δ 7.25-7.33 (m, 5H), 5.23 (bs,
1H), 5.07 (s, 2H), 4.13 (dt, J ) 5.1, 6.6 Hz, 1H), 4.11 (s, 3H),
2.48 (d, J ) 5.1 Hz, 1H), 1.24 (d, J ) 6.6 Hz, 3H).
The ester (0.420 g, 1.70 mmol) was dissolved in anhydrous
toluene (17 mL), and DIBAL-H (1.36 mL, 1.5 M in toluene, 2.04
mmol) was added slowly at -78 °C under N2. The mixture was
stirred for 30 min at -78 °C, and MeOH was added to the
solution to destroy excess DIBAL-H. After the reaction mixture
was diluted with EtOAc, the organic layer was washed with
water, dried over MgSO4, filtered, and concentrated. The crude
product was purified by column chromatography of silica gel (50
g, elution with hexane/EtOAc ) 2:1) to provide 0.170 g (45%) of
N-Cbz-amino aldehyde 7: 1H NMR (300 MHz, CDCl3) δ 9.74 (s,
1H), 7.28-7.35 (m, 5H), 5.10 (s, 2H), 5.06 (bs, 1H), 4.18 (m, 1H),
2.02 (dd, J ) 6.6, 6.6 Hz, 2H), 1.14 (d, J ) 6.6 Hz, 3H); 13C NMR
(75 MHz, CDCl3) δ 200.8, 171.1, 136.3, 128.4(2), 128.1(2), 66.6,
60.3, 42.8, 20.9; IR (neat) 3334, 1719, 1690, 1533 cm-1; mass
spectrum (EI) m/z 221 (M+).
a
Key: (a) (i) 9-BBN-H, THF, rt, (ii) 4, Pd(dppf)Cl2, AsPh3,
Cs2CO3, DMF, rt, 76%; (b) OsO4, Oxone, DMF, rt, 58%; (c) 10%
Pd/C, H2, MeOH, rt, 50%.
SCHEME 5a
a
Key: (a) (i) n-BuLi, THF, -78 to -20 °C, (ii) BuI, -20 °C,
75%; (b) (i) n-BuLi, THF, -78 to 0 °C, (ii) I2, 78%, -78 °C.
SCHEME 6a
a
Key: (a) (i) 9-BBN-H, THF, rt, (ii) 5, Pd(PPh3)4, AsPh3,
Cs2CO3, DMF, rt, 95%; (b) MMPP, EtOH/H2O,rt, 61%; (c) 10% Pd/
C, H2, MeOH, rt, 45%.
purification along with less than 4% of the known
epimeric compound 11, indolizidine 195B.8
As the 1,4-dicarbonyl group proved suitable for the
transformation, we planned an alternative direct way to
a related precursor. We envisioned that a suitable furan
derivative would be readily prepared by the Suzuki
coupling and this furan would be transformed to a R,â-
unsaturated 1,4-dicarbonyl compound.9 For the purpose,
2-iodo-5-butylfuran (5) was readily prepared in quantity
by the conventional substitution reaction condition of
furan derivatives,10 deprotonation with n-BuLi followed
by addition of BuI (75%), and the same deprotonation
condition for the resulting 2-butylfurane followed by I2
addition (78%) (Scheme 5).
(2S)-2-(N-Ben yloxyca r bon yla m in o)-4-bu ten e (3). A 20
mL, one-necked, round-bottomed flask equipped with a rubber
septum pierced with an argon inlet needle was charged with a
solution of methyltriphenylphosphonium iodide (0.220 g, 0.544
mmol) in 4 mL of THF. To this resulting solution was added
n-BuLi (2.5 M in hexane, 0.24 mL, 0.58 mmol) slowly at 0 °C.
