One-pot three-component click reaction of cyclic sulfates and cyclic sulfamidates

Article abstract of DOI:10.1002/adsc.201100813

A one-pot, three-component methodology involving tandem azidation and click copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) of cyclic sulfates or cyclic sulfamidates in the presence of sodium azides and alkynes is reported. The developed protocol takes also advantage of the concomitant use of microwave (MW) irradiation and heterogeneous catalysis. The protocol allows the fast and efficient preparation of (alkyl sulfate)- and (alkyl sulfamidate)-1H-1,2,3- triazoles in a simple manner. Copyright

Full text of DOI:10.1002/adsc.201100813

FULL PAPERS
DOI: 10.1002/adsc.201100813
One-Pot Three-Component Click Reaction of Cyclic Sulfates and
Cyclic Sulfamidates
Alicia Megia-Fernandez,a Mariano Ortega-MuÇoz,a Fernando Hernandez-Mateo,a
and Francisco Santoyo-Gonzaleza,*
a
Quꢀmica Orgꢁnica, Instituto de Biotecnologꢀa, Facultad de Ciencias, Universidad de Granada, E-18071 Granada, Spain
Fax : (+34)-95-824-3186; phone: (+34)-95-824-808; e-mail: fsantoyo@ugr.es
Received: October 19, 2011; Revised: March 8, 2012; Published online: June 5, 2012
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201100813.
Abstract: A one-pot, three-component methodology geneous catalysis. The protocol allows the fast and
involving tandem azidation and click copper(I)-cata- efficient preparation of (alkyl sulfate)- and (alkyl
lyzed azide-alkyne cycloaddition (CuAAC) of cyclic sulfamidate)-1H-1,2,3-triazoles in a simple manner.
sulfates or cyclic sulfamidates in the presence of
sodium azides and alkynes is reported. The devel-
oped protocol takes also advantage of the concomi- Keywords: click chemistry; cyclic sulfamidates; cyclic
tant use of microwave (MW) irradiation and hetero- sulfates; cycloadditions; multi-component reactions
Introduction
talyzed one-pot synthesis of 1,2,3-triazoles from alkyl
halides, alkynes and sodium azide. However, high
Multi-component reactions[1] (MCRs), where three or temperatures and long times are required in this pro-
more starting materials react to afford a product that tocol leading to a mixture of the 1,4 and 1,5 re-
essentially contains all or most of the atoms of the re- gioisomers in low yields. After the discovery of the
agents, have achieved great importance due to their Cu(I) catalytic effect in azido-alkyne cycloadditi-
broad scope since they are highly convergent process-
ons,[3a] this three-component methodology has turned
ACHTUNGTRENNUNG
es that increase the molecular complexity in just one out to be efficient and numerous examples have
process. In this context the orthogonality of “click emerged in which organic azides are generated from
chemistry”[2] is an attractive feature that turns the different precursors and then trapped in situ by al-
Cu(I)-catalyzed version of the azide-alkyne cycloaddi- kynes to obtain exclusively the corresponding 1,4-dis-
tion (CuAAC)[3] – the most relevant example of the ubstituted 1,2,3-triazole. Aromatic and aliphatic hal-
“click-chemistry” concept – into a suitable reaction ides are by far the most preferred azide precurors,[7]
for its implementation in a one-pot, multi-component although other good leaving groups, such as the tosyl
process. The appealing characteristics of CuAAC group, have also been employed.[8] Other alternatives
(modularity, regioselectivity, mild reaction conditions, for these multi-component click reactions include the
wide substrate scope, high yield and stability of the use of boronic acids,[9] aromatic and aliphatic ami-
resulting triazole ring) have brought about the success nes,[7q,10] epoxides,[11] aziridines,[12] diazonium salts,[7q]
of this powerful methodology in the last decade, with diaryliodonium salts[13] or 1,2-diaza-1,3-dienes[14] as
a growing number of applications found in many azide precursors.
areas of modern chemistry including drug discovery,
On the other hand, cyclic sulfates[15] and cyclic sul-
materials science or bioconjugation.[4]
famidates[15d,16] are versatile electrophilic synthons
Many efforts have been made over the last years in that have emerged as important intermediates in or-
order to develop CuAAC-based MCRs. One of the ganic synthesis. They show a particularly enhanced re-
major aims pursued in these approaches is to avoid activity toward nucleophilic reagents and their appli-
the manipulation and isolation of organic azides since cations have gained importance since the develop-
some of them, especially those having low molecular ment of efficient methods for their preparation. In
weights and those containing several azide functional- particular, cyclic sulfates and sulfamidates are ade-
ities, could be unstable and difficult to handle.[5] In quate precursors for accessing organic azides.[17,18] Ex-
this regard, Maksikova et al.[6] reported the first unca- amples in which this approach has been used for the
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ulterior use of the isolated azides in click reactions click catalyst, namely Si-BPMA·Cu+ or Si-BPA·Cu+
have been described.[17h–j,18e] In addition, the ring (Scheme 1),[21] was used as source of Cu(I). These cat-
opening of cyclic sulfates and sulfamidates possesses alysts proved to be very robust and efficient heteroge-
some attributes that perfectly fit the criteria required neous click catalysts. They take advantage of the
for click chemistry.[2] In spite of the fact that cyclic Cu(I) chelating capabilities of nitrogen-based ligands
sulfates are usually regarded as synthetic equivalents covalently immobilized on silica.[21] They were recent-
of epoxides,[19] their implementation in CuAAC-based ly found to be very well suited for multiple CuAAC
MCRs by combination with sodium azide and alkynes involving cyclodextrins.[22] The reaction was per-
has not been reported. However, this approach is con- formed under MW irradiation. The utility of the MW
ceptually attractive and can be postulated as a power- assistance to improve and reduce the reaction time of
ful, safe and direct methodology for the synthesis of cycloaddition reactions is well known.[23] In particular,
(alkylsulfate)-1H-1,2,3-triazoles by a tandem click– the use of this technique in three-component reac-
click process. The importance of these functionalized tions between alkyl halides, sodium azide and alky-
triazoles is illustrated in a recent report[20] that de- nes[7b] and azidation reactions has been reported.[24]
scribes the synthesis of a Cu(I) tris(triazolylmethyl)- As expected, the reaction was completed in a short
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
water-soluble click catalyst that promotes the rapid yield (85%) by simple filtration of the catalyst and
cycloaddition reaction in living systems without ap- evaporation of the solvent without further purifica-
parent toxicity. In addition, sulfate monoester 1,2,3- tion. NMR spectroscopy confirmed that triazole was
triazoles can be regarded as valuable compounds as produced in a completely regioselective manner just
they can experience other interesting transformations like the ring-opening of cyclic sulfate, affording exclu-
through hydrolysis or nucleophilic substitution of the sively 1,4-disubstituted 1,2,3-triazoles after the azide
sulfate group.[15]
attack at the least-hindered carbon of cyclic sulfate.
