Diastereoselective Michael initiated ring closure on vinyl sulfone-modified carbohydrates: A stereospecific and general route to α-substituted cyclopropanes

Article abstract of DOI:10.1021/jo701378d

(Chemical Equation Presented) Suitably designed vinyl sulfone-modified furanosides act as substrates for Michael initiated ring closure reactions yielding cyclopropanated carbohydrates. The strategy is general in nature and gives access to cyclopropanes w

Full text of DOI:10.1021/jo701378d

Diastereoselective Michael Initiated Ring Closure on Vinyl
Sulfone-Modified Carbohydrates: A Stereospecific and General
Route to r-Substituted Cyclopropanes
Indrajit Das, Tarun K. Pal, and Tanmaya Pathak*
Department of Chemistry, Indian Institute of Technology, Kharagpur 721 302, India
tpathak@chem.iitkgp.ernet.in
ReceiVed June 30, 2007
Suitably designed vinyl sulfone-modified furanosides act as substrates for Michael initiated ring closure
reactions yielding cyclopropanated carbohydrates. The strategy is general in nature and gives access to
cyclopropanes with predefined chiralities on three consecutive carbons with varying substitutions at the
R-position.
Introduction
A simple method of cyclopropane formation reported almost
three decades back3 involved the attack of a nucleophile on the
electron deficient double bond of 3-halo-1-alkenylsulfones 1
(Scheme 1; eq A; Y ) H)).4 However, desulfonylation of 2 led
Integration of cyclopropanes and carbohydrates has been
identified as an important area of research in cyclopropane
related synthetic chemistry.1 This particular combination pro-
vides access to a class of strained and reactive cyclopropanes
embedded in chiral appendages like carbohydrates. Although
study related to cyclopropanated carbohydrates is an emerging
area, chemists have long been fascinated by the cyclopropane
subunit as such because of its presence in a wide range of natural
products as well as the usefulness of this strained cycloalkane
in other areas of research.2 While unactivated cyclopropanes
have been directly utilized to a limited extent in chemical
synthesis, activated cyclopropanes, such as cyclopropanes
substituted with electron withdrawing or electron donating
groups, have been used extensively as precursors in several
chemical syntheses.2b
SCHEME 1. Michael Initiated Ring Closures with Vinyl
Sulfones
Michael initiated ring closure (MIRC) is one of the most
important strategies for the construction of cyclopropane rings.2a
to a cyclopropane derivative with only one functionalized center.
Since cyclopropanations via the MIRC reactions of acyclic
olefins are usually non-stereospecific,2a,4 we argued that a
* Corresponding author. Fax: 03222-282252.
(1) (a) Cousins, G. S.; Hoberg, J. O. Chem. Soc. ReV. 2000, 29, 165. (b)
(3) Eisch, J. J.; Galle, J. E. J. Org. Chem. 1979, 44, 3277.
(4) This type of reaction using 3-halo-1-alkenylsulfones was rarely
studied, see: (a) Ogura, K.; Iihama, T.; Takahashi, K.; Iida, H. Bull. Chem.
Soc. Jpn. 1984, 57, 3347. (c) Zindel, J.; de Meijere, A. Synthesis 1994, 2,
190.
Yu, M.; Pagenkopf, B. L. Tetrahedron 2005, 61, 321.
(2) (a) Lebel, H.; Marcoux, J.-F.; Molinaro, C.; Charette, A. B. Chem.
ReV. 2003, 103, 977. (b) Reissig, H.-U.; Zimmer, R. Chem. ReV. 2003,
103, 1151. (c) Kulinkovich, O. G. Chem. ReV. 2003, 103, 2597.
10.1021/jo701378d CCC: $37.00 © 2007 American Chemical Society
Published on Web 10/23/2007
J. Org. Chem. 2007, 72, 9181-9189
9181

Das et al.
suitably designed vinyl sulfone, such as 3, with a predesigned
chiral center (C*-Y) would generate cyclopropanes 4 with three
consecutive chiral centers provided that the first attack of the
nucleophile to 3 is stereoselective in nature (Scheme 1; eq B).
However, this hitherto unknown cyclopropanation using vinyl
sulfones would be possible only if the sulfonyl and the alkyl
chain carrying the leaving group were connected to the same
carbon of the olefin as in 3. Desulfonylation of 4 would also
generate another set of cyclopropanes with defined chiral
centers.
monoperoxyphthalate hexahydrate (MMPP) produced 5b. Me-
sylation of sulfone 5b followed by concomitant elimination of
the mesyl group afforded the vinyl sulfone 6R in 88% yield.
The â-anomeric epoxide 7 under similar reaction conditions
produced the vinyl sulfone 6â in 86% yield through intermedi-
ates 7a and 7b.
The vinyl sulfone-modified carbohydrate 6r was reacted with
NaOMe or NaOBn to obtain the cyclopropanated carbohydrates
8 and 9, respectively, in excellent yields. A bulky, sugar-derived
nucleophile, methyl-2,3-anhydro-lyxofuranoside, in the presence
of NaH easily produced disaccharide 10 in high yield (Scheme
3). Interestingly, reactions of benzylamine and the sodium salt
Results and Discussion
The diastereoselectivity of the addition of carbon and amino
nucleophiles at C-2 of vinyl sulfone-modified pent-2-enofura-
nosides was controlled by the anomeric configuration to a great
extent:5 especially carbon nucleophiles added to the C-2 position
from a direction opposite to that of the disposition of the
anomeric methoxy group (Figure 1).5b Since the first step of eq
SCHEME 3. Cyclopropanation of r-Anomeric Vinyl
Sulfonea
a Reagents and conditions: (a) NaOMe, MeOH, rt, 14 h; (b) NaH,
PhCH2OH, DMF, rt, 23 h; (c) NaH, methyl 2,3-anhydro-R-D-lyxofuranoside,
DMF, rt, 24 h; (d) (i) PhCH2NH2 (neat), rt, 1 h and (ii) K2CO3, MeOH, rt,
24 h; and (e) (i) NaH, CH2(CO2Me)2, DMF, rt, 10 h and (ii) NaH, DMF,
rt, 10 h.
of dimethylmalonate with 6r did not produce any cyclopropane
derivative but generated only addition products instead. How-
ever, these intermediates on treatment with K2CO3/MeOH or
NaH yielded cyclopropanes 11 and 12. The benzylamino
intermediate was isolated and identified as the addition product
11a. We concluded that the C-3 proton of 11a was abstracted
by K2CO3/MeOH and that the carbanion thus generated in-
tramolecularly attacked C-5 to produce 11. The amino derivative
11a did not undergo intramolecular attack by NHBn to C-5 to
produce any five-membered ring containing a bicyclic com-
pound; probably the steric bulk around the N-nucleophile in
11a increased the feasibility of formation of the cyclopropanated
carbohydrate 11 in a selective fashion. Similarly, compound 12
was also produced from the addition product of 6r and the
sodium salt of dimethylmalonate (Scheme 3). In the case of
8-10, the anions of the alcohols used were sufficiently basic
to abstract the C-3 protons, and the concomitant cyclopropane
ring formation took place. The role of the substituent at C-2 of
intermediates such as 11a, if any, remains unclear at the
moment. The other vinyl sulfone 6â, under similar conditions,
produced cyclopropanated carbohydrates 13a/13b (1:1), 14, and
15 (Scheme 4). Mg in MeOH desulfonylated 9 and 14 to
cyclopropane ethers 16 and 18, respectively, in high yields. The
aminocyclopropane 11 was desulfonylated to 17 with Mg-
NiBr2-MeOH at 60 °C in good yield (Scheme 5).5c
FIGURE 1. Attack of carbon nucleophiles to C-2 of vinyl sulfone-
modified pent-2-enofuranosides.
B (Scheme 1) (i.e. the diastereoselective addition of nucleophiles
to vinyl sulfones)3 could be achieved using a vinyl sulfone-
modified pent-2-enofuranoside, we decided to construct the vinyl
sulfone group on a carbohydrate framework having a leaving
group at the C-5 position. Therefore, vinyl sulfone-modified
carbohydrates 6R and 6â were synthesized in large scale from
easily accessible epoxides 56a and 7,6b respectively (Scheme 2).
SCHEME 2. Synthesis of Vinyl Sulfone-Modified
Carbohydratesa
a Reagents and conditions: (a) p-thiocresol, NaOMe, DMF, 100 °C, 4
h, 80-90%; (b) MMPP, MeOH, rt, 6 h; and (c) MsCl, py, 0-4 °C, 24 h,
86-88%.
(5) (a) Ravindran, B.; Sakthivel, K.; Suresh, C. G.; Pathak, T. J. Org.
Chem. 2000, 65, 2637. (b) Sanki, A. K.; Suresh, C. G.; Falgune, U. D.;
Pathak, T. Org. Lett. 2003, 5, 1285. (c) Das, I.; Pathak, T. Org. Lett. 2006,
8, 1303.
(6) (a) Baker, B. R.; Schaub, R. E.; Williams, J. H. J. Am. Chem. Soc.
1955, 77, 7. (b) Anderson, C. D.; Goodman, L.; Baker, B. R. J. Am. Chem.
Soc. 1958, 80, 5247.
Thus, R-anomeric epoxide 5 was reacted with sodium tolylthio-
late to obtain 5a in high yield. Oxidation of 5a with magnesium
9182 J. Org. Chem., Vol. 72, No. 24, 2007

Stereospecific Route to R-Substituted Cyclopropanes
SCHEME 4. Cyclopropanation of â-Anomeric Vinyl
In the â-series, compound 15 was converted to a monoester
24 that under reductive desulfonylation conditions afforded
easily a branched-chain sugar 25. In this case also, it was also
possible to convert 24 to another cyclopropanol 26 following
the route described for 23 (Scheme 7).
Sulfonea
SCHEME 7. Derivatization of â-Anomeric Cyclopropanated
Furanosidesa
a Reagents and conditions: (a) NaOMe, MeOH, rt, 12 h; (b) NaH,
PhCH2OH, DMF, rt, 21 h; (c) (i) NaH, CH2(CO2Me)2, DMF, rt, 10 h and
(ii) NaH, DMF, rt, 10 h.