After 10 min of stirring at 0 °C, 0.190 mL of HMPA was added,
and the solution was stirred for 50 min. To this mixture was
added a solution of aldehyde 7 (0.080 g, 0.362 mmol) in 6 mL of
DMF. After the resulting solution was stirred at rt overnight, it
was diluted with 5 mL of EtOAc and washed with water twice
(10 mL × 2). The organic layer was dried over MgSO4, filtered,
and concentrated. Purification by column chromatography of
The Suzuki coupling of 3 and 5 gave out 12 in 95%
yield when using Pd(PPh3)4 as a catalyst. Conversion of
the furan derivative 12 to 2b was then performed by
treatment with magnesium monoperoxyphthalate at
room temperature in 61% yield (Scheme 6).9b As expected,
the same hydrogenation condition transformed the pre-
cursor 2b to (+)-monomorine in 5 h, affording 45% yield
after purification. The two synthetic (+)-monomorine
have shown satisfactory spectral data (1H and 13C NMR
and MS).2a
In summary, we have described the concise synthesis
of (+)-monomerine from the precursors 2a and 2b, which
have been prepared using Suzuki coupling reaction. The
mild hydrogenation condition transformed the intermedi-
ates to (+)-monomorine through deprotection followed by
silica gel (elution with hexane/EtOAc ) 2:1) provided 0.054 g of
1
homoallylic amine 3 (67%): [R]24 ) -13.0 (c 1.02, CHCl3); H
D
NMR (300 MHz, CDCl3) δ 7.26-7.37 (m, 5H), 5.75 (m, 1H), 5.10
(s, 2H), 5.03-5.08 (m, 2H), 4.60 (bs, 1H), 3.79 (m, 1H), 2.63 (d,
J ) 5.1 Hz, 2H), 1.24 (d, J ) 6.6 Hz, 3H); 13C NMR (75 MHz,
CDCl3) δ 155.7, 136.7, 134.3, 128.4 (3), 128.0 (2), 117.8, 66.4,
46.5, 41.1, 20.4; IR (neat) 3327, 2972, 1697, 1586 cm-1; mass
(8) Tokuyama. T.; Nishimori, N.; Karle, I, L.; Edword, M. W.; Daly,
J . W. Tetrahedron 1986, 42, 3453.
(9) (a) Williams, R. D.; LeGoff, E. J . Org. Chem. 1981, 46, 4143. (b)
Dom´ınguez, C.; Csa´ky, A. G.; Plumet, J . Tetrahedron Lett. 1990, 31,
7669.
spectrum (EI) m/z 219 (M+ - 1); exact mass calcd for C13H16
-
NO2 (M+ - 1) 218.1180, found 218.1167.
2-Iod o-5-a cetoxy-1-n on en e (9). To a solution of 1-nonyn-
5-ol 8 (0.960 g, 6.85 mmol) and Et3N (2.87 mL, 20.6 mmol) in
(10) Bohlmann, F.; Sto¨hr, F.; Staffelt, J . Chem. Ber. 1978, 111, 3146.
5396 J . Org. Chem., Vol. 68, No. 13, 2003

20 mL of methylene chloride were added acetic anhydride (0.766
mL, 8.22 mmol) and a catalytic amount of DMAP (5%). The
solution was stirred at rt overnight and diluted with 10 mL of
methylene chloride. The organic layer was washed with water,
2% of aqueous HCl solution, water again, and brine. Drying over
MgSO4 was followed by filtration and concentration, and puri-
fication by silica gel column chromatography provided 1.21 g
(97%) of an acetate as a yellow oil: 1H NMR (300 MHz, CDCl3)
δ 4.88 (m, 1H), 2.15 (m, 2H), 1.97 (s, 3H), 1.88 (t, J ) Hz, 1H),
1.70 (m, 2H), 1.48 (m, 2H), 1.23 (m, 4H), 0.82 (t, J ) 6.94 Hz,
3H).
1H), 2.53 (t, J ) 7.5 Hz, 2H), 2.41 (t, J ) 7.0 Hz, 2H), 2.25 (t,
J ) 7.0 Hz, 2H), 2.01 (m, 2H), 1.55 (t, J ) 7.5 Hz, 2H), 1.40-
1.50 (m, 4H), 1.30 (dt, J ) 7.5, 7.5 Hz, 2H), 1.14 (d, J ) 6.0 Hz,
3H), 0.90 (t, J ) 7.5 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ 210.7,
155.7, 148.0, 136.6, 128.5 (3), 128.0 (2), 109.2, 66.4, 47.0, 42.6,
40.8, 32.0, 29.5, 26.2, 23.9, 22.3, 21.6, 21.2, 13.8; IR (neat) 2924,
1708, 1241 cm-1; mass spectrum (EI) m/z 359 (M+); exact mass
calcd for C22H33NO3 359.2460, found 359.2480.