To investigate the scope of this one-pot, three-com-
Herein, we describe a new and feasible procedure
to obtain (alkyl sulfate)- and (alkyl sulfamidate)-1H- ponent methodology, 1a as well as the 1,2 cyclic sul-
1,2,3-triazoles in a one-pot, three-component reaction fates derived from glycerol 1b and a-d-glucofuranose
through the in situ generation of organic azides by the 1c were reacted with different alkynes using identical
opening of cyclic sulfates or sulfamidates with sodium reaction conditions and experimental procedure
azide and tandem CuAAC with an alkyne present in (Table 1). The alkynes were selected to offer a variety
the reaction media (Scheme 1).
of different functional (primary aliphatic alcohols and
esters) and protective groups (acetyl, benzyl ether,
tert-butoxycarbonyl (Boc) or isopropylidene ketal). In
all cases, the expected products (4b–k) were obtained
in high to excellent yields in very short reaction times
Results and Discussion
The utility of cyclic sulfates as azide precursors in (10–20 min) (Table 1, entries 2–11). These results
CuAAC-based MCRs was first evaluated in a model highlight the compatibility of this cascade process
reaction. 1,3-Propanediol cyclic sulfate (1a) and phe- with a wide range of functionalities. Furthermore, the
nylacetylene (3a) were the substrates of choice methodology allows the easy synthesis of glycoconju-
(Table 1, entry 1). Equimolecular amounts of these re- gates (entries 5, 9–11) and also the access to multiva-
agents and sodium azide were merely dissolved in lent systems like compounds 4h and 4k (entries 8 and
aqueous t-BuOH. With the aim to simplify the manip- 11) when starting from the corresponding multialkyne
ulation and the isolation procedure, a heterogeneous derivatives of tetraethylene glycol or tripropargyla-
mine, respectively, by the simultaneous formation of
À
up to nine C N bonds in a fully selective and efficient
manner
Considering the similar reactivity between cyclic sul-
fates and sulfamidates we anticipate that these latter
compounds should also undergo a tandem nucleophilic
ring-opening and click reaction when combined with
sodium azide and an alkyne. In fact, the ring opening
of cyclic sulfamidates with sodium azide followed by
one-pot propargylation and cycloaddition has been re-
cently reported[18e] for the preparation of triazole-fused
heterocycles. However, no antecedents were found in-
volving cyclic sulfamidates in an MCR. In this exten-
Scheme 1. CuAAC-based MCRs of cyclic sulfates or cyclic
sulfamidates with alkynes and sodium azide.
sion of our study, the cyclic sulfamidates 2a and 2b
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One-Pot Three-Component Click Reaction of Cyclic Sulfates and Cyclic Sulfamidates
Table 1. One-pot three-component click reaction of cyclic sulfates.
Entry
Cyclic sulfate
Alkyne
Product
Yield
[%]
1
1a
3a
4a
85
2
3
3b
3c
4b
4c
96
90
4
5
3d
3e
4d
4e
90
87
6
7
1b
3f
4f
4g
97
3b
100
8
9
3g
3b
4h
4i
95
94
1c
10
11
3h
3i
4j
91
85
4k
were prepared from aminoethanol and Boc-l-serine Conclusion
methyl ester, respectively. Both cyclic sulfamidates re-
acted under similar conditions as those described for In summary, a one-pot three-component methodology
cyclic sulfates in the presence of sodium azide and dif- involving azidation of cyclic sulfates or sulfamidates
ferent alkynes giving an easy access to the (alkyl sulfa- by sodium azide in the presence of alkynes has been
midate)-1H-1,2,3-triazoles 4l–4p (Table 2).
developed broadening the state-of-the-art of CuAAC-
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Table 2. One-pot three-component click reaction of cyclic sulfamidates.
Entry
Cyclic sulfamidate
Alkyne
Product
Yield [%]
93
1
2a
3b
3c
4l
2
4m
89
3
4
2b
3b
3f
4n
4o
95
93
5
3e
4p
92
based MCRs allowing the synthesis of 1,4-disubstitut- in Hz. Electrospray ionization (ESI) mass spectra were re-
corded on an LCT Premier Spectrometer.
ed 1,2,3-triazoles. The reported protocol benefits from
the simultaneous use of MW irradiation and heteroge-
neous catalysis that allow fast reaction times, avoid
the need of any reducing agent or other additives
commonly used in CuAAC click chemistry and any
purification step. Other noteworthy features of this
method are its atom economy, efficiency, absence of
by-products, safety, user friendliness and simplicity
that make this process attractive for the synthesis of
screening libraries.
Typical Experimental Procedure
Cyclic sulfate or sulfamidate (1.0 mmol), sodium azide
(1.0 mmol), the alkyne derivative (1.0 mmol) and catalyst Si-
BPA·Cu+ or Si-BPMA·Cu+ (30 mg) were added to 4:1 t-
BuOH-H2O (10 mL). The reaction mixture was irradiated
by MW at 608C. Progress of the reaction was followed by
TLC until complete disappearance of the starting materials,
normally less that 15 min. Filtration of the catalyst and
evaporation of the solvent under vacuum afforded the pure
1,2,3-triazoles in the yields indicated in Table 1 and Table 2,
without any chromatographic purification.
