ORGANIC

LETTERS

Desulfonylation with Mg−MeOH−NiBr2: 2006

Vol. 8, No. 7
An Expedient Reagent System for the 1303-1306
Synthesis of 2-Amino-2,3-dideoxy
Furanosides
Indrajit Das and Tanmaya Pathak*

Department of Chemistry, Indian Institute of Technology, Kharagpur 721 302, India

tpathak@chem.iitkgp.ernet.in
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Received December 20, 2005

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ABSTRACT

A catalytic amount of NiBr2 with Mg−MeOH increases the efficiency of reductive desulfonylation of the β-sulfonylated aminosugars. The
Mg−MeOH−NiBr2 system has been utilized in the synthesis of 2-amino-2,3-dideoxypentofuranosides and 2-amino-2,3-dideoxyhexofuranosides.
The yield of the desulfonylation improved dramatically from 0% with the known reagents to 44−75% with Mg−MeOH−NiBr2.

To circumvent the problem of resistance to aminoglycoside reacted various amines with vinyl sulfone-modified hex-2-
antibiotics among resistant bacteria, several semisynthetic enopyranosides 1R and 1β (Figure 1). It emerged from these
aminoglycoside antibiotics have been designed where either
the hydroxyl groups undergoing enzymatic phosphorylation
have been removed and/or the amino groups susceptible to
acetylation have been masked by acylation or alkylation.1
We therefore considered it to be of interest to design general
methodologies for the synthesis of modified new aminosugars
having one or more deoxygenated centers and mono- or
dialkylated amino groups at specific sites. In addition, an
Figure 1. Vinyl sulfone modified hex-2-enopyranosides.
epimeric variation in the stereochemistry of the C-N bond
might also lead to different types of responses by a biological
system.2
studies that the addition of primary amines to C-2 of both
As part of an ongoing project for developing a general 1R and 1β exclusively produced C-2 equatorial (gluco)
methodology for the synthesis of deoxyaminosugars, we products. Secondary amines, on reaction with β-anomeric
glycosides 1β produced only gluco derivatives but with 1R
(1) (a) Kondo, S.; Hotta, K. J. Infect. Chemother. 1999, 5, 1. (b) Jana,
S.; Deb, J. K. Current Drug Targets 2005, 6, 353. (c) Kim, C.; Mobashery, produced mixtures in which the gluco product was still the
S. Bioorg. Chem. 2005, 33, 149. (c) Busscher, Guuske F.; Rutjes, Floris P. predominant isomer.2a,c
J. T.; Van Delft, Floris L. Chem. ReV. 2005, 105, 775.
(2) (a) Ravindran, B.; Sakthivel, K.; Suresh, C. G.; Pathak, T. J. Org. The successful application of vinyl sulfone modified
Chem. 2000, 65, 2637. (b) Ravindran, B.; Deshpande, S. G.; Pathak, T. carbohydrates in the synthesis of deoxyaminosugars crucially
Tetrahedron 2001, 57, 1093 and references therein. (c) Suresh, C. G.;
Ravindran, B.; Pathak, T.; Narasimha Rao, K.; Sasidhar Prasad, J. S.; depends on the following factors: (i) the efficiency of
Lokanath, N. K. Carbohydr. Res. 2002, 337, 1507. Michael addition of amines; (ii) the diastereoselectivity of
10.1021/ol053082a CCC: $33.50 © 2006 American Chemical Society
Published on Web 03/03/2006
addition of amines; and (iii) the efficiency of desulfonylation
under suitable reductive conditions.3 Since all of our efforts Table 1. Amination of Vinyl Sulfone Modified Carbohydrates
to deliver primary amines from the β-face of the pyranose 2-4 with Benzylamine, Cyclohexylamine, and Morpholinea
ring (1R and 1β) failed,2 we directed our attention to vinyl
sulfone-modified pent-2- and hex-2-enofuranosyl systems
such as 2-4. From our previous experience2,3 and the
previously reported reactions of various nucleophiles with
vinyl sulfone-modified pentofuranosyl nucleosides,4 we were
sure that amines would add efficiently in diastereoselective
fashion to 2-4. Thus, compound 2 on reaction with
benzylamine, cyclohexylamine, and morpholine produced
compounds 5a-c, respectively, in diastereoselective fashion
and high yield. Similarly, 3 and 4 also produced the expected
aminosugars 6a-c and 7a-c, respectively (Table 1).5
Since the success of a scheme for the synthesis of
deoxyaminosugars using carbohydrate vinyl sulfones would
depend crucially on the desulfonylation step,6 we experi-
mented with a large variety of desulfonylating agents
available in the literature. The Na-Hg-mediated reduction
is the most widely used radical-based method for the
desulfonylation of organic molecules and has been used
extensively for the desulfonylation of β-amino sulfones7 and
γ-amino sulfone derivatives.8 Another electron-transfer
method that uses Mg metal in methanol has also been
reported9 with there being at least one report where Mg in
methanol was successfully used for the desulfonylation of a
β-amino sulfone compound.7a However, none of these
reagents were able to efficiently desulfonylate the amine
Michael addition products of vinyl sulfone modified nucleo-
sides; the desired desulfonylated nucleosides were always
obtained in moderate to very poor yields.4
After successfully introducing the amino groups to the R-
or β-face of the hexofuranose and pentofuranose systems to
obtain the products 6a-c and 5a-c/7a-c, respectively, three
of these compounds 5a, 6a, and 7a were subjected to
desulfonylation using Na-Hg or Mg in methanol. None of
these two reagent systems was suitable for the removal of
the tolylsulfonyl group from these modified carbohydrates
with amino groups at the β-position. All of the reactions
produced inseparable mixtures of compounds, and the desired

