O-(2-oxopyrrolidin-5-yl)trichloroacetimidates as amidoalkylating agents - Synthesis of (+)-lentiginosine

Article abstract of DOI:10.1002/1099-0690(200212)2002:24<4137::AID-EJOC4137>3.0.CO;2-X

N-α-Hydroxyalkylamides 6a,b, readily available from L-tartrate, with trichloroacetonitrile furnish O-(2-oxopyrrolidin-5-yl)trichloroacetimidates 3a,b. α-Amido-alkylation studies of 3a,b with allyl-trimethylsilane and electron-rich benzene derivatives as C-nucleophiles afforded 5-allyl- and 5-aryl-2-pyrrolidinones 2a,b, 7a,b, and 8-10. The target compound (+)-1 and its epimer 15 were readily obtained from 1,5-diallyl-2-pyrrolidinones 2b and 7b, respectively, via ring-closing metathesis, amide group reduction, and CC-double bond hydrogenation. Wiley-VCH Verlag GmbH & Co KGaA, 69451 Weinheim, Germany, 2002.

Full text of DOI:10.1002/1099-0690(200212)2002:24<4137::AID-EJOC4137>3.0.CO;2-X

FULL PAPER
O-(2-Oxopyrrolidin-5-yl)trichloroacetimidates as Amidoalkylating Agents ؊
Synthesis of (؉)-Lentiginosine
Ahmed O. H. El-Nezhawy,[a] Hoda I. El-Diwani,[b] and Richard R. Schmidt*[a]
Keywords: Amidoalkylation / Trichloroacetimidate / Synthesis / Indolizidines / Glycosidase Inhibitor / Lentiginosine
N-α-Hydroxyalkylamides 6a,b, readily available from
L-tart-
(+)-1 and its epimer 15 were readily obtained from 1,5-dial-
rate, with trichloroacetonitrile furnish O-(2-oxopyrrolidin-5- lyl-2-pyrrolidinones 2b and 7b, respectively, via ring-closing
yl)trichloroacetimidates 3a,b. α-Amido-alkylation studies of
3a,b with allyl-trimethylsilane and electron-rich benzene de-
rivatives as C-nucleophiles afforded 5-allyl- and 5-aryl-2-
pyrrolidinones 2a,b, 7a,b, and 8−10. The target compound
metathesis, amide group reduction, and CC-double bond hy-
drogenation.
( Wiley-VCH Verlag GmbH & Co KGaA, 69451 Weinheim,
Germany, 2002)
Introduction
The N-acyl-N-α-hydroxyalkyl systems, out of the various
possibilities for extension of this reaction principle, seemed
to be of considerable interest for various reasons: (i) struc-
turally different starting materials are readily available, (ii)
they can be conveniently transformed into the required
trichloroacetimidates; (iii) activation of these O,N-acetal de-
rivatives in order to perform α-amidoalkylations[10,11] can
be carried out under mild conditions with catalytic amounts
of acid, and (iv) thus, also access to sensitive target molec-
ules is permitted. α-Amidoalkylation has been extensively
investigated[10] and the intermediates thereof have been em-
ployed in polar cycloadditions.[11]
After a specific application of this reaction principle to
the synthesis of C-glycosides of glucosidase inhibitor nojiri-
mycin,[12] we would like to demonstrate the general use-
fulness of this concept in the synthesis of the indolizidine
ring system (Scheme 2, A). Quinolizidine (Scheme 2, B) and
pyrrolizidine (Scheme 2, C) skeleton based compounds
should be equally accessible. The target compound in this
paper is (ϩ)-lentiginosine [Scheme 3, (ϩ)-1] which is also an
efficient glucosidase inhibitor.[13] Different synthetic routes
towards 1 have been reported previously.[14Ϫ19] The retro-
synthesis in Scheme 3 exhibits that 1,5-diallylpyrrolidinone
intermediate 2 which should be readily available from O-
(2-oxopyrrolidin-5-yl)trichloroacetimidate will provide this
compound in an efficient manner. The designed ring-clos-
The transformation of O,O- and N,O-halfacetals into
trichloroacetimidoyl derivatives and their acid-catalyzed ac-
tivation has proven to be a highly attractive and powerful
alternative to the classical glycosylation methods. It is cur-
rently one of the most frequently applied strategies for gly-
coside bond formation (Scheme 1, Y ϭ OR, NR1R2).[1Ϫ5]
Other systems supporting carbonium ion generation such
as benzyl, allyl, oxyallyl, cyclopropylmethyl (i.e., Y ϭ ϪAr,
ϪCHϭCH2, ϪCHϭCHϪOR, cyclopropyl, etc.) can also
be transformed into the corresponding trichloroacetimidate
(TCAI) and then employed in these valuable acid-catalyzed
alkylation reactions.[6Ϫ9]
Scheme 1. Acid-catalyzed alkylation of nucleophiles with O-alkyl
trichloroacetimedate derivatives
[a]
Fachbereich Chemie, Universität Konstanz, Fach M 725,
78457 Konstanz, Germany
Fax: (internat.) ϩ 49-(0)7531/883135
E-mail: Richard.Schmidt@uni-konstanz.de
[b]
Chemistry of Natural and Microbial Products Department,
NRC, Dokki,
Cairo, Egypt
Scheme 2. Important nitrogen-fused bicyclic systems
Eur. J. Org. Chem. 2002, 4137Ϫ4142  2002 WILEY-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim 1434Ϫ193X/02/1224Ϫ4137 $ 20.00ϩ.50/0
4137

A. O. H. El-Nezhawy, H. I. El-Diwani, R. R. Schmidt
FULL PAPER
ing metathesis to attach a cyclohexene ring to the pyrrolidi- 5a[22] and 5b, respectively. Reduction with sodium borohyd-
none ring has been already successfully probed.[19Ϫ21]
ride in methanol afforded 5-hydroxypyrrolidinone derivat-
ives 6a,b. Treatment with trichloroacetonitrile in the pres-
ence of 1,8-diazabicylo[5.4.0]undec-7-ene (DBU) as base
furnished trichloroacetimidates 3a,b in high yields. Only
one diastereoisomer was obtained, which based on the J4,5
-
coupling constant of 2.4 Hz seems to be the (5S)-isomer, as
will be shown below.
Trichloroacetimidates 3a,b were employed for the α-ami-
doalkylation studies with different C-nucleophiles. Reaction
of trichloroacetimidate 3a with allyl-trimethylsilane as C-
nucleophile in the presence of trimethylsilyl trifluorome-
thanesulfonate (TMSOTf) as catalyst afforded a 1:2 ratio of
5-C-allyl derivatives 2a and 7a (Scheme 5). Similarly, from
3b the desired 1,5-diallyl-2-pyrrolidinones 2b and 7b were
obtained in a 1:1 ratio in almost quantitative yield (96%).
