Az-a colourful azulene-derived protecting group

Article abstract of DOI:10.1016/j.tetlet.2009.10.043

Azulen-1-yl-dicarbonyl (Az) is a novel, coloured, protecting group used to mask primary and secondary alcohols. In particular, the use of Az in the construction of carbohydrates, where a number of orthogonal protecting groups are typically required, is of

Full text of DOI:10.1016/j.tetlet.2009.10.043

Tetrahedron Letters 50 (2009) 7199–7204
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Az—a colourful azulene-derived protecting group
b
a
a,
*
Mattie S. M. Timmer a,b, , Bridget L. Stocker , Peter T. Northcote , Brendan A. Burkett
*
a School of Chemical and Physical Sciences, Victoria University of Wellington, PO Box 600, Wellington, New Zealand
b Malaghan Institute of Medical Research, PO Box 7060, Wellington, New Zealand
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 14 July 2009
Revised 30 September 2009
Accepted 9 October 2009
Available online 14 October 2009
Azulen-1-yl-dicarbonyl (Az) is a novel, coloured, protecting group used to mask primary and secondary
alcohols. In particular, the use of Az in the construction of carbohydrates, where a number of orthogonal
protecting groups are typically required, is of merit. Introduction and removal of the Az-group is per-
formed easily and in near quantitative yields in the presence of other commonly used protecting groups,
and the Az-group is compatible with glycosylation reactions using trichloroacetimidate donors. The
deep-red colour of the Az-group greatly facilitates the purification of carbohydrate building blocks and
the monitoring of coupling reactions. Of particular note is that the Az-group can be selectively introduced
on diol systems and removed in the presence of esters, such as acetates.
Ó 2009 Elsevier Ltd. All rights reserved.
The use of protecting groups in organic synthesis remains of
paramount importance.1 As molecular targets become more com-
plex, the demand for novel protection and cleavage techniques
has increased.2 This is particularly the case during the construction
of oligosaccharides where recent synthetic developments have en-
abled highly branched structures to be synthesized which, in turn,
increases the number of saccharide-coupling steps and the number
and type of orthogonal protecting groups required.3 The steric and
electronic nature of protecting groups can also influence the reac-
tivity and outcome of glycosylation reactions,4 and the advent of
solid-phase oligosaccharide synthesis has also placed greater de-
mands on the choice of protecting group.5
Of particular interest to us was the development of a coloured
hydroxy-protecting group. UV–vis detectable protecting groups
have the advantage in that they aid in the monitoring of reaction
progress and the purification of synthetic intermediates. They
may also be used to monitor colorimetrically the progress of a
reaction, an application that is highly desirable for solid-phase syn-
thesis.6 The most commonly used coloured-protecting groups are
the UV-active 9-fluorenylmethoxycarbonyl (Fmoc) group, which
has been extensively used in solid-phase peptide synthesis,6 and
the (methoxy) trityl groups, originally developed as a 50-OH pro-
tecting group for the synthesis of DNA and RNA fragments.7
Although both Fmoc and trityl groups have been used in oligosac-
charide synthesis, the lability of the Fmoc group to basic condi-
tions,1,8 and the steric bulk of the trityl group (limiting its use to
the protection of primary hydroxy functions), hinders their wider
application. More recent developments in coloured-protecting
groups have mainly focused on the peptide or ribonucleoside syn-
thesis,9 although work by Pohl and co-workers10 and Manabe and
Ito11 nicely demonstrates the potential of coloured hydroxy pro-
tecting groups to facilitate the real time monitoring of solid-phase
oligosaccharide synthesis. In addition, Lindhorst and co-workers
reported on the use of functionalised guaiazulene derivatives as
coloured markers in Chromophore-Supported Purification.12
In search of a new hydroxy protecting group, our attention was
drawn towards azulene (Scheme 1). Azulene has a remarkable non-
alternant aromatic 10-p-electron system, with a polar resonance
structure that consists of a fused tropylium cation and cyclopenta-
dienyl anion. This electronic structure gives rise to some unique
physical properties, such as the intense blue colour of azulene,
and interesting chemical reactivities—azulene reacts readily with
both nucleophiles (at the 6-position and, to a lesser extent, the
4- and 8-positions) and electrophiles (at the 1- and 3-positions).13
To tailor the properties of azulene, we considered introducing an
electron-withdrawing group at the 1-position (Scheme 1). The
4
5
3
3a
6
2
8a
1
7
8
* Corresponding authors. Tel.: +64 4 463 6529; fax: +64 4 463 5241 (M.S.M.T.);
tel.: +64 6873 4805; fax: +64 6796 3700 (B.A.B.).
