A general route to mono- and disubstituted divinyl sulfones: Acyclic michael acceptors for the synthesis of polyfunctionalized cyclic sulfones

Article abstract of DOI:10.1021/jo101877r

Nucleophilic C-S bond formation using easily available β- hydroxysulfonate derivatives allowed direct access to new mono- and disubstituted divinyl sulfones. Our strategy uses thioethanol (HSCH ₂CH₂OH) and its analogues such as HSCH₂CH(Y)OH generated in situ. The strategy also allows the synthesis of modified divinyl sulfones attached to chiral appendages like carbohydrates. Bis- heteronucleophilic Michael addition reactions with 1 equiv of a primary amine afforded new generations of S,S-dioxothiomorpholine derivatives known for their therapeutic applications. Further synthetic manipulations of some of these cyclic compounds led to the synthesis of novel bicyclic derivatives.

Full text of DOI:10.1021/jo101877r

ARTICLE
pubs.acs.org/joc
A General Route to Mono- and Disubstituted Divinyl Sulfones:
Acyclic Michael Acceptors for the Synthesis of Polyfunctionalized
Cyclic Sulfones
Tarun Kumar Pal, Santu Dey, and Tanmaya Pathak*
Department of Chemistry, Indian Institute of Technology Kharagpur, Kharagpur 721 302, India
S Supporting Information
b
ABSTRACT: Nucleophilic CꢀS bond formation using easily
available β-hydroxysulfonate derivatives allowed direct access to
new mono- and disubstituted divinyl sulfones. Our strategy uses
thioethanol (HSCH2CH2OH) and its analogues such as
HSCH2CH(Y)OH generated in situ. The strategy also allows
the synthesis of modified divinyl sulfones attached to chiral
appendages like carbohydrates. Bis-heteronucleophilic Michael
addition reactions with 1 equiv of a primary amine afforded new
generations of S,S-dioxothiomorpholine derivatives known for
their therapeutic applications. Further synthetic manipulations
of some of these cyclic compounds led to the synthesis of novel
bicyclic derivatives.
’ INTRODUCTION
because of the nonavailability of suitable and efficient strategies
for the synthesis of functionalized divinyl sulfones 3, especially
the DVS skeleton attached to chiral moieties. Knoevenagel
condensation of sulfonyl acetic acids with aldehydes and other
reagents,15 metal-mediated coupling of sulfonyl chlorides and
olefins,15 FriedelꢀCrafts reactions of olefins,16 and functionali-
zation of dimethyl sulfone17 are the most popular methods used
so far for the synthesis of substituted divinyl sulfones. More
recently, commercially available DVS 1 was converted to (E)-
alkenylvinyl sulfones and (E,E)-dialkenyl sulfones by using cross-
metathesis strategy; however, this strategy depends crucially on
the availability of olefinic compounds required for coupling with
DVS and the process also incurs a loss of up to two molecules of
C2H4 for the synthesis of each molecule of disubstituted divinyl
sulfones.3
Considering the acute shortage of the synthetic strategies for
accessing substituted divinyl sulfones mentioned above, our
association with vinyl sulfone chemistry18 prompted us to opine
that one of the easiest ways of forming a CꢀS bond is to treat a
thiolate nucleophile with carbon-bearing leaving groups such as
sulfonates derived from the corresponding alcohols. Thus,
following this strategy, the thio nucleophile generated from
mercaptoethanol (HSCH2CH2OH) would easily react with a
β-hydroxysulfonate derivative 4 to generate the starting material
5 for the synthesis of substituted divinyl sulfones. Moreover, two
molecules of 4 may be coupled with a sulfur atom to generate
more complex intermediates 6 for accessing densely substituted
divinyl sulfones (Scheme 2).
Divinyl sulfone (DVS) or 1,10-sulfonylbisethene (1, Scheme 1)
is a unique molecule having diverse applications in chemistry1,2
and biology.3 Conjugate addition of carbon nucleophiles4 and
heteronucleophilic addition of primary amines,5 thiols,6 selenium,7
tellurium,7 andphosphanes8 tothetwo vinyl groups of 1 constitute
a class of efficient and synthetically useful reactions for the
generation of cyclic compounds represented by the general
structure 2 (Scheme 1).1ꢀ3 Compound 1 has also been used in
the preparation of macrocycles2,9 and polymeric compounds.10
DVS 1 is shown to be a component of the Stetter reaction in the
synthesis of 1,4-diketo derivatives.1
Compound 1 was also studied recently for its inhibitory
properties against glyceraldehyde-3-phosphate dehydrogenase,11a
inducible vascular cell adhesion molecule-1 (VCAM-1) expression,11b
SrtA, a transpeptidase required for cell wall protein anchoring
and virulence in Staphylococcus aureus,11c cysteine protease of
Plasmodium falciparum,11d etc. Functionalized divinyl sulfones
such as 3 were screened as anti-inflammatory12a and tumor cell
growth inhibitory12a agents.12bꢀd
In the quest for new chemical entities with potential biological
activities, we recently reported the synthesis of divinyl sulfone-
modified pent-2-enofuranosides for the first time; one of these
modified divinyl sulfones initiated significant cell death in
Entameaba species; the most active compound in this series
was found to be devoid of any toxicity.13
’ RESULTS AND DISCUSSION
In spite of the reported applications of DVS 1, the utilization of
DVS in chemistry and biology is restricted to a great extent
Received: September 23, 2010
Published: March 25, 2011
r
2011 American Chemical Society
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Scheme 1. Reaction Patterns of Divinyl Sulfones
Scheme 3. Synthesis of Mono- and Disubstituted Divinyl
Sulfones from Glycerol Derivatives
Scheme 2. Strategy for the Synthesis of Intermediates for
Accessing Substituted Divinyl Sulfones
To test the hypothesis, we targeted the synthesis of two triose
derived divinyl sulfones 10 and 13 (Scheme 3). Thus the
synthesis started from the easily available monotosylated and
partially protected glycerol derivative 7a,7a,19 which was treated
with mercaptoethanol in the presence of tetramethylguanidine
(TMG) at an elevated temperature to obtain the sulfide 8
contaminated with inseparable materials. The impure sulfide 8
was therefore oxidized directly with magnesium monoperoxy-
phthalate hexahydrate (MMPP) to the corresponding sulfone 9,
which was isolated in pure form in 78% overall yield in two steps.
