A diastereoselective and general route to 5-amino-5-deoxysugars: Influence of C-3 substitution on the addition of amines to C-5 of vinyl sulfone-modified Hex-5-enofuranosyl carbohydrates

Article abstract of DOI:10.1021/jo051143c

In the synthesis of vinyl sulfone-modified hex-5-enofuranosides, the E/Z ratios of the products are influenced by the stereoelectronic property of a group present at the C-3 position. This observation has been utilized to influence the diastereoselectivit

Full text of DOI:10.1021/jo051143c

A Diastereoselective and General Route to
5-Amino-5-deoxysugars: Influence of C-3 Substitution on the
Addition of Amines to C-5 of Vinyl Sulfone-Modified
Hex-5-enofuranosyl Carbohydrates
Indrajit Das and Tanmaya Pathak*
Department of Chemistry, Indian Institute of Technology, Kharagpur 721 302, India
Cheravakkattu G. Suresh
Division of Biochemical Sciences, National Chemical Laboratory, Pune 411 008, India
tpathak@chem.iitkgp.ernet.in
Received June 7, 2005
In the synthesis of vinyl sulfone-modified hex-5-enofuranosides, the E/Z ratios of the products are
influenced by the stereoelectronic property of a group present at the C-3 position. This observation
has been utilized to influence the diastereoselectivity of addition of amines to C-5 of vinyl sulfone-
modified hex-5-enofuranosides, which are efficient Michael acceptors. The stereoelectronic effect
of OMe attached to the â-face of C-3 (gluco derivative) is sufficient to impose diastereoselectivity
overwhelmingly in favor of L-ido-aminosugars when the Michael acceptor is reacted with both
primary and secondary amines. 3-O-Benzylated gluco derivative is also effective in producing L-ido-
aminosugars but only in reactions with primary amines. The selectivity is lost when an allo
derivative with OBn at the R-face of C-3 is used. Selected products were desulfonated to establish
this new approach as a general and versatile strategy for accessing 5-amino-5-deoxysugars.
Introduction
oxides, tosylates, and ketones.1 Our interest in the area
of aminosugars6 including aminonucleosides7 in general
and 5-aminosugars in particular prompted us to look for
Aminosugars in general are one of the most important
classes of modified carbohydrates.1 Several 5-amino-5-
deoxysugars such as 5-deoxy-6-O-dodecyl-1,2-O-isopro-
pylidene-5-pyrrolidinyl-R-D-glucofuranose have been iden-
tified for their antiproliferative and immunomodulatory
activities,2 and 5-aminohexoses are the key building
blocks for the synthesis of a wide variety of polyhydroxy-
lated piperidines which are glycosidase inhibitors.3-5 The
most common methods for the synthesis of aminosugars
involve the reactions of amines with sugar-derived ep-
(3) . Reviews: (a) Asano, N.; Nash, R. J.; Molyneux, R. J.; Fleet, G.
W. J. Tetrahedron: Asymmetry 2000, 11, 1645. (b) Naoki, A.; Hironobu,
H. Glycoscience 2001, 3, 2541. (c) Dhavale, D. D.; Matin, M. M.
ARKIVOC 2005, 110.
(4) For the synthesis of deoxynojirimycin from carbohydrates, see:
(a) Dhavale, D. D.; Desai, V. N.; Sindkhedkar, M. D.; Mali, R. S.;
Castellari, C.; Trombini, C. Tetrahedron: Asymmetry 1997, 8, 1475.
(b) Schaller, C.; Vogel, P.; Jager, V. Carbohydr. Res. 1998, 314, 25. (c)
Pistia-Brueggeman, G.; Hollingsworth, R. I. Tetrahedron 2001, 57,
8773. (d) Spreitz, J.; Stutz, A. E.; Wrodnigg, T. M. Carbohydr. Res.
2002, 337, 183. (e) Lemaire, M.; Veny, N.; Gefflaut, T.; Gallienne, E.;
Chenevert, R.; Bolte, J. Synlett 2002, 1359. (f) Rani, S.; Agarwal, A.;
Vankar, Y. D. Tetrahedron Lett. 2003, 44, 5001. (g) Zechel, D. L.;
Boraston, A. B.; Gloster, T.; Boraston, C. M.; MacDonald, J. M.;
Tilbrook, D. M. G.; Stick, R. V.; Davies, G. J. J. Am. Chem. Soc. 2003,
125, 14313. (h) Szczepina, M. G.; Johnston, B. D.; Yuan, Y.; Svensson,
B.; Pinto, B. M. J. Am. Chem. Soc. 2004, 126, 12458. (i) Goujon, J.-Y.;
Gueyrard, D.; Compain, P.; Martin, O. R.; Ikeda, K.; Kato, A.; Asano,
N. Bioorg. Med. Chem. 2005, 13, 2313.
(1) (a) Ferrier, R. J. Carbohydrate Chemistry; The Royal Society of
Chemistry, Cambridge: 1968-1996; Vols. 1-28. (b) Collins, P. M.;
Ferrier, R. J. Monosaccharides: Their Chemistry and Their Roles in
Natural Products; John Wiley & Sons: Chichester, 1996.
(2) (a) Arora, S. K.; Thomson, D. S. Akhtar, M. N. U.S. 1994, 10 pp.
Cont.-in-part of U.S. Ser. No. 810,906; Chem. Abstr. 1995, 122, 64320.
(b) Arora, S. K.; Thomson, D. S.; Akhtar, M. N. PCT Int. Appl. 1993,
31 pp; Chem. Abstr. 1993, 119, 271626.
10.1021/jo051143c CCC: $30.25 © 2005 American Chemical Society
Published on Web 09/02/2005
J. Org. Chem. 2005, 70, 8047-8054
8047

Das et al.
SCHEME 1. Synthesis of Vinyl Sulfone-Modified
Hex-5-enofuranosides
FIGURE 1. Vinyl sulfone-modified carbohydrates with exo-
cylic vinyl sulfone groups.
an alternative strategy for the functionalization of the
C-5 position of hexoses. A perusal of literature on the
synthesis of 5-amino-5-deoxysugars reveals that methods
for the functionalization of the C-5 position of hexose
sugars in general are limited in number. This is mainly
because of the fact that the 5-O-sulfonylated hexoses are
reluctant partners in nucleophilic displacement reactions;
moreover, because of the secondary nature of the 5-OH
group, low-boiling amines cannot be used for such
transformations because the reaction has to be carried
out at 80 °C and beyond.2,8 On the other hand, amines
react with epoxides (e.g., 7-9, Scheme 1) in a regiose-
lective fashion to attack the C-6 position.9 Except for a
single report on the azidomercuration of the 5,6-unsatur-
ated carbohydrates,10 olefinic carbohydrates have never
been employed in the synthesis of 5-amino-5-deoxysug-
ars; however, this reaction is limited only to the use of
azide as the source of masked amino function. Nucleo-
philic addition (Michael) to double bonds activated by
electron-withdrawing groups as part of carbohydrates
should serve as a useful methodology for the functional-
ization of monosaccharides. In fact, the addition of
ammonia to 3-O-acetyl-5,6-dideoxy-1,2-O-isopropylidene-
6-nitro-R-D-hex-5-enofuranose produced 5-amino-5-deoxy-
L-idofuranose and 5-amino-5-deoxy-D-glucofuranose in a
ratio of 1.5:1.5b
Interestingly, more than two decades ago, a vinyl
sulfone-modified pyranose derivative 1 (Figure 1) was
reacted with MeLi in a stereoselective fashion to generate
intermediates leading to the synthesis of maytansinol.11a
Although R,â-unsaturated or vinyl sulfones are now
commonly used intermediates in organic synthesis,6b-f,12
the strategy for the functionalization of a carbon center
away from the pyranose or furanose ring using a vinyl
sulfone-modified carbohydrate has never been explored
in spite of the efficient application of Michael addition
reaction to 1. In addition to the above example, there are
only a few reports on the synthesis and properties of vinyl
sulfone-modified carbohydrates where the vinyl sulfone
group is NOT attached to the ring carbons. Vinyl sulfone-
modified carbohydrate 2 and corresponding nucleosides
3 and 4 have been synthesized using radical chemistry
(5) For the synthesis of idonojirimycin from carbohydrates, see: (a)
Fowler, P. A.; Haines, A. H.; Taylor, R. J. K.; Chrystal, E. J. T.;
Gravestock, M. B. Carbohydr. Res. 1993, 246, 377. (b) Sasinkova, V.;
Koos, M. Chem. Paper. 1997, 51, 147. (c) Szolcsanyi, P.; Gracza, T.;
Koman, M.; Pronayova, N.; Liptaj, T. Chem. Commun. 2000, 471. (d)
Szolcsanyi, P.; Gracza, T.; Koman, M.; Pronayova, N.; Liptaj, T.