Experimental Section
Analytical and Spectroscopic Data of the 1,2,3-Tri-
azoles
General Remarks
Commercially available reagents, compounds 1a, 3a–3d, 3i
and solvents were used as purchased without further purifi-
cation. Starting materials as cyclic sulfates 1b,[25] 1c,[26] cyclic
sulfamidates 2a,[27] 2b[28] and alkynes 3e,[29] 3f,[30] 3g[31] and
3h[32] were prepared according to reported procedures in lit-
erature. TLCs were performed on Merck Silica Gel 60 F254
aluminium sheets. Reagents used for developing plates in-
clude potassium permanganate (1% w/v), ninhydrin (0.3%
w/v) in ethanol and UV light when applicable. Flash column
chromatography was performed on silica gel Merck (230–
400 mesh, ASTM). Melting points were measured on a Gal-
lenkamp melting point apparatus and are uncorrected. Opti-
cal rotations were recorded on a Perkin–Elmer 141 polarim-
eter at room temperature. IR spectra were recorded on
Sodium 3-(4-phenyl-1H-1,2,3-triazol-1-yl)propyl sulfate (4a):
Compound 4a was obtained as a syrup; yield: 259 mg
(85%). IR (film): nmax =2924, 2853, 1655, 1461, 1250, 1206,
1074, 841 cmÀ1 1H NMR (CD3OD, 400 MHz): d=8.37 (s,
;
1H), 7.81 (d, 2H, J=7.4 Hz), 7.42 (t, 2H, J=7.6 Hz), 7.33
(t, 1H, J=7.4 Hz), 4.60 (t, 2H, J=6.9 Hz), 4.06 (t, 2H, J=
5.9 Hz), 2.31 (p, 2H, J=6.4 Hz); 13C NMR (CD3OD,
100 MHz): d=148.9, 131.9, 130.1, 129.4, 126.8, 123.1, 65.6,
48.3, 31.2; HRMS (ESI): m/z=284.0701, calcd. for
C11H14N3O4S [MÀNa+2H]+: 284.0705; HPLC purity:
92.85%.
Sodium 3-[4-(3-hydroxypropyl)-1H-1,2,3-triazol-1-yl]prop-
yl sulfate (4b): Compound 4b was obtained as a syrup;
yield: 276 mg (96%). IR (film): nmax =3446, 2952, 1655, 1438,
1
1
a Satellite Mattson FTIR. H and 13C NMR spectra were re-
1224, 1022, 946, 825 cmÀ1; H NMR (CD3OD, 400 MHz): d=
corded at room temperature on a Varian Direct Drive (300,
400 and 500 MHz) spectrometer. Chemical shifts are given
in ppm and referenced to internal CDCl3. J values are given
7.80 (s, 1H), 4.50 (t, 2H, J=6.9 Hz), 4.00 (t, 2H, J=5.9 Hz),
3.58 (t, 2H, J=6.4 Hz), 2.76 (t, 2H, J=7.6 Hz), 2.24 (p, 2H,
J=6.1 Hz), 1.87 (p, 2H, J=6.5 Hz); 13C NMR (CD3OD,
1800
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One-Pot Three-Component Click Reaction of Cyclic Sulfates and Cyclic Sulfamidates
100 MHz): d=148.8, 124.0, 65.6, 62.1, 48.0, 33.4, 31.3, 22.8;
HR-MS (ESI): m/z=266.0799, calcd. for C8H16N3O5S
[MÀNa+2H]+: 266.0811; HPLC purity: 100%.
a syrup; yield: 870 mg (95%). IR (film): nmax =3467, 2872,
1
1654, 1455, 1235, 1098, 1028, 762 cmÀ1; H NMR (DMSO-d6,
400 MHz): d=7.94 (s, 2H), 7.35–7.18 (m, 10H), 4.66 (dd,
2H, J=15.4, 6.1 Hz), 4.61–4.53 (m, 4H), 4.50 (s, 4H), 4.46
(d, 4H, J=3.8 Hz), 3.54–3.31 (several m, 20H); 13C NMR
(DMSO-d6, 100 MHz): d=143.6, 138.2, 128.2, 127.5, 127.4,
124.8, 72.7, 72.4, 69.7, 69.6, 68.9, 68.7, 63.5, 50.0; HR-MS
(ESI): m/z=911.2162, calcd. for C34H46N6O15S2Na3 [M+
Na]+: 911.2156; HPLC purity: 92.32%.
Sodium
3-[4-(pyridin-3-yl)-1H-1,2,3-triazol-1-yl]propyl
sulfate (4c): Compound 4c was obtained as a syrup; yield:
275 mg (90%). IR (film): nmax =3269, 2961, 2858, 1694, 1646,
1535, 1452, 1065, 584 cmÀ1 1H NMR (CD3OD, 400 MHz):
;
d=9.02 (s, 1H), 8.53–8.50 (m, 2H), 8.26 (d, 1H, J=7.9 Hz),
7.51 (dd, 1H, J=7.5, 5.1 Hz), 4.63 (t, 2H, J=6.8 Hz), 4.05
(t, 2H, J=5.8 Hz), 2.32 (m, 2H); 13C NMR (CD3OD,
100 MHz): d=149.6, 147.4, 145.3, 135.1, 128.9, 125.7, 124.0,
65.5, 48.4, 31.2; HR-MS (ESI): m/z=285.0645, calcd. for
C10H13N4O4S [MÀNa+2H]+: 285.0658; HPLC purity: 100%.
