Photochemical transformation of levoglucosan imides to anhydrosugarannelated azepanediones and azocanediones

Article abstract of DOI:10.1007/s007060200023

By reaction of O-protected 3-amino-l,6-anhydro-β-D-glucopyranose with succinic, glutaric, and tartaric anhydride, respectively, the corresponding 3-substituted succinimido, glutarimido, and tatarimido derivatives were obtained. Irradiation of the succinim

Full text of DOI:10.1007/s007060200023

Monatshefte fuÈr Chemie 133, 485±497 ꢀ2002)
Photochemical Transformation
of Levoglucosan Imides to Anhydrosugar-
Annelated Azepanediones and Azocanediones
Christian Sund1, Swantje Thiering1, Joachim Thiem1;Ã

Jurgen Kopf , and Markus Stark
,
2
3
1
Institute of Organic Chemistry, University of Hamburg, D-20146 Hamburg, Germany
Institute of Inorganic Chemistry, University of Hamburg, D-20146 Hamburg, Germany
Bell Flavors and Fragrances, Duft und Aroma GmbH, D-04205 Leipzig, Germany
2
3
Summary. By reaction of O-protected 3-amino-1,6-anhydro-ꢀ-D-glucopyranose with succinic,
glutaric, and tartaric anhydride, respectively, the corresponding 3-substituted succinimido,
glutarimido, and tatarimido derivatives were obtained. Irradiation of the succinimido and glutarimido
derivatives at 254 nm gave 1,4-diradical intermediates by ꢁ-hydrogen abstraction ꢀNorrish Type II
reaction) which subsequently recombined ꢀYang cyclization) to form azetidinols. These in turn
fragmented and led to azepanedione and azocanedione derivatives. In contrast, irradiation of the
tartarimido derivative resulted in elimination and led to both isomeric enolethers.
Keywords. 1,6-Anhydroglucopyranose; Photochemistry; Intramolecular alkylation; Anhydrosugar-
annelated azepanediones and azocanediones.
Introduction
For access to complex heterocycles, C±C-bond formation by radical reactions
leading to highly regio- and stereospeci®c products is increasingly gaining
importance. A well established radical method for this purpose is comprised by the
Norrish Type II reaction. This photochemical induced intramolecular alkylation of
N-alkylated imides by 1,6- or 1,7-hydrogen abstraction leads to compounds
containingthe annelated "-lactame structure, an integer part of a large number of
important pharmaceuticals with multiple applications [1, 2]. Previously, Kanaoka
et al. have described the synthesis of "-lactames such as 5 by irradiation of N-
alkylsuccinimides 1 [3] ꢀScheme 1).
Irradiation of imido derivatives 1 with UV light ꢀ254 nm) generates an excited
carbonyl group. For steric reasons, hydrogen abstraction from the ꢁ-position ꢀ1,6-
abstraction) is preferred leadingto a six-membered transition state 2. The approach
of the photochemically excited carbonyl function induces the intramolecular ꢁ-
hydrogen abstraction, thus establishing the diradical intermediate 3. Its subsequent
Ã
Correspondingauthor. E-mail: thiem@chemie.uni-hamburg.de

486
C. Sund et al.
Scheme 1. Photocyclization of alkylimides
Scheme 2. Photocyclization of glycosylimides
Yang cyclization [4] results in formation of azetidinol 4 which in turn fragments in
an irreversible retro-transannular ringopeningand leads to the azepanedione 5.
Previous studies of this photoreaction of 6-imidosaccharide derivatives [5] as
well as N-glycosylimides [6±8] by Thiem et al. con®rmed that corresponding
carbohydrate compounds, e.g. 6, can be transformed into sugar-derived azepane-
diones such as 7 ꢀScheme 2).
These investigations [5±8] have shown that the regiochemistry of the hydrogen
abstraction is controlled by stereoelectronic and conformational factors. In order to
elucidate the speci®c nature of these conformational effects, the bicyclic and thus
conformationally ®xed 1,6-anhydro-ꢀ-D-hexopyranoses were investigated.
Previous studies have focused on 2-imido-galactosan and 4-imido-mannosan
derivatives [9]. In the following, we report about the synthesis of various 3-imido-
glucosan derivatives and the results of their subsequent irradiation.
Results and Discussion
Preparation of saccharide imides
The synthesis of 3-imido-glucosan derivatives ꢀSchemes 3 and 4) started from 1,6-
anhydro-ꢀ-D-glucopyranose ꢀlevoglucosan, 8) and followed the well-known
pathway described by Cerny et al. [10, 11] leadingto 1,6;3,4-dianhydro- ꢀ-D-
allopyranose 9. Regioselective opening of this epoxide by sodium azide gave the

Anhydrosugar-Annelated Derivatives from Levoglucosan Imides
487
Scheme 3. i: tert-Butyldimethylsilyl tri¯ate, pyridine, 0ꢀC ± room temperature, 20 h, 77%; ii: H2,
Pd=C, ethyl acetate=MeOH, room temperature, 24 h, 95%
Scheme 4. i: Succinic anhydride ꢀn ˆ 1), glutaric anhydride ꢀn ˆ 2), DIPEA, room temperature, 24 h;
ii: pyridine, Ac2O, room temperature, 24 h, 65%; iii: pyridine, Ac2O, 60ꢀC, 48 h, 55%
gluco-con®gurated 3-azido derivative 10 [12]. Then the hydroxyl functions were
protected as photochemically inert tert-butyldimethylsilyl ꢀTBDMS) ethers using
TBDMS-tri¯ate in pyridine at 0ꢀC. Further, reduction of the protected azide 11 by
hydrogenolysis using palladium on activated charcoal led to the corresponding
amine 12 in quantitive yield.
In a very versatile approach, imido-substituted derivatives are available by
condensation of primary amines with different dicarbonic acid anhydrides
[8, 13, 14]. Startingwith the amine derivative 12, reaction with 10 equivalents