(3) The strategy has been implemented in the synthesis of D-lividosamine

(2-amino-2,3-dideoxy-D-glucose), a constituent of aminoglycosides livido-
mycin-A, lividomycin-B, etc. Diastereoselective equatorial addition of
ammonia to 1R (Figure 1) followed by the desulfonylation of the product
at the C-3 site produced a known intermediate for accessing D-lividosamine.
Several partially and fully protected analogues of D-lividosamine could be
synthesized using N-monoalkylated and N-dialkylated amines in a similar
approach. See ref 2b.
(4) Wu, J.-C.; Pathak, T.; Tong, W.; Remaud, G.; Chattopadhyaya, J.
Tetrahedron 1988, 44, 6705.
(5) All aminosugars 5a-c, 6a-c, and 7a-c described in Table 1 are
single compounds. Structures of all compounds have been assigned on the
basis of X-ray structural analysis and comparison of NMR data. These data
will be reported elsewhere.
(6) For a review on desulfonylation, see: Najera, C.; Yus, M. Tetrahedron
1999, 40, 10547.
(7) (a) Ku, Y. Y.; Patel, R. R.; Roden, B. A.; Sawick, D. P. Tetrahedron
Lett. 1994, 35, 6017. (b) Eiji, A.; Masahiro, H. Synlett 1996, 100. (c) Giblin,
G. M. P.; Jones, C. D.; Simpkins, N. S. Synlett 1997, 589. (d) Balasubra- a All reactions were carried out at room temperature using neat amines
manian, T.; Hassner, A. Tetrahedron: Asymmetry 1998, 9, 2201. (5 mL/mmol). b Ar ) p-Tol.
(8) François, D.; Lallemand, M. C.; Selkti, M.; Tomas, A.; Kunesch,
N.; Husson, H. P. Angew. Chem., Int. Ed. 1998, 37, 104.
(9) For a review on Mg in MeOH, see: Lee, G. H.; Youn, I. K.; Choi,
E. B.; Lee, H. K.; Yon, G. H.; Yang, H. C.; Pak, C. S. Curr. Org. Chem. products 8a, 9a, or 10a (Table 2) could not be isolated. A
2004, 8, 1263. perusal of the literature revealed that reagents such as
1304 Org. Lett., Vol. 8, No. 7, 2006

