Regioselective reduction of 3-sulfonyl glutarimides to 3,4-dihydro-5-sulfonylpyridin-2-ones. Formal synthesis of the indolizidine 8a-epi-dendroprimine

Article abstract of DOI:10.1021/jo025539p

Sodium borohydride regioselectively reduced various 3-sulfonyl glutarimides 1 to hydroxy piperidones 2, which were further dehydrated to 3,4-dihydro-5-sulfonylpyridin-2-ones 3 in the presence of boron trifluoride. Formal synthesis of 8a-epi-dendroprimine (4) possessing an indolizidine ring system has been accomplished via intramolecular radical cyclization of cyclic vinyl sulfone 5.

Full text of DOI:10.1021/jo025539p

SCHEME 1
Regioselective Red u ction of 3-Su lfon yl
Glu ta r im id es to
3,4-Dih yd r o-5-su lfon ylp yr id in -2-on es.
F or m a l Syn th esis of th e In d olizid in e
8a -epi-Den d r op r im in e
Ru-Ting Hsu,† Li-Ming Cheng,†
Nein-Chen Chang,*,†,‡ and Huo-Mu Tai*,§
Department of Chemistry, National Sun Yat-Sen University,
Kaohsiung, Taiwan 804, Republic of China, and
Department of Applied Chemistry, Chia Nan University of
Pharmacy and Science, Tainan, Taiwan 717, Republic of
China
jtaihm@mail.chna.edu.tw
Received J anuary 20, 2002
Abstr a ct: Sodium borohydride regioselectively reduced
various 3-sulfonyl glutarimides 1 to hydroxy piperidones 2,
which were further dehydrated to 3,4-dihydro-5-sulfonylpy-
ridin-2-ones 3 in the presence of boron trifluoride. Formal
synthesis of 8a-epi-dendroprimine (4) possessing an indolizi-
dine ring system has been accomplished via intramolecular
radical cyclization of cyclic vinyl sulfone 5.
Previously, we reported an efficient synthesis of 4- or
5-substituted 3-sulfonyl glutarimides 1 via a stepwise [3
+ 3] cycloaddition.6 Sequential treatment of chloroacetyl
chloride with primary amines and sodium p-toluenesulfi-
nate furnished R-toluenesulfonyl acetamide 6 in 90%
yield. After the reaction of 6 with 2 equiv of sodium
hydride, the resulting dianion 7 reacted with a variety
of R,â-unsaturated esters to afford the corresponding
substituted 3-toluenesulfonyl glutarimides 1. The trans
stereochemistry of 1b was established by X-ray analysis.
The stereochemistries of all the other cycloadducts of 1
Regioselective reduction of cyclic imides has attracted
considerable interest among organic chemists,1-4 partly
because the resulting hydroxylactams can be converted
to corresponding N-acyliminium intermediates and then
further transformed into different alkaloids, such as
indolizidines, quinolizidines, isoquinolines, and indoles.5
In cases of reduction of nonsymmetrically substituted
cyclic imides, it was reported that glutarimides seem to
be preferentially reduced at the less hindered carbonyl
group.3,4 In this report, we describe a general method
which regioselectively reduces the carbonyl group on
3-sulfonyl glutarimides 1 and leads to corresponding
hydroxylactams 2, which are then further converted to
3,4-dihydro-5-sulfonylpyridin-2-ones 3. Formal synthesis
of 8a-epi-dendroprimine (4) via intramolecular radical
cyclization of cyclic vinyl sulfone 5 is also reported.
1
were compared by their H NMR spectra with that of 1b
1
(a H HNR singlet at δ 3.87 was assigned to an equatorial
proton on the C3 carbon in the boat form conformation
of 1b).6 In the course of our application of 1 in alkaloid
synthesis, we found that treatment of 1 with excess
sodium borohydride in methanol-tetrahydrofuran (1:2)
at -10 °C furnished 2 exclusively. The presence of the
strong electron-withdrawing sulfonyl group at the C3
position increased the electrophilicity of C2, which may
account for the regiochemistry of reduction. To confirm
these results, hydroxylactams 2 were treated with boron
trifluoride in the presence of anhydrous magnesium
sulfate, and the corresponding dehydration products 3
were obtained in moderate to good yields (Scheme 1).
