Enantiopure 1,4,5-trisubstituted 1,2,3-triazoles from carbohydrates: Applications of organoselenium chemistry

Article abstract of DOI:10.1021/jo5009564

A wide range of stable vinyl selenone-modified furanosides has been synthesized for the first time. These 2π-partners undergo 1,3-dipolar cycloaddition reactions with a wide range of organic azides to afford enantiopure trisubstituted triazoles. Furanosyl rings opened up during triazole synthesis to generate polyfunctionalized molecules, ready to undergo further transformations. This strategy is one of the most convenient methods for the synthesis of enantiopure 1,4,5-trisubstituted 1,2,3-triazoles where the chiral components are attached to C-4 or C-5 position of triazole ring. These triazoles are formed in a regioselective manner, and several pairs of regioisomeric triazoles have also been synthesized. The approach affords densely functionalized triazoles, which are amenable to further modifications because of the presence of aldehyde and hydroxyl groups. This powerful and practical route adds to the arsenals of chemists and biologists interested in the synthesis and applications of triazoles.

Full text of DOI:10.1021/jo5009564

Article
pubs.acs.org/joc
Enantiopure 1,4,5-Trisubstituted 1,2,3-Triazoles from Carbohydrates:
Applications of Organoselenium Chemistry
Atanu Bhaumik, Supravat Samanta, and Tanmaya Pathak*
Department of Chemistry, Indian Institute of Technology Kharagpur, Kharagpur 721302, India
*
S Supporting Information
ABSTRACT: A wide range of stable vinyl selenone-modified furanosides has been synthesized for the first time. These 2π-
partners undergo 1,3-dipolar cycloaddition reactions with a wide range of organic azides to afford enantiopure trisubstituted
triazoles. Furanosyl rings opened up during triazole synthesis to generate polyfunctionalized molecules, ready to undergo further
transformations. This strategy is one of the most convenient methods for the synthesis of enantiopure 1,4,5-trisubstituted 1,2,3-
triazoles where the chiral components are attached to C-4 or C-5 position of triazole ring. These triazoles are formed in a
regioselective manner, and several pairs of regioisomeric triazoles have also been synthesized. The approach affords densely
functionalized triazoles, which are amenable to further modifications because of the presence of aldehyde and hydroxyl groups.
This powerful and practical route adds to the arsenals of chemists and biologists interested in the synthesis and applications of
triazoles.
INTRODUCTION
It is obvious that the use of enantiopure organic azides in 1,3-
dipolar cycloaddition reactions would produce chiral triazoles.
For example diazides derived from D-mannitol or sugar azides
on reactions with different disubstituted acetylenes afforded
■
1
2
Long before the discovery of CuAAC or RuAAC strategies for
the synthesis of disubstituted triazoles, numerous 1,2,3-triazoles
3
in general and more than 7000 1,4-disubstituted 1-H-1,2,3-
4
7
triazoles were known in medicinal chemistry. These molecules
differently substituted chiral 1,2,3-triazoles. Enantiopure
were also known for their stability to acid and basic hydrolysis,
reductive and oxidative conditions, high dipole moment,
possibility of participating actively in hydrogen bond formation
azidoacids or azidoamides in a similar fashion afforded chiral
1,2,3-triazoles. Planar chiral triazole-based phosphanes derived
8
from [2.2]paracyclophanes are efficient ligands for the
4c
as well as in dipole−dipole and π stacking interactions.
9
palladium-catalyzed Suzuki−Miyaura coupling reactions. Chi-
However, the CuAAC strategy or “click” reaction has triggered
ral 1,2,3-triazolium derivatives, on the other hand, acted as
1
−5
explosive new developments in the area of 1,2,3-triazoles.
cationic organic catalysts in the asymmetric alkylation of
Increasing attention has recently been directed toward 1,2,3-
10
4
oxindoles (Figure 1). We have recently established that vinyl
triazole rings as ligation tools, and significant progress
1
1
sulfones in general and terminal ones derived from
occurred in applying triazole building blocks as either bioactive
11b
5
carbohydrates
are efficient substrates for combining with
components in biology or specially functionalized new
6
organic azides via 1,3-dipolar cycloaddition reaction in a
chemical entities in material chemistry. With the ever
increasing demands for new triazoles, a significant number of
groups are now involved worldwide in discovering new
synthetic strategies.
Received: May 1, 2014
Published: July 10, 2014
©
2014 American Chemical Society
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lectivity of the reaction remained unknown. Although
selenoxides and selenones are widely used in synthetic
15
chemistry, vinyl selenones have been used to a limited extent
16
in simpler systems. Selenosugars have also been used as
synthetic intermediates. However, virtually all these reports deal
with the leaving ability of selenones (and selenoxides) for the
17
generation of olefins. Moreover vinyl selenones derived from
carbohydrates have never been reported, although vinyl
selenone-modified nucleosides as mentioned above have been
efficiently used for accessing a plethora of modified nucleo-
14
sides. Interestingly, the stability of carbohydrate selenones or
selenoxides is notoriously unpredictable. For example, the
oxidation of methyl (R)-4,6-O-benzylidene-3-Se-phenyl-3-sele-
no-α-D-altropyranoside with 2 equiv of H O reportedly
2
2
produced a “selenoxide”, which was relatively stable but not
isolated; the crude was directly heated to afford the 3-deoxy-
Figure 1. Trisubstituted chiral 1,2,3-triazoles.
18
19
hexopyranosid-2-ulose. In another report 9 equiv of H O
2
2
were used for the conversion of sugar selenide to the
corresponding “selenoxide”, but the elemental analysis or
HRMS of the oxidized product was not reported.
regioselective fashion to afford 1,5-disubstituted-1,2,3-triazoles
in good to excellent yields.
We also reported that endocyclic vinyl sulfones derived from
furanosides and pyranosides A reacted with ethylisocyanoace-
12
RESULTS AND DISCUSSION
Interestingly the stability of β-sulfonyloxyselenides derived
from carbohydrates were attributable to steric effect and the
tate to afford enantiopure pyrrole analogues B (Scheme 1).
■
Scheme 1. Vinyl Sulfone as 2π Partner in Cycloaddition
Reactions
19
deactivating effect exerted by the anomeric center. This
information prompted us to initiate a study for using vinyl
selenone-modified carbohydrates where the rich chemistry of
vinyl selenone and the in-built chirality of a carbohydrate
molecule would lead to the formation of enantiopure
intermediates. Thus, the known methyl-2,3-anhydro-5-O-
20a,c
benzyl-α-D-ribofuranoside 1
(Scheme 2) was reacted with
Scheme 2. Synthesis of Methyl α-D-2-Selenonyl Pent-2-
enofuranoside
The latter strategy was quite effective in producing a wide range
of new enantiopure pyrroles. However, our attempts to extend
the strategy of combining organic azides with endocyclic vinyl
sulfones derived from furanosides and pyranosides A for the
generation of enantiopure triazoles C failed probably because of
the less reactive nature of organic azides in comparison to that
of ethylisocyanoacetate (Scheme 1).
Although enantiopure triazoles are easily synthesized by
7
−10,13
using chiral azides,
chiral substituents at C-4 and/or C-5 of 1,4,5-trisubstituted
,2,3-triazoles (1,4,5-TTs) may be achieved by using
carbohydrates known as “chiral pool” as was the case with
the more difficult task of introducing
1
1
2
pyrrole synthesis. Since it was not possible to activate azides
further, we planned to use a different 2π partner for the
cycloaddition reaction. Vinyl selenones have been effectively
used in the past as one of the components of cycloaddition
sodium phenyl selenide generated from diphenyl diselenide and
21
sodium borohydride to afford the corresponding β-hydroxy
selenide derivative 2 in excellent yield. The β-hydroxy selenide
2 was oxidized by magnesium monoperoxyphthalate hexahy-
drate (MMPP) in methanol to produce β-hydroxy selenone 4.
Mesylation of the selenone 4 followed by the concomitant
elimination of methanesulfonic acid afforded methyl-5-O-
benzyl-2,3-dideoxy-2-phenylselenonyl-α-D-erythro-pent-2-eno-
furanoside 5. Attempted mesylation of 2 did not produce 3 and
1
4c
reactions. We therefore intended to employ endocyclic vinyl
selenones derived from carbohydrates as the 2π component in
the cycloaddition reaction. However, as far as our knowledge
goes in the literature the reaction between any vinyl selenone
and an organic azide, expected to produce triazoles, has never
been attempted. The only report on the reactions between vinyl
selenone-modified uridine and sodium azide afforded 1-
22a
(
2′,3′dideoxy-2′,3′-(2H-1,2,3-triazolo)-β-D-glycero-pent-2′-
the olefin 6 was obtained instead (Scheme 2). Compound 5
was found to be stable and may be stored for a long period
14c
eno-furanosyl)uracil in 64% yield.