Sodium 3-[4-(ethoxycarbonyl)-1H-1,2,3-triazol-1-yl]propyl
sulfate (4d): Compound 4d was obtained as a syrup; yield:
271 mg (90%). IR (film): nmax =3260, 2966, 1716, 1649, 1539,
1-(3-O-Acetyl-6-deoxy-1,2-O-isopropyliden-5-O-sulfo-a-d-
glucofuranos-6-yl)-4-(3-hydroxypropyl)-1H-1,2,3-triazole
sodium salt (4i): Compound 4i was obtained as a syrup;
yield: 445 mg (94%); [a]D: À36.58 (c 1, MeOH). IR (film):
nmax =3471, 2932, 1739, 1639, 1376, 1244, 1067, 1017,
753 cmÀ1 1H NMR (CD3OD, 400 MHz): d=7.84 (s, 1H),
;
5.89 (d, 1H, J=3.5 Hz), 5.12 (d, 1H, J=2.8 Hz), 5.01 (dd,
1H, J=14.5, 3.1 Hz), 4.79 (m, 1H), 4.69 (dd, 1H, J=14.5,
2.9 Hz), 4.49 (d, 1H, J=3.5 Hz), 3.89 (dd, 1H, J=9.0,
2.8 Hz), 3.57 (t, 2H, J=5.3 Hz), 2.75 (t, 2H, J=7.6 Hz), 2.07
(s, 3H), 1.87 (q, 2H, J=6.8 Hz), 1.36 (s, 3H), 1.26 (s, 3H);
13C NMR (CD3OD, 100 MHz): d=172.0, 113.9, 106.7, 84.4,
77.9, 76.6, 73.5, 62.1, 51.6, 33.4, 27.3, 26.8, 22.9, 21.1; HR-MS
(ESI): m/z=450.1176, calcd. for C16H25N3O10S [MÀNa]À:
450.1182; HPLC purity: 91.37%.
1
1221, 1024, 574 cmÀ1; H NMR (CD3OD, 400 MHz): d=8.59
(s, 1H), 4.62 (t, 2H, J=6.9 Hz), 4.38 (q, 2H, J=7.1 Hz),
4.03 (t, 2H, J=5.9 Hz), 2.30 (m, 2H), 1.36 (t, 3H, J=
7.1 Hz); 13C NMR (CD3OD, 100 MHz): d=162.4, 140.6,
130.2, 65.5, 62.5, 43.6, 31.0, 14.7; HR-MS (ESI): m/z=
280.0600, calcd. for C8H14N3O6S [MÀNa+2H]+: 280.0603;
HPLC purity: 97.42%.
Sodium 3-[4-(2’,3’,4’,6’-tetra-O-acetyl-a-d-mannopyrano-
syloxymethyl)-1H-1,2,3-triazol-1-yl]propyl
sulfate
(4e):
1-(3-O-Acetyl-6-deoxy-1,2-O-isopropyliden-5-O-sulfo-a-d-
glucofuranos-6-yl)-4-(2’,3’,4’, 6’-tetra-O-acetyl-b-d-glucopyr-
anosyloxymethyl)-1H-1,2,3-triazole sodium salt (4j): Com-
pound 4j was obtained as a syrup; yield: 705 mg (91%);
[a]D: À27.88 (c 1, MeOH); IR (film): nmax = 2934, 1752,
Compound 4e was obtained as a syrup; 512 mg (87%); [a]D:
+33.28 (c 1, MeOH). IR (film): nmax =3142, 2923, 1747,
1
1436, 1370, 1226, 1134, 1048, 942 cmÀ1; H NMR (CD3OD,
400 MHz): d=8.14 (s, 1H), 5.29–5.22 (m, 3H), 4.97 (s, 1H),
4.82 (m, 1H), 4.71 (d, 1H, J=12.0 Hz), 4.57 (t, 2H, J=
6.9 Hz), 4.25 (dd, 1H, J=12.3, 4.7 Hz), 4.13–4.05 (m, 2H),
4.03 (t, 2H, J=5.9 Hz), 2.27 (p, 2H, J=6.2 Hz), 2.12 (s,
3H), 2.07 (s, 3H), 2.03 (s, 3H), 1.94 (s, 3H); 13C NMR
(CD3OD, 100 MHz): d=171.1, 170.2, 170.1, 170.1, 123.8,
96.8, 69.3, 69.2, 68.6, 64.1, 62.1, 60.0, 46.8, 29.7, 19.3, 19.2,
19.2; HR-MS (ESI): m/z=568.1422, calcd. for C20H30N3O14S
[MÀNa+2H]+: 568.1448; HPLC purity: 100%.
1374, 1224, 1162, 1046, 749 cmÀ1
;
1H NMR (CD3OD,
400 MHz): d=8.08 (s, 1H), 5.89 (d, 1H, J=3.6 Hz), 5.18 (t,
1H, J=9.4 Hz), 5.11 (d, 1H, J=2.9 Hz), 5.04 (dd, 1H, J=
14.5, 3.1 Hz), 4.99 (t, 1H, J=9.7 Hz), 4.88–4.71 (m, 6H),
4.50 (d, 1H, J=3.6 Hz), 4.28 (dd, 1H, J=12.4, 4.4 Hz), 4.14
(dd, 1H, J=12.4, 2.3 Hz), 3.92 (dd, 1H, J=8.9, 2.9 Hz), 3.89
(m, 1H), 2.08 (s, 3H), 2.05 (s, 3H), 1.98 (s, 3H), 1.95 (s,
3H), 1.92 (s, 3H), 1.38 (s, 3H), 1.27 (s, 3H); 13C NMR
(CD3OD, 100 MHz): d=172.6, 172.3, 171.9, 171.6, 113.9,
106.7, 103.2, 84.5, 78.2, 76.7, 76.5, 74.6, 73.6, 73.2, 72.9, 70.3,
63.4, 63.3, 51.8, 27.3, 26.8, 21.1, 20.9, 20.8, 20.8; HR-MS
(ESI): m/z=752.1827, calcd. for C28H38N3O19S [MÀNa]À:
752.1820; HPLC purity: 89.14%.
Sodium 1-(benzyloxy)-3-{4-[(tert-butoxycarbonylamino)-
methyl]-1H-1,2,3-triazol-1-yl}propan-2-yl sulfate (4f): Com-
pound 4f was obtained as a syrup; yield: 450 mg (97%). IR
(film): nmax =3433, 2976, 1703, 1523, 1366, 1253, 1169, 1029,
1
761 cmÀ1; H NMR (DMSO-d6, 400 MHz): d=7.78 (s, 1H),
7.35–7.19 (m, 5H), 4.65 (dd, 1H, J=15.1, 6.0 Hz), 4.65 (m,
2H), 4.56 (m, 2H), 4.45 (s, 2H), 4.16 (d, 2H, J=5.3 Hz),
3.37 (m, 3H, 1H exchangeable with D2O), 1.36 (s, 9H);
13C NMR (DMSO-d6, 75 MHz): d=156.0, 145.7, 138.6,
128.7, 127.9, 127.9, 124.0, 78.3, 73.2, 72.8, 69.0, 50.3, 36.1,
28.7; HR-MS (ESI): m/z=443.1595, calcd. for C18H27N4O7S
[MÀNa+2H]+: 443.1600; HPLC purity: 79.47%.