Mesylation of the diol and the consequent elimination of mesyl
groups generated the monosubstituted divinyl sulfone 10 in 89%
yield. On the other hand, when 2 equiv of the same starting
material 7a was treated with 1 equiv of Na2S, a symmetrical
sulfide 11 was obtained in 78% yield. The sulfide 11 was oxidized
to sulfone 12 in excellent yield and the latter was converted to
disubstituted divinyl sulfone 13 by using mesyl chloride in
pyridine (Scheme 3). It is also possible to use epoxide 7b7b as
an alternative starting material, which can also react efficiently
with sulfur nucleophiles to generate 8 or 11. Thus, 7b was treated
with mercaptoethanol in the presence of tetramethylguanidine
(TMG) to generate 8. In this case also it was difficult to obtain
sulfide 8 in pure form. Therefore the impure sulfide was isolated
as sulfone 9 in pure form as above. Reactions of epoxide 7b with
0.5 equiv of Na2S in MeOH, however, generated a mixture of
products from which 11 could not be separated. Use of DMF
instead of MeOH afforded a single product 11 in high yield.
The disappearance of the tosylate methyl signal at δ 2.44 (1H
NMR) and the appearance of two extra methylene carbon signals
at δ 35.9 and 61.3 confirmed the formation of the product 8 from
7. Compound 8 generates five methylene carbon signals as
indicated by its 13C NMR spectra. Two of these peaks (δ 35.9
and 36.2) shifted downfield (δ 56.2 and 56.8) when 8 was
oxidized to 9. These latter set of methylene carbon signals
disappeared in compound 10. Compound 10 has five olefinic
protons in the range δ 6.07ꢀ6.96. The vinylic methylene protons
at δ 6.07 (J = 9.6 Hz) and δ 6.4 (J = 16.4 Hz) indicate the cis and
trans nature, respectively. The peaks at δ 6.96 representing the
other vinyl proton possessing a J value of 15.2 Hz indicate the
trans configuration of the substituted vinyl group. The two
protons R to the SO2 group overlap in the region δ 6.59ꢀ6.61.
The vinylic methylene carbon and the other vinylic carbon
signals appeared at δ 128.9 and 144.7, respectively. The two
carbons connected to the SO2 group appeared at δ 128.4
(CH2CHdCHSO2) and 137.3 (CH2dCHSO2).
In the 1H NMR spectrum of the product obtained by treating
7a with Na2S, the tosylate methyl signal at δ 2.44 disappeared
and an extra methylene carbon signal at δ 36.4 confirmed the
formation of the product 11 from 7a and 7b. However, the 13C
NMR spectrum of the product indicated the presence of three
methylene carbon signals as opposed to five signals in the spectra
of 8. We therefore concluded that the product in this case was
dimeric and assigned the structure 11. Out of three methylene
carbon signals, the signal at δ 36.4 shifted downfield (δ 57.8 and
57.9) when 11 was oxidized to 12. Dimerization of racemic 7a or
7b is expected to produce a mixture of racemates and the meso
compound. Therefore, there should have been six methylene
signals in the 13C NMR spectra of 11. We presume that in the
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Scheme 4. Synthesis of Mono- and Disubstituted Divinyl
Sulfones from a D-Glucose Derivative
Scheme 5. Reactions of Glycerol Derived Divinyl Sulfones
with Benzylamine
establish the general application of the strategy shown above.
Thus, compound 14 was treated with mercaptoethanol and
TMG at an elevated temperature to obtain the sulfide 15 in
95% yield. The sulfide was oxidized with MMPP to the corre-
sponding sulfone 16 in 85% yield. Mesylation of the diol
generated the monosubstituted divinyl sulfone 17 in one pot
fashion in 88% yield. When 2 equiv of the same starting material
14 was treated with 1 equiv of Na2S, a symmetrical sulfide 18 was
obtained in 82% yield. The sulfide 18 was oxidized to sulfone 19
in excellent yield and the latter was converted to disubstituted
divinyl sulfone 20 in the usual way. Compound 20 was a mixture
of isomers from which the transꢀtrans isomer 20trans was
separated by crystallization (Scheme 4).
The disappearance of the tosylate methyl signal at δ 2.44 (1H
NMR) and the appearance of two extra methylene carbon signals
at δ 35.6 and 60.9 confirmed the formation of the product 15
from 14. Two (δ 35.6 and 36.9) of the four methylene carbon
signals generated from 15 shifted downfield (δ 56.1 and 56.8)
when it was oxidized to 16. As expected, the latter set of
methylene carbon signals disappeared when compound 17 was
formed. Compound 17 generated five olefinic proton signals at δ
5.98ꢀ6.92; three of them possess J values of 16.8, 15.2, and 14.8
Hz indicating the trans configuration of the substituted double
bond present in 17. Compound 18 generated only two methy-
lene carbon signals at δ 37.7 and 72.2, indicating the presence of a
dimeric structure in the product. The peak at δ 37.7 shifted
downfield to δ 58.4 when 18 was oxidized to 19. The methylene
carbon signal at δ 58.4 generated from 19 disappeared in the 13C
spectra of pure 20trans. The J values 15.2 and 14.8 Hz of the
olefinic proton signals generated by 20trans indicated the
presence of trans-configured double bonds. The structure of
compound 20trans was unambiguously established on the basis
of the X-ray diffraction studies of its single crystal.
Synthetic Applications of Divinyl Sulfones. We subjected
these new divinyl sulfones to bis-heteronucleophilic Michael
addition reactions with a primary amine because there are
numerous references on the use of S,S-dioxothiomorpholine
derivatives (2, X = NR, N-NHR) as components of therapeuti-
cally relevant compounds.3,21 Although this class of compounds
can be easily obtained by reacting a primary amine or hydrazine
with divinyl sulfone 1, a substituted variety of S,S-dioxothiomor-
pholine would be easily accessible from the new substituted
divinyl sulfones 10, 13, 17, or 20. Thus, 1 equiv of benzylamine at
room temperature reacted with the monosubstituted divinyl
sulfone 10 to afford a cyclic product 21. The disubstituted divinyl
sulfone 13 also underwent bis-heteronucleophilic Michael addi-
tion reactions with 1 equiv of benzylamine at room temperature
to afford a new thiomorpholine S,S-dioxide derivative 22
(Scheme 5). The disappearance of olefinic proton signals in
the 1H NMR spectra and the appearance of the extra methylene
case of 11 two sets of chemical shift values overlapped and thus
only three methylene carbon signals appeared. However, for the
sulfone 12, the 13C NMR spectrum did indeed show six
methylene carbon signals as expected. Two methylene carbon
signals of 12 at δ 57.8 and 57.9 disappeared in the spectra of
compound 13. For compound 13 four olefinic protons (δ 6.60
1
and 6.92) appeared in the H NMR spectrum. Both of these
proton signals possessed J values of ∼15 Hz, which once again
indicated trans configurations of both the olefinic bonds of
compound 13.
