Anchimeric assistance in the case of vicinal dimesylate: Formation of enantiomeric or meso-bimorpholine

Article abstract of DOI:10.1055/s-2006-926469

An anchimeric effect of vicinal dimesylate in the intramolecular nucleophilic substitution by amine is described. One sulfonate group of the dimesylate acts as an internal nucleophile and the other as a leaving group, affording meso-bimorpholine in the in

Full text of DOI:10.1055/s-2006-926469

PAPER
1853
Anchimeric Assistance in the Case of Vicinal Dimesylate: Formation of
Enantiomeric or meso-Bimorpholine
An
A
nchimeric
õ
E
ffect of
V
i
n
cinal
D
imesy
i
late s Kanger,*a Marju Laars,a Kadri Kriis,a Tiiu Kailas,a Aleksander-Mati Müürisepp,a Tõnis Pehk,b Margus Loppa
a
Department of Chemistry, Tallinn University of Technology, Akadeemia tee 15, 12618 Tallinn, Estonia
National Institute of Chemical Physics and Biophysics, Akadeemia tee 23, 12618 Tallinn, Estonia
Fax +372(6)202828; E-mail: kanger@chemnet.ee
b
Received 15 December 2005; revised 9 January 2006
MsO
O
Abstract: An anchimeric effect of vicinal dimesylate in the in-
tramolecular nucleophilic substitution by amine is described. One
sulfonate group of the dimesylate acts as an internal nucleophile and
the other as a leaving group, affording meso-bimorpholine in the in-
tramolecular cyclization. w,w¢-Dimesylate omits this effect and the
target compound is obtained with high ee.
H
HN
HN
O
O
BocN
OH
OH
O
O
BocN
H
O
2
MsO
(S,S)-1
Key words: neighboring-group effects, cyclizations, asymmetric
synthesis, amines, stereoselectivity
Scheme 1 Principal scheme of the synthesis of bimorpholine accor-
ding to ref. 4
chain of the tartaric acid derivative is lengthened with a
two-carbon unit; and (iii) the nucleophilic intramolecular
cyclization gives rise to a bridged cyclic system. In order
to simplify the method, we expected to introduce N-func-
tionality together with the elongation of the chain with a
two-carbon unit (Scheme 2). Using this approach, the
commercially available diol 2 was first alkylated with
N,N-dibenzyl-2-chloroethanamine, followed by acidic
hydrolysis of the acetal group. Using standard transforma-
tions (mesylation and debenzylation) the diol 4 obtained
was converted into intermediate 6 for the cyclization in
38% total yield.
The importance of asymmetric catalytic reactions is in-
creasing permanently. Both transition-metal-catalyzed
and organocatalytic reactions, exploit enantiomerically
pure compounds to create new stereogenic centers. There-
fore, the development of new chiral inducers for these
processes is essential.
Chiral 1,2-diamines have found different applications as
ligands1 as well as organocatalysts.2 Our contribution to
this area is the synthesis of C2-symmetric bridged bicyclic
systems, like bisaziridinyl3 and bimorpholines.4 One of
them – (3S,3¢S)-bimorpholine 1 – was successfully used in
the Rh-catalyzed hydrogen transfer reduction of aromatic
ketones.5 Several methods for obtaining nonracemic sub-
stituted morpholines were published recently.6 However,
the method we developed for the synthesis of C2-symmet-
ric bridged bicyclic bimorpholine is the only one pub-
lished so far (Scheme 1).4
From the synthetic standpoint, the cyclization of amino
mesylates has been thoroughly studied in the synthesis of
substituted pyrrolidines and, typically, the reaction is ste-
reospecific.7
To our surprise, the cyclization of compound 6 under ba-
sic conditions gave mainly meso-bimorpholine 1. This op-
tically inactive isomer and the enantiomeric isomer have
quite similar NMR spectra. However, the retention time
(GC) of the obtained product is clearly different from that
As the method is quite time-consuming, we tried to im-
prove it. Still, our new approach is based on the same key
points as the previous one: (i) C2-symmetry is transposed
from the tartaric acid derivative into the target; (ii) the
Bn2N
H2N
Bn2N
MsO
MsO
RO
MsO
MsO
d
c
e
a
O
O
O
O
O
O
meso-1
2
RO
3
5
6
H2N
Bn2N
Bn2N
C(CH3)2
3: R + R =
4: R = H
b
Scheme 2 Reagents and conditions: a: Cl(CH2)2NBn2, aq NaOH–dioxane, Bu4NBr, 55 °C, 48 h, 72%; b: 1 N HCl, MeOH, 50 °C, 20 h, 98%
(crude); c: MsCl, Et3N, CH2Cl2, 0 °C to r.t., 45 min, 70%; d: HCOONH4, Pd/C, MeOH, 45–55 °C, 7 h, 78%; (e) see Table 2
SYNTHESIS 2006, No. 11, pp 1853–1857
x
x.
