Furo[2,3-c]pyrans from a vinyl sulfone modified methyl 2,6-o-anhydro- α- d -hexopyranoside: An experimental and theoretical investigation

Article abstract of DOI:10.1002/ejoc.201300935

A vinyl sulfone modified bicyclic sugar molecule undergoes efficient Michael addition of hetero- and carbon nucleophiles to afford single diastereomers. The same molecule consisting of two other masked functional groups, namely an aldehyde and an oxocarbonium ion, turned out to be a unique synthetic intermediate. The adducts generated from this Michael acceptor and a series of β-dicarbonyl compounds and related reagents after acid treatment afforded a new class of furo[2,3-c]pyrans, forming up to three new bonds and three stereocenters. In-built chirality centers of the sugar derivative controlled the diastereoselectivity of formation of all new bonds without the requirement for any external reagent for asymmetric induction. DFT calculations revealed the formation of furopyrans as the only possible products, which corroborates the experimentally observed results. A vinyl sulfone modified methyl 2,6-O-anhydro-α-D-hexopyranoside has been synthesized for the first time. The β-dicarbonyl adducts of this Michael acceptor, under acidic conditions, yielded furo[2,3-c]pyrans. Computational studies rationalized the experimentally observed results. Copyright

Full text of DOI:10.1002/ejoc.201300935

FULL PAPER
DOI: 10.1002/ejoc.201300935
Furo[2,3-c]pyrans from a Vinyl Sulfone Modified Methyl 2,6-O-Anhydro-
α- -hexopyranoside: An Experimental and Theoretical Investigation
D
Chinmoy Manna,[a] Debashis Sahu,[b,c] Bishwajit Ganguly,*[b,c] and Tanmaya Pathak*[a]
Keywords: Chiral pool / Carbohydrates / Enantioselectivity / Nucleophilic substitution / Tautomerism / Density functional
calculations /1,3-Dicarbonyl compounds
A vinyl sulfone modified bicyclic sugar molecule undergoes
efficient Michael addition of hetero- and carbon nucleophiles
to afford single diastereomers. The same molecule consisting
of two other masked functional groups, namely an aldehyde
and an oxocarbonium ion, turned out to be a unique syn-
thetic intermediate. The adducts generated from this
Michael acceptor and a series of β-dicarbonyl compounds
and related reagents after acid treatment afforded a new
class of furo[2,3-c]pyrans, forming up to three new bonds and
three stereocenters. In-built chirality centers of the sugar de-
rivative controlled the diastereoselectivity of formation of all
new bonds without the requirement for any external reagent
for asymmetric induction. DFT calculations revealed the for-
mation of furopyrans as the only possible products, which
corroborates the experimentally observed results.
oxycarbonylimino-2,6-dideoxy-α-d-altropyranoside as the
key intermediate.[5] The concept of connecting C2 and C6
positions of pyranosides was extended further by using
CHCH2CO2R or CH(OR)CH(CH2CO2Et) bridges to af-
ford oxabicyclo[2.2.1] or [2.2.2] systems, respectively; the
glycosidic bonds of these bicycle carbohydrates were cleaved
to afford densely functionalized cyclopentanes or cyclohex-
anes, respectively.[6] Different variations of this approach
have highlighted further the synthetic utilities of 2,6-
bridged bicyclic carbohydrates as a special class of useful
intermediates.[7–9] A number of these newly synthesized
carbon-bridged bicyclic carbohydrates were also subjected
to conformational analysis with relevance to enzymatic
hydrolysis of glycosidic bonds.[8]
A perusal of the literature reveals that before the
CHCH2CO2R or CH(OR)CH(CH2CO2Et) bridged bicycle
carbohydrates were used as intermediates for generating
carbocycles,[6] methyl 3,4-di-O-acetyl-2,6-anhydro-α-d-
altropyranoside (A) was used as an intermediate for gener-
ating a mixture of the two diastereomers of (1R) and (1S)
methyl 2,6-anhydro-d-altrose-tetraacetate (B) by aceto-
lyzing the glycosidic bonds in the presence of concentrated
H2SO4 (Scheme 1).[3c,3h] We opined that appropriately func-
tionalized 2,6-O-anhydropyranosides would allow easy ac-
cess to densely functionalized pyrans, which are an impor-
tant class of compounds in chemistry and biology.[10] How-
ever, one of the disadvantages of using bicyclic compounds
such as A is that only the C3 and C4 positions are available
for functionalization. Although a report detailing the order
of preference of formation of 2,6-, 3,6- and 4,6-O-anhydro
compounds was published and several mesylated analogues
were reported, the synthetic utilities of these compounds
were not explored.[11] An epoxide ring was also created at
Introduction
Carbohydrates are inexpensive, readily available and ver-
satile building blocks and are easily the most prominent
members of the chiral pool.[1] Although a wide range of
simple pentoses and hexoses belonging to the carbohydrate
chiral pool have been modified as epoxides, ketones and
tosylates etc. before further multistep functionalization,[2]
synthetic chemists over the decades have also shown great
interest in intramolecularly locked bicyclic carbohydrates or
anhydro-carbohydrates (non-epoxides) as possible starting
materials for synthesis. For example, the locked structural
motif of 2,6-anhydro-2-oxopyranosides, known for more
than seven decades,[3a,3b] has triggered interest among syn-
thetic chemists as well as led to structural studies of related
compounds.[3c–3j] Furthermore, the corresponding 2,6-
anhydro-2-thiosugars were found to be useful for the syn-
thesis of erythromycin A, 2,6-dideoxysugars and 1-deoxy-
thiomannojirimycin.[4] An aza heterocycle related to cas-
tanospermine was synthesized by using methyl 2,6-benzyl-
[a] Department of Chemistry, Indian Institute of Technology
Kharagpur,
Kharagpur 721302, India
E-mail: tpathak@chem.iitkgp.ernet.in
http://www.chem.iitkgp.ernet.in/faculty/PT/index.php
[b] Computation and Simulation Unit (Analytical Discipline and
Centralized Instrument Facility), CSIR – Central Salt and
Marine Chemicals Research Institute, G. B. Marg,
Bhavnagar, Gujarat 364002, India
E-mail: ganguly@csmcri.org
https://sites.google.com/site/drbishwajitganguly/
[c] Academy of Scientific and Innovative Research, CSIR – Central
Salt and Marine Chemicals Research Institute,
Bhavnagar, Gujarat 364002, India
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201300935.
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C. Manna, D. Sahu, B. Ganguly, T. Pathak
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the C3–C4 position of 2,6-O-anhydropyranosides but the
ring-opening reactions of these synthetically useful epoxides
were not effectively pursued.[3g,11,12]
Scheme 1. Acetolysis of a 2,6-O-anhydropyranoside.
