Stereocontrolled intramolecular aziridination of glycate: Ready access to aminoglycosides and mechanistic insights from DFT studies

Article abstract of DOI:10.1002/chem.200701288

Stereocontrolled intramolecular aziridination of the glycal-derived sulfamates offers a highly efficient strategy to divergently prepare aminoglycosides. Rhodium-catalyzed nitrogen-atom transfer to C=C bonds formed semistable aziridines, which were subjected to various nucleophiles (C, O, S, and N) to give cyclic sulfamate-containing aminosugar derivatives selectively. The second nucleophilic displacement of sulfonyloxy moieties of [1,2,3]-oxathiazepane-2,2-dioxides allows straightforward access to aminoglycosides with selective α- or β-linkages. This approach is operationally simple, complements existing methods, and is a versatile protocol for the synthesis of polyfunctionalized amino sugars. In addition, the mechanism of the rhodium-catalyzed intramolecular aziridination of glycals and its ring-opening reaction was extensively studied by using DFT calculations.

Full text of DOI:10.1002/chem.200701288

FULL PAPER
DOI: 10.1002/chem.200701288
Stereocontrolled Intramolecular Aziridination of Glycals: Ready Access to
Aminoglycosides and Mechanistic Insights from DFT Studies
Rujee Lorpitthaya,[a] Zhi-Zhong Xie,[b] Jer-Lai Kuo,[b] and Xue-Wei Liu*[a]
Abstract: Stereocontrolled intramolec-
ular aziridination of the glycal-derived
tives selectively. The second nucleo-
philic displacement of sulfonyloxy
to aminoglycosides with selective a- or
b-linkages. This approach is operation-
ally simple, complements existing
methods, and is a versatile protocol for
the synthesis of polyfunctionalized
amino sugars. In addition, the mecha-
nism of the rhodium-catalyzed intra-
molecular aziridination of glycals and
its ring-opening reaction was extensive-
ly studied by using DFTcalculations.
sulfamates offers
a
highly efficient
A
strategy to divergently prepare amino-
glycosides. Rhodium-catalyzed nitro-
gen-atom transfer to C=C bonds
formed semistable aziridines, which
were subjected to various nucleophiles
(C, O, S, and N) to give cyclic sulfa-
mate-containing aminosugar deriva-
dioxides allows straightforward access
Keywords: aminoglycosides · aziri-
dine · density functional calcula-
tions · oxathiazepane · rhodium ·
ring-opening reactions
Introduction
To date, the advancement of new methods for selective
À
AHCTREUNG
Aminoglycosides have attracted growing interest, especially
concerning the modification and development of efficient
syntheses due to their broad spectrum of applications in the
chemistry, medicine, and pharmaceutical fields. Amino
sugars play crucial roles for the biological activity of amino-
glycoside antibiotics and aminoglycoside-containing natural
products.[1,2] 2-Amino sugars are also major structural ele-
ments of glycosaminoglycans, such as heparan sulfates and
chondroitin sulfates, which are implicated in cell division,
neuronal development, angiogenesis, blood coagulation,
À
transfer to C H bonds. Recently, the groups of Du Bois and
Che have independently reported that the formation of ary-
liodinanes and the insertion of metallonitrenoids into C=C
or C H bonds can be conducted with a one-pot proce-
À
dure.[8–11] This methodology has been successfully used for
the synthesis of natural aminoglycoside frameworks. For ex-
ample, Rojas showed the use of copper and rhodium cata-
lysts in amidoglycosylation reactions of d-allal-derived car-
bamates to furnish 2-aminoglycosylated products.[12] Howev-
er, not many glycal acceptors have been applied in this scaf-
fold so far. We report herein a novel method for nitrogen
transfer that allows ready access to natural and unnatural
mono-, di-, and tri- aminoglycosides with various amination
patterns and stereochemistry.
ACHTREUNG
ACHTREUNG
[a] R. Lorpitthaya, Prof. Dr. X.-W. Liu
Division of Chemistry and Biological Chemistry
School of Physical & Mathematical Sciences
Nanyang Technological University, 1 Nanyang Walk
Singapore 637616 (Singapore)
We envisioned the efficient synthesis of these functional-
ized aminoglycosides by the flexible installation of a sulfa-
mate ester on the C6 position of a glycal substrate. This
offers an exciting approach to a-selective amidoglycosyla-
tion through nitrogen atom delivery to a p-bond system on
the top face of a glycal scaffold as shown in Equation (1). A
regio- and stereospecific ring-opening reaction of the aziri-
dine with nucleophiles would simultaneously achieve the
formation of [1,2,3]oxathiazepane-2,2-dioxides with a-link-
ages. The second nucleophilic replacement of sulfonyloxy
Fax : (+65)6791-1961
E-mail: xuewei@ntu.edu.sg
[b] Dr. Z.-Z. Xie, Prof. Dr. J.-L. Kuo
Division of Physics and Applied Physics
School of Physical & Mathematical Sciences
Nanyang Technological University, 1 Nanyang Walk
Singapore 637616 (Singapore)
Supporting information for this article is available on the WWW
under http://www.chemeurj.org/ or from the author.
Chem. Eur. J. 2008, 14, 1561 – 1570
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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moieties allows ready access to unusual aminoglycosides. In
turn, the facial preference on the bottom face of this glycal
scaffold could be elaborated by introducing the sulfamate
moiety on C4, which gives an opportunity to produce func-
tionalized b-linked 2-amino sugars [Eq. (2)].
Initially, we had investigated the use of iodosobenzene di-
acetate (PhI(OAc)2) and catalytic dirhodium(II) carboxy-
AHCTREUNG
lates for the intramolecular aziridination of olefins by start-
ing from sulfamates.[17] Sulfamate glycal 6 was treated with
PhI
N
N
methane. The amidoglycosylation reaction proceeded
smoothly at room temperature to furnish the glycosyl ace-
tate 10a in good yield (Table 1, entry 1). Presumably, the
aziridine intermediate 9 could not be isolated due to the
high reactivity of C1 and the inherent ring strain. The semi-
stable aziridine was simultaneously trapped by an internal
acetoxy group in regio- and stereospecific manners. The
structure and stereochemistry of the acetate 10a was deter-
mined through NMR spectroscopic experiments (1H, 13C,
DEPT, COSY, HMQC, NOESY).
Alcohols could also be included in the reaction mixture,
and this led directly to alkoxylated glycoside derivatives in a
single step, but an excess amount of alcohol (up to 20 equiv)
was needed to suppress the formation of the glycosyl acetate
(Table 1, entries 2–5). The lower yields of coupled products
in entries 4 and 5 were most probably due to the attack of a
reactive acetoxy species. We then proceeded to investigate
the origin of the acetoxy group by replacing the iodosoben-
zene diacetate with iodosylbenzene (PhIO). Methanol was
used as an external nucleophile
Results and Discussion
To evaluate the potential of this hypothesis, we first per-
formed a model study on sulfamate glycals 6 and 8, which
were synthesized from readily available tri-O-acetyl-d-glycal
in four steps (Scheme 1).[13] Treatment of tri-O-acetyl-d-
for this case study. It was found
that the glycosyl acetate was
not observed on TLC and,
moreover, the amount of meth-
anol that was required could be
reduced, which implies that the
acetoxy group comes from the
decomposition of PhI(OAc)2.
G
Attempts were made to
expand the scope of glycosyla-
tion to other nucleophiles, such
as alkyl, thiol, amine, amino
acids, and monosaccharides.
Unfortunately, these nucleo-
philes failed to attack the C1
atom of the aziridine intermedi-
ate when catalytic amounts of
Scheme 1. Preparation of sulfamate-protected glycals. a) NaOMe, MeOH, RT, 2 h, quantitative; b) TBDMSCl,
imidazole, DMF, 08C to RT, 8 h, 80%; c) BzCl, DMAP, pyridine, 08C to RT, 6 h, 90%; d) p-TSOH, THF/H2O
10:1, 8 h, 80%; e) 1m TBAF, THF, RT, 15 h, 91%; f) ClSO2NCO, HCO2H, DMA, 08C, 3 h, 83% from 5, and
94% from 7.
[Rh
N
N
were used. Under these condi-
glycal (1) with sodium methoxide in dry MeOH provided 2,
which was selectively protected with tert-butyldimethylsilyl
chloride (TBDMSCl) to give 3, and benzoyl chloride (BzCl)
to give 4. The TBDMS protecting group in 4 was independ-
ently cleaved by a catalytic amount of p-toluene sulfonic
acid to provide 5,[14] whereas treatment with tetra-n-butyl-
tions, only glycosyl acetate, unreacted nucleophile, and de-
composed mixtures were detected. Another choice for the
specific aziridination and its ring-opening was inspired by
Du Bois.[17c] A rhodium trifluoroacetamide ([Rh2
ACHTREUNG
AHCTREUNG
A
of the aziridine intermediate, which was able to couple with
various nucleophiles.[19] In the presence of PhIO, MgO, and
a rearrangement of a benzoyl group.[15] Conversions of the
primary and secondary alcohols 5 and 7 were carried out by
using sulfamoyl chloride, which was generated in situ from
chlorosulfonyl isocyanate and formic acid, and produced sul-
famates 6 and 8 in good yields.[16]
[Rh2(tfacam)4], the iminoiodinane intermediate could be
A
generated in situ by reaction of the sulfamate substrate and
iodosylbenzene, followed by Rh-catalyzed intramolecular
aziridination. A glycal acceptor was injected into the reac-
tion mixture within 15 minutes to trap the semistable aziri-
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Chem. Eur. J. 2008, 14, 1561 – 1570

Aziridination of Glycals
FULL PAPER
Table 1. Regio- and stereoselective aziridination of 6 and a-selective gly-
cosylation.
Entry
Nucleophile (NuH)
Product
Yield [%][d]
1[a]
2[a]
3[a]
4[a]
AcOÀ
MeOH
EtOH
iPrOH
10a
10b
10c
10d
82
81
90
70
5[a]
10e
71
78
6[b,c]
10 f (Nu=allyl)
7[b,c]
10g
85
Figure 1. X-ray structure of aminoglycosyl methoxide 10b.