SCHEME 5. Desulfonylation of Cyclopropanated
Carbohydratesa
a Reagents and conditions: (a) NaCl, DMSO-H2O (10:1), 100 °C, 24 h,
83%; (b) LiAlH4, THF, rt, 20 h; (c) Ac2O, DMAP, rt, 10 h, 71%; (d) EtSH,
AlCl3, rt, 8 h; and (e) Ac2O, DMAP, rt, 12 h, 68%.
a Reagents and conditions: (a) Mg, MeOH, rt and (b) Mg, NiBr2, MeOH,
60 °C.
Structural Elucidation. Compounds 11, 12, 21, and 24 were
characterized by X-ray diffraction of the single crystals. The
identities of compounds 8 and 9 were established unambiguously
by synthesizing them through alternative routes. Thus, the
p-methoxybenzyl (PMB) protected epoxide 27, obtained from
5, was reacted with p-thiocresol to afford 28. Methylation and
benzylation of 28 produced 29 and 30, respectively. Removal
of the PMB group from 29 and 30 by 2,3-dichloro-5,6-dicyano-
1,4-benzoquinone (DDQ) produced alcohols 31 and 32. Com-
pounds 31 and 32 were oxidized with MMPP to generate
sulfones 33 and 34, respectively. Mesylation of 33 and 34
afforded 35 and 36, respectively. Mesylates 35 and 36, on
treatment with NaOMe in MeOH, afforded cyclopropanated
carbohydrates 8 and 9 (mixed 1H NMR), respectively (Scheme
8). The identity of compound 10 was established as follows. It
Although the cyclopropanated sugars would be useful for the
synthesis of a host of branched-chain sugars using the reported
methods,1 we also decided to establish a new strategy for the
conversion of cyclopropanated sugars to functionalized cyclo-
propanols 23 and 26. The synthesis of the diastereomerically
pure cyclopropanes was initiated by converting 11 to the
monoester 19 (Scheme 6). Desulfonylation of 19 by Mg in
MeOH easily afforded 20.
SCHEME 6. Derivatization of r-Anomeric
Cyclopropanated Furanosidesa
SCHEME 8. Alternative Synthesis of Cyclopropanated
Carbohydrates 8 and 9a
a Reagents and conditions: (a) NaCl, DMSO-H2O (10:1), 120 °C, 72 h,
81%; (b) Mg, MeOH, rt, 5 h, 77%; (c) TFA-H2O (9:1), rt, 2 h, 69%; (d)
LiAlH4, THF, rt, 20 h; (e) Ac2O, DMAP, rt, 10 h, 75%; (f) EtSH, AlCl3,
rt, 8 h; and (g) Ac2O, DMAP, rt, 10 h, 71%.
Monoester 20 under acidic conditions yielded lactone 21. To
explain the formation of 21, we presumed that the acid
hydrolysis of 20 resulted in the formation of a free anomeric
hydroxyl group that intramolecularly attacked the CO2Me group
to produce the cyclopropane-based lactone; alternatively, the
oxygen of the ester carbonyl group intramolecularly attacked
the oxonium ion intermediate during hydrolysis. On the other
hand, compound 19 was reduced and desulfonylated in one step,
and the product was isolated as the acetate 22. AlCl3 mediated
dithioacetal formation opened the sugar ring of 22; acetylation
of the product afforded the R-substituted cyclopropanol 23
(Scheme 6).
a Reagents and Conditions: (a) p-methoxybenzyl chloride, NaH, DMF,
rt, 2.5 h; (b) p-thiocresol, NaOMe, DMF, 120 °C, 4 h; (c) CH3I, NaH,
DMF, rt, 2 h; (d) PhCH2Br, NaH, DMF, rt, 2.5 h; (e) DDQ, DCM-H2O
(20:1), rt, 16 h; (f) MMPP, MeOH, 6 h, rt; (g) MsCl, py, 0-4 °C, 24 h;
and (h) NaOMe, MeOH, rt, 22 h.
J. Org. Chem, Vol. 72, No. 24, 2007 9183

Das et al.
is well-documented in the literature7 that the J1,2 values of
authentic methyl R-D-arabinofuranosides range between 0.0 and
3.0 Hz. The J1,2 values for authentic methyl R-D-ribofuranosides
range between 4.0 and 4.9 Hz, and for methyl R-D-xylofura-
nosides, these values always range between 4.0 and 4.7 Hz.
Excluding the possibility of any lyxo derivative formation, the
coupling constant (J1,2) value of H-1 and H-2 protons of
compound 10 was 0.0 Hz, indicating the presence of an arabino
configuration in this molecule. Futhermore, by compairing the
J1,2 values of compound 10 (0.0 Hz) with those of our
synthesized compounds 8 (0.0 Hz), 9 (0.0 Hz), 11 (0.0 Hz),
and 12 (1.1 Hz), a trans relationship between H-1 and H-2 in
the cyclopropanated sugar component of compound 10 was
concluded.7
hand, there are only scant reports on cyclopropanes built on
furanose rings.1,8 The present work reports for the first time
the hitherto unknown combination of cyclopropanes, carbohy-
drates, and an electron withdrawing group such as sulfone (8-
15/19/24).9 The desulfonylated analogues 16-18/20-22/25, on
the other hand, represent another distinct class of cyclopropanes
built on furanose appendages. The strategy also gives easy
access to cyclopropane derivatives (23 and 26) with predefined
chiralities on three consecutive carbons with varying substitu-
tions at the R-position. The scopes and limitations of these new
chiral synthons are currently under study.
Experimental Section
Compounds 13b and 14 were also identified through alterna-
tive syntheses. In this case, the lyxo epoxide 7 was protected
with the p-methoxybenzyl group to obtain 37, which with
reaction with p-thiocresol afforded the sulfide 38. Methylation
and benzylation of the alcohol 38 produced 39 and 40,
respectively. Removal of the PMB group from 39 and 40 by
DDQ produced alcohols 41 and 42, respectively. Oxidation of
41 and 42 with MMPP produced sulfones 43 and 44, respec-
tively. Mesylation of 43 and 44 afforded 45 and 46. Mesylates
45 and 46, on treatment with NaOMe in MeOH, afforded
cyclopropanes 13b and 14 (mixed 1H NMR), respectively
(Scheme 9).
General Procedure for the Synthesis of 6R and 6â. To a well-
stirred solution of 5 or 7 in dry DMF (4 mL/mmol) were added
p-thiocresol (5 equiv/mmol) and NaOMe (2.5 equiv/mmol). The
mixture was heated at 100 °C with stirring for 4 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 anhydrous Na2SO4 and filtered, and the filtrate was concen-
trated under reduced pressure to obtain a residue. The residue was
purified over a silica gel column to afford compound 5a or 7a. To
a solution of compound 5a or 7a in dry MeOH (10 mL/mmol) was
added magnesium monoperoxyphthalate hexahydrate (2.5 equiv/
mmol), and the mixture was stirred for 6 h at ambient temperature
under N2. After completion of the reaction (TLC), MeOH was
evaporated to dryness under reduced pressure, and the residue was
dissolved in saturated NaHCO3. The product was extracted with
EtOAc (3 × 10 mL). The combined organic layers were dried over
anhydrous Na2SO4 and filtered, and the filtrate was concentrated
under reduced pressure to afford compound 5b or 7b. To a solution
of compound 5b or 7b in dry pyridine (5 mL/mmol) was added
methanesulfonyl chloride (8 equiv/mmol) in dry pyridine (1 mL/
mmol of MsCl) dropwise at 0 °C under N2. The reaction mixture
was left at +4 °C. After 24 h (TLC), the reaction mixture was
poured into an ice-cold saturated solution of NaHCO3, and the
product was extracted with EtOAc (3 × 10 mL). The combined
organic layers were dried over anhydrous Na2SO4 and filtered, and
the filtrate was concentrated under reduced pressure to obtain a
residue. The residue was purified over a silica gel column to afford
6R or 6â.
SCHEME 9. Alternative Synthesis of Cyclopropanated
Carbohydrates 13b and 14a
General Procedure for the Synthesis of 8, 13a, and 13b. To
a well-stirred solution of 6R or 6â in MeOH was added sodium
methoxide (2 equiv/mmol), and the mixture was stirred at ambient
temperature for 12-14 h. After completion of the reaction (TLC),
MeOH was evaporated to dryness under reduced pressure, and the
residue was poured into a saturated solution of NH4Cl. The product
was extracted with EtOAc (3 × 10 mL). The combined organic
layers were dried over anhydrous Na2SO4 and filtered, and the
filtrate was concentrated under reduced pressure to obtain a residue.
The resulting residue was purified over a silica gel column to afford
compound 8, 13a, or 13b.
a Reagents and conditions: (a) p-methoxybenzyl chloride, NaH, DMF,
rt, 2.5 h; (b) p-thiocresol, NaOMe, DMF, 120 °C, 4 h; (c) CH3I, NaH,
DMF, rt, 2 h; (d) PhCH2Br, NaH, DMF, rt, 2.5 h; (e) DDQ, DCM-H2O
(20:1), rt, 18 h; (f) MMPP, MeOH, 6 h, rt; (g) MsCl, py, 0-4 °C, 24 h;
and (h) NaOMe, MeOH, rt, 24 h.
The overwhelming majority of donor-acceptor cyclopropanes
derived from carbohydrates was constructed on the C1-C2 bond
of the pyranosides because glycals are the only class of starting
materials useful for cyclopropanation reactions.1 On the other
(8) (a) Brimacombe, J. S.; Evans, M. E.; Forbes, E. J.; Foster, A. B.;
Webber, J. M. Carbohydr. Res. 1967, 4, 239. (b) Sasaki, T.; Minamoto,
K.; Suzuki, H. J. Org. Chem. 1973, 38, 598. (c) Kawana, M.; Kuzuhara,
H. Synthesis 1995, 5, 544. (d) Gagneron, J.; Gosselin, G.; Mathe, C. J.
Org. Chem. 2005, 70, 6891. (e) Testero, S. A.; Spanevello, R. A. Carbohydr.