Result and Discussions
Because the nucleophilic displacement of secondary
sufonylates of carbohydrates is sluggish and epoxides can-
not be effectively or easily opened by carbon nucleophiles,[2]
we have established that the incorporation of a vinyl sulfone
group into cyclic carbohydrates broadens the scope of
carbohydrate modification, especially in the case of C–C
bond formation through Michael addition of a wide range
of carbon nucleophiles along with heteronucleo-
philes.[1c,1e,13] The efficiency of this strategy led us to intro-
Scheme 2. Synthesis of bicyclic vinyl sulfone 7.
duce a vinyl sulfone group at C3–C4 of the 2,6-O-anhydro- malononitrile and dimethyl malonate to afford the addition
pyranosides. Thus, the known thiosugar 1[9] was debenzylid- products 10a–j (Scheme 4), which are structurally related to
inated by acetyl chloride in MeOH to obtain triol 2. The 8 and 9. Compound 7 has one characteristic signal in the
primary hydroxyl group of 2 was selectively tosylated by region δ = 7.42–7.44 that corresponds to the olefinic pro-
using tosyl chloride and triethylamine to afford 3. Direct ton; this proton is absent in all addition compounds 8, 9
treatment of 3 with NaOH required harsher reaction condi- and 10a–j. Compounds 10b–d are mixtures of inseparable
tions for cyclization. Therefore, 3 was acetylated to afford diastereomers and, therefore, it was difficult to extract in-
4, which, under warm alkaline conditions, underwent de- formation from their spectroscopic data. However, in the
acetylation followed by intramolecular attack of the C2 hy- 13C NMR spectra of 10a, and both the diastereomers of
droxyl group at C6 to afford the desired bicyclic compound 10e, the presence of two carbonyl signals at δ = 202.5/204.1,
5. The corresponding sulfone derivative 6 was generated in 195.9/203.3 and 194.2/201.5 ppm, respectively, are clearly
1
quantitative yield by oxidizing 5 with magnesium bis(mono- evident. Because an OH peak was also absent in the H
peroxyphthalate) hexahydrate (MMPP) in MeOH. Com- NMR spectra of all three compounds, it was concluded that
pound 6 was sulfonylated by using methanesulfonyl chlor- these molecules tend to exist in their diketo forms. On the
ide in pyridine at 0–4 °C and the product underwent elimi- other hand, compounds 10f and 10g existed preferentially
nation reaction in a one-pot fashion to afford 7 in 98% in the enol form, which is indicated by the presence of OH
1
yield over two steps (Scheme 2).
peaks at ca. δ = 9.3 ppm in the H NMR spectra, along
To test the diastereoselectivity of addition of nucleo- with a set of C=O/(O)CC=C(CH2)OH quaternary carbon
philes towards the new Michael acceptor, vinyl sulfone signals at δ = 196.9/114.1 and 196.9/113.1 ppm, respectively,
modified 2,6-O-anhydropyranoside 7 was treated with in the 13C NMR spectra of each of these compounds (see
benzylamine in tetrahydrofuran (THF) and the oxygen nu- below). However, the configuration of addition products 8
cleophile derived from a partially protected ribose sugar and 10j were unambiguously confirmed by X-ray diffrac-
with NaH/N,N-dimethylformamide (DMF) at ambient tem- tion of their single crystals (Figure 1). From the ORTEP
perature to generate single diastereomers 8 and 9, respec- diagrams of compounds 8 and 10j, we presumed that all
tively, in high yields (Scheme 3). Although the reaction was carbon addition compounds 10a–i also have similar config-
highly efficient, the acid treatment of 8 and 9 afforded a urations. Due to the presence of an O–CH2 bridge in the
mixture of inseparable mixtures. We therefore turned our bicyclic Michael acceptor 7, incoming nucleophiles were
attention to carbon nucleophiles, expecting the adducts to forced to attack the electron-deficient double bond in an
be more stable towards acid treatment. Thus, 7 was treated endocyclic fashion. Moreover, the incoming nucleophiles
with the potassium salts of acetylacetone, methyl acetoacet- and ArSO2, two sterically bulky groups, positioned them-
ate, ethyl acetoacetate, methylsulfonylacetone, 1-benzo- selves in a trans-fashion in compounds 8, 9, and 10a–j. It is
ylacetone, 1,3-cyclohexanedione, dimedone, nitromethane, also probable that due to additional stereoelectronic repul-
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Synthesis and Studies of Furo[2,3-c]pyrans
sions between the anomeric methoxy and ArSO2 groups,
the latter moved away as far as possible in the equatorial
direction.
Scheme 3. Reactivity of 7 towards oxygen and nitrogen nucleo-
philes.
Figure 1. ORTEP diagram of 8 and 10j.
Scheme 4. Reactivity of 7 towards carbon nucleophiles.
In line with our earlier argument on the probable synthe-
sis of pyrans from 2,6-anhydrosugars (Scheme 1), com-
pounds 10a–g were subjected to acid treatment at ambient
temperature, which was followed by triethylamine treatment
of the reaction mixture. Surprisingly, the reaction afforded a
new class of polycyclic compounds, namely furo[2,3-c]pyran
derivatives 11a–g (Scheme 5),[14] which are far more com-
plex than the simple pyran structures[10] proposed in
Scheme 1. Under similar reaction conditions, compounds
10h–j afforded inseparable mixtures. Although the possibil-
ity of formation of compounds 12A and 12B was not ruled
out in the beginning (see below), the reaction did not afford
either of these two compounds.
Importantly, these transformations may also be carried
out in a one-pot fashion. Thus, the potassium salt of acetyl-
acetone added to 7 in 24 h (reaction monitored by TLC) in
a Michael fashion. A mixture of trifluoroacetic acid (TFA)
Scheme 5. Synthesis of furopyrans from bicyclic carbohydrates
and TfOH (3:1 ratio, 0.1 mL/mmol) was added to the reac- 10a–g.
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C. Manna, D. Sahu, B. Ganguly, T. Pathak
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tion mixture and the solution was stirred for another 3 h.
Usual work-up and purification afforded furo[2,3-c]pyran
derivative 11a in good overall yield (Scheme 6).
Scheme 6. One-pot synthesis of furopyran 11a from 7.
The most plausible pathway of formation of this novel
class of furopyrans 11a–g has been elaborated in Scheme 7.
Deglycosylation of 10a generates the oxocarbonium ion in-
termediate 13a, which undergoes intramolecular attack by
the carbonyl oxygen atom (see below). Interestingly, the
C=O+ function, generated in situ, acts as a leaving group
and, in stark contrast to the simple ring opening depicted
in Scheme 1, the keto oxygen attacks the bridgehead carbon
affording the furopyran scaffold; elimination of ArSO2H
from the furopyran intermediate 14 affords 11a. It is ex-
pected that 10b–g would follow the same pathway to afford
other analogues 11b–g. The intermediacy of 14 was estab-
lished by isolating crystalline 15 (Figure 2), which was
formed by treating 10a with acetic anhydride and TfOH.
The diacetyl acetal 15 was easily converted into 11a by mild
base treatment (Scheme 7).
Figure 2. ORTEP diagram of 15.
analogue established that Michael addition of different nu-
cleophiles to these substrates yielded cyclopropanated
carbohydrates by forming a new C–C bond between C3 and
C5.[15a] On the other hand, we recently reported the ad-
dition of β-dicarbonyl and related reagents to vinyl sulfone
modified hex-2-enofuranosyl carbohydrates, and one of the
carbonyl groups of the β-dicarbonyl residues of the adduct,
on acid treatment, attacked the anomeric carbon in an in-
tramolecular manner under acidic conditions to afford
furo[2,3-b]furan systems.[15b] We therefore expected that
10a–g would, under similar reaction conditions, either un-
dergo cyclopropanation to afford 12A, or intramolecular
attack of the keto/enol oxygen at the anomeric carbon to
yield 12B via intermediates 16a and 13a, respectively
(Scheme 8).
To resolve the issue of selective formation of compound
11a over 12A or 12B, it was necessary to understand the
involvement of keto/enol forms of the β-dicarbonyl residues
in compound 10a. A computational study was therefore un-
dertaken to examine the formation of furopyran derivative
11a from 7 at the DFT M06–2X/6-311+G(d)//B3LYP/6-
31G(d) level of theory. Full geometrical optimizations and
frequency calculations were performed in the gas phase by
employing the Becke three-parameter hybrid density func-
tional combined with Lee–Yang–Parr correlation func-
tional (B3LYP) level[16] with a standard 6-31G(d) basis
set.[17] The ground-state and transition-state geometries
were characterized by vibrational frequency analysis. All
Scheme 7. Identification of intermediates in the formation of furo-
pyran derivatives from the Michael adducts of 7.
