An aza analogue of iso-levoglucosenone: Synthesis and application of a new building block for imino sugars

Article abstract of DOI:10.1002/ejoc.200390163

The aza analogue 3 of iso-levoglucosenone, which is easily accessible from furylglycine, was used as a flexible building block for the synthesis of various imino sugars. Enantiomerically pure products are available starting from optically active furylglycine derivatives. ( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003).

Full text of DOI:10.1002/ejoc.200390163

FULL PAPER
An Aza Analogue of iso-Levoglucosenone: Synthesis and Application of a New
Building Block for Imino Sugars
Jens Ostrowski,[a] Hans-Josef Altenbach,*[a] Ralf Wischnat,[a] and David J. Brauer[b]
Keywords: Azasugars / Inhibitors / Rearrangements
The aza analogue 3 of iso-levoglucosenone, which is easily
( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
accessible from furylglycine, was used as a flexible building Germany, 2003)
block for the synthesis of various imino sugars. Enantiomer-
ically pure products are available starting from optically act-
ive furylglycine derivatives.
Introduction
Dihydropyridone 1 has been obtained by an aza-Achma-
towicz rearrangement[12] of a protected amino alcohol de-
rived from furylglycine.[13] The unsaturated lactam 2 was
prepared by a ‘‘chiral pool’’ approach from -serine.[14]
Many publications in recent years have been testament to
the continuing interest in the synthesis of synthetically use-
ful building blocks. In this work, we present a new com-
pound 3 that is applicable generally and is a flexible key
intermediate for the preparation of imino sugars of various
configurations and substitution patterns.[15]
Glycosidases are crucial in many biochemical processes,
so interest continues in applications of their potent and se-
lective inhibitors to medicinal use or basic research.[1Ϫ3] Im-
ino sugar (‘‘azasugar’’) inhibitors are compounds that result
from the exchange of the O-ring atom in carbohydrates by
an NH group. This class of compound typically exhibits
excellent inhibitory properties.[4,5] The natural product noji-
rimycin — a classic imino sugar — and its derivatives[6]
have been studied extensively because of their high potential
in anti-HIV, anticancer, and antidiabetic therapies.[7Ϫ11]
For this reason, many efforts have been made to develop
simple syntheses of such systems. The common approach is
based on transformations of naturally occurring -hexoses.
Polyhydroxypiperidines can be synthesized, however, also
from non-carbohydrate precursors. Several routes have been
described, and our group has developed previously the flex-
ible chiral building blocks 1 and 2 as key compounds for
the synthesis of polyhydroxylated piperidines.
The structure of 3 is reminiscent of another building
block often used in the synthesis of natural products, the
well-known iso-levoglucosenone 4.[16]
iso-Levoglucosenone 4 and its isomer levoglucosenone[17]
have been chosen as starting compounds in many syntheses
over the years because the functionality is confined in a
structurally biased rigid bicyclic framework. Because of the
1,6-anhydro bridge, there is no need for protecting groups
at the anomeric carbon atom or the primary hydroxy group
at C-6. Furthermore, the β--face of the molecule is
sterically more hindered than the α-face. This selectivity of
iso-levoglucosenone also should be observed with com-
pound 3, and this feature would augment its great potential
as a versatile building block.
[a]
Organisch-Chemisches Institut der Bergischen Universität
Wuppertal,
Gaußstrasse 20, 42097 Wuppertal, Germany
Fax: (internat.) ϩ49-(0)202/439-2648
E-mail: orgchem@uni-wuppertal.de
[b]
Results and Discussion
Anorganisch-Chemisches Institut der Bergischen Universität
Wuppertal,
Gaußstrasse 20, 42097 Wuppertal, Germany
Supporting information for this article is available on the
WWW under http://www.eurjoc.org or from the author.
Our efforts in the synthesis of the building block 3 fol-
lowed a strategy, recently published by our group, starting
1104
 2003 WILEY-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim 1434Ϫ193X/03/0306Ϫ1104 $ 20.00ϩ.50/0 Eur. J. Org. Chem. 2003, 1104Ϫ1110

An Aza Analogue of iso-Levoglucosenone
FULL PAPER
from the well-known furylglycine[18] (Ϯ)-5 which was con- shows a weak coupling to the aromatic hydrogen atoms, but
verted into the amino alcohol (Ϯ)-7, as depicted in not to the CH2 group of the anhydro bridge. cis-Dihy-
Scheme 1. Oxidative ring expansion[12] occurred on reaction droxylation employing the method of Shing et al.[21] gave
with NBS leading to the dihydropyridone (Ϯ)-8 with com- diastereoisomer (Ϯ)-11 exclusively. To confirm that the ob-
plete control of diastereoselectivity in excellent yield. Intra- served stereoselectivity is again a result of a reaction from
molecular formation of the bicyclic acetal was carried out the less-hindered side, the product depicted was trans-
in benzene under reflux conditions in the presence of a cata- formed further to the known[22Ϫ24] (Ϯ)-1-deoxygulonojiri-
lytic amount of pTsOH to give the desired molecule (Ϯ)-3. mycin 12 in a straightforward manner. Presumably cleavage
of the aminal is followed by reductive removal of the amino
protecting group with Red-Al. Ion-exchange purification
led to the product shown.
Scheme 1. Synthesis of building block 3; reagents: (a) NEt(iPr)2,
TsCl, 8 h, room temp. (61%). (b) 1. LiAlH4, Ϫ5 °C, 4 h. 2. HCl,
H2O (62%). (c) NBS, 0 °C, 4 h (83%). (d) benzene, p-toluenesul-
fonic acid, 30 min, reflux (87%)
Scheme 2. Synthesis of (Ϯ)-1-deoxygulonojirimycin; reagents: (a)
1. MeOH, CeCl3, NaBH4; 2. H2O (74%). (b) Ac2O, DMAP, 2 h
The structure of 3 as drawn is suggested by the close ana-
(89%). (c) 1. RuCl3, NaIO4, MeCN, 10 min; 2. Na2S2O3 (74%). (d)
logy of its NMR spectroscopic data to that of iso-levogluco-
senone 4, and has been confirmed by an X-ray structural
study[19] (Figure 1).
1. Red-Al, DME, 24 h, reflux; 2. HCl, H2O; 3. Dowex 50X8 (29%).
To demonstrate the synthetic potential of the building
block, (Ϯ)-3 was first converted into (Ϯ)-13 by Wittig ol-
efination (Scheme 3). The resulting diene seemed to be a
very promising precursor for the synthesis of imino sugars
with more than one hydroxymethyl side chain.