Several examples were examined, and the results are
listed in Table 1.
For the synthesis of 8a-epi-dendroprimine (4) shown
in Scheme 2,7 glutarimide 8 was prepared in quantitative
yield by treatment of 1b with aluminum trichloride in
refluxing benzene. Compound 8 was converted to chloride
1j, which, upon treatment with excess sodium borohy-
dride in MeOH-THF solution at -10 °C, furnished
hydroxy lactam 2j.8 Without purification, subsequent
† National Sun Yat-Sen University.
‡ Telephone: (+886)-75253913. Fax: (+886)-75253913.
§ Chia Nan University of Pharmacy and Science.
(1) Heaney, H.; Taha, M. O. Tetrahedron Lett. 2000, 41, 1993.
(2) Ducrot, P.; Thal, C. Tetrahedron Lett. 1999, 40, 9037.
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37, 185.
(4) Watanabe, T.; Hamaguchi, F.; Ohki, S. Yakugaku Zasshi 1973,
93, 845; Chem. Abstr. 1973, 79, 78328.
(5) (a) Speckamp, W. N.; Hiemstra, H. Tetrahedron 1985, 41, 4367.
(b) Roth, E.; Altman, J .; Kapon, M.; Ben-Ishai, D. Tetrahedron 1995,
51, 801. (c) Manteca, I.; Sotomayor, N.; Villa, M.-J .; Lete, E. Tetrahe-
dron Lett. 1996, 37, 7841. (d) Metais, E.; Overman, L. E.; Rodriguez,
M. I.; Stearns, B. A. J . Org. Chem. 1997, 62, 9210. (e) Padwa, A.;
Hennig, R.; Kappe, C. O.; Reger, T. S. J . Org. Chem. 1998, 63, 1144.
(f) Chalard, P.; Remuson, R.; Gelas-Mialhe, Y.; Gramain, J . C.
Tetrahedron: Asymmetry 1998, 9, 4361. (g) Tanis, S. P.; Deaton, M.
V.; Dixon, L. A.; McMills, M. C.; Raggon, J . W.; Collins, M. A. J . Org.
Chem. 1998, 63, 6914. (h) Chalard, P.; Remuson, R.; Gelas-Mialhe,
Y.; Gramain, J . C.; Canet, I. Tetrahedron Lett. 1999, 40, 1661. (i)
Koseki, Y.; Kusano, S.; Sakata, H.; Nagasaka, T. Tetrahedron Lett.
1999, 40, 2169.
(6) Chang, M.-Y.; Chang, B.-R.; Tai, H.-M.; Chang, N.-C. Tetrahe-
dron Lett. 2000, 41, 10273.
(7) (a) Diederich, M.; Nubbemeyer, U. Synthesis 1999, 286. (b) Hua,
D. H.; Bharathi, S. N.; Panangadan, J . A. K.; Tsujimoto, A. J . Org.
Chem. 1991, 56, 6998.
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10.1021/jo025539p CCC: $22.00 © 2002 American Chemical Society
Published on Web 06/13/2002
5044
J . Org. Chem. 2002, 67, 5044-5047

TABLE 1. Syn th esis of 3 via Regioselective Na BH 4
Red u ction of 1a ,b
SCHEME 2
a
b
All yields were based on glutarimides 1. The structures of
1b and 3g were confirmed by X-ray analysis.
boron trifloride dehydration of 2j provided vinyl sulfone
3j from 1j in 97% yield.
vinyl sulfone 5 to construct indolizidine carbon skeleton
10. This methodology has proved applicable for the
synthesis of the indolizidine alkaloid 8a-epi-dendroprimine
(4). Further syntheses of piperidine, indolizidine, quino-
lizidine, and indole alkaloids are currently underway in
our laboratory.