N,N,N-Tris-[(1-(3-O-Acetyl-6-deoxy-1,2-O-isopropyliden-
5-O-sulfo-a-d-glucofuranos-6-yl)-1H-1,2,3-triazol-4-yl)me-
thyl]amine sodium salt (4k): Compound 4k was obtained as
a syrup; yield: 1103 mg (85%); [a]D: À38.78 (c 1, MeOH).
IR (film): nmax =3145, 2985, 2925, 2850, 1738, 1638, 1375,
1
1239, 1015, 751 cmÀ1; H NMR (CD3OD, 400 MHz): d=8.07
(s, 3H), 5.91 (d, 3H, J=3.1 Hz), 5.14 (s, 3H), 5.04 (d, 3H,
J=15.4 Hz), 4.88 (m, 3H), 4.73 (dd, 3H, J=13.8, 3.7 Hz),
4.53 (d, 3H, J=3.4 Hz), 4.03 (dd, 3H, J=8.1, 2.0 Hz), 3.82
(s, 6H), 2.09 (s, 9H), 1.36 (s, 9H), 1.27 (s, 9H); 13C NMR
(CD3OD, 125 MHz): d=172.0, 145.1, 127.7, 113.8, 106.6,
84.4, 78.6, 76.8, 73.7, 52.2, 49.2, 27.3, 26.7, 21; HR-MS (ESI):
m/z= 1299.2307, calcd. for C42H58N10O27S3Na3 [M+H]+:
1299.2328; m/z=1277.2560, calcd. for C42H59N10O27S3Na2
[MÀNa+2H]+: 1277.2509; m/z=1255.2726, calcd. for
C42H60N10O27S3Na [MÀ2Na+3H]+: 1255.2689; m/z=
1233.2874, calcd. for C42H61N10O27S3 [MÀ3Na+4H]+:
1233.2870; HPLC purity: 97.96%.
Sodium
1-(benzyloxy)-3-[4-(3-hydroxypropyl)-1H-1,2,3-
triazol-1-yl)propan-2-yl sulfate (4g): Compound 4g was ob-
tained as a syrup; yield: 393 mg (100%). IR (film): nmax
3406, 2933, 1599, 1259, 1036 cmÀ1 1H NMR (DMSO-d6,
=
;
400 MHz): d=7.70 (s, 1H), 7.32 (m, 5H), 4.63–4.43 (m,
5H), 3.44–3.38 (m, 4H), 2.61 (t, 2H, J=7.7 Hz), 1.71 (m,
2H); 13C NMR (DMSO-d6, 75 MHz): d=146.4, 138.2, 128.2,
127.5, 127.4, 122.7, 72.9, 72.4, 68.7, 60.0, 49.9, 32.3, 21.6; HR-
MS (ESI): m/z=416.0864, calcd. for C15H20N3O6Na2S [M+
Na]+: 416.0868; HPLC purity: 87.24%.
Sodium 3,3’-[4,4’-(2,5,8,11,14-pentaoxapentadecane-1,15-
diyl)bis(1H-1,2,3-triazole-4,1-diyl)]bis[1-(benzyloxy)pro-
pane-3,2-diyl] disulfate (4h): Compound 4h was obtained as
Sodium tert-butoxycarbonyl{2-[4-(3-hydroxypropyl)-1H-
1,2,3-triazol-1-yl]ethyl}sulfamate (4l): Compound 4l was ob-
Adv. Synth. Catal. 2012, 354, 1797 – 1803
ꢂ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
1801

Alicia Megia-Fernandez et al.
FULL PAPERS
tained as a syrup; yield: 345 mg (93%). IR (film): nmax
=
Supporting Information
1H- and 13C NMR spectra of the obtained 1,2,3-triazoles 4a–
p are available in the Supporting Information.
3355, 3142, 2928, 1698, 1522, 1366, 1251, 1169, 1067, 1011,
1
764 cmÀ1; H NMR (DMSO-d6, 400 MHz): d=7.72 (s, 1H),
4.44 (t, 3H, J=5.6 Hz), 3.83 (t, 2H, J=6.0 Hz), 3.43 (q, 2H,
J=5.9 Hz), 2.60 (t, 2H, J=7.7 Hz), 1.75–1.68 (m, 2H), 1.25
(s, 9H); 13C NMR (DMSO-d6, 125 MHz): d=152.5, 122.4,
79.1, 60.0, 48.7, 46.5, 32.2, 27.7, 21.7; HR-MS (ESI): m/z=
349.1187, calcd. for C12H21N4O6S [MÀNa]À: 349.1182.
Acknowledgements
Sodium tert-butoxycarbonyl{2-[4-(pyridin-3-yl)-1H-1,2,3-
triazol-1-yl]ethyl}sulfamate (4m): Compound 4m was ob-
The authors acknowledge Direccion General de Investigacion
Cientıfica y Tecnica (DGICYT) (CTQ2008-01754) and Junta
de Andalucia (P07-FQM-02899) for financial support. A.M.-
F. thanks University of Granada for a research grant (Progra-
ma Puente). The authors also want to thank the reviewers for
their advice.
tained as a syrup; yield: 348 mg (89%). IR (film): nmax
=
2971, 2925, 1701, 1340, 1252, 1151, 1048 cmÀ1 1H NMR
;
(CD3OD, 400 MHz): d=9.07 (s, 1H), 8.57 (s, 1H), 8.46 (s,
1H), 8.27 (d, 1H, J=7.9 Hz), 7.55 (s, 1H), 4.55 (t, 2H, J=
5.8 Hz), 3.58 (t, 2H, J=5.7 Hz), 1.36 (s, 9H); 13C NMR
(DMSO-d6, 125 MHz): d=156.9, 148.1, 145.8, 144.0, 133.5,
122.3, 79.1, 50.1, 40.1, 27.3; HR-MS (ESI): m/z=392.1019,
calcd. for C14H19N5O5SNa [M+H]+: 392.1005; HPLC purity:
98.09%.