Res. 2006, 341, 1057. (f) Besada, P.; Shin, D. H.; Costanzi, S.; Ko, H.;
Mathe, C.; Gagneron, J.; Gosselin, G.; Maddileti, S.; Harden, T. K.;
Jacobson, K. A. J. Med. Chem. 2006, 49, 5532. (g) Nowak, I.; Cannon, J.
F.; Robins, M. J. J. Org. Chem. 2007, 72, 532.
(9) Schemes 8 and 9 represent a non-Michael addition approach to the
synthesis of cyclopropanated carbohydrates containing an electron with-
drawing group at C-3 of pentofuranosides. This strategy may be explored
when the introduction of a group at C-2 is less efficient through Michael
addition to vinyl sulfone-modified carbohydrates.
(7) (a) Casini, G.; Goodman, L. J. Am. Chem. Soc. 1964, 86, 1427. (b)
Montgomery, J. N.; Thorpe, M. C.; Clayton, S. D.; Thomas, H. J.
Carbohydr. Res. 1974, 32, 404. (c) Bock, K.; Pedersen, C.; Thiem, J.
Carbohydr. Res. 1979, 73, 85. (d) Liptak, A.; Neszmelyi, A.; Kovac, P.;
Hirsch, J. Tetrahedron 1981, 37, 2379. (e) Su, T.-L.; Klein, R. S.; Fox, J.
J. J. Org. Chem. 1981, 46, 1790. (f) Kawana, M.; Kuzuhara, H.; Emoto, S.
Bull. Chem. Soc. Jpn. 1981, 54, 1492. (g) Kawana, M.; Koresawa, T.;
Kuzuhara, H. Bull. Chem. Soc. Jpn. 1983, 56, 1095.
9184 J. Org. Chem., Vol. 72, No. 24, 2007

Stereospecific Route to R-Substituted Cyclopropanes
General Procedure for the Synthesis of 9, 10, and 14. To a
well-stirred solution of 6R or 6â in DMF was added sodium salt
of benzyl oxide or methyl-2,3-anhydro-R-D-lyxofuranosyl oxide (2
equiv/mmol), and the mixture was stirred at ambient temperature
for 21-24 h. After completion of the reaction (TLC), the reaction
mixture was poured into a saturated solution of NH4Cl, and the
product was extracted with EtOAc (3 × 10 mL). The combined
organic layers were dried over anhydrous Na2SO4 and filtered, and
the filtrate was concentrated under reduced pressure to obtain a
residue. The resulting residue was purified over a silica gel column
to afford compound 9, 10, or 14.
General Procedure for the Synthesis of 12 and 15. To a well-
stirred solution of 6R or 6â in dry DMF (10 mL/mmol) was added
sodium salt of dimethyl malonate (2 equiv/mmol), and the mixture
was stirred at room temperature for 10 h. After completion of the
reaction (TLC), the reaction mixture was poured into a saturated
solution of NH4Cl, and the product was extracted with EtOAc (3
× 10 mL). The combined organic layers were dried over anhydrous
Na2SO4 and filtered, and the filtrate was concentrated under reduced
pressure to obtain a residue. The resulting residue was purified over
a silica gel column [eluent: EtOAc/petroleum ether (1:2)] to afford
a residue. The residue was stirred at ambient temperature with NaH
and dry DMF for 10 h under Ar. After completion of the reaction
(TLC), the reaction mixture was poured into a saturated solution
of NH4Cl, and the product was extracted with EtOAc (3 × 10 mL).
The combined organic layers were dried over anhydrous Na2SO4
and filtered, and the filtrate was concentrated under reduced pressure
to obtain a residue. The resulting residue was purified over a silica
gel column to afford compound 12 or 15.
General Procedure for the Synthesis of 16, 18, and 20. To a
well-stirred solution of 9, 14, or 19 in dry MeOH (10 mL) was
added Mg turnings (15 mmol) under Ar. The mixture was stirred
at ambient temperature. After 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 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 obtain a residue. The residue was purified
over a silica gel column to afford compound 16, 18, or 20.
General Procedure for the Synthesis of 19 and 24. A well-
stirred solution of 11 or 15 in a mixture of DMSO (10 mL) and
water (1 mL) containing NaCl (5 equiv/mmol) was heated at 100-
120 °C for 24-72 h. After completion of the reaction (TLC), the
reaction mixture was poured into a saturated solution of NaCl, and
the product was extracted with EtOAc (3 × 10 mL). The combined
organic layers were dried over anhydrous Na2SO4 and filtered, and
the filtrate was concentrated under reduced pressure to obtain a
residue. The residue was purified over a silica gel column to afford
19 or 24.
General Procedure for the Synthesis of 22 and 25. To a well-
stirred solution of 19 or 24 in dry THF (10 mL) was added LAH
(5 equiv/mmol) at 0 °C under Ar, and the mixture was stirred at
ambient temperature for 20 h. After completion of the reaction
(TLC), a saturated NH4Cl solution was added, and the product was
extracted with EtOAc (3 × 10 mL). The combined organic layers
were dried over anhydrous Na2SO4 and filtered, and the filtrate
was concentrated under reduced pressure to obtain a residue. The
resulting residue was purified over a silica gel column to afford a
residue. The residue was acetylated with acetic anhydride (1 mL)
and DMAP (catalytic) at room temperature for 10 h. After
completion of the reaction (TLC), a saturated NaHCO3 solution
was added, and the product was extracted with EtOAc (3 × 10
mL). The combined organic layers were dried over anhydrous Na2-
SO4 and filtered, and the filtrate was concentrated under reduced
pressure to obtain a residue. The resulting residue was purified over
a silica gel column to afford 22 or 25.
General Procedure for the Synthesis of 23 and 26. To a well-
stirred solution of 22 or 25 was added EtSH and AlCl3, and the
mixture was stirred at room temperature for 8 h. After completion
of the reaction (TLC), a saturated NH4Cl solution was added, and
the product was extracted with EtOAc (3 × 10 mL). The combined
organic layers were dried over anhydrous Na2SO4 and filtered, and
the filtrate was concentrated under reduced pressure to obtain a
residue. The resulting residue was purified over silica gel column
to afford a residue. The product, thus obtained, was acetylated with
acetic anhydride (1 mL) and DMAP (catalytic) at ambient tem-
perature for 10-12 h. After completion of the reaction (TLC), a
saturated NaHCO3 solution was added, and the product was
extracted with EtOAc (3 × 10 mL). The combined organic layers
were dried over anhydrous Na2SO4 and filtered, and the filtrate
was concentrated under reduced pressure to obtain a residue. The
resulting residue was purified over a silica gel column to afford 23
or 26.
General Procedure for the Synthesis of 27 and 37. To a well-
stirred solution of 5 or 7 (1 equiv/mmol) in DMF (8 mL/mmol)
were added p-methoxybenzyl chloride (1.3 equiv/mmol) and NaH
(1.3 equiv/mmol). The mixture was stirred at ambient temperature
for 2.5 h under N2. After completion of the reaction (TLC), the
reaction mixture was poured into a saturated solution of NH4Cl,
and the product was extracted with EtOAc (3 × 10 mL). The
combined organic layers were dried over anhydrous Na2SO4 and
filtered, and the filtrate was concentrated under reduced pressure
to obtain a residue. The residue was purified over a silica gel column
to afford 27 or 37.
General Procedure for the Synthesis of 28 and 38. To a well-
stirred solution of 27 or 37 in DMF (4 mL/mmol) were added
p-thiocresol (5 equiv/mmol) and NaOMe (2.5 equiv/mmol). The
mixture was heated at 120 °C with stirring for 4 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 anhydrous Na2SO4 and filtered, and the filtrate was concen-
trated under reduced pressure to obtain a gummy residue. The
residue was purified over a silica gel column to afford sulfides 28
or 38.
General Procedure for the Synthesis of 29 and 39. Compound
28 or 38 (1 equiv/mmol) was stirred at 0 °C with NaH (1.2 equiv/
mmol) and MeI (2 equiv/mmol) in DMF (8 mL/mmol). Then, the
mixture was stirred at ambient temperature under N2. After
completion of the reaction (TLC), the reaction mixture was poured
into a saturated solution of NH4Cl, and the product was extracted
with EtOAc (3 × 10 mL). The combined organic layers were dried
over anhydrous Na2SO4 and filtered, and the filtrate was concen-
trated under reduced pressure to obtain a residue. The residue was
purified over a silica gel column to afford 29 or 39.
General Procedure for the Synthesis of 30 and 40. Compound
28 or 38 (1 equiv/mmol) was stirred at 0 °C with NaH (1.2 equiv/
mmol) and BnBr (1.2 equiv/mmol) in DMF (8 mL/mmol). Then,
the mixture was stirred at ambient temperature under N2. After
completion of the reaction (TLC), the reaction mixture was poured
into a saturated solution of NH4Cl, and the product was extracted
with EtOAc (3 × 10 mL). The combined organic layers were dried
over anhydrous Na2SO4 and filtered, and the filtrate was concen-
trated under reduced pressure to obtain a residue. The residue was
purified over a silica gel column to afford 30 or 40.
General Procedure for the Synthesis of 31, 32, 41, and 42.
To a well-stirred solution of 29, 30, 39, or 40 in DCM--H2O (20:
1) was added DDQ (1.2 equiv/mmol), and the mixture was stirred
at ambient temperature for 16-18 h. After completion of the
reaction (TLC), the reaction mixture was poured into a saturated
solution of NaHCO3, and the mixture was extracted with DCM (3
× 10 mL). The combined organic layers were dried over anhydrous
Na2SO4 and filtered, and the filtrate was concentrated under reduced
pressure to obtain a residue. The resulting residue was purified over
a silica gel column to afford 31, 32, 41, or 42.
J. Org. Chem, Vol. 72, No. 24, 2007 9185

Das et al.