x
x
.
2
0
0
6
Advanced online publication: 05.05.2006
DOI: 10.1055/s-2006-926469; Art ID: T17405SS
© Georg Thieme Verlag Stuttgart · New York

1854
T. Kanger et al.
PAPER
Table 2 Cyclization of Dimesylate 6
of the enantiomeric isomer, excluding the possibility of
the formation of the racemic mixture of (S,S)-1 and
(R,R)-1 isomers. The small differences observed in the
chemical shifts of these diastereoisomers can be explained
on the basis of a preferential staggered conformation with
the dihedral angle of 180° between the hydrogens. This
conformation results in two N–C gauche interactions be-
tween the two rings in the meso-isomer and one N–N and
one C–C gauche interaction in the enantiomeric isomer
(Figure 1).
Entry Solvent
Base
Ratio of meso-1:(S,S)-1a
1
2
3
4
5
MeOH
MeOH
MeCN
DMF
Cs2CO3
Et3N, DIPEA
Pyridine
Et3N
12:1
17:1
40:1
100b
100b
MeOH
Pyridine
a Ratio determined by GC.
b (S,S)-1 was not detected.
Although the ratio of the meso and the enantiomeric com-
pound depends considerably on the used base and solvent,
the formation of the meso-product always dominates. The
observed stereoselectivity, i.e. the retention of the abso-
lute configuration at one of the two equivalent stereogenic
centers and the formation of the meso (not racemic) com-
pound can be explained by two consecutive SN2 reactions.
It is assumed that the anchimeric assistance of the a,b-
dimesylate moiety is responsible for that phenomenon.
Neighboring-group assistance in the solvolysis of sul-
fonates is known.9 Synthetic applications of this phenom-
enon are limited mainly with the S-atom containing
sulfinyl or the S-acetyl moiety in selective bromohydrin
formation or glycosylation reaction, respectively.10,11
Here we describe an anchimeric effect where one sul-
fonate group acts as an effective internal nucleophile and
the other as a leaving group (Scheme 3). According to the
proposed mechanism, the intramolecular activation of sul-
fonate as a leaving group by the hydrogen bond from the
amino group occurred. A SN2 attack of the O-atom of the
sulfonate group gives rise to a cyclic intermediate where
the positive charge is delocalized on the formed interme-
diate. The cyclic sulfonate is opened by an intramolecular
SN2 attack of the amino group and one of the morpholine
rings is formed with retention of the configuration. The
second morpholine ring is formed in a stereospecific man-
ner. As a result, a meso-product is obtained.
Figure 1
Thus, the key atoms for the differentiation should be C-2
together with the hydrogen atoms connected to them. It is
known that the gauche interaction between the N- and C-
atoms results in somewhat stronger high-field effects on
the 13C NMR chemical shift than the gauche interaction
between carbon atoms.8 Therefore, C-2 in the meso-iso-
mer must be shifted to higher fields. At the same time, the
electronegative N-atom induces low-field shifts on the hy-
drogen atoms connected to C-2 in the meso-isomer
(Table 1).
The preferred formation of a meso-compound was ob-
served under various conditions (Table 2).