For the synthesis of an indolizidine skeleton, chloride
3j was first converted to the corresponding iodide 5 with
sodium iodide. Intramolecular radical cyclization of 5
with tributyltin hydride in the presence of AIBN gave
indolizidine 9 (81%) as a single diastereomer. To the best
of our knowledge, this is the first example of the radical
cyclization of cyclic vinyl sulfone to build up an indolizi-
dine carbon skeleton. Reductive desulfonation of 9 with
sodium amalgam gave 10 as a single diastereomer in 88%
yield.9 The strucure of 10 was confirmed by comparison
of the 1H and 13C NMR spectra with those of an authentic
sample provided by Professor Udo Nubbemeyer.7a The
diastereoselective production of 9 can be explained by the
formation of the more stable intermediate 11a instead
of 11b in the ring formation step. This rationalization
was supported by X-ray crystallography of compound 3g
(Figure 1), prepared in our laboratory. In compound 3g,
the substituents at C4 and the nitrogen atom are cis to
each other. Since compound 10 has been transformed into
8a-epi-dendroprimine (4), this work constitutes a formal
total synthesis of racemic 8a-epi-dendroprimine (4).7a
In summary, we successfully performed the regio-
selective reaction of 3-sulfonyl glutarimides 1, leading to
3,4-dihydro-5-tosylpyridin-2-ones 3 in moderate to excel-
lent yields and intramolecular radical cyclization of cyclic
F IGURE 1. Intermediates of 11 and X-ray crystallography
of 3g.
(9) Satoh, T.; Oguro, K.; Shishikura, J .; Kanetaka, N.; Okada, R.;
Yamakawa, K. Bull. Chem. Soc. J pn. 1993, 66, 2339.
J . Org. Chem, Vol. 67, No. 14, 2002 5045

by column chromatography on silica gel (elution with hexane/
ethyl acetate 2:1) to give 3,4-dihydro-5-sulfonylpyridin-2-ones
3.
Exp er im en ta l Section
Before use, THF and benzene were distilled from a deep blue
solution resulting from sodium and benzophenone under nitro-
gen. All reagents and solvents were obtained from commercial
sources and used without further purification. Thin-layer chro-
matography (TLC) analysis was performed with precoated silica
gel (60 f254 plates), and column chromatography was carried out
on silica (70-230 mesh). All reactions were performed under
an atmosphere of nitrogen in dried (except those concerned with
aqueous solutions) spherical flasks and stirred with magnetic
bars.
(4S*,5R*)-1-Ben zyl-6-h yd r oxy-5-(t olu en e-4-su lfon yl)-4-
p h en yl-2-p ip er id in on e (2d ): IR (CDCl3, cm-1) 3365, 1653; 1H
NMR (500 MHz, CDCl3) δ 7.34-7.26 (m, 5H), 7.11-7.02 (m, 5H),
6.96-6.91 (m, 4H), 5.68 (s, 1H), 5.12 (d, J ) 14.5 Hz, 1H), 4.40
(d, J ) 14.5 Hz, 1H), 4.13 (br s, 1H), 4.01-3.95 (m, 1H), 3.68
(dd, J ) 2.5, 11.5 Hz, 1H), 3.00 (dd, J ) 7.5, 18.0 Hz, 1H), 2.52
(dd, J ) 9.5, 18.0 Hz, 1H), 2.32 (s, 3H); 13C NMR (125 MHz,
CDCl3) δ 169.2 (s), 144.2 (s), 139.4 (s), 136.9 (s), 136.3 (s), 129.3
(d, 2C), 128.8 (d, 2C), 128.5 (d, 4C), 128.1 (d, 2C), 127.9 (d, 2C),
127.8 (d), 127.2 (d), 77.5 (d), 68.5 (d), 48.3 (t), 40.0 (t), 35.8 (d),
21.5 (q). Mass m/z (EI, 30 eV): 435 (M+, 15.7%), 91 (100%).