General Procedure for the Synthesis of 33, 34, 43, and 44.
To a well-stirred solution of 31, 32, 41, or 42 in dry MeOH (10
mL/mmol) was added magnesium monoperoxyphthalate hexahy-
drate (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 saturated NaHCO3. The aqueous portion was extracted with
EtOAc (3 × 10 mL). The combined organic layers were dried over
anhydrous Na2SO4 and filtered, and the filtrate was concentrated
under reduced pressure to obtain a residue. The residue was purified
over a silica gel column to obtain 33, 34, 43, or 44.
General Procedure for the Synthesis of 35, 36, 45, and 46.
To a well-stirred solution of 33, 34, 43, or 44 in dry 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 24 h (TLC), the reaction mixture was poured into an
ice-cold saturated solution of NaHCO3, and the product was
extracted with EtOAc (3 × 10 mL). The combined organic layers
were dried over anhydrous Na2SO4 and filtered, and the filtrate
was concentrated under reduced pressure to obtain a residue. The
residue was purified over a silica gel column to afford 35, 36, 45,
or 46.
General Procedure for the Synthesis of 8, 9, 13b, and 14 (from
35, 36, 45, and 46). To a well-stirred solution of 35, 36, 45, or 46
in dry MeOH (10 mL/mmol) was added NaOMe (2.5 equiv/mmol),
and the mixture was stirred for 22-24 h at ambient temperature
under N2. After completion of the reaction (TLC), MeOH was
evaporated to dryness under reduced pressure, and the residue was
dissolved in saturated NH4Cl. The product was extracted with
EtOAc (3 × 10 mL). The combined organic layers were dried over
anhydrous Na2SO4 and filtered, and the filtrate was concentrated
under reduced pressure to obtain a residue. The residue was purified
over silica gel column to obtain 8, 9, 13b, or 14.
Methyl 3-Deoxy-3-S-(4-methylphenyl)-3-thio-r-D-arabino-
furanoside (5a). Compound 5 (1.2 g, 8.2 mmol) was converted to
5a following the general procedure (2.0 g, 90%). Eluent: EtOAc/
petroleum ether (1:6). Yellow gum. [R]27D (+) 131.6 (c 7.0, CHCl3).
1H NMR (CDCl3): δ 2.32 (s, 3H), 3.39 (s, 3H), 3.43 (m, 1H),
3.58 (m, 1H), 3.88 (m, 1H), 4.12-4.18 (m, 2H), 4.91 (s, 1H), 7.12
(d, J ) 8.0 Hz, 2H), 7.35 (d, J ) 8.1 Hz, 2H). 13C NMR (CDCl3):
δ 20.9, 52.4, 54.9, 61.7 (CH2), 81.3, 84.1, 109.6, 129.8, 131.0,
131.4, 137.2. Anal. calcd for C13H18O4S: C, 57.76; H, 6.71.
Found: C, 57.75; H, 6.48.
(1.4 g, 86%). Eluent: EtOAc/petroleum ether (1:1). Yellow
crystalline solid. Solvent of crystallization: EtOAc and petroleum
ether. Mp: 70 °C. [R]27 (-) 47.2 (c 0.4, CHCl3). 1H NMR
D
(CDCl3): δ 2.46 (s, 3H), 3.03 (s, 3H), 3.45 (s, 3H), 4.25 (dd, J )
6.0, 11.4 Hz, 1H), 4.60 (dd, J ) 2.3, 15.4 Hz, 1H), 4.95 (m, 1H),
5.67 (m, 1H), 6.60 (m, 1H), 7.39 (d, J ) 8.1 Hz, 2H), 7.80 (d, J )
8.3 Hz, 2H). 13C NMR (CDCl3): δ 21.6, 37.4, 56.0, 70.2 (CH2),
80.9, 107.5, 128.1, 130.3, 135.3, 137.3, 145.5, 145.9. Anal. calcd
for C14H18O7S2: C, 46.40; H, 5.01. Found: C, 46.20; H, 5.33.
Methyl 3,5-Cyclo-3,5-dideoxy-2-O-methyl-3-(4-methylphenyl-
)sulfonyl-r-D-arabinofuranoside (8). Compound 6R (0.53 g, 1.46
mmol) was converted to 8 following the general procedure (0.41
g, 94%). Eluent: EtOAc/petroleum ether (1:3). White crystalline
solid. Solvent of crystallization: EtOAc and petroleum ether. [R]27
D
1
(+) 125.9 (c 0.6, CHCl3). Mp: 60 °C. H NMR (CDCl3): δ 1.77
(dd, J ) 3.3, 6.4 Hz, 1H), 1.94 (t, J ) 6.3 Hz, 1H), 2.45 (s, 3H),
3.12 (s, 3H), 3.13 (s, 3H), 4.26 (s, 1H), 4.56 (m, 1H), 4.66 (s, 1H),
7.35 (d, J ) 8.3 Hz, 2H), 7.77 (d, J ) 8.3 Hz, 2H). 13C NMR
(CDCl3): δ 21.5, 22.2 (CH2), 51.3, 54.3, 56.7, 66.5, 84.7, 115.2,
128.5, 129.6, 135.9, 144.7. Anal. calcd for C14H18O5S: C, 56.36;
H, 6.08. Found: C, 56.76; H, 5.85.
Methyl 2-O-Benzyl-3,5-cyclo-3,5-dideoxy-3-(4-methylphenyl)-
sulfonyl-r-D-arabinofuranoside (9). Compound 6R (0.28 g, 0.77
mmol) was converted to 9 following the general procedure (0.25
g, 86%). Eluent: EtOAc/petroleum ether (1:5). White amorphous
solid. [R]27 (+) 63.9 (c 0.6, CHCl3). Mp: 70 °C. 1H NMR
D
(CDCl3): δ 1.92 (dd, J ) 3.3, 6.6 Hz, 1H), 1.99 (t, J ) 5.9 Hz,
1H), 2.44 (s, 3H), 3.10 (s, 3H), 4.33-4.46 (m, 3H), 4.57 (m, 1H),
4.72 (s, 1H), 7.19-7.34 (m, 7H), 7.74 (d, J ) 8.3 Hz, 2H). 13C
NMR (CDCl3): δ 21.5, 22.2 (CH2), 51.7, 54.3, 66.6, 70.9 (CH2),
82.7, 115.1, 127.7, 127.8, 128.3, 128.6, 129.6, 135.8, 136.9, 144.7.
Anal. calcd for C20H22O5S: C, 64.15; H, 5.92. Found: C, 64.19;
H, 5.78.
Methyl 3,5-Cyclo-3,5-dideoxy-2-O-(methyl 2,3-anhydro-r-D-
lyxofuranos-5-yl)-3-(4-methylphenyl)sulfonyl-R-D-arabinofura-
noside (10). Compound 6R (0.34 g, 0.94 mmol) was converted to
10 following the general procedure (0.31 g, 81%). Eluent: EtOAc/
petroleum ether (1:3). White crystalline solid. Solvent of crystal-
lization: CHCl3 and petroleum ether. Mp: 115 °C. [R]27D (+) 88.7
1
(c 0.5, CHCl3). H NMR (CDCl3): δ 1.85 (dd, J ) 3.3, 6.5 Hz,
1H), 1.95 (t, J ) 6.2 Hz, 1H), 2.45 (s, 3H), 3.13 (s, 3H), 3.37 (s,
3H), 3.41-3.53 (m, 2H), 3.61 (s, 2H), 4.00 (m, 1H), 4.43 (s, 1H),
4.56 (m, 1H), 4.71 (s, 1H), 4.90 (s, 1H), 7.36 (d, J ) 8.2 Hz, 2H),
7.79 (d, J ) 8.3 Hz, 2H). 13C NMR (CDCl3): δ 21.3, 22.0 (CH2),
51.3, 53.7, 54.2, 55.3, 55.8, 66.3, 67.2 (CH2), 74.0, 83.5, 102.0,
114.8, 128.3, 129.4, 135.7, 144.6. Anal. calcd for C19H24O8S: C,
55.33; H, 5.87. Found: C, 55.0; H, 5.77.
Methyl 2,3-Dideoxy-5-O-mesyl-3-(4-methylphenyl)sulfonyl-r-
D-erythro-pent-2-enofuranoside (6R). Compound 5a (2.0 g, 7.4
mmol) was converted to 6R via 5b following the general procedure
(2.4 g, 88%). Eluent: EtOAc/petroleum ether (1:1). Yellow gum.
[R]27D (-) 4.5 (c 10.2, CHCl3). 1H NMR (CDCl3): δ 2.46 (s, 3H),
3.04 (s, 3H), 3.37 (s, 3H), 4.35 (dd, J ) 3.8, 11.5 Hz, 1H), 4.60
(dd, J ) 2.2, 11.2 Hz, 1H), 5.13 (m, 1H), 5.86 (d, J ) 4.4 Hz,
1H), 6.54 (m, 1H), 7.39 (d, J ) 8.1 Hz, 2H), 7.80 (d, J ) 8.2 Hz,
2H). 13C NMR (CDCl3): δ 21.5, 37.4, 55.0, 68.9 (CH2), 81.1, 107.4,
128.0, 130.2, 135.3, 137.6, 145.0, 145.8. Anal. calcd for
C14H18O7S2: C, 46.40; H, 5.01. Found: C, 46.58; H, 4.90.
