D-allal- and d-galactal-derived vinyl N-mesylaziridines: Regio- and stereoselectivity in addition reactions of O-, C-, N-, and S-nucleophiles

Article abstract of DOI:10.1055/s-0031-1291137

The regioselectivity and stereoselectivity were examined of the addition reactions of O-, C-, N- and S-nucleophiles to d-allal- and d-galactal-derived N-mesylaziridines. The ratio of 1,4-regioselectivity (exclusive syn-1,4-addition) to 1,2-regioselectivit

Full text of DOI:10.1055/s-0031-1291137

SPECIAL TOPIC
▌2863
special topic
D-Allal- and D-Galactal-Derived Vinyl N-Mesylaziridines: Regio- and Stereo-
selectivity in Addition Reactions of O-, C-, N-, and S-Nucleophiles
Valeria Di Bussolo,* Ileana Frau, Mauro Pineschi, Paolo Crotti*
Dipartimento di Scienze Farmaceutiche, sede Chimica Bioorganica e Biofarmacia, Università di Pisa, Via Bonanno 33, 56126 Pisa, Italy
Fax +39(050)2219660; E-mail: paolo.crotti@farm.unipi.it
Received: 27.02.2012; Accepted after revision: 15.03.2012
allal- and D-galactal-derived N-mesyl aziridines (1α and
Abstract: The regioselectivity and stereoselectivity were examined
1β, respectively) as new glycosyl donors has been shown
of the addition reactions of O-, C-, N- and S-nucleophiles to D-allal-
to be completely 1,4-regio- and syn-stereoselective, with
exclusive formation of the corresponding alkyl α-O- or β-
and D-galactal-derived N-mesylaziridines. The ratio of 1,4-regiose-
lectivity (exclusive syn-1,4-addition) to 1,2-regioselectivity (exclu-
sive anti-1,2-addition) was strictly and directly dependent on the O-glycosides (syn-1,4-addition products) with the same
ability of the nucleophile to coordinate with the nitrogen atom of the
aziridine.
configuration as that of the starting aziridines 1α and 1β,
respectively, in an uncatalyzed, directly substrate-
Key words: glycosylations, regioselectivity, stereoselectivity, nu-
cleophilic additions, heterocycles
dependent, stereospecific glycosylation process (route a,
Scheme 1).4,5
During this process, the stereo- and regioselective intro-
duction of an N-substituted amino group at C(4) also oc-
curred (Scheme 1). The syn-1,4-addition products have
also been termed coordination products, because they are
believed to be formed as a result of coordination between
the aziridine nitrogen and the O-nucleophile with a subse-
quent entropically favored attack at C(1) from the same
side (Scheme 1).6 In an unexpected contrast with the re-
sults obtained with alcohols, the reactions of aziridines 1α
and 1β with amines (N-nucleophiles) led exclusively to
mixtures of the corresponding anti-1,2- and anti-1,4-addi-
tion products (noncoordination products) (Scheme 2).7
Glycosides with functionalized amino groups in various
positions (amino sugars) form an important category of
modified carbohydrate units that are present in several oli-
gosaccharides and glycoconjugates.1 Amino sugars are
also important as essential components of bacterial capsu-
lar polysaccharides and as structural elements of amino-
glycoside antibiotics that display antiviral and antitumor
activities.2 Because of the biological importance of natu-
ral products containing amino sugars,3 the development of
efficient routes for synthesizing these carbohydrates is an
attractive goal.
These results prompted us to check the corresponding
chemical behavior of aziridines 1α and 1β with other O-
nucleophiles (acetate, methoxide, and hydroxide ions),
another N-nucleophile (azide ion), and the previously un-
examined C-nucleophiles (organometallic compounds)
and S-nucleophiles (thiols). Our aim was to find simple
procedures for glycosylating as many nucleophiles as pos-
In this context, our interest was directed toward glycal-
derived vinyl aziridines as useful tools for the regio- and
stereoselective introduction of a nitrogen functionality at
the C(4) carbon of glycal systems with simultaneous gly-
cosylation.The addition reactions of alcohols and partially
protected monosaccharides (O-nucleophiles) to vinyl D-
BnO
alkyl α-O-glycoside
OBn
O
OR
O
ROH
O
BnO
MsHN
BnO
(3 equiv)
route a
O
1
MeCN
Ms
N
a
N
Ms
Ms
N
Ms
H
H
O
O
1
1α'
1α
1α''
syn-1,4-addition product
(coordination product)
R
R
O
N
ROH
O
OR
BnO
OBn
O
(3 equiv)
BnO
MsHN
alkyl β-O-glycoside
a
route a
MeCN
N
Ms
1β
1β'
Scheme 1
SYNTHESIS 2012, 44, 2863–2871
Advanced online publication: 14.06.2012
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0
3
9
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7
8
8
1
1
4
3
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2
1
0
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DOI: 10.1055/s-0031-1291137; Art ID: SS-2012-C0200-ST
© Georg Thieme Verlag Stuttgart · New York

2864
V. Di Bussolo et al.
SPECIAL TOPIC
NR1R2
O
O
O
BnO
BnO
MsHN
NHR1R2
BnO
MsHN
+
N
NR1R2
Ms
1α
anti-1,2-addition
anti-1,4-addition
product
product
NR1R2
O
O
O
NHR1R2
BnO
BnO
MsHN
BnO
MsHN
+
N
NR1R2
1β
Ms
Scheme 2
sible with aziridines 1α and 1β, preferably with high lev- cess with O-nucleophiles occurred only with reagents
els of regio- and stereocontrol.
such as tetrabutylammonium methoxide or tetrabutylam-
monium trimethylsilanolate, in which the noncoordinat-
ing tetrabutylammonium cation is the counterion of the
corresponding O-nucleophile (MeO– or TMSO–, the syn-
thetic equivalents of OH–).9 In this way, the trans-me-
thoxy and trans-hydroxy mesylamino derivatives 7 and 8,
respectively, were obtained, as the exclusive reaction
products in a completely 1,2-regioselective and anti-stere-
oselective fashion (Scheme 4). A corresponding regio-
and stereoselective behavior has been previously ob-
served with aziridine 1β with the same reagents under the
same reaction conditions.4b
The aziridines 1α and 1β are synthesized from the corre-
sponding epoxides with the opposite configurations (2β
and 2α, respectively). Aziridines 1α and 1β are unstable
and must be prepared in situ by base-catalyzed cyclization
of the corresponding stable precursor, the trans-N,O-
dimesylates 3 and 4, respectively, in the presence of po-
tassium tert-butoxide or potassium carbonate. The result-
ing aziridines react immediately with the selected
nucleophile (Scheme 3).4a,4b,8
A theoretical conformational study carried out on appro-
priately simplified models has indicated that aziridine 1β
exists only as the corresponding conformer 1β′ with an
equatorial side chain,4b whereas aziridine 1α exists as an
equilibrium mixture (49:51, calculated in benzene as the
solvent) of the corresponding conformers 1α′ and 1α′′
(Scheme 1).7
anti-1,2-addition
syn-1,4-addition
product
product
O
O
O
OAc
BnO
Nu
BnO
BnO
MsHN
+
MsHN
OR
5, R = Ac (9%)
7, R = Me
O-Nucleophiles
N
Ms
coordination product
The marked tendency of aziridines 1α and 1β to give syn-
1,4-addition products (coordination products) with O-nu-
cleophiles was further demonstrated by their reactions
with sodium acetate in N,N-dimethylformamide, that is to
say, under conditions that should reasonably favor a typi-
cal SN2 process at the allylic C(3) aziridine carbon with
the formation of the corresponding anti-1,2-addition
product (noncoordination product). Actually, in the case
of aziridine 1α, the α-acetyl glycoside 6α was the main ad-
dition product (91%) with only a small amount of the ex-
pected anti-1,2 addition product, the trans-mesylamino
acetate 5 (9%, Scheme 4). A selective 1,2-addition pro-
1a
6a (91%)
8, R = H
Nu = AcONa, Bu4NOMe, Bu4NOTMS
Scheme 4
N-Nucleophiles
The reaction of aziridines 1α and 1β with trimethylsilyl
azide, carried out, necessarily, by protocol B,5 led to com-
plex reaction mixtures. Evidently, the electrophilicity of
the reagent is not compatible with the base necessary for
O
t-BuOK
O
O
O
BnO
MsO
BnO
BnO
Ph3P
(1 equiv)
TMGA
MeCN
BnO
MsCl
Py
1a
(polymer-
supported)
MeCN
HO
HO
HO
HO
O
O
NHMs
N3
O
NH2
O
2b
3
O
t-BuOK
(1 equiv)
O
BnO
MsO
BnO
BnO
Ph3P
TMGA
MeCN
BnO
MsCl
Py
1b
(polymer-
supported)
MeCN
NHMs
NH2
N3
2a
4
Scheme 3
Synthesis 2012, 44, 2863–2871
© Georg Thieme Verlag Stuttgart · New York

SPECIAL TOPIC
Nucleophilic Addition Reactions of Vinyl N-Mesylaziridines
2865
the formation of the aziridines from their respective pre- sponding α-glycosyl azide 11α, which is the actual prima-
cursors.8
ry reaction product.