488
C. Sund et al.
of succinic ꢀn ˆ 1) or glutaric ꢀn ˆ 2) anhydride in dichloromethane and
N-ethyldiisopropylamine ꢀDIPEA) as auxiliary base led to the correspondingsuc-
cinamidic and glutaramidic acid derivatives 12a. These were not isolated; acetyla-
tion with acetic anhydride in pyridine led to a cyclization affordingthe desired
saccharide imides 13 and 14 in moderate to good yields.
Whereas the cyclization step of the succinamidic acid succeeded at room
temperature within 24 hours, the correspondingreaction to obtain the glutarimide
required both higher temperatures ꢀ60ꢀC) and longer reaction time ꢀ48 h).
Apparently, these different reaction conditions originate from the chain length of
the dicarbonic acids. The ratio of formation of the imidosaccharide derivates could
be monitored by NMR spectroscopy. In case of the succinimide derivative 13, the
four protons of the ®ve-membered succinimide ringcoincide in one singulet in the
1H NMR spectrum due to the free rotation of the C3±N-bond and hence their
chemical equivalence. In contrast, the six protons of the glutarimide ring in
derivative 14 appear in two characteristic signals, one triplet for the four meta-
positioned protons and one quintet for the two para-positionend protons.
In further attempts, another approach to functionalized imido derivatives was
investigated ꢀScheme 5). Such compounds with additional chirality in the imide
structure should be interestingstartingmaterials for further transformations to
derive branched-chain sugars. According to the synthesis of the succinimide and
glutarimide derivatives, the reaction of the amine 12 with 3,4-di-O-benzyl-tartaric
anhydride led to the correspondingtartaramidic acid, the subsequent cyclization
step of which afforded the substituted imido derivative 15 in good yield. Since
benzyl groups were not suitable for the following irradiation step due to their UV
Scheme 5. i: 3,4-Di-O-benzyl-tartaric anhydride, DIPEA, room temperature, 20 h; ii: Ac2O,
pyridine, room temperature, 24 h, 76%; iii: H2, Pd=C, MeOH, room temperature, 48 h, 86%; iv: tert-
butyldimethylsilyl tri¯ate, 2,6-dimethylpyridine, À40ꢀC ± room temperature, 48 h, 55%

Anhydrosugar-Annelated Derivatives from Levoglucosan Imides
489
absorption, a change of the protecting groups had to take place. By hydrogenolysis
usingpalladium on activated charcoal the deprotected tartarimido derivative 16
was obtained, the free hydroxyl groups of which were subsequently protected as
TBDMS ethers with tert-butyldimethylsilyltri¯uoromethanesulfonate in 2,6-
dimethylpyridine at À40ꢀC to give compound 17.
Irradiation of saccharide imides
All irradiations were performed with a low pressure mercury lamp at 254 nm under
an argon atmosphere on solutions in anhydrous acetonitrile. To avoid heating of the
reaction system by radiationless energy transfer, water cooling was required.
An abstraction in terms of a Norrish Type II reaction can be obtained only from
a cis-positioned hydrogen [5±9]. Considering the geometry of the glucosan
derivatives 13 and 14, two suitable cis-hydrogen atoms ꢀH-2 and H-4) are present
for abstraction. Irradiation of 13 was completed after 6 hours as indicated by TLC.
In accordance with its geometry, both isomers 18 and 19 were obtained in almost
equal yields in addition to 11% of startingmaterial ꢀScheme 6).
The 1H NMR spectrum of the heterocyclic sugar derivatives showed
characteristic signals suitable for the assignment of the above structures. The
new NH protons were located as doublets at 6.31 ppm in 18 and 5.69 ppm in 19,
respectively. The couplingconstants of these protons with H-3 of the sugar system
ꢀhighlighted in Scheme 6) were determined to 6.0 ꢀ18) and 6.5 ꢀ19) Hz. The
original singulet of the succinimide CH2-groups was split into two multiplets due
to formation of the novel seven-membered ring. The formation of a new
quarternary center C-9 was evident from the disappearance of proton H-9 and
veri®ed by the correspondingsignals in the 13C NMR spectrum at 77.65 ꢀ18) and
80.17 ꢀ19) ppm. Furthermore, the 13C NMR spectrum displayed two typical signals
of the amide groups at 175.67 ꢀ18) and 175.82 ꢀ19) ppm; the keto functions led to
resonances at 205.68 ꢀ18) and 209.13 ꢀ19) ppm in addition to two new signals of
secondary carbons instead of the former identical secondary carbon atoms of the
succinimide ring. The coupling constants of the sugar systems in these novel
tricyclic structures did not show signi®cant changes compared to the starting
material, thus indicatinga chair conformation of the pyranose ring.
Both photoproducts crystallized and allowed X-ray structural studies; the
correspondingdata are summarized in Table 1. Figure 1 shows an ORTEP drawing
of compound 19 to support the structure as deduced from the NMR data.
Scheme 6. i: 254 nm, CH3CN, 18ꢀC, 6 h; 18: 26%, 19: 28%

490
C. Sund et al.
Table 1. Crystal data, data collection parameters, and re®nement results for 19 ꢀEnraf-Nonius CAD4
diffractometer)
Formula
C22H41NO6Si2
471.74
Formula weight
Crystal dimension ꢀmm)
Crystal system
Space group
a ꢀpm)
0.6 Â 0.5 Â 0.1
orthorhombic
P212121 ꢀNo. 19)
835.4 ꢀ1)
1229.2 ꢀ1)
2664.7 ꢀ2)
2736.3 ꢀ4)
4
b ꢀpm)
c ꢀpm)
V ꢀ106 pm3)
Z
ꢂcalcd ꢀg Á cmÀ1
Fꢀ000)
)
1.145
1024
Radiation
ꢄ ꢀpm)
CuKꢃ
154.178
1.45
ꢅ ꢀmmÀ1
T ꢀꢀC)
)
À100
2ꢆmax ꢀꢀ)
152.74
Unique re¯exions
Observed re¯exions
Rall
3268
3014
0.0558
Flack parameter
S ˆ GooF
À0.06 ꢀ5)
0.857
Fig. 1. ORTEP drawingof 19
Even though the R value in case of compound 18 turned out to be less
convincingcompared to the correspondingvalue of derivative 19, its structure is
also shown here ꢀFig. 2). Apparently, the single crystal of 18 was of lower quality;