(2S)-2-(N-Ben yloxyca r bon yla m in o)-6, 9-d ioxotr id eca n e
(2a ). To a solution of methyleneamine 10 (0.500 g, 1.40 mmol)
in 7 mL of DMF was added OsO4 (0.174 mL, 0.014 mmol, 2.5%
in t-BuOH) at rt. After the mixture was stirred for 5 min at rt,
oxone (3.42 g, 5.56 mmol) was added slowly and the resulting
solution was stirred for 3 h at rt. To this solution was added
Na2SO3 (1.05 g, 8.34 mmol), and the solution was stirred until
the color turned dark. The mixture was diluted with 30 mL of
EtOAc, and the organic layer was washed with 1 N HCl three
times and brine and dried over Na2SO4. Filtration was followed
by concentration, and the crude product was purified by silica
gel column chromatography (elution with hexane/EtOAc ) 5:1)
to afford 0.30 g of 2a (58% yield): [R]24D ) -2.02 (c 1.00, CHCl3);
1H NMR (500 MHz, CDCl3) δ 7.27-7.35 (m, 5H), 5.10 (s, 2H),
4.72 (bs, 1H), 2.66 (t, J ) 7.5 Hz, 2 × 2H), 2.46 (t, J ) 7.5 Hz,
2H), 2.44 (t, J ) 7.5 Hz, 2H), 1.53-1.58 (m, 4H), 1.41 (m, 2H),
1.30 (m, 2H), 1.13 (d, J ) 6.5 Hz, 3H), 0.90 (t, J ) 7.5 Hz, 3H);
13C NMR (125 MHz, CDCl3) δ 209.7, 209.3, 155.7, 136.6, 128.4
(3), 128.0 (2), 66.4, 46.8, 42.4, 42.2, 36.2, 35.9, 35.9, 25.8, 22.2,
21.1, 20.0,13.8; IR (neat) 1698, 1686, 1545 cm-1; mass spectrum
(EI) m/z 361 (M+); exact mass calcd for C21H31NO4 361.2253,
found 361.2252.
2-Iod o-5-bu tylfu r a n (5). To a solution of furan (16 mL, 0.216
mol) in 300 mL of THF in a 1 L round-bottomed flask was added
56 mL of n-BuLi (0.14 mol, 2.5 M in hexane) slowly at -78 °C
under Ar gas. The solution was warmed to -20 °C and stirred
for 1 h at the temperature. After iodobutane (20 g, 0.108 mol)
was added slowly to the mixture at -20 °C, the solution was
warmed to rt and stirred for 2 h. Slow addition of water (100
mL) was followed by extraction with diethyl ether (250 mL ×
2). Drying over MgSO4, filtration, and concentration afforded
the crude product, which was purified by short silica gel filtration
(elution with hexane) and simple distillation (40 °C/20 mmHg)
to obtain 10 g of 2-butylfuran (75%) as a colorless oil.
The compound (8.5 g, 68.5 mmol) was dissolved in 250 mL of
THF and cooled to -78 °C. To this solution was added slowly
35 mL of n-BuLi (89.1 mmol, 2.5 M in hexane), and the resulting
solution was warmed to 0 °C, stirred for 10 min at 0 °C, and
cooled again to -78 °C. To this solution was added slowly iodine
(22.6 g, 89 mmol) in 50 mL of THF, and the solution was warmed
slowly to 0 °C and stirred for 2 h at 0 °C. After addition of 100
mL of water, the solution was extracted with ether (250 mL ×
2). The organic layer was washed with aqueous Na2S2O3 solution
(60 mL) and water, dried over MgSO4, filtered, and concentrated.
The crude product was purified by silica gel column chromatog-
raphy (elution with hexane) to afford 13.3 g of 5 (78%) as a pale
brownish oil: 1H NMR (300 MHz, CDCl3) δ 6.39 (d, J ) 3.2 Hz,
1H), 5.90 (m, 1H), 2.63 (t, J ) 7.74 Hz, 2H), 1.59 (tt, J ) 7.20,
7.20 Hz, 2H), 1.33 (tq, J ) 7.20, 7.32 Hz, 2H), 0.89 (t, J ) 7.32
Hz, 3H); 13C NMR (75 MHz, CDCl3) δ 162.2, 120.6, 108.0, 84.2,
30.1, 27.9, 22.1, 13.7; IR (neat) 1382, 1066 cm-1; mass spectrum
(EI) m/z 250 (M+).