References
Sodium (S)-tert-butoxycarbonyl{3-[4-(3-hydroxypropyl)-
1H-1,2,3-triazol-1-yl]-1-methoxy-1-oxopropan-2-yl}sulfamate
(4n): Compound 4n was obtained as a syrup; yield: 408 mg
(95%); [a]D: À43.78 (c 1, MeOH); IR (film): nmax =3422,
[1] a) L Weber, Drug Discovery Today 2002, 7, 143–147;
b) H. Bienaymꢃ, C. Hulme, G. Oddon, P. Schmitt,
Chem. Eur. J. 2000, 6, 3321–3329; c) D. J. Ramꢄn, M.
Yus, Angew. Chem. 2005, 117, 1628–1661; Angew.
Chem. Int. Ed. 2005, 44, 1602–1634; d) B. Jiang, T.
Rajale, W. Wever, S.-J. Tu, G. Li, Chem. Asian J. 2010,
5, 2318–2335.
[2] H. C. Kolb, M. G. Finn, M. G.; K. B. Sharpless, Angew.
Chem. 2001, 113, 2056–2075; Angew. Chem. Int. Ed.
2001, 40, 2004–2021.
[3] a) C. W. Tornøe, C. Christensen, M. Meldal, Peptido-
triazoles: copper(I)-catalyzed 1,3-dipolar cycloadditions
on solid-phase, in: Peptides: The Wave of the Future,
(Eds.: M. Lebl, R. A. Houghten), San Diego, American
Peptide Society and Kluwer Academic Publishers,
2001, pp 263–264; b) C. W. Tornøe, C. Christensen, M.
Meldal, J. Org. Chem. 2002, 67, 3057–3064; c) V. V.
Rostovtsev, L. G. Green, V. V. Fokin, K. B. Sharpless,
Angew. Chem. 2002, 114, 2708–2711; Angew. Chem. Int.
Ed. 2002, 41, 2596–2599.
[4] a) M. Meldal, C. W. Tornøe, Chem. Rev. 2008, 108,
2952–3015; b) J. E. Moses, A. D. Moorhouse, Chem.
Soc. Rev. 2007, 36, 1249–1262; c) J.-F. Lutz, Z. Zaraf-
shani, Adv. Drug Delivery Rev. 2008, 60, 958–970;
d) N. K. Devaraj, J. P. Collman, QSAR Comb. Sci. 2007,
26, 1253–1260; e) W. H. Binder, R. Sachsenhofer, Mac-
romol. Rapid Commun. 2008, 29, 952–981.
[5] a) E. F. V Scriven, K. Turnbull, Chem. Rev. 1988, 88,
297–368; b) S. Brꢅse, C. Gil, K. Knepper, V. Zimmer-
mann, Angew. Chem. 2005, 117, 5320–5374; Angew.
Chem. Int. Ed. 2005, 44, 5188–5240.
[6] A. V. Maksikova, E. S. Serebryakova, L. G. Tikhonova,
L. I. Vereshchagin, Chem. Heterocycl. Compd. 1980, 16,
1284–1285.
[7] a) A. K. Feldman, B. Colasson, V. V. Fokin, Org. Lett.
2004, 6, 3897–3899; b) P. Appukkuttan, W. Dehaen,
V. V. Fokin, E. van der Eycken, Org. Lett. 2004, 6,
4223–4225; c) K. Kacprzak, Synlett 2005, 943–946; d) J.
Andersen, S. Bolvig, X. Liang, Synlett 2005, 2941–2947;
e) S. Chittaboina, F. Xie, Q. Wang, Tetrahedron Lett.
2005, 46, 2331–2336; f) Y.-B. Zhao, Z.-Y. Yan, Y.-M.
Liang, Tetrahedron Lett. 2006, 47, 1545–1549; g) M. L.
Kantam, V. S. Jaya, B. Sreedhar, M. Rao, B. M. Chou-
2953, 1741, 1710, 1438, 1370, 1251, 1051 cmÀ1 1H NMR
;
(DMSO-d6, 400 MHz): d=7.79 (s, 1H), 5.12 (dd, 1H, J=
8.5, 4.4 Hz), 4.91 (dd, 1H, J=14.1, 4.3 Hz), 4.65 (dd, 1H, J=
14.1, 8.9 Hz), 3.60 (s, 3H), 3.40 (t, 2H, J=6.3 Hz), 2.56 (t,
2H, J=7.5 Hz), 1.68 (p, 2H, J=6.7 Hz), 1.23 (s, 9H);
13C NMR (DMSO-d6, 125 MHz): d=170.1, 155.1, 146.6,
122.5, 78.7, 59.9, 53.6, 52.2, 49.2, 32.2, 28.0, 21.6; HR-MS
(ESI): m/z=407.1224, calcd. for C14H23N4O8S [MÀNa]À:
407.1237; HPLC purity: 100%.
Sodium (S)-tert-butoxycarbonyl(3-{4-[(tert-butoxycarbo-
nylamino)methyl]-1H-1,2,3-triazol-1-yl}-1-methoxy-1-oxo-
propan-2-yl)sulfamate (4o): Compound 4o was obtained as
a syrup; yield: 0.46 g (93%); [a]D: À43.18 (c 1, MeOH); IR
(film): nmax =3379, 2977, 1741, 1702, 1249, 1049 cmÀ1
;
1H NMR (DMSO-d6, 400 MHz): d=7.86 (s, 1H), 7.18 (t,
1H, J=5.7 Hz, interchangeable with D2O), 5.12 (dd, 1H,
J=7.7, 4.6 Hz), 4.94 (dd, 1H, J=13.9, 4.8 Hz), 4.63 (dd, 1H,
J=13.8, 8.0 Hz), 4.09 (d, 2H, J=5.6 Hz), 3.59 (s, 3H), 1.36
(s, 9H), 1.24 (s, 9H); 13C NMR (DMSO-d6, 100 MHz): d=
169.6, 155.4, 123.6, 80.0, 58.7, 51.8, 49.9, 35.6, 28.2, 27.7; HR-
MS (ESI): m/z=478.1603, calcd. for C17H28N5O9S [MÀNa]À:
478.1608; HPLC purity: 94.96%.