Figure 1. A perspective drawing of 3 with thermal ellipsoids (20%
probability) for the non-hydrogen atoms
In order to probe its potential, the new key compound 3
was examined in de novo synthesis of known and unknown
imino sugar systems. Some successful transformations in-
volving stereospecific addition of reagents to the lower face
of the building block have provided entry into a range of
diastereoisomerically defined products, and these are re-
ported in the following sections.
Scheme 3. Synthesis of (Ϯ)-2-(hydroxymethyl)piperidine-3,5-diol;
reagents: (a) 1. Me(Ph)3PBr, nBuLi, Ϫ78 °C to room temp., 5 h. 2.
H2O (67%). (b) 1. OsO4, NMO, 4 d; 2. Na2S2O3; 3. Ac2O, pyridine,
24 h (48%). (d) 1. Red-Al, DME, 24 h, reflux; 2. HCl, H2O; 3.
Dowex 50X8 (41%)
Reduction of (Ϯ)-3 under Luche[20] conditions with
NaBH4 and CeCl3 led to allylic alcohol (Ϯ)-9 as the main
product in 74% yield (Scheme 2). As found[16,17] for iso-lev-
Because of the steric effect of the bridge unit, the two
oglucosenone 4, the 1,6-anhydro bridge effectively blocks double bonds should undergo modifications only from the
the top face of the enone and NaBH4 attacks exclusively lower face of the molecule as mentioned before. On reaction
from the less-hindered face of the enone. 2D-NOESY Spec- with OsO4/NMO in aqueous acetone, a clean double cis-
troscopic analysis of the derived acetate (Ϯ)-10 suggests the dihydroxylation occurred leading to a product that was dif-
syn-arrangement of the acetate group with respect to ficult to extract from water during workup. Therefore, after
CH2ϪO group, as the hydrogen atom at the CHOAc group evaporation of the solvent the crude reaction product was
Eur. J. Org. Chem. 2003, 1104Ϫ1110
1105

J. Ostrowski, H.-J. Altenbach, R. Wischnat, D. J. Brauer
FULL PAPER
peracetylated with acetic anhydride and pyridine for 24 h,
As depicted in Scheme 4, treatment of (ϩ)-3 with benzyl
giving two products that were separated by flash chromato- alcohol in the presence of triethylamine leads to a Michael
graphy and identified as tetraacetate (Ϯ)-14 and triacetate addition at the enone, which yields (Ϫ)-17 under complete
(Ϯ)-15 in a ratio of 1.2:1. A shorter reaction time gave more stereocontrol. The addition occurs exclusively from the less-
of the triacetate. This observation is in line with the notion hindered side of the molecule. Reduction of (Ϫ)-17 under
that a diastereoselective reaction from the less-hindered side Luche[21] conditions affords a mixture of the two possible
had occurred to form an axial hydroxy group that is diffi- diastereoisomers (ϩ)-18 and (Ϫ)-19 in a 5.2:1 ratio. With-
cult to acetylate. 2-D NOESY spectra exhibit crosspeaks out workup, reaction of the crude product with acetic an-
from the methylene group of the anhydro bridge unit to hydride and a catalytic amount of DMAP for one hour
the axial hydrogen atom at C-3 for both products, which is gives acetate (ϩ)-20 and alcohol (Ϫ)-19, which could be
evidence for the expected diastereoselective character of the separated easily by flash chromatography. The configura-
dihydroxylation of the ring. Deprotection and reduction of tions of both compounds are based on 2D-NOESY spec-
both of the compounds led to (Ϯ)-16. Again, evaluation of troscopic analyses that indicate that the main product is in
the 2-D NOESY spectroscopic data pointed to the de- the expected gulo form. Treatment of (ϩ)-20 with Red-Al,
picted structure.
followed by chromatography on a column of Dowex-50
The CH2 group attached at the quaternary carbon atom (Hϩ), gives monobenzylated (ϩ)-21. Finally, deprotection
shows a small coupling to the adjacent equatorial hydrogen using hydrogen gas in the presence of Pd/C leads to (ϩ)-
atom at C-3, but no coupling to those at the anomeric 1,3-dideoxygulonojirimycin 22.
centre C-1 or to the neighbouring hydrogen atom at C-5.
In order to substantiate the proposed structure further, we
are still trying to grow suitable crystals of 16 for X-ray crys-
tallography.
Conclusion
In summary, a new, versatile building block 3 has been
synthesized, as a racemate and in its optically pure form,
and has been used for the preparation of (Ϯ)-deoxygulono-
jirimycin 12 and (ϩ)-1,3-dideoxygulonojirimycin 22. More-
over, we have demonstrated the application of 3 in the syn-
thesis of (Ϯ)-16, the first member of a new class of imino
sugars with an interesting substitution pattern in position
C-4.
Since the enantiopure form of furylglycine also is well
known,[25] clearly it is desirable to prepare and to use it for
the synthesis of enantiomerically pure compounds. Starting
with -furylglycine, we synthesized (ϩ)-3 without any prob-
lems using the described route. In addition to the synthesis
of deoxynojirimycins in enantiomerically pure forms, our
main interest was the application of (ϩ)-3 to the prepara-
tion of 1,3-dideoxynojirimycins because up to now only a
few approaches to such systems are known.[26,27] In this
work, we demonstrate the application of the key compound
to the de novo synthesis of this class of compounds by the
preparation of (ϩ)-1,3-dideoxygulonojirimycin as a repres-
entative example.
Experimental Section
General Remarks: All solvents were distilled and purified by stand-
ard procedures.[28] Products were purified by flash chromatography
Scheme 4. Synthesis of (ϩ)-1,3-dideoxygulonojirimycin: reagents: (a) BnOH, NEt3, 24 h (69%). (b) 1. MeOH, CeCl3·7H2O, Ϫ5 °C; 2.
HCl, H2O (77%). (c) Ac2O, DMAP, 2 h (93%). (d) 1. Red-Al, DME, 24 h, reflux; 2. HCl, H2O; 3. Dowex 50X8 (54%). (e) H2, Pd/C,
24 h (92%)
1106
Eur. J. Org. Chem. 2003, 1104Ϫ1110

An Aza Analogue of iso-Levoglucosenone
on Silica gel 60 (mesh 20Ϫ63, Merck) with various mixtures of MS: m/z (%) ϭ 279 (9) [Mϩ Ϫ H2O], 267 (15), 250 (24), 249 (23),
FULL PAPER
ethyl acetate and cyclohexane. NMR spectroscopy was performed
with an ARX 400 (Bruker) at room temperature. Chemical shifts
are given in ppm (δ) relative to the solvent as internal standard.