Separation of the diastereomers 2a/7a and 2b/7b was readily
accomplished by silica gel chromatography. The structural
Scheme 3. Structure of (ϩ)-Lentiginosine (1); retrosynthesis with 2
and 3 as intermediates
Results and Discussion
Cheap -tartrate was transformed into anhydride 4
(Scheme 4) and then with methyl and allylamine into imides
1
assignment was based on the H NMR spectroscopic data
of the ring protons (J4,5 ഠ 8 Hz for 2a,b and J4,5 ഠ 5 Hz
for 7a,b, see Table 1) and the final transformation of 2b into
known target compound (ϩ)-1 and 7b into its epimer.
Scheme 5. Allylation of 3a,b with allyltrimethylsilane
Reaction of trichloroacetimidate 3a with electron-rich
phenyl ethers as potential C-nucleophiles led to 5-aryl-2-
pyrrolidinones 8؊10 (Scheme 6). Even with 3,5-dimethox-
ybenzyl alcohol as nucleophile C-amidoalkylation, presum-
ably via O-amidoalkylation,[23] was observed. In all cases
Scheme 4. Synthesis of O-(2-oxopyrrolidin-5-yl)trichloroacetimid-
ates 3a,b
1
Table 1. H NMR spectroscopic data of compounds 2a,b, 7a,b, 8؊15, and (ϩ)-1
No.
3-H
4-H
5-H
2a
2b
7a
7b
8
5.58 (d, J ϭ 8.0 Hz, 1 H)
5.61 (d, J ϭ 8.1 Hz, 1 H)
5.36 (d, J ϭ 5.0 Hz, 1 H)
5.38 (d, J ϭ 5.0 Hz, 1 H)
5.48 (d, J ϭ 5.0 Hz, 1 H)
5.49 (d, J ϭ 5.0 Hz, 1 H)
5.58 (d, J ϭ 4.6 Hz, 1 H)
5.40 (dd, J ϭ 8.0, 8.0 Hz, 1 H)
5.37 (dd, J ϭ 8.0, 8.1 Hz, 1 H)
5.13 (dd, J ϭ 5.0, 5.0 Hz, 1 H)
5.14 (dd, J ϭ 5.0, 5.0 Hz, 1 H)
5.40 (dd, J ϭ 5.0, 4.9 Hz, 1 H)
5.42 (dd, J ϭ 5.0, 5.0 Hz, 1 H)
5.45 (dd, J ϭ 4.6, 4.6 Hz, 1 H)
3.91 (ddd, J ϭ 4.0, 8.0, 10.1 Hz, 1 H)
3.99 (ddd, J ϭ 4.4, 8.0, 9.8 Hz, 1 H)
3.52 (ddd, J ϭ 3.7, 5.0, 8.2 Hz, 1 H)
3.60 (ddd, J ϭ 3.4, 5.0, 8.5 Hz, 1 H)
4.69 (d, J ϭ 5.0 Hz, 1 H)
4.62 (d, J ϭ 5.0 Hz, 1 H)
4.82 (d, J ϭ 4.6 Hz, 1 H)
9
10
2-H
1-H
8a-H
11
5.48 (d, J ϭ 7.3 Hz, 1 H)
5.45 (d, J ϭ 5.0 Hz, 1 H)
4.03 (ddd, J ϭ 1.8, 3.9, 7.4 Hz, 1 H)
4.02 (ddd, J ϭ 1.5, 6.8, 8.2 Hz, 1 H)
4.03 (ddd, J ϭ 1.8, 4.0, 7.4 Hz, 1 H)
3.97 (dd, J ϭ 6.8, 6.9 Hz, 1 H)
5.45 (dd, J ϭ 7.3, 6.6 Hz, 1 H)
5.07 (dd, J ϭ 5.0, 5.0 Hz, 1 H)
3.61 (dd, J ϭ 4.0, 8.1 Hz, 1 H)
3.91 (dd, J ϭ 1.5, 5.3 Hz, 1 H)
3.61 (dd, J ϭ 4.0, 8.8 Hz, 1 H)
3.83 (d, J ϭ 5.0 Hz, 1 H)
4.02 (ddd, J ϭ 4.4, 7.3, 11.4 Hz, 1 H)
3.50 (dt, J ϭ 5.0, 4.5 Hz, 1 H)
2.19 (dt, J ϭ 1.9, 4.0 Hz, 1 H)
2.48 (dt, J ϭ 4.7, 5.3 Hz, 1 H)
1.85, m, 1 H)
12
13
14
(ϩ)-1
15
2.12, m, 1 H)
4138
Eur. J. Org. Chem. 2002, 4137Ϫ4142

O-(2-Oxopyrrolidin-5-yl)trichloroacetimidates as Amidoalkylating Agents
FULL PAPER
only one stereoisomer was obtained in good yield. Because it is rather the 3-O-acetyl group that provides anchimeric
of the J4,5-coupling constant of ca. 5 Hz (see Table 1) (S)- assistance (see D϶ in Scheme 6), which leads to products
configuration was assigned at C-5. This result is unexpec- 8؊10.
ted, since neighboring group participation of the 4-O-acetyl
Transformation of 2b into the target molecule (ϩ)-1
group in the stereocontrol does not seem to be effective; but could be performed as indicated in Scheme 7. Ring-closing
metathesis of 2b with the Grubbs catalyst[24,25] afforded in-
dolizinone derivative 11 in 78% yield. Similarly, from 7b
epimeric indolizinone 12 was obtained. Treatment of 11 and
12 with lithium aluminium hydride in THF led to the reduc-
tion of the amide group to the corresponding amine and to
concomitant removal of the O-acetyl groups, thus affording
1,2-dihydroxyindolizines 13 and 14, respectively. The CC-
double bond in 13 and 14 was hydrogenated under standard
conditions, furnishing target compound (ϩ)-1 and its epi-
meric indolizidine derivative 15 in good overall yields. The
physical data of these compounds (m.p., [α]D, and NMR)
are in agreement with those reported in the literature [(ϩ)-
1,[14] 15[26]].
Conclusion
Readily available trichloroacetimidates 3 are excellent
precursors for α-amidoalkylation reactions, for instance, of
various C-nucleophiles. As the corresponding O-glycosyl
trichloroacetimidates, these precursors require only cata-
lytic amounts of acid for activation. This concept can be
employed in the synthesis of nitrogen fused bicyclic systems.
This is exhibited in efficient syntheses of indolizidine deriv-
Scheme 6. Arylation of 3b with electron-rich aromatic compounds
atives (ϩ)-1 and 15.