Methyl 3-Deoxy-3-S-(4-methylphenyl)-3-thio-â-D-xylofura-
noside (7a). Compound 7 (0.84 g, 5.75 mmol) was converted to
7a following the general procedure (1.2 g, 80%). Eluent: EtOAc/
petroleum ether (1:6). White crystalline solid. Solvent of crystal-
Methyl 2-N-Benzylamino-2,3-dideoxy-5-O-mesyl-3-(4-meth-
ylphenyl)sulfonyl-r-D-arabinofuranoside (11a). A mixture of
compound 6R (0.33 g, 0.91 mmol) and neat benzylamine (2 equiv/
mmol) was stirred at room temperature for 1 h. After completion
of the reaction (TLC), the reaction mixture was poured into a
saturated solution of NH4Cl, and the product was extracted with
EtOAc (3 × 10 mL). The combined organic layers were dried over
anhydrous Na2SO4 and filtered, and the filtrate was concentrated
under reduced pressure to obtain a residue. The residue was purified
over silica gel column to afford 11a (0.39 g, 92%). Eluent: EtOAc/
petroleum ether (1:1). White amorphous solid. [R]25 (+) 24.2 (c
D
0.5, CHCl3). 1H NMR (CDCl3): δ 2.45 (s, 3H), 3.04 (s, 3H), 3.26
(s, 3H), 3.46-3.74 (m, 4H), 4.29 (m, 1H), 4.52-4.60 (m, 2H),
4.82 (s, 1H), 7.10-7.34 (m, 7H), 7.67 (d, J ) 8.2 Hz, 2H). 13C
NMR (CDCl3): δ 21.6, 37.7, 51.6 (CH2), 55.1, 65.8, 69.0 (CH2),
69.1, 74.8, 108.4, 127.2, 128.2, 128.4, 128.8, 130.1, 134.3, 138.8,
145.5. Anal. calcd for C21H27NO7S2: C, 53.71; H, 5.80; N, 2.98.
Found: C, 53.41; H, 6.09; N, 3.30.
lization: DCM and petroleum ether. Mp: 73 °C. [R]27 (-) 36.4
D
1
(c 1.22, CHCl3). H NMR (CDCl3): δ 2.32 (s, 3H), 3.46 (s, 3H),
3.65-3.84 (m, 3H), 4.33 (m, 1H), 4.46 (m, 1H), 4.88 (d, J ) 2.5
Hz, 1H), 7.11 (d, J ) 8.0 Hz, 2H), 7.34 (d, J ) 8.1 Hz, 2H). 13C
NMR (CDCl3): δ 20.9, 55.2, 56.1, 63.1 (CH2), 81.6, 82.1, 109.7,
129.9, 130.7, 131.6, 137.0. Anal. calcd for C13H18O4S: C, 57.76;
H, 6.71. Found: C, 58.02; H, 6.48.
Methyl 2,3-Dideoxy-5-O-mesyl-3-(4-methylphenyl)sulfonyl-â-
D-erythro-pent-2-enofuranoside (6â). Compound 7a (1.2 g, 4.44
mmol) was converted to 6â via 7b following the general procedure
Methyl 2-N-Benzylamino-3,5-cyclo-3-(4-methylphenyl)sulfo-
nyl-2,3,5-trideoxy-r-D-arabinofuranoside (11). Compound 11a
(0.36 g, 0.77 mmol) was stirred at room temperature with K2CO3
and MeOH for 24 h. After completion of the reaction (TLC), MeOH
9186 J. Org. Chem., Vol. 72, No. 24, 2007

Stereospecific Route to R-Substituted Cyclopropanes
was evaporated to dryness under reduced pressure. The reaction
mixture was poured into a saturated solution of NH4Cl, and the
product was extracted with EtOAc (3 × 10 mL). The combined
organic layers were dried over anhydrous Na2SO4 and filtered, and
the filtrate was concentrated under reduced pressure to obtain a
residue. The resulting residue was purified over a silica gel column
to afford 11 (0.18 g, 62%). Eluent: EtOAc/petroleum ether (1:3).
(CDCl3): δ 1.66-1.73 (m, 2H), 2.45 (s, 3H), 2.66 (m, 1H), 3.27
(s, 3H), 3.73 (s, 3H), 3.80 (s, 3H), 4.36 (d, J ) 3.6 Hz, 1H), 4.81
(m, 1H), 5.35 (d, J ) 1.3 Hz, 1H), 7.35 (d, J ) 8.0 Hz, 2H), 7.70
(d, J ) 8.3 Hz, 2H). 13C NMR (CDCl3): δ 21.2, 22.9 (CH2), 45.7,
48.0, 50.0, 52.1, 52.5, 55.1, 66.8, 110.9, 127.1, 129.8, 136.9, 144.4,
166.9, 168.5. IR (KBr): 1084, 1144, 1304, 1735 cm-1. Anal. calcd
for C18H22O8S: C, 54.26; H, 5.57. Found: C, 54.45; H, 5.55.
Methyl 2-O-Benzyl-3,5-cyclo-3,5-dideoxy-r-D-arabinofura-
noside (16). Compound 9 (0.38 g, 1.01 mmol) was desulfonylated
to 16 following the general procedure (0.18 g, 80%). Eluent:
EtOAc/petroleum ether (1:12). Yellow oil. [R]27D (+) 258.7 (c 2.0,
Yellow crystalline solid. Solvent of crystallization: DCM and
1
petroleum ether. [R]27 (+) 14.0 (c 0.7, CHCl3). Mp: 140 °C. H
D
NMR (CDCl3): δ 1.80 (dd, J ) 3.0, 6.7 Hz, 1H), 1.92 (t, J ) 6.4
Hz, 1H), 2.44 (s, 3H), 3.15 (s, 3H), 3.52-3.72 (m, 3H), 4.50 (m,
1H), 4.56 (s, 1H), 7.20-7.38 (m, 7H), 7.62 (d, J ) 8.3 Hz, 2H).
13C NMR (CDCl3): δ 20.1 (CH2), 21.4, 50.7, 51.3 (CH2), 54.7,
63.8, 64.4, 115.3, 127.0, 128.0, 128.2, 128.4, 129.6, 135.3, 139.2,
144.5. Anal. calcd for C20H23NO4S: C, 64.32; H, 6.21; N, 3.75.
Found: C, 64.66; H, 5.98; N, 4.03.
1
CHCl3). H NMR (CDCl3): δ 0.73 (m, 1H), 1.14 (m, 1H), 1.80
(m, 1H), 3.33 (s, 3H), 4.15-4.27 (m, 2H), 4.41 (d, J ) 11.5 Hz,
1H), 4.63 (d, J ) 11.5 Hz, 1H), 4.73 (d, J ) 0.8 Hz, 1H), 7.28-
7.37 (m, 5H). 13C NMR (CDCl3): δ 13.8 (CH2), 18.0, 54.6, 61.5,
70.3 (CH2), 84.0, 114.2, 127.5, 127.7, 128.2, 137.6. Anal. calcd
for C13H16O3: C, 70.89; H, 7.32. Found: C, 70.53; H, 7.46.
Methyl 2-N-Benzylamino-3,5-cyclo-2,3,5-trideoxy-r-D-ara-
binofuranoside (17). To a well-stirred solution of 11 (0.25 g, 0.66
mmol) in dry MeOH (10 mL) was added Mg turnings (15 mmol)
and NiBr2 (10 mol %) under Ar. The mixture was heated at 60 °C.
After 5 h, another portion of Mg turnings (15 mmol) and dry MeOH
(5 mL) were added. The mixture was stirred for an additional 5 h
at 60 °C. The reaction mixture was filtered through Celite. The
residue was washed thoroughly with MeOH. The filtrates were
pooled together, and the liquid was evaporated under reduced
pressure. The resulting residue was dissolved in EtOAc. The
solution was washed with saturated NH4Cl solution, dried over
anhydrous Na2SO4, and filtered, and the filtrate was concentrated
under reduced pressure to obtain a residue. The residue was purified
over a silica gel column to afford 17 (0.1 g, 66%). Eluent: EtOAc/
petroleum ether (1:3). Yellow oil. [R]27D (+) 201.4 (c 0.44, CHCl3).
1H NMR (CDCl3): δ 0.62 (m, 1H), 0.94 (m, 1H), 1.75 (m, 1H),
3.33 (s, 3H), 3.55 (m, 1H), 3.72 (d, J ) 12.9 Hz, 1H), 3.86 (d, J
) 12.9 Hz, 1H), 4.10 (m, 1H), 4.52 (s, 1H), 7.27-7.35 (m, 5H).
13C NMR (CDCl3): δ 13.0 (CH2), 18.9, 52.1 (CH2), 55.1, 60.1,
64.9, 115.0, 127.1, 128.2, 128.4, 139.9. Anal. calcd for C13H17-
NO2: C, 71.21; H, 7.81; N, 6.39. Found: C, 71.47; H, 8.22; N,
6.42. HRMS [ES+, (M + H)+]; for C13H18NO2: calcd 220.1338,
obsd 220.1341.
Methyl 3,5-Cyclo-2-bis(methoxycarbonylmethyl)-3-(4-meth-
ylphenyl)sulfonyl-2,3,5-trideoxy-R-D-arabinofuranoside (12). Com-
pound 6R (0.98 g, 2.7 mmol) was converted to 12 following the
general procedure (0.95 g, 88%). Eluent: EtOAc/petroleum ether
(1:3). White crystalline solid. Solvent of crystallization: EtOAc
and petroleum ether. Mp: 90 °C. [R]27 (+) 47.5 (c 1.8, CHCl3).
D
1H NMR (CDCl3): δ 1.71 (dd, J ) 2.9, 7.6 Hz, 1H), 2.11 (t, J )
6.5 Hz, 1H), 2.46 (s, 3H), 3.04 (s, 3H), 3.26 (m, 1H), 3.43 (m,
1H), 3.71 (s, 3H), 3.77 (s, 3H), 4.34 (m, 1H), 4.67 (d, J ) 1.1 Hz,
1H), 7.37 (d, J ) 8.2 Hz, 2H), 7.77 (d, J ) 8.2 Hz, 2H). 13C NMR
(CDCl3): δ 21.5, 22.2 (CH2), 46.8, 48.5, 50.5, 52.7, 52.9, 54.7,
64.5, 113.5, 129.1, 129.6, 134.4, 144.8, 166.9, 167.9. IR (KBr):
1105, 1305, 1329, 1435, 1732, 1756 cm-1. Anal. calcd for
C18H22O8S: C, 54.26; H, 5.57. Found: C, 54.58; H, 5.39.