Mass spectra were recorded with MAT 311 A (Varian). High-res-
olution mass spectra (HRMS) were recorded at Bayer AG, Wup-
pertal (HR-EI: MAT95 Finnigan; HR-ESI: LCT Micro Mass).
Infrared spectroscopy was performed with a PerkinϪElmer 1420
156 (15), 155 (82), 139 (18), 125 (12), 124 (76), 112 (11), 108 (11),
96 (39), 95 (21), 92 (46), 91 (100), 83 (20), 79 (14), 66 (12), 55 (93),
41 (28), 39 (77). C13H15NO5S (297): calcd. C 52.53, H 5.05, N 4.71;
found C 52.25, H 5.11, N 4.69.
8-[(4-Methylphenyl)sulfonyl]-6-oxa-8-azabicyclo[3.2.1]oct-3-en-2-
one (3): 8 (3 g, 10.1 mmol) was dissolved in benzene (350 mL), a
catalytic amount of p-TsOH was added, and the reaction mixture
was heated under reflux for 30 min using a DeanϪStark trap. The
hot solution was filtered and then washed with aqueous NaHCO3
(5%, 50 mL). The organic layer was separated and dried over
MgSO4. After evaporation of the solvent, flash chromatography of
the crude product, followed by recrystallization from ethyl acetate/
hexane, gave the title compound (2.45 g, 87%). Using the same pro-
cedure, (ϩ)-3 was obtained from (ϩ)-8. M.p. 155Ϫ158 °C (dec.).
[α]2D0 ϭ ϩ99 (c ϭ 1.01, acetone). 1H NMR (400 MHz, CDCl3): δ ϭ
2.44 (s, 3 H), 3.35 (dd, J ϭ 8.9, 1.42 Hz, 1 H), 3.41 (dd, J ϭ 8.8,
5.8 Hz, 1 H), 4.62 (m, 1 H), 6.05 (dd, J ϭ 9.5, 1 Hz, 1 H), 6.11 (d,
J ϭ 4.9 Hz, 1 H), 7.18 (dd, J ϭ 4.9, 9.6 Hz, 1 H), 7.53 (m, 4 H)
ppm. 13C NMR (100.6 MHz, CDCl3): δ ϭ 21.57, 62.43, 65.49,
83.94, 127.5, 128.06, 129.92, 134.43, 145.13, 146.41, 192.43 ppm.
IR (neat): ν˜ ϭ 3080Ϫ3060, 2995Ϫ2880, 1700, 1600, 1360Ϫ1330,
1180Ϫ1150 cmϪ1. MS: m/z (%) ϭ 279 (6) [Mϩ], 155 (15), 124 (69),
96 (60), 91 (76), 83 (19), 65 (31), 55 (100), 41 (18), 39 (32).
C13H13NO4S (279.3): calcd. C 55.91, H 4.67, N 5.02; found
C 56.17, H 4.66, N 5.13.
spectrometer.
A VarioEL V2.6 (Elementar Analysensysteme
GmbH) was used for elemental analyses.
N-[1-(2-Furyl)-2-(hydroxyethyl)]-4-methylbenzenesulfonamide (7): 5
(19.6 g, 0.14 mol) was dissolved in water (225 mL). A solution of
N-ethyldiisopropylamine (47 mL, 0.28 mol) in ethyl acetate
(450 mL) was added. At 0 °C the reaction mixture was treated with
p-toluenesulfonyl chloride (29.19 g, 0.15 mol). The mixture was
stirred vigorously for 8 h at room temperature. The phases were
separated, the aqueous phase was extracted with ethyl acetate, and
then the combined organic layers were washed with NaOH (1 ).
The combined aqueous layers were treated at 0 °C with HCl (6 ).
At pH 1, the aqueous layer was extracted with ethyl acetate and
the organic phase was dried over MgSO4. Removal of solvents and
recrystallization from ethyl acetate/hexane gave 6 (25 g, 61%). Li-
thium aluminium hydride (6.4 g, 0.17 mol) was suspended in di-
ethyl ether (500 mL) and cooled to Ϫ15 °C. A solution of 6 (23 g,
78 mmol) in THF was added dropwise. After stirring at room tem-
perature for 3 h, the reaction mixture was treated at Ϫ10 °C with
HCl (1 , 300 mL) and then with ethyl acetate (200 mL). The
phases were separated and the aqueous layer was extracted with
ethyl acetate. The combined organic phases were dried over
MgSO4. Removal of solvents and recrystallization from ethyl acet-
ate/hexane gave the title compound (13.5 g, 62%). Using the same
8-[(4-Methylphenyl)sulfonyl]-6-oxa-8-azabicyclo[3.2.1]oct-3-en-2-ol
(9): 3 (837 mg, 3 mmol) was dissolved in a methanolic solution of
CeCl3·7H2O (0.4 , 200 mL) and cooled to Ϫ10 °C. NaBH4
(117 mg, 3.07 mmol) was dissolved in MeOH and added dropwise
to the reaction mixture in such a way that the temperature did not
rise higher than Ϫ5 °C. The solution was stirred for 2.5 h and then
quenched with H2O (130 mL). The MeOH was evaporated and the
aqueous layer was extracted with ethyl acetate. The combined or-
ganic phases were dried over MgSO4. The solvent was evaporated
and the crude product purified by flash chromatography, followed
by crystallization, to give the title compound (624 mg, 74%). M.p.
procedure, (ϩ)-7 was obtained from (ϩ)-6. M.p. 72 °C. [α]2D0
ϭ
1
ϩ29.7 (c ϭ 1.0, ethyl acetate). H NMR (400 MHz, CDCl3): δ ϭ
2.35 (s, 3 H), 3.78 (m, 2 H), 4.49 (s, 1 H), 6.02 (m, 1 H), 6.15 (m,
1 H), 7.13 (m, 1 H), 7.43 (m, 4 H) ppm. 13C NMR (100.6 MHz,
CDCl3): δ ϭ 21.31, 53.33, 63.83, 107.75, 110.11, 126.93, 129.33,
137.34, 142.04, 143.11, 150.85 ppm. IR (neat): ν˜ ϭ 3400, 3280,
3120, 3080, 1595, 1320Ϫ1150, 800 cmϪ1. MS: m/z (%) ϭ 281 (2)
[Mϩ], 250 (35), 155 (37), 91 (100), 65 (32). C13H15NO4S (281):
calcd. C 56.66, H 7.14; found C 56.47, H 7.21.