Anhydrosugar-Annelated Derivatives from Levoglucosan Imides
491
Fig. 2. ORTEP drawingof 18
however, the data set obtained from NMR spectroscopy was rather similar to the
correspondingdata set of compound 19.
The reaction of the glutarimido derivative 14 was complete after 4 hours of
irradiation ꢀScheme 7). According to geometric reasons, hydrogen abstraction from
position 2 and position 4 proceeded as expected and gave the heterocyclic sugars
20 and 21.
Both structures were elucidated by NMR spectroscopy showingthe charac-
teristic signals of the amide group ꢀNH proton as a doublet at 5.65 ꢀ20) and 5.97
ꢀ21) ppm; lactame carbon at 172.52 ꢀ20) and 177.23 ꢀ21) ppm) and the keto
function at 207.89 ppm for derivative 20 and 210.70 ppm for compound 21. The
new quarternary centres at C-10 ꢀ78.20 ꢀ20) and 81.69 ꢀ21) ppm) were in
1
accordance with the absence of the signals of H-10 in the H NMR spectra. The
former glutarimide system appeared in case of isomer 20 at 23.40 ꢀC-7), 33.83 ꢀC-
6), and 38.44 ꢀC-8) ppm, now ®xed in the annelated eight membered ring. Similar
data were found for compound 21: 24.53 ꢀC-7), 34.33 ꢀC-6), and 38.20 ꢀC-8) ppm.
Again, no changes concerning the coupling constants of the sugar system were
noted which proves that the conformation of the pyranose ringdid not change.
Scheme 7. i: 254 nm, CH3CN, 18ꢀC, 4 h; 20: 23%, 21: 25%

492
C. Sund et al.
Scheme 8. i: 254 nm, CH3CN, 18ꢀC, 20 h; 22: 12%, 23: 18%
In case of the tartarimido derivative 17, the irradiation was stopped after
20 hours ꢀScheme 8) due to increasingdegradation of the startingmaterial as
monitored by TLC. Two main products were isolated and characterized; they
prooved to be the unsaturated derivatives 22 and 23.
Obviously, the excited state did not react to give the expected lactames but led
after elimination of the protected imide to the enolethers 22 and 23. It may be
tentatively assumed that the TBDMS protectinggroups could stabilize the ®ve-
membered ringand assist an elimination in contrast to the photoreactions of the
succinimide and glutarimide derivatives 13 and 14.
Experimental
All reactions were monitored by TLC analysis with silica gel 60-coated sheets ꢀMerck). Compounds
were visualized by sprayingwith 20% H SO4 in EtOH followed by heatingand =or UV irradiation.
2
Column chromatography was performed on silica gel 60 ꢀ230±240 mesh, grain size 0.040±
0.063 mm, Merck). All irradiations were performed in dry acetonitrile ꢀFluka) deoxygenated by
degassing ꢀ30 min) with Ar in an ultrasonic bath employing a 60 W low-pressure Hg vapour lamp
ꢀꢄ ˆ 254 nm) from Heraeus. The photoreactor was made of quartz glass and measured 35 cm in
length and 4.5 cm in diameter. To maintain the temperature at 18ꢀC, H2O coolingwas used. Melting
points were measured on a ST-apotec apparatus and are reported uncorrected. Optical rotations were
determined at room temperature with a Perkin Elmer Polarimeter 243. Elemental analyses were
performed by the microanalytical laboratory of the Institute of Organic Chemistry of the University
of Hamburg; their results agreed favourably with the calculated values. IR spectra were recorded on
an ATI Mattson FTIR instrument ꢀGenesis Series). NMR spectra were recorded on a Bruker AMX-
400 spectrometer ꢀ1H: 400 MHz, 13C: 100 MHz); chemical shifts are referred to the solvent used,
J-values are given in Hz.
Imide formation )A)
A suspension of the amine ꢀ10.0 mmol), the quoted dicarbonic acid anhydride ꢀ100.0 mmol), and N-
ethyldiisopropylamine ꢀ10.0 mmol) in 75 cm3 dry CH2Cl2 was stirred overnight at room temperature.
After addition of 10 cm3 MeOH the solvent was evaporated under reduced pressure. The residue was
dissolved in 30 cm3 dry pyridine and 30 cm3 acetic anhydride and stirred for the quoted time at the
given temperature. The reaction mixture was concentrated under reduced pressure and codestillated
twice with toluene. The residue was taken up in CH2Cl2, neutralized with satured aqueous NaHCO3
solution, and washed with brine. Dryingand evaporation of the solvent afforded the crude product
which was puri®ed by column chromatography using the quoted eluent.