8[b]
10h
76
posite face. This proposed mechanism is further supported
by DFTcalculations, as detailed in the Computational Stud-
ies section.
9[b]
10i
10j
66
68
Likewise, these extraordinary features could be applied to
sulfamate glycal 8. This substrate nicely underwent a nitro-
gen atom delivery to the C=C bond from the bottom face,
and led to b-aminoglycoside derivatives 12a–g, via specific
ring-opening at the positively charged anomeric carbon; this
reaction gave moderate-to-excellent yields (Table 2).
Finally, we sought to access unusual amino sugars by a
ring-opening reaction at the carbon atom that bears the sul-
10[b]
[a] Reaction was treated with 10 mol% of [Rh
(1.5 equiv), MgO (5 equiv), and nucleophile in the presence of 4 ꢁ MS in
CH2Cl2 at RT. [b] Reaction was treated with 10 mol% of [Rh2(tfacam)4],
PhI=O (1.5 equiv), MgO (5 equiv) in the presence of 4 ꢁ MS in CH2Cl2
at RTfor 15 min, and then the nucleophile was added dropwise. [c] Nu-
cleophile and 0.5 equiv of BF3·OEt2 were added at À788C and then
warmed to RTfor 2–3 h. [d] % Isolated yield.
2(OAc)4], PhI
(OAc)2
AHCTREUNG
Table 2. Regio- and stereoselective aziridination of 8 and b-selective gly-
cosylation.
dine; this provided the desired oxathiazepane (Table 1, en-
tries 6–10). In the cases of trimethylallylsilane[20] and p-thio-
cresol[6a] as nucleophiles, the glycosylation step required ac-
tivation by a Lewis acid, BF3·OEt2. Even though moderate
yields of glycosylated products were obtained due to the in-
stability of the aziridine intermediate in reaction mixture,
we were successful in the synthesis of the diamino sugar, the
disaccharide as well as other functionalized 2-amino sugars
in a convenient one-step process.
Notably, the internal nitrogen transfer to the p-system,
and the nucleophilic addition of our sulfamate-protected
glycal scaffold at C1 is the facially selective version of a pre-
viously reported reaction that produces a-selective glycosy-
lated products.[21] A X-ray crystallographic study of a glyco-
syl methoxide 10b confirmed the diaxial conformation of
oxathiazepane ring and the trans-stereochemistry between
the N-sulfonyloxy moiety and the methoxy group (Figure 1).
This observation allowed us to propose that a transient aziri-
dine intermediate 9 exists in the reaction mixture by direct
nitrogen delivery on the upper face of the molecule, and
this subsequently fosters the nucleophilic attack on the op-
Entry
Nucleophile (NuH)
Product
Yield [%][c]
1[a]
2[a]
3[a]
4[a]
AcOÀ
MeOH
EtOH
iPrOH
12a
12b
12c
12d
73
96
87
86
5[a]
6[a]
12e
12 f
77
81
7[b]
12g
78
[a] Reaction was treated with [Rh2
(1.5 equiv), MgO (5 equiv), and nucleophile in the presence of 4 ꢁ MS in
CH2Cl2 at RT. [b] Reaction was treated with [Rh2(tfacam)4] (10 mol%),
PhI=O (1.5 equiv), MgO (5 equiv) in the presence of 4 ꢁ MS in CH2Cl2
at RTfor 30 min, and then p-thiocresol as well as 0.5 equiv of BF3·OEt2
were added subsequently at À788C, then warmed to RTfor 2 h. [c] %
Isolated yield.
G
A
AHCTREUNG
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X.-W. Liu et al.
famate function.[22] The methoxyoxathiazepane 10b was se-
lected to be a model compound for this reaction study. We
had tried to introduce a second nucleophile on the sulfa-
mate moiety without protection of the amino group of oxa-
thiazepane. Unfortunately, none of the desired products
were observed when it was treated with N-nucleophiles
(such as NaN3, K-phathalimide, and benzylamine) in reflux-
ing DMF. Only starting material and trace amounts of un-
identified compounds were detected. This presumably re-
sulted from the reduced electrophilic activity of the eight-
membered oxathiazepane. Accordingly, the electron-with-
drawing carboxybenzyloxy (Cbz) group was introduced at
the nitrogen atom to give 13 (Scheme 2). Treatment of 10b
Computational studies: To gain a more detailed understand-
ing of the pathways of rhodium-catalyzed intramolecular
aziridination and ring-opening, computational studies were
carried out by employing density functional theory (DFT)
calculations on a simplified model system. As depicted sche-
matically in Figure 2, our proposed mechanism involves
three main steps:
I) The Rh–Nitrene complex (Rh–N) was generated by a
rhodium-catalyzed elimination of the IPh moiety from
iminoiodinane (Sub). Our calculation demonstrated
that the Rh catalyst binding to Sub is energetically fa-
vorable (DG=À5.7 kcalmolÀ1) and is further stabilized
by the departure of the
IPh
moiety
(DG=
À7.3 kcalmolÀ1). This com-
plex initially exists in the
singlet state and then rap-
idly relaxes to the even
more energetically favora-
ble triplet state.[8a] The
triplet state of the
Rh–nitrene complex is
9.7 kcalmolÀ1 lower than
the singlet state.
II) The formation of the cata-
lyst-bound aziridine (Rh–
Azi): we attempted to
search for transition states
from both Rh–N(S) and
Rh–N(T), and only one
transition state (TS1) was
found on the triplet poten-
tial-energy surface. The
Scheme 2. Ring-opening reaction of N-Cbz oxathiazepanes. a) CbzCl, DMAP, Et3N, THF, 08C to RT , 92%; b)
CbzCl, NaHCO3, THF/H2O 1:1, 08C to RT, 82%; c) nucleophiles.
with benzyl chloroformate (CbzCl) and a catalytic amount
of 4-dimethylaminopyridine (DMAP) in Et3N and THF af-
forded N-Cbz-protected product 13 in excellent yield. This
preliminary result suggested that the oxathiazepane 12b
should be derivatized with CbzCl. Under the same condi-
tions as 13, the N-Cbz product 15 was obtained in a low
yield (40%), but by changing the base from Et3N to
NaHCO3, we managed to boost the yield to 82%
(Scheme 2).
calculated free energy of TS1 is about 1 kcalmolÀ1
lower than Rh–N(S), hence even if the transition state
on the singlet potential-energy surface can be located,
our proposed reaction, which starts from triplet
Rh–N(T) should still be energetically more favorable.
By starting from TS1, we have located an intermediate
À
INT(T) with an established N C1 bond by using the in-
trinsic-reaction-coordinate (IRC) method[23] on the trip-
let potential energy surface. The bond length of N···C1
(2.124 ꢁ) is significantly shorter than that of N···C2
(2.687 ꢁ) in the TS1 structure. Not surprisingly, the
The nucleophilic displacement of a sulfonyloxy moiety of
13 and 15 was subsequently achieved by treating with NaN3,
KSCN, p-methoxybenzylamine, and H2O to give rise to the
corresponding coupled products in moderate-to-good yields
as summarized in Table 3.
À
À
N C1 bond is more likely formed than the N C2 bond
because the C1 atom carries more positive charge due
to the neighboring oxygen atom. To form the singlet
Rh–Azi, INT(T) needs to undergo an intersystem
crossing (ISC), which is enhanced by the heavy atom
effect of Rh. Therefore, we carried out geometry opti-
mization on the singlet potential energy surface by
using INT(T) as an initial structure, and found that sin-
glet Rh–Azi can be easily derived by following this
route. Our DFTcomputational results agreed with the
mechanism that Brandt proposed for the copper-cata-
lyzed aziridination.[24]
Table 3. Nucleophilic ring-opening reaction of oxathiazepanes 13 and 15.
Entry Starting material Reaction conditions
Yield [%][a]
1
2
3
4
13
13
15
15
NaN3/DMF/1208C
KSCN/DMF/1508C
NH2CH2C5H6OMe/DMF/708C 75
67
78
H2O/K2CO3/Acetone/RT80
[a] % Isolated yield.
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Aziridination of Glycals
FULL PAPER
Figure 2. Computed Gibbs free energy profiles of the model system at 298 K, DG (kcalmolÀ1). The substrate (Sub) in our model system was obtained by
substituting the phenyl groups in 6 with methyl groups. The catalyst [Rh2(OAc)4] was simplified by replacing the methyl groups with hydrogen atoms.
G
À
À
Ad1=the adduct of Sub–[Rh2]; Rh N=Rh–nitrene; TS1=the transition state to form N C1 bond in the triplet state; INT(T)=the intermediate with a
À
N C in triplet state; Rh–Azi=catalyst-bound aziridine; Ad2=the adduct of aziridine ring opening by OMe; and TS2=the transition state to form the
catalyst-bound product (Rh-P).
III) Aziridine ring-opening by nucleophile (MeOÀ): The
transition states of nucleophilic ring-opening by MeOÀ
have been optimized. The overall process is exother-
mic. When MeOÀ approaches the C1 position, the ini-
tial complex Ad2 is formed (DG=À77.2 kcalmolÀ1,
and C1···OMe=2.818 ꢁ), followed by the transition
state TS2. The low activation energy of TS2 (DE=
0.5 kcalmolÀ1) agrees well with the fact that the aziri-
dine intermediate is a transient (semistable) species
that could not be isolated in our experiment. This cal-
culated result is also in-line with the regio- and stereo-
chemistry of our product. The nucleophile, MeOÀ ap-
proaches the positively charged C1 of the Rh–Azi ring
system from the bottom face preferably, to form the
trans product (a-glycosylation product). Furthermore,
usual aminoglycosides with selective a- and b-linkages. With
the concept described here, the intramolecular nitrogen
atom transfer to a C=C bond on the glycal scaffold is high-
lighted as an attractive alternative to conventional methods
of 2-aminoglycoside synthesis. In addition, a variety of
glycal acceptors has selectively been coupled at the anome-
ric position, which results in the high structural and func-
tional group variability of carbohydrate substrates. This
series of glycal glycosylations can be applied in the chemical
synthesis of highly complex aminosaccharide conjugates.