Table 2. Desulfonylation of Aminosugars 5-7a
a All reactions were carried out at room temperature using Mg-MeOH-
NiX2 in 6 h. b R1, R2 ) cyclohexylidenyl; Ar ) p-Tol.
HgCl2, CdCl2, and Pd-C have been used as additives with
Mg-MeOH system,9 although the exact role of these com-
pounds in the reaction medium is not well delineated. How-
ever, Mg-EtOH-HgCl29 also failed to produce the expected
compounds from 6a and 7a. On treatment with Al-Hg,6 6a
also produced an inseparable mixture of compounds. There-
Org. Lett., Vol. 8, No. 7, 2006
after, 5a, 6a, and 7a were reacted with either electron-transfer
reagent SmI210a or hydride reagents (LiAlH4) known for their
abilities to induce desulfonylation.6 Interestingly, a mixture
of NiBr2-DME, PPh3, and LiAlH4, which has previously
been reported10b to be an efficient desulfonylating agent, was
also found to be too harsh to be used for the desulfonation
of 7a. In all cases, compounds 5a, 6a, and 7a were always
converted to an inseparable mixture of compounds. Since
most of the conventional reagents or combinations of
reagents failed to deliver the desired products, we initiated
a search for an alternative method for the desulfonylation
of 5a-c, 6a-c, and 7a-c.
Reaction systems generating Ni(0) in situ11 or making
direct use of Raney nickel12 for the reduction of sulfones to
the corresponding carbon-hydrogen bonds have been re-
ported. However, compounds 5a and 7a were either inert to
Raney-Ni or produced several products under the reaction
conditions. At this point, our attention was drawn to a
reported observation that the reduction of nickel halides with
low-oxidation-potential metals such as magnesium produce
finely divided Ni(0), which exhibits general, catalytic activity
greater than commercial Raney nickel.13 We therefore
subjected compounds 5a-c, 6a-c, and 7a-c to desulfony-
lation by the Mg-MeOH-NiX2 system. Three nickel salts,
namely NiCl2, NiBr2, and NiI2, were employed for the present
study. To our pleasant surprise, we could desulfonylate
compounds 5a-c, 6a-c, and 7a-c to obtain the dideoxyami-
nosugars 8a-c, 9a-c, and 10a-c, respectively, in moderate
to good yields. The results are summarized in Table 2. It is
clear from the table that NiBr2 is the most efficient of all
nickel halides used for the desulfonylation. The use of NiCl2
caused the yield to drop in all cases. NiI2 was always the
least efficient additive in all cases. However, it appears from
Table 2 that the amino group that is present is also
responsible in helping to determine the efficiency of the
reaction. For example, benzylamino-containing analogues 5a,
6a, and 7a were always desulfonylated by Mg-MeOH-
NiBr2 most efficiently to produce 8a, 9a, and 10a in 73, 71,
and 75% yields, respectively. The desulfonylation of the
cyclohexylamino derivatives 5b, 6b, and 7b to 8b (70%),
9b (65%), and 10b (69%), respectively, was slightly less
efficient, while for the morpholino analogues 5c, 6c, and 7c
the yields of desulfonylation to 8c (50%), 9c (44%), and
10c (50%) dropped significantly. Interestingly, aminosugars
5a,b, 6a,b, and 7a,b derived from primary amines required
only 10 mol % of the nickel salts, whereas aminosugars 5c,
6c, and 7c derived from secondary amines required 20 mol
% of the nickel salts. The use of NiBr2 or other nickel halides
in stoichiometric amounts did not alter yields and in fact in
some cases yields actually dropped.14 A change of solvent
(10) (a) Serafinowski, P. J.; Barnes, C. L. Synthesis 1997, 225. (b) Ho,
K. M.; Lam, C. H.; Luh, T. Y. J. Org. Chem. 1989, 54, 4474.
(11) Chan, M. C.; Cheng, K. M.; Ho, K. M.; Ng, C. T.; Yam, T. M.;
Wang, B. S. L.; Luh, T. Y. J. Org. Chem. 1988, 53, 4466.
(12) (a) Oikawa, M.; Oikawa, H.; Ichthara, A. Tetrahedron Lett. 1993,
34, 4797. (b) Oikawa, M.; Oikawa, H.; lchihara, A. Tetrahedron 1995, 51,
6237. (c) Gamble, M. P.; Giblin, G. M. P.; Taylor. R. J. K. Synlett 1995,
779. (d) Sheehan, S. M.; Padwa, A. J. Org. Chem. 1997, 63, 4438.
(13) Mauret, P.; Alphonse, P. J. Org. Chem. 1982, 47, 3322.
1305
from MeOH to EtOH did not improve the yield or the quality
of the desulfonylation reactions.
Based on earlier reports,13 we presume that under the
reductive conditions employed, nickel halides are reduced
to Ni(0). However, it is clear from our background work
using Raney-Ni (discussed above) that mere conversion of
Ni(II) to Ni(0) is not the sole reason for the controlled activity
of the Mg-MeOH-NiX2 reported here. It is also logical to
presume at this stage that as suggested earlier, the “particle
arrangement and aggregate textures”,13 may play an important
role in determining the mechanism of action of Mg-MeOH-
NiX2 system. Several other issues such as (i) the role of
counteranion of the nickel salts, (ii) stereoelectronic proper-
ties of the amino groups, and (iii) the ring conformation also
appear to dictate the interactions of furanose systems with
the Ni(0) surface and should also be considered when
predicting the efficacy of the process.
In conclusion, we have developed a novel Mg-MeOH-
NiBr2 system for the reductive desulfonylation of the
(14) One of the reviewers suggested that the drop in yield was possibly
due to the amines irreversibly binding to the greater quantities of Ni(0)
reagent present.
1306
β-sulfonylated aminosugars that allows the synthesis of
hitherto inaccessible 2-amino-2, 3-dideoxypentofuranosides
and 2-amino-2,3-dideoxyhexofuranosides. The yields of
desulfonylation step improve dramatically from 0% with the
known reagents to 44-75% with Mg-MeOH-NiBr2. Re-
search is currently in progress to delineate the exact
mechanism of desulfonylation and further synthetic applica-
tions of the new reagent system.
Acknowledgment. T.P. thanks the Department of Science
and Technology, New Delhi, India, for financial support and
Professor Muktimoy Chaudhury for discussions. I.D. thanks
the Council of Scientific and Industrial Research, New Delhi,
India, for a fellowship.
Supporting Information Available: Experimental pro-
cedures and spectral and analytical data of compounds 8-10.
1H and 13C NMR spectra of all new compounds. Table 3
summarizes attempted desulfonylation of 5a, 6a, and 7a with
known reagents. This material is available free of charge
via the Internet at http://pubs.acs.org.
OL053082A
Org. Lett., Vol. 8, No. 7, 2006
Supporting Information