A more complex system, partially protected monotosylated
derivative 1420 (Scheme 4) of D-glucose, was selected next to
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Scheme 6. Reactions of Sugar Substituted Divinyl Sulfone
with Primary Amines
Scheme 8. SO2-Extrusion Reaction of a Sugar Derived
Thiomorpholine S,S-Dioxide
Scheme 7. Reactions of D-Glucose Derived Disubstituted
Divinyl Sulfone with Benzylamine and Hydrazine Hydrate
afford a single thiomorpholine S,S-dioxide derivative 26. Hydra-
zine hydrate too added smoothly to 20 to afford a single cyclic
analogue 27 (Scheme 7). The absence of signals of olefinic
protons in the 1H NMR spectrum of 26 and the appearance of
the new methylene carbon peaks at δ 48.9 and 51.5 clearly
indicated the formation of the product 26. For the hydrazine
derivative 27 the new methylene carbon signals appeared at
δ 56.6 and 57.2. In this case also we presumed that the bulky
sugar residues occupied equatorial position(s) of the six-mem-
bered rings and each of the compounds 26 and 27 is a single
diastereomer.
Synthetic manipulations of this new generation of thiomor-
pholine S,S- dioxides are expected to afford novel compounds.
For example, compound 23 was debenzylated efficiently in the
presence of commonly used protecting groups to generate 25
(Scheme 6) having the basic thiomorpholine S,S-dioxide skele-
ton with a sugar substitution attached to the ring as well as a
reactive secondary amino group; the compound may be used for
attaching this new scaffold with other molecules. The sulfur extrusion
reaction performed on 23 by using modified RambergꢀB€acklund
conditions afforded an olefinic derivative 28 (Scheme 8) that is
reportedly the starting material for the synthesis of sugar sub-
stituted dihydroxylated pyrrolidine 28a and uniflorine A analo-
gue 28b.22
Sugar ring opening of 23 followed by debenzylation of the
thiomorpholine group and cyclization of the intermediate 23a
afforded a new generation of octahydropyrido[2,1-c][1,4]
thiazine 2,2-dioxide derivative 29, which was isolated as the
acetylated compound 30 (Scheme 9). The structuture of the
compound was unambiguously identified by the X-ray analysis of
its single crystal. Although analogues of octahydropyrido[2,1-c]-
[1,4]thiazine-7,8,9-triol are known23 for their modest glycosidase
inhibitory activities, virtually nothing is known about the properties
of a compound like 30.
carbon signals at δ 46.9, 49.2, 51.6, and 55.1 of the product
obtained from the reactions of 10 and benzylamine clearly
indicated the formation of 21. Similar observations also indicated
the transformation of 13 to the cyclic sulfone 22. The efficiency
of transformations of 10 and 13 to 21 and 22 respectively
established the highly reactive nature of substituted divinyl
sulfones. We presumed that in both cases, the bulky ꢀOCH2OBn
group occupied equatorial position(s) of the six-membered rings
of compound 21, which is racemic, with 22 being a meso-
compound. When 21 was treated with 1 equiv of n-butylamine
in MeOH for 4 h at 40 °C, unreacted starting materialwas isolated;
this reaction established that a compound like 21 did not undergo
retro-Michael addition reaction and the process of addition
of amines to vinyl sulfone-modified carbohydrates is not
reversible.
The easy synthesis of 21 and 22 prompted us to treat
monosubstituted divinyl sulfone 17 with 1 equiv of benzylamine
and ethanolamine at room temperature; the amines added
smoothly to 17 in Michael fashion to afford the thiomorpholine
S,S-dioxide derivatives 23 and 24 in excellent yields (Scheme 6).
1
The absence of signals of olefinic protons in the H NMR
spectrum of 23 and the appearance of four additional methylene
carbon signals at δ 43.4, 49.9, 51.3, and 56.7 clearly indicated the
formation of the cyclic product containing benzylamine. Similar
change of spectral data also confirmed the formation of 24 from
17. The structure of compound 23 was unambiguously estab-
lished on the basis of the X-ray diffraction studies of its single
crystal. The mixture of sugar derived disubstituted divinyl sul-
fones 20 also underwent bis-heteronucleophilic Michael addition
reactions with 1 equiv of benzylamine at room temperature to
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Scheme 9. Synthesis of Octahydropyrido[2,1-c][1,4]thiazine
2,2-Dioxide
an inseparable compound. A small amount of compound 8 was obtained
in pure form. Eluent: EtOAc:petroleum ether (1:1). Colorless liquid. 1H
NMR (CDCl3) δ 2.55 (br s, 1H), 2.62ꢀ2.67 (m, 1H), 2.74ꢀ2.78 (m,
3H), 2.89 (br s, 1H), 3.48ꢀ3.57 (m, 2H), 3.74ꢀ3.76 (m, 2H), 3.95 (br s,
1H), 4.56 (s, 2H), 7.29ꢀ7.38 (m, 5H). 13C NMR (CDCl3) δ 35.9
(CH2), 36.2 (CH2), 61.3 (CH2), 70.1, 73.1 (CH2), 73.7 (CH2), 128.0,
128.7, 128.4, 138.0. HRMS [ESþ, (M þ Na)þ] for C12H18O3SNa obsd
265.0872, calcd 265.0874. To a well-stirred solution of the impure 8
(1.32 g) in dry MeOH (25 mL) was added MMPP (5.38 g, 11.89 mmol)
and the mixture was stirred under N2. After 6 h, MeOH was evaporated
under reduced pressure and the residue thus obtained was dissolved in
satd. NaHCO3 solution (30 mL). The solution was washed with EtOAc
(3 ꢁ 15 mL). Combined organic layers were dried over anhyd. Na2SO4
and filtered and the filtrate was concentrated under reduced pressure to
obtain a residue. The residue was purified over silica gel to obtain sulfone
9 (1.27 g, 78%). Eluent: EtOAc:petroleum ether (3:2). Colorless liquid.
1H NMR (CDCl3) δ 2.99 (br s, 1H), 3.13 (d, J = 14.8 Hz, 1H),
3.21ꢀ3.36 (m, 1H), 3.39ꢀ3.54 (m, 5H), 4.08 (br s, 2H), 4.43 (br s, 1H),
4.52ꢀ4.58 (m, 2H), 7.30ꢀ7.46 (m, 5H). 13C NMR (CDCl3) δ 56.2
(CH2), 56.8 (CH2), 57.9 (CH2), 65.7, 72.6 (CH2), 73.4 (CH2), 127.8,
128.0, 128.5, 137.3. HRMS [ESþ, (M þ Na)þ] for C12H18O5SNa obsd
297.0764, calcd 297.0773.
Compound 9 from 7b: A mixture of marcaptoethanol (2.6 mL,
36.58 mmol) and TMG (4.6 mL, 36.58 mmol) in DMF (20 mL) was
heated at 90 °C for 30 min. The epoxide 7b (3.0 g, 18.29 mmol) was
added to this mixture and the mixture was heated at 90 °C under N2.