Table 1 Comparison of 13C and 1H Chemical Shifts of 3,3¢-Bimor-
pholine Diastereoisomersa
Atom (S,S)-1
meso-1
13C
13C
1H
1H
2
3
5
6
69.6
55.7
45.6
67.8
3.28 (a), 3.74 (e)
2.65
69.4
56.8
46.1
67.6
3.38 (a), 3,79 (e)
2.75
2.89
2.85 (e), 2.91 (a)
3.46 (a), 3.75 (e)
Alternatively, the same phenomenon could be explained
by the stereospecific formation of one morpholine ring
followed by an anchimeric assistance of the N-atom lead-
ing to an aziridinium intermediate.12 However, the nu-
cleophilic opening of it is regioselective only for benzylic
3.45(a), 3.75 (e)
a Measured in CDCl3 solution from the mixture of isomers (S,S:meso
= 2:3).
H
N
H
O
H2N
O
O
O
O
HN
HN
S
S
O+
O
O
O
Base
O
O
O
O
O
S
O
O
S
HN
O
O
H2N
O
O
H2N
meso-1
H2N
6
Scheme 3 A proposed mechanism for the formation of meso-bimorpholine
Synthesis 2006, No. 11, 1853–1857 © Thieme Stuttgart · New York

PAPER
An Anchimeric Effect of Vicinal Dimesylate
1855
derivatives,13 since aliphatic amino sulfonates give a mix-
ture of regioisomers or even react in SN2 manner with in-
version of the configuration.14 As we did not detect any
formation of the regioisomer of the aziridinium ring open-
ing, this approach can be ruled out.
conducted under argon atmosphere in flame-dried glassware. Com-
mercial reagents were generally used as received. Petroleum ether
(PE) used had a bp range of 40–60 °C.
2,2¢-{[(4S,5S)-2,2-dimethyl-1,3-dioxolane-4,5-diyl]bis(methyle-
neoxy)}bis(N,N-dibenzylethanamine) (3)
To a solution of diol 2 (0.69 g, 4.2 mmol) in 50% aq NaOH soln (5
mL), were added Bu4NBr (340 mg, 1.06 mmol) and N,N-dibenzyl-
2-chloroethanamine (2.86 g, 11.0 mmol) dissolved in 1,4-dioxane
(5 mL). After stirring for 48 h at 55 °C, a sat. NH4Cl soln (4 mL)
was added and the mixture was diluted with EtOAc (4 mL). The or-
ganic layer was separated and the aqueous layer was extracted with
EtOAc (4 × 10 mL). Extracts were dried over K2CO3. Concentra-
tion in vacuo and purification of the crude product by chromatogra-
phy on silica gel (4–6% EtOAc in PE) afforded compound 3 as a
yellow oil; yield: 1.80 g, 72%; [a]54620 –6.3 (c 5.6, CH2Cl2).
This anchimeric effect can be avoided either by the substi-
tution of hydrogen bond donors by the group omitting this
property, or by a spatial separation of mesyl groups. We
used both concepts to verify our hypothesis. Previously,
we have shown that d-benzyloxy substituted a,b-dimesy-
late 7 can be stereoselectively converted into enantiomer-
ic diazide 8 without losing its enantiomeric purity.4 The
application of the second principle – a separation of mesyl
groups in the space – opens a way to our synthetic goal.
For that purpose, intermediate 10 with primary mesyl
groups was synthesized from intermediate 8.4 Reductive
cyclization of the w,w¢-dimesylate 10 led to enantiomeric
bimorpholine 1 in a single step in high enantiomeric puri-
ty (ee 98%) and chemical yield (84%; Scheme 4). No for-
mation of a meso-compound was detected by means of
NMR and GC.
IR (film): 3085, 2985, 2797, 1602, 1494, 1243, 1085, 746, 699 cm–1.
1H NMR (CDCl3): d = 7.39 (8 H, d, J = 7.4 Hz, Bn o), 7.32 (8 H, t,
J = 7.4 Hz, Bn m), 7.24 (4 H, t, J = 7.4 Hz, Bn p), 3.93 (2 H, m,
CHO), 3.67 and 3.65 (8 H, d, J = 13.8 Hz, Bn CH2), 3.60 and 3.58
(4 H, m, NCH2CH2O), 3.52 and 3.51 (4 H, m, CHCH2O), 2.72 and
2.70 (4 H, m, CH2N), 1.41 (6 H, s, CH3).