1
89Ϫ93 °C. H NMR (400 MHz, CD2Cl2): δ ϭ 2.03 (s, OH), 2.47
(s, 3 H), 3.00 (dd, J ϭ 8.3, 5.8 Hz, 1 H), 3.90 (dd, J ϭ 8.5, 1.6 Hz,
1 H), 4.25 (m, 1 H), 4.90 (m, 1 H), 5.70 (d, J ϭ 9.5 Hz, 1 H), 5.80
(d, J ϭ 4.6 Hz, 1 H), 5.96 (ddd, J ϭ 9.4, 1.5, 4.8 Hz, 1 H), 7.45 (m,
4 H) ppm. 13C NMR (100.6 MHz, CD2Cl2): δ ϭ 21.42, 60.06,
61.77, 83.82, 127.16, 128.22, 129.75, 130.31, 135.13, 144.83 ppm.
IR (neat): ν˜ ϭ 3580Ϫ3500, 3050, 2980Ϫ2920, 1600, 1380, 1160,
1095 cmϪ1. MS: m/z (%) ϭ 281 (36) [Mϩ], 234 (21), 197 (55), 155
(96), 139 (19), 133 (84), 126 (100), 106 (33), 98 (17), 96 (30), 91
(100), 89 (15), 80 (22), 70 (100), 68 (37), 57 (33), 55 (17), 41 (73),
39 (54). C13H15NO4S (281.3): calcd. C 55.52, H 5.34, N 4.98; found
C 55.85, H 5.34, N 4.72.
6-Hydroxy-2-(hydroxymethyl)-1-[(4-methylphenyl)sulfonyl]-1,6-di-
hydropyridin-3(2H)-one (8): 7 (5 g, 17.8 mmol) and sodium acetate
(1.86 g, 22.7 mmol) were dissolved in THF/H2O (80 mL, 4:1), co-
oled to Ϫ5 °C, and then treated portionwise with N-bromosuccini-
mide (4.37 g, 24.6 mmol) such that the reaction temperature did
not exceed 0 °C. The deep-orange solution was then stirred at 0 °C
for 3 h. After the addition of ethyl acetate (200 mL), the mixture
was treated subsequently with saturated aqueous KI (100 mL), sat-
urated aqueous NaS2O3 (100 mL) and saturated aqueous NaHCO3
(100 mL) for workup. The organic layer was separated, washed 8-[(4-Methylphenyl)sulfonyl]-6-oxa-8-azabicyclo[3.2.1]oct-3-en-2-yl
with saturated aqueous NaCl (80 mL), and dried over MgSO4. Re-
moval of the solvent and flash chromatography gave the title com-
pound (4.38 g, 83%). Using the same procedure, (ϩ)-8 was ob-
tained from (ϩ)-7. M.p. 132Ϫ136 °C (dec.). [α]2D0 ϭ ϩ40 (c ϭ 1.0,
Acetate (10): Acetic anhydride (0.7 mL, 6.4 mmol) and a catalytic
amount of 4-dimethylaminopyridine were added to a solution of 9
(1.8 g, 6.4 mmol) in dichloromethane (50 mL) and then the reaction
mixture was stirred for 5 h at room temperature. The solution was
acetone). 1H NMR (400 MHz, [D6]acetone): δ ϭ 2.41 (s, 3 H), 3.65 quenched with 5% aqueous NaHCO3 (20 mL) and the organic layer
(d, J ϭ 11.1 Hz, 1 H), 3.93 (m, 1 H), 4.39 (m, 1 H), 5.03 (s, 1 H), was separated and dried over MgSO4. The solvent was evaporated
5.92 (d, J ϭ 9.4 Hz, 1 H), 6.01 (d, J ϭ 10.2 Hz, 1 H), 6.06 (dd, J ϭ and the crude product was purified by flash chromatography and
4.7, 8.6 Hz, 1 H), 7.05 (dd, J ϭ 4.7, 10.2 Hz, 1 H), 7.42 (m, 4 H) crystallization to give the title compound (1.85 g, 89%). M.p.
ppm. 13C NMR (100.6 MHz, [D6]acetone): δ ϭ 22.06, 64.28, 64.91,
73.72, 128.70, 128.93, 131.39, 139.39, 145.54, 147.74, 194.33 ppm.
84Ϫ85 °C. H NMR (400 MHz, CDCl3): δ ϭ 2.06 (s, 3 H), 2.44 (s,
3 H), 3.11 (m, 1 H), 3.86 (d, J ϭ 8.5 Hz, 1 H), 4.42 (m, 1 H), 5.66
1
IR (neat): ν˜ ϭ 3193, 3113, 3068, 2980Ϫ2887, 1691, 1597, 1453, (d, J ϭ 9.6 Hz, 1 H), 5.73 (m, 1 H), 5.83 (d, 1 H, J ϭ 4.6 Hz, 1 H),
1388, 1340, 1310, 1230, 1153, 1060, 970, 917, 850, 811, 730 cmϪ1
.
6.04 (ddd, J ϭ 4.7, 7.9, 1.5 Hz, 1 H), 7.55 (m, 4 H) ppm. 13C NMR
Eur. J. Org. Chem. 2003, 1104Ϫ1110
1107

J. Ostrowski, H.-J. Altenbach, R. Wischnat, D. J. Brauer
FULL PAPER
(100.6 MHz, CDCl3): δ ϭ 20.75, 21.47, 57.43, 62.50, 72.45, 83.65,
(%) ϭ 277 (2) [Mϩ], 248 (44), 247 (76), 155 (18), 93 (32), 92 (100),
126.35, 128.04, 128.96, 129.59, 134.80, 144.46, 169.62 ppm. IR 91 (93), 70 (17), 67 (16), 66 (12), 65 (97), 63 (12), 53 (11), 43 (24), 42
(neat): ν˜ ϭ 3071, 2983Ϫ2951, 1792, 1598, 1475, 1370, 1346, 1306, (10), 41 (35), 39 (86). C14H15NO3S (277.3): calcd. C 60.65, H 5.42,
1287, 1232, 1158, 1118, 1092, 1036, 1009, 934, 878, 813, 751, 690 N 5.05; found C 60.65, H 5.82, N 4.58.
cmϪ1. MS: m/z (%) ϭ 323 (33) [Mϩ], 234 (16), 197 (37), 168 (28),
155 (34), 133 (24), 126 (40), 106 (16), 91 (83), 80 (12), 70 (11), 65
(14),43 (100), 41 (15), 39 (10). C15H17NO5S (323.4): calcd. C 55.73,
H 5.26, N 4.33; found C 55.44, H 5.31, N 4.16.