After 5 h, the reaction mixture was poured into a satd. solution of
NaHCO3 (60 mL) and the product was extracted with EtOAc (3 ꢁ
30 mL). The combined organic layers were dried over anhyd. Na2SO4
and filtered and the filtrate was concentrated under reduced pressure.
The residue was purified over silica gel column to obtain the sulfide 8
contaminated with an inseparable compound. To a solution of the
sulfide 8 (3.45 g) in dry MeOH (30 mL) was added MMPP (14.11 g,
28.52 mmol). Sulfone 9 was purified and isolated following the
procedure described above. Yield: 3.17 g (81%).
In conclusion we have designed an efficient and general
strategy for the synthesis of mono- and disubstituted divinylsul-
fones. The advantage of using our synthetic strategy would be
that mono- and disubstituted divinyl sulfones can be synthesized
from the same starting material by using different reaction
procedures. Moreover, DVSs attached to chiral appendages are
virtually unknown and none of the methods reported so far3,14ꢀ17
is shown to be capable of attaching DVS to chiral appendages like
carbohydrates. Compounds 17 and 20 depicted in Scheme 4
constitute the first generation of chirally modified divinyl sul-
fones attached to the most easily accessible chiral entities like
carbohydrates. We have delineated the synthetic potential of the
substituted divinyl sulfones by preparing a series of new S,S-
dioxide thiomorpholine derivatives which were also shown to be
useful synthetic intermediates. We are currently expanding the
scope of substituted divinyl sulfones and their derivatives as
useful synthetic intermediates.
Compound 10: To a well-stirred solution of 9 (0.4 g, 1.46 mmol) in
pyridine (15 mL) was added a solution of MsCl (1.0 mL, 8.76 mmol) in
pyridine (10 mL) dropwise at 0 °C under N2 and the reaction mixture
was kept at þ4 °C. After 24 h, the reaction mixture was poured into ice-
cold water and the solution was extracted with EtOAc (3 ꢁ 10 mL).
Combined organic layers were dried over anhyd. Na2SO4 and filtered
and the filtrate was concentrated under reduced pressure to obtain a
residue. A solution of the residue in DCM (15 mL) was treated with
triethylamine (0.5 mL, 2.92 mmol). After 15 h volatile matter was
evaporated under reduced pressure and the residue was purified over
silica gel to obtain compound 10 (0.31 g, 89%). Eluent: EtOAc:
’ EXPERIMENTAL SECTION
General Methods. See the Supporting Information.
Compound 7b: A mixture of NaOMe (0.80 g, 14.88 mmol) and 7a
(2.50 g, 7.44 mmol) in dry DMF (15 mL) was stirred at room
temperature for 12 h. After completion of the reaction (TLC), the
mixture was poured into satd. NaHCO3 solution (20 mL) and the
compound was extracted by EtOAc (3 ꢁ 15 mL). The organic layer was
separated, dried over anhyd. Na2SO4, and filtered and the filtrate was
evaporated to dryness under reduced pressure to obtain a residue. The
residual mass was purified over silica gel column to afford 7b7b (0.98 g,
80%). 1H NMR (CDCl3) δ 2.51ꢀ2.55 (m, 1H), 2.71 (t, 1H, J = 4.6 Hz),
3.06ꢀ3.14 (m, 1H), 3.30ꢀ3.39 (m, 1H), 3.69 (dd, 1H, J = 3 Hz, 11.4
Hz), 4.41ꢀ4.60 (m, 2H), 7.14ꢀ7.35 (m, 5H). 13C NMR δ 44.2 (CH2),
50.8, 70.8 (CH2), 73.3 (CH2), 127.7, 128.4, 137.9 (C).
Compound 9 from 7a: A mixture of marcaptoethanol (0.85 mL,
11.9 mmol) and TMG (1.5 mL, 11.9 mmol) in DMF (20 mL) was
heated at 90 °C for 30 min. The tosylate 7a (2.0 g, 5.95 mmol) was added
to this mixture and the mixture was heated at 90 °C under N2. After 5 h,
the reaction mixture was poured into a satd. solution of NaHCO3
(30 mL) and the product was extracted with EtOAc (3 ꢁ 20 mL). The
combined organic layers were dried over anhyd. Na2SO4 and filtered and
the filtrate was concentrated under reduced pressure. The residue was
purified over silica gel column to obtain the sulfide 8 contaminated with
1
1
1
petroleum ether (1:4). Colorless liquid. H NMR (CDCl3; Hꢀ H
COSY) δ 4.23ꢀ4.24 (CH2OBn, m, 2H), 4.58 (CH2Ph, s, 2H), 6.07 (cis-
CHdCHSO2, d, J = 9.6 Hz, 1H), 6.40 (trans-CHdCHSO2, d, J = 16.4
Hz, 1H), 6.59ꢀ6.61 (CHSO2CH, m, 2H), 6.96 (CH2CHdCHSO2, dt,
J = 15.2, 3.2 Hz, 1H), 7.30ꢀ7.39 (Ph, m, 5H). 13C NMR (CDCl3;
13
1Hꢀ C HETCOR) δ 67.7 (CH2OBn), 73.0 (CH2Ph), 127.7 (Ph), 127.9
(Ph), 128.4 (CH2CHdCHSO2), 128.5 (Ph), 128.9 (CH2dCHSO2),
137.2 (4), 137.3 (CH2dCHSO2), 144.7 (CH2CHdCHSO2). HRMS
[ESþ, (M þ Na)þ] for C12H14O3SNa obsd 261.0572, calcd 261.0561.
Compound 11 from 7a: To a well-stirred solution of compound
7a (2.0 g, 5.95 mmol) in methanol (15 mL) was added Na2S (0.23 g,
2.97 mmol). The reaction mixture was heated under reflux. After 5 h, the
reaction mixture was cooled and volatile matter was removed under
reduced pressure. The residue was dissolved in satd. NaHCO3 solution
(30 mL) and the solution was washed with EtOAc (3 ꢁ 10 mL).
Combined organic layers were dried over anhyd. Na2SO4 and filtered
and the filtrate was concentrated under reduced pressure to obtain a
residue. The residue was purified over silica gel to afford compound 11
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ARTICLE
(1.68 g, 78%). Eluent: EtOAc:petroleum ether (1:1). Colorless liquid.
1H NMR (CDCl3) δ 2.63ꢀ2.68 (m, 2H), 2.75ꢀ2.80 (m, 2H), 3.01 (br
s, 2H), 3.47ꢀ3.56 (m, 4H), 3.94 (br s, 2H), 4.55 (s, 4H), 7.28ꢀ7.37 (m,
10H). 13C NMR (CDCl3) δ 36.4 (CH2), 69.6, 69.8, 72.7 (CH2), 73.4
(CH2), 127.7, 127.8, 128.4, 137.7. HRMS [ESþ, (M þ H)þ] for
C20H27O4S obsd 363.1615, calcd 363.1630.