Methyl 3,5-Cyclo-3,5-dideoxy-2-O-methyl-3-(4-methylphenyl-
)sulfonyl-â-D-arabinofuranoside (13a) and Methyl 3,5-Cyclo-
3,5-dideoxy-2-O-methyl-3-(4-methylphenyl)sulfonyl-â-D-ribo-
furanoside (13b). Compound 6â (0.42 g, 1.2 mmol) was converted
to 13a/13b (1:1) following the general procedure (0.31 g, 90%),
which was separated by column chromatography. Compound 13a:
eluent: EtOAc/petroleum ether (1:3). Yellow gum. [R]27D (-) 120.6
1
(c 1.2, CHCl3). H NMR (CDCl3): δ 1.64 (m, 1H), 2.07 (dd, J )
3.1, 6.9 Hz, 1H), 2.43 (s, 3H), 3.21 (s, 3H), 3.38 (s, 3H), 4.50 (m,
1H), 4.63 (m, 1H), 5.00 (d, J ) 5.1 Hz, 1H), 7.33 (d, J ) 7.9 Hz,
2H), 7.75 (d, J ) 8.3 Hz, 2H). 13C NMR (CDCl3): δ 19.9 (CH2),
21.5, 48.6, 56.3, 58.2, 61.9, 80.7, 105.1, 128.0, 129.6, 136.3, 144.6.
Anal. calcd for C14H18O5S: C, 56.36; H, 6.08. Found: C, 56.73;
H, 5.98. Compound 13b: eluent: EtOAc/petroleum ether (1:3).
White crystalline solid. Solvent of crystallization: DCM and
petroleum ether. Mp: 114 °C. [R]27D (-) 75.8 (c 0.46, CHCl3). 1H
NMR (CDCl3): δ 1.70 (dd, J ) 3.1, 7.2 Hz, 1H), 2.01 (t, J ) 6.8
Hz, 1H), 2.43 (s, 3H), 3.28 (s, 6H), 3.76 (s, 1H), 4.53 (m, 1H),
4.88 (s, 1H), 7.31 (d, J ) 8.3 Hz, 2H), 7.76 (d, J ) 8.3 Hz, 2H).
13C NMR (CDCl3): δ 19.2 (CH2), 21.5, 47.8, 55.1, 57.8, 63.9, 85.7,
110.1, 128.2, 129.2, 138.5, 144.0. Anal. calcd for C14H18O5S: C,
56.36; H, 6.08. Found: C, 56.40; H, 6.00.
Methyl 2-O-Benzyl-3,5-cyclo-3,5-dideoxy-â-D-ribofuranoside
(18). Compound 14 (0.32 g, 0.85 mmol) was desulfonylated to 18
following the general procedure (0.15 g, 77%). Eluent: EtOAc/
petroleum ether (1:12). Yellow oil. [R]27D (-) 30.5 (c 1.9, CHCl3).
1H NMR (CDCl3): δ 0.56 (m, 1H), 0.87 (m, 1H), 1.63 (m, 1H),
3.29 (s, 3H), 3.92 (s, 1H), 4.15 (m, 1H), 4.59 (s, 2H), 5.04 (d, J )
0.9 Hz, 1H), 7.28-7.37 (m, 5H). 13C NMR (CDCl3): δ 10.6 (CH2),
18.5, 55.0, 59.7, 71.5 (CH2), 84.7, 111.2, 127.8, 128.4, 137.8. Anal.
calcd for C13H16O3: C, 70.89; H, 7.32. Found: C, 71.0; H, 7.47.
Methyl 3,5-Cyclo-2-(methoxycarbonylmethyl)-3-(4-meth-
ylphenyl)sulfonyl-2,3,5-trideoxy-R-D-arabinofuranoside (19). Com-
pound 11 (0.6 g, 1.51 mmol) was converted to 19 following the
general procedure (0.41 g, 81%). Eluent: EtOAc/petroleum ether
(1:3). Yellow gum. [R]27 (+) 59.7 (c 3.0, CHCl3). 1H NMR
(CDCl3): δ 1.37 (dd, J )D2.8, 7.2 Hz, 1H), 1.91 (m, 1H), 2.27-
2.39 (m, 2H), 2.46 (s, 3H), 3.11 (m, 1H), 3.17 (s, 3H), 3.66 (s,
3H), 4.45 (m, 1H), 4.59 (d, J ) 2.6 Hz, 1H), 7.37 (d, J ) 8.3 Hz,
2H), 7.77 (d, J ) 8.3 Hz, 2H). 13C NMR (CDCl3): δ 20.0 (CH2),
21.6, 33.6 (CH2), 43.5, 49.3, 51.9, 55.2, 63.2, 113.9, 128.6, 129.8,
Methyl 2-O-Benzyl-3,5-cyclo-3,5-dideoxy-3-(4-methylphenyl)-
sulfonyl-â-D-ribofuranoside (14). Compound 6â (0.22 g, 0.6
mmol) was converted to 14 following the general procedure (0.19
g, 83%). Eluent: EtOAc/petroleum ether (1:5). White amorphous
solid. Mp: 172 °C. [R]27 (-) 49.5 (c 0.3, CHCl3). 1H NMR
(CDCl3): δ 1.72 (dd, J )D3.3, 7.2 Hz, 1H), 2.04 (t, J ) 6.9 Hz,
1H), 2.35 (s, 3H), 3.20 (s, 3H), 4.07 (s, 1H), 4.50-4.55 (m, 3H),
4.82 (s, 1H), 7.08 (d, J ) 7.9 Hz, 2H), 7.18-7.35 (m, 5H), 7.64
(d, J ) 8.3 Hz, 2H). 13C NMR (CDCl3): δ 19.2 (CH2), 21.4, 47.7,
55.2, 64.4, 72.9 (CH2), 84.1, 110.8, 127.8, 128.1, 128.2, 129.1,
136.5, 138.4, 143.7. Anal. calcd for C20H22O5S: C, 64.15; H, 5.92.
Found: C, 64.48; H, 5.77.
135.2, 144.9, 171.1. IR (KBr): 1139, 1166, 1303, 1316, 1736 cm-1
.
Anal. calcd for C16H20O6S: C, 56.46; H, 5.92. Found: C, 56.79;
H, 5.80.
Methyl 3,5-Cyclo-2-(methoxycarbonylmethyl)-2,3,5-trideoxy-
R-D-arabinofuranoside (20). Compound 19 (0.42 g, 1.23 mmol)
was desulfonylated to 20 following the general procedure (0.18 g,
77%). Eluent: EtOAc/petroleum ether (1:8). Yellow oil. [R]27D (+)
Methyl 3,5-Cyclo-2-bis(methoxycarbonylmethyl)-3-(4-meth-
ylphenyl)sulfonyl-2,3,5-trideoxy-â-D-ribofuranoside (15). Com-
pound 6â (0.88 g, 2.4 mmol) was converted to 15 following the
1
210.3 (c 1.4, CHCl3). H NMR (CDCl3): δ 0.44-0.58 (m, 2H),
general procedure (0.81 g, 84%). Eluent: EtOAc/petroleum ether
1.73 (m, 1H), 2.38-2.46 (m, 2H), 2.81 (m, 1H), 3.35 (s, 3H), 3.69
1
(1:3). Yellow gum. [R]27 (-) 57.3 (c 1.64, CHCl3). H NMR
(s, 3H), 4.05 (m, 1H), 4.45 (d, J ) 2.9 Hz, 1H). 13C NMR
D
J. Org. Chem, Vol. 72, No. 24, 2007 9187

Das et al.
(CDCl3): δ 12.6 (CH2), 18.3, 34.4 (CH2), 43.2, 51.6, 55.4, 58.5,
113.1, 172.4. IR (KBr): 1083, 1105, 1169, 1260, 1736 cm-1. Anal.
calcd for C9H14O4: C, 58.05; H, 7.58. Found: C, 58.35; H, 7.29.
(3aS, 3bR, 4aR, 5aS)-Tetrahydro-3bH-cyclopropa[b]furo[3,2-
d]furan-2(3H)-one (21). Compound 20 (0.25 g, 1.34 mmol) was
stirred at room temperature with 90% trifluoroacetic acid (10 mL)
for 2 h. After completion of the reaction (TLC), the solvent was
evaporated to dryness under reduced pressure to obtain a residue.
The residue was purified over a silica gel column to obtain
compound 21 (0.13 g, 69%). Eluent: EtOAc/petroleum ether (1:
(m, 2H), 1.15-1.35 (m, 6H), 1.78-1.86 (m, 2H), 2.05 (s, 3H),
2.06 (s, 3H), 2.27 (m, 1H), 2.51-2.73 (m, 4H), 3.96 (d, J ) 2.3
Hz, 1H), 4.14-4.26 (m, 3H). 13C NMR (CDCl3): δ 11.7 (CH2),
14.6, 14.7, 19.0, 20.9, 21.0, 26.1 (CH2), 26.8 (CH2), 29.5 (CH2),
40.4, 51.4, 56.0, 63.0 (CH2), 171.0, 171.5. IR (KBr): 1036, 1230,
1369, 1742 cm-1. Anal. calcd for C15H26O4S2: C, 53.86; H, 7.83.
Found: C, 53.66; H, 8.03.
Methyl 3-Deoxy-5-O-p-methoxybenzyl-3-S-(4-methylphenyl)-
3-thio-r-D-arabinofuranoside (28). Compound 5 (1.4 g, 9.6 mmol)
was converted to 28 following the general procedure (3.3 g, 89%).
Eluent: EtOAc/petroleum ether (1:3). Yellow gum. [R]27D (+) 121.9
2). White crystalline solid. Solvent of crystallization: DCM and
1
petroleum ether. Mp: 99 °C. [R]27 (+) 242.4 (c 0.2, CHCl3). H
1
D
(c 2.1, CHCl3). H NMR (CDCl3): δ 2.31 (s, 3H), 3.39 (s, 3H),
NMR (CDCl3): δ 0.65 (m, 1H), 0.81 (m, 1H), 1.85 (m, 1H), 2.62-
2.85 (m, 2H), 3.36 (m, 1H), 4.27 (m, 1H), 6.13 (d, J ) 6.0 Hz,
1H). 13C NMR (CDCl3): δ 12.1 (CH2), 20.2, 32.9 (CH2), 40.7,
63.2, 111.4, 174.8. IR (KBr): 1006, 1129, 1189, 1364, 1764, 1781
cm-1. Anal. calcd for C7H8O3: C, 60.0; H, 5.75. Found: C, 59.77;
H, 5.56.