Experimental Section
General Remarks: All air-sensitive and/or water-sensitive reactions
were carried out under argon with dry solvents under anhydrous
conditions. Reactions were monitored by TLC carried out on
Merck silica gel-coated plastic sheets (60 F254) by using UV light
as visualizing agent and 5% (NH4)2MoO4, 0.1% Ce(SO4)2 in 10%
H2SO4 and heat as developing agents. Baker silica gel (particle size
0.040Ϫ0.063 mm) was used for flash chromatography. NMR spec-
tra were recorded with Bruker DRX 600 (600 MHz) and AC 250
(250 MHz) instruments and calibrated using tetramethylsilane as
internal standard. Optical rotations were recorded with
a
PerkinϪElmer 241 MC polarimeter in a 1-dm cell at 22 °C. FAB
mass spectra were recorded with a Finnigan MAT 312/AMD 5000
spectrometer with 3-nitrobenzyl alcohol matrix. EI mass spectra
were recorded on a Finnigan MAT 312.
(3R,4R)-4-(Acetyloxy)-1-methyl-2,5-dioxopyrrolidin-3-yl
Acetate
(5a):[22] A mixture of -tartaric acid (26.64 g, 177.6 mmol) and
acetyl chloride (90 mL, 1.27 mol) was stirred under reflux for 30 h
during which the solution became homogeneous. Excess acetyl
chloride was removed by distillation at 1 atm, and trace amounts
were removed under vacuum. The crude anhydride 4 was dissolved
in THF (120 mL) and methylamine (14.5 mL, 470 mmol) was
slowly added. After the solution was stirred for 2 h, it was concen-
trated in vacuo and the residue was refluxed with acetyl chloride
(90 mL, 1.27 mol) for another 5 h. After concentration of the reac-
tion mixture in vacuo, the residue was purified by using column
chromatography (petroleum ether/ethyl acetate, 1:1) to give 5a
(yield 24.89 g, 88%) as a pale yellow oil. [α]D ϭ ϩ53.4 (c ϭ 4,
Scheme 7. Synthesis of target molecule (ϩ)-1 and its epimer 15
Eur. J. Org. Chem. 2002, 4137Ϫ4142
4139

A. O. H. El-Nezhawy, H. I. El-Diwani, R. R. Schmidt
FULL PAPER
1
MeOH). H NMR (CDCl3, 250 MHz): δ ϭ 2.06 (s, 6 H, Ac), 2.94 62.8 MHz): δ ϭ 20.4, 20.5, 26.9, 74.1, 78.6, 85.1, 162.2, 167.9,
(s, 3 H, NCH3), 5.42 (s, 2 H, CHOAc) ppm. 13C NMR (CDCl3,
62.8 MHz): δ ϭ 19.9, 24.9, 72.4, 169.4, 169.7 ppm. EI-FAB: m/z
(%) ϭ 229 (10) [Mϩ], 187 (69), 169 (100), 145 (62), 127 (60), 116
(25), 102 (90). C9H11NO6 (229.2): calcd. C 47.16, H 4.83, N 6.11;
found C 47.20, H 4.90, N 6.12.
170.1, 170.3 ppm.
Trichloroacetimidate 3b: Preparation was performed as described
for 3a from 6b furnishing 3b as a pale yellow oil (yield 1.49 g, 75%).
[α]D ϭ ϩ72 (c ϭ 1.8, MeOH). H NMR (CDCl3, 250 MHz): δ ϭ
1
2.08 (s, 3 H, Ac.), 2.09 (s, 3 H, Ac.), 3.67 (dd, J ϭ 7.4, 15.3 Hz, 1
H, NCH2CHϭCH2), 4.30 (m, 1 H, NCH2CHϭCH2), 5.27 (m, 4
H, 3-H, 4-H, NCH2CHϭCH2), 5.68 (m, 1 H, NCH2CHϭCH2),
6.13 (d, J ϭ 2.4 Hz, 1 H, 5-H), 8.57 (br.s, 1 H, NH) ppm. 13C
NMR (CDCl3, 62.8 MHz): δ ϭ 21.0, 21.2, 44.0, 73.6, 75.3, 89.0,
120.2, 131.2, 161.2, 168.6, 169.6, 169.9 ppm. EI-FAB: m/z (%) ϭ
401 (10) [Mϩ], 342 (12), 257 (15), 240 (17), 197 (30), 155 (55), 138
(100), 117 (60).
(3R,4R)-4-(Acetyloxy)-1-allyl-2,5-dioxopyrrolidin-3-yl Acetate (5b):
Allylamine (0.34 mL, 4.6 mmol) in acetic acid (30 mL) was added
to a solution of anhydride 4 (0.99 g, 4.6 mmol). The mixture was
stirred under reflux for 3 h. The residue after solvent evaporation
was subjected to flash chromatography (petroleum ether/ethyl acet-
ate, 20:1) to give 5b (yield 1.0 g, 87%) as a pale yellow solid m.p.
53Ϫ54 °C [α]D ϭ ϩ98.3 (c ϭ 1.7, MeOH). 1H NMR (CDCl3,
250 MHz): δ ϭ 2.14 (s, 3 H, Ac.), 2.17 (s, 3 H, Ac.), 4.16 (dd, J ϭ
5.8, 9.3 Hz, 2 H, N-CH2), 5.24 (m, 2 H, NCH2CHϭCH2), 5.50 (s,
2 H, CHOAc), 5.80 (m, 1 H, NCH2CHϭCH2) ppm. 13C NMR
(CDCl3, 62.8 MHz): δ ϭ 20.3, 41.4, 72.7, 119.1, 129.4, 168.8, 169.8
ppm. EI-FAB: m/z (%) ϭ 255.2 (15) [Mϩ], 153 (37), 136 (45), 102
(57), 69 (80), 60 (100). C11H13NO6 (255.2): calcd. C 51.76, H 5.13,
N 5.49; found C 51.65, H 5.11, N 5.50.
General Procedure for the Reaction of Trichloroacetimidates with
Nucleophiles:
A solution of trichloroacetimidate 3a or 3b
(1.4 mmol) and the nucleophiles allyltrimethylsilane, anisol, di-
methylresorcin, and 3,5-dimethoxybenzyl alcohol (1.4 mmol), re-
spectively, in dry dichloromethane (15 mL) was treated with
TMSOTf (0.15 mL) and then stirred for 30Ϫ120 min. The reaction
was quenched by addition of solid sodium bicarbonate, diluted
with dichloromethane, filtered, and concentrated. The crude res-
idue was purified by column chromatography on silica gel go give
2a,b, 7a,b, 8, 9, and 10, respectively.