Compound 11 from 7b: To a well-stirred solution of compound
7b (3.2 g, 19.51 mmol) in DMF (10 mL) was added Na2S (0.76 g, 9.76
mmol). The reaction mixture was heated under reflux. After 13 h, the
reaction mixture was cooled and satd. NaHCO3 solution (30 mL)
was added. The solution was washed with EtOAc (3 ꢁ 10 mL).
Combined organic layers were dried over anhyd. Na2SO4 and filtered
and the filtrate was concentrated under reduced pressure to obtain a
residue. The residue was purified over silica gel to afford compound 11
(5.86 g, 83%).
136.7, 137.4, 141.8. HRMS [ESþ, (M þ Na)þ] for C18H22O6SNa obsd
389.1010, calcd 389.1035.
Compound 18: Compound 14 (3.0 g, 6.46 mmol) was converted
to 18 (1.64 g, 82%) following the procedure described for the synthesis
of compound 11. Eluent: EtOAc:petroleum ether (1:1). Colorless
1
liquid. [R]25.2 (ꢀ)27.3 (c 4.70, CHCl3). H NMR (CDCl3) δ 1.31
D
(s, 6H), 1.48 (s, 6H), 2.68ꢀ2.73 (m, 2H), 2.98 (d, J = 13.6 Hz, 2H), 4.08
(s, 6H), 4.56ꢀ4.62 (m, 4H), 4.69 (d, J = 12 Hz, 2H), 5.89 (d, J = 3.6 Hz,
2H), 7.30ꢀ7.34 (m, 10H). 13C NMR (CDCl3) δ 26.3, 26.8, 37.7 (CH2),
67.7, 72.2 (CH2), 81.5, 81.6, 82.3, 105.1, 111.8, 127.9, 128.1, 128.6,
137.2. HRMS [ESþ, (M þ H)þ] for C32H43O10S obsd 619.2566, calcd
619.2577.
Compound 19: Compound 18 (1.43 g, 2.31 mmol) was converted
to 19 (1.4 g, 93%) following the procedure described for the synthesis of
compound 9. Eluent: EtOAc:petroleum ether (3:2). Colorless solid. Mp
50 °C. [R]25.2D (ꢀ)25.6 (c 0.43, CHCl3). 1H NMR (CDCl3) δ 1.31 (s,
6H), 1.47 (s, 6H), 2.95 (d, J = 4.8 Hz, 2H), 3.38ꢀ3.48 (m, 4H),
4.04ꢀ4.07 (m, 4H), 4.52ꢀ4.61 (m, 6H), 4.70 (d, J = 11.6 Hz, 2H), 5.89
(d, J = 3.6 Hz, 2H), 7.30ꢀ7.37 (m, 10H). 13C NMR (CDCl3) δ 26.2,
26.8, 58.4 (CH2), 64.6, 72.2 (CH2), 80.9, 81.3, 82.2, 105.1, 111.9, 127.9,
128.3, 128.7, 136.9. HRMS [ESþ, (M þ Na)þ] for C32H42O12SNa obsd
673.2283, calcd 673.2295.
Compound 12: Compound 11 (0.281 g, 0.77 mmol) was con-
verted to 12 (0.28 g, 92%) following the procedure described for the
synthesis of compound 9. Eluent: EtOAc:petroleum ether (3:2). Color-
1
less liquid. H NMR (CDCl3) δ 3.04ꢀ3.15 (m, 2H), 3.29ꢀ3.37 (m,
2H), 3.45ꢀ3.60 (m, 6H), 4.44 (br m, 2H), 4.56 (m, 4H), 7.30ꢀ7.38 (m,
10H). 13C NMR (CDCl3) δ 57.8 (CH2), 57.9 (CH2), 65.6, 65.9, 72.4
(CH2), 72.6 (CH2), 73.4 (CH2), 73.4 (CH2), 127.7, 127.8, 127.9, 128.4,
128.5, 137.4. HRMS [ESþ, (M þ Na)þ] for C20H26O6SNa obsd
417.1317, calcd 417.1348.
Compound 20trans: Compound 19 (0.83 g, 1.27 mmol) was
converted to 20 (0.75 g, 96%) following the procedure described for the
synthesis of compound 10. The major compound of the mixture 20trans
Compound 13: Compound 12 (0.15 g, 0.38 mmol) was converted
to 13 (0.12 g, 88%) following the procedure described for the synthesis
of compound 10. Eluent: EtOAc:petroleum ether (1:4). Colorless
was separated up to 46%. Eluent: EtOAc:petroleum ether (1:2).
1
Crystalline solid. Mp 52 °C. [R]25.2 (þ)21.3 (c 0.01, CHCl3). H
D
1
NMR (CDCl3) δ 1.33 (s, 6H), 1.48 (s, 6H), 4.00 (d, J = 3.2 Hz, 2H),
4.46 (d, J = 12 Hz, 2H), 4.59ꢀ4.64 (m, 4H), 4.81 (br s, 2H), 5.96 (d, J =
3.6 Hz, 2H), 6.61 (dd, J = 1.6, 14.8 Hz, 2H), 6.88 (dd, J = 4, 15.2 Hz, 2H),
7.27ꢀ7.38 (m, 10H). 13C NMR (CDCl3) δ 26.3, 26.9, 72.3 (CH2), 78.8,
82.4, 82.7, 105.0, 112.2, 127.9, 128.2, 128.7, 131.2, 136.9, 140.9. HRMS
[ESþ, (M þ Na)þ] for C32H38O10SNa obsd 637.2075, calcd 637.2083.
Compound 21: Benzylamine (0.046 mL, 0.42 mmol) was added to
a suspension of 10 (0.1 g, 0.42 mmol) in MeOH (15 mL) and the
mixture was stirred at room temperature for 3 h. Volatile matter was
removed under reduced pressure. The product was purified over silica
gel to afford compound 21 (0.13 g, 90%). Eluent: EtOAc:petroleum
ether (1:4). Colorless liquid. 1H NMR (CDCl3) δ 2.89ꢀ3.04 (m, 3H),
3.09ꢀ3.14 (m, 1H), 3.18ꢀ3.27 (m, 2H), 3.42ꢀ3.48 (m, 1H), 3.67 (d,
J = 13.6 Hz, 1H), 3.70ꢀ3.74 (m, 1H), 3.77ꢀ3.81 (m, 1H), 3.87 (d, J =
13.6 Hz, 1H), 4.49ꢀ4.56 (m, 2H), 7.28ꢀ7.37 (m, 10H). 13C NMR
(CDCl3) δ 46.9 (CH2), 49.2 (CH2), 51.6 (CH2), 55.1 (CH2), 58.9, 68.9
(CH2), 73.3 (CH2), 127.5, 127.8, 127.9, 128.5, 128.5, 128.6, 137.5,
137.9. HRMS [ESþ, (M þ H)þ] for C19H24NO3S obsd 346.1466, calcd
346.1477.
liquid. H NMR (CDCl3) δ 4.22ꢀ4.23 (m, 4H), 4.58 (s, 4H), 6.60
(dt, J = 14.8, 2 Hz, 2H), 6.92 (dt, J = 15.2, 3.2 Hz, 2H), 7.30ꢀ7.39 (m,
10H). 13C NMR (CDCl3) δ 67.6 (CH2), 73.1 (CH2), 127.7, 127.8,
128.5, 129.1, 137.2, 143.7. HRMS [ESþ, (M þ Na)þ] for C20H22O4NaS
obsd 381.1116, calcd 381.1137.