O
O
R
R
E-mail addresses: Mattie.Timmer@vuw.ac.nz (M.S.M. Timmer), Brendan_Burket
t@ices.a-star.edu.sg (B.A. Burkett).
Scheme 1. Resonance stabilization of azulene and azulene-1-carbonyl derivatives.
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.10.043

7200
M. S. M. Timmer et al. / Tetrahedron Letters 50 (2009) 7199–7204
electron-withdrawing group would stabilise the negative charge
on the cyclopentadienyl anion, thereby reducing the overall nucle-
ophilic character of the azulene moiety and render it as a useful
protecting group. Being coloured, the incorporation of an azulene
protecting group onto a hydroxy moiety would aid in the monitor-
ing of reaction progress by TLC and in the identification of products
during column chromatography. It was also envisioned that,
following deprotection, a modified-azulene derivative would result
which could be used to monitor colorimetrically the progress of a
reaction.
Herein, we present the use of azulen-1-yl-oxo-acetyl (Az) as a
coloured protecting group. By taking advantage of the nucleophi-
licity of the azulene 1-position, we proposed that azulene could
be readily reacted with oxalyl chloride14 to give azulen-1-yl-oxo-
Table 1
Synthesis of azulene-protected carbohydrate building blocks
O
Cl
O
Cl
OR
O
O
ROH
Cl
O
O
CH2Cl2
pyridine
toluene
1
2
Entry
Alcohol
MeOH
Ester
Yield (%)
OMe
O
O
1
99
3
O
O
2
3
99
96
O
OH
O
OAz
5
4
O
O
OH
OAz
O
O
O
O
O
O
O
O
6
7
O
O
O
O
O
O
OH
OAz
4
95
O
O
O
O
8
9
Ph
O
Ph
O
O
O
O
O
OTBS
OTBS
HO
AzO
5
6
7
95
99
89
N3
N3
10
11
OBn
OBn
AcO
AcO
AzO
BnO
BnO
O
O
O
O
OBn
O
O
HO
SPh
SPh
BnO
BnO
OBn
OBn
OBn
12
13
Ph
O
Ph
O
O
O
O
O
SPh
SPh
HO
AzO
OH
OH
14
15
Ph
Ph
O
O
O
O
8
96
O
O
SPh
SPh
HO
AzO
OH
OH
16
17

M. S. M. Timmer et al. / Tetrahedron Letters 50 (2009) 7199–7204
7201
acetyl chloride (AzCl), a convenient means by which to produce
azulen-1-yl-oxo-acetic acid esters.
high yield (96%), with none of the 2-O-Az isomer observed (entry
8). Although the superior reactivity of the 3-OH position in 4,6-
O-benzylidene-protected glucose and galactose derivatives has
been noted,22 the excellent selectivity of the azulene protection
provides a convenient route for the construction of fully orthogo-
Azulene is commercially available or can be readily synthesized
from pyridine and cyclopentadiene.15 To examine its potential as a
hydroxy-protecting group, azulene (1) was reacted with oxalyl
chloride to produce the deep-red coloured AzCl (2) (Table 1). The
colour change, from royal blue to blood red, was instantaneous.
Concentration of the reaction mixture, to remove excess oxalyl
chloride, and redissolution in dichloromethane allowed for the
subsequent in situ reaction of the acyl chloride with methanol to
produce methyl ester 3 (Table 1, entry 1). As anticipated, chro-
matographic purification (silica gel) was greatly facilitated by the
bright red colour of ester 3, for this could be visualised and tracked
by eye on the column. Similarly, reaction of 1,2-O-isopropylidene-
glycerol (4)16 with AzCl also proceeded smoothly to give the red
azulene ester 5 in nearly quantitative yield (entry 2). In both in-
stances, excess AzCl in the reaction mixture17 was hydrolyzed fol-
lowing work-up to give the corresponding acid which, as a highly
polar product, allowed for the easy purification of the azulen-1-
yl-oxo-acetyl ester by SiO2 column chromatography.