Our earlier studies on Michael initiated ring closure on single point calculations were performed with the M06-2X
methyl 2,3-dideoxy-5-O-mesyl-3-(4-methylphenyl)sulfonyl- method[18] and the 6-311+G(d) basis set[19] with polarizable
α-d-erythro-pent-2-enofuranoside and the corresponding β- continuum model (PCM)[20] in TFA medium (ε = 8.22)[21]
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Synthesis and Studies of Furo[2,3-c]pyrans
be formed via intermediate 16a. The potential energy sur-
face for the formation of product intermediate 16b is given
in Figure 4. Calculations show that the activation barrier
for the formation of 16b through bridgehead ring opening
is 28.2 kcal/mol, which is much lower in energy than the
keto-enol tautomerization process in 13a. These results sug-
gest that 13a would tend to generate 11a. It is intriguing to
note that the other “likely” product 12B was also not
formed from 7 (Scheme 5). We have further undertaken
DFT calculations to examine the formation of 12B from 7.
The formation of 12B from 7 would presumably be
a multi-step process. Compound 10a is first formed upon
attack of CH2(COMe)2, followed by formation of keto-
oxonium ion 13a. The orientation of the COMe groups are
important for the attack to the bridgehead center or the
anomeric carbon center. The COMe group prefers to orient
away from the anomeric carbon center in 10a due to the
steric interactions, however, the CO group is in close prox-
imity to the bridgehead center in the calculated geometry
(Figure S1). The oxonium ion 13a formed after the depar-
ture of the methoxy group also shows that the COMe group
is oriented away from the anomeric carbon atom in the cal-
culated structure. Attack of the C=O oxygen to the anom-
eric carbon center is only possible by C–C bond rotation
(C1–C2) in 13a (Figure S1). The rotation is hindered due to
the electrostatic repulsion between the oxygen atoms of the
C=O carbonyl group and the ring oxygen atom (Figure S1).
Furthermore, the endo hydrogen atom of 13a leads to steric
crowding and rotation of the CH(COMe)2 group towards
the anomeric carbon center and would deter the process of
rotation. Hence, it is reasonable to conclude that the close
proximity of the C=O group to the bridgehead carbon cen-
ter leads to the formation of 11a.
It is interesting to note that the relative stability of the
acyclic keto oxonium intermediate 13a compared with the
acyclic enol oxonium 16a is much more favorable (18.2 kcal/
mol) (Figure 3), whereas the relative stability of the cyclic
keto oxonium 10f-keto-oxonium compared to the cyclic
Scheme 8. Mechanism of selective formation of 11a from 10a.
employing B3LYP/6-31G(d) optimized geometries. All enol oxonium 10f-enol-oxonium is only 3.3 kcal/mol (Fig-
DFT calculations were performed with the Gaussian 09 ure S2). These DFT results suggest that the presence of the
suite of programs.[22] In these calculations, the SO2Ar group enol forms of 10f and 10g is possible under similar reaction
was modeled with SO2Me for computational simplicity. The conditions, which is also supported by the NMR spectro-
process of enolization of 13a is shown in Figure 3. The cal- scopic data mentioned above. Therefore, the involvement of
culated results show that the stable keto form 13a first at- the enol form in the cyclization process cannot be ruled out
tains a sickle-shaped diketo tautomeric[23] intermediate for compounds 10f and 10g. However, it can be envisaged
through a rotational transition state, which subsequently that 10f-enol-oxonium may lead to 17 through attack of the
leads to a four-membered planar transition state for proton sp2-carbon center to the bridgehead carbon atom
transfer to form 16a. The computed activation barrier for (Scheme 9). The three-membered product intermediate 17
the rotational transition state is 2.7 kcal/mol (Figure 3). is ca. 4.0 kcal/mol (in TFA) energetically less stable than the
However, the activation barrier computed for the enol- observed product intermediate 18, as calculated at the M06-
ization of 13a to 16a is 60.5 kcal/mol. Such high energy 2X/6-311+G(d)//B3LYP/6-31G(d) level of theory (Fig-
barriers are also known for other keto-enol tautomerization ure S3). It should be noted that the enolic oxygen center
processes.[24]
bears more negative charge (–0.618) than the sp2-carbon
Furthermore, the enol form 16a was calculated to be center (–0.003) and, hence, the former center will approach
18.2 kcal/mol higher in energy than the corresponding keto- more effectively than the alternative carbon center
form 13a. These results suggest that the keto-enol process (Scheme 9). The computed results suggest that the forma-
is energetically unfavorable in this case and, hence, it is un- tion of 17, derived from 10f, is less likely and, indeed, such
likely that the three-membered pyran derivative 12A would products have not been observed.
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Figure 3. M06–2X/6-311+G(d)//B3LYP/6-31G(d) calculated relative energies of keto to enol transformation of the oxonium ion in TFA.
All distances are in Å. Relative energies are given in kcal/mol [gray: carbon; white: hydrogen; red: oxygen; yellow: sulfur].
Figure 4. M06–2X/6-311+G(d)//B3LYP/6-31G(d) calculated poten-
tial energy surface for the transformation of 13a into 16b in TFA.
Relative energies are given in kcal/mol. All distances are in Å [gray:
carbon; white: hydrogen; red: oxygen; yellow: sulfur].
Scheme 9. Schematic presentation for the formation of 17 and 18
from cyclic 10f-keto-oxonium. The Mulliken charges in cyclic 10f-
enol-oxonium are in units of electrons [calculated at B3LYP/6-
31G(d)].
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Synthesis and Studies of Furo[2,3-c]pyrans
1 H), 7.02 (d, J = 8.0 Hz, 2 H), 7.34 (d, J = 7.34 Hz, 2 H) ppm.
13C NMR: δ = 20.9, 55.1, 56.1, 61.3 (CH2), 62.6, 70.0, 71.8, 100.9,
130.0, 131.0, 133.3 (C), 136.9 (C) ppm. HRMS (ES): calcd. for
C14H20O5SNa [M + Na]+ 323.0914; found: 323.0929.
Conclusions
We have introduced vinyl sulfone modified methyl 2,6-O-
anhydro α-d-hexopyranoside for the first time as a unique
and efficient Michael acceptor. The same molecule con-
sisting of two other masked functionalities, namely an alde-
hyde and a leaving group in the form of oxocarbonium ion,
Compound 3: Compound 2 (2.53 g, 8.43 mmol) in CH2Cl2 (30 mL)
was added to triethylamine (15 mL, 126.48 mmol) at 0 °C under
N2. After 1 h, TsCl (1.93 g, 10.12 mmol) was added and the reac-
is capable of reacting with β-dicarbonyl compounds and re- tion mixture was stirred for another 16 h at 0 °C. The reaction mix-
ture was partitioned between aq. NaHCO3 and CH2Cl2 (20 mL).
Organic extracts were pooled together, dried with anhyd. Na2SO4,
filtered and the filtrate was evaporated under reduced pressure. The
resulting residue was purified by column chromatography over sil-
ica gel to yield 3 (3.29 g, 86%) as a colorless jelly. [α]3D0 = +19.2 (c
lated reagents in a sequential or one-pot fashion to form
a range of enantiomerically pure furo[2,3-c]pyrans. These
reactions do not require any external reagent for the impo-
sition of asymmetry in the products because the chirality
centers of the sugar derivatives controlled the diastereo-
selectivity of formation of all new bonds. We have also iden-
tified the intermediates involved in the reaction processes.