Anhydrosugar-Annelated Derivatives from Levoglucosan Imides
493
Irradiation )B)
The imido-substituted sugar ꢀ0.5±2.0 mmol) was dissolved in 200 cm3 dry, deoxygenated acetonitrile
and irradiated at 18ꢀC under an Ar atmosphere for the quoted time. Evaporation of the solvent and
puri®cation by column chromatography using the quoted eluent led to the product.
1,6-Anhydro-3-azido-2,4-bis-O-)tert-butyldimethylsilyl)-3-deoxy-ꢀ-D-glucopyranose
ꢀ11: C18H37N3O4Si2)
A solution of 10 ꢀ700 mg, 3.74 mmol) in 20 cm3 pyridine was cooled to 0ꢀC and treated with
tert-butyldimethylsilyltri¯uoromethanesulfonate ꢀ8.23 mmol, 2.2 equiv.). After stirringat room
temperature for 20 h the solvent was evaporated under reduced pressure. The residue was codestilled
with toluene, taken up in CH2Cl2, and washed with saturated aqueous NaHCO3 and brine. Drying
and evaporation of the solvent left the crude product. Puri®cation by column chromatography using
toluene:petroleum ether ˆ 15:1 as eluent afforded the product 11 ꢀ1.2 g, 2.89 mmol, 77%) as light
yellow crystals.
20
D
M.p.: 54ꢀC; ‰ꢃŠ ˆ À24:7 ꢀc ˆ 1.0, CHCl3); IR ꢀKBr): ꢇ ˆ 2112 ꢀN3) cmÀ1; 1H NMR ꢀCDCl3):
ꢈ ˆ 0.07, 0.09, 0.13, 0.14 ꢀ4s, 12H, 2 Me±Si), 0.93 ꢀs, 18H, 2 tert-Bu±Si), 3.31±3.32 ꢀm, 2H,
J2,3 ˆ 4.0 Hz, J2,4 ˆ 7.5 Hz, H-3, H-4), 3.37 ꢀdd, 1H, H-2), 3.60±3.67 ꢀm, 2H, J5,6a ˆ 5.0 Hz,
J6a,6b ˆ 7.0 Hz, H-6a, H-6b), 4.33 ꢀd, 1H, H-5), 5.20 ꢀs, 1H, H-1) ppm; 13C NMR ꢀCDCl3):
ꢈ ˆ À4.80, À3.54, À2.72, À2.62 ꢀ4C, 2 Me±Si), 16.89, 16.94 ꢀ2C, q, 2 tert-Bu±Si), 24.66, 24.68
ꢀ6C, 2 tert-Bu±Si), 66.63 ꢀ1C, ±CH2, C-6), 67.36 ꢀ1C, C-4), 73.87 ꢀ1C, C-2), 74.07 ꢀ1C, C-3), 77.99
ꢀ1C, C-5), 103.39 ꢀ1C, C-1) ppm.
3-Amino-1,6-anhydro-2,4-bis-O-)tert-butyldimethylsilyl)-3-deoxy-ꢀ-D-glucopyranose
ꢀ12; C18H39NO4Si2)
Compound 11 ꢀ2.23 g, 5.36 mmol) was dissolved in a mixture of 25 cm3 dry ethyl acetate and 25 cm3
dry MeOH and hydrogenated using 0.22 g ꢀ10% of weight) Pd=C ꢀ10%) by stirringat room
temperature under an atmosphere of H2 for 24 h. Removal of the catalyst by ®ltration and evapora-
tion of the solvents yielded the amine which was used in the next step without further puri®cation.
12 ꢀ1.98 g, 5.08 mmol, 95%) was obtained as a colourless oil.
20
D
1
‰ꢃŠ ˆ À26:2ꢀ ꢀc ˆ 0.5, CHCl3); H NMR ꢀCDCl3): ꢈ ˆ 0.08, 0.10, 0.11, 0.12 ꢀ4s, 12H, 2 Me±
Si), 0.91, 0.92 ꢀ2s, 18H, 2 tert-Bu±Si), 2.81 ꢀt, 1H, J2,4 ˆ 7.0 Hz, H-4), 3.25 ꢀd, 1H, J2,3 ˆ 1.0 Hz,
H-2), 3.33 ꢀdd, 1H, J3,4 ˆ 7.0 Hz, H-3), 3.61 ꢀdd, 1H, J5,6a ˆ 4.5 Hz, J6a,6b ˆ 7.0 Hz, H-6a), 3.69 ꢀm,
1H, H-6b), 4.29 ꢀd, 1H, H-5), 5.18 ꢀs, 1H, H-1) ppm; 13C NMR ꢀCDCl3): ꢈ ˆ À4.63, À4.54, À4.51,
À4.43 ꢀ4C, 2 Me±Si), 17.92, 17.98 ꢀ2C, q, 2 tert-Bu±Si), 25.75, 25.77, 25.83, 25.86 ꢀ6C, 2 tert-Bu±
Si), 56.17 ꢀ1C, C-3), 66.42 ꢀ1C, ±CH2, C-6), 72.00, 73.08 ꢀ2C, C-2, C-4), 78.00 ꢀ1C, C-5), 103.37
ꢀ1C, C-1) ppm.
1,6-Anhydro-2,4-bis-O-)tert-butyldimethylsilyl)-3-deoxy-3-N-succinimido-
ꢀ-D-gluco-pyranose ꢀ13; C22H41NO6Si2)
The protected 3-amino derivative 12 ꢀ150 mg, 0.38 mmol) was reacted with succinic anhydride
ꢀ0.38 g, 3.8 mmol) and N-ethyldiisopropylamine ꢀ0.1 cm3, 0.38 mmol) accordingto procedure A.
The cyclization was performed by stirringovernight at room temperature. The crude product was
puri®ed by column chromatography using toluene:acetone ˆ 50:1 as eluent to give 13 ꢀ117 mg,
0.25 mmol, 65%) as white needles.
20
D
M.p.: 112ꢀC; ‰ꢃŠ ˆ À27:2ꢀ ꢀc ˆ 1.0, CHCl3); IR ꢀKBr): ꢇ ˆ 1779, 1698 ꢀCˆO) cmÀ1; 1H NMR
ꢀCDCl3): ꢈ ˆ À0.12, À0.11, 0.04, 0.07 ꢀ4s, 12H, 2 Me±Si), 0.84 ꢀs, 18H, 2 tert-Bu±Si), 2.65 ꢀs, 4H,