Table 3
Deprotection reactions
O
R
O
NaOMe
MeOH
O
ROH
Entry Alcohol
Ester
Yield
(%)
O
O
OAz
O
OH
O
O
O
O
O
Encouraged by these results, we set out to react a series of
orthogonally protected carbohydrates with AzCl (Table 1, entries
3–8). First, isopropylidene protected galactose 618 was reacted
with AzCl to give ester 7 in 96% yield (entry 3). More demanding
substrates were then subjected to Az protection. The 3-position
in diacetone glucose 8 was reacted with AzCl to yield, following
purification through a short SiO2 plug, the 3-O-Az protected glu-
cose 9 in excellent yield (95%, entry 4). Glucosazide building block
1019 also reacted smoothly with AzCl to provide, after crystalliza-
tion, the corresponding azulene ester 11 as deep-purple needles
(95% yield, entry 5). Similarly, reaction of lactose building block
1220 with AzCl led to the formation of 3-O-Az protected thiolacto-
side 13 in excellent yield (entry 6). Of significant note is the ability
of AzCl to be incorporated selectively onto the 3-OH of carbohy-
drate diols (entries 7 and 8). In the presence of 1.1 equivalents of
AzCl, the more reactive 3-OH position of glucose 1421 was selec-
tively protected to give 3-O-Az-glucoside 15 in 89% yield (entry
7). Only trace amounts (ꢀ5%) of the 2-OH regioisomer were ob-
served. Similarly, selective protection of the 3-OH position of gal-
actose 1613 occurred smoothly to give 3-O-Az-galactoside 17 in
1
94
O
O
7
6
Ph
Ph
O
Ph
Ph
O
O
O
O
O
OTBS
SPh
OTBS
SPh
AzO
HO
2
3
94
98
N3
N3
11
15
10
O
O
O
O
O
O
AzO
HO
OH
OH
14
Ph
Ph
O
O
O
O
4
95
O
O
SPh
SPh
AzO
HO
OAc
OH
19
16
Table 2
Acid stability of azulene-protected monosaccharides
Entry
Starting material
Deprotected sugar
Conditions
Yield (%)
92
OH
O
80%
AcOH/H2O
50 °C, 2 h
HO
OAz
1
O
OAz
18
5
Ph
HO
AzO
OH
O
O
SPh
O
80%
AcOH/H2O
50 °C, 2 h
OAc
2
89
O
SPh
AzO
Ph
OAc
20
19
O
HO
O
O
O
HO
80%
AcOH/H2O
50 °C, 2 h
OTBS
OTBS
OTBS
AzO
AzO
3
4
78
69
N3
N3
11
11
21
OH
Ph
O
O
O
O
AzO
80%
AcOH/3 M HCl
50 °C, 1 h
HO
AzO
OH
N3
N3
22

7202
M. S. M. Timmer et al. / Tetrahedron Letters 50 (2009) 7199–7204
nally protected glucose and orthogonally-protected galactose
building blocks without the use of tin-ketals23 or lengthy protect-
ing group manipulations.
bonyl’ nature of the azulen-1-yl-oxo-acetyl group by the way of
selective Az-deprotection using 1,2-diaminobenzene (Table 4).
We also investigated whether the product of this reaction, 2-(azu-
len-1-yl)-3-hydroxy-benzopyrazine (23), could be used to monitor
colorimetrically the progress of the reaction. Indeed, subjecting Az
acetonide 7 to 1.5 equiv of 1,2-diaminobenzene and acetic acid in
ethanol at reflux yielded alcohol 6 in excellent yield (entry 1, Ta-
ble 4) and the orange 2-(azulen-1-yl)-3-hydroxybenzopyrazine
(23). Though we were delighted with the selective deprotection
of the Az-group, unfortunately the colour of benzopyrazine 23
The stability of the Az-group under conditions used to cleave
acid labile hydroxy-protecting groups was then explored (Table 2).