2,3,4-Triacetoxy-8-[(4-methylphenyl)sulfonyl]-6-oxa-8-azabicyclo-
[3.2.1]oct-2-ylmethyl Acetate (14) and 4-Acetoxy-2-acetoxymethyl-
2-hydroxy-8-[(4-methylphenyl)sulfonyl]-6-oxa-8-azabicyclo[3.2.1]oct-
3-yl Acetate (15): NMO (1.26 g, 9.32 mmol) and an aqueous solu-
3,4-Dihydroxy-8-[(4-methylphenyl)sulfonyl]-6-oxa-8-azabicyclo- tion of OsO4 (2 g/L, 12.03 mL, 0.10 mmol) were added to diene
[3.2.1]oct-2-yl Acetate (11): Acetate 10 (670 mg, 2.02 mmol) was
dissolved in acetonitrile (50 mL) and cooled to Ϫ5 °C. A mixture of
13 (1.06 g, 3.82 mmol) dissolved in acetone (80 mL), and then the
mixture was stirred for 4 d at room temperature. Na2S2O3
NaIO4 (651 mg, 3.05 mmol), RuCl3 (23 mg, 0.10 mmol) and H2O (10 equiv.) dissolved in water (30 mL) was added, the mixture
(5 mL) was added and the solution was stirred for 13 min. The
reaction was then quenched with aqueous Na2S2O3 (15%, 50 mL).
stirred for 1 h, then all the solvents were evaporated. Acetic anhyd-
ride (20 mL) and pyridine (20 mL) were added to the crude
After separation the aqueous layer was extracted several times with product, the mixture was stirred for 3 d, and then all the volatile
ethyl acetate. The combined organic phases were dried over
MgSO4. The solvent was evaporated and the residue was recrystal-
compounds were evaporated. The resulting solid was suspended in
a mixture of brine (150 mL) and ethyl acetate (150 mL). After stir-
lized from ethyl acetate/hexane to give the title compound (546 mg, ring for 1 h, the phases were separated and the aqueous layer was
1
73%). M.p. 170Ϫ175 °C (dec.). H NMR (400 MHz, [D6]DMSO): extracted several times with ethyl acetate. The combined organic
δ ϭ 1.97 (s, 3 H), 2.37 (s, 3 H), 2.60 (dd, J ϭ 4.9, 8.3 Hz, 1 H), phases were dried over MgSO4. The solvents were evaporated and
3.50Ϫ3.55 (m, 2 H), 3.69 (m, 1 H), 4.27 (t, J ϭ 4.1 Hz, 1 H), 4.72
(dd, J ϭ 3.4, 9.2 Hz, 1 H), 4.81 (d, J ϭ 6.7 Hz, 1 H), 5.10 (d, J ϭ acetate 14 (416 mg) and the triacetate 15 (484 mg) (48% yield of
4.5 Hz, 1 H), 5.44 (d, J ϭ 3.7 Hz, 1 H), 7.36Ϫ7.7 (m, 4 H) ppm. the tetrole).
13C NMR (100.6 MHz, [D6]DMSO): δ ϭ 20.09, 21.0, 55.7, 63.5, 14: H NMR (400 MHz, CDCl3): δ ϭ 1.98 (s, 3 H), 2.01 (s, 3 H),
the residue purified by flash chromatography to give the tetra-
1
66.8, 69.7, 73.1, 88.8, 127.5, 129.8, 135.6, 144.2, 169.8 ppm. IR
(neat): ν˜ ϭ 3561, 3394, 3070Ϫ3024, 2975Ϫ2914, 1731, 1595, 1356,
2.06 (s, 3 H), 2.08 (s, 3 H), 2.44 (s, 3 H), 3.19Ϫ3.23 (dd, J ϭ 5.3,
8.9 Hz, 1 H), 3.96 (d, J ϭ 8.9 Hz, 1 H), 4.50 (d, J ϭ 12.5 Hz, 1 H),
5.01 (d, J ϭ 5.1 Hz, 1 H), 5.07 (d, J ϭ 12.5 Hz, 1 H), 5.13Ϫ5.15
(dd, J ϭ 3.7 Hz; 5.4 Hz, 1 H), 5.37 (d, J ϭ 5.3 Hz, 1 H), 5.61 (d,
1249, 1187, 1167, 1066, 984, 935, 908, 923, 678, 609, 550 cmϪ1
.
MS: m/z (%) ϭ 355 (2) [Mϩ Ϫ 2H], 202 (63), 200 (27), 160 (32),
155 (80), 140 (44), 142 (66), 124 (12), 115 (32), 108 (49), 100 (67), J ϭ 3.6 Hz, 1 H), 7.33Ϫ7.78 (m, 4 H) ppm. 13C NMR (100.6 MHz,
97 (53), 91 (93), 84 (20), 69 (65), 60 (16), 57 (14), 55 (16), 46 (79),
CDCl3): δ ϭ 20.52, 20.56, 20.68, 21.60, 21.72, 57.52, 61.14, 65.22,
43 (100), 39 (24). C15H19NO7S (357): calcd. C 50.37, H 5.32, 68.75, 69.20, 82.30, 86.01, 127.72, 130.00, 135.11, 145.00, 169.02,
N 3.92; found C 50.07, H 5.18, N 3.85.
169.32, 169.60, 169.95 ppm. IR (film): ν˜ ϭ 3063, 2972Ϫ2922, 1752,
1597, 1493, 1433, 1369, 1228, 1168, 1106, 1041, 954, 908, 881, 861,
817, 737, 684, 613 cmϪ1. MS: m/z (%) ϭ 513 (2) [Mϩ], 454 (18),
358 (80), 352 (31), 326 (13), 316 (40), 292 (31), 242 (24), 238 (81),
224 (69), 210 (81), 196 (77), 168 (39), 155 (97), 138 (63), 126 (67),
108 (81), 91 (100), 84 (15), 70 (59), 55 (22), 43 (98). HRMS:
514.1406; calcd. for C22H28NO11S [M ϩ H]: 514.1383.