Desulfonylation with Mg-MeOH-NiBr2: An Expedient Reagent System for the Synthesis of

2-Amino-2,3-dideoxy Furanosides.

Indrajit Das and Tanmaya Pathak*

Department of Chemistry, Indian Institute of Technology, Kharagpur 721 302, India.

tpathak@chem.iitkgp.ernet.in

Experimental Section

General methods. Melting points were determined in open-end capillary tubes and are

uncorrected. Carbohydrates and other fine chemicals were obtained from commercial

suppliers and are used without purification. Solvents were dried and distilled following the

standard procedures. TLC was carried out on precoated plates (Merck silica gel 60, f254), and

the spots were visualized with UV light or by charring the plates dipped in 5% H2SO4-MeOH

solution or 5% H2SO4-Vanillin-EtOH solution. Column chromatography was performed on

silica gel (60-120 or 230-400 mesh). 1H and 13C NMR spectra for most of the compounds

were recorded at 200 and 50.3 MHz, respectively, in CDCl3 unless stated otherwise. Optical

rotations were recorded at 589 nm.

General procedure for desulfonylation: To a well-stirred solution of 5a-c, 6a-c or 7a-c in

dry MeOH (10 mL) was added Mg turnings (15 mmol) and the appropriate nickel halide (10

mol% for primary amines and 20 mol% for secondary amines) at 0 OC under Ar. The mixture

was stirred at ambient temp. After 2-3 h another portion of Mg turnings (15 mmol) and dry

MeOH (5 mL) were added. The mixture was stirred for an additional 2-3 h. The reaction

mixture was filtered through celite. The residue was washed thoroughly with MeOH. The

S1
filtrates were pooled together and the liquid was concentrated under reduced pressure. The

resulting residue was dissolved in EtOAc and was washed with saturated NH4Cl solution,

dried over anhydrous Na2SO4 and filtered, and the filtrate was concentrated under reduced

pressure to get a residue. The residue was purified over silica gel column to afford 8a-c, 9a-c

or 10a-c

Methyl 2-benzylamino-5,6-O-cyclohexylidene-2,3-dideoxy-α-D-altrofuranoside 8a.