Upon heating Az-protected glycol 5 in 80% aqueous acetic acid for
2 h, the isopropylidine group was cleaved to yield mono-Az-pro-
tected glycol 18 in excellent yield (entry 1). The benzylidine group
in galactoside 19 (entry 2) was also removed smoothly under the
same conditions to provide diol 20 in good yield. Subjection of azi-
doglucoside 11 to 80% acetic acid/water for 2 h led to the isolation
of diol 21 in 78% yield (entry 3). To ascertain the stability of the Az
group under more acidic conditions, azide 11 was then heated in
80% AcOH/3 M HCl for 1 h (entry 4). These conditions resulted in
the acetolysis of the benzylidene acetal and cleavage of the tert-
butyldimethylsilyl (TBS) protecting group to from triol 22 while
the Az-protecting group remained (entry 4).
Paramount to the usefulness of Az as a protecting group is its
ease of deprotection and the ability of Az to be selectively depro-
tected in the presence of other protecting groups. Not surprisingly,
removal of the Az group is readily effected by treatment of the pro-
tected carbohydrates in methanol with catalytic sodium methox-
ide (Table 3). Here esters 7, 11 and 15 were deprotected
uneventfully to afford alcohols 6, 10 and 14 in nearly quantitative
yields (entries 1–3). Unsurprisingly, removal of the Az group under
these conditions also led to the cleavage of other esters, as can be
seen in the deprotection of Az/Ac-protected galactoside 19 (entry
4).
(kmax = 437 nm; log
e0 = 4.4) was too similar to that of the azulen-
1-yl-oxo-acetyl group (kmax = 397; log
e
0 = 4.3) to enable effective
colorimetric monitoring. The colour of benzopyrazine 23 nonethe-
less facilitated during its removal from the desired alcohol by flash
chromatography. The orthogonality of the Az-group was further
exemplified by subjecting the substrates containing both an acetyl
and an Az group to treatment with 1,2-diaminobenzene (entries 2
and 3, Table 4). Again the Az group in both monosaccharide 19 and
disaccharide 13 was removed selectively in the presence of an ace-
tate to yield alcohols 24 and 12 in 92% and 87% yields, respectively.
It is of interest to note that the deprotection using o-diaminoben-
zene required both the presence of equimolar acetic acid and ele-
vated temperatures. Under neutral conditions, the addition of
hydrazine, 1,2-diaminoethane, urea, carbazides, semicarbazides
and thiosemicarbazides failed to remove the Az-group.
The compatibility of Az to reaction conditions used to function-
alize carbohydrate building blocks was further explored (Table 5).
First, 3-O-Az protected galactose building block 17 was subjected
to Ac2O in pyridine (entry 1). This led to the smooth formation of
the corresponding acetate 19 in nearly quantitative yield. To pre-
pare an azulene-protected carbohydrate donor, azidoglucose 11
The identification of reaction conditions that would enable the
Az group to be selectively removed in the presence of other esters
were then explored. Herein, we envisioned exploiting the ‘di-car-
Table 4
Selective deprotection reactions
N
N
OH
NH2
NH2
O
R
O
O
+
ROH
AcOH
EtOH
reflux
23
Entry
Ester
Alcohol
Yield (%)
O
O
OAz
O
OH
O
O
O
O
O
1
88
O
O
7
6
Ph
Ph
O
O
O
O
2
3
92
87
O
O
SPh
BnO
SPh
BnO
AzO
HO
OAc
OAc
19
24
OBn
OBn
AcO
AzO
AcO
HO
O
O
O
O
O
O
SPh
SPh
BnO
BnO
OBn
OBn
OBn
OBn
13
12

M. S. M. Timmer et al. / Tetrahedron Letters 50 (2009) 7199–7204
7203
Table 5
Compatibility of azulene protection towards building block manipulations
Entry
Starting material
Product
Conditions
Yield (%)
Ph
Ph
O
O
O
O
1
Ac2O, pyridine rt, 12 h
95
O
O
SPh
SPh
AzO
OH
AzO
Ph
OAc
17
19
Ph
O
O
O
O
O
O
OTBS
OH
AzO
AzO
OH
2
3
HFꢁpyridine THF, rt, 2 h
89
78
N3
N3
11
25
Ph
O
Ph
O
O
O
O
O
AzO
AzO
N3
N
3 O
NH
CCl3
Cl3CCN, CsCO3, CH2Cl2, rt, 2 h
25
26
was subjected to HFꢁpyridine in THF, to yield lactol 25 (entry 2).
Subsequent reaction of the anomeric hydroxy group in 25 with tri-
chloroacetonitrile,24 in the presence of Cs2CO3 as base, provided
imidate 26 in good yield (entry 3). Purification of each reaction
product was readily performed by elution of the crude reaction
products on a silica plug.