1-(3-Ch lor op r op yl)-4-m eth yl-5-(tolu en e-4-su lfon yl)-3,4-
d ih yd r op yr id in -2-on e (3j): 97% yield; IR (CDCl3, cm-1) 1692,
1644; 1H NMR (500 MHz, CDCl3) δ 7.77 (d, J ) 8.0 Hz, 2H),
7.35 (s, 1H), 7.34 (d, J ) 8.0 Hz, 2H), 3.89 (td, J ) 6.5, 13.5 Hz,
1H), 3.65-3.50 (m, 1H), 2.77-2.71 (m, 1H), 2.57 (dd, J ) 7.0,
16.0 Hz, 1H), 2.44 (s, 3H), 2.38 (dd, J ) 2.0, 16.0 Hz, 1H), 2.10
(quintet, J ) 7.0 Hz, 2H), 0.96 (d, J ) 7.0 Hz, 3H); 13C NMR
(125 M Hz, CDCl3) δ 168.3 (s), 144.3 (s), 138.0 (s), 137.6 (s), 129.9
(d, 2C), 127.6 (d, 2C), 122.8 (s), 45.2 (t), 41.6 (t), 38.7 (t), 31.2
(t), 26.6 (d), 21.6 (q), 18.5 (q). Mass (EI, 70 eV): 343 (M+, Cl )
37, 18%), 341 (M+, Cl ) 35, 49%), 91 (100%). HRMS calcd for
C16H20ClNO3S (M+): 341.0852. Found: 341.0848. Anal. Calcd
for C16H20ClNO3S: C, 56.21; H, 5.90; N, 4.10. Found: C, 56.30;
H, 5.98; N, 3.91.
Gen er a l P r oced u r e to N-Su bstitu ted 2-(Tolu en e-4-su l-
fon yl)a ceta m id e (6). A mixture of N-substituted 2-chloroac-
etamide (68.5 mmol) and toluene-4-sulfonate sodium salt (1.7
g, 75.4 mmol) in dioxane (30 mL) and water (30 mL) was refluxed
for 12 h. The solvent was removed under reduced pressure, and
the residue was recrystallized from ethyl acetate to give 6.
N-Ben zyl-2-(tolu en e-4-su lfon yl)a ceta m id e: 74% yield; IR
(CHCl3, cm-1) 3354, 1665; 1H NMR (500 MHz, CDCl3) δ 7.67 (d,
J ) 8.0 Hz, 2H), 7.37-7.25 (m, 7H), 7.08 (br s, 1H), 4.44 (d, J )
5.5 Hz, 2H), 4.02 (s, 2H), 2.44 (s, 3H); 13C NMR (125 M Hz,
CDCl3) δ 160.5 (s), 145.6 (s), 137.2 (s), 134.9 (s), 130.1 (d, 2C),
128.8 (d, 2C), 128.1 (d, 2C), 128.0 (d, 2C), 127.7 (d), 61.9 (t), 44.0
(d). Mass m/z (EI, 70 eV): 303 (M+, 1%), 148 (100%). HRMS
calcd for C16H17NO3S (M+): 303.0929. Found: 303.0935. Anal.
Calcd for C16H17NO3S: C, 63.34; H, 5.65; N, 4.62. Found: C,
63.02; H, 5.31; N, 4.56.
(3R*,4S*)-4-Meth yl-3-(tolu en e-4-su lfon yl)p ip er id in e-2,6-
d ion e (8). A suspension of 1b (2.00 g, 5.4 mol) and aluminum
chloride (3.60 g, 27.0 mmol) in benzene (30 mL) was refluxed
for 8 h under nitrogen. After removal of the solvent, water was
added to the residue, which was then extracted with ethyl
acetate. The combined organic layers were washed with brine,
dried, filtered, and concentrated. The residue was recrystallized
from ethyl acetate to give compound 8 (1.50 g, quantitative). Mp
Gen er a l P r oced u r e of [3 + 3] Cycloa d d ition to Glu ta -
r im id es 1. To a suspension of sodium hydride (2.00 g, 60%
dispersion in oil, washed three times with dry hexane) in dry
THF (100 mL) was added 2-sulfonylacetamide (1) (20 mmol) in
portions. After 20 min, R,â-unsaturated esters (20 mmol) in THF
(30 mL) were added to the suspension mixture over a period of
30 min. The mixture was stirred for 12 h at room temperature.
The reaction was quenched with aqueous sodium bicarbonate.
The layers were separated, and the aqueous layer was extracted
with ethyl acetate. The combined organic layers were washed
with brine, dried, filtered, and concentrated. The residue was
purified by column chromatography on silica gel (elution with
hexane/ethyl acetate) to give glutarimides 1.