Compound 5a (0.25 g, 0.5 mmol) was converted to 8a following the general procedure (0.11

g, 65%, NiCl2), (0.12 g, 73%, NiBr2), (0.09 g, 53%, NiI2). Eluent: EtOAc/petroleum ether

(1:2). Yellow oil. [α]23D (+) 22.0 (c 0.3, CHCl3). 1H NMR (CDCl3): δ 1.35-1.77 (m, 11H),

2.33 (m, 1H), 3.25 (m, 1H), 3.32 (s, 3H), 3.72 (m, 1H), 3.79 (s, 2H), 4.06 (m, 2H), 4.24 (m,

1H), 4.88 (s, 1H), 7.30 (m, 5H). 13C NMR (CDCl3): δ 23.6, 23.8, 25.0, 32.4, 34.5, 36.1, 51.9,

54.5, 63.1, 66.6, 76.9, 78.4, 108.3, 110.0, 126.8, 128.0, 128.2, 139.9. Anal. Calcd for

C20H29NO4: C, 69.14; H, 8.41; N, 4.03. Found: C, 69.47; H, 8.51; N, 3.97.

Methyl 2-cyclohexylamino-5,6-O-cyclohexylidene-2,3-dideoxy-α-D-altrofuranoside 8b.

Compound 5b (0.15 g, 0.3 mmol) was converted to 8b following the general procedure (0.06

g, 60%, NiCl2), (0.07 g, 70%, NiBr2). Eluent: EtOAc/petroleum ether (1:2). Yellow oil.

[α]23D (+) 40.1 (c 0.42, CHCl3). 1H NMR (CDCl3): δ 0.86-1.88 (m, 21H), 2.30 (m, 1H), 2.48

(m, 1H), 3.31 (s, 3H), 3.35 (m, 1H), 3.69 (m, 1H), 4.04 (m, 2H), 4.20 (m, 1H), 4.78 (s, 1H).
13
C NMR (CDCl3): δ 23.7, 24.0, 24.9, 25.1, 26.0, 32.9, 33.4, 33.6, 34.6, 36.1, 54.5, 54.6,

60.3, 66.7, 77.0, 78.2, 108.8, 110.1. Anal. Calcd for C19H33NO4: C, 67.22; H, 9.80; N, 4.13.

Found: C, 67.45; H, 9.97; N, 4.25.

S2
Methyl 5,6-O-cyclohexylidene-2,3-dideoxy-2-morpholino-α-D-altrofuranoside 8c.

Compound 5c (0.21 g, 0.44 mmol) was converted to 8c following the general procedure (0.05

g, 36%, NiCl2), (0.07 g, 50%, NiBr2), (0.03 g, 22%, NiI2). Eluent: EtOAc/petroleum ether

(1:1). Yellow oil. [α]23D (+) 52.8 (c 0.68, CHCl3). 1H NMR (CDCl3): δ 1.27-1.81 (m, 11H),

2.20 (m, 1H), 2.48 (m, 4H), 2.85 (m, 1H), 3.33 (s, 3H), 3.69 (m, 4H), 3.84 (m, 1H), 4.07 (m,

3H), 4.88 (d, J = 2.6 Hz, 1H). 13C NMR (CDCl3): δ 23.7, 23.9, 25.1, 32.1, 34.7, 36.3, 51.9,

55.0, 66.7, 66.9, 72.1, 77.1, 78.5, 107.4, 109.9. Anal. Calcd for C17H29NO5.1/2H2O: C, 60.69;

H, 8.98; N, 4.16. Found: C, 61.07; H, 8.64; N, 4.51.

Methyl 2-benzylamino-5,6-O-cyclohexylidene-2,3-dideoxy-β-D-glucofuranoside 9a.

Compound 6a (0.16 g, 0.32 mmol) was converted to 9a following the general procedure (0.07

g, 62%, NiCl2), (0.08 g, 71%, NiBr2). Eluent: EtOAc/petroleum ether (1:3). Yellow oil.

[α]23D (-) 35.4 (c 0.32, CHCl3). 1H NMR (CDCl3): δ 1.39-1.59 (m, 10H), 2.04 (m, 2H), 3.29

(s, 3H), 3.31 (m, 1H), 3.80 (s, 2H), 3.93 (m, 2H), 4.09 (m, 2H), 4.78 (s, 1H), 7.28 (m, 5H).
13
C NMR (CDCl3): δ 23.8, 24.0, 25.1, 34.2, 34.9, 36.5, 52.0, 54.5, 63.4, 67.3, 78.8, 80.4,

108.5, 109.8, 127.1, 128.1, 128.4, 139.8. Anal. Calcd for C20H29NO4: C, 69.14; H, 8.41; N,

4.03. Found: C, 69.13; H, 8.78; N, 3.81.

Methyl 2-cyclohexylamino-5,6-O-cyclohexylidene-2,3-dideoxy-β-D-glucofuranoside 9b.