Tetrahedron: Asymmetry 2000, 11, 2579.
(6) (a) Ravindran, B.; Pathak, T. J. Org. Chem. 1999, 64, 9715. (b)
Ravindran, B.; Sakthivel, K.; Suresh, C. G.; Pathak, T. J. Org. Chem.
2000, 65, 2637. (c) Ravindran, B.; Pathak, T. Ind. J. Chem. 2001, B
40, 1114. (d) Ravindran, B.; Deshpande, S. G.; Pathak, T. Tetrahedron
2001, 57, 1093. (e) Suresh, C. G.; Ravindran, B.; Pathak, T.; Narasimha
Rao, K.; Sasidhar Prasad, J. S.; Lokanath, N. K. Carbohydr. Res. 2002,
337, 1507. (f) Sanki, A. K.; Pathak, T. Synlett, 2002, 1241.
(7) (a) Sakthivel, K.; Kumar, R. Krishna; Pathak, T. Tetrahedron
1993, 49, 4365. (b) Sakthivel, K.; Bera, S.; Pathak, T. Tetrahedron
1993, 49, 10387. (c) Sakthivel, K.; Pathak, T.; Suresh, C. G. Tetrahe-
dron 1994, 50, 13251. (d) Bera, S.; Pathak, T.; Langley, G. J.
Tetrahedron 1995, 51, 1459. (e) Sakthivel, K.; Pathak, T. Tetrahedron
1996, 52, 4877. (f) Bera, S.; Pathak, T. Tetrahedron 1999, 55, 13051.
(g) Pathak, T. Chem. Rev. 2002, 102, 1623.
for the chain elongation at C-5 of pentose sugars.13a
A
related nucleoside 5 was also obtained13b through a much
shorter route by using a sulfone-stabilized Horner-
Emmons reagent. Except for the only report on the use
of a vinyl sulfone-modified hex-5-enofuranoside 6 as a
substrate for cycloaddition reaction,13c none of the sys-
tems represented by compounds 2-6 was studied at all
to establish their potentials as synthetic intermediates.
(11) (a) Isobe, M.; Kitamura, M.; Goto, T. J. Am. Chem. Soc. 1982,
104, 4997. (b) Kitamura, M.; Isobe, M.; Ichikawa, Y.; Goto, T. J. Am.
Chem. Soc. 1984, 106, 3252.
(12) (a) Patai, S., Rappoport, Z., Stirling, C., Eds. The Chemistry of
Sulfones & Sulphoxides; John Wiley & Sons: New York, 1988. (b)
Simpkins, N. S., Sulfones in Organic Synthesis; Pergamon Press:
Oxford, 1993.
(13) (a) Barton, D. H. R.; Gero, S. D.; Quiclet-Sire, B.; Samadi, M.
J. Chem. Soc., Chem. Commun. 1988, 1372. (b) Musicki, B.; Widlanski,
T. S. Tetrahedron Lett 1991, 32, 1267. (c) Trost, B. M.; Seoane, P.;
Mignani, S.; Acemoglu, M. J. Am. Chem. Soc. 1989, 111, 7287.
(8) (a) Robert E. G.; Robert M. B.; Susumu H.; Roy L. W. J. Org.
Chem. 1963, 28, 1401. (b) Roy L. W.; Robert E. G. J. Org. Chem. 1964,
29, 2609.
(9) Williams, N. R. Adv. Carbohydr. Chem. 1970, 25, 109.
(10) Czernecki, S.; C. Georgoulis, C.; Provelenghiou, C. Tetrahedron
Lett. 1979, 20, 4841.
8048 J. Org. Chem., Vol. 70, No. 20, 2005

Diastereoselective and General Route to 5-Amino-5-deoxysugars
On the other hand, since we have already established
the efficient and general applications of vinyl sulfone-
modified carbohydrates in the synthesis of amino-
sugars,6b-e we envisaged that it would be pertinent to
study the diastereoselectivity of addition of amines to
vinyl sulfone-modified hex-5-enofuranosides. Moreover,
efficient amination followed by desulfonation of the
addition product using a variety of reaction conditions14
would lead to a range of C-6 functionalized C-5 amino
sugars.
FIGURE 2. Vinyl sulfone-modified hex-2-enopyranosides.
in situ) to 16A by deprotonating H-4. In fact, 16A was
obtained exclusively in 3 h when 16 was treated with
DBU. Therefore, we reacted the mesylated product of 13
with several organic bases much weaker than DBU.
Thus, Et3N in dichloromethane at room temperature in
3 h and neat N,N-dimethylaniline at 110-120 °C in 6 h
produced E and Z isomers of 16 in almost equal propor-
tions (1H NMR). Pyridine at 110-120 °C in 2 h generated
a mixture of E/Z of 16 in a ratio 3:1, and 2,4,6-collidine
in toluene at 110-120 °C in 8 h changed the ratio to 4:1
(1H NMR). Compound 16A could not be identified in any
of the above reactions. However, we opted for pyridine
because of its low basicity and easy accessibility. The
above method constitutes a more efficient and general
route to compounds such as 16-18 than the radical13a
and Emmons-Wadsworth-Horner-type reagent-based
methods.13b,c If necessary, sodium tolylthiolate may be
replaced by other thiolate salts to access analogues of 16-
18 or other hexoses.
The ratios of E/Z in 16 and 17 were determined from
the peaks arising out of either H-1 protons or the methyl
protons of the tolylsulfonyl group in the 1H NMR spectra
of the purified mixtures of isomers. Since the E-isomer
of 16 is a higher homologue of 6, the isomers of the former
could be easily identified even in mixtures by comparing
peaks at δ 6.69 (dd, J ) 1.8, 15 Hz, 1H) and δ 6.96 (dd,
J ) 3.8, 15 Hz, 1H) arising out of H-5 and H-6 protons,
respectively, of the E isomer of 16 and 6.39 ppm (m, 2H)
for the same protons of the Z isomer.13c In fact, in the
case of 18, peaks at δ 6.62 (dd, J ) 1.9, 15.1 Hz, 1H) and
δ 6.99 (dd, J ) 3.9, 15.2 Hz, 1H) indicated the presence
of only E isomer. Similarly, δ 6.62 (dd, J ) 1.8, 15 Hz,
1H)/δ 6.96 (dd, J ) 3.8, 15 Hz, 1H) and δ 6.35 (m, 2H)
for 17 were indicative of the presence of the E or Z
isomers, respectively.
Reactions of Vinyl Sulfone-Modified Hex-5-eno-
furanosides. It should be noted that in the case of vinyl
sulfone-modified hex-2-enopyranosides amines added in
diastereoselective fashion to 19R and 19â (Figure 2).6b-f
The addition of primary amines to 19R and 19â exclu-
sively produced C-2 equatorial (gluco) products. Second-
ary amines, on reactions with 19â, produced only gluco
derivative but with 19R produced a mixture in which
gluco was still the predominant isomer.6b On the other
hand, sterically bulky tert-butylamine reacted only with
19â (and not 19R) at elevated temperature to produce
the gluco derivative in high yield.6e It may be concluded
from these reactions that the directive effect of the
anomeric configuration to a great extent determined the
stereochemical outcome of the reactions but the nature
of nucleophiles also played an important role. Although
no such directive group was available at C-4, adjacent
to the electrophilic reactive site C-5 of 16-18, our
observation related to the influence of C-3 substitution
on the E/Z ratios for 16-18 led us to envisage that the
same structural features would also affect the diastereo-
selectivity of addition of amines to C-5 of 16-18.
