Cyclopentanes from N-aminoglyconolactams: Reaction mechanism and improved access to diazocyclopentanones

Article abstract of DOI:10.1002/hlca.200490218

One of the two mechanisms to rationalize the Pb(OAc)₄ oxidation of 1 to 2 and 3 postulates the intermediate generation of a carbene 25 via the acetoxy-diazepinone 22 and the oxadiazoline 23 (Scheme 2). This mechanism was excluded on the basis o

Full text of DOI:10.1002/hlca.200490218

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Helvetica Chimica Acta Vol. 87 (2004)
Cyclopentanes from N-Aminoglyconolactams: Reaction Mechanism and
Improved Access to Diazocyclopentanones
by Guixian Hu and Andrea Vasella*
Laboratorium f¸r Organische Chemie, ETH-Hˆnggerberg, HCI, CH-8093Z¸rich
One of the two mechanisms to rationalize the Pb(OAc)4 oxidation of 1 to 2 and 3 postulates the
intermediate generation of a carbene 25 via the acetoxy-diazepinone 22 and the oxadiazoline 23 (Scheme 2).
This mechanism was excluded on the basis of the oxidation of the diazepinone 32 that was synthesized in six
steps from the ribonolactone 26. Oxidation of 32 with Pb(OAc)4 provided the unstable acetoxy-diazepinone
1
intermediate 22, its C(5) epimer, and the stable 5-O-acetyl-1,5-ribonolactone 33; the H-NMR spectra of the
products of the oxidation of 32 and the decomposition of 22 showed no evidence for the formation of the
acetoxy epoxide 2 and the diazo ketone 3, excluding 22 as intermediate in the oxidation of 1. To increase the
yield of the diazo-cyclopentanones, we oxidized the acetohydrazide 34, the 4-toluenesulfonohydrazide 44, and
the N,O-diacetate 46 with Pb(OAc)4. Oxidation of the acetohydrazide 34 with Pb(OAc)4 led to a higher yield of
the diazo ketone 3 (40%) than oxidation of the N-amino-ribonolactam 1 without affecting the yield of 2.
Oxidation of the 4-toluenesulfonohydrazide 44 gave mostly the product 45 of C-acetoxylation, while the
analogous oxidation of 46 gave the acetoxy lactone 33; neither 2 nor 3 could be detected among the products,
excluding 46 as intermediate of the oxidation of 34. Oxidation of the N-acetamido-lyxonolactam 47 with
Pb(OAc)4 provided the diazo ketone 8 (77 vs. 37% from 5); higher yields of diazo ketones resulted also from the
oxidation of the acetohydrazides 48 and 49.
Introduction.
Oxidation of the N-aminoribonolactam 1 (Scheme 1) with
Pb(OAc)4 led to the acetoxy epoxide 2 (49%) and the diazo ketone 3 (29%); similarly,
Pb(OBz)4 transformed 1 into the benzoyloxy epoxide 4 (33%) and 3 (42%) [1].
Oxidation of the related N-aminolyxonolactam 5, N-aminoarabinonolactam 6, and N-
aminoxylonolactam 7 provided the corresponding diazo ketones 8 (37%),9 (22%), and
10 (25%), respectively, as major products, besides a multitude of side-products. The
synthetic potential of the acetoxy epoxide 2 was illustrated by an efficient synthesis of
mannostatin A.
Two mechanisms were discussed for this novel transformation of 1 to 2 and 3
(Scheme 2) [1]. According to both hypotheses, 1 is first transformed into 17 by N-
acetoxylation ( ! 11), elimination ( ! 12), isomerization ( ! 13), addition of an AcO
group ( ! 14), and a second N-acetoxylation ( ! 15) and elimination to form 16; ring
opening of this highly electrophilic acyl derivative leads to the azo compound 17.
According to the first mechanism, 17 is transformed into the diazo anhydride 18.
Intramolecular nucleophilic addition to the acyloxycarbonyl group forms the diaste-
reoisomeric intermediates 19 and 20. The isomer 19 forms the acetoxy epoxide 2 by
nucleophilic substitution; competing elimination of the acyloxy group may also lead
(via a diastereoisomer of 21) to the diazo ketone 3. The diastereoisomeric intermediate
20 can only undergo elimination to 21, deprotonation of 21 providing 3. A comparison
of the oxidation of 1 with Pb(OBz)4 and with Pb(OAc)4 in toluene shows that
Pb(OBz)4 leads to a higher proportion of the diazo ketone 3 relative to the acyloxy
¹ 2004 Verlag Helvetica Chimica Acta AG, Z¸rich

Helvetica Chimica Acta Vol. 87 (2004)
2435
Scheme 1
a) Pb(OAc)4, toluene, 238, 2 h; 49% of 2, 29% of 3. b) Pb(OBz)4, toluene, 238, 2 h; 33% of 4, 42% of 3.
c) Pb(OAc)4, toluene, 238, 1 h; 37% of 8, 22% of 9, 25% of 10. MOMO ˆ Methoxymethoxy, TBSOˆ
(t-Bu)Me2SiO.
epoxide (4/3 3:4 vs. 2/3 5 :3); this correlates with the relative leaving-group quality of
the BzO and AcO groups, and a higher propensity of the benzoylated analogue of 19
towards elimination. According to the second mechanism, N-acylation of 17 gives a
cyclic N-acyl diazo compound 22 that cyclizes to the oxadiazoline 23. This oxadiazoline
is transformed via the carbonyl ylide 24 and the carbene 25 to the acetoxy epoxide 2,
while the diazo ketone 3 is formed via 18 and 19/20. The first mechanism appeared
more probable, and we wondered if the second one might be excluded by showing that
the intermediate 22 is not a precursor of 2. We also wished to improve the yields of the
diazo ketones, which are versatile and promising synthetic intermediates in their own right.
Results and Discussion. Synthesis and Oxidation of the N-Acyl Hydrazone 32. The
above-mentioned diazepinone intermediate 22 (Scheme 2) should also result from the
Pb(OAc)4 oxidation of the N-acyl hydrazone 32 (Scheme 3); this kind of trans-
formation, is, indeed, well-documented by Iffland et al., and by Hoffmann and
Luthardt1) [3]. We, therefore, decided to prepare the N-acyl hydrazone 32, and to
examine its reaction with Pb(OAc)4.
1
)
On the basis of Iffland×s hydrazone oxidation, Freeman [2] realized a synthesis of cyclopropyl acetates by
Pb(OAc)4 oxidation of 3-methyl-5-phenyl-2-pyrazoline.

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Helvetica Chimica Acta Vol. 87 (2004)
Scheme 2. Hypothetical Reaction Mechanisms for the Transformation of 1 to the Acetoxy Epoxide 2 and the
Diazo Ketone 3
The synthesis of 32 was based on a report by Walker and Hogenkamp [4] according
to which PfitznerÀMoffatt oxidation of the ribonolactone 26 with N,N'-dicyclohex-
ylcarbodiimide (DCC), pyridine, CF3COOH (TFA), and DMSO, followed by addition
of oxalic acid in MeOH, leads to the corresponding aldehyde and its hydrate. However,
1
the H-NMR spectrum of the crude product obtained according to this procedure
revealed predominantly the formation of the diastereoisomeric hemiacetals 27