(3R,4R)-4-(Acetyloxy)-5-hydroxy-1-methyl-2-oxopyrrolidin-3-yl
Acetate (6a): Sodium borohydride (875 mg, 23.1 mmol) was added
in one portion to a stirred solution of 5a (4.57 mmol) in methanol
(125 mL), cooled to Ϫ7 °C in an ice-salt bath, and the resulting
solution was stirred for 12 min. The reaction mixture was parti-
tioned between 200 mL of CH2Cl2, 100 mL of saturated aqueous
sodium bicarbonate and water (50 mL). The layers were separated
and the aqueous phase was extracted with three 150 mL portions
of CH2Cl2. The combined organic phases were dried (MgSO4) and
concentrated in vacuo to give 6a as a white solid (yield 0.98 g,
89%), m.p. 75 °C, which was isolated by column chromatography
on silica gel (petroleum ether/ethyl acetate, 2:1). [α]D ϭ Ϫ25.4 (c ϭ
(3R,4S,5S)-4-(Acetyloxy)-5-allyl-1-methyl-2-oxopyrrolidin-3-yl
Acetate (2a) and (3R,4S,5R)-4-(Acetyloxy)-5-allyl-1-methyl-2-oxop-
yrrolidin-3-yl Acetate (7a): Reaction of 3a with allyltrimethylsilane
afforded 2a and 7a.
2a: Column chromatography on silica gel (petroleum ether/ethyl
acetate, 2:1) afforded 2a as a colorless oil (yield 114 mg, 32%).
[α]D ϭ ϩ82.7 (c ϭ 0.7, MeOH). 1H NMR (CDCl3, 600 MHz): δ ϭ
2.11 (s, 3 H, Ac.), 2.16 (s, 3 H, Ac.), 2.27 (dt, J ϭ 4.9, 5.6 Hz, 1
H, CH2CHϭCH2), 2.40 (dt, J ϭ 6.6, 6.7 Hz, 1 H, CH2CHϭCH2),
2.87 (s, 3 H, NCH3), 3.91 (ddd, J ϭ 4.0, 8.0, 10.1 Hz, 1 H, 5.H),
5.16 (dd, J ϭ 0.9, 8.7 Hz, 2 H, CH2CHϭCH2), 5.40 (dd, J ϭ 8.0,
8.0 Hz, 1 H, 4-H), 5.58 (d, J ϭ 8.0 Hz, 1 H, 3-H), 5.72 (m, 1 H,
CH2CHϭCH2) ppm. 13C NMR (CDCl3, 150.9 MHz): δ ϭ 20.7,
28.8, 32.5, 58.5, 72.4, 73.2, 119.9, 132.3, 166.7, 169.9, 170.3 ppm.
EI-FAB: m/z (%) ϭ 214 (30) [Mϩ Ϫ allyl], 154 (40), 112 (100).
C12H17NO5 (255.3): calcd. C 56.46, H 6.71, N 5.49; found C 56.60,
H 6.54, N 5.70.
1
1.6, MeOH). H NMR (CDCl3, 250 MHz): δ ϭ 2.05 (s, 3 H, Ac.),
2.06 (s, 3 H, Ac.), 2.83 (s, 3 H, NCH3), 4.90 (br.s, 1 H, OH), 5.01
(d, J ϭ 2.9 Hz, 1 H, CHOAc), 5.04Ϫ5.15 (m, 2 H, CHOAc and
NCHO) ppm. 13C NMR (CDCl3, 62.8 MHz): δ ϭ 20.3, 20.5, 26.5,
73.8, 78.7, 84.9, 167.0, 170.1, 170.2 ppm. EI-FAB: m/z (%) ϭ 231
(5) [Mϩ], 171 (65), 129 (100), 112 (30), 102 (80), 71 (32), 60 (86).
C9H13NO6 (231.2): calcd. C 46.75, H 5.67, N 6.05; found C 46.51,
H 5.56, N 6.00.
(3R,4R)-4-(Acetyloxy)-1-allyl-5-hydroxy-2-oxopyrrolidin-3-yl Acet-
ate (6b): Preparation was performed as described for 6a furnishing
a pale yellow oil which was chromatographed on silica gel (petro-
leum ether/ethyl acetate, 2:1) to give 6b (yield 1.169 g, 89%). [α]D ϭ
7a: Column chromatography on silica gel (petroleum ether/ethyl
acetate, 2:1) afforded 7a as a colorless oil (yield 67 mg, 16%).
[α]D ϭ ϩ38.7 (c ϭ 1.6, MeOH). 1H NMR (CDCl3, 600 MHz): δ ϭ
2.07 (s, 3 H, Ac.), 2.13 (s, 3 H, Ac.), 2.40 (dt, J ϭ 6.7, 7.6 Hz, 1
H, CH2CHϭCH2), 2.52 (m, 1 H, CH2CHϭCH2), 2.87 (s, 3 H,
NCH3), 3.52 (ddd, J ϭ 3.7, 5.0, 8.2 Hz, 1 H, 5-H), 5.13 (dd, J ϭ
5.0, 5.0 Hz, 1 H, 4-H), 5.19 (m, 2 H, CH2CHϭCH2), 5.36 (d, J ϭ
5.0 Hz, 1 H, 3-H), 5.67 (m, 1 H, CH2CHϭCH2) ppm. 13C NMR
(CDCl3, 150.9 MHz): δ ϭ 20.6, 20.7, 28.9, 34.8, 60.9, 74.3, 119.9,
120.0, 130.9, 167.5, 170.0 ppm. EI-FAB: m/z (%) ϭ 214 (30) [Mϩ
Ϫ allyl], 154 (38), 112 (100). C12H17NO5 (255.3): calcd. C 56.46, H
6.71, N 5.49; found C 56.68, H 6.45, N 5.80.
1
ϩ8.1 (c ϭ 1.5, MeOH). H NMR (CDCl3, 250 MHz): δ ϭ 2.12 (s,
3 H, Ac.), 2.14 (s, 3 H, Ac.), 3.60 (dd, J ϭ 7.3, 15.2 Hz, 1 H,
NCH2CHϭCH2), 4.10 (m, 1 H, NCH2CHϭCH2), 4.90Ϫ5.30 (m,
6H), 5.70 (m, 1 H, NCH2CHϭCH2) ppm. 13C NMR (CDCl3,
62.8 MHz): δ ϭ 21.2, 21.3, 42.7, 74.9, 79.6, 84.2, 119.5, 131.7,
167.4, 171.0, 171.2 ppm. EI-FAB: m/z (%) ϭ 257 (15) [Mϩ], 197
(35), 155 (70), 138 (30), 86 (40), 94 (100). C11H15NO6 (257.2): calcd.
C 51.36, H 5.88, N 5.44; found C 51.30, H 5.56, N 4.99.