Results and Discussion
Synthesis of Vinyl Sulfone-Modified Hex-5-eno-
furanosides. To access relatively large amounts of vinyl
sulfone-modified hex-5-enofuranosides, it was necessary
to devise a simple and general methodology suitable for
the large-scale preparation of 16 and its analogues. We
intended to generate a wide variety of exocyclic vinyl
sulfones (analogues of 16-18) having various alkyl and
aryl groups attached to sulfur through simple routes. We,
therefore, avoided the use of Emmons-Wadsworth-
Horner-type reagent, which was used13c for the synthesis
of 6. At the same time, the radical chemistry reported
for the synthesis of 2-4 was also not suitable for the
large-scale preparation of 16-18. Since nucleophiles are
known to attack regioselectively9 the C-6 position of
epoxides (e.g., 7-9, Scheme 1), we reacted the easily
accessible epoxide 715a with sodium tolylthiolate to get
10 in high yield. Oxidation of 10 produced 13. Compound
13 was subjected to mesylation followed by olefination
to get the desired vinyl sulfone 16 (E/Z ) 3:1) (Scheme
1). The formation of the unexpected Z isomer in relatively
high amount prompted us to study the influence of steric
bulk at the C-3 position on the E/Z ratio. Therefore,
epoxides 815b and 915c were transformed to vinyl sulfones
17 and 18 respectively via intermediates 11/14 and 12/
15 following the same route (Scheme 1).
Interestingly, the variation of the group at C-3 affected
the E/Z ratios to some extent. Thus, by changing from
OBn in 16 to OMe in 17, the E/Z ratio changed from 3:1
to 3:2; in the case of 18, however, only E isomer could be
detected. Since the presence of â-OBn (16) or â-OMe (17)
at C-3 caused the formation of Z isomer (alongside E
isomer) as opposed to the exclusive formation of E isomer
in the case of 18, it may be argued that the stereoselec-
tivity of abstraction of protons from C-6 during the
elimination reactions of the mesylated products of 13-
15 was dictated by the stereoelectronic properties of the
group present at C-3 on the â-face of furanosides.
However, the exact cause for the loss of selectivity of
abstraction of protons in the formation of 16 and 17
cannot be established at this point.
The nature of the organic base used for the conversion
of 13 to 16 profoundly affected the product formation.
Thus, DBU at room temperature in 10 min produced the
unwanted â, γ-unsaturated sulfone 16A exclusively in
95% isolated yield as a crystalline solid. We presumed
that DBU was too strong a base to isomerize 16 (formed
(14) For a review on desulfonation, see: Najera, C.; Yus, M.
Tetrahedron 1999, 40, 10547.
(15) (a) Morillo, M.; Lequart, V.; Grand, E.; Goethals, G.; Usubillaga,
A.; Villa, P.; Martin, P. Carbohydr. Res. 2001, 334, 281. (b) Yoshimura,
J.; Tamaru, M. Carbohydr. Res. 1979, 72, C9. (c) Hanaya, T.; Sugiyama,
K.-I.; Kawamoto, H.; Yamamoto, H. Carbohydr. Res. 2003, 338, 1641.
J. Org. Chem, Vol. 70, No. 20, 2005 8049

Das et al.
SCHEME 2. Diastereoselective Addition of
Amines to Vinyl Sulfone-Modified
Hex-5-enofuranosides
SCHEME 3. Reductive Removal of p-Tolylsulfonyl
Group
with 16-18 to produce 20g/21g, 20h/21h, and 20i/21i
in 1:1, 6:1, and 1:1 ratios, respectively (Scheme 2). In
these cases, except for 17, an increase in the interaction
of bulky piperidine with OBn at C-3 (for 16) or absence
of interaction with H at C-3 (for 18) resulted into the loss
of diastereoselectivity of addition. Here also, the stereo-
electronic properties of OMe group (for 17) render
optimum interactions with piperidine for better selectiv-
ity. The major product 20h obtained from the reaction
of 17 was isolated in 69% yield. It should be noted that
the use of a solvent like THF affected the reactions
adversely in almost all cases; on an average the reaction
time increased from 5-17 h to 2.5-4 days.
To establish the usefulness of this methodology, we
desulfonated compounds 20a and 20b using two different
reagents. Compound 20a on treatment with LAH under-
went desulfonation with partial debenzylation to produce
a mixture of 22 and 23. The mixture was rebenzylated
to produce 23 in 58% overall yield in two steps. The
3-OMe derivative 20b was desulfonated smoothly to
produce 24 in 78% yields. Alternatively, 20a and 20b
could be desulfonated less efficiently to 23 and 24,
respectively, using Mg in MeOH (Scheme 3).
The second purpose of the desulfonation was to estab-
lish the structures of the synthetic aminosugars unam-
biguously because compound 23 was apparently reported
in the literature in connection with the synthesis of a
deoxynojirimycin analogue.4a However, the data reported4a
for the â-L-idofuranose and the R-D-glucofuranose deriva-
tives appear to be confusing. We therefore decided to
establish the identity of our compounds unambiguously
by synthesizing them through alternative routes. Thus,
the known glucotosyl derivative 2516a was reacted with
benzylamine to produce aminosugars, which matched
with compound 23 in every respect (Scheme 4). On the
other hand, the aminosugar obtained by reacting the
idotosyl derivative 2716b,c with benzylamine did not match
with compound 23 and was 28 instead (Scheme 4). For
the “â-L-idofuranose” derivative, the authors reported4a
[R]29D -52.8 (c ) 1.3, CHCl3)/δH 1.31 (d, J ) 6.3 Hz, 3H,
H-6)/δC 17.83 (C-6). For the “R-D-glucofuranose” deriva-
tive, the authors reported4a [R]29D -10.3 (c ) 1.3, CHCl3)/
δH 1.01 (d, J ) 6.3 Hz, 3H, H-6)/δC 15.4 (C-6). We, on the
other hand recorded the following combinations. Com-
Thus, the 3-O-benzylated gluco derivative 16 on reac-
tions with neat benzyl and isopropylamines produced
20a/21a and 20d/21d, respectively, in a ratio 9:1 (1H
NMR). In both cases, the ido derivatives 20a and 20d
were the major products, which were isolated and identi-
fied unambiguously (see later). The 3-O-methylated gluco
derivative 17 also reacted in a similar fashion with benzyl
and isopropylamines to produce the 20b/21b and 20e/
21e, respectively, in a ratio of 9:1 (1H NMR). In this case
also, the ido isomer was the major product (Scheme 2).
It is significant to note that the stereoelectronic effect of
OMe at C-3 (compound 17) is sufficient to impose
diastereoselectivity in favor of the L-ido derivative.
However, the allo derivative 18, where the steric bulk at
C-3 was significantly reduced because of the presence of
a hydrogen atom instead of â-OBn/OMe at C-3, showed
a complete or significant lack of the diastereoselectivity
of addition when reacted with benzyl and isopropy-
lamines. In these cases, 20c/21c and 20f/21f were formed
in ratios 1:1 and 3:2 (1H NMR), respectively, as insepa-
rable mixtures. A secondary amine piperidine reacted
pound 23: [R]29 -10.5 (c 0.65, CHCl3)/δH 0.98 (d, J )
D
6.5 Hz, 3H)/δC 15.6. Compound 28: [R]29D -56.2 (c 0.45,
CHCl3)/δH 1.25 (d, J ) 6.4 Hz, 3H)/δC 17.7. It is clear
(16) (a) Redlich, H.; Lenfers, J. B.; Bruns, W. Ann. 1985, 1570. (b)
Gramera, R. E.; Ingle, T. R.; Whistler, R. L. J. Org. Chem. 1964, 29,
1083. (c) Wolfrom, M. L.; Hanessian, S. J. Org. Chem. 1962, 27, 1800.
8050 J. Org. Chem., Vol. 70, No. 20, 2005

Diastereoselective and General Route to 5-Amino-5-deoxysugars
SCHEME 4. Alternative Synthesis of
5-Amino-5,6-dideoxyhexofuranosides
FIGURE 4. Proposed mode of addition of amines to vinyl
sulfone-modified hex-5-enofuranosides.
allow the formation of the hydrogen-bonded intermediate
but highly reactive piperidine reacts with 16 anyway
without any selectivity. A moderate interaction between
OMe (compound 16) and piperidine allows most of the
reaction to proceed through a 6-membered intermediate.