Before the tetramethylguanidinium ion (TMG+: On the basis of these results, we believe that because of
+
Me4N2C=NH2 ) was identified as being capable of hydro- the presence of the proton,10 the TMG ion can coordinate
gen bonding,10 we believed that tetramethylguanidinium to the aziridine nitrogen of 1α through a hydrogen bond to
azide would serve as an organosoluble noncoordinating give the α-glycosyl azide 11α by an entropically favored
source of azide ion and therefore an appropriate reagent attack on C(1) from the same side (route a). Subsequent
for a regioselective, noncoordinated, anti-1,2-addition azide migration leads to the corresponding syn-1,2-addi-
process. Actually, the reaction of aziridine 1β with tetra- tion product, as found experimentally (Scheme 5).11
methylguanidinium azide was completely regioselective
with exclusive formation of the corresponding noncoordi-
As confirmation of this rationalization, when the azidoly-
sis reaction of 1α was repeated by using tetrabutylammo-
nation product, the trans-azido mesylamino derivative 9
nium azide, an azide ion species with a noncoordinating
(anti-1,2-addition product), as expected (Scheme 5).6
and nonprotic counterion (Bu4N+), the corresponding non-
coordination product, the trans-3-azido-4-N-(mesylami-
no) derivative 10 was be the sole reaction product
(Scheme 5).
anti-1,2-addition
product
Ms
N
O
OBn
O
C-Nucleophiles
+ NH2
–
BnO
MsHN
N3
TMGA
TMGA:
Alkyl lithium reagents have been shown to react efficient-
ly and stereoselectively with epoxides 2α and 2β to give
the corresponding C-glycosides with the same configura-
tion as that of the starting epoxide (coordination prod-
ucts), in a somewhat rare example of a 1,4-addition of
these reagents to a vinyl oxirane system.9,12,13
Me2N
NMe2
N3
9 (>99%)
1b'
–
N3
BnO
b
–
N3
TMGA
O
or
BnO
This is not the case with aziridines 1α and 1β, where com-
plex reaction mixtures were obtained with both alkyllithi-
um and Grignard reagents. Only trialkylaluminum
reagents were effective in transferring a simple alkyl
group. In this way, the reaction of 1α with trimethylalumi-
num was not regioselective, affording a 75:25 mixture of
the syn-1,4-α-C-glycoside 13α (the coordination product)
and the anti-1,2-addition product, the trans 3-methyl-4-N-
mesylamino derivative 14 (the noncoordination product).
The ratio of the syn-1,4-addition product to the anti-1,2-
addition product increased to almost 9:1 when triethylalu-
minum was used, giving the α-C-glycoside 15α and trans-
3-ethyl-4-N-mesylamino derivative 16 as the sole prod-
ucts (Scheme 6).
O
anti-1,2-addition
Bu4NN3
product
route b
MsHN
N3
N
Ms
1a''
10: TMGA (70%), Bu4NN3 (>99%)
OBn
O
O
N3
O
TMGA
BnO
BnO
MsHN
1
δ+
route a
N
MsHN
1a'
Ms
a
N3
H
H
11α (15%)
–
12 (15%)
N3
+
N
syn-1,4-addition
syn-1,2-addition
product
product
Me2N
NMe2
pseudoaxial
attack
α-C-Glycosides 13α and 15α are formed as a result of the
organometallic nucleophile (which is coordinated to the
aziridine nitrogen through the metal) attacking the C(1)
carbon from the same side as the coordination, with the
aziridine reacting through conformer 1α′. This attack cor-
responds to a more favorable pseudoaxial attack (Scheme
6, route a). Even though this process appears to be entro-
pically favored, the presence in the reaction mixture of a
proportion of noncoordinated reagent cannot be excluded.
The noncoordinated reagent can attack the aziridine at the
C(3) allylic carbon in the usual trans diaxial fashion, pos-
sible with the aziridine reacting through conformer 1α′′,
to give the noncoordination products, the trans-deriva-
tives 14 (from triethylaluminum) and 16 (from triethyalu-
minum). In this context, the presence of a certain steric
and/or torsional strain between the attacking nucleophile
(AlR3) and the side chain (-CH2OBn, route b) might ex-
plain the production of a smaller amount of anti-1,2-addi-
tion product from triethylaluminum than from
trimethylaluminum (Scheme 6).
Scheme 5
However, aziridine 1α showed a decidedly different be-
havior in the same reaction. In this case, the expected anti-
1,2-addition product, the trans-3-azido-N-(mesylamino)
derivative 10 (route b, 70%) was not the sole reaction
product, but was obtained as a mixture containing a sub-
stantial amount (15%) of the corresponding syn-1,2-
addition product, the cis-3-azido-4-N-(mesylamino) de-
rivative 12, and the coordination product (syn-1,4-addi-
tion product), the α-glycosyl azide 11α (15%, Scheme 5,
route a). On the basis of experimental evidence that clear-
ly indicated that an equilibrium exists between the syn-
1,2-addition product 12 and the syn-1,4-addition product
11α, together with some previous results,11 we concluded
that syn-1,2-addition product 12 is not the primary reac-
tion product, but is the result of an isomerization by
suprafacial [3,3]-sigmatropic rearrangement of the corre-
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 2863–2871

2866
V. Di Bussolo et al.
SPECIAL TOPIC
1a
R3Al
R
R
syn-1,4-addition
anti-1,2-addition
BnO
Al
R
product
OBn
product
b
O
O
R
O
1
O
BnO
MsHN
BnO
route a
δ+
route b
N
3
a
Ms
1a'
MsHN
R
N
δ–
Ms
1α''
R
R
coordination
product
Al
pseudoaxial
attack
noncoordination
product
R
13a (75%)
15a (89%)
–
Me3Al (R = Me)
Et3Al (R = Et)
Me3Al/12-crown-4
14 (25%)
16 (11%)
14 (>99%)
Scheme 6
We confirmed this rationalization by repeating the reac- The reaction of aziridine 1α with benzenethiol or ethane-
tion of trimethylaluminum with aziridine 1α in in the pres- thiol in the presence of potassium tert-butoxide, to effect
ence of 12-crown-4. The presence of the metal- both the cyclization of the precursor 3 and the deproton-
sequestering crown ether prevented coordination of the ation of the thiol to the corresponding potassium thiolate,
aziridine nitrogen with the nucleophile and, as a result, the gave a 35:65 mixture of the corresponding coordination
corresponding noncoordination product 14 became the products, the α-thioglycoside 19α (R = Et) and 21α (R =
sole reaction product (Scheme 6).