Therefore, the regiose-
6
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below 30 °C. The successful synthesis of 5 prompted us to
expand the strategy for the preparation of other sugar based
vinyl selenone-modified carbohydrates. Interestingly attempted
synthesis of the regioisomer of 5 was unsuccessful. Although
In a similar way methyl-2,3-anhydro-5,6-O-cyclohexylidene-
23
α-D-mannofuranoside 18 was reacted with phenyl selenide to
afford β-hydroxy selenide 19 as stated above. Attempted
oxidation of 19 with MMPP in methanol at room temperature
produced the starting epoxide 18. The free hydroxyl group of
compound 19 was mesylated to afford the mesyl derivative 20,
which degraded slowly at room temperature. Therefore, the
crude mesyl derivative 20 was directly treated with potassium
tert-butoxide in DMF at room temperature to produce vinyl
selenide 21, and the latter was subjected to MMPP mediated
oxidation in methanol to produce the 3-selenonyl hex-2-
enofuranoside 22 in 48% overall yield starting from compound
2
0a,b
epoxide 7
was successfully opened by phenylselenide, the
product 8 under the oxidation conditions reverted back to the
starting material 7. On the other hand attempted mesylation of
22
8
produced the olefin 9 (Scheme 3).
Scheme 3. Attempted Synthesis of Methyl β-D-3-Selenonyl
Pent-2-enofuranoside
19 (Scheme 5).
It is evident from Schemes 2−5 that some of the
selenosugars are stable to synthetic manipulations, whereas
few of them are unstable. A closer look at the structural features
of these compounds reveals a pattern, which is in line with the
19
observations mentioned above. For example, the presence of
anomeric methoxy group in the vicinity of C-2 of 4 inhibited
the intramolecular attack of 3-OH at C-2 carbon (Scheme 2),
whereas in case of selenone generated from 8, the unhindered
attack of 2-OH at C-3 afforded the starting epoxide 7.
Mesylation of 8 destabilizes the selenide further triggering
elimination of both the functional groups at C-2 and C-3
(
Scheme 3). Once again, the anomeric β-methoxy group
imparted stability to selenone 13 by protecting the C-2 carbon
from the attack of C-3 OH (Scheme 4). On the other hand,
selenones derived from 12 (Scheme 4) and 19 (Scheme 5)
were unstable probably because C-3 positions of these
compounds were easily accessible to intramolecular nucleo-
philic attack by the C-2 hydroxyl group.
In order to synthesize the corresponding enohexofurano-
sides, methyl-2,3-anhydro-5,6-O-cyclohexylidene-β-D-manno-
2
3
furanoside 10 was treated with sodium phenyl selenide to
afford a mixture of β-hydroxy selenides 11 and 12, which were
separated by simple column chromatography. The major
isomer 11 was subjected to the MMPP mediated oxidation in
MeOH to produce the selenone derivative 13, which on
mesylation and consecutive elimination afforded methyl-5,6-O-
cyclohexylidene-2,3-dideoxy-2-phenylselenonyl-β-D-erythro-
hex-2-enofuranoside 14 (Scheme 4). Attempted oxidation of 12
produced an inseparable mixture of compounds. Therefore, 12
was mesylated to afford the mesyl derivative 15. Since 15
degraded slowly at room temperature, the crude compound 15
was immediately treated with potassium tert-butoxide in DMF
at room temperature to produce vinyl selenide 16. The latter
compound on treatment with MMPP in methanol afforded 3-
selenonyl hex-2-enofuranoside 17 in 47% overall yield starting
from compound 12 (Scheme 4).
Since the regiochemistry of triazole formation would
inevitably depend on the orientation of the vinyl selenone
group in the furanoside skeletons, it was imperative to establish
the regiochemistry of epoxide opening by phenyl selenide. The
regioselectivity of epoxide opening for 1 was unambiguously
established with the help of crystal structure of compound 4
(Figure S1, Supporting Information). The β-D-riboepoxide 7 is
2
4a
known
to afford 3-xylo analogues like 8. It is well
24b
documented
that the coupling constant (J ) values of
1,2
authentic methyl β-D-xylofuranosides range between 0.0 to 2.0
Hz, which indicated apparently trans relationship between H-1
and H-2, whereas the coupling constant (J ) values for
1,2
authentic methyl β-D-arabinofuranosides range between 3.0 to
Scheme 4. Synthesis of Methyl β-D-2-Selenonyl Hex-2-enofuranoside and Methyl β-D-3-Selenonyl Hex-2-enofuranoside
6
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Scheme 5. Synthesis of Methyl α-D-3-Selenonyl Hex-2-enofuranoside
5
.0 Hz, indicating a cis arrangement of H-1 and H-2. In case of
Scheme 6. Synthesis of 1,4,5-Trisubstituted-1,2,3-Triazoles
compound 11 (J1,2 = 0.0 Hz) H-1 and H-2 are trans to each
other whereas for 12 (J1,2 = 4.4 Hz) H-1 and H-2 are in a cis
relationship. The additional support for the structures of the
regioisomer 12 and its downstream product 17 was obtained
through an indirect route as both the vinyl selenones 17 (10 →
from Methyl α-D-2-Selenonyl Pent-2-enofuranoside
1
2
2 → 15 → 16 → 17; Scheme 4) and 22 (18 → 19 → 20 →
1 → 22; Scheme 5) afforded identical triazoles (Scheme 8; see
24a
later). Since 18, structurally related to α-D-lyxoepoxide can
exclusively afford C-3 substituted product 19 (Scheme 5), it is
obvious that 12 is also a C-3 selenofuranoside. Therefore, 11 is
a C-2 seleno derivative as depicted in Scheme 4.
1
In the H NMR of 5, the vinylic proton was masked by
aromatic protons. For compound 14, the vinylic proton
appeared as a sharp singlet at δ 7.38 ppm and that for
compound 17 the same proton appeared as a doublet (J = 1.6
1
3
Hz) at δ 6.94 ppm. The C NMR signals at δ 145.7 and 148.7
ppm are assigned to the vinylic carbons of compound 14 and
1
7 respectively. Compound 22 has a characteristic sharp singlet
1
at δ 6.91 ppm ( H NMR), corresponding to vinylic proton and
1
3
signal at δ 140.0 ppm ( C NMR) indicate the vinylic carbon.
For the synthesis of triazoles a wide variety of organic azides
a−f (Figure 2) were selected. Thus, 5-O-benzyl-2-selenonyl
Figure 2. Organic azides used for synthesis of 1,4,5-trisubstituted-
1,2,3-triazoles.
pent-2-enofuranoside 5 on reactions with 1.5 equiv of azides a,
2
5c 25c
25a 25b
25d
b, c, d,
solvent at 90 °C, afforded 1,4,5-trisubstituted-1,2,3-triazoles
3a−f respectively as single products (Scheme 6). Each of the
e
or f
(Figure 2) in tert-butanol-water
2
triazoles 23a−e contains one chiral center, one −CHO group
and a secondary alcohol group leading to the formation of
enantiomers 23a−e. In order to establish the regioselectivity of
the triazole formation, compound 23c was reduced with
to afford the identical triazoles 26b−d (Scheme 8), indicating
that the anomeric configurations do not play any significant
role on the regioselectivity of the 1,3-dipolar cycloaddition.
It should be noted that in these reactions, around 65%
starting vinyl selenone-modified carbohydrates were consumed
and the remaining unreacted portions were recovered in every
case. We checked the feasibility of the reaction in water, DMF−
water, toluene−water, THF−water and DMSO−water systems.
However, the cycloaddition reactions did not proceed in
DMF−water, toluene−water, THF−water and the desired
triazoles were formed in better yields only in tert-butanol-water
(6:1) mixture. Approximately one-third of the starting materials
remained unreacted even after the addition of excess azides or
prolonged reaction time.
NaBH to the corresponding alcohol, which on esterification
4
with 4-nitrobenzoyl chloride afforded the crystalline ester
derivative 24 (Scheme 6). 2-Selenonyl hex-2-enofuranoside 14
on treatment with organic azides a−f under similar conditions
afforded trisubstituted chiral triazole derivatives 25a−f
respectively (Scheme 7). The β-anomeric 3-selenonyl hex-2-
enofuranoside 17 also reacted with organic azides b, c and d in
a similar fashion to afford 1,4,5-trisubstituted chiral 1,2,3-
triazoles 26b−d respectively (Scheme 8). The α-anomeric 3-
selenonyl hex-2-enofuranoside 22 also reacted with azides b−d
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Scheme 7. Synthesis of 1,4,5-Trisubstituted-1,2,3-Triazoles
from Methyl β-D-2-Selenonyl Hex-2-enofuranoside
regioselective formation of compound 23c. From the ORTEP
diagram of compound 24 and the similar NMR patterns of
compound 23a−f we presumed that all the trisubstituted
triazoles 23a−f synthesized from vinyl selenone 5 have similar
26
configurations. Following an approach described to differ-
entiate between the NMR data of 1,4-disubstituted-1,2,3-
triazoles and 1,5-disubstituted-1,2,3-triazoles we concluded that
the difference (Δ) between the chemical shift values of C-4/C-
5
, i.e., (144.8 ppm − 143.0 ppm = 1.8 ppm) of 23c may be used
to identify the regioisomers. In this case it is not necessary to
know the exact chemical shifts of C-4/C-5. Thus, all other
isomers 23a,b and 23d−f described in Scheme 6 afford Δ
values ranging between 0.7−1.2 ppm. On the other hand, the
difference (Δ) between the chemical shift values of C-4/C-5 for
25a−f ranges between 0 and 1.1 ppm indicating the similarity
between compounds 23 and 25. However, the differences (Δ)
between the chemical shift values of C-4/C-5 for 26b−d are
much larger and ranges between 21.1 and 21.4 ppm, indicating
that these compounds are the regioisomers of 25b−d.