13C NMR (CDCl3): d = 139.7 (Bn s), 128.7 (Bn o), 128.1 (Bn m),
126.8 (Bn p), 109.5 (CMe2), 77.3 (CHO), 71.6 (CHCH2O), 70.4
(NCH2CH2O), 58.9 (Bn CH2), 52.7 (CH2N), 27.0 (CH3).
RO
BnO
MsO
MS (EI): m/z (%) = 609 (0.2) [M+ + 1], 608 (0.2) [M+], 593 (1), 517
N3
N3
N3
(22), 210 (100).
MsO
MsO
a
d
c
O
O
O
O
O
O
Anal. Calcd for C39H48N2O4 (608.81): C, 76.94; H, 7.95; N, 4.60.
Found: C, 76.88; H, 8.10; N, 4.65.
N3
RO
BnO
7
8
MsO
10
(2S,3S)-1,4-Bis[2-(N,N-dibenzylamino)ethoxy]butane-2,3-diol
(4)
8: R = Bn
9: R = H
b
To a solution of 3 (1.80 g, 2.95 mmol) in MeOH–CH2Cl2 (10:1, 22
mL) 1 N HCl (7 mL) was added. After stirring for 20 h at 50 °C, the
mixture was cooled and neutralized with 1 N aq NaOH soln. Sol-
vents were evaporated and the mixture was extracted with EtOAc
(4 × 10 mL), dried over K2CO3 and concentrated in vacuum to af-
ford crude diol 4 (1.64 g, 98%). An analytical sample was purified
on silica gel (33% EtOAc in PE) to afford diol 4 as a yellow oil.
MsO
H2N
H2N
O
O
(S,S)-1
MsO
IR (film): 3401, 3062, 2919, 2828, 1602, 1494, 1453, 1115, 1028,
747, 699 cm–1.
1H NMR (CDCl3): d = 7.37 (8 H, d, J = 7.4 Hz, Bn o), 7.32 (8 H, t,
J = 7.4 Hz, Bn m), 7.24 (4 H, t, J = 7.4 Hz, Bn p), 3.74 (2 H, m,
CHO), 3.64 (8 H, s, Bn CH2), 3.59 and 3.57 (4 H, m, NCH2CH2O),
3.52 and 3.48 (4 H, m, CHCH2O), 2.69 (4 H, t, J = 5.9 Hz, CH2N).
13C NMR (CDCl3): d = 139.3 (Bn s), 128.8 (Bn o), 128.2 (Bn m),
126.9 (Bn p), 72.7 (CHCH2O), 70.4 (CHO), 69.8 (NCH2CH2O),
58.9 (Bn CH2), 52.8 (CH2N).
Scheme 4 Reagents and conditions: a, b: see ref. 4; c: MsCl, Et3N,
0 °C to r.t, 3 h, 96%; d: H2, PtO2, CH2Cl2–MeOH, 48 h, 84%
In summary, we found an anchimeric effect of vicinal
dimesylate moiety supported by internal stabilization,
which can lead to the retention of the configuration at one
of the two equivalent stereogenic centers of C2-symmetric
substrate and, in our case, to the formation of meso-bimor-
pholine. We have shown a general way to avoid that ef-
fect. In the particular case, a more efficient approach to
enantiomeric bimorpholine 1 was developed.
MS (EI): m/z (%) = 568 (0.03) [M+], 477 (3), 284 (0.5), 210 (44),
91 (100).
(2S,3S)-1,4-Bis[2-(N,N-dibenzylamino)ethoxy]butane-2,3-diyl
Dimethanesulfonate (5)
Methanesulfonyl chloride (9.34 mL, 0.121 mol) was slowly added
to a solution of crude diol 4 (24.5 g, 0.04 mol) and Et3N (18 mL,
0.13 mol) in anhyd CH2Cl2 (190 mL) at 0 °C. After stirring for 10
min at 0 °C and 45 min at r.t., H2O (100 mL) was added and the or-
ganic layer was separated. The aqueous layer was extracted with
CH2Cl2 (150 mL) and EtOAc (2 × 150 mL), extracts were dried over
K2CO3 and concentrated in vacuo. The residue was purified by
chromatography on silica gel (20% EtOAc in PE) affording the tar-
get compound 5 as a yellow oil; yield: 21.8 g, 70%; [a]D21 –6.5 (c
4.1, CH2Cl2).