494
C. Sund et al.
±CH2±CH2±, imide), 3.72 ꢀdd, 1H, J5,6a ˆ 5.0 Hz, J6a,6b ˆ 7.5 Hz, H-6a), 3.80 ꢀdd, 1H, J5,6b ˆ 1.0 Hz,
H-6b), 4.01 ꢀd, 1H, J2,4 ˆ 8.5 Hz, H-2), 4.10±4.19 ꢀm, 2H, J3,4 ˆ 8.5 Hz, H-3, H-4), 4.35 ꢀd, 1H, H-5),
5.22 ꢀs, 1H, H-1) ppm; 13C NMR ꢀCDCl3): ꢈ ˆ À4.61, À3.77, À2.87, À2.68 ꢀ4C, 2 Me±Si), 16.58,
16.64 ꢀ2C, q, 2 tert-Bu±Si), 24.44 ꢀ6C, 2 tert-Bu±Si), 26.88 ꢀ2C, ±CH2±CH2±, imide), 56.27 ꢀ1C, C-
4), 66.51 ꢀ1C, ±CH2, C-6), 67.81, 70.16 ꢀ2C, C-2, C-3), 78.32 ꢀ1C, C-5), 104.21 ꢀ1C, C-1) ppm.
1,6-Anhydro-2,4-bis-O-)tert-butyldimethylsilyl)-3-deoxy-3-N-glutarimido-
ꢀ-D-glucopyranose ꢀ14; C23H43NO6Si2)
The 3-amino-derivative 12 ꢀ1.14 g, 2.93 mmol) was reacted with glutaric anhydride ꢀ3.34 g,
29.28 mmol) and N-ethyldiisopropylamine ꢀ0.5 cm3ꢀ, 2.93 mmol) accordingto procedure A. The
cyclization was performed by stirringfor 48 h at 60 C. The crude product was puri®ed by column
chromatography using petroleum ether:ethyl acetate ˆ 7:1 as eluent to give 14 ꢀ250 mg, 0.25 mmol,
65%) as yellow oil.
20
D
1
‰ꢃŠ ˆ À57:6ꢀ ꢀc ˆ 1.0, CHCl3); H NMR ꢀCDCl3): ꢈ ˆ À0.1, À0.09, À0.03, 0.02 ꢀ4s, 12H, 2
Me±Si), 0.82, 0.83 ꢀ2s, 18H, 2 tert-Bu±Si), 1.89±1.96 ꢀm, 2H, ±CH2±CH2±CH2±, imide), 2.63 ꢀt,
4H, ±CH2±CH2±CH2±, imide), 3.71 ꢀdd, 1H, J5,6a ˆ 6.0 Hz, J6a,6b ˆ 7.5 Hz, H-6a), 3.80 ꢀdd, 1H,
J5,6b ˆ 1.5 Hz, H-6b), 3.99 ꢀd, 1H, J2,3 ˆ 8.0 Hz, H-2), 4.08 ꢀd, 1H, J3,4 ˆ 8.0 Hz, H-4), 4.33 ꢀdd, 1H,
H-5), 4.84 ꢀt, 1H, H-3), 5.20 ꢀs, 1H, H-1) ppm; 13C NMR ꢀCDCl3): ꢈ ˆ À5.09, À4.95, À4.59, À4.47
ꢀ4C, 2 Me±Si); 18.06 ꢀ2C, q, 2 tert-Bu±Si); 25.46 ꢀ6C, 2 tert-Bu±Si), 33.0, 33.66 ꢀ2C, ±CH2±CH2±
CH2±, imide), 57.56 ꢀ1C, C-3), 67.01 ꢀ1C, ±CH2, C-6), 71.70 ꢀ2C, C-2, C-4), 79.33 ꢀ1C, C-5),
105.31 ꢀ1C, C-1) ppm.
1,6-Anhydro-2,4-bis-O-)tert-butyldimethylsilyl)-3-deoxy-3-N-))30R,40R)-
30,40-bis-O-benzyl)-tatarimido-ꢀ-D-glucopyranose ꢀ15; C36H53NO8Si2)
Compound 12 ꢀ700 mg, 1.8 mmol) was reacted with 3,4-di-O-benzyltataric anhydride ꢀ1.12 g,
3.59 mmol) and N-ethyldiisopropylamine ꢀ0.31 cm3, 1.8 mmol) accordingto procedure A. The
cyclization step was carried out by stirringovernight at room temperature. The crude product was
puri®ed by column chromatography using petroleum ether:acetone ˆ 30:1 as eluent to give
compound 15 ꢀ939 mg, 76%) as colourless oil.
20
D
‰ꢃŠ ˆ À100:5ꢀ ꢀc ˆ 0.008, CHCl3); IR ꢀKBr): ꢇ ˆ 1721, 1679 ꢀCˆO) cmÀ1; 1H NMR ꢀCDCl3):
ꢈ ˆ À0.12, À0.11, 0.00, 0.03 ꢀ4s, 12H, 2 Me±Si), 0.82 ꢀs, 18H, 2 tert-Bu±Si), 3.73 ꢀdd, 1H,
J5,6a ˆ 5.0 Hz, J6a,6b ˆ 7.0 Hz, H-6a), 3.79 ꢀdd, 1H, J5,6b ˆ 4.5 Hz, H-6b), 3.94 ꢀdd, 1H, J2,4 ˆ 7.0 Hz,
J3,4 ˆ 2.0 Hz, H-4), 4.09±4.16 ꢀm, 2H, H-2, H-3), 4.26 ꢀs, 2H, ±CH±CH±, imide), 4.35 ꢀd, 1H, H-5),
4.74 ꢀd, 2H, ±CH2, ±OBn), 4.99 ꢀd, 2H, ±CH2, ±OBn), 5.23 ꢀs, 1H, H-1), 7.31±7.36 ꢀm, 10H, ±CH,
±OBn) ppm; 13C NMR ꢀCDCl3): ꢈ ˆ À4.67, À4.53, À4.24, À3.98 ꢀ4C, 2 Me±Si), 17.96, 18.04 ꢀ2C,
q, 2 tert-Bu±Si), 25.87, 25.93 ꢀ6C, 2 tert-Bu±Si), 57.76 ꢀ1C, C-4), 68.04 ꢀ1C, ±CH2, C-6), 71.41,
79.64 ꢀ3C, C-2, C-3, C-5), 73.66 ꢀ2C, 2 -CH2, ±OBn), 78.76 ꢀ2C, ±CH±CH±, imide), 105.50 ꢀ1C, C-
1), 127.35 ꢀ10C, ±CH, ±OBn), 135.67 ꢀ2C, q, ±OBn), 172.00 ꢀ2C, 2 CˆO) ppm.
1,6-Anhydro-2,4-bis-O-)tert-butyldimethylsilyl)-3-deoxy-3-N-))30R,40R)-
30,40-bis-O-hydroxy)-tatarimido-ꢀ-D-glucopyranose ꢀ16; C22H41NO8Si2)
A solution of 15 ꢀ900 mg, 1.32 mmol) in 30 cm3 dry MeOH was hydrogenated using 90 mg ꢀ10% of
weight) Pd=C ꢀ10%) by stirringat room temperature under an atmosphere of H 2 for 24 h. Removal of
the catalyst by ®ltration and evaporation of the solvents yielded compound 16 ꢀ574 mg, 86%), which
was used in the next step without further puri®cation.
20
M.p.: 85ꢀC; ‰ꢃŠ ˆ À83:3ꢀ ꢀc ˆ 1.0, CHCl3); IR ꢀKBr): ꢇ ˆ 1754 ꢀCˆO) cmÀ1
;
1H NMR
D
ꢀCDCl3): ꢈ ˆ À0.09, À0.01, 0.05 ꢀ3s, 12H, 2 Me±Si), 0.84 ꢀs, 18H, 2 tert-Bu±Si), 3.10 ꢀs, 2H, 2 OH),
3.71 ꢀdd, 1H, J5,6a ˆ 5.0 Hz, J6a,6b ˆ 7.5 Hz, H-6a), 3.80 ꢀdd, 1H, J5,6b ˆ 4.5 Hz, H-6b), 3.87±3.93