3.45-3.73 (m, 3H), 3.80 (s, 3H), 4.12 (m, 1H), 4.26 (m, 1H), 4.50
(q, J ) 11.5, 11.5 Hz, 2H), 4.92 (s, 1H), 6.87 (d, J ) 8.5 Hz, 2H),
7.08 (d, J ) 8.0 Hz, 2H), 7.20-7.26 (m, 4H). 13C NMR (CDCl3):
δ 20.9, 52.9, 54.9, 55.1, 69.2 (CH2), 73.1 (CH2), 80.6, 83.7, 110.0,
113.8, 129.0, 129.4, 129.7, 130.8, 131.6, 136.8, 159.3. Anal. calcd
for C21H26O5S: C, 64.59; H, 6.71. Found: C, 64.48; H, 6.73.
Methyl 3,5-Cyclo-2-(acetyloxyethyl)-2,3,5-trideoxy-R-D-ara-
binofuranoside (22). Compound 19 (0.49 g, 1.44 mmol) was
converted to 22 following the general procedure (0.22 g, 75%).
Eluent: EtOAc/petroleum ether (1:5). Yellow oil. [R]27D (+) 202.6
(c 0.76, CHCl3). 1H NMR (CDCl3): δ 0.44-0.57 (m, 2H), 1.57-
1.98 (m, 3H), 2.05 (s, 3H), 2.46 (m, 1H), 3.34 (s, 3H), 4.03-4.19
(m, 3H), 4.41 (d, J ) 3.0 Hz, 1H). 13C NMR (CDCl3): δ 12.1
(CH2), 17.6, 20.7, 28.5 (CH2), 43.5, 55.3, 58.4, 62.8 (CH2), 113.8,
170.8. IR (KBr): 1093, 1243, 1366, 1740 cm-1. Anal. calcd for
C10H16O4: C, 59.98; H, 8.05. Found: C, 60.20; H, 8.39.
(1R,2R)-2-{(1S)-3-(Acetyloxy)-1-[bis(ethylthio)methyl]propyl}-
cyclopropyl Acetate (23). Compound 22 (0.17 g, 0.85 mmol) was
converted to 23 following the general procedure (0.2 g, 71%).
Eluent: EtOAc/petroleum ether (1:6). Yellow oil. [R]27D (+) 11.7
Methyl 3-Deoxy-2-O-methyl-3-S-(4-methylphenyl)-3-thio-r-
D-arabinofuranoside (31). Compound 28 (0.66 g, 1.7 mmol) was
converted to 31 following the general procedure (0.41 g, 85%).
Eluent: EtOAc/petroleum ether (1:3). Yellow gum. [R]27D (+) 158.4
1
(c 3.34, CHCl3). H NMR (CDCl3): δ 2.32 (S, 3H), 3.27 (s, 3H),
3.37 (s, 3H), 3.42 (m, 1H), 3.76-3.78 (m, 2H), 4.05 (m, 1H), 4.92
(s, 1H), 5.30 (s, 1H), 7.12 (d, J ) 8.0 Hz, 2H), 7.37 (d, J ) 8.1
Hz, 2H). 13C NMR (CDCl3): δ 20.9, 50.3, 54.6, 57.4, 61.7 (CH2),
83.5, 91.6, 107.2, 129.7, 130.3, 132.3, 137.5. Anal. calcd for
C14H20O4S: C, 59.13; H, 7.09. Found: C, 58.73; H, 7.36.
Methyl 2-O-Benzyl-3-deoxy-3-S-(4-methylphenyl)-3-thio-r-D-
arabinofuranoside (32). Compound 28 (0.72 g, 1.8 mmol) was
converted to 32 following the general procedure (0.55 g, 82%).
Eluent: EtOAc/petroleum ether (1:3). Yellow gum. [R]27D (+) 102.6
1
(c 0.56, CHCl3). H NMR (CDCl3): δ 0.50 (m, 1H), 1.05-1.15
1
(c 0.9, CHCl3). H NMR (CDCl3): δ 2.33 (s, 3H), 3.35 (s, 3H),
(m, 2H), 1.18-1.31 (m, 6H), 1.77-1.82 (m, 2H), 2.03 (s, 3H),
2.05 (s, 3H), 2.15 (m, 1H), 2.62-2.70 (m, 4H), 3.99 (d, J ) 2.4
Hz, 1H), 4.10-4.35 (m, 3H). 13C NMR (CDCl3): δ 11.2 (CH2),
14.5, 14.6, 19.9, 20.8, 20.9, 26.3 (CH2), 26.7 (CH2), 30.5 (CH2),
39.8, 52.4, 57.0, 62.8 (CH2), 170.8, 171.3. IR (KBr): 1037, 1241,
1371, 1732, 1732, 1747 cm-1. Anal. calcd for C15H26O4S2: C,
53.86; H, 7.83. Found: C, 53.55; H, 7.56.
Methyl 3,5-Cyclo-2-(methoxycarbonylmethyl)-3-(4-methyl-
phenyl)sulfonyl-2,3,5-trideoxy-â-D-ribofuranoside (24). Com-
pound 15 (0.52 g, 1.3 mmol) was converted to 24 following the
general procedure (0.37 g, 83%). Eluent: EtOAc/petroleum ether
3.47-3.66 (m, 2H), 3.83 (m, 1H), 3.99-4.10 (m, 2H), 4.42 (q, J
) 11.7, 11.7 Hz, 2H), 4.94 (s, 1H), 7.10 (d, J ) 8.0 Hz, 2H), 7.19-
7.37 (m, 7H). 13C NMR (CDCl3): δ 21.0, 51.0, 54.8, 61.9 (CH2),
71.8 (CH2), 83.3, 89.6, 107.7, 127.7, 127.8, 128.3, 129.9, 130.2,
132.6, 137.2, 137.7. Anal. calcd for C20H24O4S: C, 66.64; H, 6.71.
Found: C, 66.70; H, 6.86.
Methyl 3-Deoxy-5-O-mesyl-2-O-methyl-3-(4-methylphenyl)-
sulfonyl-r-D-arabinofuranoside (35). Compound 31 (0.44 g, 1.55
mmol) was converted to 35 following the general procedure (0.57
g, 93%). Eluent: EtOAc/petroleum ether (1:3). White crystalline
solid. Solvent of crystallization: DCM and petroleum ether. Mp:
(1:4). White crystalline solid. Solvent of crystallization: acetone
1
98 °C. [R]27 (+) 81.4 (c 2.0, CHCl3). H NMR (CDCl3): δ 2.47
1
and petroleum ether. [R]27 (-) 41.6 (c 0.76, CHCl3). H NMR
D
D
(s, 3H), 3.05 (s, 3H), 3.14 (s, 3H), 3.30 (s, 3H), 3.58 (dd, J ) 3.4,
8.6 Hz, 1H), 4.11-4.24 (m, 2H), 4.49-4.65 (m, 2H), 4.88 (s, 1H),
7.40 (d, J ) 8.3 Hz, 2H), 7.82 (d, J ) 8.3 Hz, 2H). 13C NMR
(CDCl3): δ 21.6, 37.7, 54.8, 57.6, 68.7 (CH2), 69.0, 75.3, 86.6,
107.0, 128.6, 130.0, 134.7, 145.7. Anal. calcd for C15H22O8S2: C,
45.67; H, 5.62. Found: C, 45.78; H, 5.40.
(CDCl3): δ 1.76 (t, J ) 6.6 Hz, 1H), 1.91 (dd, J ) 3.2, 6.6 Hz,
1H), 2.44 (s, 3H), 2.48-2.59 (m, 2H), 3.16 (m, 1H), 3.27 (s, 3H),
3.67 (s, 3H), 4.74 (m, 1H), 4.83 (s, 1H), 7.34 (d, J ) 7.9 Hz, 2H),
7.71 (d, J ) 8.3 Hz, 2H). 13C NMR (CDCl3): δ 21.3, 22.1 (CH2),
34.1 (CH2), 44.5, 46.4, 51.5, 54.9, 64.7, 112.4, 127.1, 129.8, 137.2,
144.4, 171.7. IR (KBr): 1086, 1303, 1312, 1737 cm-1. Anal. calcd
for C16H20O6S: C, 56.46; H, 5.92. Found: C, 56.56; H, 6.03.
Methyl 3,5-Cyclo-2-(acetyloxyethyl)-2,3,5-trideoxy-â-D-ribo-
furanoside (25). Compound 24 (0.24 g, 0.7 mmol) was desulfo-
nylated to 25 following the general procedure (0.1 g, 71%).
Eluent: EtOAc/petroleum ether (1:5). Yellow oil. [R]27D (-) 47.2
(c 0.7, CHCl3). 1H NMR (CDCl3): δ 0.52 (m, 1H), 0.93 (m, 1H),
1.28 (m, 1H), 1.64-1.81 (m, 2H), 2.05 (s, 3H), 2.18 (m, 1H), 3.27
(s, 3H), 4.00 (m, 1H), 4.14 (t, J ) 6.7 Hz, 2H), 4.81 (s, 1H). 13C
NMR (CDCl3): δ 12.7 (CH2), 18.6, 20.8, 31.7 (CH2), 45.0, 54.5,
59.3, 62.3 (CH2), 112.0, 170.9. IR (KBr): 772, 1086, 1245, 1741
cm-1. Anal. calcd for C10H16O4: C, 59.98; H, 8.05. Found: C,
60.20; H, 8.13.