Full assignment of 1H and 13C chemical shifts is based on the 1D and
2D FT NMR spectra on a Bruker AMX500 instrument. Chloroform
solvent peaks (CHCl3 d = 7.27, CDCl3 d = 77.00) were used as
chemical shift references. The mass spectra were recorded on a Hi-
tachi M80B spectrometer, using electron ionization (EI) at 70 eV.
IR spectra were recorded on a Perkin-Elmer Spectrum BX FTIR
spectrometer. Optical rotations were measured using a Krüss Op-
tronic GmbH automatic digital polarimeter P 3002 or a Polamat A
(Carl Zeiss). Elemental analyses were performed on a Perkin-Elmer
2400 Analyzer. Reactions sensitive to oxygen or moisture were
Synthesis 2006, No. 11, 1853–1857 © Thieme Stuttgart · New York

1856
T. Kanger et al.
PAPER
IR (film): 3061, 3028, 2800, 1601, 1494, 1360, 1176, 825, 748, 527
cm–1.
IR (film): 3029, 2941, 2110, 1456, 1352, 1268, 1175, 1135, 1020,
974, 924, 809, 529 cm–1.
1H NMR (CDCl3): d = 7.36 (8 H, d, J = 7.4 Hz, Bn o), 7.32 (8 H, t,
J = 7.4 Hz, Bn m), 7.24 (4 H, t, J = 7.4 Hz, Bn p), 4.83 (2 H, m,
CHO), 3.67 and 3.63 (4 H, m, CHCH2O), 3.63 (8 H, s, Bn CH2),
3.59 and 3.52 (4 H, m, NCH2CH2O), 2.97 (6 H, s, CH3), 2.66 (4 H,
t, J = 5.9 Hz, CH2N).
13C NMR (CDCl3): d = 139.4 (Bn s), 128.7 (Bn o), 128.3 (Bn m),
127.0 (Bn p), 78.9 (CHO), 70.0 (NCH2CH2O), 69.6 (CHCH2O),
59.0 (Bn CH2), 52.7 (CH2N), 38.6 (CH3).
1H NMR (CDCl3): d = 4.36 (4 H, m, CH2OS), 3.79 (4 H, m,
SOCH2CH2O), 3.74 (4 H, m, CHCH2O), 3.73 (2 H, m, CHN), 3.05
(6 H, s, CH3).
13C NMR (CDCl3): d = 70.8 (CHCH2O), 69.1 (SOCH2CH2O), 68.4
(CH2OS), 60.6 (CHN), 37.5 (CH3).
MS (EI): m/z (%) = 417 (3.99) [M+ + 1], 389 (15.04), 346 (8.25),
208 (22.27), 153 (86.73), 123 (100).
Anal. Calcd for C10H20N6O8S2 (416.43): C, 28.84; H, 4.84; N,
20.18. Found: C, 28.65; H, 4.71; N, 20.10.
MS (EI): m/z (%) = 724 (M+, 0.1), 633 (10), 210 (100), 91 (16).
Anal. Calcd for C38H48N2O8S2 (724.93): C, 62.96; H, 6.67; N, 3.86.
Found C, 62.26; H, 6.65; N, 4.02.
(3S,3¢S)-3,3¢-Bimorpholine [(S,S)-1]
To a solution of diazide 10 (17.98 g, 43.23 mmol) in the mixture of
CH2Cl2 (45 mL) and MeOH (255 mL) PtO2 (1.48 g, 6.51 mmol) was
added. The mixture was hydrogenated in H2 atmosphere for 48 h.
The catalyst was removed by filtration through Celite® and the sol-
vent was evaporated from the filtrate affording the yellow solid of
methanesulfonate salt of bimorpholine (16.92 g). This crude prod-
uct was purified by basic treatment affording (S,S)-bimorpholine 1
as pale-yellow crystals (yield: 6.26 g, 84%, 98% ee). Analytical
data for bimorpholine 1 are given in ref. 4.