Trichloroacetimidate 3a: A stirred solution of 6a (1.28 g, 5 mmol)
in dry CH2Cl2 (15 mL) and trichloroacetonitrile (5 mL, 50 mmol)
was treated with DBU (71 µL) at 0 °C and then left for 10 min.
The solvent was evaporated and the product purified by column
chromatography (5% triethylamine in toluene) to give 3a as a pale
(3R,4S,5S)-4-(Acetyloxy)-1,5-(diallyl)-2-oxopyrrolidin-3-yl Acetate
(2b) and (3R,4S,5R)-4-(Acetyloxy)-1,5-(diallyl)-2-oxopyrrolidin-3-yl
Acetate (7b): Reaction of 3b with allyltrimethylsilane afforded 2b
and 7b.
1
yellow oil (yield 1.48 g, 72%). [α]D ϭ ϩ50.9 (c ϭ 1.8, MeOH). H
NMR (CDCl3, 250 MHz): δ ϭ 2.01 (s, 3 H, Ac.), 2.03 (s, 3 H, Ac.), 2b: Column chromatography on silica gel (petroleum ether/ethyl
2.91 (s, 3 H, NCH3), 5.30 (m, 2 H, 3-H, 4-H), 6.19 (d, J ϭ 2.4 Hz, acetate, 1:1) afforded 2b as a colorless oil (yield 0.17 g, 48%) [α]D ϭ
1 H, 5-H), 8.60 (br.s, 1 H, NH) ppm. 13C NMR (CDCl3, ϩ69.8 (c ϭ 0.5, MeOH). H NMR (CDCl3, 600 MHz): δ ϭ 2.11
1
4140
Eur. J. Org. Chem. 2002, 4137Ϫ4142

O-(2-Oxopyrrolidin-5-yl)trichloroacetimidates as Amidoalkylating Agents
FULL PAPER
(s, 3 H, Ac.), 2.15 (s, 3 H, Ac.), 2.25 (dd, J ϭ 5.2, 14.7 Hz, 1 H,
CHCH2CHϭCH2), 2.40 (dd, J ϭ 7.8, 14.0 Hz, 1 H, CHCH2CHϭ
CH2), 3.49 (dd, J ϭ 7.7, 15.2 Hz, 1 H, NCH2CHϭCH2), 3.99 (ddd,
Ph-H), 6.43 (d, J ϭ 2.4 Hz, 1 H, Ph-H) ppm. 13C NMR (CDCl3,
62.8 MHz): δ ϭ 20.6, 20.7, 27.4, 55.3, 55.4, 60.4, 63.3, 74.8, 75.0,
98.4, 106.0, 114.1, 142.0, 159.7, 160.9, 168.1, 170.0, 170.4 ppm. EI-
J ϭ 4.4, 8.0, 9.8 Hz, 1 H, 5-H), 4.42 (dd, J ϭ 4.6, 15.2 Hz, 1 H, FAB: m/z (%) ϭ 351 (10) [Mϩ Ϫ CHO], 291 (35), 249 (100), 232
NCH2CHϭCH2), 5.15Ϫ5.25 (m,
4
H, CHCH2CHϭCH2, (30), 180 (45), 149 (35), 91 (20), 77 (25). C18H23NO8 (381.4): calcd.
NCH2CHϭCH2), 5.37 (dd, J ϭ 8.0, 8.1 Hz, 1 H, 4-H), 5.61 (d,
J ϭ 8.1 Hz, 1 H, 3-H) 5.69 (m, 2 H, CHCH2CHϭCH2, NCH2CHϭ
CH2) ppm. 13C NMR (CDCl3, 150.9 MHz): δ ϭ 20.7, 32.4, 43.9,
55.3, 72.7, 73.2, 119.4, 119.9, 131.2, 132.4, 166.4, 169.9, 170.3 ppm.
EI-FAB: m/z (%) ϭ 281 (10) [Mϩ], 240 (35), 181 (48), 138 (100),
55 (20). C14H19NO5 (281.3): calcd. C 59.78, H 6.81, N 4.98; found
C 60.03, H 6.96, N 4.55.
C 56.68, H 6.08, N 3.67; found C 56.69, H 6.51, N 3.92.
General Procedure for Olefin Metathesis
Synthesis of Dehydroindolizinones 11 and 12: A solution of
{bis(tricyclohexylphosphane)benzylidene}ruthenium(IV)
dichloride (Grubbs’) catalyst (0.003 g, 0.004 mmol) in CH2Cl2
(5 mL) was added to a solution of 2b or 7b (281 mg, 1 mmol) in
CH2Cl2 (10 mL), under an argon atmosphere. The mixture was re-
fluxed for 12 h. The solvent was removed under reduced pressure
and the oily residue was purified by column chromatography on
silica gel (petroleum ether/ethyl acetate, 5:1) to give dehydroindoliz-
inones 11 or 12, respectively.
7b: Column chromatography on silica gel (petroleum ether/ethyl
acetate, 1:1) afforded 7b as a colorless oil (yield 170 mg, 48%).
[α]D ϭ ϩ177 (c ϭ 1.0, MeOH). 1H NMR (CDCl3, 600 MHz): δ ϭ
2.07 (s, 3 H, Ac.), 2.13 (s, 3 H, Ac.), 2.37 (dd, J ϭ 7.2, 14.3 Hz, 1 H,
CHCH2CHϭCH2), 2.51 (m, 1 H, CHCH2CHϭCH2), 3.51 (dd, J ϭ
7.5, 15.5 Hz, 1 H, NCH2CHϭCH2), 3.60 (ddd, J ϭ 3.4, 5.0, 8.5 Hz,
1 H, 5-H), 4.42 (dd, J ϭ 4.5, 15.5 Hz, 1 H, NCH2CHϭCH2), 5.14
(dd, J ϭ 5.0, 5.0 Hz, 1 H, 4-H), 5.18Ϫ5.23 (m, 4 H, CHCH2CHϭ
CH2, NCH2CHϭCH2), 5.38 (d, J ϭ 5.0 Hz, 1 H, 3-H), 5.67 (m,
2 H, CHCH2CHϭCH2, NCH2CHϭCH2) ppm. 13C NMR (CDCl3,
150.9 MHz): δ ϭ 20.7, 20.8, 34.8, 43.1, 58.6, 74.4, 118.9, 119.9,
131.1, 131.4, 167.3, 169.9 ppm. EI-FAB: m/z (%) ϭ 281 (10) [Mϩ],
240 (32), 181 (50), 138 (100), 55 (20). C14H19NO5 (281.3): calcd. C
59.78, H 6.81, N 4.98; found C 59.38, H 6.78, N 4.78.