A DFTcomputational study was undertaken to better un-
derstand the mechanism of rhodium-catalyzed intramolecu-
lar aziridination as well as regio- and stereoselective aziri-
dine ring-opening. Our results demonstrate that the nitrene-
transfer and aziridination reactions proceed stepwise to
form semistable aziridine intermediates, which are regiose-
lectively attacked by nucleophiles at the positively charged
anomeric carbons. Significantly, the facial preference, which
is controlled by the substrate was found to be the key factor
that determines the stereoselectivity.
À
À
C1 N bond is partially cleaved (C1 N=1.654 ꢁ in
TS2) even when MeOÀ is still 2.592 ꢁ away from C1.
The reaction coordinate of TS2 involves the simultane-
À
ous breaking of the N C1 bond, and the formation of
À
glycosidic C1 OMe bond, which also reflects the high
activity of Rh–Azi upon the attack of MeOÀ.
Application of this new methodology to asymmetric and
total synthesis is currently under active investigation in our
laboratory.
Conclusion
Experimental Section
We have described a new route to aminoglycosides that is
based on the intramolecular oxidative aziridination on a
glycal scaffold, followed by an efficient ring-opening of azir-
idine with various nucleophiles (C, O, S, and N). The second
nucleophilic replacement of the sulfonyloxy moieties of
[1,2,3]oxathiazepane-2,2-dioxides allows ready access to un-
General: Unless otherwise noted, all reactions were carried out in oven-
dried glassware under an atmosphere of nitrogen, and distilled solvents
were transferred by syringe. Solvents and reagents were purified accord-
ing to standard procedures prior to use. Evaporation of organic solutions
was achieved by rotary evaporation with a water bath temperature below
408C. Product purification by flash column chromatography was accom-
Chem. Eur. J. 2008, 14, 1561 – 1570
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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1565

X.-W. Liu et al.
plished using silica gel 60 (0.010–0.063 nm). Technical grade solvents
were used for chromatography and were distilled prior to use. NMR
5.7, 1.3 Hz, 1H; H2), 2.17 ppm (s, 3H; CH3); 13C NMR (125 MHz,
[D6]acetone): d=168.4 (CO), 165.4 (CO), 164.8 (CO), 133.6 (Ph), 133.5
(Ph), 129.8 (Ph), 129.6 (Ph), 129.4 (Ph), 128.6 (Ph), 128.5 (Ph), 90.9 (C1),
77.6 (C5), 75.1 (CH2), 71.9 (C4), 69.3 (C3), 51.8 (C2), 20.2 ppm (CH3);
IR (CHCl3): n˜ =3018, 1755, 1697 cmÀ1; HR-MS (ESI): m/z: calcd for
C22H21NO10SNa: 514.0778 [M+Na]+; found: 514.0759.
spectra were recorded at room temperature on
a 300 MHz Bruker
ACF 300, 400 MHz Bruker DPX 400, and 500 MHz Bruker AMX 500
NMR spectrometers. The residual solvent signals were taken as the refer-
1
ence (7.26 ppm for H NMR spectra and 77.0 ppm for 13C NMR spectra).
Chemical shift (d) is reported in ppm, coupling constants (J) are given in
Hz. The following abbreviations classify the multiplicity: s=singlet, d=
doublet, t=triplet, q=quartet, m=multiplet or unresolved, br=broad
signal. Infrared spectra were recorded on a Bio-RAD FTS 165 FT-IR
spectrometer and reported in cmÀ1. Samples were prepared by using the
thin film technique. HR-MS (ESI) spectra were recorded on a Finnigan/
MATLCQ quadrupole ion trap mass spectrometer, coupled with the
TSP4000 HPLC system and the Crystal 310 CE system. X-ray crystallo-
graphic data was collected by using a Bruker X8 Apex diffractometer
with MoKa radiation (graphite monochromator).
8-O-Acetyl-9,10-di-O-benzoyl-5,7-dioxa-3-thia-2-azabicyclo[3.3.1]decane-
N
1
3,3-dioxide (12a): Yield: 73%; colorless oil; H NMR (400 MHz, CDCl3):
d=8.08 (d, J=7.9 Hz, 2H; Ph), 8.01 (d, J=7.9 Hz, 2H; Ph), 7.65 (t, J=
7.4 Hz, 1H; Ph), 7.58 (t, J=7.4 Hz, 1H; Ph), 7.51 (t, J=7.6 Hz, 2H; Ph),
7.44 (t, J=7.6 Hz, 2H; Ph), 6.50 (s, 1H; H1), 6.09 (brs, 1H; NH), 5.94
(brt, 1H; H3), 5.06 (m, 1H; H4), 5.04 (t, J=7.3 Hz , 1H; H5), 4.97 (dd,
J=11.0, 7.3 Hz, 1H; CH2), 4.67 (dd, J=11.0, 7.3 Hz, 1H; CH2), 4.07 (m,
1H; H2), 1.81 ppm (s, 3H; CH3); 13C NMR (100 MHz, CDCl3): d=168.7
(CO), 165.9 (CO), 165.3 (CO), 134.4 (Ph), 133.5 (Ph), 129.9 (Ph), 129.7
(Ph), 129.0 (Ph), 128.9 (Ph), 128.5 (Ph), 127.9 (Ph), 91.1 (C1), 75.7 (C4),
72.7 (C5), 63.7 (CH2), 62.2 (C3), 49.8 (C2), 20.8 ppm (CH3); IR (CHCl3):
n˜ =1710, 1635, 1273 cmÀ1; HR-MS (ESI): m/z: calcd for C22H20NO10S:
490.0802 [MÀH]+; found: 490.0825.
General procedure for sulfomylation of glycal: Formic acid (2 equiv) was
added dropwise to a neat chlorosulfonyl isocyanate (2 equiv) at 08C with
rapid stirring. Vigorous gas evolution was observed during the addition
process. The resulting viscous suspension was stirred for 5 min at 08C,
during which time the mixture solidified. Dry CH3CN (10 equiv) was
added, and the resulting clear solution was stirred for 1 h at 08C, then 6 h
at room temperature. This solution mixture was cooled to 08C, and a so-
lution of glycal (1 equiv) in N,N-dimethylacetamide (33 equiv) was added
General procedure for rhodium-catalyzed aziridination with alcohols as
nucleophiles: The nucleophile (20 equiv) was added dropwise to a mix-
ture of sulfamate ester (1 equiv), [Rh
N
N
(1.5 equiv), MgO (5 equiv), and 4 ꢁ molecular sieves in dry CH2Cl2
(2 mL). The suspension was stirred vigorously at room temperature and
monitored by TLC. The reaction mixture was filtered through a pad of
Celite. The filter cake was rinsed with CH2Cl2 and the combined filtrates
were evaporated under reduced pressure. The residue was purified by
flash chromatography on silica gel (eluent: 30% ethyl acetate in hexane)
to afford the desired oxathiazepane.
dropwise. The reaction was stirred at 08C over
a 3 h period, and
quenched by the successive addition of Et3N. The mixture was poured
into diethyl ether (20 mL) and water (10 mL), the organic phase was col-
lected, and the aqueous layer was extracted with diethyl ether (3ꢂ). The
combined organic extracts were washed with brine, dried over MgSO4,
and concentrated under reduced pressure. Purification of the residue by
flash chromatography (eluent: 30% ethyl acetate in hexane) afforded the
desired sulfamate ester.
9-O-Methyl-7,8-di-O-benzoyl-4,10-dioxa-3-thia-2-azabicyclo[4.2.2]decane-
U
3,3-dioxide (10b): Yield: 81%; white solid; 1H NMR (400 MHz, CDCl3):
d=8.06 (m, 4H; Ph), 7.60 (m, 2H; Ph), 7.44 (m, 4H; Ph), 5.84 (dd, J=
5.8, 4.0 Hz, 1H; H3), 5.53 (d, J=4.0 Hz, 1H; H4), 5.51 (d, J=1.1 Hz,
1H; H1), 5.18 (brd, J=3.1 Hz, 1H; NH), 4.72 (dd, J=12.4, 2.5 Hz, 1H;
CH2), 4.63 (dd, J=12.4, 2.5 Hz, 1H; CH2), 4.44 (m, 1H; H5), 4.03 (m,
1H; H2), 3.51 ppm (s, 3H; OCH3); 13C NMR (100 MHz, CDCl3): d=
166.1 (CO), 165.1 (CO), 133.9 (Ph), 133.7 (Ph), 129.98 (Ph), 129.90 (Ph),
128.9 (Ph), 128.7 (Ph), 128.6 (Ph), 96.9 (C1), 76.6 (C5), 75.6 (CH2), 72.1
(C4), 69.5 (C3), 55.4 (OCH3), 53.3 ppm (C2); IR (CHCl3): n˜ =3018, 1714,
1697, 1269 cmÀ1; HR-MS (ESI): m/z: calcd for C21H20NO9S: 462.0853
[MÀH]+; found: 462.0838.
(2R,3S,4R)-2-Sulfamoyloxymethyl-3,4-dihydro-2H-pyran-3,4-diyldiben-
1
zoate (6): Yield: 83%; colorless oil; H NMR (400 MHz, CDCl3): d=7.99
(m, 4H; Ph), 7.56 (m, 2H; Ph), 7.42 (m, 4H; Ph), 6.57 (d, J=6.1 Hz, 1H;
H1), 5.71 (brs, 2H; H3 and H4), 5.14 (brs, 2H; NH2), 5.10 (d, J=6.1 Hz,
1H; H2), 4.56 (m, 2H; H5 and CH2), 4.46 ppm (d, J=8.2 Hz, 1H; CH2);
13C NMR (100 MHz, CDCl3): d=165.8 (CO), 165.5 (CO), 145.5 (C1),
133.8 (Ph), 133.4 (Ph), 129.9 (Ph), 129.7 (Ph), 129.3 (Ph), 128.7 (Ph),
128.6 (Ph), 128.5 (Ph), 99.2 (C2), 73.6 (C5), 67.6 (C4), 67.5 (CH2),
67.3 ppm (C3); IR (CHCl3): n˜ =3421, 3288, 3018, 1718, 1649, 1377 cmÀ1
;
HR-MS (ESI): m/z: calcd for C20H18NO8S: 432.0748 [MÀH]+; found:
432.0733.