Helvetica Chimica Acta Vol. 87 (2004)
2437
Scheme 3
a) 1. DCC, DMSO, pyridine, TFA, 238, 1.5 h; 2. (COOH)2 ¥ 2 H2O, MeOH, 238, 0.5 h. b) TESCl, pyridine,
CH2Cl2, 08, 3h; 65% from 26. c) NH2NH2 ¥ H2O, CHCl3, 238, 24 h. d) TBSOTf, pyridine, CH2Cl2, 08, 1.5 h; 53%
from 28. e) AcOH, MeOH, 238, 48 h, 508, 8 h; 56%. f) Mol. sieves (4 ä), toluene, reflux, 22 h; 60%.
g) Pb(OAc)4, CH2Cl2, 238, 12 h; 28%. DCC ˆ N,N'-Dicyclohexylcarbodiimide, TBSO ˆ (t-Bu)Me2SiO,
TESO ˆ Et3SiO, Tf ˆ CF3SO2.
(Scheme 3). O-Triethylsilylation2) of the crude hemiacetals led to a mixture of the
diastereoisomeric acetals 28 that were isolated in a yield of 65%. Treatment of 28 with
NH2NH2 ¥ H2O gave a mixture of the ring-opened hydrazides 29. Protection as the (t-
Bu)Me2Si (TBS) ethers provided a 6 :4 mixture of the diastereoisomeric hydrazides 30
(53% from 28) that were separated by flash chromatography (FC). Treatment of the
mixture 30 under acidic conditions provided the N,O-hemiacetal 31 (56%) rather than
the expected diazepinone 32 that was obtained only upon heating 31 for 22 h in toluene
in the presence of molecular sieves (4 ä)3). Molecular sieves proved crucial, and
several portions had to be added to complete the transformation of 31 into 32, which
was isolated as white crystals in a yield of 60%.
Oxidation of 32 with Pb(OAc)4 in CH2Cl2 at room temperature for 12 h, followed
by usual workup, gave a crude product without loss of material. Its 1H-NMR spectrum
showed no signals for either the acetoxy epoxide 2 or the diazo ketone 3, and the only
product that could be isolated by chromatography was the acetoxy lactone 33.
Oxidation of 32 with Pb(OAc)4 in toluene at room temperature for 1 h, followed by
usual workup, led similarly without loss of material to a 4 :2 :1 mixture of three
products: according to 1H-NMR analysis, the desired intermediate 22, its C(5)-epimer,
and the lactone 33. No signals of either 2 or 3 could be detected. The major product is
characterized by a d at 5.81 (J ˆ 10.0, HÀC(5)), a d at 4.86 (J ˆ 6.5, HÀC(2)), a dd at
4.42 (J ˆ 6.5, 4.5, HÀC(3)), and a dd at 3.81 ppm (J ˆ 10.0 and 4.5, HÀC(4)). The
2
)
The hemiacetals were originally protected by trimethylsilylation. Treating the resulting mixed acetals with
NH2NH2 ¥ H2O led to a complex mixture, indicating that the Me3SiO (TMSO) group is insufficiently stable
to the conditions of hydrazinolysis.
3
)
See [5] for analogous transformations to pyridazinones.

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Helvetica Chimica Acta Vol. 87 (2004)
second major product showed a br. s at 6.04 (HÀC(5)), a d at 4.65 (J ˆ 7.0, HÀC(2)), a
dd at 4.57 (J ˆ 7.0 and 4.5, HÀC(3)), and a br. d at 4.35 ppm (J ˆ 4.5, HÀC(4)). The
stability of the products was evaluated by periodically taking 1H-NMR spectra. Signals
of the first product, 22, disappeared within 24 h at room temperature, those of the
second product disappeared more slowly, and only 33 remained after 4 days. It was
isolated by FC in a yield of 17%.
The isolation of the acetoxy lactone 33, the formation of 224) and its C(5)-epimer,
and the absence of signals for 2 or 3 in the crude products resulting from Pb(OAc)4
oxidation of the diazepinone 32 constitute strong evidence against the alternative
mechanism involving 22 as intermediate. This is also in agreement with the observation
that the transformation of D3-1,3,4-oxadiazolines to the corresponding ylides requires
higher temperatures (> 808) [7]. The formation of the acetoxy lactone 33 from N-acyl
diazo compounds is precedented [8].
The 1H-NMR spectra of crude 27 showed two MeO s at 3.40 and 3.37 ppm (60 :40).
An IR band for 28 at 1793cm À1 and the 13CˆO s at 174.26 ppm evidence a 1,4-lactone,
the isopropylidene Me groups (s) resonate at 1.47 and 1.37 ppm, and two m at 1.05
0.85 and at 0.75 0.50 ppm indicate the Et3Si group. The mixed acetal moiety of the
diastereoisomers 28 is characterized by two d at 4.80 and 4.79 ppm, and two d at 96.61
and 96.13ppm.
The hydrazide moiety of the major isomer 30 is evidenced by a br. s at 7.53, a br. d at
3.70 ppm, and an IR band at 1682 cmÀ1. The mixed acetal moiety gives rise to a MeO s
at 3.38 ppm, a t at 0.98 ppm and a q at 0.69 ppm, a HÀC(1) d at 5.22 ppm, and a 13C(1) d
at 99.52 ppm. The minor isomer 30 shows very similar data.
Cyclization of 30 to the N-amino-5-hydroxyribonolactam 31 is evidenced by a new
IR band at 1651 cmÀ1, the disappearance of the MeO and Et3Si signals, the replacement
of the br. s at 7.53and the br. d at 3.70 ppm for the hydrazide group by a br. s at 4.52
4.20 ppm, and a br. OH s at 3.82 ppm. The coupling constants for the ring CÀH ds are
similar to those of 45 (Scheme 5, and Table in Exper. Part), suggesting the same
configuration and a similar conformation.
Elemental analysis and the mass spectrum of 32 evidence the empirical formula
C14H26N2O4Si. The formation of the N-acylhydrazone 32 from 31 was revealed by the
disappearance of the OH and exo-NH2 signals. A strong IR band at 1679 cmÀ1 and the
shoulder at 1639 cmÀ1 indicate a CˆO and a CˆN group, as confirmed by a 13C s at
168.61 and a br. d at 163.38 ppm. The br. s at 8.09 and the d at 7.44 ppm revealed an N-
acylhydrazone substructure.
The empirical formula C16H28O7Si of 33 is based on elemental analysis and the HR-
ESI-MS. NMR Data evidence a (t-Bu)Me2Si and an isopropylidene group. Two 13CˆO
1
resonate as two s at 167.84 and 167.41 ppm. The H s at 2.15 ppm and the 13C q at
20.96 ppm show that one of them is part of an AcO group. A strong, broad IR band at
1769 cmÀ1 results from the overlap of the AcO and the 1,5-lactone CˆO bands [9]. A
1H-NMR spectrum in CDCl3 showed overlapping signals at 4.67 ppm (2 H), but a
1H-NMR spectrum in C6D6 was well-resolved and showed that 33 possesses the same
configuration and conformation as 31 and 45 (Table in Exper. Part).
The transformation of acyclic N-acyl hydrazones with Pb(OAc)4 to D3-1,3,4-oxadiazolines is well-
4
)
documented [6]