Ph) (Scheme 8, route a; 35%), respectively, and the non-
coordination product, the trans-4-N-(mesylamino)-3-eth-
ylsulfanyl derivative 20 (R = Et) and trans-4-N-
(mesylamino)-3-phenylsulfanyl derivative 22 (R = Ph)
(route b, 65%), respectively.
Similar results were obtained in the reaction of the diaste-
reoisomeric aziridine 1β with trimethylaluminum (syn-
1,4-addition product 17β/anti-1,2-addition product 18 ra-
tio = 65:35). In this case, the configuration (β) of the start-
ing aziridine and its coordination with the reagent The coordination of the aziridine with the thiolate nucleo-
determines the configuration (β) of the only 1,4-addition phile through the metal and attack on the C(1) carbon
product that was obtained, the β-C-glycoside 17β, which through conformer 1α′ is responsible, as usual, for the for-
is the coordination product (Scheme 7).
mation of the coordination products.
Actually, the noncoordination products 20 (R = Et) and 22
(R = Ph) were the sole products when the reaction was
carried out in the presence of a polymer-bound basic cat-
alyst (polystyrene-bound 1,5,7-triazabicyclo[4.4.0]dec-5-
ene; TBD resin) to effect both the cyclization of the pre-
cursor 3 to aziridine 1α and the deprotonation of the thiol
to give the corresponding thiolate in the absence of any
metal counterion.
anti-1,2-addition
syn-1,4-addition
product
product
O
O
Me
O
BnO
BnO
MsHN
BnO
Me3Al
+
MsHN
N
Ms
1b
Me
18 (35%)
17b (65%)
coordination
product
noncoordination
product
The same results were also obtained with aziridine 1β in
the reaction with benzenethiol (Scheme 9). In this case, a
progressive increase in the yield of the coordination prod-
uct, the β-phenyl thioglycoside 23β was observed when
base necessary for the formation of the aziridine in situ
from trans N,O-dimesylate 4 was changed from potassi-
Scheme 7
S-Nucleophiles
RSH
base
Y = K or basic resin
3
[1a]
δ+
anti-1,2-addition
syn-1,4-addition
Y
product
product
δ–
BnO
b
RSY
S
OBn
R
O
O
SR
O
BnO
MsHN
BnO
MsHN
route b
route a
Ms
O
1
δ+
3
N
δ+
δ–
a
SR
N
1a'
1a''
Ms
base
t-BuOK
t-BuOK
K
S
coordination
product
noncoordination
product
R
19a, R = Et (35%)
21a, R = Ph (35%)
<1%
20, R = Et (65%)
22, R = Ph (65%)
>99%
basic resin (PS-TBD)
Scheme 8
Synthesis 2012, 44, 2863–2871
© Georg Thieme Verlag Stuttgart · New York

SPECIAL TOPIC
Nucleophilic Addition Reactions of Vinyl N-Mesylaziridines
2867
The configuration of 1,4-addition products was determined by
means of appropriate NOE experiments.
um tert-butoxide to lithium tert-butoxide and then to lith-
ium hydride, indicating the importance of the metal
counterion to the occurrence of a coordination process.
The use of the PS-TBD resin simplified the composition
of reaction mixture and gave the noncoordination product,
the trans N-(mesylamino)phenylthio derivative 24, exclu-
sively (Scheme 9).
1,5-Anhydro-6-O-benzyl-2,4-dideoxy-4-(mesylamino)-D-arabi-
no-hex-1-enitol (8)
A soln of dimesylate 3 (0.035 g, 0.090 mmol) in anhyd THF (1.0
mL) containing Bu4NOTMS [4 equiv, prepared from TBAB (0.116
g, 0.36 mmol) and TMSOK (0.046 g, 0.36 mmol)] was treated with
t-BuOK (0.010 g, 0.090 mmol, 1 equiv), and the mixture was stirred
for 30 min at r.t. The mixture was diluted with Et2O (15 mL),
washed with sat. brine (2 × 2 mL), and concentrated to give a crude
product [yield: 0.027 g (96%)] that was purified by flash chroma-
tography [hexanes–EtOAc (3:7)] to give a pale yellow liquid; yield:
0.023 g (81%); Rf = 0.26 (hexanes–EtOAc, 3:7).
syn-1,4-addition
anti-1,2-addition
product
product
O
O
SPh
PhSH
base
BnO
BnO
1H NMR (250 MHz, CDCl3): δ = 7.22–7.41 (m, 5 H), 6.42 (dd,
J = 6.1, 1.1 Hz, 1 H), 4.79–4.96 (m, 1 H), 4.84 (dd, J = 6.1, 2.9 Hz,
1 H), 4.59 (s, 2 H), 4.52–4.62 (m, 1 H), 4.15–4.26 (m, 1 H), 3.80–
3.85 (m, 3 H), 3.55–3.67 (m, 1 H), 3.04 (s, 3 H).
4
[1b]
+
MsHN
MsHN
SPh
24
23b
13C NMR (62.5 MHz, CDCl3): δ = 144.3, 138.0, 128.6, 127.9,
128.1, 102.9, 75.7, 73.7, 69.5, 67.7, 56.2, 41.3.
coordination
product
noncoordination
product
base: t-BuOK
t-BuOLi
5
12
34
95
88
66
Anal. Calcd for C14H19NO5S: C, 53.66; H, 6.12; N, 4.47. Found: C,
53.95; H, 5.91; N, 4.18.
LiH
PS-TBD
<1%
>99%
3-O-Acetyl-1,5-anhydro-6-O-benzyl-2,4-dideoxy-4-(mesylami-
no)-D-arabino-hex-1-enitol (5)
Scheme 9
A solution of allyl alcohol 8 (0.020 g, 0.064 mmol) in anhydrous
pyridine (0.2 mL) was treated at 0 °C with Ac2O (0.15 mL) and the
reaction mixture was stirred at r.t. for 12 h. Dilution with toluene
(3 × 10 mL) and co-evaporation of the organic solvent and reagents
at reduced pressure (rotating evaporator) afforded a crude pale yel-
low liquid consisting of acetate 5, practically pure; yield: 0.019 g
(83%); Rf = 0.32 (hexanes–EtOAc, 1:1).
1H NMR (250 MHz, CDCl3): δ = 7.24–7.37 (m, 5 H), 6.50 (dd,
J = 6.3, 0.9 Hz, 1 H), 5.14–5.21 (m, 1 H), 4.82 (dd, J = 6.3, 3.9 Hz,
1 H), 4.62–4.67 (m, 1 H), 4.58 (s, 2 H), 4.27 (q, J = 5.5 Hz, 1 H),
3.85–3.98 (m, 1 H), 3.76–3.80 (m, 2 H), 3.04 (s, 3 H), 2.05 (s, 3 H).