1
172-173 °C; IR (CDCl3, cm-1) 3360, 1711; H NMR (500 MHz,
CDCl3) δ 8.08 (br s, 1H), 7.76 (d, J ) 8.0 Hz, 2H), 7.40 (d, J )
8.0 Hz, 2H), 3.82 (s, 1H), 3.40 (dd, J ) 5.5, 18.0 Hz, 1H), 3.30-
3.24 (m, 1H), 2.52 (d, J ) 18.0 Hz, 1H), 2.48 (s, 3H), 1.21 (d, J
) 7.5 Hz, 3H); 13C NMR (125 M Hz, CDCl3) δ 170.3 (s), 164.1
(s), 146.1 (s), 134.6 (s), 130.0 (d, 2C), 129.0 (d, 2C), 71.0 (d), 35.3
(t), 25.2 (d), 21.8 (q), 20.3 (q). Mass (EI, 70 eV): 282 (M+, 1%),
91 (100%). HRMS calcd for C13H15NO4S (M+): 281.0722.
Found: 281.0725. Anal. Calcd for C13H15NO4S: C, 55.50; H, 5.37;
N, 4.98. Found: C, 55.41; H, 5.51; N, 4.63.
(3R*,4S*)-1-(3-Ch lor op r op yl)-4-m eth yl-3-(tolu en e-4-su l-
fon yl)-3,4-d ih yd r o-5H-p yr id in e-2,6-d ion e (1j). A solution of
8 (300 mg, 0.10 mol), potassium carbonate (0.5 g), and 1-bromo-
3-chloropropane (400 mg, 2.3 mmol) in acetone (15 mL) was
stirred at room temperature for 10 h. After removal of the
solvent, the residue was added to saturated aqueous sodium
bicarbonate and extracted with dichloromethane. The combined
organic layers were washed with brine, dried, filtered, and
concentrated. The residue was recrystallized from dichlo-
romethane to afford compound 1j (300 mg, 80%). Mp 133-134
°C; IR (CDCl3, cm-1) 1677; 1H NMR (500 MHz, CDCl3) δ 7.73
(d, J ) 8.0 Hz, 2H), 7.40 (d, J ) 8.0 Hz, 2H), 3.96 (dt, J ) 2.5,
7.0 Hz, 2H), 3.91 (s, 1H), 3.55 (t, J ) 7.0 Hz, 2H), 3.44 (dd, J )
6.0, 18.0 Hz, 1H), 3.21-3.14 (m, 1H), 2.59 (d, J ) 18.0 Hz, 1H),
2.48 (s, 3H), 2.03 (quintet, J ) 7.0 Hz, 2H), 1.18 (d, J ) 7.0 Hz,
3H); 13C NMR (125 M Hz, CDCl3) δ 170.2 (s), 164.5 (s), 146.1
(s), 134.8 (s), 130.0 (d, 2C), 128.8 (d, 2C), 71.8 (d), 42.0 (t), 37.9
(t), 36.0 (t), 30.8 (t), 24.0 (d), 21.8 (q), 20.3 (q). Mass (EI, 70 eV):
360 (M+ + 1, Cl ) 37, 0.6%), 358 (M+ + 1, Cl ) 37, 1.6%), 91
(100%). Anal. Calcd for C16H20ClNO4S: C, 53.70; H, 5.63; N, 3.91.
Found: C, 53.38; H, 5.78; N, 3.85.
(3R*,4S*)-1-Ben zyl-4-m et h yl-3-(t olu en e-4-su lfon yl)-3,4-
d ih yd r o-5H-p yr id in e-2,6-d ion e (1b): 95% yield; mp 202-203
°C; IR (CHCl3, cm-1) 1675; 1H NMR (500 MHz, CDCl3) δ 7.47
(d, J ) 8.0 Hz, 2H), 7.36-7.24 (m, 7H), 5.09 (d, J ) 14.0 Hz,
1H), 4.88 (d, J ) 14.0 Hz, 1H), 3.87 (s, 1H), 3.51 (dd, J ) 6.0,
18.0 Hz, 1H), 3.21-3.15 (m, 1H), 2.60 (d, J ) 18.0 Hz, 1H), 2.43
(s, 3H), 1.13 (d, J ) 7.0 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ
170.3 (s), 164.2 (s), 145.6 (s), 136.4 (s), 134.3 (s), 129.7 (d, 2C),
128.8 (d, 2C), 128.6 (d, 2C), 128.3 (d, 2C), 127.4 (d), 71.7 (d),
117.5 (s), 43.2 (t), 36.0 (t), 23.9 (d), 21.7 (q), 20.3 (q). Mass m/z
(EI, 70 eV): 371 (M+, 1%), 91 (100%). HRMS calcd for C20H21
-
-
NO4S (M+): 371.1191. Found: 371.1187. Anal. Calcd for C20H21
NO4S: C, 64.67; H, 5.70; N, 3.77. Found: C, 64.20; H, 5.92; N,
3.80.