In the absence of any such intermediates in case of 18,
both primary and secondary amines attack C-5 from both
sides without any diastereoselectivity.
from the above comparisons that the data reported4a for
“R-D-glucofuranose derivative”4a compares favorably with
compound 23, which in fact is a â-L-idofuranose deriva-
tive. Further analysis of the data revealed that the 6-Me
peak for the 6-deoxy-gluco derivative in a pair of gluco/
ido compounds such as 25 (δ 1.34, d) and 27 (δ 1.26, d)
appears at a higher δ value. The chemical shifts for the
6-Me groups of 3-O-benzyl-6-deoxy-1,2-O-isopropylidene-
R-D-gluco-1,4-furanose and 3-O-benzyl-6-deoxy-1,2-O-iso-
propylidene-â-L-ido-1,4-furanose16c are 1.25 (d) and 1.14
(d), respectively. The same trend is followed in the case
of 28 (δ 1.25, d) and 23 (δ 0.98, d) pair. The identity of
3-O-methyl analogue 24 was also established unambigu-
ously through alternative synthesis from 2616b (Scheme
4). The identity of the major isomer 20h was established
by X-ray diffraction of the single crystal; the configuration
of the three groups around the asymmetric carbon C5 as
viewed from the side of H atom can be clearly seen in
Figure 3. Since all of 20a, 20b, and 20h were identified
To conclude, we have developed an efficient and
general strategy for the synthesis of vinyl sulfone-
modified hex-5-enofuranosides. The usefulness of these
compounds as Michael acceptors leading to the synthesis
of 5-amino-5-deoxysugars has been established for the
first time. The stereoelectronic properties of the substit-
uents at C-3 position and their interactions with the
incoming nitrogen nucleophiles have been used to control
the diastereoselectivity of addition. Primary amines, on
reaction with vinyl sulfone-modified gluco derivatives
(compounds 16 and 17) imparted better selectivity pat-
terns in favor of L-ido isomers. The selectivity is absent
in most cases with a bulky secondary amine or in all cases
with vinyl sulfone-modified allo derivative (compound 18)
as the Michael acceptor. It may be suggested that the
influence of the OMe group present at C-3 is optimum
because even piperidine, a secondary amine, reacted with
17 to produce the L-ido-aminosugar as a major compo-
nent. The application of these amination reactions for the
generation of a wide variety of intermediates for poly-
hydroxylated piperidines and other related molecules as
well as the diastereoselectivity of addition of carbon
nucleophiles to these systems are currently being ex-
plored.
Experimental Section
FIGURE 3. ORTEP diagram of compound 20h. Only one
molecule of the crystallographic asymmetric unit is shown with
the H-atom attached to C-5.
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
plate dipped in 5% H2SO4-MeOH solution. Column chroma-
tography 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. Compound 7 was synthesized from 3-O-benzyl-1,2-O-
isopropylidene-6-O-tosyl-R-D-glucofuranose following a re-
ported procedure.15a Compounds 815b and 915c were synthesized
from the corresponding tosyl derivatives following the same
route.
as L-ido isomers, compounds 20d and 20e were also
assigned the L-ido configuration.
To explain the diastereoselectivity of addition of amines
to 16-18, one could postulate the formation of an
H-bonded precursor having the geometry of a six-
membered ring (Figure 4). This system fixes the transi-
tion state in the L-ido configuration. It may be argued
that the stereoelectronic interactions between the R
group (OBn/OMe/H) would allow the amine nucleophile
to take up the position as shown in Figure 4. Minimum
interactions of primary amines with OBn (compound 16)
or OMe (compound 17) allow the amines to attack C-5
in a diastereoselective fashion via the H-bonded inter-
mediate. A more severe interaction of OBn (compound
16) with a bulky secondary amine piperidine does not
General Procedure for the Synthesis of Sulfides 10-
12. To a well-stirred solution of 7, 8, or 9 in DMF (4 mL/mmol)
were added p-thiocresol (5 equiv/mmol) and NaOMe (2.5 equiv/
J. Org. Chem, Vol. 70, No. 20, 2005 8051

Das et al.
1
mmol). The mixture was heated at 100-120 °C with stirring
for 4-5 h under N2. After completion of the reaction (TLC),
the reaction mixture was poured into a saturated solution of
NaHCO3, and the product was extracted with EtOAc (3 × 10
mL). The combined organic layers were dried over anhyd Na2-
SO4 and filtered, and the filtrate was concentrated under
reduced pressure to get a gummy residue. The residue was
purified over silica gel column to afford sulfides 10-12.
General Procedure for the Synthesis of Sulfones 13-
15. To a well-stirred solution of sulfides 10, 11, or 12 in dry
MeOH (10 mL/mmol) was added magnesium monoperoxyph-
thalate hexahydrate (2.5 equiv/mmol), and the mixture was
stirred for 6 h under N2. After completion of the reaction (TLC),
MeOH was evaporated to dryness under reduced pressure, and
the residue was dissolved in satd NaHCO3. The aqueous part
was washed with EtOAc (3 × 10 mL). The combined organic
layers were dried over anhyd Na2SO4 and filtered, and the
filtrate was concentrated under reduced pressure to get a
residue. The residue was purified over silica gel column to
obtain sulfones 13-15.
General Procedure for the Synthesis of Vinyl Sulfone-
Modified Carbohydrates 16-18. To a well-stirred solution
of sulfones 13, 14, or 15 in pyridine (5 mL/mmol) was added
methanesulfonyl chloride (4 equiv/mmol) in pyridine (1 mL/
mmol of MsCl) dropwise at 0 °C under N2. After completion of
the addition, the reaction mixture was kept at 4 °C. After 16
h (TLC), the reaction mixture was poured into ice-cold water,
and the aqueous layer was washed with EtOAc (3 × 10 mL).
The combined organic layers were dried over anhyd Na2SO4
and filtered, and the filtrate was concentrated under reduced
pressure to get a residue. The residue was heated under reflux
with pyridine (4 mL/mmol). After 2 h (TLC), the reaction
mixture was poured into ice-cold water, and the aqueous layer
was extracted with EtOAc (3 × 10 mL). The combined organic
layers were dried over anhyd 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 16-18.
General Procedure for the Synthesis of 20a-i and
21a-i. A mixture of 16, 17, or 18 and the appropriate amine
(neat; 5 equiv/mmol) was stirred at ambient temperature. After
completion of the reaction (TLC), satd NH4Cl solution was
added, and the mixture was extracted with EtOAc (3 × 10 mL).
The combined organic layers were dried over anhyd 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 20a-i and 21a-i.
Eluent: EtOAc/petroleum ether (1:5). Yellow gum. H NMR
(CDCl3): δ 1.34 (s, 3H), 1.57 (s, 3H), 2.30 (s, 3H), 2.93 (dd, J
) 9.3, 13.8 Hz, 1H), 3.13 (dd, J ) 3.5, 14.0 Hz, 1H), 3.88-4.00
(m, 2H), 4.09 (dd, J ) 3.2, 8.6 Hz, 1H), 4.56 (m, 2H), 4.75 (d,
J ) 12.0 Hz, 1H), 5.72 (d, J ) 3.6 Hz, 1H), 7.08 (d, J ) 8.1 Hz,
2H), 7.24-7.37 (m, 7H). 13C NMR (CDCl3): δ 20.9, 26.5, 26.7,
37.7, 68.8, 72.0, 77.0, 77.6, 79.8, 104.0, 113.0, 127.9, 128.0,
128.4, 129.7, 130.7, 131.3, 136.6, 137.2. Anal. Calcd for
C23H28O5S: C, 66.32; H, 6.78. Found: C, 66.02; H, 6.50.