DFT calculations revealed that after C–C bond formation,
the oxygen nucleophiles of R-C(O)Me moieties of 10a–g
1
= 0.51, CHCl3). H NMR: δ = 2.30 (s, 3 H), 2.44 (s, 3 H), 3.48 (s,
3 H), 3.57 (t, J = 4.4 Hz, 1 H), 3.83–3.87 (m, 1 H), 3.99–4.03 (m,
1 H), 4.16–4.17 (m, 1 H), 4.23–4.27 (m, 1 H), 4.36 (dd, J = 1.6,
10.4 Hz, 1 H), 4.58 (s, 1 H), 7.09 (d, J = 8.0 Hz, 2 H), 7.34 (t, J =
7.6 Hz, 4 H), 7.79 (d, J = 8.4 Hz, 2 H) ppm. 13C NMR: δ = 21.0,
attack the bridgehead carbon center and not the anomeric 21.6, 55.4, 56.7, 63.3, 68.8, 69.5 (CH2), 71.5, 101.0, 127.9, 129.8,
130.0, 131.3, 132.3 (C), 132.8 (C), 137.5 (C), 144.9 (C) ppm. HRMS
(ES): calcd. for C21H26O7S2Na [M + Na]+ 477.1029; found
477.1018.
carbon center of intermediates such as 13a for the cycliza-
tion to afford furopyrans. In line with the concept of gener-
ating products that are useful as potential substrates for
further transformations, the furopyrans reported here are
decorated with reactive functional groups, such as
R-C=CC(O)-RЈ, R-C=CSO2RЈ and R-C=CCHO, which
are capable of combining with other suitably functionalized
compounds to generate more complex scaffolds. Work in
our laboratory is in progress in this direction.
Compound 4: To a cooled (0 °C) solution of 3 (3.01 g, 6.62 mmol)
in anhyd. pyridine (40 mL) was added Ac2O (1.9 mL, 26.52 mmol)
in the presence of a catalytic amount of DMAP at 0 °C under N2
and the mixture was stirred at ambient temperature for 24 h. After
completion of reaction (TLC), the reaction mixture was partitioned
between aq. NaHCO3 and EtOAc (3ϫ 20 mL). Organic extracts
were pooled together, dried with anhyd. Na2SO4, filtered, and the
filtrate was evaporated under reduced pressure. The resulting resi-
due was purified by column chromatography over silica gel to yield
4 (3.35 g, 94%) as a white solid, m.p. +113 °C; [α]3D0 = +69.9 (c =
Experimental Section
1
0.84, CHCl3). H NMR: δ = 1.50 (s, 3 H), 2.11 (s, 3 H), 2.29 (s, 3
General Methods: All reactions were conducted under an N2 atmo-
sphere. Melting points were determined in open-ended capillary
tubes and are uncorrected. Carbohydrates and other fine chemicals
were obtained from commercial suppliers and were used without
purification. Solvents were dried and distilled by following the stan-
dard procedures. TLC was carried out on precoated plates (Merck
silica gel 60, f254) and spots were visualized with UV light or by
charring the plate dipped in 5% H2SO4/MeOH solution. Column
chromatography was performed on silica gel (230–400 mesh). 1H
and 13C NMR analysis of new compounds were recorded at 200/
400 and 50/100 MHz, respectively, by using CDCl3 as solvent un-
less stated otherwise. DEPT experiments were carried out to ident-
ify the methylene and quaternary carbon signals. Optical rotations
were recorded at 589 nm. Mass spectroscopy data were obtained
from a mass spetrometer consisting of TOF and quadrupole op-
erating in either ESI+ or ESI– mode.
H), 2.43 (s, 3 H), 3.37 (s, 3 H), 3.89–3.91 (m, 1 H), 4.21 (d, J =
3.2 Hz, 2 H), 4.38–4.39 (m, 1 H), 4.58 (s, 1 H), 5.09 (dd, J = 4.4,
10.0 Hz, 1 H), 5.193 (d, J = 1.6 Hz, 1 H), 7.05–7.12 (m, 2 H), 7.28–
7.34 (m, 4 H), 7.78 (d, J = 8.4 Hz, 2 H) ppm. 13C NMR: δ = 20.0,
21.0 (ϫ 2), 21.6, 48.9, 55.3, 64.9, 66.7, 68.4 (CH2), 72.6, 98.6, 128.0,
130.0 (ϫ 2), 132.0, 132.5 (C), 132.8 (C), 137.3 (C), 144.8 (C), 169.6
(C), 169.7 (C). HRMS (ES) calcd. for C25H30O9S2Na [M + Na]+
561.1219; found 561.1229.
Compound 5: Compound 4 (2.0 g, 3.72 mmol) in dioxane (35 mL)
was added to NaOH (1n, 0.75 g, 18.59 mmol) solution and the re-
sulting solution was heated to reflux for 1 h. After completion of
reaction (TLC), the reaction mixture was partitioned between aq.
NaHCO3 and EtOAc (3ϫ 20 mL). Organic extracts were pooled
together, dried with anhyd. Na2SO4, filtered, and the filtrate was
evaporated under reduced pressure. The resulting residue was puri-
fied by column chromatography over silica gel to yield 5 (1.02 g,
98%) as a colorless jelly. [α]3D0 = –66.6 (c = 1.33, CHCl3). 1H NMR:
δ = 2.29 (s, 3 H), 3.29 (br. s, 1 H), 3.50 (s, 3 H), 3.63–3.67 (m, 2
H), 3.94–3.98 (m, 3 H), 4.09–4.11 (m, 1 H), 4.96 (d, J = 3.6 Hz, 1
H), 7.08 (d, J = 8 Hz, 2 H), 7.35 (d, J = 8 Hz, 2 H) ppm. 13C
NMR: δ = 21.0, 50.8, 55.6, 64.1 (CH2), 66.2, 68.8, 69.5, 100.0,
129.8, 131.6, 132.6 (C), 137.4 (C) ppm. HRMS (ES): calcd. for
C14H18O4SNa [M + Na]+ 305.0807; found 305.0824.
Compound 2: To a well-stirred, cooled (0 °C) solution of sulfide
1 (4.0 g, 10.31 mmol) in anhyd. MeOH (30 mL) was added AcCl
(0.89 mL, 12.37 mmol) at 0 °C and the resulting solution was
stirred for 2 h at ambient temperature. After completion of reaction
(TLC) pyridine (5 mL) was added and the resulting residue was
evaporated to dryness under reduced pressure. The reaction mix-
ture was partitioned between aq. NaHCO3 and EtOAc (3ϫ
20 mL). Organic extracts were pooled together, dried with anhyd.
Na2SO4, filtered and the filtrate was evaporated under reduced
pressure. The resulting residue was purified by column chromatog-
raphy over silica gel to yield 2 (2.78 g, 90%) as a colorless jelly.
Compound 6: To a solution of 5 (2.19 g, 7.77 mmol) in MeOH
(35 mL) was added MMPP (15.37 g, 31.07 mmol) and the mixture
was stirred for 6 h at ambient temperature. The mixture was then
filtered through Celite and the filtrates were evaporated and dis-
solved in EtOAc (30 mL). The organic layer was washed with satd.
aq. NaHCO3 (3ϫ 30 mL) and separated, dried with anhyd.