Finally, the compatibility of the Az-group to glycosylation con-
ditions was investigated (Scheme 2). Trichloroacetimidate cou-
pling reactions proved successful, and the coupling of the
azulene-protected imidate 26 to di-isopropylidene-galactose
acceptor 6 produced the desired disaccharide 27 in 83% yield. Gly-
cosylation of Az-protected acceptor 17 with mannosyl-imidate
283b also gave the desired disaccharide 29 in good yield and with
complete -selectivity. In both instances, the bright red colour of
a
the acceptor/donor and the dimeric product greatly facilitated in
the monitoring of the reaction and in the isolation of the products
via column chromatography. Unfortunately, the coupling of Az-
protected thiol donor 19 with di-isopropylidene-galactose accep-
tor 6 using NIS and TfOH as the activating system25 led to the for-
mation of the phenylthio-substituted coupling product 30. This
result was disappointing, though not highly unexpected given
the nucleophilicity of the 3-position of the azulen-1-yl-oxo-acetyl
group. Herein, we postulate that phenylsulfenyl iodide, the by-
product of the glycosylation reaction, reacts with azulene in an
O
OH
O
Ph
O
O
O
O
Ph
O
O
O
O
O
AzO
O
O
AzO
N3
6
N3
O
O
O
NH
CCl3
O
TMSOTf
MeCN
83%
O
26
27 α:β = 1:5
Ph
Ph
O
O
O
O
O
OBz
O
O
SPh
AzO
BnO
BnO
BnO
SPh
OH
17
AzO
O
O
CCl3
OBn
TMSOTf
CH2Cl2
83%
OBn
O
OBn
NH
OBz
28
29
O
OH
O
Ph
O
Ph
O
O
O
O
O
O
O
O
O
O
O
O
6
O
O
O
O
SPh
AzO
NIS, TfOH
CH2Cl2
78%
OAc
O
OAc
19
PhS
30
Scheme 2. Coupling reactions.

7204
M. S. M. Timmer et al. / Tetrahedron Letters 50 (2009) 7199–7204
2007, 72, 9963; (e) Crich, D.; Vinogradova, O. J. Org. Chem. 2007, 72, 6513; (f)
Dudkin, V. Y.; Miller, J. S.; Dudkina, A. S.; Antczak, C.; Scheinberg, D. A.;
Danishefsky, S. J. J. Am. Chem. Soc. 2008, 130, 13598; (g) Tanaka, H.; Nishiura, Y.;
Takahashi, T. J. Am. Chem. Soc. 2008, 130, 17244; (h) Fraser-Reid, B.; Ray
Chaudhuri, S.; Jayaprakash, K. N.; Lu, J.; Ramamurty, C. V. S. J. Org. Chem. 2008,
73, 9732; (i) Imamura, A.; Ando, H.; Ishida, H.; Kiso, M. J. Org. Chem. 2009, 74,
3009; (j) Cid, M. B.; Alfonso, F.; Martín-Lomas, M. Chem. Eur. J. 2005, 11, 928.
electrophilic aromatic substitution reaction to give the 3-iodo
azulenyl product.26 Subsequent nulceophilic substitution of the io-
dide by thiophenol leads to the 3-phenylthioazulene derivative.27
Given this result, the electrophilicy of the Az-group would also
make it incompatible with pentenyl glycoside donors where NIS
is commonly used as the activator. Removal of the 3-phenylthio-
azulene group can nonetheless be achieved as subjection of disac-
charide 30 to NaOMe in MeOH resulted in the complete
methanolysis of both the Az and acetyl protecting groups.
Azulen-1-yl-oxo-acetyl (Az) is a novel coloured hydroxy-pro-
tecting group for primary and secondary alcohols and is a useful
addition to the arsenal of protecting groups currently available.
The Az-group can be readily introduced and is stable to a variety
of reaction conditions. Importantly, the Az group can be regioselec-
tively incorporated onto the 3-OH position of benzylidene-pro-
tected glucosides and benzylidene-protected galactosides and its
orthogonality has been illustrated by its selective removal in the
presence of various silyl, ether and/or acetate protecting groups.