2-((2S)-2-N-Be n zyloxyca r b on yla m in op e n t yl)-5-b u t yl-
fu r a n (12). To a solution of 3 (0.50 g, 2.5 mmol) in 8 mL of THF
was added 9-BBN (0.61 g, 2.5 mmol), and then the solution was
stirred at rt for 2 h under argon gas. To the solution was added
water (0.50 g, 28 mmol), and the solution was stirred for 20 min.
The resulting solution was cannulated to a solution of 5 (0.750
g, 3.0 mmol), Pd(PPh3)4 (0.24 g, 0.21 mmol), Cs2CO3 (1.30 g, 4.0
mmol), Ph3As (0.064 g, 0.21 mmol), and H2O (0.40 g, 22 mmol)
in 10 mL of dry DMF. The combined mixture was stirred for 4
h at rt and diluted with 30 mL of EtOAc. The organic layer was
washed with saturated NH4Cl solution, saturated NaHCO3
solution, water twice, and brine and dried over MgSO4. After
filtration and concentration, the crude product was separated
by silica gel column chromatography (elution with hexane/EtOAc
To an acetonitrile solution (40 mL) containing NaI (2.86 g,
19.1 mmol) and TMSCl (2.42 mL, 19.1 mmol) was added water
(0.17 mL, 9.55 mmol), and the mixture was stirred at rt for 10
min. To this resulting mixture was added the acetate intermedi-
ate in 2 mL of acetonitrile via syringe, and the solution was
stirred at rt for 1 h. After the addition of water to the mixture
and dilution with diethyl ether, the organic layer was washed
with saturated sodium thiosulfate solution and dried over
MgSO4. Filtration and concentration were followed by separation
by column chromatography on silica gel (40 g, elution with
hexane/EtOAc ) 100:1) to afford 3.36 g of the iodoacetate 9
(69%): 1H NMR (300 MHz, CDCl3) δ 6.00 (d, J ) 1.20 Hz, 1H),
5.67 (m, J ) 1.20 Hz, 1H), 4.86 (m, 1H), 2.39 (m, 2H), 2.02 (s,
3H), 1.75 (m, 2H), 1.52 (m, 2H), 1.27 (m, 4H), 0.87 (t, J ) 6.96
Hz, 3H); 13C NMR (125 MHz, CDCl3) δ 170.7, 125.8, 111.0, 72.9,
41.3, 33.5, 27.4, 22.5, 21.2, 13.9; IR (neat) 1735, 1234 cm-1; mass
spectrum (EI) m/z 251 (M+ - OAc); exact mass calcd for C11H19
IO2 310.0430, found 218.0420.
-
2-Iod o-5-oxo-1-n on en e (4). The mixture of iodoacetate 9 (3
g, 9.67 mmol) in 6 mL of MeOH and 3.14 g of NaOMe (3.14 g,
58 mmol) was stirred at rt overnight under N2 atmosphere. After
dilution of the mixture with diethyl ether, the organic layer was
washed with saturated NH4Cl solution twice, water, and brine
and dried over MgSO4. Filtration was followed by concentration
and silica gel column chromatography (elution with hexane/
EtOAc ) 30:1) to afford 2.1 g of an alcohol intermediate (81%):
1H NMR (300 MHz, CDCl3) δ 6.04 (d, J ) 1.20 Hz, 1H), 5.68 (d,
J ) 1.20 Hz, 1H), 3.60 (m, 1H), 2.50 (m, 2H), 1.30-1.68 (m, 8H),
0.88 (t, J ) 6.96 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ 125.6,
112.1, 70.4, 41.6, 37.4, 36.8, 27.7, 22.7, 14.0; IR (neat) 3320, 2927
cm-1; mass spectrum (EI) m/z 268 (M+); exact mass calcd for
C9H17IO 268.0324, found 267.0322.