(2S,3S)-1,4-Bis(2-aminoethoxy)butane-2,3-diyl Dimethane-
sulfonate (6)
To a solution of 5 (14.9 g, 0.0206 mol) in MeOH–CH2Cl2 (25:2, 270
mL) was added 10% Pd/C (7.4 g) by portions under Ar atmosphere.
Ammonium formate (15.5 g, 0.246 mol) was added by portions and
the mixture was stirred at 45–55 °C for 7 h. The catalyst was re-
moved by filtration through Celite®, the residue was concentrated in
vacuo and purified by chromatography on silica gel eluting with
CH2Cl2–17% methanolic NH3 soln (7:1) to afford free amine 6 as a
yellow oil; yield: 5.78 g, 78%; [a]D22 –7.0 (c 4.5, MeOH).
Acknowledgment
IR (film): 3374, 2933, 1604, 1355, 1174, 916, 527 cm–1.
The authors thank Estonian Science Foundation for financial sup-
port (grants nos 6662, 5628 and 5133).
1H NMR (CDCl3 + CD3OD): d = 4.92 (2 H, m, CHO), 3.60 and 3.58
(4 H, m, NCH2CH2O), 3.52 and 3.51 (4 H, m, CHCH2O), 2.72 and
2.70 (4 H, m, CH2N), 1.41 (6 H, s, CH3).
13C NMR (CDCl3 + CD3OD): d = 77.5 (CHO), 72.4 (NCH2CH2O),
68.9 (CHCH2O), 40.6 (CH2NH2), 38.4 (CH3).
MS (EI): m/z (%) = 365 (0.2) [M+ + 1], 269 (2), 210 (0.6), 173 (15),
References
(1) (a) Fache, F.; Schulz, E.; Tommasino, M. L.; Lemaire, M.
Chem. Rev. 2000, 100, 2159. (b) Ma, Y.; Liu, H.; Chen, L.;
Cui, X.; Zhu, J.; Deng, J. Org. Lett. 2003, 5, 2103.
(c) Mealy, M. J.; Luderer, M. R.; Bailey, W. F.; Sommer, M.
B. J. Org. Chem. 2004, 69, 6042. (d) Bassindale, M. J.;
Crawford, J. J.; Henderson, K. W.; Kerr, W. J. Tetrahedron
Lett. 2004, 45, 4175.
86 (73), 44 (100).
Anal. Calcd for C10H24N2O8S2 (364.44): C, 32.96; H, 6.64; N, 7.69.
Found: C, 32.91; H, 6.59; N, 7.84.
(3R,3¢S)-3,3¢-Bimorpholine (meso-1)
(2) (a) Notz, W.; Tanaka, F.; Barbas, C. F. III Acc. Chem. Res.
2004, 37, 580. (b) Andrey, O.; Alexakis, A.; Bernardinelli,
Org. Lett. 2003, 5, 2559. (c) Alexakis, A.; Andrey, O. Org.
Lett. 2002, 4, 3611.
(3) Kanger, T.; Ausmees, K.; Müürisepp, A.-M.; Pehk, T.;
Lopp, M. Synlett 2003, 1055.
Compound 6 (826 mg, 2.27 mmol) was dissolved in MeOH (23 mL)
and pyridine (1.8 mL, 22 mmol) was added. The mixture was heated
to reflux for 5 d. Concentration in vacuo and purification of the
crude product by chromatography on silica gel eluting with
CH2Cl2–17% methanolic NH3 soln (13:1) afforded meso-1 as white
crystals; yield: 122 mg, 31%; mp 97–98 °C; [a]D 0 (c 4.42,
MeOH).
IR (KBr): 3269, 2972, 2850, 1218, 1128, 1109 cm–1.
20
(4) Kanger, T.; Kriis, K.; Pehk, T.; Müürisepp, A.-M.; Lopp, M.
Tetrahedron: Asymmetry 2002, 13, 857.