Compound 6b (0.15 g, 0.3 mmol) was converted to 9b following the general procedure

(0.061 g, 61%, NiCl2), (0.065 g, 65%, NiBr2), (0.051 g, 51%, NiI2). Eluent: EtOAc/petroleum

ether (1:2). Yellow oil. [α]23D (-) 23.1 (c 0.45, CHCl3). 1H NMR (CDCl3): δ 0.87-1.68 (m,

20H), 1.94 (m, 1H), 2.06 (m, 1H), 2.47 (m, 1H), 3.29 (s, 3H), 3.36 (m, 1H), 3.94 (m, 2H),

4.10 (m, 2H), 4.71 (s, 1H). 13C NMR (CDCl3): δ 23.8, 24.0, 25.0, 25.1, 26.0, 33.7, 33.8, 34.5,

S3
34.9, 36.5, 54.5, 54.7, 60.7, 67.3, 78.8, 80.2, 109.2, 109.8. Anal. Calcd for

C19H33NO4.1/4H2O: C, 66.34; H, 9.80; N, 4.07. Found: C, 66.55; H, 9.86; N, 4.13.

Methyl 5,6-O-cyclohexylidene-2,3-dideoxy-2-morpholino-β-D-glucofuranoside 9c.

Compound 6c (0.21 g, 0.44 mmol) was converted to 9c following the general procedure (0.03

g, 23%, NiCl2), (0.06 g, 44%, NiBr2). Eluent: EtOAc/petroleum ether (1:1). Yellow oil.

[α]23D (-) 44.3 (c 0.22, CHCl3). 1H NMR (CDCl3): δ 1.20-1.59 (m, 10H), 2.08 (m, 1H), 2.21

(m, 1H), 2.50 (m, 4H), 2.99 (m, 1H), 3.29 (s, 3H), 3.69 (m, 4H), 3.87-4.12 (m, 4H), 4.86 (d, J

= 1.8 Hz, 1H). 13C NMR (CDCl3): δ 23.8, 24.0, 25.0, 30.4, 34.5, 36.5, 51.2, 54.8, 66.9, 67.3,

71.0, 78.0, 81.3, 107.7, 110.0. Anal. Calcd for C17H29NO5: C, 62.36; H, 8.93; N, 4.28. Found:

C, 62.53; H, 8.53; N, 4.48.

Methyl 5-O-benzyl-2-benzylamino-2,3-dideoxy-α-D-arabinofuranoside 10a. Compound

7a (0.15 g, 0.31 mmol) was converted to 10a following the general procedure (0.06 g, 61%,

NiCl2), (0.075 g, 75%, NiBr2), (0.053 g, 53%, NiI2). Eluent: EtOAc/petroleum ether (1:2).

Yellow oil. [α]23D (+) 24.9 (c 0.48, CHCl3). 1H NMR (CDCl3): δ 1.61 (m, 1H), 2.27 (m, 1H),

3.23 (m, 1H), 3.34 (s, 3H), 3.48-3.67 (m, 2H), 3.74 (s, 2H), 4.29 (m, 1H), 4.57 (s, 2H), 4.91

(s, 1H), 7.30 (m, 10H). 13C NMR (CDCl3): δ 32.8, 51.9, 54.6, 63.2, 71.9, 73.4, 76.7, 108.5,

126.8, 127.6, 127.7, 128.0, 128.3, 137.9, 139.9. Anal. Calcd for C20H25NO3.1/4H2O: C,

72.36; H, 7.74; N, 4.22. Found: C, 72.48; H, 7.73; N, 4.03.

Methyl 5-O-benzyl-2-cyclohexylamino-2,3-dideoxy-α-D-arabinofuranoside 10b.

Compound 7b (0.19 g, 0.4 mmol) was converted to 10b following the general procedure

(0.07 g, 52%, NiCl2), (0.09 g, 69%, NiBr2). Eluent: EtOAc/petroleum ether (1:2). Yellow oil.