3-O-Benzyl-1,2-O-isopropylidene-(6-C-p-tolylsulfonyl)-
R-D-gluco-1,4-furanose 13. Compound 10 (2.8 g, 6.72 mmol)
was converted to 13 following the general procedure (2.8 g,
95%). Eluent: EtOAc/petroleum ether (1:2). White needles. 1H
NMR (CDCl3): δ 1.27 (s, 3H), 1.44 (s, 3H), 2.43 (s, 3H), 3.26
(dd, J ) 10.1, 14.4 Hz, 1H), 3.58 (dd, J ) 3.1, 14.4 Hz, 1H),
4.06 (m, 2H), 4.41-4.69 (m, 4H), 5.80 (d, J ) 3.7 Hz, 1H),
7.27-7.37 (m, 7H), 7.77 (d, J ) 8.3 Hz, 2H). 13C NMR
(CDCl3): δ 21.5, 26.1, 26.7, 59.8, 64.0, 72.4, 81.0, 81.4, 82.3,
104.9, 111.9, 127.7, 127.8, 128.0, 128.5, 129.9, 136.2, 137.2,
144.9. Anal. Calcd for C23H28O7S: C, 61.59; H, 6.29. Found:
C, 61.22; H, 6.21.
1,2-O-Isopropylidene-3-O-methyl-(6-C-p-tolylsulfonyl)-
R-D-gluco-1,4-furanose 14. Compound 11 (1.6 g, 4.7 mmol)
was converted to 14 following the general procedure (1.6 g,
1
92%). Eluent: EtOAc/petroleum ether (1:3). Yellow gum. H
NMR (CDCl3): δ 1.29 (s, 3H), 1.44 (s, 3H), 2.45 (s, 3H), 3.28
(dd, J ) 10.0, 14.5 Hz, 1H), 3.41 (s, 3H), 3.58 (dd, J ) 1.6,
14.3 Hz, 1H), 3.84 (d, J ) 3.1 Hz, 1H), 4.02 (dd, J ) 3.1, 8.0
Hz, 1H), 4.39-4.43 (m, 1H), 4.53 (d, J ) 3.7 Hz, 1H), 5.79 (d,
J ) 3.7 Hz, 1H), 7.36 (d, J ) 8.2 Hz, 2H), 7.81 (d, J ) 8.3 Hz,
2H). 13C NMR (CDCl3): δ 21.5, 26.1, 26.7, 58.1, 60.0, 63.9, 81.3,
81.5, 83.2, 104.9, 111.8, 127.8, 129.9, 136.5, 144.9. Anal. Calcd
for C17H24O7S: C, 54.82; H, 6.50. Found: C, 55.22; H, 6.53.
3-O-Benzyl-1,2-O-isopropylidene-(6-C-p-tolylsulfonyl)-
R-D-allo-1,4-furanose 15. Compound 12 (0.98 g, 2.34 mmol)
was converted to 15 following the general procedure (1.0 g,
1
96%). Eluent: EtOAc/petroleum ether (1:2). Yellow gum. H
NMR (CDCl3): δ 1.32 (s, 3H), 1.53 (s, 3H), 2.44 (s, 3H), 3.25
(m, 2H), 3.91 (m, 2H), 4.35 (m, 1H), 4.54 (m, 2H), 4.73 (d, J )
11.6 Hz, 1H), 5.69 (d, J ) 3.6 Hz, 1H), 7.25-7.36 (m, 7H), 7.76
(d, J ) 8.2 Hz, 2H). 13C NMR (CDCl3): δ 21.5, 26.4, 26.7, 58.5,
65.3, 72.0, 76.6, 77.3, 79.7, 104.0, 113.0, 127.9, 128.0, 128.4,
129.4, 129.8, 136.1, 136.9, 144.9. Anal. Calcd for C23H28O7S:
C, 61.59; H, 6.29. Found: C, 61.26; H, 6.20.
3-O-Benzyl-5,6-didehydro-5,6-dideoxy-(E)- and 3-O-
Benzyl-5,6-didehydro-5,6-dideoxy-(Z)-1,2-O-isopropyl-
idene-(6-C-p-tolylsulfonyl)-R-D-gluco-1,4-furanose 16. Com-
pound 13 (2.8 g, 5.3 mmol) was converted to 16 (mixture)
following the general procedure (2.0 g, 90%). Eluent: EtOAc/
petroleum ether (1:3). Yellow solid. 1H NMR (CDCl3): E-isomer
δ 1.27 (s, 3H), 1.45 (s, 3H), 2.40 (s, 3H), 4.02 (d, J ) 3.3 Hz,
1H), 4.46 (d, J ) 11.9 Hz, 1H), 4.56 (s, 1H), 4.63 (d, J ) 8.1
Hz, 1H), 4.87-4.82 (m, 1H), 5.94 (d, J ) 3.7 Hz, 1H), 6.69 (dd,
J ) 1.8, 15.0 Hz, 1H), 6.96 (dd, J ) 3.8, 15.0 Hz, 1H), 7.22-
7.36 (m, 7H), 7.72 (d, J ) 8.3 Hz, 2H); Z-isomer δ 1.33 (s, 3H),
1.55 (s, 3H), 2.43 (s, 3H), 4.34 (d, J ) 3.3 Hz, 1H), 4.56-4.65
(m, 3H), 5.74 (m, 1H), 5.98 (d, J ) 3.7 Hz, 1H), 6.39 (m, 2H),
7.25-7.34 (m, 7H), 7.77 (d, J ) 8.3 Hz, 2H).
3-O-Benzyl-1,2-O-isopropylidene-(6-C-p-tolyl sulfide)-
R-D-gluco-1,4-furanose 10. Compound 7 (2.2 g, 7.53 mmol)
was converted to 10 following the general procedure (2.9 g,
1
93%). Eluent: EtOAc/petroleum ether (1:5). Yellow gum. H
NMR (CDCl3): δ 1.30 (s, 3H), 1.44 (s, 3H), 2.30 (s, 3H), 2.96
(dd, J ) 7.8, 13.9 Hz, 1H), 3.33 (dd, J ) 3.4, 13.9 Hz, 1H),
4.06 (m, 3H), 4.50-4.71 (m, 3H), 5.90 (d, J ) 3.8 Hz, 1H), 7.08
(d, J ) 8.1 Hz, 2H), 7.26-7.37 (m, 7H). 13C NMR (CDCl3): δ
20.7, 26.0, 26.5, 39.6, 66.8, 71.9, 81.5, 82.0, 104.8, 111.4, 127.5,
127.7, 128.2, 129.5, 130.0, 131.4, 136.0, 137.0. Anal. Calcd for
C23H28O5S‚1/4H2O: C, 65.61; H, 6.82. Found: C, 65.49; H, 6.79.
1,2-O-Isopropylidene-3-O-methyl-(6-C-p-tolyl sulfide)-
R-D-gluco-1,4-furanose 11. Compound 8 (1.9 g, 8.8 mmol) was
converted to 11 following the general procedure (2.6 g, 88%).
3-O-Benzyl-4,5-didehydro-5,6-dideoxy-1,2-O-isopropyl-
idene-(6-C-p-tolylsulfonyl)-R-D-gluco-1,4-furanose 16A:
Method A. Compound 13 (0.2 g, 0.45 mmol) was mesylated
following the general procedure. A solution of the crude
mesylated product in dichloromethane (10 mL) was treated
with DBU (0.13 mL, 0.9 mmol) for 10 min at ambient
temperature. Solvent was evaporated under reduced pressure,
and the resulting residue was purified over silica gel to afford
16A (0.18 g, 95%). Method B. A solution of 16 (0.11 g, 0.25
mmol) in dichloromethane (10 mL) was treated with DBU (0.07
mL, 0.3 mmol) for 3 h at ambient temperature. Usual workup
and purification afforded 16A (0.1 g, 91%). Eluent: EtOAc/
petroleum ether (1:3). White crystals. Mp: 110 °C. [R]29D -94.2
(c 0.32, CHCl3). 1H NMR (CDCl3): δ 1.22 (s, 3H), 1.32 (s, 3H),
1
Eluent: EtOAc/petroleum ether (1:6). Yellow gum. H NMR
(CDCl3): δ 1.31 (s, 3H), 1.46 (s, 3H), 2.30 (s, 3H), 3.00 (dd, J
) 8.2, 13.9 Hz, 1H), 3.38 (m, 1H), 3.42 (s, 3H), 3.85 (d, J ) 3.0
Hz, 1H), 3.93-4.11 (m, 2H), 4.56 (d, J ) 3.8 Hz, 1H), 5.88 (d,
J ) 3.8 Hz, 1H), 7.08 (d, J ) 7.9 Hz, 2H), 7.30 (d, 2H). 13C
NMR (CDCl3): δ 20.9, 26.2, 26.7, 39.8, 57.9, 67.2, 81.5, 84.2,
105.0, 111.6, 129.7, 130.0, 131.6, 136.4. Anal. Calcd for
C17H24O5S‚1H2O: C, 56.96; H, 7.30. Found: C, 56.56; H, 7.28.