The reactions of aziridines 1α and 1β with O-nucleophiles
(sodium acetate, tetrabutylammonium methoxide, or tet-
rabutylammonium trimethylsilanolate), C-nucleophiles
(trimethylaluminum or triethylaluminum), N-nucleo-
philes (tetramethylguanidinium azide or tetrabutylammo-
nium azide), or S-nucleophiles (ethanethiol or
benzenethiol) confirmed the marked tendency of these ac-
tivated vinyl aziridines to show a high-to-complete degree
of 1,4-regioselectivity in association with complete syn-
stereoselectivity (coordination products) in nucleophilic
addition reactions when the nucleophile can coordinate
the aziridine nitrogen through a metal or by means of a hy-
drogen bond. On the other hand, the use of reaction con-
ditions where no coordinating agent (metal or protic
species) is present leads to complete 1,2-regioselectivity
and anti-stereoselectivity (noncoordination products) in
an elegant regioalternating process.14
13C NMR (62.5 MHz, CDCl3): δ = 170.2, 146.5, 137.2, 130.8,
128.6, 128.0, 98.4, 78.2, 73.8, 68.2, 67.8, 51.6, 42.1, 21.2.
Anal. Calcd for C16H21NO6S: C, 54.07; H, 5.96; N, 3.94. Found: C,
54.26; H, 5.74; N, 3.76.
1-O-Acetyl-6-O-benzyl-2,3,4-trideoxy-4-(mesylamino)-α-D-
erythro-hex-2-enopyranose (6α)
A soln of dimesylate 3 (0.021 g, 0.050 mmol) in anhyd DMF (0.5
mL) was treated with anhyd NaOAc (0.009 g, 0.10 mmol, 2 equiv),
and the mixture was stirred for 16 h at r.t. The resulting mixture was
diluted with sat. aq NaCl (2 mL) and extracted with Et2O (3 × 10
mL). The extracts were concentrated to give a crude product [yield:
0.016 g (89%)] consisting of a 91:9 mixture of α-acetyl glycoside
6α and the trans-acetoxy derivative 5 (1H NMR) that was purified
by preparative TLC (hexanes–EtOAc, 4:6). Extraction of the most
intense band gave 6α as a colorless liquid; yield: 0.012 g (67%);
Rf = 0.24 (hexanes–EtOAc, 3:7).
All reactions were performed under a positive pressure of argon in
flame-dried, modified, Schlenk (Kjeldahl-shaped) flasks fitted with
glass stoppers or rubber septa. Flash column chromatography was
performed on 230–400 mesh silica gel (Macherey-Nagel). Analyti-
cal TLC was performed on Alugram SIL G/UV254 silica gel sheets
(Macherey-Nagel) with detection by 0.5% phosphomolybdic acid
soln in 95% EtOH. IR spectra were recorded on a Mattson 3000
FTIR spectrophotometer. 1H and 13C NMR spectra were recorded at
250 and 62.5 MHz, respectively, on a Bruker Avance II 250 spec-
trometer. Benzene, toluene, Et2O, and THF were distilled from so-
dium/benzophenone. N-Mesylaziridines 1α and 1β were prepared in
situ by cyclization under basic conditions (t-BuOK) of the corre-
sponding stable precursors, the trans-N,O-dimesylates 34a and 4,4b
respectively, as previously described. Tetramethylguanidinium
1H NMR (250 MHz, CDCl3): δ = 7.25–7.38 (m, 5 H), 6.30 (unre-
solved t, J = 1,4 Hz, 1 H), 6.12 (d, J = 10.0 Hz, 1 H), 5.83 (dt,
J = 10.0, 2.6 Hz, 1 H), 4.64 (d, J = 11.8 Hz, 1 H), 4.55 (d, J = 11.8
Hz, 1 H), 4.51–4.69 (m, 1 H), 4.16–4.31 (m, 1 H), 3.71–3.87 (m, 3
H), 2.89 (s, 3 H), 2.08 (s, 3 H).
13C NMR (62.5 MHz, CDCl3): δ = 170.2, 137.9, 133.4, 128.9,
128.6, 128.5, 126.2, 88.7, 74.6, 71.9, 69.3, 48.8, 41.7, 21.9.
Anal. Calcd for C16H21NO6S: C, 54.07; H, 5.96; N, 3.94. Found: C,
53.88; H, 5.59; N, 3.60.
16
azide (TMGA),15 Bu4NOTMS,9a Bu4NOMe,9b and Bu4NN3 were
prepared as previously described. Bu4NOMe and Bu4NN3 are also
commercially available (Aldrich). PS-TBD resin was purchased
from Aldrich. The structures of the 1,2- and 1,4-addition products
were determined by simple examination of their 1H NMR spectra.
1,5-Anhydro-6-O-benzyl-2,4-dideoxy-3-O-methyl-4-(mesylami-
no)-D-arabino-hex-1-enitol (7)
A soln of dimesylate 3 (0.032 g, 0.082 mmol) in anhyd THF (1 mL)
containing Bu4NOMe (0.090 g, 0.33 mmol, 4 equiv) was treated
© Georg Thieme Verlag Stuttgart · New York
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2868
V. Di Bussolo et al.
SPECIAL TOPIC
with t-BuOK (0.009 g, 0.083 mmol) and the mixture was stirred for
2 h at r.t. The resulting mixture was diluted with sat. aq NaCl (2 mL)
and extracted with Et2O (3 × 10 mL). The extracts were concentrat-
ed to give a crude product [yield: 0.025 g (93%)] that was purified
by flash chromatography [hexanes–EtOAc (1:1)] to give a colorless
liquid: yield: 0.018 g (67%); Rf = 0.42 (hexanes–EtOAc, 1:1).
1H NMR (250 MHz, CDCl3): δ = 7.24–7.38 (m, 5 H), 6.44 (d,
J = 6.2 Hz, 1 H), 4.93 (dd, J = 6.2, 3.8 Hz, 1 H), 4.50–4.62 (m, 1 H),
4.57 (s, 2 H), 4.10–4.22 (m, 1 H), 3.71–3.87 (m, 4 H), 3.38 (s, 3 H),
3.06 (s, 3 H).
0.043 g (98%)] was purified by flash chromatography [hexanes–
EtOAc (1:1) to give a pale yellow liquid: yield: 0.034 g (77%); Rf =
0.36 (hexanes–EtOAc, 1:1).
IR (neat): 2106 cm–1.
1H NMR (250 MHz, CDCl3): δ = 7.24–7.42 (m, 5 H), 6.67 (d,
J = 6.0 Hz, 1 H), 4.95 (td, J = 6.0, 1.5 Hz, 1 H), 4.75 (d, J = 9.3 Hz,
1 H), 4.57 (s, 2 H), 4.07–4.19 (m, 1 H), 3.95 (dd, J = 5.3, 2.2 Hz, 1
H), 3.61–3.79 (m, 3 H), 2.90 (s, 3 H).
13C NMR (62.5 MHz, CDCl3): δ = 148.4, 137.2, 128.8, 128.3,
128.2, 96.0, 74.0, 71.4, 68.2, 55.5, 51.1, 41.4.
13C NMR (62.5 MHz, CDCl3): δ = 145.1, 138.1, 128.6, 128.1,
128.0, 99.2, 75.0, 73.8, 69.0, 55.7, 51.8, 42.0.
Anal. Calcd for C14H18N4O4S: C, 49.69; H, 5.36; N, 16.56. Found:
C, 49.35; H, 5.11; N, 16.29.