9-O-Ethyl-7,8-di-O-benzoyl-4,10-dioxa-3-thia-2-azabicyclo
3,3-dioxide (10c): Yield: 90%; colorless oil; H NMR (400 MHz, CDCl3):
A
1
(2R,3S,4R)-3-Sulfamoyloxy-3,4-dihydro-2H-pyran-2-benzoyloxymethyl-
1
d=8.07 (m, 4H; Ph), 7.61 (m, 2H; Ph), 7.47 (m, 4H; Ph), 5.88 (dd, J=
6.0, 3.6 Hz, 1H; H3), 5.60 (s, 1H; H1), 5.51 (d, J=3.6 Hz, 1H; H4), 5.09
(brd, J=2.9 Hz, 1H; NH), 4.72 (dd, J=12.4, 2.3 Hz, 1H; CH2), 4.62 (dd,
J=12.4, 2.3 Hz, 1H; CH2), 4.43 (m, 1H; H5), 4.03 (m, 1H; H2), 3.91 (dt,
J=16.5, 7.2 Hz, 1H; CH2CH3), 3.63 (dt, J=16.5, 7.2 Hz, 1H; CH2CH3),
1.27 ppm (t, J=7.2 Hz, 3H; CH2CH3); 13C NMR (100 MHz, CDCl3): d=
166.1 (CO), 165.1 (CO), 133.9 (Ph), 133.7 (Ph), 129.96 (Ph), 129.91 (Ph),
128.9 (Ph), 128.7 (Ph), 128.6 (Ph), 128.5 (Ph), 95.5 (C1), 76.5 (C5), 75.7
(CH2), 72.2 (C4), 69.5 (C3), 63.8 (CH2CH3), 53.5 (C2), 15.1 ppm
(CH2CH3); IR (CHCl3): n˜ =3020, 1714, 1452, 1274 cmÀ1; HR-MS (ESI):
m/z: calcd for C22H23NO9SNa: 500.0986 [M+Na]+; found: 500.0967.
4-yl-benzoate (8): Yield: 94%; colorless oil; H NMR (400 MHz, CDCl3):
d=7.99 (m, 4H; Ph), 7.57 (m, 2H; Ph), 7.40 (m, 4H; Ph), 6.56 (d, J=
6.1 Hz, 1H; H1), 5.70 (dd, J=4.1, 3.6 Hz, 1H; H3), 5.49 (brs, 2H; NH2),
5.16 (t, J=5.5 Hz, 1H; H4), 4.98 (dd, J=6.1, 3.6 Hz, 1H; H2), 4.77 (dd,
J=13.0, 6.9 Hz, 1H; CH2), 4.59 ppm (m, 2H; H5 and CH2); 13C NMR
(100 MHz, CDCl3): d=166.4 (CO), 166.3 (CO), 146.2 (C1), 133.6 (Ph),
133.4 (Ph), 129.8 (Ph), 129.7 (Ph), 129.2 (Ph), 129.1 (Ph), 128.5 (Ph),
128.4 (Ph), 98.0 (C2), 74.3 (C4), 73.7 (C5), 67.4 (C3), 61.5 ppm (CH2); IR
(CHCl3): n˜ =3385, 3275, 3020, 1718, 1647, 1382 cmÀ1; HR-MS (ESI): m/z:
calcd for C20H18NO8S: 432.0748 [MÀH]+; found: 432.0729.
General procedure for rhodium-catalyzed aziridination with actetoxy as a
nucleophile:
(10 mol%), PhI
A
mixture of sulfamate ester (1 equiv), [Rh2
G
9-O-Isopropyl-7,8-di-O-benzoyl-4,10-dioxa-3-thia-2-azabicyclo-
ACHTREUNG
A
sieves in dry CH2Cl2 (2 mL) was stirred at room temperature. The reac-
tion was monitored by TLC. The suspension was filtered through a pad
of Celite. The filter cake was rinsed with CH2Cl2 and the combined fil-
trates were evaporated under reduced pressure. The residue was purified
by flash chromatography on silica gel (eluent: 30% ethyl acetate in
hexane) as eluent to afford the desired oxathiazepane.
(400 MHz, CDCl3): d=8.08 (d, J=7.6 Hz, 4H; Ph), 7.60 (m, 2H; Ph),
7.46 (m, 4H; Ph), 5.91 (dd, J=5.8, 3.6 Hz, 1H; H3), 5.67 (s, 1H; H1),
5.50 (d, J=3.6 Hz, 1H; H4), 5.11(brd, J=3.2 Hz, 1H; NH), 4.71 (dd, J=
12.3, 2.0 Hz, 1H; CH2), 4.62 (dd, J=12.3, 2.0 Hz, 1H; CH2), 4.43 (m, 1H;
H5), 4.09 (m, 1H; CH(CH3)2), 3.98 (m, 1H; H2), 1.25 (d, J=6.1 Hz, 3H;
A
CH3), 1.22 ppm (d, J=6.1 Hz, 3H; CH3); 13C NMR (100 MHz, CDCl3):
d=166.2 (CO), 165.1 (CO), 133.9 (Ph), 133.7 (Ph), 129.9 (Ph), 128.9
(Ph), 128.7 (Ph), 128.6 (Ph), 128.5 (Ph), 93.7 (C1), 76.4 (C5), 75.9 (CH2),
9-O-Acetyl-7,8-di-O-benzoyl-4,10-dioxa-3-thia-2-azabicyclo[4.2.2]decane-
A
3,3-dioxide (10a): Yield: 82%; white solid; 1H NMR (500 MHz,
[D6]acetone): d=8.10 (m, 4H; Ph), 7.65 (m, 2H; Ph), 7.53 (m, 4H; Ph),
6.85 (d, J=1.3 Hz , 1H; H1), 5.87 (dd, J=5.7, 4.5 Hz, 1H; H3), 5.76 (d,
J=4.5 Hz, 1H; H4), 4.75 (m, 1H; H5), 4.72 (m, 2H; CH2), 4.23 (dd, J=
72.3 (C4), 70.0 (CH(CH3)2), 69.6 (C3), 53.8 (C2), 23.5 (CH3), 21.5 ppm
A
(CH3); IR (CHCl3): n˜ =3018, 1718, 1452, 1377, 1276 cmÀ1; HR-MS (ESI):
m/z: calcd for C23H25NO9SNa: 514.1142 [M+Na]+; found: 514.1118.
1566
www.chemeurj.org
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2008, 14, 1561 – 1570

Aziridination of Glycals
FULL PAPER
9-O-Benzyl-7,8-di-O-benzoyl-4,10-dioxa-3-thia-2-azabicyclo
A
H3), 5.75 (ABX system, JAX =17.0, JBX =10.5, JAB =5.4 Hz, 1H; CH2CH=
CH2), 5.55 (brd, J=4.6 Hz, 1H; NH), 5.32 (s, 1H; H1), 5.05–5.17 (m,
3H; CH2CH=CH2 and H4), 4.97 (t, J=7.4 Hz, 1H; H5), 4.88 (dd, J=
11.5, 7.4 Hz, 1H; CH2), 4.80 (dd, J=12.4, 5.4 Hz, 1H; CH2CH=CH2),
4.75 (dd, J=11.5, 7.4 Hz, 1H; CH2), 4.38 (dd, J=12.4, 5.4 Hz, 1H;
CH2CH=CH2), 4.03 ppm (m, 1H; H2); 13C NMR (100 MHz, CDCl3): d=
165.8 (CO), 165.4 (CO), 134.0 (Ph), 133.5 (Ph), 132.8 (CH2CH=CH2),
130.0 (Ph), 129.6 (Ph), 129.2 (Ph), 128.7 (Ph), 128.5 (Ph), 128.2 (Ph),
118.2 (CH2CH=CH2), 97.5 (C1), 76.5 (C4), 71.9 (C5), 69.6 (CH2CH=
CH2), 64.0 (CH2), 62.7 (C3), 51.3 ppm (C2); IR (CHCl3): n˜ =3018, 1722,
1627, 1274 cmÀ1; HR-MS (ESI): m/z: calcd for C23H22NO9S: 488.1010
[MÀH]+; found: 488.1003.
1
3,3-dioxide (10e): Yield: 71%; colorless oil; H NMR (500 MHz, CDCl3):
d=8.08 (d, J=8.0 Hz, 2H; Ph), 7.96 (d, J=8.0 Hz, 2H; Ph), 7.61 (t, J=
7.5 Hz, 1H; Ph), 7.56 (t, J=7.5 Hz, 1H; Ph), 7.48 (t, J=7.8 Hz, 2H; Ph),
7.34 (m, 7H; Ph), 5.90 (dd, J=6.3, 3.2 Hz, 1H; H3), 5.67 (d, J=1.6 Hz,
1H; H1), 5.53 (d, J=3.2 Hz, 1H; H4), 5.09 (brd, J=3.8 Hz, 1H; NH),
4.91 (d, J=11.8 Hz, 1H; CH2Ph), 4.76 (dd, J=12.6, 2.4 Hz, 1H; CH2),
4.67 (d, J=11.8 Hz, 1H; CH2Ph), 4.62 (dd, J=12.6, 2.4 Hz, 1H; CH2),
4.45 (m, 1H; H5), 4.12 ppm (ddd, J=6.3, 3.8, 1.6 Hz, 1H; H2); 13C NMR
(125 MHz, CDCl3): d=166.1 (CO), 165.0 (CO), 136.9 (Ph), 133.9 (Ph),
133.6 (Ph), 129.97 (Ph), 129.95 (Ph), 128.8 (Ph), 128.7 (Ph), 128.6 (Ph),
128.55 (Ph), 128.52 (Ph), 127.9 (Ph), 127.8 (Ph), 95.1 (C1), 76.5 (C5), 75.7
(CH2), 72.1 (C4), 69.6 (CH2Ph), 69.4 (C3), 53.2 ppm (C2); IR (CHCl3):
n˜ =3018, 1720, 1452 cmÀ1; HR-MS (ESI): m/z: calcd for C27H25NO9SNa:
562.1142 [M+Na]+; found: 562.1174.