Helvetica Chimica Acta Vol. 87 (2004)
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Synthesis and Oxidation of N'-Acetyl-N-aminoribonolactams; Improved Access to
Carbohydrate-Derived Diazo-cyclopentanones. According to the reaction mechanism
formulated in Scheme 2, nucleophilic addition of acetate (or AcOH) to the
intermediate 16 leads via ring opening and elimination of acetate to an intramolecular
acylation of the diazo anhydride 18. Suppressing the oxidation of 12 to 16, or enhancing
the electrophilic character of 12, e.g., by N-acylation or N-sulfonylation, might lead to
an analogous nucleophilic addition of acetate (or AcOH) to 12 (or a derivative of 12),
followed by ring opening, formation of a hydrazone, and intramolecular C-acylation. A
hypothetical reaction mechanism is formulated in Scheme 4 for the N'-acetyl-N-
aminolactam 34. N-Acetoxylation to 35 and elimination of acetate generates 36, an
analogue of 12 with enhanced electrophilic character. Ring opening to 37 and
tautomerisation yields the N-acetylated hydrazone 38, or the deacetylated 39.
Intramolecular C-acylation to 40 or 41, followed by tautomerization, should lead to
42 or 43; a final oxidation step [10] (with, in the case of 42, concomitant deacetylation)
will then lead to 3.
Scheme 4
The N-amino-ribonolactam 1 was acetylated (Ac2O/MeOH) to provide 34 in a yield
of 99%; 1 was similarly tosylated (TsCl/pyridine) to yield 90% of the 4-toluenesulfo-
nohydrazide 44 (Scheme 5). Oxidation of the acetohydrazide 34 with Pb(OAc)4 gave
the acetoxy epoxide 2 (43%) and the diazo ketone 3 (40%). The higher yield of 3 and
the ratio 2/3 1:1, as compared to 2/3 5 :3from the oxidation of 1 evidence the value of
the hypothesis and, within its framework, a competing N-deacylation of the
intermediate 36. Oxidation of the 4-toluenesulfonohydrazide 44 with Pb(OAc)4
yielded 25% of 2, 14% of 3, and 50% of the C(5)-acetoxylated 45. In this case, the
ratio 2/3 5 :3was not affected, but the yields were considerably lowered in favor of 45.
Although 45 resisted further oxidation with Pb(OAc)4, this result prompted us to check
if the analogous acetate 46 is an intermediate in the oxidation of 34 to the acetoxy
epoxide 2 and the diazo ketone 3. The acetate 46 was readily prepared in a yield of 58%

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Helvetica Chimica Acta Vol. 87 (2004)
from 31 (Schemes 3 and 5). It reacted slowly with Pb(OAc)4 to yield 57% of the acetoxy
lactone 33; neither 2 nor 3 were detected in the crude product. Although these
observations do not falsify the reaction mechanism proposed for the oxidation of 1,
they suggest that the oxidation of 1 to 16 may not occur via 14; thus, C-acetoxylation of
11 could directly lead to 15.
Scheme 5
a) Ac2O, MeOH, 238, 1 h; 99%. b) Pb(OAc)4, toluene/CH2Cl2, 238, 2 h; 43% of 2, 40% of 3. c) TsCl, pyridine,
CH2Cl2, 238, 3h; 90%. d) Pb(OAc)4, toluene/CH2Cl2, 238, 2 h; 25% of 2, 14% of 3, 50% of 45. e) Ac2O,
pyridine, 08, 3h, 23 8, 24 h; 58%. f) Pb(OAc)4, toluene/CH2Cl2, 238, 12 h; 57%.
Oxidation of the N-acetate 34 resulted in a higher amount of the diazo ketone 3
(40%) and in a higher combined yield (83%) of the cyclopentanes 2 and 3. We,
therefore, also subjected the N'-Ac derivates of the N-amino lactams 5 7 to the action
of Pb(OAc)4. The N'-acetylated 47, 48, and 49 were prepared in high yields by N-
acetylation of 5 7. As expected, their oxidation with Pb(OAc)4 gave the corresponding
diazo ketones 8 10 (Scheme 6). Compared to the results of the oxidation of 5 7, the
yield of 8 10 increased considerably, from 37 to 77% for the N-amino-d-lyxonolac-
tam-derived diazo ketone 8, from 22 to 39% for the N-amino-d-arabinonolactam
derived 9, and from 25 to 46% for the N-amino-d-xylonolactam derived 10,
respectively.
Acetylation of 1 to 34 is evidenced by the replacement of the NH2 s by a broad s at
9.04 ppm, and, additionally, a s at 2.00 ppm, a new 13C s at 167.25 (or 167.23) ppm, and a
13C q at 21.08 ppm, typical for an NHAc moiety. The 4-toluenesulfonohydrazide 44 is
recognized by a new broad s at 7.90 ppm and the s at 2.41 ppm, by the 13C q at 22.03ppm

Helvetica Chimica Acta Vol. 87 (2004)
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Scheme 6
a) Ac2O, MeOH, 238, 1 3h; 99% of 47, 99% of 48, 94% of 49. b) Pb(OAc)4, toluene, 238, 1 2 h; 77% of 8,
39% of 9, 46% of 10.
‡
besides the aromatic 13C×s signals showing a Ts group, and by [M ‡ Na] (493, 100%).
The structure of the oxidation product 45 was established by X-ray crystal-structure
analysis5) (Fig.). The AcO group is oriented trans to the (t-Bu)Me2SiO group at C(4),
in keeping with J(4,5) (Table in Exper. Part). The O,N-di-acetylation of 31 to 46 is
evidenced by IR bands at 1757, 1731, and 1707 cmÀ1, two s at 2.12 and 2.01 ppm, a q at
21.13ppm, and three s at 169.88, 169.42, and 167.75 ppm. The trans-arrangement of
AcOÀC(5) and (t-Bu)Me2SiOÀC(4) in 46 is confirmed by a comparison of the J(4,5)
value to that of 45 (Table in Exper. Part). Similarly to 34, the structures of the
Figure. Crystal structure of the 5-acetoxy-N-(tosylamino)ribonolactam 45
5
)
The crystallographic data have been deposited with the Cambridge Crystallographic Data Centre as
deposition No. CCDC-239384. Copies of the data can be obtained, free of charge, on application to the
CCDC, 12 Union Road, Cambridge CB21EZ, UK (fax: ‡44(1223)336033; e-mail: deposit@ccdc.cam.ac.uk).