Methyl 2-O-Benzyl-3-deoxy-5-O-mesyl-3-(4-methylphenyl)-
sulfonyl-r-D-arabinofuranoside (36). Compound 32 (0.27 g, 0.75
mmol) was converted to 36 following the general procedure (0.31
g, 90%). Eluent: EtOAc/petroleum ether (1:3). White crystalline
solid. Solvent of crystallization: DCM and petroleum ether. Mp:
105 °C. [R]27D (+) 37.9 (c 2.6, CHCl3). 1H NMR (CDCl3): δ 2.45
(s, 3H), 3.02 (s, 3H), 3.27 (s, 3H), 3.71 (dd, J ) 3.7, 8.6 Hz, 1H),
4.22-4.32 (m, 4H), 4.53-4.62 (m, 2H), 4.90 (s, 1H), 7.05-7.10
(m, 2H), 7.26-7.38 (m, 5H), 7.77 (d, J ) 8.3 Hz, 2H). 13C NMR
(CDCl3): δ 21.5, 37.6, 54.8, 68.7 (CH2), 69.2, 72.0 (CH2), 75.0,
84.7, 107.1, 127.7, 127.9, 128.2, 130.0, 134.6, 136.3, 145.5. Anal.
calcd for C21H26O8S2: C, 53.60; H, 5.57. Found: C, 53.70; H, 5.54.
(1R,2R)-2-{(1R)-3-(Acetyloxy)-1-[bis(ethylthio)methyl]propyl}-
cyclopropyl Acetate (26). Compound 25 (0.08 g, 0.4 mmol) was
converted to 26 following the general procedure (0.09 g, 68%).
Eluent: EtOAc/petroleum ether (1:7). Yellow oil. [R]27D (-) 63.8
Methyl 3,5-Cyclo-3,5-dideoxy-2-O-methyl-3-(4-methylphenyl)-
sulfonyl-r-D-arabinofuranoside (8). Compound 35 (0.14 g, 0.35
mmol) was converted to 8 following the general procedure (0.09
g, 82%). Eluent: EtOAc/petroleum ether (1:3). White crystalline
solid.
1
(c 0.56, CHCl3). H NMR (CDCl3): δ 0.51 (m, 1H), 1.03-1.14
9188 J. Org. Chem., Vol. 72, No. 24, 2007

Stereospecific Route to R-Substituted Cyclopropanes
Methyl 2-O-Benzyl-3,5-cyclo-3,5-dideoxy-3-(4-methylphenyl)-
sulfonyl-r-D-arabinofuranoside (9). Compound 36 (0.2 g, 0.42
mmol) was converted to 9 following the general procedure (0.13
g, 81%). Eluent: EtOAc/petroleum ether (1:5). White amorphous
solid.
2.46 (s, 3H), 3.06 (s, 3H), 3.08 (s, 3H), 3.45 (s, 3H), 3.85 (m, 1H),
4.13 (dd, J ) 1.9, 6.6 Hz, 1H), 4.64-4.88 (m, 4H), 7.38 (d, J )
8.0 Hz, 2H), 7.79 (d, J ) 8.3 Hz, 2H). 13C NMR (CDCl3): δ 21.6,
37.4, 55.9, 58.0, 69.5 (CH2), 70.1, 77.0, 86.6, 109.2, 128.3, 129.9,
135.9, 145.5. Anal. calcd for C15H22O8S2: C, 45.67; H, 5.62.
Found: C, 45.29; H, 5.47.
Methyl 2-O-Benzyl-3-deoxy-5-O-mesyl-3-(4-methylphenyl)-
sulfonyl-â-D-xylofuranoside (46). Compound 42 (0.15 g, 0.42
mmol) was converted to 46 following the general procedure (0.18
g, 90%). Eluent: EtOAc/petroleum ether (1:3). White crystalline
Methyl 3-Deoxy-5-O-p-methoxybenzyl-3-S-(4-methylphenyl)-
3-thio-â-D-xylofuranoside (38). Compound 7 (0.44 g, 3.0 mmol)
was converted to 38 following the general procedure (0.85 g, 72%).
Eluent: EtOAc/petroleum ether (1:3). Yellow gum. [R]27D (+) 22.4
1
(c 4.2, CHCl3). H NMR (CDCl3): δ 2.31 (s, 3H), 3.41 (s, 3H),
3.60-3.75 (m, 3H), 3.80 (s, 3H), 4.28 (m, 1H), 4.51 (s, 2H), 4.59
(m, 1H), 4.84 (d, J ) 2.2 Hz, 1H), 6.86 (d, J ) 8.5 Hz, 2H), 7.08
(d, J ) 7.9 Hz, 2H), 7.24-7.32 (m, 4H). 13C NMR (CDCl3): δ
20.7, 54.8, 55.0, 55.3, 70.8 (CH2), 72.7 (CH2), 79.8, 81.2, 109.3,
113.5, 129.2, 129.6, 130.0, 130.4, 132.0, 136.5, 158.9. Anal. calcd
for C21H26O5S: C, 64.59; H, 6.71. Found: C, 64.78; H, 7.01.
Methyl 3-Deoxy-2-O-methyl-3-S-(4-methylphenyl)-3-thio-â-
D-xylofuranoside (41). Compound 38 (0.4 g, 1.02 mmol) was
converted to 41 following the general procedure (0.24 g, 81%).
Eluent: EtOAc/petroleum ether (1:3). Yellow gum. [R]27D (-) 49.7
solid. Solvent of crystallization: DCM and petroleum ether. Mp:
1
134 °C. [R]27 (+) 5.1 (c 0.4, CHCl3). H NMR (CDCl3): δ 2.41
D
(s, 3H), 3.09 (s, 3H), 3.41 (s, 3H), 4.00 (m, 1H), 4.12-4.39 (m,
3H), 4.67 (m, 1H), 4.81-4.90 (m, 3H), 6.85-6.89 (m, 2H), 7.23-
7.33 (m, 5H), 7.77 (d, J ) 8.3 Hz, 2H). 13C NMR (CDCl3): δ
21.5, 37.3, 55.9, 69.5 (CH2), 70.2, 72.7 (CH2), 76.9, 85.2, 109.3,
127.5, 127.8, 128.1, 128.2, 129.9, 135.8, 136.2, 145.4. Anal. calcd
for C21H26O8S2: C, 53.60; H, 5.57. Found: C, 53.71; H, 5.37.
Methyl 3,5-Cyclo-3,5-dideoxy-2-O-methyl-3-(4-methylphenyl-
)sulfonyl-â-D-ribofuranoside (13b). Compound 45 (0.12 g, 0.3
mmol) was converted to 13b following the general procedure (0.07
g, 77%). Eluent: EtOAc/petroleum ether (1:3). White crystalline
solid.
1
(c 1.08, CHCl3). H NMR (CDCl3): δ 2.32 (s, 3H), 3.40 (s, 3H),
3.46 (s, 3H), 3.65-3.93 (m, 4H), 4.45 (m, 1H), 4.88 (d, J ) 2.1
Hz, 1H), 7.10 (d, J ) 8.5 Hz, 2H), 7.33 (d, J ) 8.2 Hz, 2H). 13C
NMR (CDCl3): δ 20.9, 53.3, 55.8, 58.3, 63.1 (CH2), 82.6, 91.2,
108.5, 129.2, 129.8, 130.9, 131.9, 137.0. Anal. calcd for
C14H20O4S: C, 59.13; H, 7.09. Found: C, 59.34; H, 7.19.
Methyl 2-O-Benzyl-3,5-cyclo-3,5-dideoxy-3-(4-methylphenyl)-
sulfonyl-â-D-ribofuranoside (14). Compound 46 (0.1 g, 0.21
mmol) was converted to 14 following the general procedure (0.06
g, 72%). Eluent: EtOAc/petroleum ether (1:5). White amorphous
solid.
Methyl 2-O-Benzyl-3-deoxy-3-S-(4-methylphenyl)-3-thio-â-D-
xylofuranoside (42). Compound 38 (0.33 g, 0.84 mmol) was
converted to 42 following the general procedure (0.24 g, 80%).
Eluent: EtOAc/petroleum ether (1:3). Yellow gum. [R]27D (-) 61.9
Acknowledgment. T.P. thanks the DST, New Delhi, India
for financial support. I.D. and T.K.P. thank the Council of
Scientific and Industrial Research, New Delhi, India for fel-
lowships. The authors thank one of the referees for suggesting
one of the pathways for the formation of lactone 21.
1
(c 1.2, CHCl3). H NMR (CDCl3): δ 2.32 (s, 3H), 3.41 (s, 3H),
3.75-3.89 (m, 3H), 4.15 (dd, J ) 1.9, 6.6 Hz, 1H), 4.44-4.59 (m,
3H), 4.91 (d, J ) 2.0 Hz, 1H), 7.09 (d, J ) 8.0 Hz, 2H), 7.23-
7.36 (m, 7H). 13C NMR (CDCl3): δ 20.9, 53.7, 55.8, 63.2 (CH2),
72.7 (CH2), 82.6, 89.7, 108.8, 127.7, 128.3, 129.8, 131.0, 131.9,
137.0, 137.4. Anal. calcd for C20H24O4S: C, 66.64; H, 6.71.
Found: C, 66.33; H, 6.69.
Supporting Information Available: General experimental
methods, ORTEP diagrams, and crystallographic information files
for 11, 12, 21, and 24 and spectra of all new compounds. This
material is available free of charge via the Internet at http:
//pubs.acs.org.
Methyl 3-Deoxy-5-O-mesyl-2-O-methyl-3-(4-methylphenyl)-
sulfonyl-â-D-xylofuranoside (45). Compound 41 (0.2 g, 0.7 mmol)
was converted to 45 following the general procedure (0.25 g, 89%).
Eluent: EtOAc/petroleum ether (1:3). White crystalline solid.
Solvent of crystallization: EtOAc and petroleum ether. Mp:
1
108 °C. [R]27 (-) 25.2 (c 0.76, CHCl3). H NMR (CDCl3): δ
JO701378D
D
J. Org. Chem, Vol. 72, No. 24, 2007 9189