1-Deoxygulonojirimycin (12): Red-Al (3.5  solution in toluene,
2.8 mL) was added to a solution of diol 11 (357 mg, 1 mmol) in
dry dimethoxyethane (40 mL) and then the reaction mixture was
heated under reflux for 24 h. The deeply yellow solution then was
quenched with HCl (0.75 , 10 mL). The mixture was filtered, the
volatile solvents were evaporated, the aqueous layer was lyophil-
ized, and the residue was purified over Dowex 50 eluting with
1
15: H NMR (400 MHz, CDCl3): δ ϭ 2.06 (s, 6 H), 2.13 (s, 3 H),
NH4OH, to give of the title compound (47 mg, 29%) as a hygro- 2.45 (s, 3 H), 3.10Ϫ3.14 (dd, J ϭ 5.2, 8.6 Hz, 1 H), 4.06 (d, J ϭ
scopic syrup. The analytical data are consistent with those reported
8.7 Hz, 1 H), 4.31 (d, J ϭ 12.1 Hz, 1 H), 4.38 (d, J ϭ 5.0 Hz, 1 H),
4.50 (d, J ϭ 12.1 Hz, 1 H), 5.10 (d, J ϭ 5.1 Hz, 1 H), 5.16Ϫ5.19
(dd, J ϭ 3.7 Hz; 5.1 Hz, 1 H), 5.62 (d, J ϭ 3.6 Hz, 1 H), 7.32Ϫ7.77
(m, 4 H) ppm. 13C NMR (100.6 MHz, CDCl3): δ ϭ 20.57, 20.61,
20.78, 21.60, 58.74, 64.81, 64.86, 68.47, 71.83, 74.47, 85.90, 127.54,
129.95, 135.50, 144.85, 169.48, 170.47, 170.51 ppm. IR (film): ν˜ ϭ
3476, 3083, 2973Ϫ2906, 1751, 1597, 1372, 1231, 1167, 1128, 1090,
1044, 947, 910, 855, 817, 728, 685, 615 cmϪ1. MS: m/z (%) ϭ 412
(16) [Mϩ Ϫ OAc], 316 (88), 274 (43), 224 (10), 214 (12), 196 (23),
172 (15), 155 (68), 138 (58), 130 (14), 124 (13), 111 (13), 108 (17),
103 (12), 96 (11), 91 (100), 84 (16), 71 (43), 65 (30), 55 (36), 43 (74),
in the literature.[23Ϫ25]
2-Methylene-8-[(4-methylphenyl)sulfonyl]-6-oxa-8-azabicyclo[3.2.1]-
oct-3-ene (13): n-BuLi (5.4 mmol) was added to a suspension of
methyltriphenylphosphonium bromide (1.92 g, 5.4 mmol) in dry
THF (50 mL) at Ϫ78 °C and then the mixture was stirred for
15 min. A solution of 3 (1 g, 3.58 mmol) in dry THF (50 mL) then
was added dropwise. The reaction mixture was warmed to room
temperature, stirred for 3 h, and then quenched with H2O (50 mL).
The aqueous layer was separated, extracted with ethyl acetate, and
then the combined organic phases were dried over MgSO4. The
solvent was evaporated and the residue purified by flash chromato-
graphy, and recrystallization from ethyl acetate/hexane, to give of
39 (16).
HRMS: 516.116; calcd.
for C21H26NO12S
[M ϩ HCOOH]: 516.1176.
a colorless solid (669 mg, 67%). M.p. 140Ϫ145 °C (dec.). 1H NMR 2,3-Bis(hydroxymethyl)piperidine-3,4,5-triol (16): Red-Al (3.5 
(400 MHz, CDCl3): δ ϭ 2.40 (s, 3 H), 3.24 (m, 1 H), 3.34 (m, 1 H), solution in toluene, 2.1 mL) was added of a solution of trisacetate
4.61 (d, J ϭ 5.6 Hz, 1 H), 4.89 (s, 1 H), 5.00 (s, 1 H), 5.81 (d, J ϭ
4.6 Hz, 1 H), 6.05 (dd, J ϭ 4.5, 9.3 Hz, 1 H), 6.10 (d, J ϭ 9.2 Hz,
15 (365 mg, 0.71 mmol) in dry dimethoxyethane (40 mL), and then
the reaction mixture was heated under reflux for 24 h. The light-
1 H), 7.51 (m, 4 H) ppm. 13C NMR (100 MHz, CDCl3): δ ϭ 21.51, green solution then was quenched with HCl (0.75 , 10 mL), fil-
61.12, 68.76, 83.82, 112.25, 127.99, 128.64, 129.09, 129.56, 135.40, tered, and the volatile solvents were evaporated. The aqueous layer
144.20, 144.24 ppm. IR (neat): ν˜ ϭ 3090Ϫ3040, 2960Ϫ2890, 1735,
1640, 1590, 1345Ϫ1325, 1185Ϫ1156, 1100Ϫ1080, 1050,
1030Ϫ1010, 890, 870, 815Ϫ800, 773, 692, 678, 661 cmϪ1. MS: m/z
was lyophilized and the residue was purified over Dowex 50 eluting
with NH4OH to give the title compound (56 mg, 41%). H NMR
(400 MHz, CDCl3): δ ϭ 2.70Ϫ2.76 (t, J ϭ 11.8 Hz; 12.0 Hz, 1 H),
Eur. J. Org. Chem. 2003, 1104Ϫ1110
1
1108

An Aza Analogue of iso-Levoglucosenone
FULL PAPER
2.86Ϫ2.88 (dd, J ϭ 4.1 Hz; 6.5 Hz, 1 H), 2.93Ϫ2.98 (m, 1 H), (16), 59 (22), 43 (78), 41 (17), 39 (12). HRMS: 432.1447; calcd. for
3.63Ϫ3.80 (m, 4 H), 3.90 (d, J ϭ 2.7 Hz, 1 H), 4.00Ϫ4.05 (m, 1 H) C22H22NO6S [M ϩ H]: 432.1481.
ppm. 13C NMR (100.6 MHz, CDCl3): δ ϭ 46.15, 57.37, 62.69,
(؊)-19: M.p. 125Ϫ128 °C. [α]2D0 ϭ Ϫ19.2 (c ϭ 1.10, acetone). 1H
66.29, 67.85, 72.21, 77.33 ppm. IR (neat): ν˜ ϭ 3382, 2928, 1284,
NMR (400 MHz, CDCl3): δ ϭ 1.28 (s, 1 H), 1.88 (d, J ϭ 3.1 Hz,
1050, 1005. MS: m/z (%) ϭ 193 (11) [Mϩ], 162 (74), 144 (12), 114
1 H), 2.41 (s, 3 H), 3.26Ϫ3.29 (dd, J ϭ 5.2, 8.2 Hz, 1 H), 3.57 (d,
(12), 102 (21), 84 (15), 73 (52), 60 (100), 56 (19), 43 (37) cmϪ1
.