(1S,2R,8aS)-1,2-Diacetyloxy-1,2,3,5,8,8a-hexahydro-3-indolizinone
(11): Colorless oil (196 mg, 78%). [α]D ϭ ϩ26.2 (c ϭ 0.9, MeOH).
1H NMR (CDCl3, 600 MHz): δ ϭ 2.05 (m, 1 H, 8-H), 2.15 (s, 3 H,
Ac.), 2.17 (s, 3 H, Ac.), 2.22 (m, 1 H, 8-H), 3.61 (br d, J ϭ 18.4 Hz,
1 H, 5-H), 4.02 (ddd, J ϭ 4.4, 7.3, 11.4 Hz, 1 H, 8a-H), 4.39 (dd,
J ϭ 2.4, 18.8 Hz, 1 H, 5-H), 5.45 (dd, J ϭ 7.3, 6.6 Hz, 1 H, 1-H),
5.48 (d, J ϭ 7.3 Hz, 1 H, 2-H), 5.71 (dd, J ϭ 3.0, 10.3 Hz, 1 H, 6-
H), 5.83 (m, 1 H, 7-H) ppm. 13C NMR (CDCl3, 150.9 MHz): δ ϭ
20.7, 30.4, 40.6, 65.6, 74.8, 78.1, 122.6, 123.8, 166.4, 169.9, 170.3
ppm.
(3R,4S)-4-(Acetyloxy)-5-(4-methoxyphenyl)-1-methyl-2-oxo-
pyrrolidin-3-yl Acetate (8): Column chromatography on silica gel
(petroleum ether/ethyl acetate, 1:1) afforded 8 as a colorless oil
(310 mg, 68%). [α]D ϭ Ϫ21.68 (c ϭ 1.9, MeOH). 1H NMR (CDCl3,
250 MHz): δ ϭ 2.02 (s, 3 H, Ac.), 2.10 (s, 3 H, Ac.), 2.61 (s, 3 H,
NCH3), 3.79 (s, 6 H, OCH3), 4.69 (d, J ϭ 5.0 Hz, 1 H, 5-H), 5.40
(dd, J ϭ 5.0, 4.9 Hz, 1 H, 4-H), 5.48 (d, J ϭ 5.0, 1 H, 3-H),
6.90Ϫ7.30 (m, 4 H, Ph-H) ppm. 13C NMR (CDCl3, 62.8 MHz):
δ ϭ 20.6, 27.9, 55.3, 62.2, 74.6, 76.5, 111.0, 114.4, 120.8, 123.6,
128.8, 130.2, 157.6, 167.8, 169.6, 169.8 ppm. EI-FAB: m/z (%) ϭ
321 (20) [Mϩ], 261 (55), 219 (100), 202 (20), 150 (40), 91 (20).
C16H19NO6 (321.3): calcd. C 59.81, H 5.96, N 4.35; found C 59.89,
H 6.29, N 4.33.
(1S,2R,8aR)-1,2-Diacetyloxy-1,2,3,5,8,8a-hexahydro-3-indolizinone
(12): Colorless oil (196 mg, 78%). [α]D ϭ ϩ17 (c ϭ 1, MeOH). H
1
NMR (CDCl3, 600 MHz): δ ϭ 2.13 (s, 3 H, Ac.), 2.15 (s, 3 H, Ac.),
2.20 (m, 1 H, 8-H), 2.55 (br d, J ϭ 16.8 Hz, 1 H, 8-H), 3.50 (dt,
J ϭ 5.0, 4.5 Hz, 1 H, 8a-H), 3.64 (br d, J ϭ 18.7 Hz, 1 H, 5-H),
4.34 (dd, J ϭ 2.4, 18.8 Hz, 1 H, 5-H), 5.07 (dd, J ϭ 5.0, 5.0 Hz,
1 H, 1-H), 5.45 (d, J ϭ 5.0 Hz, 1 H, 2-H), 5.72 (dd, J ϭ 2.6,
10.3 Hz, 1 H, 7-H), 5.82 (t, J ϭ 7.9 Hz, 1 H, 6-H) ppm. 13C NMR
(CDCl3, 150.9 MHz): δ ϭ 20.7, 20.9, 25.4, 40.9, 52.7, 73.1, 74.1,
123.8, 123.9, 167.3, 169.8 ppm. EI-FAB: m/z (%) ϭ 252 (40) [Mϩ
Ϫ 1], 211 (20), 193 (40), 151 (100), 134 (20), 82 (25). C12H15NO5
(253.2): calcd. C 56.91, H 5.97, N 5.53; found C 56.66, H 6.35,
N 5.23.
(3R,4S)-4-(Acetyloxy)-5-(2,4-dimethoxyphenyl)-1-methyl-2-oxo-
pyrrolidin-3-yl Acetate (9): Column chromatography on silica gel
(petroleum ether/ethyl acetate, 5:1) afforded 9 as a colorless oil
(yield 350 mg, 70%). [α]D ϭ Ϫ40.8 (c ϭ 1.0, MeOH). 1H NMR
(CDCl3, 250 MHz): δ ϭ 2.03 (s, 3 H, Ac.), 2.13 (s, 3 H, Ac.), 2.61
(s, 3 H, NCH3), 3.79 (s, 6 H, OCH3), 4.62 (d, J ϭ 5.0 Hz, 1 H, 5-
H), 5.42 (dd, J ϭ 5.0, 5.0 Hz, 1 H, 4-H), 5.49 (d, J ϭ 5.0, 1 H, 3-
H), 6.46 (m, 2 H, Ph-H), 7.04 (d, J ϭ 8.5 Hz, 1 H, Ph-H) ppm.
13C NMR (CDCl3, 62.8 MHz): δ ϭ 20.8, 28.0, 55.5, 55.6, 62.0,
74.9, 76.7, 99.1, 104.2, 104.9, 116.1, 130.1, 159.0, 162.0, 167.7,
169.9, 170.1 ppm. EI-FAB: m/z (%) ϭ 351 (7) [Mϩ], 291 (55), 249
(100), 232 (37), 180 (47), 149 (17). C17H21NO7 (351.3): calcd. C
58.11, H 6.02, N 3.99; found C 58.54, H 6.41, N 3.83.