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Helvetica Chimica Acta Vol. 87 (2004)
acetohydrazides 47 49 are evidenced by a br. s between 9.5 and 8.2 ppm for a NH
group, a s around 2.00 ppm, two 13C s around 167 170 ppm, and a 13C q around 21 ppm.
We thank Dr. B. Schweizer for the crystal-structure determination, Dr. B. Bernet for checking the Exper.
Part, and the Swiss National Science Foundation, F. Hoffman-La Roche AG, Basel, and OxfordGlycosciences,
Abingdon GB, for generous support.
Experimental Part
General. Unless specified otherwise, reactions were carried under N2. Solvents were removed under
reduced pressure (rotatory evaporator). CH2Cl2 was distilled over CaH2 and toluene over Na immediately
before use. Org. phases were dried with MgSO4. TLC: Merck silica gel 60F-254 plates; detection with UVand/or
by heating with Mostain (400 ml of 10% H2SO4 soln., 20 g of (NH4)6 Mo7O24 ¥ 6 H2O, 0.4 g of Ce(SO4)2). M.p.:
uncorrected. Optical rotations [a]2D5 were determined at 589 nm.
(1R/1S)-3,4-O-Isopropylidene-l-riburono-5,2-lactone Methyl Triethylsilyl Acetals (28). A soln. of 26
(1.88 g, 10 mmol) in DMSO (40 ml) was treated sequentially with DCC (6.25 g, 30 mmol), pyridine (0.4 ml,
5 mmol), and TFA (0.37 ml, 5 mmol), stirred at r.t. for 1.5 h, and diluted with AcOEt (100 ml). The mixture was
treated dropwise with a soln. of oxalic acid dihydrate (3.2 g, 25 mmol) in MeOH (10 ml) and stirred at r.t. for
0.5 h. After the addition of brine (60 ml), the mixture was filtered. The org. layer was extracted with AcOEt
(2 Â 60 ml), washed with brine (2 Â 60 ml), and a mixture of brine (60 ml) and sat. NaHCO3 soln. (3ml,
adjusting the mixture to pH of ca. 7), dried, and evaporated. A cooled (08) soln. of the residue (3.46 g of crude
27) in CH2Cl2 (20 ml) was treated with Et3SiCl (3.5 ml, 20 mmol) and pyridine (5 ml), stirred for 3 h, treated
with H2O, and extracted with CH2Cl2 (3 Â 50 ml). The combined org. layers were dried and evaporated. FC
(cyclohexane/AcOEt 20 :1) gave 28 (2.08 g, 65% from 26). Rf (cyclohexane/AcOEt 4 :1) 0.63. IR (CHCl3):
2957m, 2914w, 2878w, 1793s, 1457w, 1414w, 1375m, 1332w, 1238m, 1214m, 1173s, 1151s, 1130s, 1069vs, 1003s, 977s,
1
855s, 784m, 729s. H-NMR (CDCl3, 300 MHz, 2 :1 mixture of diastereoisomers): signals of both isomers: 1.47,
1.37 (2s, Me2C); 1.05 0.85 (m, (MeCH2)3Si); 0.75 0.50 (m, (MeCH2)3Si); signals of the major isomer: 4.87 (d,
J ˆ 5.9, HÀC(4)); 4.80 (d, J ˆ 2.2, HÀC(1)); 4.63( d, J ˆ 5.9, HÀC(3)); 4.48 (d, J ˆ 2.2, HÀC(2)); 3.43 (s, MeO);
signals of the minor isomer: 4.88 (d, J ˆ 5.9, HÀC(4)); 4.79 (d, J ˆ 2.2, HÀC(1)); 4.68 (d, J ˆ 5.6, HÀC(3)); 4.33
(d, J ˆ 2.5, HÀC(2)); 3.33 (s, MeO). 13C-NMR (CDCl3, 75 MHz, 2 :1 mixture of diastereoisomers): signals of
both isomers: 112.94 (s, Me2C); 26.74 (q, MeC); 6.70 (t, (MeCH2)3Si); 4.87 (q, (MeCH2)3Si); signals of the major
isomer: 173.98 (s, CˆO); 96.61 (d, C(5)); 82.07, 75.78, 75.31 (3d, C(2), C(3), C(4)); 56.10 (q, MeO); 25.44 (q,
MeC); signals of the minor isomer: 174.26 (s, CˆO); 96.13( d, C(5)); 83.00, 75.71, 75.39 (3d, C(2), C(3), C(4));
‡
‡
56.34 (q, MeO); 25.50 (q, MeC). ESI-MS: 687 (45, [2 M ‡ Na] ), 387 (39, [M ‡ MeOH ‡ Na] ), 371 (33, [M ‡
‡
‡
K] ), 355 (100, [M ‡ Na] ).
(1R/1S)-2-O-[(tert-Butyl)dimethylsilyl]-3,4-O-isopropylidene-l-riburonohydrazide Methyl Triethylsilyl
Acetals (30). A soln. of 28 (800 mg, 2.4 mmol) in CHCl3 (5 ml) was treated with NH2NH2 ¥ H2O (150 ml,
3mmol), stirred at r.t. for 24 h, washed with brine (10 ml), dried, and evaporated. A cooled (0 8) soln. of the
residue (805 mg of crude 29) in CH2Cl2 (10 ml) was treated with pyridine (2 ml) and TBSOTf (1.15 ml, 5 mmol),
stirred for 1.5 h, treated with brine (15 ml), stirred at r.t. for 0.5 h, and extracted with CH2Cl2 (3 Â 15 ml). The
combined org. layers were dried and evaporated. FC (cyclohexane/AcOEt 6 :1 ! 4 :1) gave the major and the
minor diastereoisomers of 30 (430 and 180 mg, resp.; 53% from 28).
Data of 30 (major isomer a): Oil. Rf (cyclohexane/AcOEt 2 :1) 0.55. [a]2D5 ˆ ‡6.5 (c ˆ 0.55, CHCl3). IR
(CHCl3): 3452w, 3334w, 2956s, 2932m, 2879m, 2857m, 1682s, 1625m, 1493m, 1473m, 1462m, 1413w, 1384m,
1255m, 1155m, 1135m, 1067s, 1004m, 83 7m, 827m. 1H-NMR (CDCl3, 300 MHz): 7.53 (br. s, NH); 5.22 (d, J ˆ 7.2,
HÀC(1)); 4.60 (dd, J ˆ 8.1, 2.5, HÀC(3)); 4.44 (d, J ˆ 8.1, HÀC(4)); 3.95 (dd, J ˆ 7.2, 2.5, HÀC(2)); 3.70 (br. d,
J ˆ 2.8, NH2); 3.38 (s, MeO); 1.55, 1.31 (2s, Me2C); 0.98 (t, J ꢀ 8.0, (MeCH2)3Si); 0.85 (s, Me3C); 0.69 (q, J ꢀ
8.0, (MeCH2)3Si); 0.06, 0.05 (2s, Me2Si). 13C-NMR (CDCl3, 75 MHz): 171.20 (s, CˆO); 108.13( s, Me2C); 99.52
(d, C(1)); 78.51 (d, C(4)); 74.85, 74.67 (2d, C(2), C(3)); 55.99 (q, MeO); 26.43, 23.72 (2q, Me2C); 26.03( q,
Me3C); 18.48 (s, Me3C); 7.00 (q, (MeCH2)3Si); 5.50 (t, (MeCH2)3Si); À 4.02, À 4.77 (2q, Me2Si). ESI-MS: 979
‡
‡
‡
‡
(21, [2 M ‡ Na] ), 947 (24, [2 M À MeOH ‡ Na] ), 745 (100), 517 (14, [M ‡ K] ), 501 (57, [M ‡ Na] ), 479 (26,
‡
[M ‡ H] ). Anal. calc. for C21H46N2O6Si2 (478.78): C 52.68, H 9.68, N 5.85; found: C 52.93, H 9.76, N 5.75.
Data of 30 (minor isomer b): Oil. Rf (cyclohexane/AcOEt 2 :1) 0.30. [a]2D5 ˆ À25.9 (c ˆ 0.5, CHCl3). IR
(neat): 3452w, 3327w, 2953m, 2933w, 2879w, 2856w, 1683m, 1626w, 1496w, 1473w, 1462w, 1413w, 1381w, 1372w,
1
1244m, 1215m, 1168m, 1153m, 1114m, 1072s, 1004s, 897m, 83 3s, 778s, 727s. H-NMR (CDCl3, 300 MHz): 7.66