We believed that the cascade of reactions is initiated by the
cycloaddition reactions between vinyl selenones and azides as
11
was the case with vinyl sulfones and organic azides. We
presumed that the first step is most likely the 1,3 dipolar
cycloaddition reaction between a vinyl selenone and an organic
azide to form the cyclic intermediate D followed by the
elimination of phenyl seleninic acid (PhSeO H) to produce the
2
intermediate E. The planarity of the triazole ring attached to
the furanoside system created sufficient strain to cleave the
hemiacetal bond of the furanoside ring via intermediates F and
G to afford the triazole H (Scheme 9). The opening of the
sugar ring is similar to the ring rupture in case of pyrrole
12
formation reported earlier. It is probable that phenylseleninic
acid catalyzes the cleavage of the acetal bond. It has been
Scheme 8. Synthesis of 1,4,5-Trisubstituted-1,2,3-Triazoles
from 3-Selenonyl Hex-2-enofuranosides
Scheme 9. Plausible Mechanism of the Trisubstituted 1,2,3-
Triazole Formation
For all triazoles sharp singlets between δ 10.04−10.24 ppm
(1
H NMR) and peaks between δ 181.2−189.1 ppm ( C
13
NMR) indicate the presence of aldehyde group. The single
crystal X-ray analysis of compound 24 (Scheme 6; Figure S2,
Supporting Information) unambiguously established the
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1
1d
established from theoretical calculations
that a particular
3H), 4.11−4.12 (m, 1H), 4.15−4.19 (m, 1H), 4.60−4.64 (m, 2H),
1
3
5
.08 (s, 1H), 7.24−7.36 (m, 8H), 7.53−7.56 (m, 2H); C NMR (50
orientation of the azido group of an organic azide with respect
to the vinyl sulfone group dictates the regiochemistry of triazole
formation. On the basis of this information, we presume that
the regioselectivity of triazole formation is dictated by a severe
steric interaction between the R′-group of the organic azides
MHz, CDCl ) δ 51.8, 55.3, 70.4 (CH ), 73.6 (CH ), 78.1, 84.2, 109.5,
3
2
2
+
1
27.8, 127.9, 128.5, 129.0, 129.5, 133.6, 138.0; HRMS [ES , (M +
+
Na) ] for C H O SeNa found 417.0593, calcd 417.0581.
19
22
4
Methyl-5-O-benzyl-2-deoxy-2-phenylselenonyl-α-D-arabino-
furanoside 4. To the solution of compound 2 (0.1 g, 0.25 mmol) in
MeOH (10 mL) MMPP (0.370 g, 0.75 mmol) was added, and the
reaction mixture was stirred for 2 h at room temperature. After
completion of the reaction (TLC) mixture was filtered, and the filtrate
was evaporated under reduced pressure to get a residue, which was
partitioned between water (50 mL) and EtOAc (3 × 10 mL). The
combined organic layer was dried over anhyd. Na SO , filtered, and
and the PhO Se group attached to the sugar ring, which
2
positions two reactive species in such a way that these two
groups move away from each other. The regioisomeric triazole
I is formed from the opposite orientation of the reactants
involved as depicted in Scheme 9. Thus, both vinyl selenones 5
and 14 having the PhO Se group attached to C-2 afforded
2
4
2
the filtrate was concentrated under reduced pressure to get a residue.
The residue was purified over silica gel to afford compound 4 (0.082 g,
triazoles where the −CHO group and the -R′ group are furthest
away from each other whereas vinyl selenones 17 and 22
7
6%). [Eluent: EtOAc:pet ether (1:1)] White solid: mp 81 °C (from
26 1
functionalized with PhO Se group at C-3 afforded the identical
2
EtOH); [α]D +4.7 (c 1.30 in CHCl ); H NMR (400 MHz, CDCl )
3
3
triazoles having the −CHO group and the -R′ group on the
same side of the triazole ring. However, further studies are
required to establish the exact mechanism of these reactions.
δ 3.33 (s, 3H), 3.57−3.70 (m, 2H), 4.11−4.15 (m, 2H), 4.52 (s, 2H),
4
.79−4.82 (m, 1H), 5.33 (d, 1H, J = 2.4 Hz), 7.27−7.35 (m, 5H),
13
7.56−7.60 (m, 2H), 7.66−7.69 (m, 1H), 7.97 (d, 2H, J = 7.6 Hz);
NMR (50 MHz, CDCl ) δ 55.9, 68.9 (CH ), 71.9, 73.8 (CH ), 81.0,
C
3
2
2
8
1.5, 102.0, 127.6, 128.0, 128.6, 130.6, 134.9, 137.9, 140.6; HRMS
CONCLUSION
■
+
+
[
ES , (M + Na) ] for C H O SeNa found 449.0501, calcd 449.0479.
19 22 6
We have successfully synthesized a group of stable vinyl
selenone-modified carbohydrates from D-xylose and D-glucose.
The yields of intermediate steps are good to excellent. We have
demonstrated one pot regioselective synthesis of enantiomeri-
cally pure 1,4,5-trisubstituted 1,2,3-triazoles having chiral
components attached to C-4 or C-5 depending on the
structures of the starting vinyl selenones. The reactions are
operationally simple and require no catalyst, metal or otherwise.
The triazoles are densely functionalized, and depending on the
requirements these compounds may be derivatized further
because of the presence of at least an aldehyde group and a
secondary hydroxyl group. In some cases additional groups like
a primary hydroxyl as well as an azido group are also available.
This strategy provides an efficient route to the chemists and
biologists for accessing a wide variety of trisubstituded 1,2,3-
triazoles.
Methyl-5-O-benzyl-2,3-dideoxy-2-phenylselenonyl-α-D-er-
ythro-pent-2-enofuranoside 5. To a well-stirred solution of 4
(0.04 g, 0.094 mmol) in anhyd. pyridine (5 mL) methanesulfonyl
chloride (0.014 mL, 0.188 mmol) was added at 0 °C, and the mixture
was left overnight at +4 °C. The reaction mixture was poured into
satd. aq. NaHCO solution (50 mL), which was then extracted with
EtOAc (3 × 15 mL). The combine extracts were dried over anhyd.
Na SO , filtered, and the filtrate was evaporated under reduced
pressure. Residual pyridine was coevaporated with toluene. The
residue was purified over silica gel to furnish compound 5 (0.033 g,
3
2
4
26
8
1
7%). [Eluent: EtOAc:pet ether (2:3)] Brownish gum: [α]D −6.8 (c
1
.27 in CHCl ); H NMR (400 MHz, CDCl ) δ 3.25 (s, 3H), 3.53−
3
3
3.65 (m, 2H), 4.49 (s, 2H), 5.16 t, 1H, J = 4.4 Hz), 6.03 (d, 1H, J = 4.4
Hz), 7.27−7.33 (m, 6H), 7.55−7.68 (m, 3H), 7.96 (d, 2H, J = 8.0
Hz); 13C NMR (50 MHz, CDCl
) δ 54.9, 70.6 (CH ), 73.7 (CH ),
3 2 2
8
1
4
4.8, 106.7, 127.1, 127.8, 128.0, 128.5, 130.2, 134.5, 137.5, 141.7,
+
+
42.1, 145.4; HRMS [ES , (M + Na) ] for C H O SeNa found
19 20
5
31.0389, calcd 431.0374.