General procedure for rhodium-catalyzed aziridination with alkyl, thiol,
amine, amino acid, and glycal as nucleophiles: A mixture of sulfamate
ester (1 equiv), [Rh2
(tfacam)4] (10 mol%),[25] PhIO (1.5 equiv),[26] MgO
G
8-O-Methyl-9,10-di-O-benzoyl-5,7-dioxa-3-thia-2-azabicyclo
[3.3.1]decane-
(5 equiv), and 4 ꢁ molecular sieves in dry CH2Cl2 (2 mL) was stirred at
room temperature for 15 min, then the nucleophile (1.5 equiv) was added
dropwise. The suspension was stirred vigorously at room temperature
and monitored by TLC. The resulting mixture was filtered through a pad
of Celite. The filter cake was rinsed with CH2Cl2 and the combined fil-
trates were evaporated under reduced pressure. The residue was purified
by chromatography on silica gel (eluent: 30% ethyl acetate in hexane) to
afford the oxathiazepane.
1
3,3-dioxide (12b): Yield: 96%; colorless oil; H NMR (500 MHz, CDCl3):
d=8.00 (m, 4H; Ph), 7.58 (m, 2H; Ph), 7.45 (m, 4H; Ph), 5.86 (m, 2H;
H3 and NH), 5.20 (s, 1H; H1), 5.03 (m, 1H; H4), 4.98 (t, J=7.4 Hz, 1H;
H5), 4.88 (dd, J=11.1, 7.4 Hz, 1H; CH2), 4.73 (dd, J=11.1, 7.4 Hz, 1H;
CH2), 3.99 (m, 1H; H2), 3.48 ppm (s, 3H; OCH3); 13C NMR (125 MHz,
CDCl3): d=165.9 (CO), 165.6 (CO), 134.0 (Ph), 133.4 (Ph), 129.9 (Ph),
129.7 (Ph), 129.2 (Ph), 128.8 (Ph), 128.5 (Ph), 128.3 (Ph), 99.5 (C1), 76.6
(C4), 71.8 (C5), 64.1 (CH2), 63.0 (C3), 56.6 (OCH3), 51.3 ppm (C2); IR
9-Allyl-7,8-di-O-benzoyl-4,10-dioxa-3-thia-2-azabicyclo[4.2.2]decane-3,3-
A
(CHCl3): n˜ =1718, 1635, 1274 cmÀ1
; HR-MS (ESI): m/z: calcd for
dioxide (10 f): Yield: 78%; white solid; 1H NMR (500 MHz, CDCl3): d=
7.89 (d, J=7.3 Hz, 2H; Ph), 7.82 (d, J=7.3 Hz, 2H; Ph), 7.46 (m, 2H;
Ph), 7.32 (m, 2H; Ph), 7.27 (m, 2H; Ph), 6.09 (t, J=10.0 Hz, 1H; H3),
5.79 (ABX system, JAX =17.1 Hz, JBX =10.1, JAB=7.0 Hz, 1H; CH2CH=
CH2), 5.66 (d, J=9.0 Hz, 1H; H4), 5.17 (dd, J=10.1, 1.4 Hz, 1H;
CH2CH=CH2), 5.12 (dd, J=10.1, 1.4 Hz, 1H; CH2CH=CH2), 4.62 (dd,
J=12.6, 4.4 Hz, 1H; CH2), 4.56 (dd, J=12.6, 4.4 Hz, 1H; CH2), 4.49 (m,
1H; H5), 4.23 (brs, 1H; NH), 3.74 (m, 1H; H1 and H2), 2.48 (dd, J=
14.4, 7.0 Hz, 1H; CH2CH=CH2), 2.41 ppm (dd, J=14.4, 7.0 Hz, 1H;
CH2CH=CH2); 13C NMR (100 MHz, CDCl3): d=166.4 (CO), 166.0 (CO),
133.9 (Ph), 133.68 (CH2CH=CH2), 133.63 (Ph), 129.8 (Ph), 129.6 (Ph),
128.55 (Ph), 128.52 (Ph), 128.4 (Ph), 128.3 (Ph), 118.9 (CH2CH=CH2),
75.8 (C4), 73.1 (C5), 72.4 (CH2), 69.4 (C3), 68.7 (C1), 57.0 (C2), 37.7 ppm
(CH2CH=CH2); IR (CHCl3): n˜ =2956, 1714, 1600, 1367, 1278 cmÀ1; HR-
MS (ESI): m/z: calcd for C23H23NO8S: 473.1144 [M]+; found: 473.0993.
C21H20NO9S: 462.0853 [MÀH]+; found: 462.0869.
8-O-Ethyl-9,10-di-O-benzoyl-5,7-dioxa-3-thia-2-azabicyclo
3,3-dioxide (12c): Yield: 87%; colorless oil; H NMR (400 MHz, CDCl3):
A
1
d=7.99 (m, 4H; Ph), 7.59 (m, 2H; Ph), 7.45 (m, 4H; Ph), 5.87 (m, 1H;
H3), 5.62 (brd, J=4.2 Hz, 1H; NH), 5.26 (s, 1H; H1), 5.04 (m, 1H; H4),
4.96 (t, J=7.4 Hz, 1H; H5), 4.88 (dd, J=11.0, 7.4 Hz, 1H; CH2), 4.77
(dd, J=11.0, 7.4 Hz, 1H; CH2), 4.01 (m, 1H; H2), 3.96 (q, J=7.2 Hz,
1H; CH2CH3), 3.51 (q, J=7.0 Hz, 1H; CH2CH3), 1.06 ppm (t, J=7.0 Hz,
3H; CH2CH3); 13C NMR (100 MHz, CDCl3): d=165.9 (CO), 165.4 (CO),
134.0 (Ph), 133.4 (Ph), 129.9 (Ph), 129.6 (Ph), 129.2 (Ph), 128.7 (Ph),
128.5 (Ph), 128.3 (Ph), 98.1 (C1), 76.7 (C4), 71.8 (C5), 64.7 (CH2), 64.1
(CH2), 62.8 (C3), 51.3 (C2), 14.7 ppm (CH2CH3); IR (CHCl3): n˜ =3018,
1718, 1273, 1217 cmÀ1
; HR-MS (ESI): m/z: calcd for C22H22NO9S:
476.1010 [MÀH]+; found: 476.0987.
8-O-Isopropyl-9,10-di-O-benzoyl-5,7-dioxa-3-thia-2-azabicyclo-
9-p-Tolylthio-7,8-di-O-benzoyl-4,10-dioxa-3-thia-2-azabicyclo-
[3.3.1]decane-3,3-dioxide (12d): Yield: 86%; colorless oil; 1H NMR
[4.2.2]decane-3,3-dioxide (10g): Yield: 85%; colorless oil; 1H NMR
(400 MHz, CDCl3): d=8.02 (m, 4H; Ph), 7.59 (m, 2H; Ph), 7.45 (m, 4H;
Ph), 5.84 (m, 1H; H3), 5.53 (brs, 1H; NH), 5.36 (s, 1H; H1), 5.05 (m,
1H; H4), 4.95 (t, J=7.5 Hz, 1H; H5), 4.84 (m, 2H; CH2), 4.09 (m, 1H;
(500 MHz, CDCl3): d=8.06 (m, 4H; Ph), 7.59 (m, 2H; Ph), 7.51 (d, J=
8.0 Hz, 2H; Ph), 7.47 (m, 4H; Ph), 7.18 (d, J=8.0 Hz, 2H; Ph), 6.27 (s,
1H; H1), 5.99 (t, J=5.5 Hz, 1H; H3), 5.68 (d, J=5.5 Hz, 1H; H4), 5.08
(brd, J=2.9 Hz, 1H; NH), 4.77 (dd, J=13.0, 3.5 Hz, 1H; CH2), 4.71 (dd,
J=13.0, 1.5 Hz, 1H; CH2), 4.51 (m, 1H; H5), 4.27 (brt, J=3.8 Hz, 1H;
H2), 2.36 ppm (s, 3H; CH3); 13C NMR (100 MHz, CDCl3): d=166.3
(CO), 165.0 (CO), 139.2 (Ph), 134.1 (Ph), 134.0 (Ph), 133.8 (Ph), 130.2
(Ph), 130.0 (Ph), 128.7 (Ph), 128.6 (Ph), 128.5 (Ph), 127.7 (Ph), 81.5 (C1),
78.4 (C5), 75.4 (CH2), 71.9 (C4), 70.4 (C3), 54.5 (C2), 21.2 ppm (CH3);
IR (CHCl3): n˜ =3018, 1722, 1273 cmÀ1; HR-MS (ESI): m/z: calcd for
C27H25NO8S2Na: 578.0914 [M+Na]+; found: 578.0939.
CH(CH3)2), 3.97 (m, 1H; C2), 1.09 (d, J=6.1 Hz, 3H; CH3), 1.06 ppm (d,
A
J=6.1 Hz, 3H; CH3); 13C NMR (100 MHz, CDCl3): d=165.9 (CO), 165.4
(CO), 134.0 (Ph), 133.4 (Ph), 129.9 (Ph), 129.6 (Ph), 129.2 (Ph), 128.6
(Ph), 128.5 (Ph), 128.3 (Ph), 95.8 (C1), 76.7 (C4), 71.7 (C5), 70.4 (CH-
A
(CHCl3): n˜ =2926, 1722, 1645, 1273 cmÀ1; HR-MS (ESI): m/z: calcd for
C23H24NO9S: 490.1166 [MÀH]+; found: 490.1149.