J ϭ 8.2 Hz, 1 H), 3.67Ϫ3.69 (dd, J ϭ 2.9, 6.1 Hz, 1 H), 3.73 (d,
J ϭ 3.1 Hz, 1 H), 4.32Ϫ4.34 (t, J ϭ 4.5 Hz, 1 H), 4.53Ϫ4.67 (2 ϫ
d, J ϭ 11.6 Hz, 2 H), 5.86 (d, J ϭ 4.5 Hz, 1 H), 7.24Ϫ7.80 (m,
9 H) ppm. 13C NMR (100.6 MHz, CDCl3): δ ϭ 21.53, 29.43, 61.92,
66.19, 67.46, 71.14, 73.94, 87.03, 127.67, 127.82, 128.42, 129.75,
135.96, 137.41, 144.28 ppm. IR (neat): ν˜ ϭ 3557, 3414, 2972Ϫ2874,
1596, 1492, 1454, 1399, 1385, 1354, 1335, 1308, 1289, 1258, 1188,
1168, 1138, 1138, 1097, 1044, 1021, 993, 915, 873, 818, 751, 688,
577 cmϪ1. MS: m/z (%) ϭ 298 (11) [Mϩ Ϫ benzyl], 281 (10), 250
(16), 234 (79), 155 (53), 126 (59), 108 (35), 98 (20), 96 (12), 91 (100),
84 (76), 79 (25), 70 (47), 65 (54), 57 (33), 55 (20), 51 (16), 47 (35),
HRMS: 194.1021; calcd. for C7H16NO5 [M ϩ H]: 194.1028.
4-Benzyloxy-8-[(4-methylphenyl)sulfonyl]-6-oxa-8-azabicyclo[3.2.1]-
octan-2-one [(؊)-17]: Triethylamine (0.2 mL) was added to a solu-
tion of (ϩ)-3 (800 mg, 2.86 mmol) in benzyl alcohol (30 mL) and
the mixture was stirred for 24 h at room temperature. The benzyl
alcohol was evaporated in vacuo and the resulted yellow oil was
crystallized from ethanol to give the title compound (764 mg, 69%).
M.p. 144Ϫ145 °C. [α]2D0 ϭ Ϫ32.4 (c ϭ 1.19, acetone). 1H NMR
(400 MHz, CDCl3): δ ϭ 2.39 (s, 3 H), 2.52 (dd, J ϭ 17.7, 2.5 Hz,
1 H), 2.63 (dd, J ϭ 17.7, 6.6 Hz, 1 H), 3.46 (dd, J ϭ 8.6, 5.2 Hz,
1 H), 3.70 (d, J ϭ 8.6 Hz, 1 H), 3.87 (m, 1 H), 4.47 (d, J ϭ 5.1 Hz,
1 H), 4.51 (d, J ϭ 11.7 Hz, 1 H), 4.57 (d, J ϭ 11.7 Hz, 1 H), 5.89 (d,
J ϭ 2.0 Hz, 1 H), 7.23Ϫ7.79 (m, 9 H) ppm. 13C NMR (100.6 MHz,
CDCl3): δ ϭ 21.56, 39.84, 64.88, 67.14, 71.32, 74.96, 87.86, 127.68,
127.78, 127.93, 128.45, 129.87, 135.70, 137.16, 144.74, 199.71 ppm.
IR (neat): ν˜ ϭ 3071Ϫ3023, 2978Ϫ2870, 1730, 1593, 1490, 1452,
1394, 1347, 1170, 1138, 1080, 1000, 931, 889, 818, 747, 693, 682,
620 cmϪ1. MS: m/z (%) ϭ 296 (11) [Mϩ], 250 (13), 232 (74), 156
(13), 155 (76), 124 (12), 108 (13), 107 (12), 96 (11), 92 (62), 91 (100),
90 (11), 89 (12), 79 (17), 77 (20), 70 (46), 65 (65), 55 (23), 51 (16), 43
(24), 42 (32), 41 (17), 39 (32). C20H21NO5S (387.5): calcd. C 62.02,
H 5.43, N 3.62; found C 61.94, H 5.43, N 3.61.
43 (31), 39 (30). HRMS: 434.1298; calcd. for C21H24NO7S [Mϩ
Ϫ
H ϩ HCOOH]: 434.1273.
5-Benzyloxy-2-(hydroxymethyl)piperidin-3-ol [(؉)-21]: Red-Al (3.5
 solution in toluene, 3.0 mL) was added to a solution of acetate
(ϩ)-20 (430 mg, 1 mmol) in dry dimethoxyethane (40 mL), and
then the reaction mixture was heated under reflux for 24 h. The
deeply yellow solution then was quenched with HCl (0.75 ,
12 mL), filtered, and the volatile solvents were evaporated. The
aqueous layer was lyophilized and purified over Dowex 50 eluting
with NH4OH to give the title compound (123 mg, 53%). [α]2D0
ϭ
1
ϩ7.8 (c ϭ 0.45, H2O). H NMR (400 MHz, D2O): δ ϭ 1.60Ϫ1.67
(q, J ϭ 2.2, 11.3 Hz, 1 H), 2.32Ϫ2.36 (m, 1 H), 2.62Ϫ2.67 (t, J ϭ
11.7 Hz, 1 H), 3.00Ϫ3.03 (t, J ϭ 6.8 Hz, 1 H), 3.43Ϫ3.47 (dd, J ϭ
12.2 Hz, 1 H), 3.63Ϫ3.68 (dd, J ϭ 8.1, 11.8 Hz, 1 H), 3.71Ϫ3.76
(dd, J ϭ 5.5, 11.7 Hz, 1 H), 3.97Ϫ4.03 (m, 1 H), 4.20 (s, 1 H), 4.63
(s, 2 H), 7.42 (s, 5 H) ppm. 13C NMR (100.6 MHz, D2O): δ ϭ
38.93, 50.44, 61.34, 63.66, 67.88, 72.98, 73.16, 130.59, 130.77,
131.01, 139.05 ppm. IR (neat): ν˜ ϭ 3373, 3062Ϫ3031, 2931, 1675,
1605, 1496, 1454, 1399Ϫ1371, 1092, 1077, 1028, 911, 876, 741, 699,
616 cmϪ1. MS: m/z (%) ϭ 206 (56) [Mϩ Ϫ CH2OH], 115 (9), 100
(6), 91 (100), 74 (7), 65 (8), 56 (9), 43 (5),36 (15). HRMS: 238.1465;
calcd. for C13H20NO3 [M ϩ H]: 238.1443.