Anhydrosugar-Annelated Derivatives from Levoglucosan Imides
495
ꢀm, 1H, J2,4 ˆ 6.5 Hz, J3,4 ˆ 2.0 Hz, H-4), 4.11±4.14 ꢀm, 2H, H-2, H-3), 4.35 ꢀd, 1H, H-5), 4.49
ꢀs, 2H, ±CH±CH±, imide), 5.23 ꢀs, 1H, H-1) ppm; 13C NMR ꢀCDCl3): ꢈ ˆ À4.50, À4.53, À4.17,
À3.97 ꢀ4C, 2 Me±Si), 17.94, 18.04 ꢀ2C, q, 2 tert-Bu±Si), 25.83, 25.88 ꢀ6C, 2 tert-Bu±Si), 58.30 ꢀ1C,
C-4), 68.21 ꢀ1C, ±CH2, C-6), 71.31, 71.55 ꢀ2C, C-2, C-3), 74.95 ꢀ2C, ±CH±CH±, imide), 79.65 ꢀ1C,
C-5), 105.37 ꢀ1C, C-1), 175.00 ꢀ1C, 2 CˆO) ppm.
1,6-Anhydro-2,4-bis-O-)tert-butyldimethylsilyl)-3-deoxy-3-N-))30R,40R)-
30,40-bis-O-)tert-butyldimethylsilyl))-tatarimido-ꢀ-D-glucopyranose ꢀ17; C34H69NO8Si4)
Compound 16 ꢀ574 mg, 1.14 mmol) was dissolved in 10 cm3 dry CH2Cl2 cooled to À40ꢀC and
treated with tert-butyldimethylsilyltri¯uoromethanesulfonate ꢀ0.65 cm3, 2.85 mmol) and 2,6-
dimethylpyridine ꢀ0.33 cm3, 2.85 mmol). After stirringunder warmingto room temperature for
48 h the mixture was washed with saturated aqueous NH4Cl, saturated aqueous NaHCO3, and brine.
Dryingand evaporation of the solvent afforded the crude product which was puri®ed by column
chromatography with petroleum ether:ethyl acetae ˆ 100:1 to give 17 ꢀ460 mg, 55%) as a white
solid.
20
D
1
M.p.: 101ꢀC; ‰ꢃŠ ˆ À103:3ꢀ ꢀc ˆ 1.0, CHCl3); IR ꢀKBr): ꢇ ˆ 1725 ꢀCˆO) cmÀ1; H NMR
ꢀCDCl3): ꢈ ˆ À0.10, À0.09, 0.00, 0.03, 0.14, 0.20 ꢀ6s, 24H, 4 Me±Si), 0.83, 0.83, 0.93 ꢀ3s, 36H,
4 tert-Bu±Si), 3.68 ꢀdd, 1H, J5,6a ˆ 5.0 Hz, J6a,6b ˆ 7.0 Hz, H-6a), 3.80 ꢀdd, 1H, H-6b), 3.91 ꢀd, 1H,
J2,4 ˆ 8.5 Hz, H-2), 4.08±4.14 ꢀm, 2H, H-3, H-4), 4.32 ꢀd, 1H, H-5), 4.34 ꢀs, 2H, ±CH±CH±, imide),
5.20 ꢀs, 1H, H-1) ppm; 13C NMR ꢀCDCl3): ꢈ ˆ À5.53, À4.11 ꢀ8C, 2 Me±Si), 16.56±17.84 ꢀ4C, q,
2 tert-Bu±Si), 25.83, 25.93, 26.03 ꢀ12C, 4 tert-Bu±Si), 57.37 ꢀ1C, C-4), 68.14 ꢀ1C, ±CH2, C-6),
71.27, 71.49 ꢀ2C, C-2, C-3), 77.17 ꢀ2C, ±CH±CH±, imide), 79.71 ꢀ1C, C-5), 105.54 ꢀ1C, C-1),
176.20 ꢀ2C, 2 CˆO) ppm.
)1R,2R,8S,9S,10R)-4-Aza-2,9-bis-tert-butyldimethylsiloxy-11,13-dioxa-tricyclo
[8.2.1.0 3,9]tridecane-5,8-dione ꢀ18; C22H41NO6Si2)
and )1R,2S,8R,9R,10R)-4-Aza-2,9-bis-tert-butyldimethylsiloxy-12,13-dioxa-tricyclo
[8.2.1.0 3,9]tridecane-5,8-dione ꢀ19; C22H41NO6Si2)
A solution of succinimide 13 ꢀ500 mg, 1.06 mmol) was irradiated for 6 h according to procedure B.
Puri®cation by column chromatography with toluene:acetone ˆ 50:1 afforded 19 ꢀ146 mg,
0.31 mmol, 28%) and 18 ꢀ134 mg, 0.28 mmol, 26%), both as white crystals.
20
18: M.p.: 153ꢀC; ‰ꢃŠ ˆ ‡16:0ꢀ ꢀc ˆ 0.5, CHCl3); IR ꢀKBr): ꢇ ˆ 3241 ꢀNH), 1711, 1679
D
1
ꢀCˆO) cmÀ1; H NMR ꢀCDCl3): ꢈ ˆ À0.07, 0.00, 0.11 ꢀ3s, 12H, 2 Me±Si), 0.79, 0.81 ꢀ2s, 18H,
2 tert-Bu±Si), 2.30 ꢀdd, 1H, H-4a), 2.45±2.55 ꢀm, 1H, H-5a), 2.88±2.98 ꢀm, 2H, H-4b, H-5b), 3.57
ꢀs, 1H, H-9), 3.61 ꢀdd, 1H, J10,11a ˆ 5.0 Hz, J11a,11b ˆ 8.5 Hz, H-11a), 3.72±3.76 ꢀm, 2H,
J3,NH ˆ 6.0 Hz, H-3, H-11b), 4.34 ꢀdd, 1H, H-10), 5.62 ꢀs, 1H, H-1), 6.31 ꢀd, 1H, NH) ppm; 13C
NMR ꢀCDCl3): ꢈ ˆ À2.18, À1.03, À0.85 ꢀ4C, 2 Me±Si), 22.69 ꢀ2C, q, 2 tert-Bu±Si), 28.33, 28.49
ꢀ6C, 2 tert-Bu±Si), 31.73, 38.05 ꢀ2C, 2-CH2, C-4, C-5), 65.87 ꢀ1C, C-8), 68.08 ꢀ1C, ±CH2, C-11),
74.45 ꢀ1C, C-9), 77.65 ꢀ1C, q, C-2), 80.80 ꢀ1C, C-10), 102.87 ꢀ1C, C-1), 175.67 ꢀ1C, q, NHCˆO),
205.68 ꢀ1C, q, CˆO) ppm.
20
19: M.p.: 148ꢀC; ‰ꢃŠ ˆ À44:4ꢀ ꢀc ˆ 0.5, CHCl3); IR ꢀKBr): ꢇ ˆ 3369 ꢀNH), 1704, 1684 ꢀCˆO)
D
ppm; 1H NMR ꢀCDCl3): ꢈ ˆ 0.04, 0.11, 0.12, 0.24 ꢀ4s, 12H, 2 Me±Si), 0.92 ꢀs, 18H, 2 tert-Bu±Si),
2.47±2.61 ꢀm, 2H, H-6a, H-7a), 3.02±3.12 ꢀm, 1H, H-7b), 3.19±3.27 ꢀm, 1H, H-6b), 3.52 ꢀs, 1H,
H-2), 3.79 ꢀdd, 1H, J10,11a ˆ 5.5 Hz, J11a,11b ˆ 8.5 Hz, H-11a), 3.83 ꢀd, 1H, J3,NH ˆ 6.5 Hz,
H-3), 3.90 ꢀdd, 1H, J10,11b ˆ 1.0 Hz, H-11b), 4.73 ꢀdd, 1H, H-10), 5.31 ꢀs, 1H, H-1), 5.69 ꢀd, 1H,
NH) ppm; 13C NMR ꢀCDCl3): ꢈ ˆ À2.00, À1.93, À0.89, 3.85 ꢀ4C, 2 Me±Si), 21.24 ꢀ2C, q, 2 tert-
Bu±Si), 28.58, 28.78 ꢀ6C, 2 tert-Bu±Si), 32.05, 36.69 ꢀ2C, ±CH2±, C-6, C-7), 63.52 ꢀ1C, C-3), 68.20
ꢀ1C, ±CH2±, C-11), 74.04 ꢀ1C, C-10), 77.70 ꢀ1C, C-2), 80.17 ꢀ1C, q, C-9), 104.98 ꢀ1C, C-1), 175
ꢀ1C, q, CO, NHCˆO), 209.13 ꢀ1C, q, CˆO) ppm.