Anal. Calcd for C15H21NO5S: C, 55.03; H, 6.46; N, 4.28. Found: C,
54.71; H, 6.15; N, 4.17.
Reaction of Aziridine 1α with Tetrabutylammonium Azide
A soln of dimesylate 3 (0.024 g, 0.061 mmol) in anhyd MeCN (1
mL) was treated with t-BuOK (0.007 g, 0.061 mmol, 1 equiv) and
Bu4NN3 (0.052 g, 0.18 mmol, 3 equiv), and the mixture was stirred
for 2 h at r.t. The usual workup gave practically pure product 10 (1H
NMR); yield: 0.018 g (87%).
Reaction of Aziridine 1a with TMGA
A soln of dimesylate 3 (0.051 g, 0.13 mmol) in anhyd benzene (2
mL) was treated with t-BuOK (0.015 g, 0.13 mmol, 1 equiv) in the
presence of TMGA (0.082 g, 0.52 mmol, 4 equiv), and the mixture
was stirred for 4 h at r.t. The resulting mixture was partitioned be-
tween Et2O (15 mL) and brine (3 mL), and the aqueous layer was
further extracted with Et2O (3 × 8 mL). The combined organic ex-
tracts were concentrated to give a crude product [yield: 0.042 g
(95%)] consisting of a 70:15:15 mixture of trans-azido derivative
10, the cis-azido derivative 12, and the α-glycosyl azide 11α (1H
NMR) that was separated by flash chromatography [CH2Cl2–
EtOAc (9:1)] to give 10 and 12.
Reaction of Aziridine 1a with Me3Al
A soln of dimesylate 3 (0.056 g, 0.143 mmol) in anhyd toluene (1
mL) was treated with t-BuOK (0.016 g, 0.014 mmol, 1 equiv) and a
2.0 M soln of Me3Al in toluene (0.215 mL, 0.43 mmol, 3 equiv), and
the mixture was stirred for 18 h at r.t. The soln was then partitioned
between Et2O (20 mL) and brine (8 mL), and the aqueous layer was
extracted with Et2O (2 × 10 mL). The combined organic extracts
were concentrated to give a crude product [yield: 0.042 g (94%)]
consisting of a 75:25 mixture of α-C-glycoside 13α and trans-meth-
yl derivative 14 (1H NMR). This was separated by preparative TLC
[hexanes–EtOAc (6:4)]. Extraction of the two most intense bands
gave pure 13α and 14 (faster band).
1,5-Anhydro-3-azido-6-O-benzyl-2,3,4-trideoxy-4-(mesylami-
no)-D-arabino-hex-1-enitol (10)
Pale yellow liquid: yield: 0.020 g (45%); Rf = 0.28 (CH2Cl2–EtOAc,
9:1).
IR (neat): 2106 cm–1.
(1R)-1,5-Anhydro-6-O-benzyl-2,3,4-trideoxy-1-methyl-4-(me-
sylamino)-D-erythro-hex-2-enitol (13α)
Colorless liquid: yield: 0.020 g (44%); Rf = 0.23 (hexanes–EtOAc,
1:1).
1H NMR (250 MHz, CDCl3): δ = 7.24–7.39 (m, 5 H), 5.78–5.82 (m,
2 H), 4.58 (s, 2 H), 4.45–4.60 (m, 1 H), 4.24–4.40 (m, 1 H), 3.77–
3.97 (m, 2 H), 3.58–3.74 (m, 2 H), 2.92 (s, 3 H), 1.25 (d, J = 6.8 Hz,
3 H).
1H NMR (250 MHz, CDCl3): δ = 7.24–7.41 (m, 5 H), 6.52 (dd,
J = 6.1, 1.5 Hz, 1 H), 5.10 (d, J = 8.6 Hz, 1 H), 4.81 (dd, J = 6.1, 2.6
Hz, 1 H), 4.62 (d, J = 11.7 Hz, 1 H), 4.55 (d, J = 11.7 Hz, 1 H),
3.90–4.12 (m, 2 H), 3.74–3.88 (m, 2 H), 3.65 (q, J = 8.8 Hz, 1 H),
3.08 (s, 3 H).
13C NMR (62.5 MHz, CDCl3): δ = 145.5, 137.8, 128.6, 128.2,
128.1, 97.8, 77.0, 73.9, 69.1, 58.7, 53.3, 42.6.
13C NMR (62.5 MHz, CDCl3): δ = 137.8, 134.0, 128.6, 128.1,
128.0, 124.7, 73.8, 73.2, 69.1, 67.4, 48.0, 41.9, 19.7.
Anal. Calcd for C14H18N4O4S: C, 49.69; H, 5.36; N, 16.56. Found:
C, 49.50; H, 5.09; N, 16.74.
Anal. Calcd for C15H21NO4S: C, 57.86; H, 6.80; N, 4.50. Found: C,
57.55; H, 6.53; N, 4.32.
1,5-Anhydro-3-azido-6-O-benzyl-2,3,4-trideoxy-4-(mesylami-
no)-D-ribo-hex-1-enitol (12)
Pale yellow liquid; yield: 0.004 g (9%); Rf = 0.62 (CH2Cl2–EtOAc,
9:1).
1,5-Anhydro-6-O-benzyl-2,3,4-trideoxy-3-methyl-4-(mesylami-
no)-D-arabino-hex-1-enitol (14)
Colorless liquid: yield: 0.006 g (13%); Rf = 0.38 (hexanes–EtOAc,
1:1).
1H NMR (250 MHz, CDCl3): δ = 7.24–7.39 (m, 5 H), 6.25 (dd,
J = 6.1, 2.2 Hz, 1 H), 4.61 (d, J = 11.2 Hz, 1 H), 4.52 (d, J = 11.2
Hz, 1 H), 4.44–4.53 (m, 2 H), 4.20 (q, J = 5.8 Hz, 1 H), 3.61–3.81
(m, 2 H), 3.55 (dd, J = 10.0, 6.1 Hz, 1 H), 2.97 (s, 3 H), 2.35–2.54
(m, 1 H), 1.06 (d, J = 7.1 Hz, 3 H).
IR (neat): 2105 cm–1.
1H NMR (250 MHz, CDCl3): δ = 7.30–7.38 (m, 5 H), 6.62 (d,
J = 5.9 Hz, 1 H), 4.96 (t, J = 5.9 Hz, 1 H), 4.83 (d, J = 8.7 Hz, 1 H),
4.63 (d, J = 11.9 Hz, 1 H), 4.56 (d, J = 11.9 Hz, 1 H), 4.18–4.25 (m,
1 H), 3.78–3.96 (m, 4 H), 2.94 (s, 3 H).
13C NMR (62.5 MHz, CDCl3): δ = 147.9, 137.4, 128.7, 128.1,
127.9, 95.7, 74.1, 73.2, 68.7, 55.2, 50.9.
13C NMR (62.5 MHz, CDCl3): δ = 141.6, 137.7, 128.7, 128.1,
104.3, 75.6, 73.8, 69.2, 51.8, 42.2, 26.9, 16.7.
The 1H NMR spectrum of cis-azido alcohol 12 showed the presence
(10%) of the α-glycosyl azide 11α. Neither 12 nor 11α could be ob-
tained in a pure form.
11α: 1H NMR (250 MHz, CDCl3): δ = 6.05 (dt, J = 10.1, 1.2 Hz, 1
H), 5.77 (dt, J = 10.1, 2.2 Hz, 1 H), 5.57–5.60 (m, 1 H, H-1).