Gen er a l P r oced u r e of Regioselective Red u ction of Glu -
ta r im id es 1 to 3,4-Dih yd r o-5-su lfon ylp yr id in -2-on es 3. A
suspension of sodium borohydride (106 mg, 2.8 mmol) and
glutarimides 1 (1.5 mmol) in THF (30 mL) and methanol (15
mL) was stirred for 2 h at -10 °C. After saturated aqueous
sodium bicarbonate was added to destroy the excess reduction
agent at this temperature, organic solvents were removed under
reduced pressure. The residue was extracted with dichlo-
romethane, and the combined organic extracts were washed with
brine, dried, filtered, and concentrated to afford 2. Without
further purification, boron trifloride diethyl etherate (0.5 mL)
was added to a solution of the residue and anhydrous magne-
sium sulfate (50 mg) in dichloromethane (20 mL) at 0 °C and
stirred at this temperature for 30 min. The reaction mixture was
quenched with saturated aqueous sodium bicarbonate. The
layers were separated, and the aqueous layer was extracted with
dichloromethane. The combined organic layers were washed with
brine, dried, filtered, and concentrated. The residue was purified
1-(3-Iod op r op yl)-4-m eth yl-5-(tolu en e-4-su lfon yl)-3,4-d i-
h yd r op yr id in -2-on e (5). A solution of 3j (1.00 g, 2.90 mol) and
sodium iodide (0.40 g, 8.0 mmol) in acetone (20 mL) was refluxed
for 5 h. After removal of the solvent, water was added to the
residue, which was then extracted with dichloromethane. The
combined organic layers were washed with brine, dried, filtered,
and concentrated. The residue was chromatographed on silica
5046 J . Org. Chem., Vol. 67, No. 14, 2002

(hexane/ethyl acetate 1:1) to furnish compound 5 (1.00 g, 80%):
IR (CDCl3, cm-1) 1691, 1644; 1H NMR (500 MHz, CDCl3) δ 7.78
(d, J ) 8.0 Hz, 2H), 7.36 (s, 1H), 7.34 (d, J ) 8.0 Hz, 2H), 3.83
(td, J ) 7.0, 13.5 Hz, 1H), 3.53 (td, J ) 7.0, 13.5 Hz, 1H), 3.18-
3.08 (m, 2H), 2.77-2.71 (m, 1H), 2.57 (dd, J ) 7.0, 16.0 Hz, 1H),
2.45 (s, 3H), 2.38 (dd, J ) 2.0, 16.0 Hz, 1H), 2.15 (quintet, J )
7.5 Hz, 2H), 0.96 (d, J ) 7.5 Hz, 3H); 13C NMR (125 M Hz,
CDCl3) δ 168.3 (s), 144.3 (s), 137.9 (s), 137.6 (s), 130.0 (d, 2C),
127.7 (d, 2C), 122.9 (s), 48.1 (t), 38.7 (t), 32.1 (t), 26.6 (d), 21.6
(q), 18.6 (q), 1.3 (t). Mass (EI, 70 eV): 433 (M+, 18%), 91 (100%).
HRMS calcd for C16H20INO3S (M+): 433.0209. Found: 433.0206.
Anal. Calcd for C16H20INO3S: C, 44.35; H, 4.65; I, 29.29; N, 3.23;
O, 11.08; S, 7.40. Found: C, 44.21; H, 4.71; N, 3.05.