8-O-Benzyl-9,10-di-O-benzoyl-5,7-dioxa-3-thia-2-azabicyclo[3.3.1]decane-
3,3-dioxide (12e): Yield: 77%; colorless oil; H NMR (400 MHz, CDCl3):
d=8.00 (d, J=8.0 Hz, 2H; Ph), 7.84 (d, J=8.0 Hz, 2H; Ph), 7.55 (m,
2H; Ph), 7.44 (m, 2H; Ph), 7.26 (m, 7H; Ph), 5.89 (m, 1H; H3), 5.45
(brd, J=4.0 Hz, 1H; NH), 5.39 (s, 1H; H1), 5.05 (m, 1H; H4), 4.97 (m,
2H; H5 and CH2Ph), 4.89 (dd, J=11.1, 7.4 Hz, 1H; CH2), 4.77 (dd, J=
11.1, 7.4 Hz, 1H; CH2), 4.57 (d, J=11.3 Hz, 1H; CH2Ph), 4.03 ppm (m,
1H; C2); 13C NMR (100 MHz, CDCl3): d=166.1 (CO), 166.0 (CO), 136.2
(Ph), 133.8 (Ph), 133.4 (Ph), 130.0 (Ph), 129.9 (Ph), 129.7 (Ph), 129.6
(Ph), 129.5 (Ph), 129.2 (Ph), 128.8 (Ph), 128.6 (Ph), 128.5 (Ph), 128.4
(Ph), 128.1 (Ph), 128.0 (Ph), 97.7 (C1), 76.4 (C4), 72.1 (C5), 71.1
(CH2Ph), 64.0 (CH2), 62.5 (C3), 51.4 ppm (C2); IR (CHCl3): n˜ =2954,
9-N-(3,5-Bis(trifluoromethyl)phenyl-7,8-di-O-benzoyl-4,10-dioxa-3-thia-2-
azabicyclo[4.2.2]decane-3,3-dioxide (10h): Yield: 76%; colorless oil;
A
1H NMR (400 MHz, CDCl3): d=8.07 (d, J=7.4 Hz, 2H; Ph), 8.00 (d, J=
7.4 Hz, 2H; Ph), 4.10 (m, 1H; H2), 7.60 (m, 2H; Ph), 7.45 (m, 4H; Ph),
7.35 (s, 1H; Ph), 7.21 (s, 2H; Ph), 6.46 (d, J=9.0 Hz, 1H; H1), 5.85 (dd,
J=6.6, 4.2 Hz, 1H; H3), 5.79 (d, J=6.6 Hz, 1H; H4), 5.29 (brs, 1H;
NH), 5.13 (brd, J=9.0 Hz, 1H; NHPh), 4.89 (dd, J=13.3, 1.5 Hz, 1H;
CH2), 4.80 (dd, J=13.3, 1.5 Hz, 1H; CH2), 4.52 (m, 1H; H5), 4.10 ppm
(m, 1H; H2); 13C NMR (100 MHz, CDCl3): d=166.1 (CO), 165.7 (CO),
145.3 (Ph), 134.3 (Ph), 134.0 (Ph), 132.6 (Ph), 130.0 (Ph), 129.8 (Ph),
128.8 (Ph), 128.6 (Ph), 128.4 (Ph), 128.0 (Ph), 114.0 (CF3), 113.4 (CF3),
78.7 (C1), 77.6 (C5), 75.2 (CH2), 71.8 (C4), 70.5 (C3), 55.1 ppm (C2); IR
(CHCl3): n˜ =3018, 1720, 1624, 1473, 1388, 1278 cmÀ1; HR-MS (ESI): m/z:
calcd for C28H23F6N2O8S: 661.1079 [M+H]+; found: 661.1029.
1708, 1635, 1269 cmÀ1
; HR-MS (ESI): m/z: calcd for C27H24NO9S:
538.1166 [MÀH]+; found: 538.1189.
8-O-Allyl-9,10-di-O-benzoyl-5,7-dioxa-3-thia-2-azabicyclo
3,3-dioxide (12 f): Yield: 81%; colorless oil; H NMR (300 MHz, CDCl3):
d=8.01 (m, 4H; Ph), 7.58 (m, 2H; Ph), 7.36 (m, 4H; Ph), 5.88 (m, 1H;
A
1
9-N-[Methyl-N-(dibenzyl)-l-serinate-3-yl]-7,8-di-O-benzoyl-4,10-dioxa-3-
thia-2-azabicyclo[4.2.2]decane-3,3-dioxide (10i): Yield: 66%; colorless
A
Chem. Eur. J. 2008, 14, 1561 – 1570
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
1567

X.-W. Liu et al.
1
oil; H NMR (500 MHz, CDCl3): d=8.09 (m, 2H; Ph), 7.89 (m, 2H; Ph),
8-O-Methyl-9,10-di-O-benzoyl-5,7-dioxa-3-thia-2-azidobicyclo-
[3.3.1]decane-3,3-dioxide (15): Aqueous NaHCO3 (100 mg in 1 mL of
7.61 (m, 1H; Ph), 7.55 (m, 1H; Ph), 7.48 (m, 2H; Ph), 7.38 (m, 6H; Ph),
7.30 (m, 4H; Ph), 7.21 (m, 2H; Ph), 5.80 (dd, J=5.6, 4.3 Hz, 1H; H3),
5.61 (d, J=1.2 Hz, 1H; H1), 5.50 (d, J=4.3 Hz, 1H; H4), 5.08 (brs, 1H;
NH), 4.69 (dd, J=12.1, 2.6 Hz, 1H; CH2OSO2), 4.62 (dd, J=12.1, 2.6 Hz,
1H; CH2OSO2), 4.39 (m, 1H; H5), 4.18 (dd, J=10.3, 6.3 Hz, 1H; CH2O),
3.99 (dd, J=5.6, 1.2 Hz, 1H; H2), 3.94 (d, J=13.9 Hz, 1H; CH2Ph), 3.85
(dd, J=10.3, 6.3 Hz, 1H; CH2O), 3.75 (m, 1H; CHN), 3.74 (s, 3H;
OCH3), 3.70 ppm (d, J=13.9 Hz, 1H; CH2Ph); 13C NMR (125 MHz,
CDCl3): d=171.2 (CO), 166.1 (CO), 164.9 (CO), 139.2 (Ph), 133.9 (Ph),
133.6 (Ph), 129.9 (Ph), 129.8 (Ph), 128.77 (Ph), 128.73 (Ph), 128.6 (Ph),
128.5 (Ph), 128.3 (Ph), 127.1 (Ph), 95.9 (C1), 76.8 (C5), 75.7 (CH2OSO2),
72.0 (C4), 69.4 (C3), 66.3 (CH2O), 61.0 (OCH3), 55.2 (CH2Ph), 53.3 (C2),
51.4 ppm (CHN); IR (CHCl3): n˜ =2926, 1724, 1452, 1261 cmÀ1; HR-MS
(ESI): m/z: calcd for C38H39N2O11S: 731.2269 [M+H]+; found: 731.2286.
ACHTREUNG
water) and CbzCl (350 mL, 2.46 mmol) were sequentially added to a solu-
tion of oxathiazepane 12b (116 mg, 0.24 mmol) in THF (1 mL) with vigo-
rous stirring at 08C. The reaction mixture was kept at this temperature
for 1 h and then warmed up to room temperature overnight. The mixture
was extracted with EtOAc (3ꢂ). The combined organic layers were dried
over anhydrous MgSO4, filtered, and concentrated. The residue was puri-
fied by chromatography on silica gel (eluent: 50% ethyl acetate in
hexane) to yield 15 (120 mg, 82%) as white solid. 1H NMR (500 MHz,
CDCl3): d=8.15 (d, J=7.7 Hz, 2H; Ph), 8.05 (d, J=7.7 Hz, 2H; Ph), 7.57
(m, 2H; Ph), 7.34 (m, 4H; Ph), 7.31 (m, 5H; Ph), 5.71 (d, J=3.2 Hz, 1H;
H3), 5.10 (ABq, J=16.0, 12.2 Hz, 2H; CH2), 4.59 (dd, J=11.3, 6.5 Hz,
1H; CH2), 4.49 (d, J=7.9 Hz, 1H; H1), 4.38 (dd, J=11.3, 6.5 Hz, 1H;
CH2), 4.12 (m, 1H; H4), 4.12 (m, 1H; H4), 4.08 (t, J=6.4 Hz, 1H; H5),
3.71 (m, 1H; H2), 3.55 ppm (s, 3H; OCH3); 13C NMR (125 MHz,
CDCl3): d=166.2 (CO), 166.1 (CO), 157.4 (CO), 135.8 (Ph), 133.4 (Ph),
133.2 (Ph), 130.0 (Ph), 129.7 (Ph), 129.5 (Ph), 129.3 (Ph), 128.6 (Ph),
128.5 (Ph), 128.4 (Ph), 128.3 (Ph), 128.2 (Ph), 101.8 (C1), 71.5 (C5), 71.4
(C4), 69.5 (C3), 67.4 (CH2), 62.4 (CH2), 57.1 (OCH3), 56.1 ppm (C2); IR
9-O-[3,4-Di-O-benzoyl-1,2-dideoxy-d-glcopyranosyl]-7,8-di-O-benzoyl-
4,10-dioxa-3-thia-2-azabicyclo
A
(10j):
Yield:
68%; colorless oil; 1H NMR (500 MHz, CDCl3): d=8.03 (m, 9H; Ph),
7.61 (m, 1H; Ph), 7.49 (m, 6H; Ph), 7.35 (m, 4H; Ph), 6.51 (d, J=6.2 Hz,
1H; H1’), 5.86 (dd, J=5.9, 3.9 Hz, 1H; H3), 5.76 (dd, J=6.7, 5.7 Hz, 1H;
H4’), 5.63 (m, 2H; H1 and H3’), 5.49 (d, J=3.9 Hz, 1H; H4), 5.06 (dd,
J=6.2, 3.4 Hz, 1H; H2’), 4.98 (d, J=3.6 Hz, 1H; NH), 4.66 (dd, J=12.4,
2.5 Hz, 1H; CH2OSO2), 4.61 (dd, J=12.4, 2.5 Hz, 1H; CH2OSO2), 4.56
(ABq, J=11.2, 5.7 Hz, 1H; H5’), 4.49 (m, 1H; H5), 4.13 (dd, J=11.2,
5.7 Hz, 1H; CH2O), 4.06 (dd, J=11.2, 5.7 Hz, 1H; CH2O), 3.97 ppm (m,
1H; H2); 13C NMR (100 MHz, CDCl3): d=166.2 (CO), 165.8 (CO), 164.9
(CO), 164.8 (CO), 145.9 (C1’), 133.9 (Ph), 133.5 (Ph), 133.39 (Ph), 133.30
(Ph), 129.95 (Ph), 129.87 (Ph), 129.83 (Ph), 129.7 (Ph), 129.6 (Ph), 129.2
(Ph), 128.97 (Ph), 128.7 (Ph), 128.6 (Ph), 128.5 (Ph), 128.48 (Ph), 128.45
(Ph), 98.8 (C2’), 96.4 (C1), 76.7 (C5), 75.7 (CH2OSO2), 74.5 (C5’), 72.1
(C4), 69.3 (C3), 68.0 (C4’), 67.7 (C3’), 66.3 (CH2O), 53.1 ppm (C2); IR
(CHCl3): n˜ =3018, 1720, 1647, 1602, 1273 cmÀ1; HR-MS (ESI): m/z: calcd
for C40H35NO14SNa: 808.1676 [M+Na]+; found: 808.1468.