Helvetica Chimica Acta Vol. 87 (2004)
2443
(br. s, NH); 4.92 (d, J ˆ 4.0, HÀC(1)); 4.50 4.42 (m, HÀC(3), HÀC(4)); 4.05 (dd, J ˆ 4.0, 1.2, HÀC(2)); 3.71
(br. s, NH2); 3.40 (s, MeO); 1.60, 1.34 (2s, Me2C); 0.97 (t, J ˆ 7.8, (MeCH2)3Si); 0.87 (s, Me3C); 0.66 (q, J ˆ 7.8,
(MeCH2)3Si); 0.084, 0.075 (2s, Me2Si). 13C-NMR (CDCl3, 75 MHz): 171.68 (s, CˆO); 108.58 (s, Me2C); 99.13( d,
C(1)); 77.81 (d, C(4)); 75.44, 74.01 (2d, C(2), C(3)); 55.00 (q, MeO); 26.78, 25.11 (2q, Me2C); 26.36 (q, Me3C);
18.65 (s, Me3C); 7.06 (q, (MeCH2)3Si); 5.34 (t, (MeCH2)3Si); À 4.06, À 4.35 (2q, Me2Si). ESI-MS: 479 (34, [M ‡
‡
H] ), 365 (80), 129 (100). Anal. calc. for C21H46N2O6Si2 (478.78): C 52.68, H 9.68, N 5.85; found: C 52.78, H 9.76,
N 5.74.
(5R)-4-O-[(tert-Butyl)dimethylsilyl]-5-C-hydrazino-2,3-O-isopropylidene-d-ribono-1,5-lactam (31). a) A
soln. of 30 (major isomer a; 330 mg, 0.71 mmol) in MeOH (5 ml) was treated with AcOH (0.12 ml) and stirred
at r.t. for 48 h and at 508 for 8 h. Removal of the solvents by co-evaporation with toluene and FC (cyclohexane/
AcOEt 1:1 ! 1:3) gave 31 as a solid (132 mg, 56%).
b) A soln. of 30 (mixture of two diastereoisomers; 2.39 g, 5 mmol) in MeOH (50 ml) was treated with
AcOH (0.9 ml, 15 mmol) and stirred at 508 for 8 h. Removal of the solvents by co-evaporation with toluene and
FC (cyclohexane/AcOEt 1:1 ! 1 :3) gave 31 as a solid (860 mg, 52%).
Data of 31: Rf (cyclohexane/AcOEt 1:1) 0.12. IR (neat): 3324w (br.), 2951w, 2929w, 2897w, 2857w, 1651m,
1472w, 1462w, 1381m, 1374m, 1252m, 1208m, 1149m, 1099m, 1070s, 980m, 93 8m, 910m, 884m, 867m, 83 4s, 776s.
1H-NMR (CDCl3, 300 MHz): see the Table; additionally, 4.52 4.20 (m, NH2); 3.82 (br. s, HOÀC(5)); 1.46, 1.39
(2s, Me2C); 0.89 (s, Me3C); 0.12 (s, Me2Si). 13C-NMR (CDCl3, 75 MHz): see the Table; additionally, 167.94 (s,
CˆO); 110.96 (s, Me2C); 26.46, 24.86 (2q, Me2C); 25.83( q, Me3C); 18.23( s, Me3C); À 4.41, À 4.85 (2q, Me2Si).
‡
‡
‡
MALDI-MS: 355 (100, [M ‡ Na] ), 333 (16, [M ‡ H] ). HR-MALDI-MS: 355.1656 (100, [M ‡ Na] ,
‡
C14H28N2NaO5 ; calc. 355.1660).
Table 1. Selected 1H- and 13C-NMR Chemical Shifts [ppm] and Coupling Constants [Hz] of 31 34, and 44 46
in CDCl3
31
4.62 4.52
4.62 4.52
4.06
32
33a)
34
44
45
46
HÀC(2)
HÀC(3)
HÀC(4)
HÀC(5)
H'ÀC(5)
J(2,3)
4.70 84.634.3 4.52
4.16
4.45
4.35
3.45
3.83
5.9
4.26
4.37
4.14
3.79
3.86
7.5
4.77
4.60
4.18
6.23
4.70 4.63
4.53
4.23
3.84
6.59
4.67
4.15
6.05
5.02
7.44
b
b
)
)
1.5
3.7
8.1
3.7
4.7
8.7
3.4
4.0
8.4
3.4
4.4
J(3,4)
J(4,5)
2.5
5.0
2.2
4.2
3.1
3.4
J(4,5')
J(5,5')
C(2)
C(3)
C(4)
9.36.9
11.0
12.7
73.73d)
72.72d)
67.76
85.55c)
77.35
73.36d)
72.65d)
66.0365.81
92.72
76.53d)
74.08d)
76.36d)
73.02d)
72.91d)
72.32d)
65.82
88.41
72.97d)
72.88d)
70.31c)
2
65.3 64.87
c
C(5)
.68 86.23163
)
51.92
54.59
85.22
a) In C6D6. b) Not assigned. c) Broad signal. d) The assignments may be interchanged.
4-O-[(tert-Butyl)dimethylsilyl]-5-deoxy-5-hydrazono-2,3-O-isopropylidene-d-ribono-1,51-lactam (32). A
soln. of 31 (132 mg, 0.4 mmol) in toluene (8 ml) was treated with molecular sieves (4 ä; 1 g), boiled under
reflux for 18 h, treated with more molecular sieves (4 ä; 1 g), and again boiled under reflux for 4 h. Filtration
and evaporation gave 115 mg of residue, which was purified by FC (cyclohexane/AcOEt 3:1) to afford 32
(75 mg, 60%). White crystals M.p. 135.5 1378 (hexane). Rf (cyclohexane/AcOEt 1:1) 0.73. [a]2D5 ˆ À231.1 (c ˆ
1.6, CHCl3). IR (CHCl3): 3400m, 3018m, 2955m, 2931s, 1679s, 1639w, 1603w, 1471w, 1463w, 1384m, 1378m,
1363m, 1260s, 1163m, 1113s, 1063s, 1006w, 977m, 93 7w, 912w, 888m, 861m, 83 9s, 806m. IR (neat): 3203w (br.),
3092w, 2931w, 2857w, 1667s, 1636m, 1472w, 1463w, 1383m, 1375m, 1361m, 1251m, 1211s, 1162m, 1134m, 1113s,
1058s, 1007w, 979m, 93 6w, 889m, 862s, 83 6vs, 774s, 73 3s, 674m. 1H-NMR (CDCl3, 300 MHz): see the Table;
additionally, 8.09 (br. s, NH); 1.54, 1.34 (2s, Me2C); 0.90 (s, Me3C); 0.104, 0.099 (2s, Me2Si). 13C-NMR (CDCl3,
75 MHz): see the Table; additionally, 168.61 (s, CˆO); 163.68 (br. d, C ˆ N); 111.28 (s, Me2C); 25.83( q, Me3C);