The Az-group is also amenable to glycosylation reactions with
the commonly used trichloroacetimidate donors. Unfortunately,
removal of the Az-group cannot be used to colorimetrically moni-
tor the reaction progress, however the colour of the Az-group itself
aids in the monitoring of reactions by TLC and in the isolation of
products via column chromatography. Investigation into the use
of the Az-group during the construction of more complex oligosac-
charides is currently underway.
4. For
a review on factors influencing glycosylation reactions, see: Zhu, X.;
Schmidt, R. R. Angew. Chem., Int. Ed. 2009, 48, 1900.
5. (a) Osborn, H. M. I.; Khan, T. H. Tetrahedron 1999, 55, 1807; (b) Roussel, F.;
Knerr, L.; Grathwihl, M.; Schmidt, R. R. Org. Lett. 2000, 2, 3043; (c) Palmacci, E.
R.; Hewitt, M. C.; Seeberger, P. H. Angew. Chem., Int. Ed. 2001, 40, 4433.
6. (a) Sewald, Norbert; Jakubke, Hans-Dieter Peptides: Chemistry and Biology;
Wiley-VCH: Weinheim, 2002; (b) Atherton, E.; Sheppard, R. C. Solid Phase
Peptide Synthesis: A Practical Approach; IRL Press: Oxford, 1989.
7. Sonveaux, E. Protecting Groups in Oligonucleotide Synthesis. In Protocols for
Oligonucleotide Conjugates, Synthesis and Analytical Techniques; Agrawal, S., Ed.;
Humana Press: Totowa, New Jersey, 1994.
8. Gioeli, C.; Chattopadhyaya, J. B. J. Chem. Soc., Chem. Commun. 1982, 672.
9. (a) Zhuravlev, V. G.; Mazurov, A. A.; Andronati, S. A. Collect. Czech. Chem.
Commun. 1992, 57, 1495; (b) Caton-Williams, J.; Huang, Z. Angew. Chem., Int. Ed.
2008, 120, 1747; (c) Abell, A. D.; Martyn, D. C.; May, B. C. H.; Nabbs, B. K.
Tetrahedron Lett. 2002, 43, 3673; (d) Sekine, M.; Aoyagi, M.; Ushioda, M.;
Ohkubo, A.; Seio, K. J. Org. Chem. 2005, 70, 8400; (e) Leikauf, E.; Köster, H.
Tetrahedron 1995, 51, 5557.
10. Ko, K.-S.; Park, G.; Yu, Y.; Pohl, N. L. Org. Lett. 2008, 10, 5381.
11. Manabe, S.; Ito, Y. J. Am. Chem. Soc. 2002, 124, 12638.
12. (a) Aumüller, I.; Lindhorst, T. K. Eur. J. Org. Chem. 2006, 1103; (b) Dubber, M.;
Patel, A.; Sadalapure, K.; Aumüller, I.; Lindhorst, T. K. Eur. J. Org. Chem. 2006,
5357.
13. (a) Anderson, A. G.; Nelson, J. A.; Tazuma, J. J. J. Am. Chem. Soc. 1953, 75, 4980;
(b) Hafner, K.; Bernhard, C. Angew. Chem. 1957, 69, 533; (c) Kedziorek, M.;
Mayer, P.; Mayr, H. Eur. J. Org. Chem. 2009, 1202.
14. For the reaction of azulene with oxalyl bromide (and the product with
methanol or ethanol), see: (a) Treibs, W. Chem. Ber. 1959, 92, 2152–2163; (b)
Ito, S.; Okujima, T.; Kikuchi, S.; Shoji, T.; Morita, N.; Asao, T.; Ikoma, T.; Tero-
Kubota, S.; Kawakami, J.; Tajiri, A. J. Org. Chem. 2008, 73, 2256–2263.
15. (a) Ziegler, K.; Hafner, K. Angew. Chem. 1955, 67, 301; (b) Hafner, K.; Meinhardt,
K.-P. Org. Synth. 1990, Coll. Vol. 7, 15.
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2009.10.043.