Methyl-5-O-benzyl-2,3-dideoxy-α-D-pent-2-enofuranoside
. To a well-stirred solution of 2 (0.1 g, 0.25 mmol) in anhyd. pyridine
EXPERIMENTAL SECTION
6
■
(
5 mL) methanesulfonyl chloride (0.028 mL, 0.37 mmol) was added
General Methods. Melting points were determined in open-end-
capillary tubes and are uncorrected. Carbohydrates and other fine
chemicals were obtained from commercial suppliers and used without
purification. Solvents were dried and distilled following the standard
procedures. TLC was carried out on precoated plates (Merck silica gel
at 0 °C, and the mixture was left overnight at +4 °C. The reaction
mixture was poured into ice-cold water (50 mL), which was then
extracted with EtOAc (3 × 15 mL). The combined organic layer was
dried over anhyd. Na SO , filtered and evaporated under reduced
pressure. Residual pyridine was coevaporated with toluene. The
residue was purified over silica gel to furnish compound 6 (0.043 g,
76%). [Eluent: EtOAc:pet ether (1:4)] Colorless oil: H NMR (400
MHz, CDCl
2 4
6
0, f254), and the spots were visualized with UV light or by charring the
plates dipped in 5% H SO −MeOH solution. Column chromatog-
2
4
1
13
1
raphy was performed on silica gel (230−400 mesh). H and C NMR
for compounds were recorded at 400/200 MHz instrument and 50.3
3
) δ 3.41 (s, 3H), 3.53−3.55 (m, 2H), 4.55−4.63 (m, 2H),
MHz instrument, respectively, using CDCl as the solvent. DEPT
5.06−5.09 (m, 1H), 5.82−5.83 (m, 1H), 5.86−5.88 (m, 1H), 6.20 (dd,
1H, J = 1.2 Hz, 6.0 Hz), 7.28−7.35 (m, 5H); C NMR (50 MHz,
CDCl ) δ 54.4, 72.4 (CH ), 73.6 (CH ), 84.6, 109.5, 127.6, 127.9,
3
13
experiments were carried out to identify the methylene carbons. High
resolution mass spectra were recorded using QTOF mass analyzer.
Optical rotations were recorded at 589 nm.
3
2
2
+
+
128.1, 128.6, 133.4, 138.2; HRMS [ES , (M + H) ] for C13
H O
17 3
Methyl-5-O-benzyl-2-deoxy-2-phenylselanyl-α-D-arabino-
furanoside 2. A solution of sodium phenyl selenide in absolute
ethanol (10 mL) was prepared from diphenyl diselenide (0.237 g, 0.76
found 221.1188, calcd 221.1178.
Methyl-5-O-benzyl-3-deoxy-3-phenylselanyl-β-D-xylofura-
noside 8. Compound 7 (0.3 g, 1.27 mmol) was converted to 8 (0.456
g, 91%) following the procedure described for the preparation of
mmol) and NaBH , (0.051 g, 1.52 mmol). To the solution of selenide
4
2
6
was added a solution of oxirane 1 (0.3 g, 1.27 mmol) in absolute
ethanol (5 mL), and the mixture was stirred at room temperature.
After 2 h ethanol was evaporated under reduced pressure, and the
compound 2. [Eluent: EtOAc:pet ether (1:3)] Colorless oil: [α]D
1
+27.5 (c 1.00 in CHCl ); H NMR (200 MHz, CDCl ) δ 2.01 (d, 1H,
3
3
J = 5.0 Hz), 3.38 (s, 3H), 3.58−3.64 (m, 1H), 3.76 (d, 2H, J = 5.0 Hz),
residue was partitioned between satd. aq. solution of NH Cl and
4.47 (s, 1H), 4.56 (s, 2H), 4.60−4.66 (m, 1H), 4.81 (d, 1H, J = 1.8
4
13
EtOAc (3 × 10 mL). The combined organic layer was dried over
Hz), 7.21−7.33 (m, 8H), 7.51−7.56 (m, 2H); C NMR (50 MHz,
CDCl ) δ 49.5, 55.3, 70.3 (CH ), 73.5 (CH ), 78.0, 86.7, 111.6, 127.8,
anhyd. Na SO , filtered, and the filtrate was concentrated under
2
4
3
2
2
+
reduced pressure to get a residue. The residue was purified over silica
127.9, 128.4, 128.9, 129.2, 129.4, 133.5, 137.9; HRMS [ES , (M +
+
gel to afford compound 2 (0.46 g, 92%). [Eluent: EtOAc:pet ether
Na) ] for C H O SeNa found 417.0593, calcd 417.0581.
19
22
4
1
(
1:3)] Colorless gum: [α]D26 +8.1 (c 1.31 in CHCl ); H NMR (400
Attempted Oxidation of Methyl-5-O-benzyl-3-deoxy-3-phe-
nylselanyl-β-D-xylofuranoside 8. Compound 8 (0.1 g, 0.25 mmol)
3
MHz, CDCl ) δ 2.59 (d, 1H, J = 8.4 Hz), 3.38 (s, 3H), 3.56−3.72 (m,
3
6
900
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The Journal of Organic Chemistry
Article
was converted to compound 7 (0.039 g, 71%) while oxidized following
at 0 °C, and the stirring was continued at room temperature for 2 h.
the procedure described for the preparation of compound 4. [Eluent:
The solution was partitioned between satd. aq. NH Cl and EtOAc (3
4
1
EtOAc:pet ether (1:5)] Colorless gum: H NMR (200 MHz, CDCl )
× 10 mL). The combined organic layer was dried over anhyd. Na SO ,
3
2
4
δ 3.37 (s, 3H), 3.40−3.63 (m, 2H), 3.66 (d, 1H, J = 2.6 Hz), 3.82 (d,
filtered, and the filtrate was evaporated under reduced pressure to give
compound 16. To a solution of 16 in MeOH (10 mL) MMPP (0.74 g,
1.50 mmol) was added. The reaction mixture was stirred for 2 h at
room temperature and filtered. The filtrate was evaporated under
reduced pressure, and the residue was partitioned between satd. aq.
1
H, J = 2.6 Hz), 4.32 (q, 1H, J = 6.0 Hz), 4.57 (s, 2H), 4.95 (s, 1H),
.35−7.50 (m, 5H).
7
Methyl-5-O-benzyl-2,3-dideoxy-β-D-pent-2-enofuranoside
. Compound 8 (0.1 g, 0.25 mmol) was converted to compound 9
9
(
0.044 g, 77%) while mesylated following the procedure described for
NaHCO (60 mL) and EtOAc (3 × 10 mL). Organic layers were
3
the preparation of compound 6. [Eluent: EtOAc:pet ether (1:5)]
pooled together, dried over anhyd. Na SO , filtered, and the filtrate
2
4
1
Colorless gum: H NMR (200 MHz, CDCl ) 3.41 (s, 3H), 3.51−3.61
was evaporated to dryness under reduced pressure to get a gummy
residue. The resulting residue was purified over silica gel to yield
compound 17. (0.102 g, 47% in three steps). [Eluent: EtOAc:pet ether
3
(
m, 2H), 4.53−4.67 (m, 2H), 4.90 (t, 1H, J = 5.6 Hz), 5.73 (s, 1H),
5
.87 (d, 1H, J = 6.0 Hz), 6.20 (d, 1H, J = 6.0 Hz), 7.27−7.35 (m, 5H).
(1:2)] Colorless gum: [α]D26 −99.7 (c 0.92 in CHCl ); H NMR (400
1
Methyl-5,6-O-cyclohexylidene-2-deoxy-2-phenylselanyl-β-D-
3
glucofuranoside 11 and Methyl-5,6-O-cyclohexylidene-3-
deoxy-3-phenylselanyl-β-D-mannofuranoside 12. Compound
MHz, CDCl ) δ 1.25−1.64 (m, 10H), 3.45 (s, 3H), 3.87−3.91 (m,
3
1
5
7
H), 3.96−3.99 (m, 1H), 4.05−4.10 (m, 1H), 5.01−5.03 (m, 1H),
1
0 (0.58 g, 2.26 mmol) was converted to compound 11 (0.356 g,
.73 (d, 1H, J = 0.8 Hz), 6.94 (d, 1H, J = 1.6 Hz), 7.62−7.72 (m, 3H),
38%) and 12 (0.302 g, 32%), following the procedure described for
13
.99−8.01 (m, 2H); C NMR (50 MHz, CDCl ) δ 23.7 (CH ), 24.0
3
2
the preparation of compound 2. Compound 11: [Eluent: EtOAc:pet
(CH ), 25.2 (CH ), 34.6 (CH ), 36.1 (CH ), 56.5, 65.5 (CH ), 77.1,
2 2 2 2 2
26
1
ether (1:5)] Colorless gum; [α]D +22.2 (c 0.92 in CHCl ); H NMR
3
84.1, 107.4, 111.2, 127.1, 127.2, 130.2, 130.3, 134.6, 139.8, 142.2,
(
3
1
400 MHz, CDCl ) δ 1.33−1.62 (m, 10H), 3.34 (s, 3H), 3.73 (s, 1H),
+
+
3
148.7; HRMS [ES , (M + Na) ] for C H O SeNa found 451.0640,
19 24 6
.98−4.01 (m, 1H), 4.12−4.16 (m, 1H), 4.29−4.37 (m, 3H), 4.99 (s,
calcd 451.0636.