Compound 15: Compound 14 (0.5 g, 1.07 mmol) was converted
to 15 (0.38 g, 95%) following the procedure described for the synthesis
of compound 8. Eluent: EtOAc:petroleum ether (1:1). Colorless liquid.
[R]25.2D (þ) 15.4 (c 0.10, CHCl3). 1H NMR (CDCl3) δ 1.32 (s, 3H),
1.49 (s, 3H), 2.42 (br s, 1H), 2.66ꢀ2.77 (m, 4H), 2.96 (dd, J = 3.2, 14.4
Hz, 1H), 3.73ꢀ3.75 (m, 2H), 4.07ꢀ4.11 (m, 3H), 4.56 (d, J = 11.6 Hz,
1H), 4.62 (d, J = 3.6 Hz, 1H), 4.73 (d, J = 12 Hz, 1H), 5.91 (d, J = 3.6 Hz,
1H), 7.30ꢀ7.39 (m, 5H). 13C NMR (CDCl3) δ 26.2, 26.7, 35.6 (CH2),
36.9 (CH2), 60.9 (CH2), 67.7, 72.2 (CH2), 81.6, 82.2, 105.0, 111.8,
127.8, 128.1, 128.6, 137.2. HRMS [ESþ, (M þ Na)þ] for C18H26O6SNa
obsd 393.1329, calcd 393.1348.
Compound 16: Compound 15 (0.38 g, 1.02 mmol) was converted
to 16 (0.35 g, 85%) following the procedure described for the synthesis
of compound 9. Eluent: EtOAc:petroleum ether (3:2). Semi solid.
[R]25.2D (ꢀ)11.5 (c 0.79, CHCl3). 1H NMR (CDCl3) δ 1.32 (s, 3H),
1.48 (s, 3H), 2.62 (br s, 1H), 3.03 (br s, 1H), 3.23ꢀ3.39 (m, 3H),
3.49ꢀ3.59 (m, 1H), 4.08ꢀ4.09 (m, 4H), 4.52ꢀ4.55 (m, 2H), 4.63 (br d,
J = 2.8 Hz, 1H), 4.73 (d, J = 12 Hz, 1H), 5.91 (br d, J = 2.8 Hz, 1H),
7.34ꢀ7.41 (m, 5H). 13C NMR (CDCl3) δ 26.2, 26.7, 56.1 (CH2), 56.8
(CH2), 58.2 (CH2), 64.5, 72.2 (CH2), 81.1, 81.5, 82.1, 105.0, 112.0,
127.8, 128.2, 128.7, 137.0. HRMS [ESþ, (M þ Na)þ] for C18H26O8SNa
obsd 425.1227, calcd 425.1246.
Compound 22: Compound 13 (0.09 g, 0.25 mmol) was converted
to compound 22 (0.108 g, 92%) in 3 h following the procedure
described for the synthesis of compound 21. Eluent: EtOAc:petroleum
ether (1:4). Colorless liquid. 1H NMR (CDCl3) δ 3.01ꢀ3.09 (m, 2H),
3.14ꢀ3.21 (m, 2H), 3.41ꢀ3.45 (m, 1H), 3.51ꢀ3.55 (m, 1H), 3.61 (br s,
1H), 3.67ꢀ3.69 (m, 1H), 3.74ꢀ3.76 (m, 1H), 3.80ꢀ3.84 (m, 1H), 3.89
(s, 1H), 4.04 (d, J = 14.4 Hz, 1H), 4.20 (d, J = 12 Hz, 1H), 4.29 (d, J = 12
Hz, 1H), 4.43ꢀ4.52 (m, 2H), 7.14ꢀ7.34 (m, 15H). 13C NMR (CDCl3)
δ 47.4 (CH2), 48.9 (CH2), 50.9 (CH2), 55.1, 60.4, 69.6 (CH2), 70.7
(CH2), 73.1 (CH2), 73.2 (CH2), 126.8, 127.1, 127.4, 127.7, 127.8,
128.1, 128.2, 128.3, 128.4, 128.5, 137.6, 138.3, 140.7. HRMS [ESþ, (M
þ H)þ] for C27H32NO4S obsd 466.2031, calcd 466.2052.
Compound 17: Compound 16 (0.35 g, 0.87 mmol) was converted
to 17 (0.28 g, 88%) following the procedure described for the synthesis
of compound 10. Eluent: EtOAc:petroleum ether (1:4). Colorless
1
liquid. [R]25.2 (ꢀ)30.8 (c 1.94, CHCl3). H NMR (CDCl3) δ 1.33
Compound 23: Compound 17 (1.0 g, 2.7 mmol) was converted to
compound 23 (1.25 g, 97%) in 5 h following the procedure described for
D
(s, 3H), 1.48 (s, 3H), 4.04 (s, 1H), 4.46 (d, J = 12 Hz, 1H), 4.61ꢀ4.66
(m, 2H), 4.88 (s, 1H), 5.98ꢀ6.02 (m, 2H), 6.36 (d, J = 16.8 Hz, 1H),
6.48ꢀ6.55 (m, 1H), 6.64 (d, J = 14.8 Hz, 1H), 6.92 (dd, J = 2.8, 15.2 Hz,
1H), 7.26ꢀ7.37 (m, 5H). 13C NMR (CDCl3) δ 26.2, 26.8, 72.2 (CH2),
78.7, 82.3, 82.5, 104.9, 112.2, 127.8, 128.2, 128.6, 128.8, 130.4 (CH2),
the synthesis of compound 21. Eluent: EtOAc:petroleum ether (1:3).