1
[α]3D0 = +58.2 (c = 1.41, CHCl3). H NMR: δ = 2.25 (s, 3 H), 3.32
(s, 3 H), 3.61 (s, 1 H), 3.54 (d, J = 9.6 Hz, 2 H), 3.67–3.75 (m,
2 H), 3.85–3.88 (m, 2 H), 4.16 (s, 1 H), 4.22–4.26 (m, 1 H), 4.57 (s,
Eur. J. Org. Chem. 2013, 8197–8207
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
8203

C. Manna, D. Sahu, B. Ganguly, T. Pathak
FULL PAPER
Na2SO4, filtered, and the filtrate was evaporated under reduced
(CH2), 65.3, 66.8, 69.3 (CH2), 73.3, 81.0, 84.7, 85.0, 98.7, 109.4,
112.2 (C), 128.8, 130.0, 134.8 (C), 145.1 (C) ppm. HRMS (ES):
calcd. for C23H32O10SNa [M + Na]+ 523.1603; found 523.1614.
pressure to give pure 6 in quantitative yield as a colorless jelly.
1
[α]3D0 = –11.2 (c = 0.92, CHCl3). H NMR: δ = 2.42 (s, 3 H), 3.48
(s, 3 H), 3.51 (d, J = 10.4 Hz, 1 H), 3.59 (d, J = 6.0 Hz, 1 H), 3.94–
4. (m, 4 H), 4.46 (s, 1 H), 5.00 (s, 1 H), 7.31 (d, J = 8.0 Hz, 2 H),
7.90 (d, J = 8.0 Hz, 2 H) ppm. 13C NMR: δ = 21.6, 55.6, 63.6
(CH2), 64.5, 64.6, 65.4, 69.6, 98.4, 128.6, 129.7, 137.3 (C), 144.7
(C) ppm. HRMS (ES): calcd. for C14H18O6SNa [M + Na]+
337.0703; found 337.0722.
General Procedure for the Synthesis of 10a–g from 7: To a suspen-
sion of tBuOK (1.2 equiv) in anhyd. THF (2 mL) at ambient tem-
perature was added β-dicarbonyl compound (1.6 equiv) and the
resulting solution was stirred for 30 min under nitrogen. A solution
of sugar derived vinyl sulfone 7 (1 equiv) in anhyd. THF (1 mL)
was added dropwise to the reaction mixture and the resulting solu-
tion was then stirred for 6–30 h. After completion of the reaction
(TLC), the reaction mixture was evaporated under reduced pres-
sure. The crude mass obtained was dissolved in EtOAc and the
organic layer was washed with satd. aq. NaHCO3 and separated.
The organic layer was dried with anhyd. Na2SO4, filtered and the
filtrate was evaporated under reduced pressure to give a crude mass.
The resulting residue was purified by column chromatography over
silica gel (EtOAc/petroleum ether) to give the product. Compound
7 was treated with methanesulfonylacetone in a similar fashion.
Compound 7: To a solution of 6 (1.36 g, 4.33 mmol) in anhyd. pyr-
idine (20 mL) was added methanesulfonyl chloride (1.35 mL,
17.33 mmol) in pyridine (5 mL) at 0 °C. The mixture was left over-
night at 4 °C, then the reaction mixture was poured into satd. aq.
NaHCO3 (70 mL) and filtered through Celite. The filtrate was ex-
tracted with CH2Cl2 (3ϫ 30 mL) and the organic extracts were
collected together. The CH2Cl2 solution was dried with anhydrous
Na2SO4 and filtered. Et3N (2 mL) was added to the filtrate. The
mixture was stirred for 15 min and all volatile matters were evapo-
rated under reduced pressure. The resulting residue was purified on
silica gel to afford 7 (1.23 g, 98%) as a white solid; Mp: 90 °C; [α]
Compound 10a: Following the general procedure, acetylacetone
(0.22 mL, 2.16 mmol) was treated with 7 (0.40 g, 1.35 mmol) in the
presence of tBuOK (0.18 g, 1.62 mmol) for 24 h to give 10a (0.51 g,
95%) as white crystalline solid, m.p. 116 °C; [α]3D0 = +148.9 (c =
30
1
= +61.8 (c = 1.65, CHCl3). H NMR: δ = 2.44 (s, 3 H), 3.06 (s,
D
3 H), 3.21 (d, J = 8.8 Hz, 1 H), 3.97 (dd, J = 2.4, 8.8 Hz, 1 H),
4.71 (t, J = 2.4 Hz, 1 H), 4.74–4.76 (m, 1 H), 4.96 (d, J = 2.8 Hz,
1 H), 7.32 (d, J = 8.0 Hz, 2 H), 7.42–7.44 (m, 1 H), 7.77 (d, J =
8.0 Hz, 2 H) ppm. 13C NMR: δ = 21.7, 54.6, 64.9, 65.7 (CH2),
65.7, 99.1, 128.6, 129.7, 135.6 (C), 138.4, 143.6 (C), 144.8 (C) ppm.
HRMS (ES): calcd. for C14H16O5SNa [M + Na]+ 319.0620; found
319.0616.
1
2.16, CHCl3). H NMR: δ = 2.22 (s, 3 H), 2.26 (s, 3 H), 2.41 (s, 3
H), 3.09–3.15 (m, 1 H), 3.39 (s, 3 H), 3.49 (d, J = 3.6 Hz, 1 H),
3.62 (d, J = 9.6 Hz, 1 H), 3.74 (s, 1 H), 3.79 (dd, J = 3.6, 9.6 Hz,
1 H), 3.93 (s, 1 H), 4.13 (d, J = 9.6 Hz, 1 H), 4.83 (d, J = 2.8 Hz,
1 H), 7.32 (d, J = 7.6 Hz, 2 H), 7.77 (d, J = 8.0 Hz, 2 H) ppm. 13C
NMR: δ = 21.6, 28.4, 31.8, 35.9, 55.2, 60.6, 65.0, 66.8ϫ 2, 66.9
(CH2), 69.9, 99.3, 129.4, 129.8, 133.5 (C), 145.3 (C), 202.5 (C),
204.1 (C). HRMS (ES): calcd. for C19H24O7SNa [M + Na]+
419.1119; found 419.1140.
Compound 8: To a solution of 7 (0.50 g, 1.69 mmol) in anhyd. THF
(8 mL) was added the benzylamine (0.92 mL, 8.45 mmol) and the
solution was stirred at ambient temperature for 3 h. After comple-
tion of the reaction (TLC), THF was evaporated under reduced
pressure. The residue thus obtained was dissolved in EtOAc
(30 mL) and the organic layer was washed with satd. aq. NaHCO3
(3ϫ 30 mL). The organic layer was separated, dried with anhyd.
Na2SO4, filtered, and the filtrates were evaporated under reduced
pressure. The residues were purified over silica gel to give 8 (0.64 g,
95%) as solid crystals, m.p. 131 °C; [α]3D0 = +8.8 (c = 1.38, CHCl3).
1H NMR: δ = 2.45 (s, 3 H), 3.31 (s, 1 H), 3.41 (s, 3 H), 3.58 (s, 1
H), 3.66 (d, J = 9.6 Hz, 1 H), 3.71 (d, J = 13.2 Hz, 1 H), 3.79 (d,
J = 13.6 Hz, 1 H), 3.91 (dd, J = 3.2, 9.2 Hz, 1 H), 4.12–4.13 (m, 2
H), 4.94 (d, J = 2.8 Hz, 1 H), 7.22–7.34 (m, 7 H), 7.78 (d, J =
8.4 Hz, 2 H) ppm. 13C NMR: δ = 21.6, 50.1 (CH2), 53.5, 55.4, 64.9,
65.2, 65.5, 68.1, 99.2, 127.0, 128.0, 128.3, 129.0, 129.7, 134.9 (C),
139.5 (C), 144.9 (C) ppm. HRMS (ES): calcd. for C21H25O5NSNa
[M + Na]+ 426.1330; found 426.1351.