13
H), 7.30−7.32 (m, 3H), 7.56 (t, 2H, J = 3.6 Hz); C NMR (50
Methyl-5,6-O-cyclohexylidene-3-deoxy-3-phenylselanyl-α-
D-mannofuranoside 19. Compound 18 (0.58 g, 2.26 mmol) was
converted to compound 19 (0.66 g, 70%) following the procedure
described for the preparation of compound 2. [Eluent: EtOAc:pet
MHz, CDCl ) δ 24.0 (CH ), 24.2 (CH ), 25.2 (CH ), 34.9 (CH ),
3
2
2
2
2
3
1
6.6 (CH ), 51.1, 55.5, 66.9 (CH ), 74.0, 76.4, 83.8, 109.2, 110.0,
2
2
+
+
28.2, 129.6, 134.0; HRMS [ES , (M + Na) ] for C H O SeNa
19
26
5
ether (1:5)] Yellowish gum: [α]D26 −35.2 (c 0.66 in CHCl ); H
1
found 437.0828, calcd 437.0843. Compound 12: [Eluent: EtOAc:pet
3
26
1
ether (1:3)] Yellowish gum; [α]D +47.3 (c 1.22 in CHCl ); H NMR
3
NMR (400 MHz, CDCl ) δ 1.38−1.64 (m, 10H), 3.34−3.39 (m, 5H),
3
(
3
7
400 MHz, CDCl ) δ 1.37−1.59 (m, 10H), 3.43 (s, 3H), 3.73 (s, 1H),
3
3.47 (bs, 1H), 3.94−3.98 (m, 1H), 4.31 (bs, 1H), 4.35−4.39 (m, 2H),
1
3
.98−4.05 (m, 4H), 4.26−4.39 (m, 2H), 4.77 (d, 1H, J = 4.4 Hz),
4
.92 (s, 1H), 7.29−7.30 (m, 3H), 7.59−7.61 (m, 2H); C NMR (50
13
.26−7.33 (m, 3H), 7.55−7.58 (m, 2H); C NMR (50 MHz, CDCl )
3
MHz, CDCl ) δ 23.7 (CH ), 24.0 (CH ), 25.2 (CH ), 34.1 (CH ),
3 2 2 2 2
δ 23.9 (CH ), 24.1 (CH ), 25.2 (CH ), 34.9 (CH ), 36.3 (CH ), 46.4,
2
2
2
2
2
35.6 (CH ), 44.8, 55.0, 65.2 (CH ), 75.5, 81.0, 87.2, 109.7, 111.0,
2 2
+
+
5
1
5.5, 65.8 (CH ), 74.2, 77.2, 82.9, 102.0, 110.3, 128.5, 129.3, 129.5,
36.0; HRMS [ES , (M + Na) ] for C H O SeNa found 437.0823,
19 26 5
2
128.0, 129.6, 130.6, 133.9; HRMS [ES , (M + Na) ] for
+
+
C H O SeNa found 437.0828, calcd 437.0843.
19
26
5
calcd 437.0843.
Methyl-5,6-O-cyclohexylidene-2,3-dideoxy-3-phenylsele-
Methyl-5,6-O-cyclohexylidene-2-deoxy-2-phenylselenonyl-
β-D-glucofuranoside 13. Compound 11 (0.1 g, 0.24 mmol) was
converted to compound 13 (0.08 g, 75%) following the procedure
described for the preparation of compound 4. [Eluent: EtOAc:pet
nonyl-α-D-erythro-hex-2-enofuranoside 22. Compound 19 (0.2
g, 0.48 mmol) was converted into compound 22 (0.099 g, 48% in
three steps) following the procedure described under the preparation
of compound 17. [Eluent: EtOAc:pet ether (1:2)] Colorless gum:
ether (3:2)] Colorless gum: [α]D26 +7.7 (c 0.47 in CHCl ); H NMR
1
26
1
3
[α]D −77.7 (c 1.00 in CHCl ); H NMR (400 MHz, CDCl ) δ
3
3
(
400 MHz, CDCl ) δ 1.25−1.62 (m, 10H), 3.32 (bs, 1H), 3.38 (s,
1.23−1.62 (m, 10H), 3.38 (s, 3H), 3.83−3.88 (m, 1H), 3.94−3.97 (m,
1H), 4.07−4.11 (m, 1H), 5.12−5.14 (m, 1H), 5.86 (d, 1H, J = 4.4
Hz), 6.91 (s, 1H), 7.53−7.55 (m, 2H), 7.61−7.70 (m, 1H), 7.99 (d,
3
3
5
7
H), 3.96−4.04 (m, 2H), 4.11−4.15 (m, 2H), 4.35−4.40 (m, 1H),
.00 (t, 1H, J = 1.6 Hz), 5.47 (d, 1H, J = 2.0 Hz), 7.67−7.70 (m, 2H),
13
13
.74−7.78 (m, 1H), 8.00−8.02 (m, 2H); C NMR (50 MHz, CDCl )
2H, J = 7.2 Hz); C NMR (50 MHz, CDCl ) δ 23.8 (CH ), 24.0
3
3
2
δ 24.0 (CH ), 24.2 (CH ), 25.2 (CH ), 34.8 (CH ), 36.6 (CH ), 56.5,
(CH ), 25.2 (CH ), 34.7 (CH ), 36.0 (CH ), 55.1, 65.4 (CH ), 76.2,
2
2
2
2
2
2 2 2 2 2
6
7.2 (CH ), 71.6, 73.7, 79.8, 83.1, 103.1, 110.9, 127.5, 130.7, 135.0,
84.5, 107.2, 111.4, 127.3, 130.4, 134.7, 140.0, 142.1, 148.7; HRMS
2
+
+
+
+
140.8; HRMS [ES , (M + Na) ] for C H O SeNa found 469.0728,
[ES , (M + Na) ] for C H O SeNa found 451.0646, calcd 451.0636.
19
26
7
19 24 6
calcd 469.0741.
Attempted Oxidation of Methyl-5,6-O-cyclohexylidene-3-
deoxy-3-phenylselanyl-α-D-mannofuranoside 19. Compound
19 (0.1 g, 0.24 mmol) was converted to compound 18 (0.048 g,
77%) while oxidized following the procedure described for the
preparation of compound 4. [Eluent: EtOAc:pet ether (1:5)]
Methyl-5,6-O-cyclohexylidene-2,3-dideoxy-2-phenylsele-
nonyl-β-D-erythro-hex-2-enofuranosid 14. Compound 13 (0.08
g, 0.18 mmol) was converted to compound 14 (0.070 g, 92%)
following the procedure described for the preparation of compound 5.
2
6
Colorless gum: 1H NMR (400 MHz, CDCl ) δ 1.22−1.64 (m,
[
Eluent: EtOAc:pet ether (1:1)] Yellowish gum: [α]D −149.4 (c 1.00
3
1
in CHCl ); H NMR (400 MHz, CDCl ) δ 1.25−1.70 (m, 10H), 3.33
10H), 3.39 (s, 3H), 3.67 (d, 1H, J = 2.8 Hz), 3.83−3.88 (m, 2H),
3.93−3.96 (m, 1H), 4.08−4.16 (m, 2H), 4.90 (s, 1H).
3
3
(
7
(
s, 3H), 3.91−4.06 (m, 3H), 4.75 (d, 1H, J = 8.0 Hz), 5.98 (s, 1H),
13
.38 (s, 1H), 7.62−7.73 (m, 3H), 8.02 (d, 2H, J = 8.0 Hz); C NMR
General Procedure for the Synthesis of 1,4,5-Trisubstituted-
1,2,3-Triazoles 23a−f, 25a−f, 26b−d. A mixture of vinyl selenone
(1 mmol), and organic azide (1.5 mmol) in tert-butanol-water (6 mL +
1 mL)/mmol of vinyl selenone was heated at 90 °C. Heating was
continued until the reaction reached a saturation point (TLC) and
then cooled to room temperature. Volatile matters were evaporated
under a vacuum, and the residue was partitioned between EtOAc and
50 MHz, CDCl ) δ 23.9 (CH ), 24.2 (CH ), 25.2 (CH ), 34.7
3 2 2 2
(
1
CH ), 36.8 (CH ), 56.0, 66.8 (CH ), 77.2, 86.6, 107.3, 111.1, 127.3,
2 2 2
+
+
30.3, 134.6, 142.4, 145.7; HRMS [ES , (M + H) ] for C H O Se
19 25 6
found 429.0817, calcd 429.0816.
Methyl-5,6-O-cyclohexylidene-2,3-dideoxy-3-phenylsele-
nonyl-β-D-erythro-hex-2-enofuranoside 17. To a well-stirred
solution of 12 (0.209 g, 0.5 mmol) in anhyd. pyridine (10 mL)
methanesulfonyl chloride (0.076 mL, 1.00 mmol) was added at 0 °C,
and the reaction mixture was left overnight at +4 °C. Ice cold water
satd. aq. NaHCO solution. Then organic part was separated, dried
3
over anhyd. Na SO , filtered, and the filtrate was evaporated to dryness
2
4
under reduced pressure. The residue was purified by silica column
chromatography to afford the corresponding 1,4,5-trisubstituted 1,2,3-
triazoles.