(1S,2S,8aS)-(؊)-1,2-Dihydroxy-1,2,3,5,8,8a-hexahydroindolizine
(13): A solution of 11 (267 mg, 1.13 mmol) dissolved in THF
(10 mL) was added under argon to a suspension of LiAlH4 in THF
(0.088 g, 2.3 mmol in 5 mL) and heated at reflux for 4 h. Excess
hydride was destroyed at 0 °C with 10% aq. NH4Cl (0.3 mL), the
solid was filtered and washed with ethyl acetate (30 mL). The or-
ganic phase was dried (MgSO4) and after solvent evaporation, the
crude material was purified by column chromatography on silica
gel (CH2Cl2/MeOH, 10:1) to give 13 (yield 117 mg, 73%) as a white
1
solid, m.p. 92Ϫ93 °C. [α]D ϭ ϩ88.2 (c ϭ 2.4, MeOH). H NMR
(D2O, 600 MHz): δ ϭ 1.97 (m, 1 H, 8-H), 2.19 (dt, J ϭ 1.9, 4.0 Hz,
1 H, 8a-H), 2.26 (dd, J ϭ 4.2, 7.1 Hz, 1 H, 8-H), 2.60 (dd, J ϭ 7.5,
11.3 Hz, 1 H, 3-H), 2.71 (dt, J ϭ 2.2, 1.7 Hz, 1 H, 5-H), 2.88 (dd,
J ϭ 1.7, 11.3 Hz, 1 H, 3-H), 3.19 (ddt, J ϭ 2.2, 4.2, 2.2 Hz, 1 H,
5-H), 3.61 (dd, J ϭ 4.0, 8.1 Hz, 1 H, 1-H), 4.03 (ddd, J ϭ 1.8, 3.9,
7.4 Hz, 1 H, 2-H), 5.59 (dd, J ϭ 1.4, 10.1 Hz, 1 H, 6-H), 5.68 (m,
1 H, 7-H) ppm. 13C NMR (CDCl3, 150.9 MHz): δ ϭ 28.2, 51.3,
63.3, 74.9, 83.1, 123.8, 124.1 ppm. EI-FAB: m/z (%) ϭ 155 (40)
[Mϩ], 95 (100), 82 (35), 67 (65), 54 (45). C8H13NO2 (155.2): calcd.
C 61.91, H 8.44, N 9.02; found C 61.69, H 8.54, N 8.62.
(3R,4S)-4-(Acetyloxy)-5-(6-hydroxymethyl-2,4-dimethoxyphenyl)-1-
methyl-2-oxopyrrolidin-3-yl Acetate (10): Column chromatography
on silica gel (petroleum ether/ethyl acetate, 1:1) afforded 10 as a
colorless oil (yield 350 mg, 65%). [α]D ϭ Ϫ15.9 (c ϭ 2.2, MeOH).
1H NMR (CDCl3, 250 MHz): δ ϭ 1.97 (s, 3 H, Ac.), 2.10 (s, 3 H,
Ac.), 2.40 (br s, 1 H, OH), 2.48 (s, 3 H, NCH3), 3.72 (s, 3 H,
OCH3), 3.73 (s, 3 H, OCH3), 4.54 (2d, J ϭ 12.0 Hz, 2 H, CH2OH),
4.82 (d, J ϭ 4.6 Hz, 1 H, 5-H), 5.45 (dd, J ϭ 4.6, 4.6 Hz, 1 H, 4-
H), 5.58 (d, J ϭ 4.6 Hz, 1 H, 3-H), 6.36 (d, J ϭ 2.4 Hz, 1 H,
(1S,2S,8aR)-(؊)-1,2-Dihydroxy-1,2,3,5,8,8a-hexahydroindolizine
(14): Preparation was performed from 12 as described for 13 fur-
Eur. J. Org. Chem. 2002, 4137Ϫ4142
4141

A. O. H. El-Nezhawy, H. I. El-Diwani, R. R. Schmidt
FULL PAPER
nishing a white solid (yield 149 mg, 75%) m.p. 86Ϫ87 °C. [α]D
ϩ6.1 (c ϭ 1.3, MeOH). H NMR (D2O, 600 MHz): δ ϭ 1.94 (dd, and in structural assignments is gratefully acknowledged.
J ϭ 4.3, 7.4 Hz, 1 H, 8-H), 2.01 (dd, J ϭ 6.4, 10.5 Hz, 1 H, 3-H),
ϭ
program. The help of Mrs. A. Friemel in recording NMR spectra
1
2.16 (ddd, J ϭ 2.2, 4.5, 6.5 Hz, 1 H, 8-H), 2.48 (dt, J ϭ 4.7, 5.3 Hz,
1 H, 8a-H), 2.74 (dd, J ϭ 2.4, 16.2 Hz, 1 H, 5-H), 3.23 (tt, J ϭ 2.4,
[1]
R. R. Schmidt, Angew. Chem. 1986, 98, 213Ϫ236; Angew.
Chem. Int. Ed. Engl. 1986, 25, 212Ϫ235.
[2]
2.4 Hz, 1 H, 5-H), 3.37 (dd, J ϭ 6.9, 10.5 Hz, 1 H, 3-H), 3.91 (dd,
J ϭ 1.5, 5.3 Hz, 1 H, 1-H), 4.02 (ddd, J ϭ 1.5, 6.8, 8.2 Hz, 1 H, 2-
H), 5.58 (m, 1 H, 6-H), 5.72 (dt, J ϭ 2.2, 2.3 Hz, 1 H, 7-H) ppm.
13C NMR (CDCl3, 150.9 MHz): δ ϭ 23.7, 51.4, 59.0, 61.2, 76.1,
77.4, 123.5, 124.7 ppm. EI-FAB: m/z (%) ϭ 155 (40) [Mϩ], 95 (100),
82 (30), 67 (65), 54 (45). C8H13NO2 (155.2): calcd. C 61.91, H 8.44,
N 9.02; found C 61.78, H 8.61, N 8.98.
R. R. Schmidt, W. Kinzy, Adv. Carbohydr. Chem. Biochem.
1994, 50, 21Ϫ123.
R. R. Schmidt, K.-H. Jung, in: Carbohydrates in Chemistry and
Biology (Eds.: B. Ernst, G. W. Hart, P. Sinay¨), Wiley-VCH,
Weinheim, 2000, part 1, vol. 1, p. 5.
F. Roussel, M. Takhi, R. R. Schmidt, J. Org. Chem. 2001, 66,
8540Ϫ8548.
A. A.-H. Abdel-Rahman, S. Jonke, E. S. H. El Ashry, R. R.
Schmidt, Angew. Chem. 2002, 114, 3100Ϫ3103; Angew. Chem.
Int. Ed. 2002, 41, 2972Ϫ2974.
T. Iversen, D. R. Bundle, J. Chem. Soc., Chem. Commun.
1981, 1240Ϫ1241.
H.-P. Wessel, T. Iversen, D. R. Bundle, J. Chem. Soc., Perkin
Trans. 1 1985, 2247Ϫ2250.
A. A.-H. Abdel-Rahman, G. A. Winterfeld, M. Takhi, R. R.
Schmidt, Eur. J. Org. Chem. 2002, 713Ϫ717.