Compound 10b: Following the general procedure, methyl acetoacet-
ate (0.15 mL, 1.35 mmol) was treated with 7 (0.25 g, 0.85 mmol) in
the presence of tBuOK (0.11 g, 1.01 mmol) for 26 h to give a mix-
ture of inseparable diastereomers 10b (0.33 g, 95%). The mixture
was taken directly for the next step.
Compound 10c: Following the general procedure, ethyl acetoacetate
(0.10 mL, 1.08 mmol) was treated with 7 (0.20 g, 0.68 mmol) in the
presence of tBuOK (0.19 g, 0.81 mmol) for 30 h to give a mixture
of inseparable diastereomers 10c (0.27 g, 92%). The mixture was
taken directly for the next step.
Compound 10d: Following the general procedure, methylsulfon-
ylacetone (0.22 g, 1.62 mmol) was treated with
7 (0.30 g,
1.01 mmol) in the presence of tBuOK (0.14 g, 1.22 mmol) for 9 h
to give a colorless solid mixture of inseparable diastereomers 10d
(0.37 g, 85%). The mixture was taken directly for the next step.
Compound 9: To a well-stirred solution of 7 (0.50 g, 1.69 mmol) in
DMF was added the sodium salt of (6-methoxy-2,2-dimethyltetra-
hydrofuro[3,4-d][1,3]dioxol-4-yl)methanol (0.65 g, 3.38 mmol), and
the mixture was stirred at ambient temperature for 6 h. After com-
pletion of the reaction, the mixture was partitioned between aq.
NaHCO3 and EtOAc (3ϫ 20 mL), organic extracts were pooled
together, dried with anhyd. Na2SO4, filtered and the filtrate was
evaporated under reduced pressure. The resulting residue was puri-
fied by column chromatography over silica gel (EtOAc/petroleum
Compound 10e: Following the general procedure, 1-benzoylacetone
(0.31 g, 1.89 mmol) was treated with 7 (0.35 g, 1.18 mmol) in the
presence of tBuOK (0.16 g, 1.42 mmol) for 6 h to give a white crys-
talline solid 10e (0.53 g, 90%) as a mixture of separable dia-
stereomers with distinct Rf values. The diastereomers were sepa-
rated. Faster moving diastereomer: M.p. 142 °C; [α]3D0 = +94.1 (c =
1
1.60, CHCl3). H NMR: δ = 2.19 (s, 3 H), 2.45 (s, 3 H), 3.32 (s, 3
H), 3.39–3.43 (m, 1 H), 3.70–3.77 (m, 3 H), 3.83 (dd, J = 3.2,
9.2 Hz, 1 H), 4.03 (s, 1 H), 4.81 (d, J = 2.8 Hz, 1 H), 4.98 (d, J =
ether) to give 9 (0.72 g, 87%) as a colorless jelly. [α]3D0 = –7.0 (c
1
1.33, CHCl3). H NMR: δ = 1.26 (s, 3 H), 1.43 (s, 3 H), 2.41 (s, 3 10.0 Hz, 1 H), 7.37 (d, J = 8.0 Hz, 2 H), 7.48–7.52 (m, 2 H), 7.60–
H), 3.26 (s, 3 H), 3.37 (s, 3 H), 3.42 (d, J = 7.0 Hz, 2 H), 3.64–3.69 7.63 (m, 1 H), 7.84 (d, J = 8.0 Hz, 2 H), 8.02 (d, J = 7.2 Hz, 2 H)
(m, 2 H), 3.93 (dd, J = 3.2, 9.8 Hz, 1 H), 3.99–4.02 (m, 1 H), 4.06–
4.13 (m, 3 H), 4.53 (q, J = 6.0, 16.6 Hz, 2 H), 4.89 (s, 1 H), 4.92
(d, J = 2.8 Hz, 1 H), 7.33 (d, J = 8.2 Hz, 2 H), 7.79 (d, J = 8.2 Hz,
2 H) ppm. 13C NMR: δ = 21.6, 24.9, 26.4, 54.8, 54.9, 64.6, 65.0
ppm. 13C NMR: δ = 21.7,28.1, 36.0, 55.1, 59.9, 64.4, 65.0, 66.9
(CH2), 67.0, 99.2, 128.6, 129.0, 129.4, 129.8, 133.6 (C), 134.2, 136.6
(C), 145.3 (C), 195.9 (C), 203.3 (C) ppm. HRMS (ES): calcd. for
C24H26O7SNa [M + Na]+ 481.1285; found 481.1297. Slower moving
8204
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© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2013, 8197–8207

Synthesis and Studies of Furo[2,3-c]pyrans
1
diastereomer: M.p. 139 °C; [α]3D0 = +42.93 (c = 0.909, CHCl3). H
Compound 10j: Following the general procedure, dimethyl malonate
NMR: δ = 2.15 (s, 3 H), 2.40 (s, 3 H), 3.17–3.21 (m, 1 H), 3.53 (s, (0.25 mL, 2.16 mmol) was treated with 7 (0.40 g, 1.35 mmol) in the
1 H), 3.54 (s, 3 H), 3.60 (d, J = 9.6 Hz, 1 H), 3.87 (dd, J = 3.2,
9.2 Hz, 1 H), 4.19–4.20 (m, 2 H), 5.00 (d, J = 2.8 Hz, 1 H), 5.07
(d, J = 8.8 Hz, 1 H), 7.24 (d, J = 8.0 Hz, 2 H), 7.46–7.50 (m, 2 H),
7.61–7.66 (m, 3 H), 7.88 (d, J = 7.6 Hz, 2 H) ppm. 13C NMR: δ =
21.6, 30.6, 37.9, 55.4, 61.2, 61.5, 67.0 (CH2), 67.3, 99.6, 128.8,
129.0, 129.5ϫ 2, 134.1, 134.2 (C), 136.6 (C), 144.9 (C), 194.2 (C),
presence of tBuOK (0.18 g, 1.62 mmol) for 3 h to give 10j (0.54 g,
93%) as a white crystalline solid, m.p. 98 °C; [α]3D0 = +25.7 (c =
1.23, CHCl3). 1H NMR: δ = 2.43 (s, 3 H), 2.98–3.06 (m, 1 H), 3.47
(s, 3 H), 3.50 (d, J = 9.6 Hz, 1 H), 3.75 (s, 3 H), 3.78 (s, 3 H), 3.80–
3.88 (m, 4 H), 4.09–4.11 (m, 1 H), 4.86 (d, J = 3.0 Hz, 1 H), 7.39
(d, J = 8.0 Hz, 2 H), 7.82 (d, J = 8.2 Hz, 2 H) ppm. 13C NMR: δ
201.5 (C). HRMS (ES): calcd. for C24H26O7SNa [M + Na]+ = 21.7, 36.4, 52.5, 52.7, 53.2, 55.3, 60.0, 65.3, 66.8 (CH2), 67.2,
481.1285; found 481.1297.
99.3, 129.7, 129.8, 133.9 (C), 145.2 (C), 168.0 (C), 168.2 (C) ppm.
HRMS (ES): calcd. for C19H24O9SNa [M + Na]+ 451.1045; found
451.1039.