1
Crystalline solid. Mp 124 °C. [R]25.2 (þ)37.4 (c 0.10, CHCl3). H
D
NMR (CDCl3) δ 1.35 (s, 3H), 1.52 (s, 3H), 2.78ꢀ2.81 (m, 1H), 2.94
(br s, 2H), 3.04ꢀ3.07 (m, 2H), 3.29ꢀ3.34 (m, 1H), 3.80ꢀ3.86 (m,
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ARTICLE
2H), 3.95ꢀ4.01 (m, 2H), 4.44 (d, J = 12 Hz, 1H), 4.67 (d, J = 3.2 Hz,
1H), 4.72 (d, J = 12 Hz, 1H), 4.90 (d, J = 9.2 Hz, 1H), 6.00 (s, 1H),
7.26ꢀ7.38 (m, 10H). 13C NMR (CDCl3) δ 26.3, 26.9, 43.4 (CH2), 49.9
(CH2), 51.3 (CH2), 56.7 (CH2), 57.8, 71.4 (CH2), 76.2, 81.2, 81.9,
105.0, 111.8, 127.3, 128.1, 128.3, 128.4 (2 ꢁ C), 128.5, 128.6, 128.7,
136.5, 138.6. HRMS [ESþ, (M þ Na)þ] for C25H32NO6S obsd
474.1927, calcd 474.1950.
Compound 24: Ethanolamine (0.016 mL, 0.27 mmol) was added
to a suspension of 17 (0.1 g, 0.27 mmol) in MeOH (15 mL) and the
mixture was stirred at room temperature for 3 h. Volatile matter was
removed under reduced pressure. The product was purified over silica
gel to afford compound 24 (0.097 g, 83%). Eluent: EtOAc:petroleum
ether (4:1). Colorless solid. Hygroscopic material. [R]25.2D (þ)9.37 (c
0.10, CHCl3). 1H NMR (CDCl3) δ 1.33 (s, 3H), 1.51 (s, 3H),
2.60ꢀ2.65 (m, 1H), 2.79ꢀ2.88 (m, 3H), 2.95 (br s, 3H), 3.26ꢀ3.29
(m, 1H), 3.58 (br s, 3H), 3.70ꢀ3.72 (m, 1H), 3.95 (s, 1H), 4.42 (d, J =
11.6 Hz, 1H), 4.64ꢀ4.74 (m, 3H), 5.94 (s, 1H), 7.32ꢀ7.39 (m, 5H). 13C
NMR (CDCl3) δ 26.3, 26.8, 46.1 (CH2), 47.9 (CH2), 48.7 (CH2), 52.4
(CH2), 57.5, 59.4 (CH2), 71.5 (CH2), 76.8, 80.7, 81.5, 104.8, 111.9,
128.2, 128.5, 128.7, 136.3. HRMS [ESþ, (M þ Na)þ] for C20H30NO7S
obsd 428.1747, calcd 428.1743.
79.6, 79.7, 81.3, 81.6, 81.9, 82.0, 104.8, 105.1, 111.5, 112.1, 127.6, 127.9,
128.0, 128.3, 128.4, 128.5, 128.7, 128.9, 135.9, 137.4. HRMS [ESþ,
(M þ H)þ] for C32H43N2O10S obsd 647.2640, calcd 647.2638.
Compound 28: CBr2F2 (1 mL) was dropwise added to a vigorously
stirred mixture of the sulfone 23 (0.1 g, 0.21 mmol), alumina-supported
KOH (2 g), tBuOH (20 mL), and DCM (10 mL) kept at 5ꢀ10 °C. The
reaction mixture was stirred at room temperature for an additional 1 h
after which the solid catalyst was removed by suction filtration through a
Celite bed. The filtrate was evaporated to dryness. The filter cake was
washed thoroughly with DCM and the washes were combined with the
residue from the first filtrate. The resultant organic solution was washed
with brine and water, dried, and evaporated. The residue was purified on
silica gel to obtain compound 27 (0.028 g, 33%). Eluent: EtOAc:
petroleum ether (1:4). Colorless liquid. 1H NMR (CDCl3) δ 1.34
(s, 3H), 1.51 (s, 3H), 3.20ꢀ3.28 (m, 1H), 3.55ꢀ3.67 (m, 2H), 3.94 (br
s, 1H), 4.12 (br m, 2H), 4.39ꢀ4.51 (m, 2H), 4.62ꢀ4.75 (m, 2H), 5.39
(d, J = 6.6 Hz, 1H), 5.77 (d, J = 6.3 Hz, 1H), 6.01 (d, J = 3.9 Hz, 1H),
7.21ꢀ7.39 (m, 10H). 13C NMR (CDCl3) δ 26.3, 26.7, 59.8, 60.4, 69.7,
71.7, 81.6, 82.8, 85.1, 105.2, 111.4, 126.6, 127.4, 127.9, 128.0, 128.1,
128.5, 128.9, 129.4, 137.3. HRMS [ESþ, (M þ H)þ] for C25H30NO4
obsd 408.2143, calcd 408.2175.
Compound 30: A solution of compound 23 (0.2 g, 0.42 mmol) in
10 mL of aqueous 90% CF3CO2H was stirred for an hour at 0 °C. It was
allowed to come to room temperature within this time. Then this
reaction mixture was coevaporated with toluene to afford a syrupy
residue, which was immediately used for the next reaction. A solution of
this crude material, 10% Pd/C (0.01 g), and ammonium formate
(catalytic amount) in MeOH (15 mL) was heated under reflux for an
hour under H2 atmosphere. The reaction mixture was brought to room
temperature, the suspension was filtered through a Celite bed and
washed with MeOH, and the filtrate was concentrated to give a thick
viscous liquid containing compound 29. The residue was dissolved in
pyridine (10 mL) and acetic anhydride (0.2 mL, 2.1 mmol) was added.
After 6 h, the reaction mixture was poured into ice-cold water and an
aqueous layer was extracted with EtOAc (3 ꢁ 10 mL). The combined
organic layers were dried over anhydr. Na2SO4 and filtered and the
filtrate was concentrated under reduced pressure to obtain a residue.
The residue was purified over silica gel to afford the product 30 (0.059 g,
34%). Eluent: EtOAc:petroleum ether (1:4). Crystalline solid. Mp
196 °C. [R]25.2D (þ)32.1 (c 0.12, CHCl3). 1H NMR (CDCl3) δ 2.10
(s, 3H), 2.11 (s, 3H), 2.80ꢀ2.84 (m, 2H), 2.92ꢀ2.98 (m, 3H),
3.12ꢀ3.23 (m, 2H), 3.29ꢀ3.39 (m, 2H), 3.63ꢀ3.65 (m, 1H), 4.68 (s,
2H), 4.88 (br s, 1H), 4.98 (d, J = 2.8 Hz, 1H), 7.26ꢀ7.39 (m, 5H). 13C
NMR (CDCl3) δ 20.9, 21.3, 49.9 (CH2), 51.0 (CH2), 52.1 (CH2), 52.9
(CH2), 56.3, 68.4, 70.4, 71.2, 72.9 (CH2), 127.7, 128.1, 128.6, 137.1,
169.8, 170.2. HRMS [ESþ, (M þ Na)þ] for C19H26NO7S obsd
412.1407, calcd 412.1430.