2444
Helvetica Chimica Acta Vol. 87 (2004)
‡
25.54, 24.38 (2q, Me2C); 18.35 (s, Me3C); À 4.61 (q, Me2Si). MALDI-MS: 337 (61, [M ‡ Na] ), 315 (100, [M ‡
‡
‡
‡
H] ). HR-MALDI-MS: 315.1734 (100, [M ‡ H] , C14H27NaN2O4 ; calc. 315.1735). Anal. calc. for C14H26N2O4Si
(314.46): C 53.47, H 8.33, N 8.91; found: C 53.55, H 8.30, N 8.70.
(5S)-5-C-Acetoxy-4-O-[(tert-butyl)dimethylsilyl]-2,3-O-isopropylidene-d-ribono-1,5-lactone (33). A soln.
of Pb(OAc)4 (133 mg, 0.2 mmol) in CH2Cl2 (5 ml) was treated with a soln. of 32 (32 mg, 0.1 mmol) in CH2Cl2
(5 ml). The mixture was stirred at r.t. for 12 h, treated with H2O, and extracted with Et2O (25 ml and 2 Â 10 ml).
The combined org. layers were dried and evaporated. FC (cyclohexane/AcOEt 10 :1 ! 4 :1) gave 33 (10 mg,
28%) Oil. Rf (cyclohexane/AcOEt 2 :1) 0.40. [a]2D5 ˆ ‡56.6 (c ˆ 0.25, CHCl3). IR (CHCl3): 2954m, 2931m,
2859w, 1779s (br.), 1472w, 1463w, 1377m, 1258m, 1162s, 1108s, 1081m, 1014s, 990m, 940w, 840m. IR (neat):
2952w, 2931w, 2858w, 1769s (br.), 1473w, 1463w, 1376m, 1252m, 1210m, 1154s, 1104s, 1076m, 1012s, 990s, 940m,
837s. 1H-NMR (CDCl3, 300 MHz): 6.37 (d, J ˆ 3.9, HÀC(5)); 4.67 (d, J ˆ 2.1, HÀC(2), HÀC(3)); 4.17 (dt, J ˆ
4.0, 2.0, HÀC(4)); 2.15 (s, AcO); 1.54, 1.42 (2s, Me2O); 0.90 (s, Me3C); 0.13, 0.12 (2s, Me2Si). 1H-NMR (C6D6,
300 MHz): see the Table; additionally, 3.84 (dd, J ˆ 4.7, 3.7, irrad. at 6.59 ! d, J ˆ 3.6, HÀC(4)); 1.54 (s, AcO);
1.41, 1.13(2 s, Me2C); 0.91 (s, Me3C); 0.06, 0.00 (2s, Me2Si). 13C-NMR (CDCl3, 75 MHz): 167.84, 167.41 (2s, 2
CˆO); 111.71 (s, Me2C); 92.86 (d, C(5)); 72.65, 71.79 (2d, C(2), C(3)); 64.88 (d, C(4)); 26.10, 24.83(2 q, Me2C);
25.68 (q, Me3C); 20.96 (q, MeCˆO); 18.24 (s, Me3C); À 4.32, À 5.05 (2q, Me2Si). 13C-NMR (C6D6, 75 MHz):
see Table; additionally, 167.67, 166.20 (2s, 2 CˆO); 111.72 (s, Me2C); 26.40, 25.05 (2q, Me2C); 25.87 (q, Me3C);
‡
20.29 (q, MeCˆO); 18.46 (s, Me3C); À 4.24, À 4.94 (2q, Me2Si). HR-ESI-MS: 383.1485 (100, [M ‡ Na] ,
‡
C16H28NaO7Si ; calc. 383.1497). Anal. calc. for C16H28O7Si (360.48): C 53.31, H 7.83; found: C 53.13, H 7.96, N
0.08.
N-Acetamido-5-amino-4-O-[(tert-butyl)dimethylsilyl]-5-deoxy-2,3-O-isopropylidene-d-ribono-1,5-lactam
(34). A soln. of 1 (680 mg, 2.15 mmol) in MeOH (10 ml) was treated with Ac2O (0.44 ml, 4.3mmol) and stirred
at r.t. for 1 h. Co-evaporation with toluene and crystallization (cyclohexane/Et2O) gave 34 (760 mg, 99%).
White crystals. M.p. 233 2358. Rf (CH2Cl2/MeOH/Et3N 200 :10 :1.5) 0.34. [a]2D5 ˆ À30.9 (c ˆ 1.0, CHCl3). IR
(CHCl3): 3394w, 3252w (br.), 2955m, 2932m, 2859m, 1712m, 1674s, 1471m, 1421w, 1384m, 1375m, 1259s, 1165m,
1135m, 1093m, 1054m, 994m, 882m, 83 9s. 1H-NMR (300 MHz, CDCl3): see the Table; additionally, 9.04 (br. s,
NH); 2.00 (s, AcN); 1.45, 1.40 (2s, Me2C); 0.90 (s, Me3C); 0.14, 0.12 (2s, Me2Si). 13C-NMR (75 MHz, CDCl3): see
the Table; additionally, 167.25, 167.23(2 s, 2 CˆO); 111.52 (s, Me2C); 27.11, 25.49 (2q, Me2C); 26.06 (q, Me3C);
‡
21.08 (q, MeCˆO); 18.51 (s, Me3C); À 4.38, À 4.43(2 q, Me2Si). MALDI-MS: 739 (100, [2 M ‡ Na] ), 381 (63,
‡
‡
‡
[M ‡ Na] ). HR-MALDI-MS: 381.1814 (63, [M ‡ Na] , C21H34N2NaO6SSi ; calc. 381.1816). Anal. calc. for
C16H30N2O5Si (358.51): C 53.60, H 8.43, N 7.81; found: C 53.64, H 8.37, N 7.54.
5-Amino-4-O-[(tert-butyl)dimethylsilyl]-5-deoxy-2,3-O-isopropylidene-{[(4-methylphenyl)sulfonyl]ami-
no}-d-ribono-1,5-lactam (44). A cooled (08) soln. of 1 (158 mg, 0.5 mmol) in CH2Cl2 (2 ml) was treated with a
soln. of pyridine (0.5 ml) and TsCl (143mg, 0.75 mmol) in CH 2Cl2 (2 ml). The mixture was stirred at r.t. for 3h,
treated with H2O, and extracted with CH2Cl2 (3 Â 15 ml). The combined org. layers were dried and evaporated.
FC (cyclohexane/AcOEt 4 :1) gave 44 (212 mg, 90%). White foam. Rf (cyclohexane/AcOEt 2 :1) 0.33. [a]D25
ˆ
À7.8 (c ˆ 0.34, CHCl3). IR (CHCl3): 3249w, 3031m, 2955m, 2933m, 2860m, 1688s, 1598w, 1472m, 1385s, 1352s,
1257s, 1187m, 1169s, 1091s, 981m, 959m, 895m, 83 9s, 813m. 1H-NMR (300 MHz, CDCl3): see the Table;
additionally, 7.90 (br. s, NH); 7.73( d, J ˆ 8.4, 2 arom. H); 7.27 (d, J ˆ 8.4, 2 arom. H); 2.41 (s, MeC6H4); 1.40, 1.32
(2s, Me2C); 0.88 (s, Me3C); 0.12, 0.11 (2s, Me2Si). 13C-NMR (75 MHz, CDCl3): see the Table; additionally, 167.27
(s, CˆO); 145.18, 132.29 (2s); 129.74 (2d); 128.53(2 d); 111.74 (s, Me2C); 26.49, 24.96 (2q, Me2C); 25.99 (q,
‡
Me3C); 22.03( q, MeC6H4); 18.40 (s, Me3C); À 4.31, À 4.59 (2q, Me2Si). MALDI-MS: 493(100, [ M ‡ Na] ), 471
‡
(28, [M ‡ H] ). Anal. calc. for C21H34N2O6SSi (470.66): C 53.59, H 7.28, N 5.95, S 6.81; found: C 53.62, H 7.42, N
5.84, S 6.67.
Oxidation of 34 with Pb(OAc)4. A soln. of Pb(OAc)4 (1.06 g, 2.4 mmol) in CH2Cl2 (3ml) was added
dropwise to a soln. of 34 (288 mg, 0.8 mmol) in toluene (40 ml). The mixture was stirred at r.t. for 2 h, treated
with H2O, and extracted with Et2O (3 Â 30 ml). The combined org. layers were dried and evaporated. FC
(cyclohexane/AcOEt 5 :1) gave 2 (119 mg, 43%) and 3 (100 mg, 40%).
Oxidation of 44 with Pb(OAc)4. A soln. of Pb(OAc)4 (178 mg, 0.4 mmol) in CH2Cl2 (2 ml) was added
dropwise to a soln. of 44 (94 mg, 0.2 mmol) in toluene (10 ml). The mixture was stirred at r.t. for 2 h, treated
with H2O (10 ml), and extracted with Et2O (3 Â 15 ml). The combined org. layers were dried and evaporated.
FC (cyclohexane/AcOEt 5 :1) gave 45 (53mg, 50%), 2 (17 mg, 25%), and 3 (9 mg, 14%).
Data of (5R)-5-O-Acetyl-5-amino-4-O-[(tert-butyl)dimethylsilyl]-2,3-O-isopropylidene-N-{[(4-methylphen-
yl)sulfonyl]amino}-d-ribono-1,5-lactam (45). White crystals. M.p. 205 2068 (hexane/CH2Cl2). Rf (cyclohexane/
AcOEt 2 :1) 0.34. [a]2D5 ˆ ‡92.1 (c ˆ 0.34, CHCl3). IR (CHCl3): 3259w, 3028w, 2982w, 2956w, 2932m, 2886w,
2861w, 1757m, 1718m, 1597w, 1471w, 1462w, 1426m, 1383m, 1377m, 1358m, 1307w, 1290w, 1257m, 1234m, 1194s,