Compound 10f: Following the general procedure, 1,3-cyclohexane-
dione (0.15 g, 1.35 mmol) was treated with 7 (0.25 g, 0.85 mmol) in
the presence of tBuOK (0.11 g,1.01 mmol) for 22 h to give 10f
(0.32 g, 93%) as a white glassy crystalline solid, m.p. 162 °C; [α]3D0
= +78.6 (c = 1.16, CHCl3). 1H NMR: δ = 1.75–1.78 (m, 1 H), 2.09–
2.35 (m, 4 H), 2.39 (s, 3 H), 3.55 (s, 3 H), 3.65 (d, J = 9.2 Hz, 2
H), 3.85–3.88 (m, 2 H), 4.06 (d, J = 8.4 Hz, 1 H), 4.52 (s, 1 H),
5.18 (d, J = 1.2 Hz, 1 H), 7.28 (d, J = 8.0 Hz, 2 H), 7.77 (d, J =
8.4 Hz, 2 H), 9.33 (s, 1 H) ppm. 13C NMR: δ = 19.6 (CH2), 21.6,
29.9 (CH2), 32.4, 36.0 (CH2), 57.0, 61.7, 66.3, 68.6 (CH2), 73.0,
101.4, 114.0 (C), 129.2, 129.7, 134.7 (C), 144.7 (C), 173.6 (C), 196.9
(C) ppm. HRMS (ES): calcd. for C20H24O7SNa [M + Na]+
431.1124; found 431.1140.
General Procedure for the Conversion of 10a–g into 11a–g: Com-
pounds 10a–g were treated with TFA (2 equiv) for 3–28 h at ambi-
ent temperature. After completion of the reaction (TLC), the reac-
tion mixture was poured into satd. aq. NaHCO3 (30 mL), then par-
titioned between aq. NaHCO3 and EtOAc (3ϫ 20 mL). Organic
extracts were pooled, dried with anhyd. Na2SO4 and filtered. The
filtrate was stirred for 0.5 h with Et3N and the mixture was evapo-
rated to dryness under reduced pressure. The resulting residue was
purified by column chromatography over silica gel to give the pure
product.
Compound 11a: Following the general procedure, in 3 h, 10a
(0.30 g, 0.75 mmol) was converted into 11a (0.13 g, 80%) as a col-
Compound 10g: Following the general procedure, dimedone (0.30 g,
2.16 mmol) was treated with 7 (0.40 g, 1.35 mmol) in the presence
of tBuOK (0.18 g, 1.62 mmol) for 20 h to give 10g (0.21 g, 96%) as
a white crystalline solid, m.p. 74 °C; [α]3D0 = +24.0 (c = 0.95,
CHCl3). 1H NMR: δ = 0.95 (s, 3 H), 1.02 (s, 3 H), 2.17 (d, J =
2.4 Hz, 2 H), 2.25 (d, J = 17.6 Hz, 1 H), 2.35 (d, J = 17.6 Hz, 1
H), 2.41 (s, 3 H), 3.43 (d, J = 9.2 Hz, 1 H), 3.57 (s, 3 H), 3.75 (d,
J = 8.4 Hz, 1 H), 3.82 (d, J = 12 Hz, 2 H), 4.03 (d, J = 8.4 Hz, 1
H), 4.47 (s, 1 H), 5.16 (d, J = 1.6 Hz, 1 H), 7.32 (d, J = 8.4 Hz, 2
H), 7.89 (d, J = 8.4 Hz, 2 H), 9.35 (s, 1 H) ppm. 13C NMR: δ =
21.6, 26.8, 29.2, 31.0, 32.3, 43.7 (CH2), 49.9 (CH2), 57.0, 62.2, 66.8,
68.6 (CH2), 73.0, 101.5, 113.1 (C), 129.3, 130.2, 134.2 (C), 144.8
orless jelly. [α]3D0 = +25.4 (c = 1.27, CHCl3). H NMR: δ = 2.24 (s,
1
3 H), 2.32 (s, 3 H), 3.95–4.00 (m, 2 H), 4.42 (dd, J = 2.4, 12.8 Hz,
1 H), 4.88–4.92 (m, 1 H), 6.23 (d, J = 3.6 Hz, 1 H), 9.12 (s, 1 H)
ppm. 13C NMR: δ = 15.7, 29.2, 38.7 (CH), 65.1 (CH2), 79.3 (CH),
117.6 (C), 123.3 (CH), 152.2 (C), 168.1 (C), 186.6 (CH), 193.1 (C)
ppm. HRMS (ES): calcd. for C11H13O4 [M + H]+ 209.0794; found
209.0814.
Compound 11b: Following the general procedure, in 16 h, com-
pound 10b (0.16 g, 0.40 mmol) was converted into a 11b (0.06 g,
71%) as a colorless jelly. [α]3D0 = +20.9 (c = 0.47, CHCl3). 1H NMR:
δ = 2.19 (s, 3 H), 3.78 (s, 3 H), 3.88–3.90 (m, 1 H), 3.99 (d, J =
(C), 172.0 (C), 196.9 (C) ppm. HRMS (ES): calcd. for C22H29O7S 3.2 Hz, 1 H), 4.39 (dd, J = 2.4, 12.8 Hz, 1 H), 4.93–4.95 (m, 1 H),
[M + H]+ 437.1626; found 437.1634.
6.20 (d, J = 3.6 Hz, 1 H), 9.17 (s, 1 H) ppm. 13C NMR: δ = 14.3,
38.0, 51.2, 65.1 (CH2), 79.2, 105.3 (C), 122.8, 152.2 (C), 165.4 (C),
169.4 (C), 186.5 ppm. HRMS (ES): calcd. for C11H13O5 [M + H]+
225.0770; found 225.0763.
Compound 10h: Following the general procedure, nitromethane
(0.12 mL, 2.16 mmol) was treated with 7 (0.40 g, 1.35 mmol) in the
presence of tBuOK (0.18 g, 1.62 mmol) for 4 h to give 10h (0.44 g,
92%) as a white crystalline solid, m.p. 128 °C; [α]3D0 = +11.9 (c =
1.47, CHCl3). 1H NMR: δ = 2.45 (s, 3 H), 3.10–3.14 (m, 1 H),
3.28–3.29 (m, 1 H), 3.41 (s, 3 H), 3.58 (d, J = 9.6 Hz, 1 H), 3.89
(dd, J = 3.2, 9.6 Hz, 1 H), 4.01 (s, 1 H), 4.10 (s, 1 H), 4.25 (dd, J
= 4.0, 13.6 Hz, 1 H), 4.68–4.74 (m, 1 H), 4.94 (d, J = 2.8 Hz, 1 H),
7.38 (d, J = 8.0 Hz, 2 H), 7.83 (d, J = 8.0 Hz, 2 H) ppm. 13C NMR:
δ = 21.7, 35.4, 55.4, 59.6, 64.5, 65.9, 66.5 (CH2), 74.8 (CH2), 99.0,
129.2, 130.1, 133.6 (C), 145.7 (C) ppm. HRMS (ES): calcd. for
C15H19NO7SNa [M + Na]+ 380.0800; found 380.0780.
Compound 11c: Following the general procedure, in 20 h, com-
pound 10c (0.16 g, 0.40 mmol) was converted into 11c (0.06 g,
75%) as a colorless jelly. [α]3D0 = –11.3 (c = 2.53, CHCl3). 1H NMR:
δ = 1.16–1.30 (m, 3 H), 2.14 (d, J = 1.2 Hz, 3 H), 3.82–3.91 (m, 2
H), 4.08–4.22 (m, 2 H), 4.33 (dd, J = 2.8, 12.6 Hz, 1 H), 4.85–4.92
(m, 1 H), 6.15 (dd, J = 0.6, 3.8 Hz, 1 H), 9.11 (s, 1 H) ppm. 13C
NMR: δ = 14.5ϫ 2, 38.2, 60.1 (CH2), 65.3 (CH2), 79.3, 105.7 (C),
122.9, 152.4 (C), 165.2 (C), 169.2 (C), 186.5. HRMS (ES): calcd.
for C12H14O4Na [M + Na]+ 245.0793; found 245.0789.