Anal. Calcd for C15H21NO4S: C, 57.86; H, 6.80; N, 4.50. Found: C,
57.64; H, 6.65; N, 4.26.
Reaction of Aziridine 1a with Et3Al
By following the typical procedure, a soln of dimesylate 3 (0.062 g,
0.16 mmol) in anhyd toluene (2 mL) was treated with t-BuOK
(0.018 g, 0.16 mmol, 1 equiv) and a 1.9 M soln of Et3Al in toluene
(0.25 mL, 0.48 mmol, 3 equiv). The crude product [yield: 0.048 g
(92%)] consisted of an 89:11 mixture of α-C-glycoside 15α and the
trans-ethyl derivative 16 (1H NMR), which was subjected to prepar-
1,5-Anhydro-3-azido-6-O-benzyl-2,3,4-trideoxy-4-(mesylami-
no)-D-xylo-hex-1-enitol (9)
A soln of dimesylate 4 (0.051 g, 0.13 mmol) in anhyd MeCN (1.5
mL) was treated with t-BuOK (0.015 g, 0.13 mmol, 1 equiv) in the
presence of TMGA (0.082 g, 0.52 mmol, 4 equiv) and the mixture
was stirred for 30 min at r.t. The crude reaction product [yield:
Synthesis 2012, 44, 2863–2871
© Georg Thieme Verlag Stuttgart · New York

SPECIAL TOPIC
Nucleophilic Addition Reactions of Vinyl N-Mesylaziridines
2869
ative TLC [hexanes–EtOAc (1:1)]. Extraction of the two most in-
tense bands gave pure 15α and 16 (faster band).
13C NMR (62.5 MHz, CDCl3): δ = 143.0, 135.0, 128.7, 128.1,
128.0, 99.7, 79.4, 75.4, 72.2, 52.4, 42.1, 29.9, 21.1.
Anal. Calcd for C15H21NO4S: C, 57.86; H, 6.80; N, 4.50. Found: C,
57.55; H, 6.51; N, 4.25.
(1R)-1,5-Anhydro-6-O-benzyl-2,3,4-trideoxy-1-ethyl-4-(mesyl-
amino)-D-erythro-hex-2-enitol (15α)
Colorless liquid; yield: 0.029 g (55%); Rf = 0.30 (hexanes–EtOAc,
1:1).
Reaction of Aziridine 1α with Trimethylaluminum in the Pres-
ence of 12-Crown-4
1H NMR (250 MHz, CDCl3): δ = 7.27–7.38 (m, 5 H), 5.78–5.89 (m,
2 H), 4.61 (d, J = 12.0 Hz, 1 H), 4.55 (d, J = 12.0 Hz, 1 H), 4.48 (d,
J = 9.3 Hz, 1 H, NH), 4.01–4.09 (m, 1 H), 3.88–3.94 (m, 1 H), 3.83
(q, J = 5.1 Hz, 1 H), 3.71 (dd, J = 10.1, 5.3 Hz, 1 H), 3.63 (dd,
J = 10.1, 5.1 Hz, 1 H), 2.93 (s, 3 H), 1.58 (q, J = 7.4 Hz, 2 H), 0.97
(t, J = 7.4 Hz, 3 H).
A 2.0 M soln of Me3Al in toluene (0.12 mL, 0.24 mmol, 3 equiv)
was treated with 12-crown-4 (0.044 g, 0.040 mL, 0.25 mmol) in an-
hyd toluene (1 mL), and the mixture was stirred for 18 h at r.t.
Dimesylate 3 (0.031 g, 0.080 mmol) and t-BuOK (0.009 g, 0.080
mmol, 1 equiv) were added and the mixture was stirred for a further
18 h at r.t. The mixture was then diluted with Et2O and the organic
phase was washed with sat. brine, and concentrated to give a mix-
ture of the trans-methyl derivative 14 and excess crown ether (1H
NMR).
13C NMR (62.5 MHz, CDCl3): δ = 138.3, 133.2, 128.8, 128.2,
125.1, 73.9, 73.5, 72.5, 69.4, 48.5, 42.1, 27.1, 10.1.
Anal. Calcd for C16H23NO4S: C, 59.05; H, 7.12; N, 4.30. Found: C,
58.65; H, 6.89; N, 4.11.
Reaction of Aziridine 1a with EtSH
By following the typical procedure; a soln of dimesylate 3 (0.031 g,
0.080 mmol) in anhyd benzene (2.2 mL) was treated with t-BuOK
(0.009 g, 0.080 mmol) and EtSH (0.015 g, 0.018 mL, 0.24 mmol, 3
equiv) to give a crude product [yield: 0.027 g (94%)] consisting of
a 35:65 mixture of thioglycoside 19α and trans-ethysulfanyl deriv-
ative 20 (1H NMR), which was subjected to preparative TLC [hex-
anes–CH2Cl2–i-Pr2O (3:5:2)]. Extraction of the two most intense
bands gave pure 19α and 20 (faster band).
1,5-Anhydro-6-O-benzyl-2,3,4-trideoxy-3-ethyl-4-(mesylami-
no)-D-arabino-hex-1-enitol (16)
Colorless liquid; yield: 0.003 g (6%); Rf = 0.40 (hexanes–EtOAc,
1:1).
1H NMR (250 MHz, CDCl3): δ = 7.24–7.38 (m, 5 H), 6.26 (dd,
J = 6.3, 2.5 Hz, 1 H), 4.62 (d, J = 12.0 Hz, 1 H), 4.50 (d, J = 12.0
Hz, 1 H), 4.45–4.58 (m, 3 H), 4.23–4.37 (m, 1 H), 3.74–3.89 (m, 1
H), 3.64 (dd, J = 10.0, 6.4 Hz, 1 H), 3.48 (dd, J = 10.0, 6.1 Hz, 1 H),
2.99 (s, 3 H), 1.30 (q, J = 7.4 Hz, 2 H), 0.96 (t, J = 7.4 Hz, 3 H).
Ethyl 6-O-Benzyl-2,3,4-trideoxy-4-(mesylamino)-1-thio-α-D-
erythro-hex-2-enopyranoside (19α)
Pale yellow liquid; yield: 0.006 g (21%); Rf = 0.25 (hexanes–
EtOAc, 1:1).
13C NMR (62.5 MHz, CDCl3): δ = 141.6, 137.7, 128.7, 128.1,
102.2, 73.8, 68.9, 50.3, 42.5, 33.2, 27.5, 23.9, 11.3.
1H NMR (250 MHz, CDCl3): δ = 7.22–7.41 (m, 5 H), 5.94 (dd,
J = 10.7, 2.3 Hz, 1 H), 5.85 (d, J = 10.7 Hz, 1 H), 5.58 (br s, 1 H),
4.67 (d, J = 11.8 Hz, 1 H), 4.56 (d, J = 11.8 Hz, 1 H), 4.24–4.31 (m,
2 H), 3.94–4.05 (m, 1 H), 3.83 (dd, J = 10.8, 3.5 Hz, 1 H), 3.71 (dd,
J = 10.8, 2.7 Hz, 1 H), 2.88 (s, 3 H), 2.55–2.81 (m, 2 H), 1.29 (t,
J = 7.5 Hz, 3 H).
Anal. Calcd for C16H23NO4S: C, 59.05; H, 7.12; N, 4.30. Found: C,
58.89; H, 6.95; N, 4.15.