Sodium
(S)-tert-butoxycarbonyl{1-methoxy-1-oxo-3-[4-
(2’,3’,4’,6’-tetra-O-acetyl-a-d-mannopyranosyloxymethyl)-
1H-1,2,3-triazol-1-yl]}sulfamate (4p): Compound 4p was ob-
tained as a syrup; yield: 0.67 g (92%); [a]D: À3.38 (c 1,
MeOH). IR (film): nmax =2926, 1749, 1437, 1370, 1230,
1
1048 cmÀ1; H NMR (DMSO-d6, 400 MHz): d=8.10 (s, 1H),
5.18 (dd, 1H, J=8.6, 4.5 Hz), 5.13–4.99 (m, 4H), 4.96 (dd,
1H, J=14.2, 4.6 Hz), 4.72 (dd, 1H, J=14.1, 8.8 Hz), 4.64 (d,
1H, J=12.0 Hz), 4.56 (d, 1H, J=12.0 Hz), 4.15 (dd, 1H, J=
12.2, 5.0 Hz), 4.07–3.95 (m, 2H), 3.61 (s, 3H), 2.08 (s, 3H),
2.02 (s, 3H), 2.00 (s, 3H), 1.90 (s, 3H), 1.24 (s, 9H);
13C NMR (DMSO-d6, 100 MHz): d=170.1, 169.6, 169.6,
169.4, 155.1, 142.3, 125.3, 95.9, 78.8, 68.6, 68.6, 68.0, 65.3,
61.8, 59.8, 53.6, 52.3, 49.5, 28.0, 20.6, 20.5, 20.4, 20.4; HR-MS
(ESI): m/z= 709.1851, calcd. for C26H37N4O17S [MÀNa]À:
709.1874.
1802
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ꢂ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2012, 354, 1797 – 1803

One-Pot Three-Component Click Reaction of Cyclic Sulfates and Cyclic Sulfamidates
dary, J. Mol. Catal. A: Chemical 2006, 256, 273–277;
h) B. Sreedhar, P. S. Reddy, Synth. Commun. 2007, 37,
805 À812; i) B. Saha, S. Sharma, D. Sawant, B. Kundu,
Synlett 2007, 1591–1594; j) T. Miao, L. Wang, Synthesis
2008, 363–368; k) H. Sharghi, R. Khalifeh, M. M. . Dor-
oodmand, Adv. Synth. Catal. 2009, 351, 207–218; l) V.
Bꢃnꢃteau, A. Olmos, T. Boningari, J. Sommer, P. Pale,
Tetrahedron Lett. 2010, 51, 3673–3677; m) T. Shamim,
S. Paul, Catal. Lett. 2010, 136, 260–265; n) J. Yan, L.
Wang, Synthesis 2010, 447–452; o) K. A. Dururgkar,
R. G. Gonnade, C. V. Ramana, Tetrahedron 2009, 65,
3974–3979; p) A. R. Bogdan, N. W. Sach, Adv. Synth.
Catal. 2009, 351, 849–854; q) F. Alonso, Y. Moglie, G.
Radivoy, M. Yus, Org. Biomol. Chem. 2011, 9, 6385–
6395.
Lett. 2001, 3, 3557–3559; d) A. Avenoza, J. H. Busto, F.
Corzana, J. I. Garcꢀa, J. M. Peregrina, J. Org. Chem.
2003, 68, 4506–4513; e) D. D. Dhavale, S. D. Markad,
N. S. Karanjule, J. P. Reddy, J. Org. Chem. 2004, 69,
4760–4766; f) P. Gupta, S. V. Naidu, P. Kumar, Tetrahe-
dron Lett. 2004, 45, 9641–9643; g) O. Andriuzzi, C.
Gravier-Pelletier, G. Bertho, T. Prangeꢆ, Y. Le Merrer,
Beilstein J. Org. Chem. 2005, 1; h) V. F. V. Prazeres, L.
Castedo, C. Gonzꢁlez-Bello, Eur. J. Org. Chem. 2008,
3991–4003; i) K. Koroniak, G. Haufe, Synthesis 2010,
498,504; j) J. Lalot, T. Tite, A. Wadouachi, D. Postel, A.
Nguyen Van Nhien, Tetrahedron 2011, 67, 6006–6017.
[18] a) J. E. Baldwin, A. C. Spivey, C. J. Schofield, Tetrahe-
dron: Asymmetry 1990, 1, 881–884; b) M. Atfani, L.
Wei, W. D. Lubell, Org. Lett. 2001, 3, 2965–2968; c) J. J.
Posakony, T. J. Tewson, Synthesis 2002, 859–864; d) A.
Avenoza, J. H. Busto, F. Corzana, G. Jimenez-Oses,
J. M. Peregrina, Chem. Commun. 2004, 980–981; e) V.
Sai-Sudhir, N. Y. Phani-Kumar, R. B. Nasir Baig, S.
Chandrasekaran, J. Org. Chem. 2009, 74, 7588–7591.
[19] Y. Gao, K. B. Sharpless, J. Am. Chem. Soc. 1988, 110,
7538–7539.
[8] D. Kumar, V. B. Reddy, R. S. Varma, Tetrahedron Lett.
2009, 50, 2065–2068.
[9] C.-Z. Tao, X. Cui, J. Li, A.-X. Liu, L. Liu, Q.-X. Guo,
Tetrahedron Lett. 2007, 48, 3525–3529.
[10] a) H. S. G. Beckmann, V. Wittmann, Org. Lett. 2007, 9,
1–4; b) K. Barral, A. D. Moorhouse, J. E. Moses, Org.
Lett. 2007, 9, 1809–1811; c) A. D. Moorhouse, J. E.
Moses, Synlett 2008, 2089–2092; d) N. M. Smith, M. J.
Greaves, R. Jewell, M. W. D. Perry, M. J. Stocks, J. P.
Stonehouse, Synlett 2009, 1391–1394; e) C.-T. Lee, S.