Compound 25: To a solution of compound 23 (0.1 g, 0.21 mmol),
10% Pd/C (0.01 g) in MeOH, and ammonium formate (catalytic
amount) was refluxed for an hour under H2 atmosphere. The reaction
mixture was cooled to room temperature. The suspension was filtered
througha Celite bed and thebed was washedwith MeOH. The filtrate was
concentrate under vacuuo to give a thick viscous liquid. The residue was
dissolved in water and the water layer was washed with CHCl3. The
CHCl3 layers were pooled together, dried over anhyd. Na2SO4, and
filteredandthe filtrate was evaporatedtodryness. The residuewas purified
over silica gel to give product 25 (0.07 g, 86%). Eluent: EtOAc:petroleum
ether (2:3). Colorless solid. Mp 164 °C. [R]25.2 (ꢀ)16.3 (c 0.11,
D
1
CHCl3). H NMR (CDCl3) δ 1.34 (s, 3H), 1.47 (s, 3H), 2.58ꢀ2.70
(m, 2H), 2.92ꢀ3.07 (m, 2H), 3.22ꢀ3.29 (m, 1H), 3.33ꢀ3.38 (m, 1H),
3.55ꢀ3.60 (m, 1H), 3.84 (d, J = 3.2 Hz, 1H), 3.96ꢀ3.99 (m, 1H), 4.41 (d,
J = 12 Hz, 1H), 4.67 (d, J = 3.6 Hz, 1H), 4.75 (d, J = 12 Hz, 1H), 5.94 (d,
J = 3.6 Hz, 1H), 7.34ꢀ7.44 (m, 5H). 13C NMR (CDCl3) δ 26.2, 26.7,
43.6 (CH2), 52.7 (CH2), 53.7 (CH2), 54.2, 71.6 (CH2), 79.8, 81.1, 81.7,
104.9, 112.1, 128.6, 128.7, 128.9, 136.1. HRMS [ESþ, (M þ Na)þ] for
C18H26NO6S obsd 384.1466, calcd 384.1481.
Compound 26: Compound 20 (0.56 g, 0.91 mmol) wasconvertedto
compound 26 (0.64 g, 97%) in 48 h following the procedure described for
the synthesis of compound 21. Eluent: EtOAc:petroleum ether (1:2).
Colorless solid. Mp 62 °C. [R]25.2D (ꢀ)52.3 (c 0.17, CHCl3). 1H NMR
(CDCl3) δ1.29 (s, 6H), 1.35 (s, 6H), 2.85ꢀ2.94 (m, 4H), 3.76 (d, J =13.6
Hz, 1H), 3.89 (d, J = 2.0 Hz, 2H), 3.98 (br s, 2H), 4.10 (d, J = 14 Hz, 1H),
4.40 (d, J = 12 Hz, 4H), 4.56ꢀ4.59 (m, 4H), 5.93 (d, J = 3.6 Hz, 2H),
7.20ꢀ7.43 (m, 15H). 13C NMR (CDCl3) δ 26.4, 26.7, 48.9 (CH2), 51.5
(CH2), 53.9, 71.2 (CH2), 77.3, 81.2, 81.6, 104.9, 111.7, 127.2, 127.9, 128.2,
128.3, 128.7, 128.9, 136.7, 138.9. HRMS [ESþ, (M þ H)þ] for
C39H48NO10S obsd 722.2967, calcd 722.2999.
’ ASSOCIATED CONTENT
S
Supporting Information. General methods, full spectro-
b
scopic data of all new compounds, and ORTEPs and CIF files of
compounds 20trans, 23 and 30. This material is available free of
charge via the Internet at http://pubs.acs.org.
Compound 27: Hydrazine hydrate (0.016 mL, 0.32 mmol) was
added to a suspension of 20 (0.2 g, 0.32 mmol) in MeOH (25 mL) and
the mixture was stirred at room temperature for 6 h. Volatile matter was
removed under reduced pressure. The product was purified over silica
gel to afford compound 27 (0.17 g, 81%). Eluent: EtOAc:petroleum
’ AUTHOR INFORMATION
ether (1:4). Colorless solid. Mp 74 °C. [R]25.2 (ꢀ)17.1 (c 0.70,
D
1
Corresponding Author
*E-mail: tpathak@chem.iitkgp.ernet.in.
CHCl3). H NMR (CDCl3) δ 1.29 (s, 3H), 1.33 (s, 3H), 1.48 (s,
3H), 1.49 (s, 3H), 2.65 (d, J = 13.6 Hz, 1H), 2.77ꢀ2.83 (m, 1H),
3.26ꢀ3.31 (m, 2H), 3.42ꢀ3.46 (m, 1H), 3.52ꢀ3.58 (m, 1H),
3.65ꢀ3.71 (m, 1H), 3.76 (s, 1H), 3.84 (d, J = 9.2 Hz, 1H), 4.02ꢀ4.15
(m, 2H), 4.41 (d, J = 11.6 Hz, 1H), 4.53ꢀ4.74 (m, 4H), 5.85 (s, 1H),
5.94 (s, 1H), 7.26ꢀ7.43 (m, 10H). 13C NMR (CDCl3) δ 26.0, 26.1,
26.6, 26.7, 50.5, 56.6 (CH2), 57.2 (CH2), 57.7, 71.6 (CH2), 72.4 (CH2),
’ ACKNOWLEDGMENT
T.P. thanks the Department of Science and Technology
(D.S.T.), New Delhi, for financial support. T.K.P. thanks C.S.I.R.,
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The Journal of Organic Chemistry
ARTICLE
New Delhi for a fellowship. D.S.T. is also thanked for the creation
of 400 MHz facility under the I.R.PHA program and D.S.T.-F.
IST for the single crystal X-ray facility.
(17) (a) Amosova, S. V.; Skatova, N. N.; Tarasova, O. A.; Trofimov,
B. A. Z. Org. Khim. 1979, 15, 2038–42. (b) Selvaraj, S.; Dhanabalan, A.;
Perumal, S.; Arumugam, N. Phosphorus, Sulfur Relat. Elem. 1988,
39, 217–220. (c) Selvaraj, S.; Dhanabalan, A.; Amaithirani, J. S. A.;
Arumugam, N. Indian J. Chem. 1991, 30B, 871–872.
(18) For reviews on vinyl sulfone-modified carbohydrates, see: (a)
Pathak, T. Tetrahedron 2008, 64, 3605–3628. (b) Pathak, T.;
Bhattacharya, R. Carbohydr. Res. 2008, 343, 1980–1998.
(19) Staellberg, G. A. M. Acta Chem. Scand. 1990, 44, 368–376.
(20) Marco, J. A.; Carda, M.; Gonzalez, F.; Rodriguez, S.; Murga, J.
Liebigs Ann. 1996, 1801–1810.
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