496
C. Sund et al.
)1R,2R,9S,10S,11R)-4-Aza-2,10-bis-tert-butyldimethylsiloxy-12,14-dioxa-tricyclo
[9.2.1.0 3,10]tetradecane-5,7-dione ꢀ20; C23H43NO6Si2)
and )1R,2S,9R,10R,11R)-4-Aza-2,10-bis-tert-butyldimethylsiloxy-13,14-dioxa-tricyclo
[9.2.1.0 3.10]tetradecane-5,9-dione ꢀ21; C23H43NO6Si2)
A solution of the 3-glutarimide 14 ꢀ250 mg, 0.51 mmol) was irradiated for 4 h according to procedure
B. Puri®cation by column chromatography with toluene:acetone ˆ 30:1 afforded 20 ꢀ58.29 mg,
0.12 mmol, 23%) and 21 ꢀ61.93 mg, 0.13 mmol, 25%), both as colourless oils.
20
D
1
20: ‰ꢃŠ ˆ À123:5ꢀ ꢀc ˆ 0.5, CHCl3); H NMR ꢀCDCl3): ꢈ ˆ 0.02, 0.11, 0.13, 0.23 ꢀ4s, 12H,
2 Me±Si), 0.92, 0.95 ꢀ2s, 18H, 2 tert-Bu±Si), 1.95±1.98 ꢀm, 1H, H-7a), 2.08±2.13 ꢀm, 1H, H-7b),
2.22±2.26 ꢀm, 1H, H-8a), 2.43±2.54 ꢀm, 2H, H-6a, H-6b), 3.31±3.36 ꢀdt, 1H, H-8b), 3.62 ꢀs, 1H,
H-2), 3.79±3.83 ꢀm, 2H, J3,NH ˆ 10.0 Hz, J11,12a ˆ 5.0 Hz, J12a,12b ˆ 8.5 Hz, H-3, H-12a), 4.26 ꢀd,
1H, H-12b), 4.55 ꢀd, 1H, H-11), 5.34 ꢀs, 1H, H-1), 5.98 ꢀd, 1H, NH) ppm; 13C NMR ꢀCDCl3):
ꢈ ˆ À4.96, À4.71, À3.37, À2.68 ꢀ4C, 2 Me±Si), 18.53 ꢀ2C, q, 2 tert-Bu±Si), 24.53 ꢀ1C, ±CH2, C-7),
25.96, 26.00 ꢀ6C, 2 tert-Bu±Si), 34.33 ꢀ1C, ±CH2, C-6), 38.20 ꢀ1C, ±CH2, C-8), 58.30 ꢀ1C, C-3),
65.32 ꢀ1C, C-12), 72.20 ꢀ1C, C-2), 75.37 ꢀ1C, C-11), 79.01 ꢀ1C, C-10), 102.42 ꢀ1C, C-1), 174.55
ꢀ1C, q, NH±CˆO), 210.70 ꢀ1C, q, CˆO) ppm.
20
D
1
21: ‰ꢃŠ ˆ ‡34:7ꢀ ꢀc ˆ 1.0, CHCl3); H NMR ꢀCDCl3): ꢈ ˆ 0.02, 0.12, 0.13, 0.20 ꢀ4s, 12H, 2
Me±Si), 0.93 ꢀ2s, 18H, 2 tert-Bu±Si), 2.00 ꢀm, 1H, ±CH2, H-7a), 2.25 ꢀm, 2H, ±CH2, H-8a, H-7b),
2.45 ꢀm, 1H, ±CH2, H-6a), 2.58 ꢀm, 1H, ±CH2, H-6b), 3.20 ꢀm, 1H, ±CH2, H-8b), 3.70 ꢀs, 1H, H-2),
3.76 ꢀdd, 1H, J1,13a ˆ 5.0 Hz, J13a,13b ˆ 9.0 Hz, H-13a), 3.90 ꢀd, 1H, J3,NH ˆ 11.50 Hz), 3.95 ꢀd, 1H,
H-13b), 4.42 ꢀd, 1H, H-1), 5.62 ꢀs, 1H, H-11), 5.64 ꢀd, 1H, NH) ppm; 13C NMR ꢀCDCl3): ꢈ ˆ À4.87,
À4.73, À3.26, À2.37 ꢀ4C, 2 Me±Si), 17.85 ꢀ2C, q, 2 tert-Bu±Si), 23.40 ꢀ1C, ±CH2, C-7), 25.88,
25.90 ꢀ6C, 2 tert-Bu±Si), 33.83 ꢀ1C, ±CH2, C-6), 38.44 1C, ±CH2, C-8), 60.08 ꢀ1C, C-3), 65.88 ꢀ1C,
±CH2, C-13), 73.04 ꢀ1C, C-2), 78.20 ꢀ2C, C-1, C-10), 100.30 ꢀ1C, C-11), 172.52 ꢀ1C, q, NH±CˆO),