[α]23D (+) 32.4 (c 0.47, CHCl3). 1H NMR (CDCl3): δ 0.87-1.71 (m, 11H), 2.32 (m, 2H), 3.28-

S4
3.34 (m, 4H), 3.41-3.67 (m, 2H), 4.25 (m, 1H), 4.56 (s, 2H), 4.83 (s, 1H), 7.30 (m, 5H). 13C

NMR (CDCl3): δ 24.9, 26.0, 33.0, 33.2, 33.4, 54.3, 54.5, 60.1, 71.8, 73.4, 76.6, 108.9, 127.6,

127.9, 128.3, 137.9. Anal. Calcd for C19H29NO3: C, 71.44; H, 9.15; N, 4.38. Found: C, 71.13;

H, 9.06; N, 4.29.

Methyl 5-O-benzyl-2,3-dideoxy-2-morpholino-α-D-arabinofuranoside 10c. Compound 7c

(0.24 g, 0.52 mmol) was converted to 10c following the general procedure (0.05 g, 31%,

NiCl2), (0.08 g, 50%, NiBr2). Eluent: EtOAc/petroleum ether (1:1). Yellow oil. [α]23D (+)

34.5 (c 0.38, CHCl3). 1H NMR (CDCl3): δ 1.60 (m, 1H), 2.04 (m, 1H), 2.46 (m, 4H), 2.85 (m,

1H), 3.36 (s, 3H), 3.58 (m, 2H), 3.69 (m, 4H), 4.26 (m, 1H), 4.58 (m, 2H), 4.92 (d, J = 2.4

Hz, 1H), 7.30 (m, 5H). 13C NMR (CDCl3): δ 31.5, 51.8, 55.1, 66.7, 71.6, 72.0, 73.3, 76.7,

107.3, 127.5, 127.6, 128.3, 138.1. Anal. Calcd for C17H25NO4: C, 66.43; H, 8.20; N, 4.56.

Found: C, 66.07; H, 8.0; N, 4.77.

Table 3 : Attempted desulfonylation of compounds 5a, 6a

and 7a with reagents reported in the literature

Starting Reaction Product

Material Conditions

5a Na-Hg2,3 Inseparable mixtures

Mg/MeOH4 Inseparable mixtures
Ra-Ni6 Inseparable mixtures
SmI2/THF5a Inseparable mixtures
LiAlH4/THF1 Inseparable mixtures
6a Mg/EtOH/HgCl24 Inseparable mixtures
Al-Hg1 Inseparable mixtures
7a Na-Hg2,3 Inseparable mixtures
Mg/EtOH/HgCl24 Inseparable mixtures
Ra-Ni6 Inseparable mixtures
SmI2/THF5a Inseparable mixtures
LiAlH4/THF1 Inseparable mixtures
LiAlH4/NiBr2/ Inseparable mixtures
DME/PPh3/THF5b

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References:

(1) For a review on desulfonation, see: Najera, C.; Yus, M. Tetrahedron 1999, 40, 10547.

(2) (a) Ku, Y. Y.; Patel, R. R.; Roden, B. A.; Sawick, D. P. Tetrahedron Lett. 1994, 35, 6017.

(b) Eiji, A.; Masahiro, H. Synlett 1996, 100. (c) Giblin, G. M. P.; Jones, C. D.; Simpkins,

N. S. Synlett 1997, 589. (d) Balasubramanian, T.; Hassner, A. Tetrahedron: Asymmetry 1998,

9, 2201.

(3) François, D.; Lallemand, M. C.; Selkti, M.; Tomas, A.; Kunesch, N.; Husson, H. P.

Angew. Chem. Int. Ed. Engl. 1998, 37, 104.

(4) For a review on Mg in MeOH , see: Lee, G. H.; Youn, I. K.; Choi, E. B.; Lee, H. K.; Yon,

G. H.; Yang, H. C.; Pak, C. S. Curr. Org. Chem. 2004, 8, 1263.

(5) (a) Serafinowski, P. J.; Barnes, C. L. Synthesis 1997, 225. (b) Ho, K. M.; Lam, C. H.;

Luh, T. Y. J. Org. Chem. 1989, 54, 4474.

(6) (a) Oikawa, M.; Oikawa, H.; Ichthara, A. Tetrahedron Lett. 1993, 34, 4797. (b) Oikawa,

M.; Oikawa, H.; lchihara, A. Tetrahedron 1995, 51, 6237. (c) Gamble, M. P.; Giblin, G. M.

P.; Taylor. R. J. K. Synlett 1995, 779. (d) Sheehan, S. M.; Padwa, A. J. Org. Chem. 1997, 63,

438.

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