(S)-5-(2-O-Benzyl-1-hydroxyethyl)-1-(2-hydroxyethyl)-1H-
1,2,3-triazole-4-carboxaldehyde 23a. Following the general
procedure compound 5 (0.1 g, 0.24 mmol) was converted to
(
50 mL) was added to the reaction mixture, and the mixture was
extracted with EtOAc (3 × 20 mL). The combined extract was
evaporated, and the residual pyridine was coevaporated with toluene to
obtain compound 15 quantitatively. To a solution of crude 15 in dry
DMF (8 mL), potassium tert-butoxide (0.11 g, 1.00 mmol) was added
6
901
dx.doi.org/10.1021/jo5009564 | J. Org. Chem. 2014, 79, 6895−6904

The Journal of Organic Chemistry
Article
compound 23a (0.03 g, 42%; 66% based on 0.036 g recovered starting
(400 MHz, CDCl ) δ 1.28 (s, 3H), 1.43 (s, 3H), 3.59−3.63 (m, 1H),
3
26
material). [Eluent: EtOAc:pet ether (3:2)] Colorless oil: [α] −12.4
3.73−3.77 (m, 1H), 4.14 (d, 1H, J = 2.0 Hz), 4.65−4.71 (m, 6H), 5.33
D
−1
1
(
c 1.10 in CHCl ); IR 1635 cm (CHO); H NMR (400 MHz,
(d, 1H, J = 4.8 Hz), 5.91 (d, 1H, J = 3.6 Hz), 7.12−7.14 (m, 2H),
3
1
3
CDCl ) δ 3.60−3.67 (m, 1H), 3.81−3.85 (m, 1H), 3.96−4.05 (m,
7.26−7.32 (m, 3H), 10.05 (s, 1H); C NMR (50 MHz, CDCl ) δ
3
3
2
7
5
1
H), 4.38−4.61 (m, 4H), 5.29−5.32 (m, 1H), 7.09−7.11 (m, 2H),
26.3, 27.0, 47.4 (CH ), 65.3, 72.1 (CH ), 73.6 (CH ), 74.3, 79.1, 85.4,
2
2
2
13
.28−7.35 (m, 3H), 10.04 (s, 1H); C NMR (50 MHz, CDCl ) δ
105.2, 112.4, 128.0, 128.3, 128.7, 137.2, 143.3, 144.0, 187.6; HRMS
3
+
+
2.3 (CH ), 61.2 (CH ), 65.0, 72.4 (CH ), 73.8 (CH ), 128.0, 128.4,
[ES , (M + H) ] for C H N O found 420.1784, calcd 420.1771.
2
2
2
2
20 26 3 7
+
+
28.7, 137.0, 143.7, 144.0, 187.8; HRMS [ES , (M + H) ] for
(S)(1-Benzyl-5-(2-O-benzyl-1-hydroxyethyl)-1H-1,2,3-tria-
C H N O found 292.1299, calcd 292.1297.
zole-4-yl)methyl 4-nitrobenzoate 24. NaBH (0.012 g, 0.3 mmol)
14
18
3
4
4
(
S)-5-(2-O-Benzyl-1-hydroxyethyl)-1-octyl-1H-1,2,3-triazole-
was added to a solution of compound 23c (0.035 g, 0.1 mmol) in
ethanol (6 mL), and the mixture was stirred at room temperature for 2
h. Volatile matters were evaporated under a vacuum, and the residue
4
5
7
-carboxaldehyde 23b. Following the general procedure compound
(0.1 g, 0.24 mmol) was converted to compound 23b (0.043 g, 49%;
2% based on 0.032 g recovered starting material). [Eluent: EtOAc:pet
was partitioned between EtOAc and satd. aq. NH Cl solution. Organic
4
26
D
ether (1:4)] Colorless oil: [α] +19.6 (c 1.13 in CHCl ); IR 1636
layers were pooled together, dried over anhyd. Na SO , filtered, and
3
2
4
−
1
1
cm (CHO); H NMR (400 MHz, CDCl ) δ 0.88 (t, 3H, J = 6.6 Hz),
the filtrate was evaporated to dryness. The residue thus obtained was
dissolved in pyridine (5 mL), and 4-nitrobenzoyl chloride (0.055 g, 0.3
mmol) was added to the solution at room temparature. After 3 h
(TLC), the mixture was partitioned between EtOAc (2 × 10 mL) and
3
1
3
2
.26−1.31 (m, 10H), 1.86−1.94 (m, 2H), 3.55 (t, 1H, J = 7.8 Hz),
.81−3.83 (m, 1H), 4.30−4.48 (m, 4H), 5.12 (bs, 2H), 7.11−7.13 (m,
13
H), 7.28−7.36 (m, 3H), 10.06 (s, 1H); C NMR (50 MHz, CDCl )
3
δ 14.2, 22.7 (CH ), 26.7 (CH ), 29.1 (CH ), 29.2 (CH ), 30.0 (CH ),
2
2
2
2
2
satd. aq. NaHCO solution. Organic layers were pooled together, dried
3
3
1
1.8 (CH ), 49.8 (CH ), 65.0, 72.7 (CH ), 73.6 (CH ), 127.9, 128.2,
28.6, 137.2, 143.0, 144.2, 188.2; HRMS [ES , (M + H) ] for
C H N O found 360.2272, calcd 360.2287.
0
(
zole-4-carboxaldehyde 23c. Following the general procedure
compound 5 (0.1 g, 0.24 mmol) was converted to compound 23c
0.034 g, 43%; 67% based on 0.038 g recovered starting material).
Eluent: EtOAc:pet ether (1:3)] Colorless oil: [α] +23.5 (c 0.93 in
CHCl ); IR 1639 cm (CHO); H NMR (400 MHz, CDCl ) δ
2 2 2 2
over anhyd. Na SO , filtered, and the filtrate was evaporated to dryness
2
4
+
+
to give a residue. The residue thus obtained was purified over silica gel
coloumn to afford compound 24 (0.03 g, 60% in two steps). [Eluent:
2
30
3
3
S)-1-Benzyl-5-(2-O-benzyl-1-hydroxyethyl)-1H-1,2,3-tria-
26
EtOAc:pet ether (1:3)] White solid: mp 118 °C (from EtOH); [α]D
1
+
32.7 (c 1.00 in CHCl ); H NMR (400 MHz, CDCl ) δ 3.30−3.42
3
3
(
m, 2H), 4.37 (q, 2H, J = 12.0 Hz), 5.20−5.23 (m, 1H), 5.55 (s, 2H),
(
[
5
8
5
1
1
4
.67 (q, 2H, J = 15.2 Hz), 7.16−7.22 (m, 4H), 7.27−7.34 (m, 6H),
26
D
13
.21 (q, 4H, J = 8.8 Hz); C NMR (100 MHz, CDCl ) δ 53.0 (CH ),
−1
1
3
2
3
3
8.6 (CH ), 64.8, 72.1 (CH ), 73.4 (CH ), 123.5, 127.4, 127.6, 128.1,
28.5, 128.5, 129.0, 130.9, 134.6, 134.9, 135.0, 136.9, 140.2, 150.5,
64.7; HRMS [ES , (M + H) ] for C H N O found 489.1752, calcd
89.1774.
S)-5-(2,3-O-Cyclohexylidene-1-hydroxypropyl)-1-(2-hydrox-
2
2
2
3
5
1
(
1
.38−3.61 (m, 2H), 4.33−4.41 (m, 2H), 4.91 (d, 1H, J = 10.4 Hz),
.09−5.19 (m, 1H), 5.63 (q, 2H, J = 15.6 Hz), 7.11−7.33 (m, 10H),
+
+
0.08 (s, 1H); 13C NMR (50 MHz, CDCl ) δ 53.4 (CH ), 65.1, 72.6
26 25
4
6
3
2
CH ), 73.6 (CH ), 127.8, 127.9, 128.2, 128.7, 129.0, 129.3, 134.1,
37.3, 143.0, 144.8, 188.1; HRMS [ES , (M + H) ] for C H N O
found 338.1532, calcd 338.1505.