16. Fischer, E. Chem. Ber. 1895, 28, 1167.
17. AzCl (1.1–1.5 equiv) are used with respect to the alcohol.
18. Ohle, H.; Berend, G. Chem. Ber. 1925, 58, 2585.
19. Toepfer, A.; Kinzy, W.; Schmidt, R. R. Liebigs Ann. Chem. 1994, 5, 449.
20. Mukhopadhyay, B.; Field, R. A. Carbohydr. Res. 2003, 338, 2149.
21. Liptak, A.; Jodal, I.; Harangi, J.; Nanasi, P. Acta Chim. Hungarica 1983, 113, 415.
22. (a) Zhu, X.; Kawatkar, S.; Rao, Y.; Boons, G.-J. J. Am. Chem. Soc. 2006, 128, 11948;
(b) Wang, H.; She, J.; Zhang, L.-H.; Ye, X.-S. J. Org. Chem. 2004, 69, 5774; (c)
Jiang, L.; Chan, T.-H. J. Org. Chem. 1998, 63, 6035.
23. (a) Dasgupta, F.; Garegg, P. J. Synthesis-Stuttgart 1994, 11, 1121; (b) Fernandez-
Mayoralas, A.; Marra, A.; Trumtel, M.; Veyrieres, A.; Sinay, P. Carbohydr. Res.
1989, 188, 81; (c) Nicolaou, K. C.; Mitchell, H. J.; Rodriguez, R. M.; Fylaktakidou,
K. C.; Suzuki, H. Angew. Chem., Int. Ed. 1999, 38, 3345.
24. (a) Schmidt, R. R.; Michel, J. Angew. Chem., Int. Ed. Engl. 1980, 19, 731; (b)
Schmidt, R. R.; Michel, J.; Roos, M. Liebigs Ann. Chem. 1984, 1343.
25. Veeneman, G. H.; Van Leeuwen, S. H.; Van Boom, J. H. Tetrahedron Lett. 1990,
31, 1331.
26. See for examples: (a) Ueno, T.; Toda, H.; Yasunami, M.; Yoshifuji, M. Bull. Chem.
Soc. Jpn. 1996, 69, 1645; (b) Thanh, N. C.; Ikai, M.; Kajioka, T.; Fujikawa, H.;
Taga, Y.; Zhang, Y.; Ogawa, S.; Shimada, H.; Miyahara, Y.; Kuroda, S.; Oda, M.
Tetrahedron 2006, 62, 11227.
References and notes
1. Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic Synthesis, 3rd ed.; John
Wiley & Sons: New York, 1999.
2. For some recent examples, see: (a) Vatèle, J.-M. Tetrahedron 2007, 63, 10921–
10929; (b) Bufali, S.; Hölemann, A.; Seeberger, P. H. J. Carbohydr. Res. 2005, 24,
441; (c) Cai, F.; Crich, D. Org. Lett. 2007, 9, 1613; (d) Komba, S.; Kitaoka, M.;
Kasumi, T. Eur. J. Org. Chem. 2005, 5313; (e) Baek, J. Y.; Shin, Y.-S.; Jeon, H. B.;
Kim, K. S. Tetrahedron Lett. 2005, 46, 5143–5147; (f) Yu, H.; Williams, D. L.;
Ensley, H. E. Tetrahedron Lett. 2005, 46, 3417–3421; (g) Chery, F.; Rollin, P.; De
Lucchi, O. D.; Cossu, S. Synthesis 2001, 2, 286; (h) Gum, A. G.; Kappes-Roth, T.;
Waldmann, H. Chem. Eur. J. 2000, 6, 3714; (i) Plante, O. J.; Buchwald, S. L.;
Seeberger, P. H. J. Am. Chem. Soc. 2000, 122, 7148; (j) Kuo, P.-Y.; Chuang, R.-R.;
Yang, D.-Y. Mol. Divers 2009, 13, 253.
3. For recent examples, see: (a) Codée, J. D. C.; Stubba, B.; Schiattarella, M.;
Overkleeft, H. S.; Van Boeckel, C. A. A.; Van Boom, J. H.; Van der Marel, G. A. J.
Am. Chem. Soc. 2005, 127, 3767; (b) Hölemann, A.; Stocker, B. L.; Seeberger, P. H.
J. Org. Chem. 2006, 71, 8071; (c) Liu, X.; Stocker, B. L.; Seeberger, P. H. J. Am.
Chem. Soc. 2006, 128, 3638; (d) Fulse, D. B.; Jeon, H. B.; Kim, K. S. J. Org. Chem.
27. Iodo- and phenylthio-substituted products were formed in a 1:4 ratio.