Helvetica Chimica Acta Vol. 87 (2004)
2445
1170vs, 1104m, 1091m, 1080m, 1020s, 994w, 975m, 959w, 920m, 862w, 841m, 813w. 1H-NMR (300 MHz, CDCl3):
see the Table; additionally, 7.85 (s, NH); 7.74 (d, J ˆ 8.1, 2 arom. H); 7.28 (d, J ˆ 8.1, 2 arom. H); 2.43( s,
MeC6H4); 2.22 (s, AcO); 1.45, 1.32 (2s, Me2C); 0.85 (s, Me3C); 0.15, 0.07 (2s, Me2Si). 13C-NMR (75 MHz,
CDCl3): see the Table; additionally, 168.53, 168.33 (2s, 2 CˆO); 145.13, 132.80 (2s); 129.61 (2d); 128.53(2 d);
111.93( s, Me2C); 25.74 (q, Me3C); 25.74, 24.44 (2q, Me2C); 21.94 (q, MeC6H4); 20.84 (q, MeCˆO); 18.11 (s,
‡
Me3C); À 4.43, À 5.17 (2q, Me2Si). MALDI-MS: 551 (22, [M ‡ Na] ), 491 (20), 441 (28), 307 (100). Anal. calc.
for C23H36N2O8SSi (528.70): C 52.25, H 6.86, N 5.30, S 6.07; found: C 52.40, H 6.91, N 5.29, S 5.96.
Crystal Structure of 45. Recrystallization of 45 in hexane/CH2Cl2 gave crystals suitable for X-ray analysis:
C23H36N2O8SSi (528.70); monoclinic P21; a ˆ 10.0022 (5) ä, b ˆ 13.2022 (7) ä, c ˆ 11.3778 (6) ä, b ˆ 111.803
(2)8; Vˆ 1394.97 (13) ä3; Dcalc. ˆ 1.316 Mg/m3; Z ˆ 2. 2787 reflections were measured on a KappaCCD
diffractometer with MoKa radiation (graphite monochromator, l ˆ 0.71073ä) at 298 K. R ˆ 0.059, Rw ˆ 0.105.
The structure was solved by direct methods with SIR-97. The non-H-atoms were refined anisotropically with
SHELXS-97.
(5R)-N-Acetamido-5-O-acetyl-5-amino-4-O-[(tert-butyl)dimethylsilyl]-2,3-O-isopropylidene-d-ribono-
1,5-lactam (46). A cooled (08) soln. of 31 (34 mg, 0. 1 mmol) in CH2Cl2 (1 ml) was treated with pyridine (0.1 ml)
and Ac2O (40 ml, 0.4 mmol), stirred for 3h, warmed to r.t., stirred for 24 h, treated with H 2O, and extracted with
CH2Cl2 (3 Â 10 ml). The combined org. layers were dried (MgSO4) and evaporated. FC (cyclohexane/AcOEt
1:2) gave 46 (24 mg, 58%). White crystals. M.p. 167 1688 (CHCl3). Rf (cyclohexane/AcOEt 1 :4) 0.30. [a]D25
ˆ
‡69.2 (c ˆ 0.95, CHCl3). IR (CHCl3): 3385m, 3026m, 2954m, 2932m, 2859w, 1757m, 1731s, 1707s, 1485w, 1472w,
1463w, 1425w, 1383m, 1375m, 1255m, 1203s, 1164m, 1106s, 1081m, 1017m, 974m, 863w, 840s. 1H-NMR (CDCl3,
300 MHz): see the Table; additionally, 7.74 (s, NH); 2.12 (s, AcO); 2.01 (s, AcN); 1.53, 1.39 (2s, Me2C); 0.88 (s,
Me3C); 0.12, 0.11 (2s, Me2Si). 13C-NMR (CDCl3, 75 MHz): see the Table; additionally, 169.88, 169.42, 167.75 (3s,
3 CˆO); 111.65 (s, Me2C); 26.16, 24.65 (2q, Me2C); 26.02 (q, Me3C); 21.13( q, 2 MeCˆO); 18.40 (s, Me3C);
‡
‡
À 4.09, À 4.91 (2q, Me2Si). HR-MALDI-MS: 439.1865 (100, [M ‡ Na] , C18H32O7N2NaSi ; calc. 439.1871).
Anal. calc. for C18H32O7N2Si (416.55): C 51.90, H 7.74, N 6.73; found: C 51.93, H 7.62, N 6.67.
Oxidation of 46 with Pb(OAc)4. A suspension of Pb(OAc)4 (443mg, 1.0 mmol) in toluene (22 ml) was
treated with a soln. of 46 (142 mg, 0.34 mmol) in CH2Cl2 (8 ml), stirred at r.t. for 12 h, treated with H2O, and
extracted with Et2O (3 Â 20 ml). The combined org. layers were dried and evaporated. FC (cyclohexane/AcOEt
4 :1) gave 33 (72 mg, 57%) Syrup.
N-Acetamido-5-amino-4-O-[(tert-butyl)dimethylsilyl]-5-deoxy-2,3-O-isopropylidene-d-lyxono-1,5-lactam
(47). A soln. of 5 (68 mg, 0.215 mmol) in MeOH (2 ml) was treated with Ac2O (22 ml, 0.215 mmol) and stirred at
r.t. for 3h. Co-evaporation with toluene and FC (cyclohexane/AcOEt 1:2) gave 47 (76 mg, 99%). White
crystals. M.p. 187 1888 (CHCl3). Rf (cyclohexane/AcOEt 1:2) 0.23. [a]2D5 ˆ À17.8 (c ˆ 0.55, CHCl3). IR
(CHCl3): 3393w, 3252w (br.), 3026w, 3015m, 2955m, 2932m, 2903w, 2859m, 1711s, 1673vs, 1471m, 1421w, 1385m,
1375m, 1348w, 1291w, 1259m, 1163w, 1128m, 1102s, 1044w, 1000w, 93 7w, 908w, 892w, 83 9s, 809m. 1H-NMR
(300 MHz, CDCl3): 9.46 (s, NH); 4.54 (d, J ˆ 6.2, HÀC(2)); 4.26 (br. t, J ꢀ 5.6, HÀC(3)); 4.20 4.14 (m,
HÀC(4)); 4.10 (dd, J ˆ 12.4, 2.5, HÀC(5)); 3.33 (dd, J ˆ 12.8, 3.7, H'ÀC(5)); 2.00 (s, AcN); 1.50, 1.38 (2s,
Me2C); 0.85 (s, Me3C); 0.093, 0.087 (2s, Me2Si). 13C-NMR (75 MHz, CDCl3): 169.39, 167.22 (2s, 2 CˆO); 111.68
(s, Me2C); 76.94 (d, C(2)); 74.36 (d, C(3)); 67.27 (d, C(4)); 54.06 (d, C(5)); 27.26, 25.88 (2q, Me2C); 25.88 (q,
‡
Me3C); 21.13( q, MeCˆO); 18.18 (s, Me3C); À 4.59, À 4.64 (2q, Me2Si). MALDI-MS: 381 (100, [M ‡ Na] ),
‡
‡
‡
359 (17, [M ‡ H] ). HR-MALDI-MS: 381.1812 (100, [M ‡ Na] , C21H34N2NaO6SSi ; calc. 381.1816). Anal. calc.
for C16H30N2O5Si (358.51): C 53.60, H 8.43, N 7.81; found: C 53.49, H 8.48, N 7.58.
N-Acetamido-5-amino-4-O-[(tert-butyl)dimethylsilyl]-5-deoxy-2,3-bis-O-(methoxymethyl)-d-arabinono-
1,5-lactam (48). A soln. of 6 (114 mg, 0.31 mmol) in MeOH (2 ml) was treated with Ac2O (65 ml, 0.62 mmol) and
stirred at r.t. for 1 h. Co-evaporation with toluene and FC (cyclohexane/AcOEt 1:2) gave 48 (126 mg, > 99%).
Colourless oil. Rf (cyclohexane/AcOEt 1:2) 0.20. [a]2D5 À 103.6 (c ˆ 0.42, CHCl3). IR (CHCl3): 3394w, 3259w,
2955m, 2931m, 2898m, 2858m, 1710m, 1671s, 1472m, 1441w, 1368m, 1255m, 1140s, 1106s, 1039vs, 919m, 868m,
838m. 1H-NMR (300 MHz, CDCl3): 8.29 (s, NH); 5.00 (d, J ˆ 6.5, MeOCH); 4.76 (s, MeOCH2); 4.75 (d, J ˆ 6.8,
MeOCH); 4.38 (d, J ˆ 7.1, H ÀC(2)); 4.35 (ddd, J ˆ 5.6, 4.0, 1.9, HÀC(4)); 3.95 (dd, J ˆ 7.1, 1.9, HÀC(3)); 3.72
(dd, J ˆ 11.5, 4.0, HÀC(5)); 3.53 (dd, J ˆ 11.5, 5.3, H'ÀC(5)); 3.43, 3.39 (2s, 2 MeO); 2.02 (s, AcN); 0.89 (s,
Me3C); 0.12, 0.10 (2s, Me2Si). 13C-NMR (75 MHz, CDCl3): 169.39, 168.02 (2s, 2 CˆO); 97.36, 96.37 (2t, 2
MeOCH2); 75.83( d, C(2)); 73.25 (d, C(3)); 66.35 (d, C(4)); 56.21, 55.94 (2q, 2 MeOCH2); 54.34 (t, C(5)); 25.83
‡
(q, Me3C); 21.10 (q, MeCˆO); 18.22 (s, Me3C); À 4.62, À 4.78 (2q, Me2Si). ESI-MS: 445 (18, [M ‡ K] ), 429
‡
‡
(100, [M ‡ Na] ), 407 (7, [M ‡ H] ). Anal. calc. for C17H34N2O7Si (406.55): C 50.22, H 8.43, N 6.89; found: C
50.47, H 8.55, N 6.79.