3-O-Benzyl-1,2-O-isopropylidene-(6-C-p-tolylsulfide)-R-
D-allo-1,4-furanose 12. Compound 9 (1.2 g, 4.1 mmol) was
converted to 12 following the general procedure (1.5 g, 88%).
8052 J. Org. Chem., Vol. 70, No. 20, 2005

Diastereoselective and General Route to 5-Amino-5-deoxysugars
2.40 (s, 3H), 3.84-4.10 (m, 2H), 4.22 (m, 1H), 4.38-4.73 (m,
4H), 5.92 (d, J ) 3.1 Hz, 1H), 7.24-7.40 (m, 7H), 7.78 (d, J )
8.2 Hz, 2H). 13C NMR (CDCl3): δ 21.5, 27.0, 27.6, 53.8, 70.4,
80.1, 82.8, 90.6, 107.0, 114.2, 127.8, 128.0, 128.4, 128.5, 129.6,
136.0, 136.8, 144.4, 157.7. Anal. Calcd for C23H26O6S‚2H2O:
C, 59.21; H, 6.48. Found: C, 59.06; H, 6.09.
5,6-Didehydro-5,6-dideoxy-(E)- and 5,6-didehydro-5,6-
dideoxy-(Z)-1,2-O-isopropylidene-3-O-methyl-(6-C-p-tolyl-
sulfonyl)-R-D-gluco-1,4-furanose 17. Compound 14 (1.6 g,
4.30 mmol) was converted to 17 (mixture) following the general
procedure (1.3 g, 88%). Eluent: EtOAc/petroleum ether (1:3).
Yellow gum.1H NMR (CDCl3): E-isomer δ 1.30 (s, 3H), 1.46
(s, 3H), 2.42 (s, 3H), 3.35 (s, 3H), 3.81 (d, J ) 3.1 Hz, 1H),
4.59 (d, J ) 3.7 Hz, 1H), 4.83 (m, 1H), 5.90 (d, J ) 3.7 Hz,
1H), 6.62 (dd, J ) 1.8, 15.0 Hz, 1H), 6.96 (dd, J ) 3.8, 15.0
Hz, 1H), 7.32 (d, J ) 8.1 Hz, 2H), 7.74 (d, J ) 8.1 Hz, 2H);
Z-isomer δ 1.34 (s, 3H), 1.56 (s, 3H), 2.44 (s, 3H), 3.39 (s, 3H),
4.10 (d, J ) 3.2 Hz, 1H), 4.62 (d, J ) 3.8 Hz, 1H), 5.72 (m,
1H), 5.95 (d, J ) 3.8 Hz, 1H), 6.35 (m, 2H), 7.37 (d, J ) 8.2
Hz, 2H), 7.76 (d, J ) 8.2 Hz, 2H).
3-O-Benzyl-5,6-didehydro-5,6-dideoxy-(E)-1,2-O-isopro-
pylidene-(6-C-p-tolylsulfonyl)-R-D-allo-1,4-furanose 18.
Compound 15 (0.5 g, 1.11 mmol) was converted to 18 following
the general procedure (0.4 g, 84%). Eluent: EtOAc/petroleum
ether (1:4). Yellow gum. [R]29D +18.3 (c 0.18, CHCl3). 1H NMR
(CDCl3): δ 1.34 (s, 3H), 1.56 (s, 3H), 2.42 (s, 3H), 3.52 (dd, J
) 3.9, 9.2 Hz, 1H), 4.55-4.75 (m, 4H), 5.72 (d, J ) 3.6 Hz,
1H), 6.62 (dd, J ) 1.9, 15.1 Hz, 1H), 6.99 (dd, J ) 3.9, 15.2
Hz, 1H,), 7.25-7.38 (m, 7H), 7.72 (d, J ) 8.3 Hz, 2H). 13C NMR
(CDCl3): δ 21.5, 26.3, 26.6, 72.4, 76.1, 77.2, 81.4, 103.9, 113.4,
127.7, 128.0, 128.2, 128.5, 129.8, 131.4, 136.7, 137.0, 140.8,
144.4. Anal. Calcd for C23H26O6S‚1/2H2O: C, 62.85; H, 6.19.
Found: C, 62.49; H, 5.96.
petroleum ether (1:2). Yellow gum. [R]29D -14.1 (c 0.55, CHCl3).
1H NMR (CDCl3): δ 0.95 (d, J ) 6.1 Hz, 6H), 1.29 (s, 3H),
1.46 (s, 3H), 2.42 (s, 3H), 2.85 (m, 1H), 3.27 (m, 1H), 3.52 (dd,
J ) 3.7, 14.8 Hz, 1H), 3.60 (m, 1H), 4.03 (d, J ) 3.3 Hz, 1H),
4.32 (m, 1H), 4.47 (d, J ) 11.7 Hz, 1H), 4.55 (d, J ) 3.9 Hz,
1H), 4.66 (d, J ) 11.7 Hz, 1H), 5.87 (d, J ) 3.9 Hz, 1H), 7.26-
7.36 (m, 7H), 7.71 (d, J ) 8.2 Hz, 2H). 13C NMR (CDCl3): δ
21.3, 22.9, 23.3, 26.2, 26.7, 46.6, 50.0, 57.9, 71.8, 80.4, 81.6,
82.4, 104.8, 111.6, 127.9, 128.1, 128.6, 129.6, 136.9, 137.3,
144.2. Anal. Calcd for C26H35O6NS‚1H2O: C, 61.51; H, 6.94;
N, 2.76. Found: C, 61.01; H, 7.14; N, 2.69.
5,6-Dideoxy-5-isopropylamino-1,2-O-isopropylidene-3-
O-methyl-(6-C-p-tolylsulfonyl)-â-L-ido-1,4-furanose 20e.
Compound 17 (0.25 g, 0.71 mmol) was converted to 20e
following the general procedure (0.23 g, 78%). Eluent: EtOAc/
petroleum ether (1:2). Yellow gum. [R]29D -23.4 (c 0.95, CHCl3).
1H NMR (CDCl3): δ 0.99 (m, 6H), 1.30 (s, 3H), 1.47 (s, 3H),
2.44 (s, 3H), 2.89 (m, 1H), 3.24 (m, 1H), 3.34 (s, 3H), 3.52 (m,
2H), 3.79 (d, J ) 3.3 Hz, 1H), 4.29 (m, 1H), 4.50 (d, J ) 3.9
Hz, 1H), 5.84 (d, J ) 3.9 Hz, 1H), 7.34 (d, J ) 8.0 Hz, 2H),
7.79 (d, J ) 8.2 Hz, 2H). 13C NMR (CDCl3): δ 21.2, 22.7, 23.0,
25.9, 26.3, 46.3, 49.8, 56.9, 57.8, 80.3, 80.6, 84.4, 104.4, 111.2,
127.6, 129.4, 136.8, 144.1. Anal. Calcd for C20H31O6NS‚
1/4H2O: C, 57.46; H, 7.59; N, 3.35. Found: C, 57.29; H, 7.39;
N, 3.24.
3-O-Benzyl-5,6-dideoxy-5-isopropylamino-1,2-O-isopro-
pylidene-(6-C-p-tolylsulfonyl)-R-D-allo- and -â-L-talo-1,4-
furanose 20f and 21f. Compound 18 (0.2 g, 0.46 mmol) was
converted to an inseparable mixture of two diastereomers 20f/
21f (3:2) following the general procedure (0.21 g, 91%).