(Nujol): n˜ =1720, 1714, 1273 cmÀ1
; HR-MS (ESI): m/z: calcd for
C29H26NO11S: 596.1221 [MÀH]+; found: 596.1221.
Methyl-6-azido-2-benzyloxycarbonylamino-3,4-di-O-benzoyl-2,6-dideoxy-
d-glucopyranoside (14a): NaN3 (6 mg, 9.2ꢂ10À2 mmol) was added to a
solution of N-Cbz oxathiazepane 13 (28 mg, 4.7ꢂ10À2 mmol) in dry DMF
(0.3 mL) in the presence of 4 ꢁ molecular sieves. After heating at 1208C
for 5 h, the reaction mixture was cooled to room temperature. NaH2PO4
(2 mL, 1 m) was added and the mixture was stirred for an hour. The mix-
ture was filtered and the filtrate was washed with water (3ꢂ), dried over
anhydrous MgSO4, filtered, and concentrated in vacuo. The residue was
purified by chromatography on silica gel (eluent: 50% ethyl acetate in
hexane) to yield 14a (18 mg, 67%) as
a
colorless oil; 1H NMR
(400 MHz, CDCl3): d=7.94 (d, J=7.4 Hz, 2H; Ph), 7.87 (d, J=7.4 Hz,
2H; Ph), 7.49 (m, 3H; Ph), 7.35 (m, 8H; Ph), 5.71 (dd, J=10.6, 4.1 Hz,
1H; H3), 5.47 (t, J=10.6 Hz, 1H; H4), 5.20 (brd, J=8.2 Hz, 1H; NH),
5.01 (m, 2H; CH2), 4.84 (m, 1H; H1), 4.60 (m, 1H; H2), 4.13 (m, 1H;
H5), 3.51 (s, 3H; CH3), 3.48 ppm (m, 2H; CH2N3); 13C NMR (100 MHz,
CDCl3): d=170.5 (CO), 165.3 (CO), 155.8 (CO), 133.6 (Ph), 133.0 (Ph),
129.8 (Ph), 129.7 (Ph), 128.6 (Ph), 128.5 (Ph), 128.4 (Ph), 128.28 (Ph),
128.20 (Ph), 100.3 (C1), 69.8 (C5), 69.5 (C3), 67.4 (CH2), 67.1 (C4), 55.5
(OCH3), 52.3 (CH2N3), 51.2 ppm (C2); IR (CHCl3): n=2102, 1724, 1672,
8-p-Tolylthio-9,10-di-O-benzoyl-5,7-dioxa-3-thia-2-azabicyclo-
[3.3.1]decane-3,3-dioxide (12g): Yield: 78%; colorless oil; 1H NMR
(400 MHz, CDCl3): d=8.08 (m, 2H; Ph), 8.00 (m, 2H; Ph), 7.67 (m, 1H;
Ph), 7.54 (m, 3H; Ph), 7.42 (m, 4H; Ph), 7.14 (d, J=7.9 Hz, 2H; Ph),
5.79 (m, 1H; H3), 5.58 (brs, 1H; NH), 5.37 (m, 1H; H5), 5.26 (m, 1H;
H4), 5.12 (m, 1H; H2), 4.94 (m, 1H; H1), 4.86 (dd, J=12.2, 3.7 Hz, 1H;
CH2), 4.25 (dd, J=12.2, 3.7 Hz, 1H; CH2), 2.33 ppm (s, 3H; CH3);
13C NMR (100 MHz, CDCl3): d=165.8 (CO), 164.8 (CO), 134.35 (Ph),
133.4 (Ph), 133.0 (Ph), 130.3 (Ph), 130.1 (Ph), 129.7 (Ph), 128.8 (Ph),
128.5 (Ph), 123.6 (Ph), 80.1 (C4), 66.7 (C1), 66.6 (C2 and C5), 62.7 (C3),
61.1 (CH2), 21.1 ppm (CH3); IR (CHCl3): n˜ =3018, 2929, 1718, 1649,
1388, 1269 cmÀ1; HR-MS (ESI): m/z: calcd for C27H25NO8S2Na: 578.0914
[M+Na]+; found: 578.0891.
1273 cmÀ1
; HR-MS (ESI): m/z: calcd for C29H28N4O8Na: 583.1804
[M+Na]+; found: 583.1822.
Methyl-6-thiocyanato-2-benzyloxycarbonylamino-3,4-di-O-benzoyl-2,6-di-
deoxy-d-glucopyranoside (14b): Potassium thiocyanate (23 mg,
0.23 mmol) was added to a solution of N-Cbz oxathiazepane 13 (28 mg,
4.7ꢂ10À2 mmol) in dry DMF (0.5 mL) in the presence of 4 ꢁ molecular
sieves. The mixture was stirred at 1508C for 12 h under a nitrogen atmos-
phere. After cooling the reaction to room temperature, 1m NaH2PO4
(2 mL) was added and the mixture was stirred for another hour. The mix-
ture was filtered and the filtrate was washed with water (3ꢂ), dried over
anhydrous MgSO4, filtered, and concentrated in vacuo. The residue was
purified by chromatography on silica gel (eluent 50% ethyl acetate in
9-O-Methyl-7,8-di-O-benzoyl-4,10-dioxa-3-thia-2-azidobicyclo-
[4.2.2]decane-3,3-dioxide (13): CbzCl (0.3 mL, 2.11 mmol) and a catalytic
U
amount of DMAP (30 mg, 0.25 mmol) were subsequently added to a mix-
ture solution of oxathiazepane 10b (110 mg, 0.23 mmol) in THF (1 mL)
and Et3N (0.7 mL, 5.02 mmol) at 08C. The reaction was stirred at room
temperature for 2.5 h and then quenched with saturated aqueous NH4Cl.
The mixture was extracted with EtOAc (2ꢂ). The combined organic
layers were dried over anhydrous MgSO4, filtered, and concentrated. The
residue was purified by chromatography on silica gel (eluent: 50% ethyl
acetate in hexane) to yield 13 (130 mg, 92%) as white solid. 1H NMR
(400 MHz, CDCl3): d=7.96 (d, J=7.4 Hz, 2H; Ph), 7.88 (d, J=7.4 Hz,
2H), 7.47 (m, 4H; Ph), 7.30 (m, 7H; Ph), 5.73 (dd, J=10.1, 4.2 Hz, 1H;
H3), 5.54 (t, J=10.1 Hz, 1H; H4), 5.00 (s, 2H; CH2), 4.85 (brs, 1H; H1),
4.72 (dd, J=8.8, 4.3 Hz, 1H; H2), 4.21 (m, 1H; H5), 3.72 (dd, J=12.1,
6.0 Hz, 1H; CH2), 3.66 (dd, J=12.1, 6.0 Hz, 1H; CH2), 3.50 ppm (s, 3H;
OCH3); 13C NMR (100 MHz, CDCl3): d=165.5 (CO), 165.4 (CO), 155.8
(CO), 136.0 (Ph), 133.6 (Ph), 133.0 (Ph), 129.8 (Ph), 129.7 (Ph), 129.3
(Ph), 128.7 (Ph), 128.59 (Ph), 128.51 (Ph), 128.29 (Ph), 128.22 (Ph), 100.4
(C1), 70.0 (C5), 69.7 (C4), 67.7 (C3), 67.1 (CH2), 55.5 (OCH3), 52.3 (C2),
43.8 ppm (CH2); IR (CHCl3): n˜ =3018, 1726, 1512, 1274 cmÀ1; HR-MS
(ESI): m/z: calcd for C29H26NO11S: 596.1221 [MÀH]+ found: 596.1226.
hexane) to yield 14b (21 mg, 78%) as
a
colorless oil; 1H NMR
(500 MHz, CDCl3): d=7.98 (m, 2H; Ph), 7.89 (d, J=7.4 Hz, 2H; Ph),
7.57 (t, J=7.4 Hz, 2H; Ph), 7.50 (t, J=7.4 Hz, 1H; Ph), 7.42 (t, J=
7.8 Hz, 2H; Ph), 7.34 (m, 7H; Ph), 5.78 (dd, J=10.0, 4.1 Hz, 1H; H3),
5.43 (t, J=10.0 Hz, 1H; H4), 5.22 (d, J=9.1 Hz, 1H; NH), 5.05 (m, 2H;
CH2), 4.90 (m, 1H; H1), 4.63 (dd, J=9.1, 4.1 Hz, 1H; H2), 4.29 (t, J=
7.9 Hz, 1H; H5), 3.57 (s, 3H; CH3), 3.29 (dd, J=13.9, 2.6 Hz, 1H;
CH2SCN), 3.15 ppm (dd, J=13.9, 8.4 Hz, 1H; CH2SCN); 13C NMR
(125 MHz, CDCl3): d=165.9 (CO), 165.3 (CO), 155.7 (CO), 135.9 (Ph),
133.9 (Ph), 133.1 (Ph), 129.9 (Ph), 129.7 (Ph), 129.2 (Ph), 128.6 (Ph),
128.3 (Ph), 128.2 (Ph), 111.9 (CN), 100.5 (C1), 69.5 (C3), 69.2 (C4), 68.9
(C5), 67.2 (CH2), 55.8 (OCH3), 52.3 (C2), 35.9 ppm (CH2SCN); IR
(CHCl3): n˜ =3018, 1780, 1703, 1386, 1215 cmÀ1; HR-MS (ESI): m/z: calcd
for C30H28N2O8SNa: 599.1459 [M+Na]+; found: 599.1445.