I. A. I. Ali, A. A.-H. Abdel-Rahman, R. R. Schmidt, publica-
tion in preparation.
H. E. Zaugg, Synthesis 1970, 49Ϫ73; and references therein.
R. R. Schmidt, Angew. Chem. 1973, 85, 235Ϫ247; Angew.
Chem. Int. Ed. Engl. 1973, 12, 212Ϫ224.
T. Fuchss, R. R. Schmidt, Synthesis 2000, 259Ϫ264.
I. Pastuszak, F. J. Molyneux, L. F. James, A. D. Elbein, Bio-
chemistry 1990, 29, 1886Ϫ1891.
A. Braudi, S. Cicchi, F. M. Cordero, R. Frignoli, A. Goti, S.
Picasso, P. Vogel, J. Org. Chem. 1995, 60, 6806Ϫ6812.
R. Giovannini, E. Marcantoni, M. Petrini, J. Org. Chem. 1995,
60, 5706Ϫ5707.
S. Nukui, M. Sodeoka, H. Sasai, M. Shibasaki, J. Org. Chem.
1995, 60, 398Ϫ404.
D.-C. Ha, C.-S. Yun, Y. Lee, J. Org. Chem. 2000, 65, 621Ϫ623.
H. Yoda, H. Katah, Y. Ujihara, K. Takabe, Tetrahedron Lett.
2001, 42, 2509Ϫ2512.
[3]
[4]
[5]
(؉)-Lentiginosine [(1S,2S,8aS)-(؉)-1,2-Dihydroxyindolizidine] [(؉)-
1]: Concd HCl (8 drops) was added to a solution of 13 (92 mg,
0.596 mmol, in 10 mL MeOH) and the mixture was hydrogenated
at 3.4 bar (0.07 g of 10% Pd on carbon). TLC monitoring indicated
the reaction was complete after 14 h. NaOH soln (1.5 mL, 3 ) was
added followed by filtration through Celite and column chromato-
graphy (CH2Cl2/MeOH/aq. NH3, 80:18:2). The title compound
(ϩ)-1 was obtained as a white solid (yield 69 mg, 75%), m.p.
106Ϫ107 °C (ref.[14] 106Ϫ107 °C). [α]D ϭ ϩ4.0 (c ϭ 0.3, MeOH)
{ref.[14] [α]D ϭ ϩ3.2 (c ϭ 0.21, MeOH)}. 1H NMR (D2O,
600 MHz): δ ϭ 1.13Ϫ1.69 (m, 5 H, 2 7-H, 2 6-H, 1 8-H), 1.81Ϫ1.85
(m, 2 H, 1 8-H, 8a-H), 2.07 (ddd, J ϭ 2.9, 11.8, 16.7 Hz, 1 H, 5-
H), 2.59 (dd, J ϭ 7.6, 11.3 Hz, 1 H, 3-H), 2.78 (br d, J ϭ 11.3 Hz,
1 H, 3-H), 2.91 (br d, J ϭ 11.1 Hz, 1 H, 5-H), 3.61 (dd, J ϭ 4.0,
8.8 Hz, 1 H, 1-H), 4.03 (ddd, J ϭ 1.8, 4.0, 7.4 Hz, 1 H, 2-H) ppm.
13C NMR (D2O, 150.9 MHz): δ ϭ 24.4, 25.2, 29.1, 54.1, 62.1, 70.2,
78.2, 84.6 ppm. EI-FAB: m/z (%) ϭ 157 (15) [Mϩ], 97 (100), 84
(20), 69 (30), 55 (20). C8H15NO2 (157.2): calcd. C 61.12, H 9.62,
N 8.91; found C 61.16, H 9.48, N 8.58.
[6]
[7]
[8]
[9]
[10]
[11]
[12]
[13]
[14]
[15]
[16]
[17]
[18]
(1S,2S,8aR)-(؊)-1,2-Dihydroxyindolizidine (15): Preparation was
performed as described for (ϩ)-1. The title compound was ob-
tained as a white solid (yield 75 mg, 81%), m.p. 137Ϫ138 °C (ref.[26]
137Ϫ138 °C). [α]D ϭ Ϫ5.3 (c ϭ 0.3, MeOH) {ref.[26] [α]D ϭ Ϫ5.8
[19]
[20]
C. F. Klitzke, R. A. Pilli, Tetrahedron Lett. 2001, 42,
5605Ϫ5608.
C. M. Schuch, R. A. Pilli, Tetrahedron: Asymmetry 2000, 11,
753Ϫ764.
M. Lennartz, E. Steckhan, Synlett 2000, 319Ϫ322.
H. Yoda, T. Katagiri, K. Tanabe, Tetrahedron Lett. 1991, 32,
6771Ϫ6774.
J. A. Makling, R. R. Schmidt, Synthesis 1993, 325Ϫ328; and
references therein.
P. Schwab, M. B. France, J. W. Ziller, R. H. Grubbs, Angew.
Chem. 1995, 107, 2179Ϫ2181; Angew. Chem. Int. Ed. Engl.
1995, 35, 2039Ϫ2041.
1
(c ϭ 0.885, MeOH)}. H NMR (D2O, 600 MHz): δ ϭ 1.19Ϫ2.12
(m, 9 H, 2 7-H, 2 6-H, 2 8-H, 1 5-H, 1 8a-H, 1 3-H), 2.92 (br d,
J ϭ 11.3 Hz, 1 H, 5-H), 3.28 (dd, J ϭ 7.1, 10.4 Hz, 1 H, 3-H), 3.83
(d, J ϭ 5.0 Hz, 1 H, 1-H), 3.97 (dd, J ϭ 6.8, 6.9 Hz, 1 H, 2-H)
ppm. 13C NMR (D2O, 150.9 MHz): δ ϭ 23.9, 24.4, 24.8, 53.3, 61.6,
66.8, 77.7, 80.6 ppm. EI-FAB: m/z (%) ϭ 157 (15) [Mϩ], 97 (100),
84 (22), 69 (37), 55 (20). C8H15NO2 (157.2): calcd. C 61.12, H 9.62,
N 8.91; found C 60.99, H 9.62, N 8.75.
[21]
[22]
[23]
[24]
[25]
[26]
S. Chang, R. H. Grubbs, Tetrahedron 1998, 54, 4413Ϫ4450.
C. Paolucci, L. Musiani, F. Venturelli, A. Fava, Synthesis
1997, 1415Ϫ1419.
Acknowledgments
This work was supported by the Deutsche Forschungsgemeinschaft
and the Fonds der Chemischen Industrie. A.O.H. E.-N. is grateful
for a stipend within the framework of the NRC-BMBF cooperation
Received June 10, 2002
[O02310]
4142
Eur. J. Org. Chem. 2002, 4137Ϫ4142