Eluent: EtOAc/petroleum ether (1:2). Yellow gum. Selected
NMR data of the mixture: 1H NMR (CDCl3): δ 0.97-0.92 (m,
12H), 2.43 (each s, 6H), 5.64/5.66 (each d, 2H).
3-O-Benzyl-5-benzylamino-5,6-dideoxy-1,2-O-isopropyl-
idene-(6-C-p-tolylsulfonyl)-â-L-ido-1,4-furanose 20a. Com-
pound 16 (0.35 g, 0.813 mmol) was converted to 20a following
3-O-Benzyl-5,6-dideoxy-1,2-O-isopropylidene-5-piperi-
dino-(6-C-p-tolylsulfonyl)-R-D-gluco- and -â-L-ido-1,4-
furanose 20g and 21g. Compound 16 (0.27 g, 0.63 mmol) was
converted to an inseparable mixture of two diastereomers 20g/
21g (1:1) following the general procedure (0.28 g, 88%).
Eluent: EtOAc/petroleum ether (1:3). Yellow gum. Selected
NMR of the mixture: 1H NMR (CDCl3) δ 0.88-1.31 (m, 12H),
2.31 (m, 4H), 2.41/2.39 (each s, 6H), 2.58 (m, 4H), 5.88/5.92
(each d, 2H).
5,6-Dideoxy-1,2-O-isopropylidene-3-O-methyl-5-piperi-
dino-(6-C-p-tolylsulfonyl)-â-L-ido-1,4-furanose 20h. Com-
pound 17 (0.27 g, 0.759 mmol) was converted to 20h following
the general procedure (0.23 g, 69%). Eluent: EtOAc/petroleum
ether (1:3). Yellow crystalline solid. Mp: 135 °C. [R]29D -80.5
(c 0.3, CHCl3). 1H NMR (CDCl3): δ 1.01 (m, 2H), 1.23 (m, 4H),
1.30 (s, 3H), 1.45 (s, 3H), 2.32 (m, 2H), 2.45 (s, 3H), 2.61 (m,
2H), 2.94 (m, 1H), 3.39 (s, 3H), 3.43 (m, 2H), 3.53 (d, J ) 3.1
Hz, 1H), 4.18 (m, 1H), 4.53 (d, J ) 3.9 Hz, 1H), 5.86 (d, J )
3.9 Hz, 1H), 7.31 (d, J ) 8.0 Hz, 2H), 7.80 (d, J ) 8.2 Hz, 2H).
13C NMR (CDCl3): δ 21.9, 24.7, 26.2, 26.6, 27.2, 55.9, 57.8,
59.4, 79.1, 80.9, 85.2, 105.1, 111.9, 128.7, 129.7, 138.3, 144.2.
Anal. Calcd for C22H33O6NS: C, 60.11; H, 7.57; N, 3.19.
Found: C, 60.34; H, 7.84; N, 3.05.
3-O-Benzyl-5,6-dideoxy-1,2-O-isopropylidene-5-piperi-
dino-(6-C-p-tolylsulfonyl)-R-D-allo- and -â-L-talo-1,4-fura-
nose 20i and 21i. Compound 18 (0.17 g, 0.39 mmol) was
converted to an inseparable mixture of two diastereomers 20i/
21i (1:1) following the general procedure (0.13 g, 63%).
Eluent: EtOAc/petroleum ether (1:3). Yellow gum. Selected
NMR data of the mixture: 1H NMR (CDCl3): δ 1.23-1.31 (m,
12H), 2.26 (m, 4H), 2.44 (s, 6H), 2.58 (m, 4H), 5.65/5.83 (each
d, 2H).
3-O-Benzyl-5-benzylamino-5,6-dideoxy-1,2-O-isopropyl-
idene-â-L-ido-1,4-furanose 23: Method A. To a well-stirred
solution of 20a (0.4 g, 0.74 mmol) in dry THF (10 mL) was
added LAH (5 equiv/mmol) at 0 °C under Ar, and the mixture
was stirred at ambient temperature. After completion of the
reaction (TLC), satd NH4Cl solution was added, and the
product was extracted with EtOAc (3 × 10 mL). The combined
the general procedure (0.37 g, 83%). Eluent: EtOAc/petroleum
1
ether (1:3). Yellow gum. [R]29 -28.5 (c 0.5, CHCl3). H NMR
D
(CDCl3): δ 1.29 (s, 3H), 1.44 (s, 3H), 2.40 (s, 3H), 3.34 (m, 1H),
3.43 (dd, J ) 3.4, 14.8 Hz, 1H), 3.54 (m, 1H), 3.74 (s, 2H), 3.98
(d, J ) 3.25 Hz, 1H), 4.30 (m, 1H), 4.47 (d, J ) 11.6 Hz, 1H),
4.55 (d, J ) 3.9 Hz, 1H), 4.64 (d, J ) 11.6 Hz, 1H), 5.87 (d, J
) 3.9 Hz, 1H), 7.16-7.33 (m, 12H), 7.65 (d, J ) 8.2 Hz, 2H).
13C NMR (CDCl3): δ 22.0, 26.7, 27.2, 52.3, 53.0, 57.6, 72.2,
80.6, 82.1, 82.7, 105.2, 112.1, 127.3, 128.4, 128.5, 128.7, 129.0,
130.2, 137.3, 140.4, 144.8. Anal. Calcd for C30H35O6NS: C,
67.02; H, 6.56; N, 2.61. Found: C, 67.40; H, 6.54; N, 2.45.
5-Benzylamino-5,6-dideoxy-1,2-O-isopropylidene-3-O-
methyl-(6-C-p-tolylsulfonyl)-â-L-ido-1,4-furanose 20b. Com-
pound 17 (0.29 g, 0.824 mmol) was converted to 20b following
the general procedure (0.31 g, 82%). Eluent: EtOAc/petroleum
1
ether (1:3). Yellow gum. [R]29 -30.8 (c 0.7, CHCl3). H NMR
D
(CDCl3): δ 1.29 (s, 3H), 1.45 (s, 3H), 2.42 (s, 3H), 3.30 (s, 3H),
3.32-3.48 (m, 3H), 3.73 (d, J ) 3.3 Hz, 1H), 3.79 (s, 2H), 4.28
(m, 1H), 4.50 (d, J ) 3.9 Hz, 1H), 5.85 (d, J ) 3.9 Hz, 1H),
7.22-7.31 (m, 7H), 7.70 (d, J ) 8.3 Hz, 2H). 13C NMR
(CDCl3): δ 22.0, 26.6, 27.1, 52.3, 52.8, 57.7, 57.8, 80.9, 81.4,
85.0, 105.2, 112.0, 127.4, 128.5, 128.7, 128.8, 130.0, 130.2,
137.1, 140.5, 144.9. Anal. Calcd for C24H31O6NS‚1/2H2O: C,
61.25; H, 6.85; N, 2.98. Found: C, 61.49; H, 6.73; N, 3.0.
3-O-Benzyl-5-benzylamino-5,6-dideoxy-1,2-O-isopropyl-
idene-(6-C-p-tolylsulfonyl)-R-D-allo- and -â-L-talo-1,4-
furanose 20c and 21c. Compound 18 (0.22 g, 0.51 mmol) was
converted to an inseparable mixture of two diastereomers 20c/
21c (1:1) following the general procedure (0.22 g, 83%).
Eluent: EtOAc/petroleum ether (1:3). Yellow gum. Selected
NMR data of the mixture: 1H NMR (CDCl3): δ 2.41/2.42 (each
s, 6H), 3.75 (s, 4H), 5.60/5.64 (each d, 2H).
3-O-Benzyl-5,6-dideoxy-5-isopropylamino-1,2-O-isopro-
pylidene-(6-C-p-tolylsulfonyl)-â-L-ido-1,4-furanose 20d.