2 2
(
+
+
19 20 3 3
yethyl)-1H-1,2,3-triazole-4-carboxaldehyde 25a. Following the
general procedure compound 14 (0.1 g, 0.23 mmol) was converted to
compound 25a (0.032 g, 44%; 65% based on 0.032 g recovered
starting material). [Eluent: EtOAc:pet ether (1:3)] Colorless oil:
(
S)-1-(4-Azidobutyl)-5-(2-O-benzyl-1-hydroxyethyl)-1H-
1
,2,3-triazole-4-carboxaldehyde 23d. Following the general
procedure compound 5 (0.1 g, 0.24 mmol) was converted to
compound 23d (0.038 g, 46%; 69% based on 0.035 g recovered
starting material). [Eluent: EtOAc:pet ether (1:2)] Colorless oil:
26
−1
1
[
(
4
α]D −38.7 (c 1.50 in CHCl ); IR 1635 cm (CHO); H NMR
3
400 MHz, CDCl ) δ 1.29−1.64 (m, 10H), 3.37−3.49 (m, 1H), 4.07−
3
.24 (m, 5H), 4.52−4.65 (m, 2H), 4.86 (s, 1H), 5.20 (d, 1H, J = 8.0
2
6
−1
−1
[
(
(
4
(
α]D −18.8 (c 1.05 in CHCl ); IR 1642 cm (CHO), 2098 cm
3
13
1
Hz), 10.11 (s, 1H); C NMR (50 MHz, CDCl
) δ 23.6 (CH
3
), 24.1
2
N ); H NMR (400 MHz, CDCl ) δ 1.53−1.60 (m, 2H), 1.92−2.04
3
3
(
6
CH ), 25.1 (CH ), 34.0 (CH ), 36.3 (CH ), 52.0 (CH ), 61.1 (CH ),
7.4 (CH ), 67.8, 77.5, 111.3, 144.2, 188.6; HRMS [ES , (M + H) ]
2
2
2
2
2
2
2
m, 2H), 3.20−3.26 (m, 2H), 3.51−3.58 (m, 1H), 3.81−3.85 (m, 1H),
.35−4.47 (m, 4H), 4.95 (bs, 1H), 5.12 (d, 1H, J = 4.8 Hz), 7.10−7.12
+
+
13
for C14
S)-5-(2,3-O-Cyclohexylidene-1-hydroxypropyl)-1-octyl-1H-
,2,3-triazole-4-carboxaldehyde 25b. Following the general
H N O found 312.1538, calcd 312.1559.
22 3 5
m, 2H), 7.29−7.35 (m, 3H), 10.07 (s, 1H); C NMR (100 MHz,
(
CDCl ) δ 25.8 (CH ), 26.9 (CH ), 48.9 (CH ), 50.5 (CH ), 64.7,
3
2
2
2
2
1
7
1
3
2.4 (CH ), 73.5 (CH ), 127.8, 128.1, 128.5, 136.9, 142.9, 144.0,
88.0; HRMS [ES , (M + H) ] for C H N O found 345.1680, calcd
2 2
procedure compound 14 (0.1 g, 0.23 mmol) was converted to
compound 25b (0.039 g, 45%; 65% based on 0.029 g recovered
starting material). [Eluent: EtOAc:pet ether (1:3)] Brownish oil:
+
+
16
21
6
3
45.1675.
(
S)-1-(N-(2-Azidoethyl)-N-ethyl-4-methyl-benzenesulfona-
26
−1
1
[
(
1
1
α]D −22.3 (c 1.05 in CHCl ); IR 1636 cm (CHO); H NMR
3
mide)-5-(2-O-benzyl-1-hydroxyethyl)-1H-1,2,3-triazole-4-car-
400 MHz, CDCl ) δ 0.87 (t, 3H, J = 6.6 Hz), 1.24−1.67 (m, 20H),
boxaldehyde 23e. Following the general procedure compound 5
3
.96−2.00 (m, 2H), 4.09−4.42 (m, 5H), 4.56 (bs, 1H), 5.30 (bs, 1H),
(
7
0.1 g, 0.24 mmol) was converted to compound 23e (0.058 g, 46%;
7% based on 0.04 g recovered starting material). [Eluent: EtOAc:pet
0.11 (s, 1H); 13C NMR (50 MHz, CDCl ) δ 14.2, 22.8 (CH ), 23.6
3
2
2
6
(CH ), 24.2 (CH ), 25.2 (CH ), 26.8 (CH ), 29.2 (CH ), 29.9 (CH ),
2 2 2 2 2 2
ether (1:4)] Colorless oil: [α] −23.3 (c 1.05 in CHCl ); IR 1638
D
3
−
1
−1
1
31.9 (CH ), 33.9 (CH ), 36.5 (CH ), 49.7 (CH ), 67.5 (CH ), 68.0,
cm (CHO), 2104 cm (N ); H NMR (400 MHz, CDCl ) δ 2.42
2 2 2 2 2
7.5, 111.2, 143.5, 144.5, 189.1; HRMS [ES , (M + H) ] for
3
3
+
+
7
(
s, 3H), 3.10−3.22 (m, 2H), 3.56−3.44 (m, 2H), 3.57−3.64 (m, 3H),
C H N O found 380.2525, calcd 380.2549.
3
4
7
(
7
.82−3.85 (m, 1H), 3.81−3.84 (m, 1H), 4.44 (q, 2H, J = 12.0 Hz),
.64−4.79 (m, 3H), 5.32 (d, 1H, J = 5.2 Hz), 7.09−7.11 (m, 2H),
20 34
3
4
(
S)-1-Benzyl-5-(2,3-O-cyclohexylidene-1-hydroxypropyl)-
13
1H-1,2,3-triazole-4-carboxaldehyde 25c. Following the general
procedure compound 14 (0.1 g, 0.23 mmol) was converted to
compound 25c (0.042 g, 51%; 71% based on 0.029 g recovered
starting material). [Eluent: EtOAc:pet ether (1:3)] Colorless oil:
.24−7.35 (m, 5H), 7.67 (d, 2H, J = 8.4 Hz), 10.06 (s, 1H); C NMR
50 MHz, CDCl ) δ 21.7, 49.1 (CH ), 49.6 (CH ), 50.9 (CH ), 65.1,
3 2 2 2
2.6 (CH ), 73.7 (CH ), 127.5, 128.0, 128.2, 128.7, 130.2, 135.3,
2 2
37.2, 143.3, 144.0, 144.5, 187.7; HRMS [ES , (M + H) ] for
C H N O S found 514.1854, calcd 514.1873.
3
(
+
+
1
2
6
−1
1
[
(
(
α]D +29.8 (c 1.00 in CHCl ); IR 1641 cm (CHO); H NMR
3
2
28
7
5
400 MHz, CDCl ) δ 1.28−1.73 (m, 10H), 4.07−4.24 (m, 3H), 4.59
S)-5-(2-O-Benzyl-1-hydroxyethyl)-1-(((3aS,5R,6R,6aS)-6-hy-
3
s, 1H), 5.28 (bs, 1H), 5.70 (q, 2H, J = 15.4 Hz), 7.19−7.39 (m, 5H),
droxy-2,2-dimethyl-dihydro-5H-furo[2,3-d][1,3]dioxol-5-yl)-
methyl)-1H-1,2,3-triazole-4-carboxaldehyde 23f. Following the
general procedure compound 5 (0.1 g, 0.24 mmol) was converted to
compound 23f (0.040 g, 39%; 65% based on 0.041 g recovered
starting material). [Eluent: EtOAc:pet ether (2:3)] Colorless oil:
13
10.13 (s, 1H); C NMR (50 MHz, CDCl
) δ 23.7 (CH
), 53.2 (CH ), 67.5 (CH
67.9, 77.7, 111.3, 127.5, 129.0, 129.4, 133.7, 143.8, 144.9, 189.0;
), 24.2
3
2
(CH
), 25.1 (CH
), 34.0 (CH
), 36.5 (CH
),
2
2
2
2
2
2
+
+
HRMS [ES , (M + Na) ] for C H N O Na found 380.1607, calcd
19
23
3
4
−1
1
[
α]D26 −45.2 (c 1.40 in CHCl ); IR 1635 cm (CHO); H NMR
380.1586.
3
6
902
dx.doi.org/10.1021/jo5009564 | J. Org. Chem. 2014, 79, 6895−6904

The Journal of Organic Chemistry
Article
(
S)-1-(4-Azidobutyl)-5-(2,3-O-cyclohexylidene-1-hydroxy-
(S)-3-(4-Azidobutyl)-5-(2,3-O-cyclohexylidene-1-hydroxy-
propyl)-3H-1,2,3-triazole-4-carboxaldehyde 26d. Following the
general procedure compound 17 (0.1 g, 0.23 mmol) was converted to
compound 26d (0.04 g, 47%; 66% based on 0.031 g recovered starting
propyl)-1H-1,2,3-triazole-4-carboxaldehyde 25d. Following the
general procedure compound 14 (0.1 g, 0.23 mmol) was converted to
compound 25d (0.041 g, 48%; 72% based on 0.031 g recovered
starting material). [Eluent: EtOAc:pet ether (1:4)] Colorless oil:
2
6
material). [Eluent: EtOAc:pet ether (1:3)] Colorless oil: [α] +42.2
D
−1
−1
−1
−1
1
[
(
(
5
α]D26 −16.7 (c 1.00 in CHCl ); IR 1655 cm (CHO), 2093 cm
(c 1.50 in CHCl ); IR 1660 cm (CHO), 2102 cm (N ); H NMR
3
3
3
1
N ); H NMR (400 MHz, CDCl ) δ 1.25−1.71 (m, 12H), 2.06−2.16
(400 MHz, CDCl ) δ 1.15−1.64 (m, 12H), 1.94−2.01 (m, 2H), 3.33
3
3
3
m, 2H), 3.36−3.39 (m, 2H), 4.09−4.26 (m, 3H), 4.36−4.61 (m, 3H),
(t, 2H, J = 6.6 Hz), 3.91−3.95 (m, 1H), 4.06−4.10 (m, 1H), 4.55−
4.59 (m, 1H), 4.72 (t, 2H, J = 7.0 Hz), 5.23 (d, 1H, J = 4.8 Hz), 10.24
(s, 1H); 13C NMR (50 MHz, CDCl ) δ 23.8 (CH ), 24.1 (CH ), 25.2
13
.27 (d, 1H, J = 12.0 Hz), 10.12 (s, 1H); C NMR (50 MHz, CDCl )
3
δ 23.7 (CH ), 24.2 (CH ), 25.1 (CH ), 26.3 (CH ), 27.1 (CH ), 33.9
2
2
2
2
2
3
2
2
(
(CH ), 25.9 (CH ), 27.3 (CH ), 34.4 (CH ), 36.3 (CH ), 50.7 (CH ),
2
2
2
2
2
2 2 2 2 2 2
+
+
1
50.9 (CH ), 65.2 (CH ), 68.5, 77.5, 110.8, 131.2, 152.5, 181.4; HRMS
2 2
+
+
found 365.1933, calcd 365.1937.