Huang, B. H. Lipshutz, Adv. Synth. Catal. 2009, 351,
3139–3142; f) J. R. Suarez, B. Trastoy, M. E. Perez-
Ojeda, R. Marꢀn-Barrios, J. L. Chiara, Adv. Synth.
Catal. 2010, 352, 2515–2520.
[20] D. Soriano del Amo, W. Wang, H. Jiang, C. Besance-
ney, A. C. Yan, M. Levy, Y. Liu, F. L. Marlow, P. Wu, J.
Am. Chem. Soc. 2010, 132, 16893–16899.
[21] A. Megia-Fernandez, M. Ortega-MuÇoz, J. Lopez-Jara-
millo, F. Hernandez-Mateo, F. Santoyo-Gonzalez, Adv.
Synth. Catal. 2010, 352, 3306–3320.
[22] A. Mendez-Ardoy, N. Guilloteau, C. Di Giorgio, P.
Vierling, F. Santoyo-Gonzalez, C. Ortiz-Mellet, J. M.
Garcꢀa-Fernandez, J. Org. Chem. 2011, 76, 5882–5894.
[23] a) F. Langa, P. de La Cruz, A. de La Hoz, A. Diaz-
Ortiz, E. Diez-Barra, Contemp. Org. Synth. 1997, 4,
373–386; b) P. Lidstrçm, J. Tierney, B. Wathey, J. West-
man, Tetrahedron 2001, 57, 9225–9283; c) P. Appukkut-
tan, V. P. Mehta, E. V. van Der Eycken, Chem. Soc.
Rev. 2010, 39, 1467–1477; d) F. Perez-Balderas, M.
Ortega-MuÇoz, J. Morales-Sanfrutos, F. Hernandez-
Mateo, F. G. Calvo-Flores, J. A. Calvo-Asin, J. Isac-
Garcia, F. Santoyo-Gonzalez, Org. Lett. 2003, 5, 1951–
1954.
[24] S. H. Park, Bull. Korean Chem. Soc. 2003, 24, 253–255.
[25] K. Wasek, J. Kedzia, H. Krawczyk, J. Wojciechowski,
W. M. Wolf, Arkivoc 2010, 9, 146–154.
[26] F. G. Calvo-Flores, P. Garcꢀa-Mendoza, F. Hernꢁndez-
Mateo, J. Isac-Garcꢀa, F. Santoyo-Gonzꢁlez, J. Org.
Chem. 1997, 62, 3944–3961.
[11] a) J. S. Yadav, B. V. S. Reddy, G. M. Reddy, D. N.
Chary, Tetrahedron Lett. 2007, 48, 8773–8776; b) K. R.
Reddy, C U. Maheswari, K. Rajgopal, M. L. Kantam,
Synth. Commun. 2008, 38, 2158–2167; c) H. Sharghi,
M. H. Beyzavi, A. Safavi, M. M. Doroodmand, R. Kha-
lifeh, Adv. Synth. Catal. 2009, 351, 2391–2410; d) T.
Boringari, A. Olmos, B. M. Reddy, J. Sommer, P. Pale,
Eur. J. Org. Chem. 2010, 6338–6347; e) H. Sharghi, M.
Hosseini-Sarvari, F. Moeini, R. Khalifeh, A. S. Beni,
Helv. Chim. Acta 2010, 93, 435–449; f) L. S. Campbell-
Verduyn, W. Szymanski, C. P. Postema, R. A. Dierckx,
P. H. Elsinga, D. B. Janssen, B. L. Feringa, Chem.
Commun. 2010, 46, 898–900; g) F. Alonso, Y. Moglie,
G. Radivoy, M. Yus, J. Org. Chem. 2011, 76, 8394–8405.
[12] G. Kumaraswamy, K. Ankamma, A. Pitchaiah, J. Org.
Chem. 2007, 72, 9822–9825.
[13] D. Kumar, V. B. Reddy, Synthesis 2010, 1687–1691.
[14] O. A. Attanasi, G. Favi, P. Filippone, F. Mantellini, G.
Moscatelli, F. R. Perrulli, Org. Lett. 2010, 12, 468–471.
[15] a) B. B. Lohray, Synthesis 1992, 1035–1052; b) H. S.
Byun, L. L. He, R. Bittman, Tetrahedron 2000, 56,
7051–7091; c) B. B. Lohray, V. Bhushan, Adv. Hetero-
cycl. Chem. 1997, 68, 89–180; d) A. Megia-Fernandez,
J. Morales-Sanfrutos, F. Hernandez-Mateo, F. Santoyo-
Gonzalez, Curr. Org. Chem. 2011, 15, 401–432.
[27] S. J. Kim, H. B. Park, J. S. Lee, N. H. Jo, K. H. Yoo, D.
Baek, B.-W. Kang, J.-H. Cho, C.-H. Oh, Eur. J. Med.
Chem. 2007, 42, 1176–1183.
[28] R. B. Nasir Baig, R. N. Chandrakala, V. Sai Sudhir, S. J.
Chandrasekaran, J. Org. Chem. 2010, 75, 2910–2921.
[29] R. J. Kaufman, R. S. Sidhu, J. Org. Chem. 1982, 47,
4941–4947.
[16] R. E. Melendez, W. D. Lubell, Tetrahedron 2003, 59,
2581–2616.
[30] D. L. Boger, C. M. Tarby, P. L. Myers, L. H. Caporale,
J. Am. Chem. Soc. 1996, 118, 2109–2110.
[17] a) B. B. Lohray, Y. Gao, K. B. Sharpless, Tetrahedron
Lett. 1989, 30, 2623–2626; b) K. P. A. M. Van, W. File-
mon, G. H. Veeneman, M. G. A. Van, B. J. H. Van, J.
Carbohydr. Chem. 1992, 11, 837–848; c) J. G. Stein-
mann, J. H. Phillips, W. J. Sanders, L. L. Kiessling, Org.
[31] L. A. Canalle, S. S. van Berkel, L. T. de Haan, J. C. M.
van Hest, Adv. Funct. Mater. 2009, 19, 3464–3470.
[32] T. N. Hoheisel, H. Frauenrath, Org. Lett. 2008, 10,
4525–4528.
Adv. Synth. Catal. 2012, 354, 1797 – 1803
ꢂ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
1803