To a solution of pyridinium dichromate (2.95 g, 7.83 mmol)
in CH2Cl2 containing 4 Å molecular sieves (1 g) was added the
alcohol obtained (0.700 g, 2.61 mmol) in 1 mL of methylene
chloride. The mixture was stirred at rt overnight, filtered
through Celite on a glass filter, concentrated, and separated by
silica gel column chromatography (elution with hexane/EtOAc
) 50:1) to afford 2.43 g of the iodoketone (83%): 1H NMR (300
MHz, CDCl3) δ 6.09 (d, J ) 1.1 Hz, 1H), 5.68 (d, J ) 1.1 Hz,
1H), 2.65 (t, J ) 6.90 Hz, 2H), 2.45 (t, J ) 7.40 Hz, 2H), 1.59 (t,
J ) 7.40 Hz, 2H), 1.33 (m, 2H), 1.27 (m, 4H), 0.94 (t, J ) 7.35
Hz, 3H); 13C NMR (125 MHz, CDCl3) δ 209.0, 126.4, 110.2, 42.5,
42.1, 41.1, 25.9, 22.3, 13.8; IR (neat) 2955, 1712 cm-1; mass
spectrum (EI) m/z 267 (M+ + H); exact mass calcd for C9H15IO
((M+ + H) 267.0246, found 267.0254.
(2S)-2-(N-Ben yloxyca r bon yla m in o)-6-m eth ylen e-9-oxo-
tr id eca n e (10). To a solution of homoallylamine 3 (0.283 g, 1.30
mmol) in 5 mL of THF was added 9-BBN (0.317 g, 1.30 mmol),
the solution was stirred at rt for 2 h under Ar, and water (234
µL, 130 mmol) was added. After 30 min, the resulting solution
was cannulated to a solution of 4 (0.378 g, 1.42 mmol), Ph3As
(40 mg, 0.130), Cs2CO3 (0.847 g, 2.60 mmol), water (234 µL, 130
mmol) in 10 mL of DMF in a 50 mL, one-necked, round-bottomed
flask. The combined mixture was stirred at rt for 6 h and diluted
with 50 mL of EtOAc. The organic layer was washed with
saturated NH4Cl solution (20 mL), saturated NaHCO3 solution
(20 mL), water (10 mL), and brine and dried over MgSO4. After
filtration and concentration, the crude product was separated
by column chromatography using 50 g of silica gel and eluting
solvents, hexane/EtOAc ) 10:1, to afford 0.353 g of 10 (76%):
[R]24D ) 1.06 (c 1.09, CHCl3); 1H NMR (500 MHz, CDCl3) δ 7.26-
7.36 (m, 5H), 5.08 (s, 2H), 4.72 (s, 1H), 4.67 (s, 1H), 4.63 (bs,
J . Org. Chem, Vol. 68, No. 13, 2003 5397

) 5:1) to afford 0.820 g of 11 (96%): [R]24 ) -1.30 (c 1.13,
amount of gas, and the solution was stirred under hydrogen
balloon at rt for 1 h. The solution was filtered through Celite
and concentrated carefully. The crude product was separated
by silica gel column chromatography (elution with pentane/ether
) 10:1) to afford 7.8 mg of 1 (50%) and 0.6 mg of 11 (4%).
A 15 mL, one-necked, round-bottomed flask equipped with a
rubber septum was charged with a solution of 2b (30.0 mg, 0.08
mmol) in 5 mL of MeOH containing 10% palladium on activated
carbon (2.04 mg, 0.004 mmol). The flask atmosphere was
replaced by hydrogen gas via blowing an excess amount of gas,
and the solution was stirred under hydrogen balloon at rt for 5
h. The solution was filtered through Celite and concentrated
carefully. The crude product was separated by silica gel column
chromatography (elution with pentane/ether ) 10:1) to afford
D
1
CHCl3); H NMR (300 MHz, CDCl3) δ 7.28-7.34 (m, 5H), 5.82
(s, 2H), 5.07 (s, 2H), 4.52 (bs, 1H), 3.73 (m, 1H), 2.57 (t, J ) 4.2
Hz, 2H), 2.53 (t, J ) 3.9 Hz, 2H), 1.62 (m, 2H), 1.57 (m, 2H),
1.47 (m, 2H), 1.37 (m, 2H), 1.12 (d, J ) 6.5 Hz, 3H), 0.91 (t, J )
7.3 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ 155.7, 154.8, 154.7,
136.6, 128.5(3), 128.0(2), 105.2, 104.8, 66.5, 47.0, 36.5, 30.2, 27.8,
27.7, 24.6, 22.2, 21.2, 13.8; IR (neat) 3329, 2932, 1697, 1532 cm-1
;
mass spectrum (EI) m/z 343 (M+); exact mass calcd for C21H29
-
NO3 343.2147, found 343.2147.