[ES , (M + H) ] for C H N O found 365.1939, calcd 365.1937.
16 25 6 4
(
S)-1-(N-(2-Azidoethyl)-N-ethyl-4-methyl-benzenesulfona-
mide)-5-(2,3-O-cyclohexylidene-1-hydroxypropyl)-1H-1,2,3-tri-
azole-4-carboxaldehyde 25e. Following the general procedure
compound 14 (0.1 g, 0.23 mmol) was converted to compound 25e
ASSOCIATED CONTENT
Supporting Information
Full spectroscopic data of all new compounds and crystal data
(CIF). This material is available free of charge via the Internet
at http://pubs.acs.org.
■
*
S
(
0.052 g, 41%; 66% based on 0.036 g recovered starting material).
26
[
Eluent: EtOAc:pet ether (1:2)] Colorless oil: [α] +15.5 (c 0.53 in
CHCl ); IR 1640 cm (CHO), 2120 cm (N ); H NMR (400
D
−1
−1
1
3
3
MHz, CDCl ) δ 1.21−1.68 (m, 10H), 2.43 (s, 3H), 3.22−3.25 (m,
3
2
4
7
H), 3.41−3.46 (m, 2H), 3.61−3.71 (m, 2H), 4.10−4.17 (m, 2H),
.23−4.25 (m, 1H), 4.74−4.86 (m, 3H), 5.12 (d, 1H, J = 11.6 Hz),
AUTHOR INFORMATION
Corresponding Author
E-mail: tpathak@chem.iitkgp.ernet.in.
Notes
■
*
13
.33 (d, 2H, J = 8.4 Hz), 7.70 (d, 2H, J = 8.0 Hz), 10.13 (s, 1H);
C
NMR (50 MHz, CDCl ) δ 21.8 (CH ), 23.8 (CH ), 24.3 (CH ), 25.2
3
2
2
2
(
CH ), 34.3 (CH ), 36.2 (CH ), 49.3 (CH ), 49.8 (CH ), 51.0 (CH ),
2
2
2
2
2
2
6
1
5
7.6 (CH ), 67.9, 77.7, 100.2, 111.4, 127.6, 130.3, 135.3, 144.0, 144.5,
The authors declare no competing financial interest.
2
+
+
44.6, 188.6; HRMS [ES , (M + Na) ] for C H N O SNa found
23
31
7
6
56.1960, calcd 556.1954.
ACKNOWLEDGMENTS
■
(
S)-5-(2,3-O-Cyclohexylidene-1-hydroxypropyl)-1-
A.B. thanks the Council of Scientific and Industrial Research
(CSIR), New Delhi, India for a fellowship. Financial support by
the Council of Scientific and Industrial Research (CSIR), New
Delhi, India is gratefully acknowledged. The Department of
Science and Technology, New Delhi, India is also thanked for
the creation of 400 MHz facility under IRPHA program and
DST-FIST for single crystal X-ray facility.
(
[
((3aS,5R,6R,6aS)-6-hydroxy-2,2-dimethyl-dihydro-5H-furo-
2,3-d][1,3]dioxol-5-yl)methyl)-1H-1,2,3-triazole-4-carboxalde-
hyde 25f. Following the general procedure compound 14 (0.1 g, 0.23
mmol) was converted to compound 25f (0.047 g, 46%; 63% based on
0
.03 g recovered starting material). [Eluent: EtOAc:pet ether (1:2)]
26
−1
Colorless oil: [α] +13.3 (c 1.00 in CHCl ); IR 1638 cm (CHO);
D
3
1
H NMR (400 MHz, CDCl ) δ 1.23−1.67 (m, 16H), 3.17 (bs, 1H),
3
4
(
1
.10−4.22 (m, 4H), 4.57 (d, 1H, J = 3.6 Hz), 4.66 (s, 3H), 4.82−4.85
m, 1H), 5.23 (d, 1H, J = 11.2 Hz), 5.97 (d, 1H, J = 3.6 Hz), 10.12 (s,
H); 1 C NMR (100 MHz, CDCl ) δ 23.5 (CH ), 23.9 (CH ), 24.8
3
DEDICATION
■
3
2
2
(
CH ), 26.0, 26.7, 33.9 (CH ), 35.9 (CH ), 46.5 (CH ), 67.0 (CH ),
Dedicated to Prof. Jyoti Chattopadhyaya on the occasion of his
65th birthday.
2
2
2
2
2
6
7.6, 73.9, 77.1, 78.6, 85.2, 104.9, 111.2, 112.0, 143.7, 143.8, 188.3;
+
+
HRMS [ES , (M + H) ] for C H N O found 440.2018, calcd
20
30
3
8
4
40.2033.
S)-5-(2,3-O-Cyclohexylidene-1-hydroxypropyl)-3-octyl-3H-
,2,3-triazole-4-carboxaldehyde 26b. Following the general
REFERENCES
■
(
(
2
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1
002, 67, 3057−3062. (b) Rostovtsev, V. V.; Green, L. G.; Fokin, V.
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(
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1
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[
(
3
4
1
3
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1
.18 (d, 1H, J = 3.2 Hz), 3.92−3.96 (m, 1H), 4.07−4.10 (m, 1H),
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.54−4.58 (m, 1H), 4.65−4.69 (m, 2H), 5.22 (d, 1H, J = 4.8 Hz),
0.24 (s, 1H); 1 C NMR (50 MHz, CDCl ) δ 14.3, 22.8 (CH ), 23.9
3
3
2
(
CH ), 24.2 (CH ), 25.3 (CH ), 26.6 (CH ), 29.2 (CH ), 29.3 (CH ),
2 2 2 2 2 2
3
0.2 (CH ), 31.9 (CH ), 34.4 (CH ), 36.3 (CH ), 51.5 (CH ), 65.3
2 2 2 2 2
+
+
(
CH ), 68.5, 77.5, 110.8, 131.1, 152.3, 181.2; HRMS [ES , (M + H) ]
2
2
for C H N O found 380.2563, calcd 380.2549.
20
34
3
4
(
S)-3-Benzyl-5-(2,3-O-cyclohexylidene-1-hydroxypropyl)-
3
H-1,2,3-triazole-4-carboxaldehyde 26c. Following the general
procedure compound 17 (0.1 g, 0.23 mmol) was converted to
compound 26c (0.038 g, 45%; 68% based on 0.033 g recovered
starting material). [Eluent: EtOAc:pet ether (1:4)] Colorless oil:
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α]D26 +47.5 (c 1.20 in CHCl ); IR 1681 cm (CHO); H NMR (400
−1
1
[
3
MHz, CDCl ) δ 1.15−1.59 (m, 10H), 3.87−3.91 (m, 1H), 4.06 (t, 1H,
J = 7.6 Hz), 4.55 (d, 1H, J = 5.6 Hz), 5.20 (d, 1H, J = 4.4 Hz), 5.86 (s,
2
3
H), 7.30 (s, 5H), 10.17 (s, 1H); 13C NMR (50 MHz, CDCl ) δ 23.8
3
(
6
1
CH ), 24.1 (CH ), 25.2 (CH ), 34.4 (CH ), 36.2 (CH ), 54.4 (CH ),
2 2 2 2 2 2
5.2 (CH ), 68.6, 77.2, 110.8, 128.4, 128.8, 129.0, 131.1, 134.6, 152.5,
2
+
+
81.2; HRMS [ES , (M + Na) ] for C H N O Na found 380.1563,
19 23 3 4
calcd 380.1586.
6
903
dx.doi.org/10.1021/jo5009564 | J. Org. Chem. 2014, 79, 6895−6904

The Journal of Organic Chemistry
Article
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6
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