(7S*,8R*,8aS*)-7-Meth yl-8-(tolu en e-4-su lfon yl)h exah ydr o-
6H-in d olizin -5-on e (9). To a solution of 5 (300 mg, 0.70 mol)
and AIBN (9.5 mg) in benzene (30 mL) was added tributyltin
hydride (250 mg) in benzene (30 mL) via syringe pump over a
period of 2 h under nitrogen at refluxing temperature. The
mixture was refluxed for 4 h. After the addition of water, the
layers were separated and the aqueous layer was extracted with
ethyl acetate. The combined organic layers were washed with
brine, dried, filtered, and concentrated. The residue was chro-
matographed on silica (hexane/ethyl acetate 1:1) to provide
compound 9 (200 mg, 81%): IR (CDCl3, cm-1) 1655; 1H NMR
(500 MHz, CDCl3) δ 7.80 (d, J ) 8.0 Hz, 2H), 7.41 (s, 1H), 3.88
(dt, J ) 6.5, 9.0 Hz, 1H), 3.63-3.58 (m, 1H), 3.40-3.34 (m, 1H),
2.82 (dd, J ) 3.0, 9.0 Hz, 1H), 2.73-2.65 (m, 1H), 2.51-2.46 (m,
1H), 2.48 (s, 3H), 2.35-2.28 (m, 1H), 2.15 (dd, J ) 2.0, 15.0 Hz,
1H), 1.96-1.89 (m, 1H), 1.83-1.67 (m, 2H), 0.89 (d, J ) 7.5 Hz,
3H); 13C NMR (125 M Hz, CDCl3) δ 169.3 (s), 145.5 (s), 134.6
(s), 130.2 (d, 2C), 128.8 (d, 2C), 71.5 (d), 55.3 (d), 44.1 (t), 38.1
(t), 34.8 (t), 29.0 (d), 23.4 (t), 22.6 (q), 21.7 (q). Mass (EI, 70 eV):
308 (M+, 5%), 136 (100%). HRMS calcd for C16H21NO3S (M+):
307.1242. Found: 307.1237.
(7R*,8a S*)-7-Meth ylh exa h yd r oin d olizin -5-on e (10). A so-
lution of 9 (200 mg, 0.60 mol), disodium hydrogen phosphate
(60 mg), and sodium amalgam (2.0 g, 6%) in methanol (10 mL)
was stirred at room temperature under nitrogen for 3 h. The
mercury was removed, and the solvent was stripped off under
reduced pressure. Water was added to the residue, which was
then extracted with ethyl acetate. The combined organic layers
were washed with brine, dried, filtered, and concentrated. The
residue was chromatographed on silica (hexane/ethyl acetate 1:1)
to afford compound 10 (88 mg, 88%): IR (CDCl3, cm-1) 1625;
1H NMR (500 MHz, CDCl3) δ 3.62-3.55 (m, 1H), 3.46-3.39 (m,
2H), 2.51 (dd, J ) 3.0, 16.0 Hz, 1H), 2.10-2.02 (m, 2H), 1.99-
1.86 (m, 3H), 1.81-1.77 (m, 1H), 1.41 (dq, J ) 7.0, 11.5 Hz, 1H),
1.07-0.98 (m, 4H), 1.02 (d, J ) 6.5 Hz, 3H); 13C NMR (125 M
Hz, CDCl3) δ 169.0 (s), 59.0 (d), 44.6 (t), 39.7 (t), 37.6 (t), 33.3
(t), 28.5 (d), 22.2 (t), 21.6 (q). Mass (EI, 70 eV): 153 (M+, 65%),
83 (100%). HRMS calcd for C9H15NO (M+): 153.1154. Found:
153.1157.
Ack n ow led gm en t. Financial support from the Na-
tional Science Council of the Republic of China is
gratefully acknowledged. The authors would also like
to thank Professor Michael Yen-Nan Chiang (National
Sun Yat-Sen University) for X-ray analysis and Profes-
sor Udo Nubbemeyer (Freie University) for sending
spectra data of compound 10 to us for comparison.
Su p p or tin g In for m a tion Ava ila ble: Characterization
data for compounds 1d -h and 3a -i. This information is
available free of charge via the Internet at http://pubs.acs.org.
J O025539P
J . Org. Chem, Vol. 67, No. 14, 2002 5047