Reaction of Aziridine 1b with Me3Al
By following the typical procedure, a soln of dimesylate 4 (0.031 g,
0.080 mmol) in anhyd toluene (1 mL) was treated with t-BuOK
(0.009 g, 0.080 mmol, 1 equiv) and a 2.0 M soln of Me3Al in toluene
(0.12 mL, 0.24 mmol, 3 equiv) to give a crude product [yield: 0.024
g (96%)] consisting of a 65:35 mixture of β-C-glycoside 17β and
trans-methyl derivative 18 (1H NMR), which was subjected to pre-
parative TLC [hexanes–EtOAc, (6:4)]. Extraction of the two most
intense bands gave pure 17β and 18 (faster band).
13C NMR (62.5 MHz, CDCl3): δ = 137.9, 129.3, 129.2, 128.7,
128.2, 128.1, 80.0, 74.0, 69.5, 69.3, 48.6, 41.7, 26.3, 15.5.
Anal. Calcd for C16H23NO4S2: C, 53.76; H, 6.49; N, 3.92. Found: C,
53.39; H, 6.24; N, 3.77.
1,5-Anhydro-6-O-benzyl-2,3,4-trideoxy-3-(ethylsulfanyl)-4-
(mesylamino)-arabino-hex-1-enitol (20)
Pale yellow liquid; yield: 0.015 g (52%); Rf = 0.38 (hexanes–
EtOAc, 1:1).
1H NMR (250 MHz, CDCl3): δ = 7.24–7.40 (m, 5 H), 6.44 (dd,
J = 6.0, 1.9 Hz, 1 H), 4.80 (dd, J = 6.0, 3.2 Hz, 1 H), 4.49–4.61 (m,
1 H), 4.62 (d, J = 11.7 Hz, 1 H), 4.55 (d, J = 11.7 Hz, 1 H), 3.70–
4.10 (m, 4 H), 3.29–3.37 (m, 1 H), 3.13 (s, 3 H), 2.61 (q, J = 7.4 Hz,
2 H), 1.26 (t, J = 7.4 Hz, 3 H).
(1S)-1,5-Anhydro-6-O-benzyl-2,3,4-trideoxy-1-methyl-4-(me-
sylamino)-D-threo-hex-2-enitol (17β)
Colorless liquid: yield: 0.012 g (48%); Rf = 0.24 (hexanes–EtOAc,
6:4).
1H NMR (250 MHz, CDCl3): δ = 7.27–7.41 (m, 5 H), 6.02 (ddd,
J = 10.1, 5.5, 1.9 Hz, 1 H), 5.85 (dd, J = 10.1, 2.9 Hz, 1 H), 4.59 (d,
J = 11.8 Hz, 1 H), 4.53 (d, J = 11.8 Hz, 1 H), 4.56 (d, J = 10.0 Hz,
1 H, NH), 4.31–4.47 (m, 1 H), 4.04 (td, J = 6.1, 2.6 Hz, 1 H), 3.79
(ddd, J = 10.0, 5.5, 2.6 Hz, 1 H), 3.69 (dd, J = 9.8, 6.5 Hz, 1 H), 3.61
(dd, J = 9.8, 6.1 Hz, 1 H), 2.94 (s, 3 H), 1.26 (d, J = 6.8 Hz, 3 H).
13C NMR (62.5 MHz, CDCl3): δ = 144.4, 137.9, 128.6, 128.2,
128.0, 101.9, 78.0, 73.7, 69.6, 53.5, 43.5, 43.0, 23.8, 14.8.
13C NMR (62.5 MHz, CDCl3): δ = 137.9, 134.2, 128.6, 128.0,
127.9, 125.1, 73.8, 69.9, 69.8, 68.9, 47.3, 42.0, 18.2.
Anal. Calcd for C16H23NO4S2: C, 53.76; H, 6.49; N, 3.92. Found: C,
53.41; H, 6.18; N, 3.71.
Anal. Calcd for C15H21NO4S: C, 57.86; H, 6.80; N, 4.50. Found: C,
57.48; H, 6.57; N, 4.32.
Reaction of Aziridine 1a with PhSH
By following the typical procedure, a soln of dimesylate 3 (0.040 g,
0.10 mmol) in anhyd benzene (3 mL) was treated with t-BuOK
(0.011 g, 0.10 mmol) and PhSH (0.033 g, 0.030 mL, 0.30 mmol, 3
equiv) to give, after 48 h stirring at r.t., a crude product [yield: 0.038
g (94%)] consisting of a 35:65 mixture of thioglycoside 21α and
trans-phenylsulfanyl derivative 22 (1H NMR), which was subjected
to preparative TLC [hexanes–CH2Cl2–i-Pr2O (4:3:3)]. Extraction of
the two most intense bands gave pure 21α (faster band) and 22.
1,5-Anhydro-6-O-benzyl-2,3,4-trideoxy-3-methyl-4-(mesylami-
no)-D-xylo-hex-1-enitol (18)
Pale yellow liquid: yield: 0.005 g (20%); Rf = 0.30 (hexanes–
EtOAc, 1:1).
1H NMR (250 MHz, CDCl3): δ = 7.28–7.40 (m, 5 H), 6.37 (t, J = 2.5
Hz, 1 H), 4.81 (t, J = 2.5 Hz, 1 H), 4.59 (d, J = 12.0 Hz, 1 H), 4.53
(d, J = 12.0 Hz, 1 H), 4.38 (d, J = 10.7 Hz, 1 H, NH), 4.20–4.30 (m,
1 H), 3.77–3.90 (m, 1 H), 3.56–3.70 (m, 2 H), 3.34–3.46 (m, 1 H),
2.92 (s, 3 H), 1.24 (d, J = 6.7 Hz, 3 H).
© Georg Thieme Verlag Stuttgart · New York
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V. Di Bussolo et al.
SPECIAL TOPIC
Phenyl 6-O-Benzyl-2,3,4-trideoxy-4-(mesylamino)-1-thio-α-D-
erythro-hex-2-enopyranoside (21α)
Pale yellow liquid; yield: 0.010 g (24%); Rf = 0.28 (hexanes–
CH2Cl2–i-Pr2O, 4:3:3).
1H NMR (250 MHz, CDCl3): δ = 7.47–7.58 (m, 2 H), 7.21–7.40 (m,
8 H), 6.06 (ddd, J = 10.0, 2.9, 1.8 Hz, 1 H), 5.93 (dt, J = 10.0, 1.4
Hz, 1 H), 5.73–5.80 (m, 1 H), 4.66 (d, J = 11.8 Hz, 1 H), 4.56 (d,
J = 11.8 Hz, 1 H), 4.08–4.45 (m, 3 H), 3.86 (dd, J = 10.8, 3.8 Hz, 1
H), 3.78 (dd, J = 10.8, 2.6 Hz, 1 H), 2.91 (s, 3 H).
Reaction of Aziridine 1β with Benzenethiol in the Presence of
PS-TBD
By following the typical procedure, a soln of dimesylate 4 (0.014 g,
0.035 mmol) in anhyd THF (0.5 mL) was treated with PS-TBD res-
in (0.076 g) and PhSH (0.016 g, 0.014 mL, 0.14 mmol, 4 equiv) to
give a crude product consisting of practically pure trans-phenylsul-
fanyl derivative 24 (1H NMR); yield: 0.030 g (91%).
Reaction of Aziridine 1β with Benzenethiol in the Presence of
Lithium tert-Butoxide
13C NMR (62.5 MHz, CDCl3): δ = 137.9, 134.9, 132.0, 129.2,
128.7, 128.6, 128.2, 128.1, 127.8, 83.7, 73.9, 70.1, 69.3, 48.6, 41.8.