207.89 ꢀ1C, q, CˆO) ppm.
1,6-Anhydro-2,4-bis-O-)tert-butyldimethylsilyl)-3-deoxy-ꢀ-D-erythro-hex-2-enopyranose
ꢀ22; C18H36O4Si2) and 1,6-Anhydro-2,4-bis-O-)tert-butyldimethylsilyl)-3-deoxy-
ꢀ-D-erythro-hex-3-enopyranose ꢀ23; C18H36O4Si2)
Compound 17 ꢀ410 mg, 0.56 mmol) was irradiated for 20 h according to procedure B. Subsequent
column chromatography with petroleum ether:ethyl acetate ˆ 100:1 yielded compounds 22 ꢀ38 mg,
18%) and 23 ꢀ25 mg, 12%).
22: 1H NMR ꢀCDCl3): ꢈ ˆ 0.1, 0.17, 0.22, ꢀ3s, 12H, 2 Me±Si), 0.90, 0.92 ꢀ2s, 18H, 2 tert-Bu±Si),
3.60±3.72 ꢀm, 2H, J5,6a ˆ 4.0 Hz, J6a,6b ˆ 6.0 Hz, H-6a, H-6b), 3.90 ꢀdd, 1H, J3,4 ˆ 4.0 Hz,
J4,5 ˆ 1.0 Hz, H-4), 4.41 ꢀd, 1H, H-5), 4.59 ꢀd, 1H, H-3), 5.34 ꢀs, 1H, H-1) ppm; 13C NMR
ꢀCDCl3): ꢈ ˆ À4.83, À3.64, À2.35, À1.98 ꢀ4C, 2 Me±Si), 16.97, 17.30 ꢀ2C, q, 2 tert-Bu±Si), 24.51,
24.90 ꢀ6C, 2 tert-Bu±Si), 67.22 ꢀ1C, C-4), 67.94 ꢀ1C, ±CH2, C-6), 72.74 ꢀ1C, C-5), 98.20 ꢀ1C, C-3),
101.94 ꢀ1C, C-1), 152.51 ꢀ1C, q, C-2) ppm.
1
23: H NMR ꢀCDCl3): ꢈ ˆ 0.11, 0.17, 0.18 ꢀ3s, 12H, 2 Me±Si), 0.91, 0.92 ꢀ2s, 18H, 2 tert-
Bu±Si), 3.37 ꢀdd, 1H, J5,6a ˆ 1.5 Hz, J6a,6b ˆ 7.5 Hz, H-6a), 3.84 ꢀdd, J5,6b ˆ 6.5 Hz, H-6b), 3.87 ꢀdd,
1H, J1,2 ˆ 1.5 Hz, J2,3 ˆ 5.0 Hz, H-2), 4.49±4.52 ꢀm, 1H, H-5), 4.61±4.64 ꢀm, 1H, H-3), 5.20 ꢀd, 1H,
H-1) ppm; 13C NMR ꢀCDCl3): ꢈ ˆ À4.64, À3.37, À2.81, À1.99 ꢀ4C, 2 Me±Si), 17.03, 17.29 ꢀ2C, q,
2 tert-Bu±Si), 24.51, 24.69 ꢀ6C, 2 tert-Bu±Si), 62.43 ꢀ1C, ±CH2, C-6), 67.59 ꢀ1C, C-2), 76.31 ꢀ1C,
C-5), 97.95 ꢀ1C, C-1), 98.09 ꢀ1C, C-3), 152.70 ꢀ1C, q, C-4) ppm.
Complete crystallographic data have been deposited with the Cambridge Crystallographic Data
Centre, CCDC no. 167716 ꢀ19). Copies may be obtained free of charge from The Director, CCDC,
12 Union Road, Cambridge CB2 1EZ, UK ꢀfax: ‡ 44-1223-336033, e-mail: deposit@ccdc.cam.
ac.uk or http:== www.ccdc.cam.ac.uk).

Anhydrosugar-Annelated Derivatives from Levoglucosan Imides
497
Acknowledgements
Support of this work by the Fonds der Chemischen Industrie and the Deutsche Forschungsge-
meinschaft ꢀGRK 464) is gratefully acknowledged.
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Received September 3, 2001. Accepted October 31, 2001