Compound 11d: Following the general procedure, in 9 h, compound
10d (0.15 g, 0.35 mmol) was converted into 11d (0.06 g, 85%) as a
Compound 10i: Following the general procedure, malononitrile
(0.14 mL, 2.16 mmol) was treated with 7 (0.40 g, 1.35 mmol) in the
presence of tBuOK (0.18 g, 1.62 mmol) for 1.5 h to give 10i (0.46 g,
colorless jelly. [α]3D0 = +18.6 (c = 0.64, CHCl3). H NMR: δ = 2.19
1
(d, J = 0.4 Hz, 3 H), 3.02 (s, 3 H), 4.00–4.04 (m, 2 H), 4.41 (dd, J
= 2.8, 12.8 Hz, 2 H), 5.00–5.03 (m, 1 H), 6.24 (d, J = 3.6 Hz, 1 H),
9.21 (s, 1 H) ppm. 13C NMR: δ = 13.5, 38.7, 45.2, 64.8 (CH2), 79.5,
112.7 (C), 120.5, 152.7 (C), 168.3 (C), 186.1 ppm. HRMS (ES):
calcd. for C10H12O5SNa [M + Na]+ 267.0301; found 267.0303.
95%) as a white crystalline solid compound, m.p. 135 °C; [α]3D0
=
1
+16.9 (c = 10.27, CHCl3). H NMR: δ = 2.45 (s, 3 H), 3.02–3.06
(m, 1 H), 3.42 (s, 3 H), 3.52–3.53 (m, 1 H), 3.91 (d, J = 9.6 Hz, 1
H), 4.00 (dd, J = 3.2, 10.0 Hz, 1 H), 4.09–4.10 (m, 1 H), 4.25 (s, 1
H), 4.40 (d, J = 10.0 Hz, 1 H), 4.97 (d, J = 2.8 Hz, 1 H), 7.39 (d,
J = 8.0 Hz, 2 H), 7.85 (d, J = 8.0 Hz, 2 H) ppm. 13C NMR: δ = Compound 11e: Following the general procedure, in 28 h, com-
21.8, 24.8, 38.2, 56.1, 60.1, 64.3, 65.8 (CH2), 66.1, 99.3, 110.7 (C),
111.1 (C), 130.0, 130.1, 133.5 (C), 146.2 (C) ppm. HRMS (ES):
calcd. for C17H19N2O5S [M + H]+ 363.1006; found 363.1014.
pound 10e (0.24 g, 0.51 mmol) was converted into 11e (0.11 g,
76%) as a colorless jelly. [α]3D0 = +17.5 (c = 1.26, CHCl3). 1H NMR:
δ = 1.70 (s, 3 H), 4.05 (d, J = 12.4 Hz, 1 H), 4.16 (d, J = 8.4 Hz, 1
Eur. J. Org. Chem. 2013, 8197–8207
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
8205

C. Manna, D. Sahu, B. Ganguly, T. Pathak
FULL PAPER
H), 4.41–4.44 (m, 1 H), 4.99 (d, J = 8.8 Hz, 1 H), 6.41 (d, J = Supporting Information (see footnote on the first page of this arti-
3.6 Hz, 1 H), 7.42–7.61 (m, 5 H), 9.20 (s, 1 H) ppm. 13C NMR: δ cle): 1H and 13C NMR spectra of all new compounds, quantum
= 15.8, 39.7, 64.9 (CH2), 78.8, 116.1 (C), 123.3, 127.9, 128.4, 131.5,
chemical calculation details, tables of atom coordinates and abso-
140.1 (C), 152.1 (C), 169.0 (C), 186.5, 192.8 (C) ppm. HRMS (ES): lute energies and Figures S1–S3.
calcd. for C16H15O4 [M + H]+ 271.0966; found 271.0970.
Compound 11f: Following the general procedure, in 20 h, com-
Acknowledgments
pound 10f (0.24 g, 0.59 mmol) was converted into 11f (0.09 g, 75%)
as a colorless jelly. [α]3D0 = +168.4 (c = 0.93, CHCl3). H NMR: δ
1
T. P and B. G. thank the Department of Science and Technology
= 1.93–2.06 (m, 2 H), 2.27–2.45 (m, 4 H), 3.89–4.02 (m, 2 H), 4.33–
4.42 (m, 1 H), 5.03–5.09 (m, 1 H), 6.22–6.25 (m, 1 H), 9.09 (d, J
= 1.8 Hz, 1 H) ppm. 13C NMR: δ = 21.4 (CH2), 23.8 (CH2), 35.2,
36.4 (CH2), 65.4 (CH2), 87.2, 115.9 (C), 122.9, 152.4 (C), 178.1 (C),
186.3, 195.0 (C) ppm. HRMS (ES): calcd. for C12H13O4 [M + H]+
221.0803; found 221.0814.
(DST), New Delhi, India for financial support. C. M. thanks the
Council of Scientific and Industrial Research (CSIR), New Delhi,
India and D. S. thanks the University Grant Commission (UGC),
New Delhi for fellowships. DST is also thanked for the creation of
the 400 MHz facility under the IRPHA program and DST-FIST
for the single-crystal X-ray facility. The authors thank the reviewers
for their critical comments.
Compound 11g: Following the general procedure, in 24 h, com-
pound 10g (0.30 g, 0.69 mmol) was converted into 11g (0.13 g,
77%) as a white solid. [α]3D0 = +175.5 (c = 1.02, CHCl3). 1H NMR:
δ = 1.05 (s, 3 H), 1.12 (s, 3 H), 2.24 (d, J = 4.2 Hz, 2 H), 2.32 (d,
J = 1.2 Hz, 2 H), 3.93–4.07 (m, 2 H), 4.42 (dd, J = 2.8, 12.6 Hz, 1
H), 5.08–5.15 (m, 1 H), 6.29 (d, J = 4.0 Hz, 1 H), 9.14 (s, 1 H)
ppm. 13C NMR: δ = 28.1, 28.8, 34.2 (C), 35.2, 37.6 (CH2), 50.9
(CH2), 65.4 (CH2), 82.2, 114.2 (C), 122.6, 152.4 (C), 176.8 (C),
186.2, 194.2 (C) ppm. HRMS (ES): calcd. for C14H17O4 [M + H]+
249.1131; found 249.1127.
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One-Pot Synthesis of 11a: To a suspension of tBuOK (0.042 g,
0.37 mmol) in anhyd. THF (0.5 mL) at ambient temperature was
added acetylacetone (0.05 mL, 0.473 mmol) and the resulting solu-
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11a (0.05 g, 71%).
Compound 15: A well-stirred solution of 10a in Ac2O (1 mL) was
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H), 2.27 (s, 3 H), 2.46 (s, 3 H), 3.94 (d, J = 13.2 Hz, 1 H), 4.03–
4.13 (m, 2 H), 4.28 (d, J = 2.4 Hz, 1 H), 4.64–4.66 (m, 1 H), 4.81
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CCDC-936542 (for 8), -936543 (for 10j), and -891087 (for 15) con-
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© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Received: June 25, 2013
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