A soln of dimesylate 4 (0.017 g, 0.043 mmol) in anhyd benzene (1.2
mL) was treated with t-BuOLi (0.0034 g, 0.042 mmol, 1 equiv) and
PhSH (0.014 g, 0.013 mL, 0.13 mmol, 3 equiv), and the mixture was
stirred for 2 h at r.t. The resulting mixture was diluted with sat. aq
NaCl (2 mL) and extracted with Et2O (2 × 10 mL). The extracts
were concentrated to give a crude product [yield: 0.014 g (80%)]
consisting of a 12:88 mixture of thioglycoside 23β and trans-phe-
nylsulfanyl derivative 24 (1H NMR).
Anal. Calcd for C20H23NO4S2: C, 59.24; H, 5.72; N, 3.45. Found: C,
59.05; H, 5.41; N, 3.12.
1,5-Anhydro-6-O-benzyl-2,3,4-trideoxy-3-(phenylsulfanyl)-4-
(mesylamino)-D-arabino-hex-1-enitol (22)
Pale yellow liquid: yield: 0.021 g (51%); Rf = 0.24 (hexanes–
CH2Cl2–i-Pr2O, 4:3:3).
1H NMR (250 MHz, CDCl3): δ = 7.41–7.53 (m, 2 H), 7.23–7.40 (m,
8 H), 6.42 (dd, J = 6.0, 1.4 Hz, 1 H), 4.81–4.94 (m, 2 H), 4.64 (d,
J = 11.8 Hz, 1 H), 4.57 (d, J = 11.8 Hz, 1 H), 4.06–4.24 (m, 2 H),
3.71–3.98 (m, 3 H), 2.93 (s, 3 H).
Reaction of Aziridine 1β with Benzenethiol in the Presence of
Lithium Hydride
A soln of dimesylate 4 (0.052 g, 0.132 mmol) in anhyd toluene (4
mL) was treated with LiH (0.004 g, 0.53 mmol, 4 equiv) and PhSH
(0.044 g, 0.040 mL, 0.40 mmol, 3 equiv), and the mixture was
stirred for 48 h at r.t. The resulting mixture was diluted with sat. aq
NaCl (2 mL) and extracted with Et2O (2 × 10 mL). The extracts
were concentrated to give a crude product [yield: 0.047 g (88%)]
consisting of a 66:34 mixture of trans-phenylsulfanyl derivative 24
and thioglycoside 23β (1H NMR), which was subjected to prepara-
tive TLC [hexanes–CH2Cl2–i-Pr2O (4:3:3)]. Extraction of the two
most intense bands gave 24 [yield: 0.021 g (39%)] and 23β.
13C NMR (CDCl3): δ = 144.5, 137.9, 133.2, 133.1, 129.5, 128.6,
128.2, 128.0, 100.7, 77.8, 73.7, 69.4, 52.8, 46.4, 42.6.
Anal. Calcd for C20H23NO4S2: C, 59.24; H, 5.72; N, 3.45. Found: C,
59.19; H, 5.54; N, 3.39.
Reaction of Aziridine 1b with PhSH
By following the typical procedure, a soln of dimesylate 4 (0.050 g,
0.13 mmol) in anhyd benzene (3.0 mL) was treated with t-BuOK
(0.015 g, 0.13 mmol) and PhSH (0.014 g, 0.013 mL, 0.39 mmol, 3
equiv) to give a crude product [yield: 0.051 g (97%)] consisting of
a 5:95 mixture of thioglycoside 23β and trans-phenylsulfanyl deriv-
ative 24 (1H NMR), which was subjected to preparative TLC [hex-
anes–CH2Cl2–i-Pr2O (4:3:3)]. Extraction of the two most intense
bands (the faster band contained 23β) gave pure 24.
Phenyl 6-O-Benzyl-2,3,4-trideoxy-4-(mesylamino)-1-thio-β-D-
threo-hex-2-enopyranoside (23β)
Pale yellow liquid: yield: 0.009 g (16%); Rf = 0.34 (hexanes–
CH2Cl2–i-Pr2O, 4:3:3).
1H NMR (250 MHz, CDCl3): δ = 7.48–7.60 (m, 2 H), 7.22–7.45 (m,
8 H), 5.88–6.07 (m, 2 H), 5.51 (s, 1 H, H-1), 4.55 (s, 2 H), 3.87–3.98
(m, 1 H), 3.59–3.78 (m, 3 H), 3.43 (d, J = 10.6 Hz, 1 H, NH), 2.75
(s, 3 H).
1,5-Anhydro-6-O-benzyl-2,3,4-trideoxy-3-(phenylsulfanyl)-4-
(mesylamino)-D-xylo-hex-1-enitol (24)
Pale yellow liquid; yield: 0.035 g (66%)]; Rf = 0.26 (hexanes–
CH2Cl2–i-Pr2O, 4:3:3).
1H NMR (250 MHz, CDCl3): δ = 7.45–7.57 (m, 2 H), 7.23–7.42 (m,
8 H), 6.55 (d, J = 6.1 Hz, 1 H), 4.94 (t, J = 6.1 Hz, 1 H), 4.71 (d,
J = 9.3 Hz, 1 H, NH), 4.54–4.65 (m, 1 H), 4.57 (s, 2 H), 3.61–3.83
(m, 4 H), 2.64 (s, 3 H).
13C NMR (62.5 MHz, CDCl3): δ = 137.9, 135.5, 131.2, 130.7,
129.4, 129.1, 128.7, 128.4, 128.0, 81.4, 75.9, 73.9, 69.6, 46.7, 42.0.
Anal. Calcd for C20H23NO4S2: C, 59.24; H, 5.72; N, 3.45. Found: C,
58.91; H, 5.49; N, 3.17.
Acknowledgment
13C NMR (62.5 MHz, CDCl3): δ = 146.6, 137.6, 133.6, 132.2,
129.5, 128.7, 128.2, 128.0, 98.5, 73.8, 70.9, 68.8, 51.2, 45.7, 41.1.
This work was supported by the Università di Pisa and MIUR (Mi-
nistero dell’Istruzione, della Università e della Ricerca, PRIN
2008), Roma. P.C. gratefully acknowledges generous financial sup-
port from Merck Research Laboratories through the 2005 ADP
Chemistry Award.
Anal. Calcd for C20H23NO4S2: C, 59.24; H, 5.72; N, 3.45. Found: C,
59.11; H, 5.35; N, 3.22.
Reaction of Aziridine 1α with Benzenethiol in the Presence of a
Polymer-Bound Basic Catalyst (PS-TBD); Typical Procedure
A soln of dimesylate 3 (0.016 g, 0.040 mmol) in anhyd THF (1 mL)
was treated with PS-TBD resin (0.080 g) and PhSH (0.018 g, 0.016
mL, 0.16 mmol, 4 equiv), and the mixture was stirred for 18 h at r.t.
The mixture was then diluted with Et2O (15 mL) and the organic
phase was filtered, washed with sat. brine (2 × 2 mL), and concen-
trated to give crude product consisting of practically pure trans-phe-
nylsulfanyl derivative 22 (1H NMR); yield: 0.015 g (92%).
References
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Synthesis 2012, 44, 2863–2871
© Georg Thieme Verlag Stuttgart · New York

SPECIAL TOPIC
Nucleophilic Addition Reactions of Vinyl N-Mesylaziridines
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© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 2863–2871