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Helvetica Chimica Acta Vol. 87 (2004)
N-Acetamido-5-amino-4-O-[(tert-butyl)dimethylsilyl]-5-deoxy-2,3-bis-O-(methoxymethyl)-d-xylono-1,5-
lactam (49). A soln. of 7 (56 mg, 0.15 mmol) in MeOH (1.5 ml) was treated with Ac2O (23 ml, 0.22 mmol) and
stirred at r.t. for 3h. Co-evaporation with toluene and FC (cyclohexane/AcOEt 1:2) gave 49 (57 mg, 94%).
White crystals. M.p. 85.5 878. Rf (hexane/AcOEt 1:4) 0.30. [a]2D5 ˆ ‡33.0 (c ˆ 0.51, CHCl3). IR (CHCl3):
3309w, 2956m, 2932m, 2897m, 2859m, 1716s, 1681s, 1472m, 1464m, 1442w, 1423w, 1390w, 1368w, 1259m, 1153s,
1104s, 1081m, 1037vs, 1007m, 917m, 83 9s. 1H-NMR (300 Hz, CDCl3): 8.81 (s, NH); 4.96 (d, J ˆ 6.5), 4.85 (d, J ˆ
6.5), 4.80 (d, J ˆ 6.5), 4.75 (d, J ˆ 6.5) (2 MeOCH2); 4.16 (d, J ˆ 7.8, HÀC(2)); 4.06 (td, J ꢀ 7.8, 5.0, HÀC(4));
3.79 (t, J ꢀ 7.5, HÀC(3)); 3.69 (dd, J ˆ 11.8, 4.7, HÀC(5)); 3.44, 3.40 (2s, 2 MeO); 3.35 (dd, J ˆ 11.8, 8.1,
H'ÀC(5)); 1.99 (s, AcN); 0.86 (s, Me3C); 0.10, 0.09 (2s, Me2Si). 13C-NMR (CDCl3): 169.07, 168.42 (2s, 2 CˆO);
97.38 (t, 2 MeOCH2); 79.70, 74.71 (2d, C(2), C(3)); 68.82 (d, C(4)); 56.46, 56.24 (2q, 2 MeOCH2); 54.38 (t, C(5));
25.88 (q, Me3C); 21.00 (q, MeCˆO); 18.12 (s, Me3C)); À 4.49, À 4.64 (2q, Me2Si). HR-MALDI-MS: 429.2025,
‡
‡
(100, [M ‡ Na] , C17H34N2NaO7Si ; calc. 429.2028). Anal. calc. for C17H34N2O7Si (406.55): C 50.22, H 8.43, N
6.89; found: C 50.20, H 8.41, N 6.69.
Oxidation of 47 with Pb(OAc)4. A soln. of 47 (36 mg, 0.1 mmol) in toluene (5 ml) was treated with a
suspension of Pb(OAc)4 (134 mg, 0.3 mmol) in toluene (5 ml), stirred at r.t. for 1 h, treated with H2O, and
extracted with Et2O (3 Â 5 ml). The combined org. layers were dried and evaporated. FC (cyclohexane/AcOEt
10 :1) gave the diazo ketone 8 (24 mg, 77%).
Oxidation of 48 with Pb(OAc)4. A soln. of 48 (92 mg, 0.23mmol) in toluene (8 ml) was treated with a
suspension of Pb(OAc)4 (335 mg, 0.75 mmol) in toluene (6 ml), stirred at r.t. for 2 h, treated with H2O, and
extracted with Et2O (3 Â 10 ml). The combined org. layers were dried and evaporated. FC (cyclohexane/AcOEt
8 :1) gave the diazo ketone 9 (32 mg, 39%).
Oxidation of 49 with Pb(OAc)4. A soln. of 49 (354 mg, 0.87 mmol) in toluene (20 ml) was treated with a
suspension of Pb(OAc)4 (1.16 g, 2.61 mmol) in toluene (25 ml), stirred at r.t. for 2 h, treated with H2O, and
extracted with Et2O (3 Â 40 ml). The combined org. layers were dried and evaporated. FC (cyclohexane/AcOEt
15 :1 ! 8 :1) gave the diazo ketone 10 (146 mg, 46%).
REFERENCES
[1] G. Hu, A. Vasella, Helv. Chim. Acta 2004, 87, 2405.
[2] J. P. Freeman, J. Org. Chem. 1964, 29, 1379.
[3] D. C. Iffland, L. Salisbury, W. R. Schafer, J. Am. Chem. Soc. 1961, 83, 747; R. W. Hoffmann, H. J. Luthardt,
Tetrahedron Lett. 1966, 7, 411.
[4] T. E. Walker, H. P. C. Hogenkamp, Carbohydr. Res. 1974, 32, 413.
[5] I. Maeba, M. Suzuki, O. Hara, T. Takeuchi, T. Iijima, H. Furukawa, J. Org. Chem. 1987, 52, 4521; F. Delgado,
M. M. MartÌn, M. V. MartÌn, Tetrahedron 2001, 57, 4389; A. Dinsmore, P. M. Doyle, M. Steger, D. W.
Young, J. Chem. Soc., Perkin Trans 1 2002, 613.
[6] R. N. Butler, F. L. Scott, T. A. F. O×Mahony, Chem. Rev. 1973, 73, 93; R. N. Butler, Chem. Rev. 1984, 84,
249; A. Kotali, Curr. Org. Chem. 2002, 6, 965.
[7] M. Bekhazi, P. J. Smith, J. Warkentin, Can. J. Chem. 1984, 62, 1646; J. Warkentin, J. Chem. Soc., Perkin
Trans. 1 2000, 2161; N. Merkley, J. Warkentin, Can. J. Chem. 2002, 80, 1187; W. Czardybon, A. Klys, J.
Warkentin, N. H. Werstiuk, Can. J. Chem. 2003, 81, 1438.
[8] T. J. Kealy, J. Am. Chem. Soc. 1962, 84, 966.
[9] G. R. Pettit, D. C. Fessler, K. D. Paull, P. Hofer, J. C. Knight, J. Org. Chem. 1970, 35, 1398.
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[10] A. Stojiljkovic, N. Orbovic, S. Sredojevic, M. L. Mihailovic, Tetrahedron 1970, 26, 1101; E. Ciganek, J. Org.
Chem. 1965, 30, 4198; D. M. Gale, W. J. Middleton, C. G. Krespan, J. Am. Chem. Soc. 1965, 87, 657.
Received May 28, 2004