(2S )-2-(N -B e n y lo x y c a r b o n y la m in o )-6,9-d io x o -7-t r i-
d ecen e (2b). To a solution of 11 (0.023 g, 0.067 mmol) in EtOH
(0.3 mL) was added MMPP (0.023 g, 0.046 mmol) in water (0.3
mL) at rt. The mixture was stirred at rt for 3 h. Addition of
saturated aqueous NaHCO3 solution to the mixture was followed
by extraction with 3 mL of CH2Cl2 twice. The combined organic
layer was dried over MgSO4, filtered, concentrated, and purified
by silica gel column chromatography (elution with hexane/EtOAc
7.0 mg of 1 (45%) and 0.5 mg of 11 (less than 4%): [R]24 ) 29.0
D
(c 0.80, hexane) and 30.2 (c 2.05, hexane), respectively [lit.2a [R]
35.7 (c 0.370, hexane)]; 1H NMR (500 MHz, CD3OD) δ 2.45-
2.51 (m, 1H), 2.19-2.21 (m, 1H), 2.07-2.10 (m, 1H), 1.19-1.94
) 3:1) to provide 0.015 g of 2b (62% yield): [R]24 ) 0.8 (c 1.50,
(m, 16H), 1.15 (d, J ) 6.4 Hz, 3H), 0.90 (t, J ) 7.2 Hz, 3H); 13
C
D
1
CHCl3); H NMR (300 MHz, CDCl3) δ 7.26-7.34 (m, 5H), 6.25
NMR (125 MHz, CD3OD) δ 68.8, 65.0, 62.3, 39.7, 36.0, 30.7, 30.6,
30.5, 30.3, 25.5, 23.9, 22.9, 14.5; mass spectrum (EI) m/z 195
(M+); exact mass calcd for C13H25N 195.1987, found 195.1970.
(s, 2H), 5.06 (s, 2H), 4.52 (bd, J ) 9.3 Hz, 1H), 3.58 (m, 1H),
2.54 (t, J ) 6.9 Hz, 2H), 2.49 (t, J ) 7.3 Hz, 2H), 1.61 (m, 2H),
1.46 (m, 2H), 1.38 (m, 2H), 1.35 (m, 2H), 0.89 (t, J ) 7.3 Hz,
3H), 0.85 (d, J ) 4.2 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ 202.7
(2), 155.8, 136.6, 136.0, 135.2, 128.5 (3), 128.0 (2), 66.5, 46.8,
42.3, 41.8, 36.1, 25.5, 22.2, 21.2, 19.7, 13.8; IR (neat) 3342, 2958,
1700, 1699, 1527 cm-1; mass spectrum (EI) m/z 359 (M+); exact
mass calcd for C21H29NO4 359.4593, found 359.4499.
Ack n ow led gm en t. We acknowledge financial sup-
port from the Korea Science and Engineering Founda-
tion (R01-2000-000-00048-0).
1
Su p p or tin g In for m a tion Ava ila ble: Copies of H NMR
1
spectra of 4, 7, and 9 and H and 13C NMR spectra of 2a ,b, 3,
(+)-Mon om or in e 1. A 15 mL, one-necked, round-bottomed
flask equipped with a rubber septum was charged with a solution
of 2a (30.0 mg, 0.08 mmol) in 5 mL of MeOH containing 10%
palladium on activated carbon (2.04 mg, 0.004 mmol). The flask
atmosphere was replaced by hydrogen gas via blowing an excess
5, 10, and 12. This material is available free of charge via the
Internet at http://pubs.acs.org.
J O030083C
5398 J . Org. Chem., Vol. 68, No. 13, 2003