4-Benzyloxy-8-[(4-methylphenyl)sulfonyl]-6-oxa-8-azabicyclo[3.2.1]-
oct-2-yl Acetate [(؉)-20] and 4-Benzyloxy-8-[(4-methylphenyl)sulf-
onyl]-6-oxa-8-azabicyclo[3.2.1]octan-2-ol [(؊)-19]: The Michael ad-
duct (Ϫ)-17 (348 mg, 0.9 mmol) was dissolved in a methanolic solu-
tion of CeCl3·7H2O (0.4 , 140 mL) and cooled to Ϫ10 °C. NaBH4
(75 mg, 1.27 mmol) was dissolved in MeOH and added dropwise
to the reaction mixture in a way such that the temperature did not
rise above Ϫ5 °C. The solution was stirred for 2.5 h and then
quenched with H2O (100 mL). The MeOH was evaporated, the
aqueous layer was extracted with ethyl acetate, and the combined
organic layers were dried over MgSO4. Evaporation of the solvent
yielded a mixture of diastereoisomers of 18 and 19 (5.2:1; 271 mg,
77%). The crude product (200 mg, 0.51 mmol) was dissolved in
dichloromethane (20 mL), acetic anhydride (0.52 mmol) and a cata-
lytic amount of 4-dimethylaminopyridine were added, and then the
reaction mixture was stirred for 2 h at room temperature. The solu-
tion then was quenched with aqueous NaHCO3 (5%, 10 mL), and
the organic layer was separated and dried over MgSO4. After evap-
oration of the solvent, the crude product was purified by flash chro-
matography, followed by recrystallization from ethyl acetate/hex-
ane, to give acetate (ϩ)-20 (127 mg) and alcohol (Ϫ)-19 (71 mg)
(93%; alcohols after separation).
2-(Hydroxymethyl)piperidin-3,5-diol [(؉)-22]: Benzyl ether (ϩ)-21
(70 mg, 0.30 mmol) was dissolved in H2O (30 mL) and then stirred
for 24 h under an atmosphere of hydrogen gas in the presence of
Pd/C. Filtration and evaporation of the solvent gave the title com-
pound (40 mg, 92%). [α]2D0 ϭ ϩ7.2 (c ϭ 0.91, H2O). 1H NMR
(400 MHz, D2O): δ ϭ 1.63Ϫ1.70 (q, J ϭ 2.5, 11.3 Hz, 1 H),
2.23Ϫ2.27 (d, J ϭ 13.6 Hz, 1 H), 2.78Ϫ2.84 (t, J ϭ1.6 Hz, 1 H),
3.28Ϫ3.32 (dd, J ϭ 4.8, 8.6 Hz, 1 H), 3.46Ϫ3.50 (dd, J ϭ 4.0,
12.2 Hz, 1 H), 3.70Ϫ3.76 (dd, J ϭ 8.9, 12.3 Hz, 1 H), 3.83Ϫ3.87
(dd, J ϭ 4.6, 12.2 Hz, 1 H), 4.20Ϫ4.25 (m, 1 H), 4.28 (s, 1 H) ppm.
13C NMR (100.6 MHz, D2O): δ ϭ 39.60, 50.10, 61.38, 62.13, 62.51,
65.71 ppm. IR (neat): ν˜ ϭ 3355, 2956Ϫ2819, 1407, 1299, 1115,
1073, 1044, 1011 cmϪ1. MS: m/z (%) ϭ 147 (2) [Mϩ], 116 (100),
100 (8), 98 (19), 74 (17), 70 (169, 60 (46), 56 (39), 43 (30), 36 (96).
HRMS: 148.0976; calcd. for C6H14NO3 [M ϩ H]: 148.0974.
(؉)-20: M.p. 107Ϫ109 °C. [α]2D0 ϭ ϩ12.8 (c ϭ 0.96, acetone). 1H
NMR (400 MHz, CDCl3): δ ϭ 1.62Ϫ1.69 (ddd, J ϭ 14.6, 10.8 Hz,
1 H), 2.00 (s, 3 H), 2.15Ϫ2.20 (dd, J ϭ 14.2, 6.2 Hz, 1 H), 2.40 (s,
3 H), 3.30 (dd, J ϭ 8.1, 4.8 Hz, 1 H), 3.67 (m, 1 H), 3.90 (d, J ϭ
8.2 Hz, 1 H), 4.35 (m,1 H), 4.49Ϫ4.58 (2 ϫ d, J ϭ 11.7 Hz, 2 H),
5.07Ϫ5.13 (m, 1 H), 5.73 (d, J ϭ 3.3 Hz, 1 H), 7.22Ϫ7.82 (m, 9 H)
ppm. 13C NMR (100.6 MHz, CDCl3): δ ϭ 20.78, 21.40, 28.83,
57.24, 64.24, 68.26, 70.97, 86.34, 127.51, 127.55, 127.59, 128.22,
129.58, 136.15, 137.65, 144.10, 169.41 ppm. IR (neat): ν˜ ϭ 3039,
2977Ϫ2931, 1741, 1598, 1496, 1455, 1349, 1239, 1141, 1064, 980,
Acknowledgments
We thank Dr. Swen Allerheiligen and his coworkers at Bayer AG
(Wuppertal-Aprath) for obtaining the HRMS data.
900, 858, 813, 737, 688 cmϪ1. MS: m/z (%) ϭ 340 (4) [Mϩ
benzyl], 277 (14), 276 (91), 155 (29), 108 (9), 92 (26), 91 (100), 65
Ϫ
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[O02596]
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Eur. J. Org. Chem. 2003, 1104Ϫ1110