Compound 16 (0.23 g, 0.53 mmol) was converted to 20d
following the general procedure (0.19 g, 73%). Eluent: EtOAc/
J. Org. Chem, Vol. 70, No. 20, 2005 8053

Das et al.
organic layers were dried over anhyd Na2SO4 and filtered, and
the filtrate was concentrated under reduced pressure to get a
residue. The residue was benzylated to afford compound 23
(0.17 g, 58%). Method B. To a well-stirred solution of 20a (0.3
g, 0.56 mmol) in dry MeOH (10 mL) was added Mg turnings
(20 equiv/mmol) at 0 °C under Ar. Then the mixture was
stirred at ambient temperature. Solvent was evaporated to
dryness under reduced pressure. The resulting residue was
dissolved in EtOAc (20 mL) and filtered. The filtrate was
washed with water, dried over anhyd Na2SO4, and filtered,
and the filtrate was concentrated under reduced pressure to
get a residue. The residue was purified over silica gel column
144.1. Anal. Calcd for C23H28O7S: C, 61.59; H, 6.29. Found:
C, 62.02; H, 5.97.
3-O-Benzyl-5-benzylamino-5,6-dideoxy-1,2-O-isopropyl-
idene-R-D-gluco-1,4-furanose 28. A mixture of 27 (0.3 g, 0.26
mmol) and neat benzylamine was heated in an oil bath at 100
°C for 14 h. After usual workup and purification, compound
28 was isolated (0.2 g, 78%). Eluent: EtOAc/petroleum ether
(1:3). Yellow oil. [R]29 -56.2 (c 0.45, CHCl3). 1H NMR
D
(CDCl3): δ 1.25 (d, J ) 6.4 Hz, 3H), 1.31 (s, 3H), 1.47 (s, 3H),
3.20 (m, 1H), 3.67 (d, J ) 13.0 Hz, 1H), 3.88 (m, 2H), 4.05 (d,
J ) 3.2 Hz, 1H), 4.49 (d, J ) 11.7 Hz, 1H), 4.62 (d, J ) 3.9 Hz,
1H), 4.69 (d, J ) 11.7 Hz, 1H), 5.91 (d, J ) 3.9 Hz, 1H), 7.18-
7.27 (m, 10H). 13C NMR (CDCl3): δ 17.7, 26.2, 26.6, 50.7, 51.0,
71.7, 81.4, 81.8, 84.4, 104.7, 111.3, 126.8, 127.7, 127.8, 127.9,
128.3, 128.4, 137.3, 140.4. Anal. Calcd for C23H29O4N: C, 72.04;
H, 7.62; N, 3.65. Found: C, 72.05; H, 7.71; N, 3.71.
to afford compound 23 (0.09 g, 44%). Eluent: EtOAc/petroleum
1
ether (1:2). Yellow oil. [R]29 -10.5 (c 0.65, CHCl3). H NMR
D
(CDCl3): δ 0.98 (d, J ) 6.5 Hz, 3H), 1.31 (s, 3H), 1.47 (s, 3H),
3.21 (m, 1H), 3.75 (d, J ) 12.6 Hz, 1H), 3.98 (m, 2H), 4.05 (dd,
J ) 3.0, 9.1 Hz, 1H), 4.47 (d, J ) 11.7 Hz, 1H), 4.65 (m, 2H),
5.92 (d, J ) 3.8 Hz, 1H), 7.20-7.32 (m, 10H). 13C NMR
(CDCl3): δ 15.6, 26.2, 26.6, 29.6, 51.4, 51.8, 71.7, 81.5, 81.7,
84.2, 104.7, 111.5, 126.7, 127.9, 128.0, 128.2, 128.3, 128.4,
137.1, 140.4. Anal. Calcd for C23H29O4N‚1/4H2O: C, 71.20; H,
7.66; N, 3.61. Found: C, 71.45; H, 7.57; N, 3.58.
3-O-Benzyl-5-benzylamino-5,6-dideoxy-1,2-O-isopropyl-
idene-â-L-ido-1,4-furanose 23. A mixture of 2516a (0.26 g,
0.58 mmol) and neat benzylamine was heated in an oil bath
at 100 °C for 13 h. After usual workup and purification,
compound 23 was isolated (0.15 g, 69%).
5-Benzylamino-5,6-dideoxy-1,2-O-isopropylidene-3-O-
methyl-â-L-ido-1,4-furanose 24. A mixture of 26 (0.28 g, 0.75
mmol) and neat benzylamine was heated in an oil bath at 100
°C for 10 h. After usual workup and purification, compound
24 was isolated (0.09 g, 40%).
Crystal data of 20h: C22H33NO6S, M ) 439.56, monoclinic,
a ) 13.948(5) Å, b ) 11.955(5) Å, c ) 14.073(6) Å, â ) 95.826-
(9)°, U ) 2334(2) Å3, T ) 295(2) K, space group P21(No. 4), Z
) 2, µ(Mo KR) ) 0.175 mm-1, 7863 reflections processed, 5717
unique (Rint ) 0.028), which were used in refinement, wR(F2)
was 0.0786 for all data. The compound crystallized in mono-
clinic cell with two molecules in the asymmetric unit. The two
molecules in the asymmetric unit differ only slightly.
5-Benzylamino-5,6-dideoxy-1,2-O-isopropylidene-3-O-
methyl-â-L-ido-1,4-furanose 24. Compound 20b (0.35 g, 0.76
mmol) was converted to 24 by LAH/THF (0.18 g, 78%) or by
Mg/MeOH (0.12 g, 52%) following the procedure mentioned
above. Eluent: EtOAc/petroleum ether (1:2). Yellow oil. [R]29
D
-31.3 (c 0.9, CHCl3). 1H NMR (CDCl3): δ 1.09 (d, J ) 6.2 Hz,
3H), 1.31 (s, 3H), 1.47 (s, 3H), 3.10 (m, 1H), 3.39 (s, 3H), 3.64
(d, J ) 3.1 Hz, 1H), 3.71 (d, J ) 12.7 Hz, 1H), 3.89 (d, J )
12.9 Hz, 1H), 3.98 (dd, J ) 3.0, 9.0 Hz, 1H), 4.57 (d, J ) 3.9
Hz, 1H), 5.90 (d, J ) 3.9 Hz, 1H), 7.24-7.32 (m, 5H). 13C NMR
(CDCl3): δ 16.2, 26.7, 27.1, 51.8, 52.3, 57.9, 81.7, 84.4, 84.7,
105.2, 111.9, 127.2, 128.6, 128.8, 140.9. Anal. Calcd for
C17H25O4N: C, 66.43; H, 8.20; N, 4.56. Found: C, 66.07; H,
8.0; N, 4.77.
Acknowledgment. This work has been supported
by a research grant from the Department of Science and
Technology, New Delhi, India. I.D. thanks the Council
of Scientific and Industrial Research, New Delhi, India,
for a fellowship. T.P. and I.D. thank Mr. Amritraj Patra
for carrying out a few preliminary experiments.
3-O-Benzyl-6-deoxy-1,2-O-isopropylidene-5-O-tosyl-â-
L-ido-1,4-furanose 27. 3-O-Benzyl-6-deoxy-1,2-O-isopropy-
lidene-â-L-ido-1,4-furanose16c (0.8 g, 2.72 mmol) was tosylated
to afford compound 27 (1.12 g, 92%). Eluent: EtOAc/petroleum
1
ether (1:5). Yellow gum. [R]29 -4.1 (c 0.25, CHCl3). H NMR
D
(CDCl3): δ 1.26 (d, J ) 6.7 Hz, 3H), 1.28 (s, 3H), 1.55 (s, 3H),
2.41 (s, 3H), 3.82 (d, J ) 3.3 Hz, 1H), 4.08 (dd, J ) 3.4, 8.5
Hz, 1H), 4.4 (d, J ) 11.7 Hz, 1H), 4.5 (d, J ) 3.9 Hz, 1H), 4.6
(d, J ) 11.7 Hz, 1H), 4.84 (m, 1H), 5.74 (d, J ) 3.9 Hz, 1H),
7.18-7.41 (m, 7H), 7.82 (d, J ) 8.3 Hz, 2H). 13C NMR
(CDCl3): δ 17.2, 21.5, 26.1, 26.6, 71.5, 78.2, 81.2, 81.4, 81.6,
104.9, 111.6, 127.9, 128.0, 128.1, 128.5, 129.3, 134.1, 136.4,
Supporting Information Available: Crytallographic in-
formation file for 20h. This material is available free of charge
via the Internet at http://pubs.acs.org.
JO051143C
8054 J. Org. Chem., Vol. 70, No. 20, 2005