(5) (a) Kriis, K.; Kanger, T.; Müürisepp, A.-M.; Lopp, M.
Tetrahedron: Asymmetry 2003, 14, 2271. (b) Kriis, K.;
Kanger, T.; Lopp, M. Tetrahedron: Asymmetry 2004, 15,
2687.
(6) (a) Dave, R.; Sasaki, N. A. Org. Lett. 2004, 6, 15.
(b) Brenner, E.; Baldwin, R. M.; Tamagnan, G. Org. Lett.
2005, 7, 937. (c) Lanman, B. A.; Myers, A. Org. Lett. 2004,
6, 1045. (d) Dastlik, K. A.; Sundermeier, U.; Johns, D. M.;
Chen, Y.; Williams, R. M. Synlett 2005, 693.
NMR: see Table 1.
MS (EI): m/z (%) = 173 (1.4) [M+ + 1], 114 (0.9), 86 (100), 56 (45).
Anal. Calcd for C8H16N2O2 (172.22): C, 55.79; H, 9.36; N, 16.27.
Found: C, 55.86; H, 9.42; N, 16.21.
(5S,6S)-5,6-Diazido-3,8-dioxadecane 1,10-Dimethanesulfonate
(10)
Methanesulfonyl chloride (1.2 mL, 15 mmol) was slowly added to
a cooled solution of diol 9 (1.68 g, 6.45 mmol) and Et3N (2.7 mL,
19 mmol) in anhyd CH2Cl2 (20 mL) at 0 °C. The mixture was al-
lowed to warm to r.t. during 3 h. After H2O was added, the organic
layer was separated and the aqueous layer was extracted with
EtOAc (3 × 40 mL). The combined organic layers were washed with
brine and dried over MgSO4. Concentration in vacuo and purifica-
tion of the crude product by chromatography on silica gel (50%
EtOAC in PE) afforded dimesylate 10 as a colorless oil; yield: 2.58
g, 96%; [a]D20 –26.7 (c 2.66, CH2Cl2).
(7) (a) Pichon, M.; Figadere, B. Tetrahedron: Asymmetry 1996,
7, 927. (b) Kotsuki, H.; Kuzume, H.; Gohda, T.; Fukuhara,
M.; Ochi, M.; Oishi, T.; Hirama, M.; Shiro, M. Tetrahedron:
Asymmetry 1995, 6, 2227. (c) Alexakis, A.; Tomassini, A.;
Chouillet, C.; Roland, S.; Mangeney, P.; Bernardinelli, G.
Angew. Chem. Int. Ed. 2000, 39, 4093.
(8) Schneider, H. J.; Hoppen, V. J. Org. Chem. 1978, 43, 3866.
(9) (a) Bentley, T. W.; Norman, S. J.; Gerstner, E.; Kemmer, R.;
Christl, M. Chem. Ber. 1993, 126, 1749. (b) Borodkin, G.
I.; Pushkareva, O. A.; Gatilov, Y. V.; Shubin, V. G. Zh. Org.
Synthesis 2006, No. 11, 1853–1857 © Thieme Stuttgart · New York

PAPER
Khim. 1988, 24, 2505; Chem. Abstr. 1989, 111, 77248.
(c) Borodkin, G. I.; Konradi, N. R.; Shubin, V. G. Zh. Org.
Khim. 1987, 23, 1599; Chem. Abstr. 1988, 108, 111510.
(10) Raghavan, S.; Tony, K. A. J. Org. Chem. 2003, 68, 5002.
(11) Knapp, S.; Kirk, B. A. Tetrahedron Lett. 2003, 44, 7601.
An Anchimeric Effect of Vicinal Dimesylate
1857
(12) de Sousa, S. E.; O’Brien, P.; Steffens, H. C. Tetrahedron
Lett. 1999, 40, 8423.
(13) Dieter, R. K.; Deo, N.; Lagu, B.; Dieter, J. W. J. Org. Chem.
1992, 57, 1663.
(14) Rosen, T.; Fesik, S. W.; Chu, D. T.; Pernet, A. G. Synthesis
1988, 40.
Synthesis 2006, No. 11, 1853–1857 © Thieme Stuttgart · New York