1568
www.chemeurj.org
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2008, 14, 1561 – 1570

Aziridination of Glycals
FULL PAPER
Methyl-N-4-methoxybenzylamino-2-benzyloxycarbonylamino-3,6-di-O-
benzoyl-2,4-dideoxy-d-glucopyranoside (16a): A solution of compound
15 (11 mg, 2.4ꢂ10À2 mmol) in dry DMF (0.5 mL) was treated with p-me-
[3] a) C. I. Gama, L. C. Hsieh-Wilson, Curr. Opin. Chem. Biol. 2005, 9,
609–619; b) S. Mizuguchi, T. Uyama, H. Kitagawa, K. H. Nomura,
K. Dejima, K. Gengyo-Ando, S. Nitani, K. Sugahara, K. Nomura,
Nature 2003, 423, 443–448; c) E. J. Bradbury, L. D. F. Moon, R. J.
Popat, V. R. King, G. S. Bennett, P. N. Patel, J. W. Fawcett, S. B.
MacMahon, Nature 2002, 416, 636–640.
[4] For reviews of aminoglycoside synthesis and the associated protect-
ing group manipulations, see: J. Banoub, P. Boullanger, D. Lafont,
Chem. Rev. 1992, 92, 1167–1195.
[5] a) D. A. Griffith, S. J. Danishefsky, J. Am. Chem. Soc. 1990, 112,
5811–5819; b) D. A. Griffith, S. J. Danishefsky, J. Am. Chem. Soc.
1991, 113, 5863–5864; c) S. J. Danishefsky, M. T. Bilodeau, Angew.
Chem. 1996, 108, 1482–1522; Angew. Chem. Int. Ed. Engl. 1996, 35,
1380–1419; d) J. M. Owens, B. K. S. Yeung, D. C. Hill, P. A. Petillo,
J. Org. Chem. 2001, 66, 1484–1486.
[6] a) J. Du Bois, C. S. Tomooka, J. Hong, E. M. Carreira, J. Am. Chem.
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Chem. Soc. 2004, 126, 8356–8357.
thoxybenzylamine (15 mL, 11.4ꢂ10À2 mmol) under
a nitrogen atmos-
phere. The reaction mixture was heated at 708C for 30 h and then cooled
to room temperature. The solvent was removed under reduced pressure,
then EtOAc (10 mL) was added to the residue, and the solution was
washed with water (3ꢂ). The combined organic layers were dried over
anhydrous MgSO4, filtered, and concentrated. Purification by chromatog-
raphy on silica gel (eluent: 30% ethyl acetate in hexane) gave 16a (9 mg,
75%) as colorless viscous oil; 1H NMR (400 MHz, CDCl3): d=8.02 (d,
J=7.6 Hz, 2H; Ph), 7.77 (d, J=8.0 Hz, 2H; Ph), 7.56 (m, 1H; Ph), 7.39
(m, 6H; Ph), 7.27 (m, 2H; Ph), 7.18 (m, 4H; Ph), 6.88 (d, J=8.0 Hz, 2H;
Ph), 5.30 (m, 1H; H1), 5.03 (m, 3H; CH2 and NH), 4.59 (m, 5H; H3,
CH2 and CH2N), 4.23 (m, 1H; H4), 4.15 (m, 1H; H2), 3.98 (m, 1H; H5),
3.80 (s, 3H; OCH3), 3.54 (s, 3H; OCH3), 2.50 ppm (brs, 1H; NH);
13C NMR (100 MHz, CDCl3): d=166.4 (CO), 166.1 (CO), 159.1 (CO),
136.2 (Ph), 134.4 (Ph), 133.5 (Ph), 133.3 (Ph), 131.5 (Ph), 130.2 (Ph),
129.9 (Ph), 129.7 (Ph), 129.5 (Ph), 129.3 (Ph), 129.1 (Ph), 128.59 (Ph),
128.52 (Ph), 128.4 (Ph), 128.3 (Ph), 127.9 (Ph), 127.7 (Ph), 126.9 (Ph),
114.2 (Ph), 73.2 (C5), 72.1 (C1), 66.8 (C4 and CH2), 62.7 (C3 and CH2),
56.9 (OCH3), 55.3 (OCH3), 52.4 (C2), 43.6 ppm (CH2); IR (Nujol): n˜ =
[7] a) V. Di Bussolo, J. Liu, L. G. Huffman, Jr., D. Y. Gin, Angew.
Chem. 2000, 112, 210–213; Angew. Chem. Int. Ed. 2000, 39, 204–
207; b) J. Liu, D. Y. Gin, J. Am. Chem. Soc. 2002, 124, 9789–9797;
c) J. Liu, V. Di Bussolo, D. Y. Gin, Tetrahedron Lett. 2003, 44, 4015–
4018.
1720, 1689, 1635 cmÀ1
; HR-MS (ESI): m/z: calcd for C37H39N2O9:
655.2650 [M+H]+; found: 655.2634.
À
[8] For a review on nitrene insertion into C H and C=C bonds, see
a) C. G. Espino, J. Du Bois in Modern Rhodium-Catalyzed Organic
Reaction (Eds.: P. A. Evans), Wiley-VCH, Weinheim, 2005, pp. 379–
416; b) P. Muller, C. Fruit, Chem. Rev. 2003, 103, 2905–2920.
[9] a) J. L. Liang, J. S. Huang, X. Q. Yu, N. Zhu, C.-M. Che, Chem. Eur.
J. 2002, 8, 1563–1572; b) J. L. Liang, S. X. Yuan, J. S. Huang, W. Y.
Yu, C.-M. Che, Angew. Chem. 2002, 114, 3615–3618; Angew. Chem.
Int. Ed. 2002, 41, 3465–3468; c) F. J. Duran, A. A. Ghini, P. Dauban,
R. H. Dodd, G. Burton, J. Org. Chem. 2005, 70, 8613–8616.
[10] For rhodium-catalyzed intramolecular aziridination, see a) J. L.
Liang, S. X. Yuan, P. W. H. Chan, C.-M. Che, Org. Lett. 2002, 4,
4507–4510; b) P. M. Wehn, J. Lee, J. Du Bois, Org. Lett. 2003, 5,
4823–4826; c) K. Guthikonda, P. M. Wehn, B. J. Caliando, J.
Du Bois, Tetrahedron 2006, 62, 11331–11342; d) A. Padwa, A. C.
Flick, C. A. Leverett, T. Stengel, J. Org. Chem. 2004, 69, 6377–6386;
e) C. Fruit, P. Muller, Tetrahedron: Asymmetry 2004, 15, 1019–1026.
[11] For copper-catalyzed intramolecular aziridination, see a) P. Dauban,
R. H. Dodd, Org. Lett. 2000, 2, 2327–2329; b) P. Dauban, L. Sa-
niere, A. Tarrade, R. H. Dodd, J. Am. Chem. Soc. 2001, 123, 7707–
7708; c) F. Duran, L. Leman, A. Ghini, G. Burton, P. Dauban, R. H.
Dodd, Org. Lett. 2002, 4, 2481–2483.
Methyl-2-benzyloxycarbonylamino-3,6-di-O-benzoyl-2-deoxy-d-glucopyr-
anoside (16b): A solution of compound 15 (7 mg, 1.2ꢂ10À2 mmol) in ace-
tone (0.3 mL) and water (0.3 mL) was treated with K2CO3 (4 mg, 2.9ꢂ
10À2 mmol). The reaction mixture was stirred at room temperature for
14 h and then quenched with 1m NaH2PO4 (0.5 mL). The organic phase
was separated and the aqueous phase was extracted with EtOAc (2ꢂ).
The combined organic layers were dried over anhydrous MgSO4, filtered,
and concentrated. Purification by chromatography on silica gel (eluent:
50% ethyl acetate in hexane) gave 16b (5 mg, 80%) as a white solid;
1H NMR (400 MHz, CDCl3): d=8.04 (m, 4H; Ph), 7.58 (m, 2H; Ph),
7.44 (m, 4H; Ph), 7.20 (m, 5H; Ph), 5.32 (m, 1H; H1), 5.03 (q, J=
12.4 Hz, 2H; CH2), 4.86 (brs, 1H; NH), 4.62 (m, 3H; H3 and CH2), 4.23
(m, 1H; H4), 4.13 (q, J=7.4 Hz, 1H; H2), 3.98 (t, J=6.2 Hz, 1H; H5),
3.54 (s, 3H; OCH3), 2.51 ppm (brs, 1H; OH); 13C NMR (100 MHz,
CDCl3): d=166.4 (CO), 166.0 (CO), 156.1 (CO), 136.2 (Ph), 133.5 (Ph),
133.3 (Ph), 129.9 (Ph), 129.7 (Ph), 129.5 (Ph), 129.1 (Ph), 128.5 (Ph),
128.4 (Ph), 128.3 (Ph), 127.9 (Ph), 127.7 (Ph), 73.3 (C5), 72.1 (C1), 66.8
(C4 and CH2), 62.7 (C3 and CH2), 56.9 (OCH3), 52.4 ppm (C2); IR
(Nujol): n=3294, 1722, 1685 cmÀ1
; HR-MS (ESI): m/z: calcd for
C29H29NO9Na: 558.1735 [M+Na]+; found: 558.1760.
[12] E. Levites-Agababa, E. Menhaji, L. N. Perlson, C. M. Rojas, Org.
Lett. 2002, 4, 863–865.
[13] a) L. A. Paquette, J. A. Oplinger, J. Org. Chem. 1988, 53, 2953–
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Published online: November 28, 2007
1570
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Chem. Eur. J. 2008, 14, 1561 – 1570